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BACKGROUND: Berberine has the potential to induce osteogenic differentiation of various mesenchymal stem cells under normal conditions and special conditions such as high glucose, infection and inflammation. It is a natural small molecule drug that can induce bone formation in seed cells instead of growth factors, and has great application prospect in bone tissue engineering. OBJECTIVE: To review and summarize the research progress in the osteogenic mechanism and efficacy of berberine, especially its osteogenic potential under high glucose, infection and inflammation conditions, and its biological safety, so as to provide theoretical basis for its development and application in bone tissue engineering. METHODS: PubMed, WanFang, and CNKI were searched for relevant literature using the keywords of “berberine, bone defects, bone repair, bone regeneration, osteoinductive, osteoporosis, osteoblast, osteoclast, bone tissue engineering, bone, high glucose, diabetes, inflam*, infect*” in English and Chinese, respectively. A total of 105 literatures were selected for review. RESULTS AND CONCLUSION: Berberine can be used to treat multiple diseases including bone diseases, and it has the ability to promote bone regeneration. This article systematically reviews the mechanism of berberine on bone regeneration and in vivo and in vitro studies. Studies have shown that it can play a role in bone repair by promoting osteogenesis, inhibiting osteoclast formation and activity, and preventing osteoporosis. It shows excellent osteogenic differentiation potential mainly via Wnt/β-catenin, PI3K/AKT, EGFR/MEK/p38MAPK, cAMP/PKA/CREB, ERK and other signaling pathways. Berberine can also relieve the inhibition of osteogenic differentiation caused by high glucose, infection and inflammation, which provides more possibilities for the treatment of bone defects in patients with diabetes or infection and inflammation in the bone defect site. Berberine also has the advantages of low toxicity, low price, easy access (currently it can be synthesized), which is a relatively ideal bone induction potential drug. In recent years, the application of berberine in the treatment of bone defect tends to be localized, mainly through the combination with bone tissue engineering technology to improve bioavailability, and has shown good bone repair effect and excellent biological safety in animal experiments. In addition, preclinical experiments have shown splendid bone regeneration potential in the conditions of diabetes, local infection and inflammation. In the future, more studies are needed to fully reveal the osteogenic mechanism and biological safety of berberine, and seek the most suitable controlled release loading system to make artificial bone replacement materials with good mechanical strength, efficacy and biological safety. [ABSTRACT FROM AUTHOR]

BACKGROUND: At present, the treatment methods for necrotizing fasciitis mostly use negative pressure sealing suction after thorough debridement. This method requires repeated debridement to completely remove necrotic infected tissue, causing serious physical and economic burdens to patients. OBJECTIVE: To introduce a rare clinical case of calf compartment syndrome caused by diabetic foot necrotizing fasciitis, and summarize the clinical experience of using antibiotic-loaded bone cement for treatment and comprehensive management. METHODS: A total of 6 patients with calf compartment syndrome caused by diabetic necrotizing fasciitis admitted to Wuxi 9th Affiliated Hospital of Soochow University from August 2017 to August 2020 were selected, including 5 males and 1 female with an average age of 54 years. During the perioperative period, the patients’ general condition was evaluated and systemic nutritional support treatment was given. In the first stage, all patients received complete debridement to control infection, antibiotic-loaded bone cement packing, and negative pressure sealed drainage. In the second stage, bone cement was removed and wound repair was performed. The wound healing, as well as the occurrence of redness, swelling, and exudation was observed during the follow-up. RESULTS AND CONCLUSION: (1) The wounds of four patients were fresh after twice antibiotic-loaded bone cement packing, and the membrane formation was good, and one patient was good after three times of antibiotic-loaded bone cement packing, and the wounds of all five patients healed well after the second stage of skin grafting. Due to the difficulty in maintaining intraoperative blood pressure and infection in all four compartments of the lower leg, a patient underwent emergency knee amputation. Meanwhile, the stump wound was placed with antibiotic-loaded bone cement. The wound was closed directly after the secondary bone cement was removed, and the wound healed in the first stage. (2) The six patients were followed up for 6-24 months after discharge. At the last follow-up, all six patients had good wound healing and no symptoms such as redness, swelling, and exudation. The quality of life of the patients was significantly improved, and all of them were satisfied with the curative effect. (3) The occurrence of calf compartment syndrome should be vigilant when diabetic foot necrotizing fasciitis is highly suspected. Early diagnosis and timely incision decompression are of great importance. Besides, the application of antibiotic-loaded bone cement in the treatment of calf compartment syndrome caused by diabetic necrotizing fasciitis has a good short-term effect. [ABSTRACT FROM AUTHOR]

BACKGROUND: Total knee arthroplasty is the main therapeutic regimen for end-stage osteoarthritis. However, diabetes mellitus can affect the treatment effect and prognosis. OBJECTIVE: To explore the effect of diabetes mellitus on perioperative blood loss and postoperative pain in patients undergoing primary total knee arthroplasty. METHODS: A retrospective study was conducted on 154 patients who underwent primary total knee arthroplasty and met the inclusion criteria in the Osteonecrosis and Joint Reconstruction Ward of Xi’an Honghui Hospital Affiliated to Xi’an Jiaotong University from January to April 2021. Patients were divided into a non-diabetic group and a diabetic group according to their diagnosis, with 32 cases in the diabetic group, 9 males and 23 females, aged 55 to 80 (66.58±7.16) years and 122 cases in the non-diabetic group, 34 males and 88 females, aged 44 to 83 (66.69±6.63) years. Perioperative blood loss (including total blood loss, hidden blood loss, the falling value of hemoglobin and hematocrit) was calculated for both groups. Visual analog scale scores, hospital for special surgery knee score, and Caprini scores were recorded preoperatively and postoperatively. RESULTS AND CONCLUSION: (1) Total blood loss was significantly lower in the non-diabetic group (729.93±233.83 mL) than that in the diabetic group (853.69±184.91 mL) (P < 0.05). Latent hidden blood loss was also significantly lower in the non-diabetic group (624.40±233.19 mL) than that in the diabetic group (749.08±179.49 mL) (P < 0.05). (2) In the non-diabetic group, the visual analog scale scores preoperatively and 1 month postoperatively were significantly lower than those in the diabetic group (P < 0.05). The differences in visual analog scale scores at 3 days and 3 months postoperatively between the nondiabetic group and the diabetic group were not statistically significant (P > 0.05). (3) The hospital for special surgery knee score at 1 month postoperatively was significantly higher in the non-diabetic group than that in the diabetic group (P < 0.05). There was no significant difference in hospital for special surgery knee score between the two groups at 3 months postoperatively (P > 0.05). (4) There was no statistically significant difference in preoperative and postoperative Caprini scores between the two groups (P > 0.05). (5) It is concluded that having diabetes increases total and occult hidden blood loss in primary total knee arthroplasty. In the short term after total knee arthroplasty, diabetes increases the patient’s pain and affects the recovery of joint function, but the negative effects fade with time. [ABSTRACT FROM AUTHOR]

BACKGROUND: Transplantation of stem cell-derived islet β cells has been considered effective for the treatment of type 1 diabetes. Human umbilical cord mesenchymal stem cell is an ideal cellular source, but with a low differentiation efficiency to islet β cells. OBJECTIVE: To explore the possibility of human umbilical cord mesenchymal stem cells modified by MAFA and PDX1 to differentiate into insulin-producing cells. METHODS: MAFA-PDX1 lentivirus expression vectors were constructed. The efficiency and potentiality of human umbilical cord mesenchymal stem cells differentiated into insulin-producing cells with three methods were compared by cell morphology, RT-qPCR, and dithizone staining [protocol A: Simple lentivirus group; protocol B: Drug (nicotinamide β-mercaptoethanol) induction followed by lentivirus group; protocol C: lentivirus and drug induction group]. RESULTS AND CONCLUSION: (1) Morphological change of cells: Cell morphology was all altered after the induction of three protocols. At day 11, human umbilical cord mesenchymal stem cells induced by protocol B showed the most cell clusters among the three protocols, appearing aggregated islet-like cell clusters. (2) Islet-related gene expression detected by RT-qPCR: Horizontal comparison of the three protocols at the same induction time point showed that the expression levels of MAFA and PDX1 genes were the highest in protocol C on day 5 of induction, and those in protocol B were the highest on day 11 of induction. Human umbilical cord mesenchymal stem cells induced by protocol B had the greatest expression of GCG gene at day 5, INS and GLUT2 genes at day 11. (3) Dithizone staining to identify zinc ions: parts of the post-induced cells were stained brownish red by dithizone on day 11. The partial small island cells were stained brownish red with a darker color (positive expression) in protocol B. (4) It is concluded that the overexpression of MAFA and PDX1 can promote the differentiation of human umbilical cord mesenchymal stem cells into insulin-producing cells. The combination of MAFA-PDX1 gene modification and drug induction is superior to the single gene modification. [ABSTRACT FROM AUTHOR]

BACKGROUND: High plantar pressure is one of the critical factors causing diabetic foot ulcers. Studying the plantar pressure in multi-phase during gait cycle of diabetic patients contributes to offloading footwear development. OBJECTIVE: To analyze the plantar pressure distribution in diabetic patients at heel strike and push off, and design midsole to optimize offloading effect. METHODS: Plantar pressure was tested to analyze the difference in plantar pressure at heel strike and push off between diabetics patients with diabetic peripheral neuropathy and without diabetic peripheral neuropathy and healthy subjects. Finite element model of foot was constructed. Ethylene vinyl acetate copolymer midsole and thermoplastic polyurethane diamond lattice structure midsole with different modulus were designed. Changes in plantar pressure and stress of soft tissue at heel strike and push off in diabetic peripheral neuropathy patient were analyzed to optimize the structure size of diabetes footwear. RESULTS AND CONCLUSION: (1) The peak plantar pressure at push off in diabetic peripheral neuropathy group (22.2%) was higher than healthy control group (P < 0.05). (2) Ethylene vinyl acetate copolymer midsole reduced the peak plantar pressure at heel strike and push off by 13.0% and 12.9%, reduced the peak stress of soft tissue at two phases by 18.2% and 11.1%. (3) The optimized diamond lattice structure reduced the peak plantar pressure at two phases by 41.6% and 48.4%, reduced the peak stress of soft tissue at two phases by 41.4% and 49.8%. (4) In conclusion, offloading at push off should be noticed in development of diabetic footwear. The diamond lattice structure midsole could archive better effect than ethylene vinyl acetate copolymer midsole. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the field of pancreatic tissue engineering, constructing biomimetic microenvironment to promote the survival and functional exertion of insulin-secreting cells remains difficult point and hot problem. OBJECTIVE: To construct a biomimetic microenvironment based on gelatin methacrylamide/platelet-rich plasma hydrogel to promote the survival and cellular functional of MIN6. METHODS: 10%, 30% and 50% platelet-rich plasmas were mixed with 50 g/L final concentration of gelatin methacrylamide, gelation by the activation of Ca2+/ thrombin and ultraviolet irradiation (abbreviated as G+10P, G+30P, G+50P). Simultaneously, pure gelatin methacrylamide hydrogel was prepared (denoted as G). The porosity, Young’s modulus, swelling properties and rheological behavior of hydrogels of the four groups were tested. MIN6 cells were seeded on the gel surface, and cell morphology and proliferation were detected, followed by qRT-PCR, immunofluorescence and release assays of insulin. RESULTS AND CONCLUSION: (1) The porosity of the composite-component hydrogel was smaller than that of the single-component hydrogel, and the Young's modulus was higher than that of the single-component hydrogel. Furthermore, the porosity and Young's modulus of the composite hydrogel decreased with the increase of the platelet-rich plasma concentration. The swelling rate of the G+30P and G+50P groups was lower than that of the G and G+10P groups (P < 0.05). The storage modulus and dissipation modulus of the composite hydrogels were higher than those of the single-component hydrogels (P < 0.05). (2) Under the light microscope, the cells on the surface of the monocomponent hydrogel were clumpy and scattered; the cells on the surface of the compositecomponent hydrogel were clumps, but grew faster and the cell clusters were tightly connected. Live-dead staining showed that the hydrogels in each group could promote cell survival; the number of dead cells in G+30P and G+50P groups was significantly less than that in G+10P and G groups. The CCK-8 assay displayed that the composite-component hydrogel had a stronger promoting effect on cell proliferation than the monocomponent hydrogel. Moreover, with the increase of platelet-rich plasma concentration, the promoting effect on proliferation was more obvious. (3) qRT-PCR demonstrated that compared with the monocomponent hydrogel, the composite-component hydrogel could significantly up-regulate the mRNA expression levels of islet-duodenum homeobox 1, insulin, and glucokinase; among them, the G+30P group was the most obvious. Immunofluorescence and insulin release assays exhibited that compared with monocomponent hydrogels, composite-component hydrogels could promote insulin protein expression and insulin release. (4) The results confirm that the gelatin methacrylamide/platelet-rich plasma hydrogel can be used to simulate the microenvironment of insulin-secreting cells and can significantly improve their survivals and functions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Adipose-derived stem cells have a great potential in wound healing and regeneration and we have proven that a direct-current electric-field can promote the proliferation of human adipose-derived stem cells without changing biological characteristics. OBJECTIVE: To investigate the effect of rat adipose-derived stem cells stimulated by a direct-current electric-field on refractory wound healing in diabetic rats. METHODS: (1) Rat adipose-derived stem cells were obtained. After identification, they were pretreated with 100 mV/mm or 0 mV/mm of direct-current electric-field stimulation, with a frequency of 1 h/d, for 3 days. (2) Diabetic refractory wound models were constructed and randomly divided into three groups, with 7 rats in each group, totaling 21 rats. Animals in the electric-field-rat adipose-derived stem cell and rat adipose-derived stem cell groups were injected with 1 mL of electric-field-rat adipose-derived stem cells or normal rat adipose-derived stem cells, respectively, at multiple points of the wound, with a cell concentration of 1×109 cells/L. The PBS group was given the same amount of PBS. (3) At 3, 7, and 14 days after model establishment, the degree of wound healing was observed. Laser speckle contrast imaging was used to record the blood perfusion of rat wounds. The histological changes of wound healing were evaluated by hematoxylin and eosin staining. Microvessels were counted. The expression of vascular endothelial growth factor in the wound tissue was observed by immunohistochemistry. The expression of CD31 was observed by immunofluorescence. RESULTS AND CONCLUSION: (1) Compared the normal rat adipose-derived stem cells and PBS groups, wounds in the electric-field-rat adipose-derived stem cell group were nearly completely healed on day 14, and the wound-healing speed was significantly accelerated (P < 0.05). (2) In the electric-field-rat adiposederived stem cell group, wound epithelization began on day 3. On day 14, the epidermal structure was more complete and continuous in the electric-field-rat adipose-derived stem cell group than those of the other two groups; moreover, the wound angiogenesis was increased (P < 0.05) and the expression levels of vascular endothelial growth factor and CD31 were significantly greater (P < 0.05). (3) The wound blood perfusion of the three groups gradually reached a peak and retreated with the progression of time. The blood perfusion of the electric-field-rat adipose-derived stem cell group was significantly higher than that of the PBS group at different time points after treatment (P < 0.05) and was significantly higher than that of the normal rat adipose-derived stem cell group on day 7 (P < 0.05). (4) The results showed that rat adipose-derived stem cells stimulated by direct-current electric-field exposure could accelerate the healing process of diabetic refractory wounds. The potential mechanism here may be related to the ability of rat adipose-derived stem cells to increase blood perfusion, promote vascular endothelial growth factor expression, and increase the rate of angiogenesis, which provides a new idea for culturing adipose-derived stem cells in vitro and accelerating the actual clinical transformation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diabetes mellitus will cause damage to the hippocampus and induce cognitive dysfunction. Oxidative stress and reduced neurotrophic factor expression are the main mechanism of diabetes-induced hippocampal damage. Long-term regular exercise is a positive intervention for diabetes-induced hippocampal damage; however, the related mechanism still needs further research. OBJECTIVE: To observe the effects of aerobic and resistance exercise on the expression of heat shock protein 70, nuclear factor erythroid 2 p45-related factor 2, heme oxygenase 1, and brain-derived neurotrophic factor in the hippocampus of type 2 diabetic rats. METHODS: The rats that had been fed with high-fat and high-sugar diet for 8 weeks were given a single intraperitoneal injection of streptozotocin to prepare a model of type 2 diabetes. Type 2 diabetic rats were randomly divided into diabetic control group, diabetic aerobic exercise group and diabetic resistance exercise group, with seven rats in each group. Another control rats were randomly divided into quiet control group, aerobic exercise group, and resistance exercise group, with seven rats in each group. The control rats continued to be fed with ordinary feed, while the diabetic rats continued to be fed with highfat and high-sugar diet. The aerobic and resistance exercise lasted for 8 weeks in each exercise group. After 8-week exercises, fasting blood glucose and insulin resistance index were measured. Hematoxylin-eosin staining was used to observe the changes of hippocampal structure. The level of malondialdehyde and the activity of superoxide dismutase in brain were measured. The expression of heat shock protein 70, nuclear factor erythroid 2 p45-related factor 2, heme oxygenase 1, and brain-derived neurotrophic factor in the hippocampus were detected by western blot assay. RESULTS AND CONCLUSION: After 8 weeks of exercise, compared with the quiet control group, fasting blood glucose and insulin resistance index of all diabetic rats were significantly increased (P < 0.01). The hippocampus of all diabetic rats showed pathological changes such as decreased number of vertebral cell layers, cell cavitation, cell necrosis, and disappearance of nucleoli. Compared with the diabetic control group, fasting blood glucose and insulin resistance index were significantly decreased (P < 0.01, P < 0.05) and the pathological changes of the hippocampus, such as cell cavitation, cell necrosis, and disappearance of nucleoli, were alleviated in the two diabetic exercise groups. Compared with the quiet control group, the malondialdehyde level was significantly increased in all diabetic rats (P < 0.01) and the superoxide dismutase activity was significantly decreased in the quiet diabetic group (P < 0.01). Compared with the diabetic control group, the malondialdehyde level was significantly decreased and the superoxide dismutase activity was significantly increased in the two diabetic exercise groups (P < 0.01, P < 0.05). Compared with the quiet control group, the expression levels of heat shock protein 70, nuclear factor erythroid 2 p45- related factor 2, heme oxygenase 1, and brain-derived neurotrophic factor were significantly decreased in all diabetic rats (P < 0.01). Compared with the diabetic control group, the expression levels of heat shock protein 70, nuclear factor erythroid 2 p45-related factor 2, and brain-derived neurotrophic factor were significantly increased in the two diabetic exercise groups (P < 0.05), and the expression of heme oxygenase 1 was significantly increased in the diabetic aerobic exercise group (P < 0.05). To conclude, aerobic and resistance exercises can both increase the expression of heat shock protein 70, nuclear factor erythroid 2 p45-related factor 2, heme oxygenase 1, and brain-derived neurotrophic factor proteins in the hippocampus of diabetic rats, thereby reducing hippocampal oxidative stress and promoting hippocampal nerve repair [ABSTRACT FROM AUTHOR]

BACKGROUND: Some studies have shown that down-regulation of Wnt/β-catenin signaling is closely related to the pathogenesis of cognitive impairments and exercise can delay the pathological process of diabetes, but its molecular mechanism needs further investigation. OBJECTIVE: To investigate the effect and molecular mechanism of 8-week treadmill training on cognitive impairment in diabetic rats. METHODS: A total of 30 male Sprague-Dawley rats were randomly divided into a control group (n=10) and a diabetes model group (n=20) according to the random number table. After the model was successfully established, 10 model rats were randomly selected as the diabetes exercise group. After 8 weeks of exercise intervention, the expressions of neurotrophic factors, cell cycle, apoptosis, aging and Wnt signaling pathway-related proteins in the rat hippocampus of each group were detected by Morris water maze, Nissl and NeuN staining, and western blot assay. RESULTS AND CONCLUSION: The results of Morris water maze showed that compared with the control group, the escape latency of rats was longer, the number of platform crossing was significantly reduced, and the swimming trajectory was more complex in the diabetes model group (P < 0.05). After 8 weeks of treadmill intervention, the escape latency was significantly shortened and the behavioral trajectory was simpler. The Nissl staining results showed that compared with the control group, the Nissl bodies in the hippocampus of diabetic rats were smaller and the number was decreased, with the cell body shrinking, nucleus shrinking and loose arrangement. However, compared with the diabetes model group, the hippocampal Nissl bodies in the diabetes exercise group were increased in size and number, and the morphological structure tended to be normal. Western blot results showed that the expression levels of cAMP response element binding protein and brain-derived neurotrophic factor protein in the diabetes model group were significantly decreased compared with those in the control group (P < 0.001, P < 0.05), while the 8-week treadmill exercise increased their expressions. Meanwhile, compared with the control group, the expression levels of CDK5, cyclin D1 and Caspase-3 were significantly increased in the diabetes model group (P < 0.001, P < 0.05), while the 8-week treadmill exercise reduced the expression of cell cycle and apoptosis-related proteins. In addition, compared with the control group, the expression of Sirt1 protein was significantly down-regulated in the diabetes model group (P < 0.001), and the expressions of p53 and p16 were increased (P < 0.001, P < 0.05). However, the 8-week treadmill exercise reduced the expressions of p53 and p16 proteins (P < 0.05) and increased the level of longevity protein Sirt1 (P < 0.001). In terms of mechanism, the expression level of DKK-1, a negative regulator of Wnt signaling, was increased in the rat hippocampus of the diabetes model group (P < 0.001), while the 8-week treadmill exercise inhibited the expression of DKK-1 (P < 0.001) and reduced the expression levels of Axin1 and β-catenin, downstream key proteins of the Wnt signaling pathway (P < 0.05, P < 0.001). To conclude, treadmill exercise may regulate cell cycle, inhibit apoptosis and promote the secretion of neurotrophic factors by up-regulating the Wnt/β-catenin signaling pathway, thereby improving aging and cognitive impairment in diabetic rats. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is a lack of effective treatment methods to promote the healing of the skin wounds of diabetic patients. Human umbilical cord mesenchymal stem cells have been proven to have a variety of therapeutic effects on skin regeneration. Injectable hydrogels have good biocompatibility and adjustability, which can improve the effect of stem cell therapy. OBJECTIVE: Taking the hydrogel loaded with human umbilical cord mesenchymal stem cells as a starting point, to observe its curative effect on diabetic skin wounds in mice, and explore the possible mechanism of action. METHODS: (1) A diabetic model of C57BL/6J mouse was constructed by continuous intraperitoneal injection of streptozotocin solution for 5 days, and the success of the model was evaluated by blood glucose values collected from the tail vein. (2) A mouse back skin injury model was established by using a puncher. The hydrogel group was treated with pure hydrogel. The composite hydrogel group was treated with hydrogel loaded with human umbilical cord mesenchymal stem cells. The control group was treated with the same amount of normal saline. The wound healing was observed on the 7th and 14th days of treatment. RESULTS AND CONCLUSION: (1) The skin wound area of mice in the composite hydrogel group and hydrogel group was significantly smaller than that in the control group at 14 days after gum application (P < 0.05). The skin wound area of mice was significantly smaller in the composite hydrogel group than that in the hydrogel group (P < 0.05). (2) Hematoxylin-eosin staining results illustrated that the new granulation tissue in the composite hydrogel group was significantly more than that in the control group and hydrogel group (P < 0.05). (3) Masson’s staining results clarified that the collagen deposition in the composite hydrogel group was significantly increased compared with the control group and hydrogel group (P < 0.05). (4) The results of immunohistochemical CD31 staining confirmed that the number of new microvessels in the skin trauma was significantly higher in the composite hydrogel group than that in the control group and hydrogel group (P < 0.05). (5) The results of immunohistochemical CD45 staining showed that the area of inflammation in the new skin was significantly reduced in the composite hydrogel group compared with the control group and hydrogel group (P < 0.05). (6) The results of immunofluorescence staining and qRT-PCR showed that compared with the control group and hydrogel group, the amount of M2 macrophages and the level of interleukin 10 in the trauma tissue were significantly higher, and the amount of M1 macrophages and the level of interleukin 6 were significantly lower in the composite hydrogel group (P < 0.05). (7) The above results illustrate that the chlorinated chitosan-β-sodium glycerophosphate composite hydrogel loaded with human umbilical cord mesenchymal stem cells can promote the formation of granulation tissue and microvessels on diabetic wounds, reduce inflammatory response, and promote wound repair. [ABSTRACT FROM AUTHOR]

BACKGROUND: Xianling Gubao Capsules (a commonly used Chinese medicine in orthopedic surgery) can improve bone metabolism and prevent osteoporosis; however, whether it has a preventive effect or a possible mechanism on osteoporosis complicated by diabetes has been rarely reported. OBJECTIVE: To investigate the effects of Xianling Gubao Capsules on bone metabolism and related osteogenic marker factors Wnt3a, β-catenin and bone morphogenetic protein-2 in rats with diabetes mellitus complicated by osteoporosis and to explore their mechanisms of action. METHODS: Thirty-six male healthy 8-week-old Sprague-Dawley rats were treated with streptozotocin at a dose of 60 mg/kg to establish a diabetes mellitus model and were then randomly divided into model group, Xianling Gubao Capsule group and alendronate group, with 12 rats in each group. Another 12 normal rats were used as the normal group. Rats in the Xianling Gubao Capsule group and alendronate group were given Xianling Gubao Capsule and alendronate sodium suspension by gavage for 12 weeks, respectively. Rats in the normal and model groups were gavaged with the same amount of double-distilled water for 12 weeks. Blood glucose level of model rats was measured once a week during the administration period to ensure the accuracy of the experiment. Femur, tibia and systemic bone mineral density in each group were measured by dual energy X-ray absorptiometry. Hematoxylin-eosin staining was used to observe the morphological changes of the right femur in each group. Immunohistochemistry and RT-PCR were applied to detect the expression of osteogenic marker factors Wnt3a, β-catenin, and bone morphogenetic protein-2 at protein and mRNA levels. RESULTS AND CONCLUSION: Compared with the model group, the femur, tibia and systemic bone mineral density values of rats increased significantly in the Xianling Gubao Capsule group (P < 0.05). The mRNA and protein expressions of Wnt3a, β-catenin, and bone morphogenetic protein-2 in bone tissues decreased significantly in the model group (P < 0.05). While compared with the model group, the mRNA and protein expressions of Wnt3a, β-catenin, and bone morphogenetic protein-2 were significantly increased in the Xianling Gubao Capsule group (P < 0.05). In addition, there was no significant difference in the expressions of above-mentioned indicators between the Xianling Gubao Capsule group and alendronate group. These findings confirmed that Xianling Gubao Capsules exert a protective effect on bone metabolism in diabetic rats by the Wnt /β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Wentong Huoxue Cream can improve oxidative stress, reduce blood viscosity, restore microcirculation, relieve diabetic peripheral nerve injury, and inhibit sensory conduction and pain formation, but its regulatory mechanism remains unclear. OBJECTIVE: To observe the effects of Wentong Huoxue Cream on JNK signaling pathway proteins and inflammatory factors in diabetic peripheral neuropathy rats. METHODS: A rat model of diabetic peripheral neuropathy was established in adult Wistar rats. Forty diabetic peripheral neuropathy rats were randomly divided into five groups (n=8 per group): model group, low-, middle- and high-dose Wentong Huoxue Cream groups (given 2 mL of 0.75, 1.5, 3.0 g/mL Wentong Huoxue Cream to the lower limbs of rats, respectively) and Western medicine group (given 2 mL of control cream). Skin treatment in each group was performed twice a day for 28 days. Additionally, six rats were taken as normal group. After the last administration, nerve conduction tests were performed and the expressions of interleukin-6, interleukin-18, tumor necrosis factor α, high-sensitivity C-reactive protein, and myelin basic protein in serum were detected by ELISA. The expression of JNK and P-JNK protein in sciatic ganglia was detected by western blot and the expression of JNK mRNA was determined by RT-PCR. RESULTS AND CONCLUSION: The velocity of sensory nerve conduction and motor nerve conduction was significantly decreased in the model group compared with the normal group (P < 0.05). Compared with the model group, the sensory nerve conduction velocity increased significantly after intervention with different doses of Wentong Huoxue Cream (P < 0.05), especially in the high-dose Wentong Huoxue Cream group (P < 0.05). Compared with the model group, the motor nerve conduction velocity was significantly increased in the high-dose Wentong Huoxue Cream group and Western medicine group (P < 0.05). Compared with the normal group, the serum levels of interleukin-6, tumor necrosis factor α, high-sensitivity C-reactive protein, and myelin basic protein were significantly increased (P < 0.05) and the serum level of interleukin-18 was significantly decreased in the model group (P < 0.05). Compared with the model group, the serum levels of interleukin-6, interleukin-18, tumor necrosis factor α, high-sensitivity C-reactive protein, and myelin basic protein were significantly decreased in all the treatment groups (P < 0.05), especially in the high-dose Wentong Huoxue Cream group and Western medicine group. Compared with the normal group, p-JNK protein and JNK mRNA expression levels were significantly increased in the model group (P < 0.05). Compared with the model group, p-JNK protein and JNK mRNA expression levels were significantly decreased in the middle- and high-dose Wentong Huoxue Cream groups and Western medicine group (P < 0.05). Therefore, Wentong Huoxue Cream can inhibit the abnormal activation of JNK signal transduction pathway, reduce inflammatory reactions, and protect the peripheral nerve function of diabetic peripheral neuropathy rats. [ABSTRACT FROM AUTHOR]

BACKGROUND: Up to now, dental implant has become an important restoration for patients with tooth loss, and bone formation around dental implants is the key to the success of dental implantation. There is often a poor bone formation around dental implants under diabetic conditions and the mechanism remains unclear. Recent studies have shown that miR-203-3p regulates bone formation in different diseases, and strongly expressed in jaw bone tissues under diabetic conditions. However, it is unclear whether miR-203-3p can influence bone formation around dental implants. OBJECTIVE: To investigate the effect of inhibiting miR-203-3p expression on bone formation around dental implants in diabetic mice. METHODS: Twelve mice with normal blood glucose were randomly selected as normal group from forty-eight C57BL/6J mice. The other 36 mice were selected to make diabetic models and then randomly divided into diabetic group, diabetes+antago miR-NC group, and diabetes+antago miR-203-3p group (n=12 per group). Single implant was inserted into the left maxilla of each mouse. Diabetic+antago miR-NC group was injected with antago miR-203-3p negative control, antago miR-NC (0.25 mmol/L). Diabetes+antago miR-203-3p group was injected with antago miR-203-3p (0.25 mmol/L). The other two diabetic groups were injected with the equal volume of normal saline. After 3 months, the left maxillary bone tissue of mice was collected, and the bone formation around dental implants was detected using micro-CT and hematoxylin-eosin staining. qRT-PCR was used to detect the gene expression of miR-203-3p, Smad1, alkaline phosphatase, Runx2, Osterix, and type I collagen in bone tissue around dental implants. RESULTS AND CONCLUSION: Micro-CT results showed that compared with the diabetic group and diabetes+antago miR-NC group, the diabetes+antago miR203-3p group showed better alveolar bone formation around dental implants and higher bone volume fraction and bone trabecular thickness (P < 0.05). Hematoxylin-eosin staining results showed that the Lane-Sandhu score of bone formation around dental implants was higher in the diabetes+antago miR-203- 3p group than the diabetic group and the diabetes+antago miR-NC group (P < 0.05). qRT-PCR results showed that the expression level of miR-203-3p gene in bone tissue around dental implants was lower (P < 0.05), while the expression levels of Smad1, alkaline phosphatase, Runx2, Osterix, and type I collagen genes were higher in the diabetes+antago miR-203-3p group than the diabetic group and the diabetes+antago miR-NC group (P < 0.05). All these findings indicate that the inhibition of miR-203-3p expression is beneficial to bone formation around dental implants in diabetic hyperglycemia, and these effects may be related to the regulation of Smad signaling pathway and the expression of osteogenesis-related factors such as alkaline phosphatase, Runx2, Osterix, and type I collagen. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hyperglycemia caused by diabetes are closely related to male infertility, and Ganoderma lucidum spores are considered to be anti-aging and improve blood glucose levels. However, the protective effect of Ganoderma lucidum spores on diabetic epididymis remains unclear. OBJECTIVE: To investigate the protective effects of Ganoderma lucidum spores on diabetic epididymis. METHODS: Male Sprague-Dawley rats were randomly divided into normal group (n=10), high fat/high glucose group (n=10), and model group (n=20). Rats in the normal group were fed with normal diet, while those in the high fat/high glucose group and model group were fed with high fat and high glucose diet. The rats in the model group were then intraperitoneally injected with streptozotocin (30 mg/kg) to induce diabetes mellitus. Model rats were randomly divided into diabetes mellitus group (n=10) and Ganoderma lucidum spores group (GLS, n=10). The rats in the GLS group were treated with Ganoderma lucidum spores (300 mg/kg per day) by gavage, and the rats in the high fat/high glucose group and diabetes mellitus group were gavaged with the equal volume of normal saline and fed with high fat and high glucose diet for 12 weeks. Body mass, fasting blood glucose, superoxide dismutase activity, malondialdehyde level and sperm deformity rate were measured in each group. Structural changes in the epididymis in diabetic rats were observed by hematoxylin-eosin staining. The protein expression levels of cleaved caspase-3, beclin1, p62, and LC3 in the rat epididymal tissue were detected by western blot and immunohistochemical staining. RESULTS AND CONCLUSION: Ganoderma lucidum spores could significantly recovery epididymal function, improve the epididymal histopathology, and promote cell autophagy and antioxidant capacity. Immunohistochemical staining results showed that the immune intensity of p62 and cleaved caspase-3 decreased significantly. Western blot analysis showed that Ganoderma lucidum spores obviously upregulated beclin1 and LC3 protein expression levels and decreased p62 and Cleaved caspase-3 protein expression levels when compared with the diabetes mellitus group. To conclude, Ganoderma lucidum spores may induce autophagy, increase antioxidant capacity and inhibit apoptosis to protect against epididymal injury in diabetic rats. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diabetes is prone to cause multiple organ diseases in the body. Periodontitis is one of the complications. The more severe the inflammation of periodontitis is, the less favorable it is for glycemic control. OBJECTIVE: To investigate the effect of periodontitis on autophagy of pancreatic tissue in a rat model of type 2 diabetes mellitus. METHODS: Forty 6-week-old male Sprague-Dawley rats were randomly divided into a control group and an experimental group, and rats in the experimental group were subdivided into three groups (n=10 per group): a diabetes group, a periodontitis group, and a diabetes+periodontitis group. High fat and high sugar feeding+intraperitoneal injection of streptozotocin was used to establish a diabetic model, and silk thread ligation was used to establish a periodontitis model. Enzyme-linked immune sorbent assay was used to detect the expression of inflammatory factors in rat serum. Real-time fluorescent quantitative PCR was used to detect the expression of autophagy and insulin secretion-related genes in rat pancreatic tissue. Western blot was used to detect the protein expression of autophagy-related in rat pancreatic tissue. RESULTS AND CONCLUSION: The results of enzyme-linked immunosorbent assay showed that the expression of tumor necrosis factor α, interleukin 1β, and interleukin 6 was increased sequentially in the diabetes group, the periodontitis group, and the diabetes+periodontitis group compared with that in the control group (P < 0.05). The results of real-time fluorescent quantitative PCR showed that, compared with the control group, the mRNA expression of glucokinase and recombinant glucose transporter 2 was decreased in the diabetes group and the diabetes+periodontitis group, especially in the diabetes+periodontitis group (P < 0.05). At the same time, the mRNA expression of uncoupling protein 2, Beclin1, and LC3II was increased in the diabetes group and the diabetes+periodontitis group, and increased most in the diabetes+periodontitis group (P < 0.05). However, there was no significant difference between the periodontitis group and the control group (P > 0.05). The results of western blot showed that, compared with the control group, the expression of Beclin1, LC3II/LC3I was increased in the diabetes group and the diabetes+periodontitis group, and increased most in the diabetes+periodontitis group (P < 0.05). And there was no significant difference between the periodontitis group and the control group (P > 0.05). Therefore, it is speculated that type 2 diabetes mellitus with periodontitis may induce excessive autophagy of pancreatic islet cells, then impact the secretion function of insulin in islet cells, and finally aggravate the development of diabetes mellitus in the rat models. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diabetes can cause dysfunction of the whole body tissues and organs. 6-Phosphofructokinase-2/fructose bisphosphatase-2 isoenzyme 3 (PFKFB3) and sphingosine 1-phosphate receptor 2 (S1P2) may be related to the complications of diabetes. Tertiary butylhydroquinone has a certain protective effect on the complications of diabetes. OBJECTIVE: To study the expression of PFKFB3 and S1P2 in various organs (heart, retina, kidney, and aorta) of type 2 diabetic rats and to explore the relationship between tertiary butylhydroquinone and PFKFB3 and S1P2. METHODS: Twenty-four male Sprague-Dawley rats were divided into normal control group, diabetic group and tertiary butylhydroquinone group. Diabetic models were made in the latter two groups. At 7 days after modeling, the rats in the tertiary butylhydroquinone group were fed with high-fat and high-sugar diet containing 1% tertiary butylhydroquinone, while those in the diabetic group continued to be fed with high-fat and high-sugar diet. After 12 weeks of intervention, the blood glucose and insulin levels were detected; immunohistochemistry and qRT-PCR were used to detect the distribution and expression of PFKFB3 and S1P2 at protein and mRNA levels, respectively; and TUNEL method was used to detect the apoptosis index in different rat organ cells. RESULTS AND CONCLUSION: There was an overall significant difference in the blood glucose and insulin levels between groups (P=0.000, P=0.000). PFKFB3 and S1P2 were mainly distributed in the retinal ganglion cell layer, the inner nuclear layer, aortic intima endothelial cells, cardiomyocytes, interstitial myocardial endothelial cells, and renal tubular cells. The relative protein and mRNA levels of PFKFB3 and S1P2 were significantly different in the retina, aortic intimal endothelial cells, cardiomyocytes, interstitial myocardial endothelial cells, and renal tubular cells (all P < 0.05). The overall difference in the relative expression of S1P2 protein and mRNA in the glomerulus was statistically significant (all P < 0.05). Compared with the normal control group, the expression of PFKFB3 and S1P2 was significantly increased in the diabetic group (P < 0.05), while compared with the diabetic group, the expression of PFKFB3 and S1P2 was significantly decreased in the tertiary butylhydroquinone group (P < 0.05). TUNEL results indicated that there was an overall significant difference in the apoptotic index of rat retinal ganglion cells, cardiomyocytes, renal tubular cells, and aortic full-thickness cells between groups (all P < 0.05). The overall apoptotic index of various organs in the diabetic group was significantly higher than that in the normal control group (P < 0.05), while compared with the diabetic group, the overall apoptotic index was significantly reduced in the tertiary butylhydroquinone group (P < 0.05). To conclude, PFKFB3 and S1P2 are the metabolites involved in the pathological process of various organs in diabetic rats and may be related to the apoptosis of cells in various organs of diabetic rats. Tertiary butylhydroquinone can reduce the expression of PFKFB3 and S1P2 and reduce cell apoptosis in various organs, indicating that tertiary butylhydroquinone has a certain protective effect on various organs of type 2 diabetic rats. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recent studies have found that exercise can improve myocardial fibrosis in type II diabetic rats. OBJECTIVE: To investigate the regulatory role of angiotensin II/transforming growth factor β1/Smad2 signaling pathway and its downstream factors in the process of diabetic myocardial fibrosis through swimming exercises in an animal model of diabetic myocardial fibrosis. METHODS: Forty male Sprague-Dawley rats were randomly divided into two groups: a blank control group (n=10) and a diabetes model group (n=30). Rats in the blank control group were raised under a normal diet, and rats in the diabetes model group were fed with high-sugar and high-fat diet and treated with a single injection of 1% streptozotocin to establish a diabetic model. After successful modeling, 15 rats were randomly selected from the diabetes model group as a diabetes exercise group. Rats in the diabetes exercise group were subjected to non-weight bearing swimming, 60 minutes per day, 6 days per week. After training for 8 weeks, the fasting blood glucose and fasting insulin levels of rats were tested. Hematoxylin-eosin staining was used to observe the morphological changes of myocardial cells. Masson staining was used to observe the deposition of collagen fibers in the myocardial interstitium. Immunohistochemical staining was used to analyze the content of type I and III collagen fibers in myocardial tissue. Reverse transcription PCR was used to detect the mRNA expression of angiotensin II, type I collagen fiber, type III collagen fiber, transforming growth factor β1, and Smad2. RESULTS AND CONCLUSION: Compared with the blank control group, the fasting blood glucose level and insulin resistance index were increased in the diabetes model group (P < 0.01). Compared with the diabetes model group, the fasting blood glucose and insulin resistance index were decreased in the diabetes exercise group (P < 0.05). Results of hematoxylin-eosin staining and Masson staining showed that disordered arrangement of myocardial cells, widened intercellular space, inflammatory cell infiltration, and obvious myocardial fibrosis in the diabetic model group. Whereas the arrangement of myocardial cells was still in order, the intercellular space was basically normal, and myocardial fibrosis was significantly relieved in the diabetic exercise group compared with the diabetic model group. The content of type I collagen fibers in rat myocardial tissue was increased in the diabetic model group compared with the blank control group (P < 0.05). There was no significant difference in the content of type I and III collagen fibers in rat myocardial tissue between the diabetic model group and the diabetic exercise group (P > 0.05). Compared with the blank control group, the mRNA expression of type I collagen fibers and transforming growth factor β1 in rat myocardial tissue was increased in the diabetic model group (P < 0.05). Compared with the diabetic model group, the mRNA expression of type I and III collagen fibers and transforming growth factor β1 in rat myocardial tissue was decreased in the diabetic exercise group (P < 0.01). To conclude, swimming can effectively prevent the occurrence and development of diabetic myocardial fibrosis, which may be related to the inhibition of the angiotensin II/ transforming growth factor β1/Smad2 pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Our previous studies have confirmed that diabetes mellitus promotes the occurrence and development of periodontitis. However, it is unclear whether periodontitis can promote the development of diabetes. OBJECTIVE: To explore the molecular mechanism by which periodontitis promotes the development of diabetes mellitus. METHODS: Mouse βtc6 insulinoma cells cultured in vitro were divided into control group, glucose group, lipopolysaccharide group, and glucose+lipopolysaccharide group. The cells in the latter three groups were treated with different concentrations of glucose (0, 25, 50, 100 mmol/L) and lipopolysaccharide (0, 10, 20, 40 mg/L) alone or in combination for 12 hours. Insulin secretion was measured in each group. In addition, 3-methyladenine (an autophagy inhibitor, 5 μmol/L) and rapamycin (an autophagy activator, 10 mmol/L) were used to intervene with the phosphatidylinositol 3-kinase/rotein kinase B/the mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. The cells were then further divided into rapamycin+lipopolysaccharide group, rapamycin+glucose group, rapamycin+glucose+lipopolysaccharide group, 3-methyladenine+lipopolysaccharide group, 3-methyladenine+glucose group, and 3-methyladenine+glucose+lipopolysaccharide group. The cell counting kit-8 method was used to detect the proliferation of βtc6 cells. Fluorescent probes were used to detect the amount of reactive oxygen species in βtc6 cells. Production of autophagosomes in βtc6 cells was observed by transmission electron microscopy. Western blot method was used to detect the expression of autophagy proteins and PI3K/AKT/mTOR signaling pathway-related proteins. RESULTS AND CONCLUSION: The insulin secretion was out of control as the glucose concentration exceeded 50 mmol/L (P > 0.05), whereas the insulin secretion was inhibited as the lipopolysaccharide concentration exceeded 20 mg/L (P < 0.05). After addition of 3-methyladenine, the expression levels of Becline1, p-PI3K, p-AKT/AKT, p-AKT/AKT, p-AKT/AKT, and p-PI3K were significantly decreased in the 3-methyladenine+glucose group, 3-methyladenine+lipopolysaccharide group, and 3-methyladenine+lipopolysaccharide+glucose group compared with the control group. While the expression of p62 protein showed the opposite trend (P < 0.05). After addition of rapamycin, the expression of Becline1, p-PI3K, and p-mTOR/mTOR was significantly increased in comparison with the control group (P < 0.05). These findings indicate that lipopolysaccharides can induce excessive autophagy of pancreatic β cells and downregulate insulin secretion. This mechanism may be related to the silencing of PI3K/AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diabetes belongs to the category of “diabetes” in traditional Chinese medicine. According to the development process and clinical manifestations of the disease, there are often different syndrome manifestations. In most cases, excessive heat mainly appears in the early stage, which is called excessive heat type diabetes, and deficiency of both qi and yin is mainly present in the middle and late stages, which is called deficiency of both qi and yin type diabetes. OBJECTIVE: To establish a mouse model of interior heat and diabetes by compound method, which can reflect the characteristics of traditional Chinese medicine symptoms, and lay a foundation for studying the evolution of diabetes and related drugs. METHODS: Thirty ICR mice were randomly divided into blank control group, short-term model group and long-term model group. The short-term model group was intraperitoneally injected with 40 mg/kg streptozotocin for 5 consecutive days, and then given 20 g/kg warm drugs via gavage for 14 days to establish the interior heat and diabetes model. On the basis of short-term models, the long-term model group was given the same dose of warm drugs for 21 days. The body mass, fasting blood glucose, water intake, food intake, urine volume and serum insulin levels of mice in each group were measured after modeling. Insulin resistance index and insulin sensitivity index were calculated. The activities of mitochondrial respiratory chain complexes III and V in liver and kidney tissues were measured. Hematoxylin-eosin staining was used to detect the pathological changes of mouse pancreas. The study protocol was approved by the Animal Ethics Committee of Henan University of Chinese Medicine (approval No. DWLL202003270). RESULTS AND CONCLUSION: Compared with the blank control group, the mice in the short-term and long-term model groups showed typical symptoms of diabetes, such as polydipsia, polyuria, body mass loss, rise in the rectal temperature (P < 0.05); the levels of fasting blood glucose and insulin resistance index were significantly increased; the levels of insulin sensitivity index were significantly decreased (P < 0.05); and the activities of mitochondrial respiratory chain complexes III and V in liver and kidney tissues were significantly increased (P < 0.05). The pancreatic tissue of mice in the short-term and long-term model groups was damaged in varying degrees by pathological observation of the pancreas. Compared with the short-term model group, the long-term model group had more drinking, more food, more urine, slower growth of body mass, and significantly lower rectal temperature with the progression of the disease (P < 0.05); the levels of fasting blood glucose and insulin resistance index were significantly increased, while the levels of insulin sensitivity index were significantly decreased (P < 0.05); the activities of mitochondrial respiratory chain complexes III and V in liver and kidney tissues were significantly decreased (P < 0.05). Pathological findings indicated that the pancreatic function was further damaged in the long-term model group as the disease progressed. To conclude, the combination of streptozotocin and warm drugs for modeling can improve the disease-syndrome further combination model of interior heat and diabetes, and in the model, the syndrome is evolved. The short-term model shows excessive heat and the long-term model shows deficiency of both qi and yin. [ABSTRACT FROM AUTHOR]

BACKGROUND: Long noncoding RNA (LncRNA)-DANCR can regulate multiple biological processes, including bone metabolism. Our gene microarray results showed that LncRNA-DANCR was significantly overexpressed in diabetic osteoporosis mice. OBJECTIVE: To investigate the effect of LncRNA-DANCR on the osteogenic ability of adipose stem cells in diabetic osteoporosis through Wnt/β-catenin signaling pathway. METHODS: Diabetic osteoporosis adipose-derived stem cells and control adipose-derived stem cells were isolated and cultured. After 3 days of osteogenic induction, real-time fluorescence quantitative PCR and western blot assay were used to examine the expression of LncRNA-DANCR, Wnt signaling molecules β-catenin and osteogenic transcription factors (RUNX2 and OPN). Diabetic osteoporosis adipose-derived stem cells transfected with lncRNA-DANCR-specific siRNA were designed. After 3 days of osteogenic induction, real-time fluorescence quantitative PCR, western blot assay and alkaline phosphatase staining were used to examine the expression of Wnt signaling molecules β-catenin, osteogenic transcription factors RUNX2 and OPN and osteogenic ability changes. RESULTS AND CONCLUSION: (1) After 3 days of osteogenic induction, the expression level of LncRNA-DANCR in diabetic osteoporosis adipose-derived stem cells group was significantly higher than that in control group. The expression levels of Wnt signaling molecule β-catenin and osteogenic transcription factors RUNX2 and OPN were significantly lower than those in control adipose-derived stem cells. (2) After 3 days of osteogenic induction, β-catenin and RUNX2 and OPN were highly expressed in the siRNA silent group, and the ability of bone formation was enhanced. (3) The results confirmed that LncRNA-DANCR decreased the osteogenic capacity of diabetic osteoporosis adipose-derived stem cells by inhibiting the Wnt/β-catenin signaling pathway. Silencing of LncRNA-DANCR can restore the reduced osteogenic capacity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Preliminary studies have confirmed that deep seawater not only affects the tolerance and immunity of mice, but also has an important regulatory effect on wound repair. OBJECTIVE: To explore the effect of deep seawater on the PI3K/Akt pathway in the process of wound repair in diabetic mice. METHODS: Forty-eight Kunming mice were enrolled to establish a diabetes model. A 1 cm2 wound was made on the back after successful modeling, and all the mouse models were randomized into four groups for corresponding treatments, including drinking purified water (control), tap water, deep seawater and deep seawater+LY294002, with 12 rats in each group. On the 3rd, 7th, and 10th days after wound modeling, the wound healing was observed, and western blot was used to detect the expression levels of vascular endothelial growth factor, basic fibroblast growth factor, hypoxia-inducible factor 1α, p-PI3K, p-Akt, PI3K and Akt in the wound tissue. qRT-PCR and western blot were used to detect the expression levels of collagen type I, collagen type III, interleukin-1β, tumor necrosis factor-α and transforming growth factor-β1 mRNA. On the 3rd and 10th days after wound modeling, hematoxylin-eosin staining was used to observe the morphological changes of the wound. The study protocol was approved by the Animal Ethic Committee of Kunming Institute of Zoology, Chinese Academy of Science with an approval No. KPRC-2017091. RESULTS AND CONCLUSION: The wound healing rate of the deep seawater group was higher than that of the control group and the tap water group (P < 0.01), while there was no significant difference in the wound healing rate between the tap water group and deep seawater+LY294002 group (P > 0.05). Hematoxylineosin staining showed that there were a large number of inflammatory cells infiltrated and a few fibroblasts on the wound surface in the control group, tap water group, and deep seawater+LY294002 group on the 3rd day, and granulation tissue, capillaries and fibroblasts were visible on the 10th day. In the deep seawater group, fibroblasts, capillaries and a few inflammatory cells were seen on the 3rd day, and new granulation tissue, more collagen fibers and a few capillaries were seen on the 10th day. Western blot analysis showed that the expressions of vascular endothelial growth factor, basic fibroblast growth factor, hypoxia-inducible factor 1α, p-PI3K and p-Akt in the deep seawater group were higher than those in the control group and the tap water group on each observational time point (P < 0.01). qRT-PCR and western blot results showed that the expressions of collagen type I, collagen type III and transforming growth factor-β1 in the deep seawater group were higher than those in the control group and deep seawater+LY294002 group on each observational time point (P < 0.05 or P < 0.01), while the expression levels of interleukin-1β and tumor necrosis factor-α were lower than those in the control group and deep seawater+LY294002 group (P < 0.05 or P < 0.01). To conclude, deep seawater can promote wound healing in diabetic mice via activating the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have suggested that intervention for the expression of brain-derived neurotrophic factor and nuclear factor-κB in the skeletal muscle is beneficial to improve the glucose and lipid metabolism of the skeletal muscle. Whether exercise has a positive intervention effect on the above indicators in the skeletal muscle of type 2 diabetic rats is rarely reported. OBJECTIVE: To observe the effects of aerobic and resistance exercises on the expression of brain-derived neurotrophic factor, nuclear factor-κB and inflammatory indexes in the skeletal muscle of type 2 diabetic rats. METHODS: Type 2 diabetic rats were made through high-fat and high-sugar diet combined with low-dose streptozotocin and randomly divided into diabetic control group, diabetic aerobic exercise group and diabetic resistance exercise group. In the diabetic control group, the rats were randomly divided into a quiet control group, an aerobic exercise group, and a resistance exercise group. The aerobic and resistance exercise lasted for 8 weeks. After 8-week exercises, fasting blood glucose, insulin resistance index, triglyceride, total cholesterol, low density lipoprotein, wet weight of gastrocnemius muscle and mass fraction of gastrocnemius muscle were measured. Hematoxylin-eosin staining was used to observe the changes of gastrocnemius muscle structure, The changes of interleukin-1β, interleukin-10 and tumor necrosis factor-α in gastrocnemius muscle were detected by ELISA. The expression of brain-derived neurotrophic factor and nuclear factor-κB in gastrocnemius muscle were detected by western blot. RESULTS AND CONCLUSION: Compared with the quiet control group, fasting blood glucose, insulin resistance index, triglyceride, total cholesterol, low density lipoprotein of all diabetic rats increased; the wet weight of gastrocnemius muscle decreased, and microscopic examination indicated skeletal muscle atrophy and inflammatory lesions; the expression of nuclear factor-κB in skeletal muscle increased, and the level of tumor necrosis factor-α increased; and the expression of brain-derived neurotrophic factor protein in skeletal muscle increased significantly. After 8 weeks of exercise, compared with the diabetic control group, all the blood glucose and lipid indexes in the two diabetic exercise groups decreased, inflammatory cell infiltration, atrophy and degeneration of skeletal muscles were reduced, the wet weight and mass fraction of gastrocnemius muscle increased, the expression of nuclear factor-κB and tumor necrosis factor-α in skeletal muscle decreased, and the expression of brain-derived neurotrophic factor increased significantly in the diabetic aerobic exercise group. Compared with the diabetic aerobic exercise group, the fasting blood glucose and nuclear factor-κB expression in skeletal muscle were significantly reduced in the diabetic resistance exercise group (P < 0.05), the wet weight and mass fraction of gastrocnemius muscle increased significantly (P < 0.05); however, the blood lipid indexes were significantly lower in the diabetic aerobic exercise group than the diabetic resistance exercise group (P < 0.05, P < 0.01). To conclude, both aerobic exercise and resistance exercise can promote the expression of brain-derived neurotrophic factor in skeletal muscle of diabetic rats and improve blood lipid metabolism. Resistance exercise can reduce the expression of nuclear factor-κB protein, reduce the level of tumor necrosis factor-α, improve the inflammation of skeletal muscle, and improve blood glucose level in diabetic rats. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Transverse tibial bone transport technique is an emerging treatment for diabetic foot in recent years. At present, a large number of studies have confirmed its significant efficacy and high safety in the treatment of diabetic foot, but there is still a lack of evidence. Therefore, a Meta-analysis on the treatment of diabetic foot by transverse tibial bone transport technique was conducted. METHODS: CNKI, VIP, WanFang, PubMed, Cochrane library, and EMbase were searched for randomized controlled trials regarding transverse tibial bone transport technique for the treatment of diabetic foot. The retrieval time was from inception to February 2020. The quality of the included literature was strictly evaluated, and the Rev Man5.3 software was used for the meta-analysis of amputation rate, healing rate, healing time, skin temperature and Visual Analogue Scale pain score. RESULTS: A total of 8 randomized controlled trials involving 837 cases were included, with 428 cases in treatment group and 409 in control group. The literature quality evaluation results showed that: the quality evaluation of the case-control experiment was carried out according to the Newcastle-Ottawa Scale, with 2 papers scoring 7 points; according to the improved Jadad scale, four randomized controlled trials were evaluated with 4 marks and two evaluated with 2 marks. Meta-analysis results showed that compared with the control group, the amputation rate [odds ratio (OR)=0.12, 95% confidence interval (CI) (0.05, 0.26), P < 0.000 01), healing rate [OR=28.65, 95%CI (16.45, 49.88), P < 0.000 01), healing time (OR=2.61, 95%CI (-4.23, -0.98), P=0.002], skin temperature (OR=2.44, 95%CI (2.27, 2.61), P < 0.000 01), Visual Analogue Scale score (standard mean difference=-6.41, 95%CI (-9.50, -3.32), P < 0.000 1) were all improved in the treatment group with transverse tibial bone transport for treating diabetic foot . CONCLUSION: Transverse tibial bone transport technique is of high safety and has significant advantages over conventional treatments in the treatment of diabetic foot. Limited by the quantity and quality of included studies, the above conclusions need to be verified by more high-quality studies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Stem cell transplantation has been used in the clinical treatment of diabetic lower limb vascular diseases. The conclusions were inconsistent due to the small sample size of each study. This article systematically reviewed the safety and efficacy of stem cells transplantation for diabetic patients with lowerextremity arterial disease. METHODS: PubMed, The Cochrane Library (Issue 11, 2019), EMbase, CNKI, CBM, VIP and Wanfang databases were electronically searched to collect randomized controlled trials of stem cell transplantation for diabetic patients with lower-extremity arterial disease from inception to December 10, 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies. Meta-analysis was then performed using RevMan 5.3 software. RESULTS: A total of 13 randomized controlled trials involving 546 patients, with 287 patients in stem cell transplantation group and 259 patients in conventional treatment group were included. The meta-analysis results showed that compared with the conventional treatment group, stem cell transplantation could significantly decrease the rate of lower limb amputation (RR=0.29, 95%CI: 0.10-0.84, P=0.02], improve the collateral angiogenesis (RR=3.16, 95%CI: 2.12-4.70, P < 0.000 01), increase ankle brachial pressure index (MD=0.17, 95%CI: 0.10-0.24, P < 0.000 01), transcutaneous oxygen pressure (MD=7.71, 95%CI: 3.99- 11.43, P < 0.000 01), skin temperature (MD=1.90, 95%CI: 1.28-2.53, P < 0.000 01) and intermittent limp distance (MD=150.61, 95%CI: 43.49-257.74, P=0.006), reduce the scores of rest pain (MD=-1.16, 95%CI: -1.92 to -1.30, P < 0.000 01), and cold feeling (MD=-2.00, 95%CI: -2.49 to -1.50, P < 0.000 01). No severe complications such as death, neoplasm, or hepatorenal function impairment were observed in all of our included studies. CONCLUSION: Stem cell transplantation maybe an effective and safe therapeutic method for diabetic patients with lower-extremity arterial disease. However, due to the limited quantity and quality of included studies, more high-quality, long-term follow-up and large sample size randomized controlled trials are needed to confirm the above conclusions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Under high glucose conditions, inflammatory responses in the defect site of alveolar bone are intensified, resulting in delayed bone healing. Previous studies have shown that enhanced aryl hydrocarbon receptor (AhR) expression can inhibit inflammatory responses and promote tissue healing. OBJECTIVE: To study the effect and mechanism of enhanced AhR expression on inflammatory response and healing of alveolar bone defects in diabetic rats. METHODS: Ten of 40 Sprague-Dawley rats were randomly selected as normal controls. Diabetic models were established in the other 30 rats, and randomly divided into AhR enhancement, negative control, and blank control groups, with 10 rats in each group. Bone defects were made by surgery in both sides of maxillae of each diabetic rat. After surgery, AteloGene gel with AhR lentiviruses was injected into the defect sites of rats in the AhR enhancement group. AteloGene gel with control lentiviruses was injected into the defect sites of rats in the negative control group. Rats in blank control group and normal control group received no injection. Twenty-eight days after defects were made, all rats were sacrificed, and left maxillary bone tissues were collected to detect bone healing using hematoxylin-eosin staining. Tissues from right maxillary bone defect sites were detached, and qRT-PCR was used to detect the gene expression of AhR and Notch signaling pathway members and inflammatory factors and alkaline phosphatase. Animal experiment was approved by the Animal Experimental Ethics Committee of Guangxi Medical University. RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that the Lane-Sandhu scores of bone tissue regeneration in the AhR enhancement group were higher than those of negative control and blank control groups (P < 0.05); and the levels of inflammatory cell infiltration were lower than those of negative control and blank control groups (P < 0.05). qRT-PCR results showed that the levels of tumor necrosis factor α, interleukin-6, Notch1, Jagged1 levels, and Jagged2 in the AhR enhancement group were lower than those in the negative control and blank control groups (P < 0.05), and the levels of interleukin-10 and alkaline phosphatase were higher than those in the negative control and blank control groups (P < 0.05). These findings suggest that under high glucose conditions, enhanced AhR expression could reduce inflammatory response in alveolar bone defect sites of diabetic rats and promote the healing of bone defects, which may be associated with the inhibition of Notch signaling activation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diabetes-induced liver damage is easy to be ignored in the early stage. Exercise therapy can increase the sensitivity of insulin, which is an important means of prevention and treatment of diabetes. OBJECTIVE: To explore the effect of moderate intensity exercise intervention on liver injury during the occurrence of diabetes mellitus. METHODS: The experimental protocol was approved by the Laboratory Animal Care Ethics Committee of Wuhan Sports University. Thirty SPF Sprague-Dawley rats were divided into three groups: normal control group, diabetic control group and diabetic exercise intervention group. Normal control group was fed with normal diet, with no exercise. Diabetes control group was fed with high sugar and high fat diet for 8 weeks, followed by a small dose of streptozotocin (30 mg/kg) injected intraperitoneally, with o exercise. Diabetes exercise intervention group was fed and injected in the same way as diabetes control group, and at the same time carried out moderate intensity treadmill training. After 7 days of streptozotocin injection, hematoxylin-eosin and Masson staining were used to observe the cell morphology, the expression of α-smooth muscle actin was observed by immunohistochemistry, and orbital blood samples were collected to detect the concentration of serum type IV collagen using ELISA. RESULTS AND CONCLUSION: Compared with the normal control group, hematoxylin-eosin staining showed that the structure of liver lobule in the diabetic control group was disordered, a large number of fat vacuoles were seen, and the bile duct in the portal area was obviously proliferated; Masson staining that there were showed fat vacuoles, the structure of liver lobule was seriously damaged, and blue stained collagen fibers were seen in the portal area, and light blue stained collagen fibers were seen between liver cells. The above pathological changes were alleviated in the diabetic exercise intervention group, and the fatty degeneration of liver cells was obviously reduced. The expression of α-smooth muscle actin in the diabetic control group and diabetic exercise intervention group was significantly higher than that in the normal control group (P < 0.05), and that in the diabetic exercise intervention group was significantly lower than that in the diabetic control group (P < 0.05). The level of type IV collagen in the diabetic exercise intervention group was significantly lower than that in the diabetic control group (P < 0.05), to slow down the progress of fibrosis. To conclude, moderate intensity exercise has a good effect on streptozotocin induced liver fibrosis in diabetic rats. [ABSTRACT FROM AUTHOR]

BACKGROUND: Currently, it was confirmed that encapsulating islets with natural or synthetic biomaterials to form a barrier with the function of immune isolation can not only reduce the systematic use of immunosuppressive agents to a certain extent, but also make heterogenous islet transplantation possible. OBJECTIVE: To introduce the research progress of the biomaterials for islet transplantation, describe several models for encapsulating islet, and eventually discuss current research focus and prospects of islets encapsulating models. METHODS: The authors searched PubMed and Web of Science databases with the search terms “islet encapsulation, islet transplantation biomaterials, islet transplantation hydrogel” for relevant papers published. Initially, a total of 447 papers were retrieved, and 89 of them were included in the final analysis. RESULTS AND CONCLUSION: There are two main deficiencies in islet encapsulation for transplantation: one is the attack of immune rejection by the recipient; the other is the shortage of supply of oxygen and nutrient. Encapsulation of islet with a single material, synthetic or natural biomaterial, cannot address the two issues mentioned above. Herein, the biomaterial used for islet encapsulation must be modified. Current islet hydrogel models tend to combine synthetic biomaterials with natural biomaterials to take full advantage of the two kinds of biomaterials. In addition, immune-regulating drugs, angiogenic factors, or factors promoting the survival or function of islets can also be incorporated into the biomaterial. Besides, other cells can be involved to co-transplant with islets in the hydrogel. How to incorporate various strategies for addressing the above issues properly is the key of future research. [ABSTRACT FROM AUTHOR]

BACKGROUND: A high-fat and high-sugar diet to induce a diabetic osteoporosis model is time-consuming, with high cost and poor model stability. Induction by streptozotocin is one of the most common methods to establish an animal model of postmenopausal osteoporosis. At present, there are few reports on the identification of this disease model. OBJECTIVE: To establish a rat model of type 2 diabetic osteoporosis rat models, and to identify the animal model established. METHODS: Thirty-two male 7-week-old Sprague-Dawley rats were selected and randomly divided into a normal control group (n=16) and a model group (n=16) according to their body mass using a random number table method. The model group was fed with high-fat and high-sugar diet for 4 weeks, and a small dose of streptozotocin was intraperitoneally injected at 35 mg/kg to induce a type 2 diabetic osteoporosis model; the normal control group was fed with normal maintenance feed for 4 weeks, and an equal dose of 10 mL/kg citric acid-sodium citrate buffer was intraperitoneally injected. Two groups of rats were studied from the aspects of morphology, histology and imaging. An approval was obtained from the Animal Experimental Ethics Committee of Southwest Medical University. RESULTS AND CONCLUSION: There were 16 rats in the model group, 12 rats were modeled, and the modeling rate was 75%. Compared with the normal control group, in the model group, the body mass of rats showed a gradual downward trend and a slightly upward trend after the injection of streptozotocin. These rats presented symptoms of diabetes, such as polydipsia, polyuria and polyphagia. Fasting blood glucose level increased significantly (P < 0.05), and showed a continuous state. The histological section showed that the trabecular bone was sparsely distributed. Imaging results showed that the bone volume fraction and the number of trabeculae in rats were significantly reduced, and the separation of trabecular bone was significantly increased, indicating a significant osteoporosis. To conclude, the 7-week-old Sprague-Dawley rats which are fed with high-sugar and high-fat diet for 4 weeks can be given low-dose streptozotocin (35 mg/kg) to successfully establish the animal model of type 2 diabetic osteoporosis. From the aspects of morphology, histology, imaging, the successful establishment of diabetic osteoporosis model can be determined. [ABSTRACT FROM AUTHOR]

BACKGROUND: Islet cell transplantation is one of the most effective methods to treat diabetes. However, the shortage of transplanted cells has limited its clinical application. Direct reprogramming of hepatocytes to islet β cells in vitro is a new idea to solve this problem, but differentiation of hepatocytes to islet β cells is a complicated process. OBJECTIVE: Direct reprogramming hepatocytes into islet-like cells by efficient targeting and activating the endogenous genes of hepatocytes with Casilio system (constructed CRISPR/Cas9-Pumilio system) through modifying guide RNA sequence combined with the transcriptional activator PUFa-P65-HSF1. METHODS: The endogenous PNM (Pdx1, Ngn3, MafA) genes of hepatocytes were targeted and activated by using the Casilio system, which was transfected to the HEK293T cell line by liposome transfection. The expression of endogenous PNM was detected by real-time fluorescence quantitative PCR and immunofluorescence. The Ins-EGFP cell line with stable expression of enhanced green fluorescent protein was constructed by the lentivirus carrying Inspromoter-EGFP. The Ins-EGFP-HepG2-Cas9-PUFa-p65-HSF1 cell line (referred to as stable translocated cell lines) with stable expression of dCas9 and PUFa-P65-HSF1 in Ins-EGFP-HepG2 cell line was constructed by the PiggyBac(PB) transposon system. By using liposome, the gRNAs were transfected to stable translocated cell line, and the expression level of endogenous gene PNM was detected by real-time fluorescence quantitative PCR and immunofluorescence. Simultaneously, reprogramming efficiency was observed. RESULTS AND CONCLUSION: (1) The activation of endogenous genes by Casilio system was verified in 293T cell line. (2) The expression of EGFP, dCas9 and PUFa-P65-HSF1 in stable cell line was detected by RT-PCR, western blot assay and immunofluorescence. (3) The real-time fluorescence quantitative PCR results confirmed that this new Casilio system could target and activate the PNM which led to the up-regulation of the endogenous PNM gene expression. The efficiency of direct reprogramming was 10%-15%. (4) Based on CRISPR/dCas9, the new Casilio system can efficiently activate the endogenous PNM gene in hepatocytes, enabling the hepatocyte line to be directly reprogrammed as islet-like cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: It has been found that drug-coated balloons can reduce the loss of lumen in the advanced stage of coronary small-vessel disease, and the incidence of major adverse cardiovascular events at 6 months after surgery with drug-coated balloons is similar to that of drug-eluting stents. However, clinical studies on the efficacy of drug-eluting stents in older adult patients with type 2 diabetes mellitus complicated by coronary artery small vessel disease are still lacking. OBJECTIVE: To investigate the efficacy and safety of drug-coated balloon versus drug-eluting stent in the treatment of type 2 diabetes mellitus complicated by coronary artery small vessel disease in older adult patients. METHODS: A total of 122 older adult patients with type 2 diabetes mellitus complicated by coronary artery small vessel disease who received treatment in Jiaozuo People’s Hospital between January 2016 and September 2018 were included in this study. These patients were randomly divided into a drug-eluting stent group(n=62) and a drug-coated balloon group(n=60). Patients in both groups underwent coronary artery predilation with a semi-compliant balloon, followed by implantation of corresponding stents. Selective quantitative coronary angiography was performed before surgery, immediately, 6 months and 12 months after surgery. The minimum lumen diameter, residual stenosis, lumen increase and late lumen loss of target lesions were observed in the two groups. At 6 and 12 months after surgery, major adverse cardiovascular events and bleeding events were followed up. This study was approved by the Medical Ethics Committee of Jiaozuo People’s Hospital, China(approval No. 201503). RESULTS AND CONCLUSION:(1) The success rate of surgery in the drug-coated balloon group was significantly higher than that in the drug-eluting group(P=0.028).(2) Immediately after surgery, the minimum lumen diameter and lumen increase in the drug-coated balloon group were less than those in the drug-eluting stent group(both P < 0.01). The residual stenosis in the drug-coated balloon group was significantly greater than that in the drug-eluting stent group(P < 0.01).(3) At 6 months after surgery, late lumen loss of target vessels in the drug-coated balloon group was smaller than that in the drug-eluting stent group(P < 0.001). The rates of target vessel revascularization and major adverse cardiovascular events in the drug-coated balloon group were lower than those in the drug-eluting stent group(P=0.028, 0.010).(4) At 12 months after surgery, the minimum lumen diameter in the drug-coated balloon group was larger than that in the drug-eluting stent group(P=0.033). The residual stenosis and late lumen loss in the drug-coated balloon group were lower than those in the drug-eluting stent group(P=0.008, 0.002, 0.019).(5) These results suggest that drug-coated balloon for treatment of type 2 diabetes mellitus complicated by coronary artery small vessel disease is simple and easy to operate, with a high surgical success rate. Drug-coated balloon can reduce residual stenosis degree and late lumen loss, decrease the revascularization rate of target vessels, and reduce the incidences of major adverse cardiovascular disease and bleeding events. The clinical prognosis of drug-coated balloon is superior to that of drug-eluting stent. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diabetic wound healing disorder is one of the common complications of diabetes, but its pathogenesis has not yet been elucidated. Electrical stimulation therapy is one of the commonly used methods in the clinical treatment of wound injury, which can effectively promote the healing of injured skin. OBJECTIVE: To investigate the effects of electrical stimulation therapy on wound healing and angiogenesis in diabetic rats and its potential mechanism. METHODS: Forty-two SPF male Sprague-Dawley rats were enrolled in this study. A rat model of diabetic refractory wounds was established in 24 rats by tail vein injection of streptozotocin (50 mg/kg) combined with back skin wounds, and model rats were randomly divided into model group and electrical stimulation group. Meanwhile, normal rats were taken to cause back wounds as a blank control group. The electrical stimulation group was treated with electrical stimulation for 21 days. The blank control group and the model group were fed normally. The wound healing was evaluated on the 3rd, 7th, 14th and 21st days after treatment. After treatment, the rat serum and wound tissue were taken for index detection. The pathological morphology of rat wounds was observed by hematoxylin-eosin staining. The serum endothelial nitric oxide synthase, angiopoietin 1 and vascular endothelial growth factor levels were detected by enzyme-linked immunosorbent assay. The expression levels of angiopoietin receptor 2 and vascular endothelial growth factor receptor 2 proteins were detected by immunohistochemistry and western blot. An ethical approval was obtained from the Animal Experimental Ethics Committee of the Affiliated Hospital of Southwest Medical University. RESULTS AND CONCLUSION: The wound healing rate of diabetic rats was close to 90% on the 14th day after electrical stimulation, while the healing rate in the model group was less than 60% (P < 0.01). The serum endothelial nitric oxide synthase, angiopoietin 1 and vascular endothelial growth factor levels were significantly higher in the electrical stimulation group than the model group (P < 0.05 or P < 0.01). Meanwhile, compared with the model group, the electrical stimulation group had more neovascularization, larger vascular lumen, higher expression of angiopoietin receptor 2 and vascular endothelial growth factor receptor 2 around the blood vessels (P < 0.05 or P < 0.01). These findings indicate that electrical stimulation therapy can significantly promote wound healing and neovascularization in diabetic rats, and its mechanism is related to the increase of endothelial nitric oxide synthase, angiopoietin 1 and vascular endothelial growth factor levels and up-regulation of angiopoietin receptor 2 and vascular endothelial growth factor receptor 2 levels. [ABSTRACT FROM AUTHOR]

BACKGROUND: In rodent models of type 2 diabetes mellitus and human, the expression level of pyruvate dehydrogenase complex is decreased, and PDHA1 deficiency is the most common cause of changed pyruvate dehydrogenase complex activity.OBJECTIVE: To construct and identify the inducible islet-specific PDHA1 knockout mice, so as to provide basis for the study on the role of PDHA1 in pathogenesis of diabetes mellitus.METHODS: The study was approved by the Ethics Committee of Southern Medical University. By using Cre-loxP recombination system,PDHA1flox/floxCre+/-mice were generated by crossing PDHA1flox/flox mice with Cre+/-mice. Genotypic identification was performed by PCR at the age of 3-4 weeks and the PDHA1flox/floxCre+/-mice were the required mouse model. PDHA1flox/floxCre+/-mice（βKO group, n=5） and Cre+/-mice（control group, n=5） at the age of 4 weeks were selected and received the same water and feed. Tamoxifen（50 mg/kg） was intraperitoneally injected at the age of 8 week to induce gene knockout. Three weeks later, pancreatic tissue, adipose tissue, and liver tissue were removed under anesthesia. qPCR, western blot and immunohistochemical staining were applied to identify the PDHA1 knockout effect and to observe the mouse phenotype.RESULTS AND CONCLUSION:（1） PCR analysis selected PDHA1flox/floxCre+/-mice.（2） qPCR method was used to test the pancreas, fat and liver tissues of mice, and it was confirmed that the knockout effect had tissue specificity. The expression level of PDHA1 mRNA in islet in theβKO group was significantly lower than that in the control group.（3） The results of western blot and immunohistochemical scanning showed a significant decrease in PDHA1 protein in the βKO group compared with the control group, suggesting the PDHA1 knockout effect was obvious.（4） In summary, the β cell-specific deletion of the PDHA1 gene is successfully constructed by Cre-loxP system, which provides a novel target for studying the pathogenesis of diabetes at animal level. [ABSTRACT FROM AUTHOR]

BACKGROUND: Deep seawater has been shown to effectively alleviate the process of diabetes in mice induced by high fat diet through activating AMPK pathway, but there are few studies about the role of deep seawater in the wound healing of diabetes mellitus. OBJECTIVE: To explore the mechanism of deep seawater on the cutaneous wound healing in diabetic mice. METHODS: Forty-eight healthy male Kunming mice (provide by Laboratory Animal Center of Kunming Medical University) were selected and were given intraperitoneal injection of streptozotocin to establish diabetic model. After 14 days of incubation, the back would model was established, and the mouse models were randomly divided into four groups: control group (purified water), tap water group, deep seawater group and inhibitor group (deep seawater + venous injection of Wnt/β-catenin inhibitor, XAV-939). Subsequently, the blood glucose and body mass of model mice were observed at 3, 7 and 10 days after wound modeling, and the healing of the wound was observed. The morphological changes of the wound were evaluated. The expression levels of β-catenin, GSK-3β and Rspo-3, malondialdehyde, superoxide dismutase and glutathione peroxidase in the serum were detected. The study was approved by the Laboratory Animal Ethics Committee of Kunming Institute of Zoology, China Academy of Sciences, approval No. KPRC-2017091. RESULTS AND CONCLUSION: (1) Deep seawater showed no significant effect on the body mass and blood glucose. (2) The wound healing rate in the deep seawater group was significantly higher than that in the tap water and control groups at different time points (all P < 0.01). (3) Western blot results showed that the expression levels of β-catenin and Rspo-3 were higher in the deep seawater group than the control and tap water groups, but GSK-3β was down-regulated. (4) Hematoxylin-eosin staining showed that compared with the control group, vascular endothelial cells, new capillaries and fibroblast cells proliferation in the deep seawater group were increased, but the number of inflammatory cells got opposite results. However, there was no significant difference between the deep seawater + XAV-939 group and control group (P > 0.05). The healing rate of wound at different time points in the deep seawater group was significantly higher than that in the tap water and control groups (all P < 0.01). (5) Compared with the control group, the expression levels of superoxide dismutase and glutathione peroxidase in serum in the deep seawater group were increased (P < 0.01 and P < 0.001), and malondialdehyde decreased (P < 0.05 and P < 0.01). There was no significant difference between deep seawater + XAV-939 and control groups (P > 0.05). (6) To conclude, deep seawater promotes cutaneous wound healing in diabetic mice via activating Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Low level of adiponectin plays a significant role in the occurrence and development of periodontitis and diabetes mellitus. OBJECTIVE: To investigate the therapeutic effect of adiponectin injection on diabetic periodontitis model mice and its mechanism. METHODS: Sixty 8-week old Kunming mice (provided by Beijing Weitong Lihua Animal Experimental Technology Co., Ltd.) were randomly divided into three groups: control group, model group and adiponectin group. The mice in the model and adiponectin groups received intraperitoneal injection of streptozotin to establish a mouse model of diabetes mellitus, and then the periodontitis model was established by applying the combined bacterial fluid to the ligation site. The mice in the control and model groups received intraperitoneal injection of 1 mL normal saline once daily, while adiponectin group received intraperitoneal injection of 15 μg/kg adiponectin once daily, for 6 consecutive weeks. The three experimental groups of mice were treated for 6 weeks, after which physiological and biochemical indicators were tested. The levels of adiponectin in serum and periodontal tissue, the blood sugar and plasma insulin levels were then detected by ELISA. The depth of periodontal examination and the vertical absorption of alveolar bone were observed. The pathological changes of periodontal tissue were detected by hematoxylin-eosin staining. The changes of apoptosis level of gingival epithelial cells were detected by TUNEL method. The expression levels of RAGE and reactive oxygen species mRNA and protein were detected by RT-PCR and western blot assay. RESULTS AND CONCLUSION: (1) The levels of adiponectin in serum and periodontal tissue in the adiponectin group were significantly higher than those in the control and model groups (P < 0.05). (2) The blood sugar level in the adiponectin group was significantly lower than that in the model group (P < 0.05) and the serum insulin level was significantly increased (P < 0.05). (3) The depth of periodontal examination and vertical absorption of alveolar bone were decreased significantly in the adiponectin group compared with the model group, and the apoptotic rate of gingival epithelial cells was decreased significantly. (4) The expression levels of RAGE and reactive oxygen species mRNA and protein in the adiponectin group were significantly lower than those in the model group (P < 0.05). (5) These results suggest that adiponectin can improve the adiponectin level in periodontal tissue and plasma in the diabetic periodontitis model mice and can significantly improve the blood sugar status, and reduce the pathological changes of periodontal tissue and the apoptosis of periodontal cells possibly via regulating RAGE-ROS signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Intervertebral disc degeneration (IDD) is the main cause of low back pain, and nucleus pulposus cell apoptosis is an important risk factor for IDD. However, the underling mechanism at molecular level remains unknown. OBJECTIVE: To investigate whether endoplasmic reticulum stress participates in the high glucose-induced apoptosis in nucleus pulposus cells. METHODS: Passage 3 rabbit nucleus pulposus cells were randomized into four groups, and cultured in the normal culture medium (blank control group), culture medium containing 100 mmol/L glucose (high-glucose group), capspase inhibitor Z-ATAD-FMK (inhibitor group) or Z-ATAD-FMK and 100 mmol/L glucose (combination group). After 6 hours of culture, the viability, reactive oxygen species level, and apoptosis rate were examined in nucleus pulposus cells. The protein expression levels of Grp78 and Caspase-12 were assayed. RESULTS AND CONCLUSION: Compared with the blank control group, high glucose increased the nucleus pulposus cell apoptosis, reactive oxygen species accumulation, as well as expression of Grp78 and Caspase-12. Whereas, Z-ATAD-FMK (the inhibitor of Caspase-12) abrogated the cytotoxic effect caused by high glucose. Therefore, endoplasmic reticulum stress-mediated apoptosis is a new signaling pathway of high-glucose induced apoptosis in nucleus pulposus cells. The generation and accumulation of reactive oxygen species is the main contributor of endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

BACKGROUND: Islet transplantation is an effective method for diabetes treatment. Using biomedical engineering technology to introduce biomaterials into islet transplantation can maintain the vitality of islet and improve the efficiency of transplantation. OBJECTIVE: To transplant the cultured polyglycolic acid (PGA)-islet into the muscle of diabetic recipient rats and to observe the effect of PGA-islet in the treatment of diabetes mellitus. METHODS: A diabetic model was established in 18 Wistar rats by the method of intraperitoneal injection of streptozotocin, and the model rats were randomly assigned into three groups. In the control group, normal saline was injected into the muscle of the rat leg. In the experimental group 1, allogeneic islet cells were intramuscularly injected into the rat leg. In the experimental group 2, PGA-allogeneic islet cell graft was intramuscularly injected into the rat leg. At 3, 7, 14, 21 and 30 days after transplantation, blood glucose and serum insulin levels were detected in each rat. At 14 and 30 days after transplantation, graft specimens were taken from the experimental groups and observed by scanning electron microscopy. RESULTS AND CONCLUSION: (1) At 3 and 7 days after transplantation, the blood glucose levels in the two experimental groups were significantly lower than that in the control group (P < 0.05), while the serum insulin levels in the two experimental groups were significantly higher than that in the control group (P < 0.05). Compared with the experimental group 1, the blood glucose level in the experimental group 2 was significantly lower at 14, 21 and 30 days after transplantation, while the serum insulin level in the experimental group 2 was significantly higher at each time point after transplantation (P < 0.05). Under the scanning electron microscope, in the experimental groups, plenty of well-formed islet cells were adhered to the PGA fiber scaffold at 14 days after transplantation; a visible network of extracellular matrix with fine fibers formed in islet cells; and a small number of red blood cells were visible around the islet cells. With the extension of embedded time, PGA fiber scaffolds began to degrade and crack. Long fibers degraded into short fibers, and after 30 days, the scaffold layer was broken into pieces finally. All these findings indicate that the transplantation of PGA-islet can effectively reduce the blood glucose level and increase the serum insulin level in diabetic rats. [ABSTRACT FROM AUTHOR]

BACKGROUND: There are two methods for constructing the protein overexpression model in cells by adenovirus infection. In Method I, 3 mL of 1640 medium was supplemented 4 hours after cell infection by adenovirus, and 24 hours later, culture medium was refreshed with complete medium for further 48 hour culture, In Method II, 4 hours after cell infection by adenovirus, PBS was used to wash 1640 culture medium containing adenovirus, and then 4 mL of complete culture was added for further culture till 48 hours. The main difference between the two methods is that the adenovirus in Method I has a longer action time and a better infection effect, but the damage of the adenovirus itself to cells is more severe, and it disturbs the stability of the experimental model. The effect of adenovirus in Method II is short lasting, and the toxicity of adenovirus to cells is lower, but the efficiency of adenovirus infection is weaker, and the expression of target protein is weaker. OBJECTIVE: To find a more stable and efficient way to establish the thioredoxin-interacting protein (TXNIP) overexpression model by adenovirus infection in INS-1 islet β-cells. METHODS: The adenovirus vector (Ad-GFP) with green fluorescent protein (GFP) and TXNIP overexpressing adenovirus vector (Ad-TXNIP-GFP) with green fluorescent protein (GFP) were constructed. Three groups (normal, Ad-GFP, Ad-TXNIP-GFP) were transfected with methods I and II, respectively. RESULTS AND CONCLUSION: The GFP fluorescence intensity and the GFP positive percent in Method II were greater than those in the Method I. The cell morphology and survival rate in Method II were better than those in Method I. The expression of TXNIP at mRNA and protein levels in Method II was significantly higher than that in Method I. These findings show that the method II is more conducive to INS-1 cells in the construction of TXNIP overexpression model. [ABSTRACT FROM AUTHOR]

BACKGROUND: Researches have shown that nerve growth factor can promote wound healing, but there are few reports on the topical application of nerve growth factor combined with medication on diabetic scald wound. OBJECTIVE: To explore the changes of microvessel density and proliferating cell nuclear antigen expression after topical application of nerve growth factor-insulin gel on deep II scald wound in diabetic rats. METHODS: Seventy-five Wistar rats were randomly divided into five groups. Deep II scald models were made on the back of rats in normal control group followed by topical application of Carbopol 980. Diabetic models and deep II scald models were both made in the remaining rats with an interval of 3 days. Then, the rats in the latter four groups were subjected to topical application of Carbopol 980 alone, or Carbopol 980 containing nerve growth factor, insulin and combination of nerve growth factor and insulin, respectively. The wound in each rat was redressed once a day, for 21 consecutive days. Wound healing rate, microvessel density and proliferating cell nuclear antigen expression in rats were detected at 3, 7, 11, 15, 21 days after scald. RESULTS AND CONCLUSION: Wound healing rate, microvessel density and proliferating cell nuclear antigen expression were higher in the combination group than the other four groups at different time after scald (P < 0.05). Results from hematoxylin-eosin staining showed that different structure damages, angiectasis and inflammatory cell infiltration were observed in different groups at 1 day after scald. A small amount of new capillaries were visible in each group, especially in the combination group at 3 days after scald. The number of capillary vessels and inflammatory cells increased gradually at 7-11 days after scald. Marked re-epithelialization and regular arrangement of collagen fibers were observed in the combination group at 15 days after scald. Meanwhile, compared with the normal control group and model group, the number of new vessels was increased in the nerve growth factor and insulin groups, but collagen fibers arranged disorderly. The wound in the combination group was covered with epithelial cells and collagen fibers arranged orderly at 21 days after scald, while there are different levels of epithelization in the other four groups. Higher level of epithelization was found in the nerve growth factor and insulin groups than the normal control and model groups. To conclude, topical application of nerve growth factor-insulin gel on deep II scald wound can promote wound healing by increasing microvessel density and proliferating cell nuclear antigen expression. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diabetic foot is a common chronic complication of diabetes, and an increasing risk of amputation is found in such patients. The current common treatments include control of blood glucose, debridement of local tissues, anti-infection and revascularization, but none of them has achieved ideal curative effects. Further investigation on more effective treatment is needed. Recent studies have shown that mesenchymal stem cells can promote the healing of diabetic foot and improve the clinical symptoms. OBJECTIVE: To review the mechanism and clinical application of mesenchymal stem cells in the treatment of diabetic foot. METHODS: The first author searched the relevant literature (original articles and reviews) published in the PubMed and CNKI databases from 2012 to 2017, using the keywords of “mesenchymal stem cell, diabetic foot” in English and Chinese, respectively. After excluding irrelevant articles or those out of date, 44 articles fulfilling the inclusive criteria were reviewed. RESULTS AND CONCLUSION: Mesenchymal stem cells regardless of source are a promising and effect therapy for diabetic foot. Bone marrow mesenchymal stem cells have no immune limitation and are the most effective via intramuscular injection. Umbilical cord blood derived mesenchymal stem cells have some advantages, such as rich sources, short doubling time, long survival time. Adipose derived mesenchymal stem cells are widely distributed and can be easily isolated and extracted. Placenta derived mesenchymal stem cells have good proliferation ability, which are the most effective via intraperitoneal injection. Among them, bone marrow mesenchymal stem cells may be the best choice for diabetic foot treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that high glucose environment has a significant inhibitory effect on the survival of adipose-derived stem cells, which significantly affects the therapeutic efficacy of adipose-derived stem cells on type 2 diabetes mellitus. OBJECTIVE: To investigate the therapeutic effect of rosiglitazone combined with adipose-derived stem cell transplantation in rats with type 2 diabetes mellitus. METHODS: A total of 108 male Sprague-Dawley rats were chosen, 20 of which were randomly taken as normal controls and the rest 88 rats were used to make type 2 diabetes mellitus models through intraperitoneal injection of low-dose streptozotocin combined with high-sugar/high-fat diet. At 20 days after modeling, the model rats were randomized into model, rosiglitazone, cell transplantation and combined groups, followed by administration of normal saline (by gavage and via tail vein), rosiglitazone (by gavage), adipose-derived stem cells (via tail vein), and rosiglitazone (by gavage)+adipose-derived stem cells (via tail vein), once a day, for consecutive 7 days. Three weeks after treatment, fasting blood glucose level, insulin level, C-peptide level, body mass changes were detected; distribution and survival of adipose-derived stem cells were observed; the changes of pancreas histomorphology was observed, the apoptosis in islet cells was detected, and the CXCL1, CXCL2 and CXCR2 protein expression levels in the pancreas tissue were determined. RESULTS AND CONCLUSION: Compared with the normal control group, the fasting blood glucose level was increased (P < 0.05), while the insulin level, C-peptide level and body mass were significantly decreased in the model group (P < 0.05); the number of apoptotic islet cells was increased (P < 0.05); the expression levels of CXCL1, CXCL2 and CXCR2 in the pancreas tissue were elevated (P < 0.05); and the pancreas tissue morphologies were in disorder, with few islet cell masses. Compared with the model group, the fasting blood glucose level was decreased (P < 0.05), while the insulin level, C-peptide level and body mass were significantly increased in the rosiglitazone, cell transplantation and combined groups (P < 0.05); the number of apoptotic islet cells was decreased (P < 0.05); the expression levels of CXCL1, CXCL2 and CXCR2 in the pancreas tissue were declined (P < 0.05); and the pancreas tissue morphologies were improved to different extents, and the combined group showed the best improvement. There were many transplanted adipose-derived stem cells in the cell transplantation and combined groups, especially in the latter one. Overall findings indicate that rosiglitazone combined with adipose-derived stem cell transplantation is an effective treatment for type 2 diabetes mellitus in rats, which is better to inhibit inflammations. [ABSTRACT FROM AUTHOR]

BACKGROUND: In previous studies, the human umbilical cord mesenchymal stem cells (hUC-MSCs) have been successfully differentiated into islet-like cells in vitro, and insulin expressions have been found. OBJECTIVE: To compare the therapeutic effects of different induced stages of islet-like cells differentiated from hUC-MSCs in a diabetic rat in vivo, so as to find the most suitable induced time in vitro and provide a theoretical basis for clinical treatment of diabetes mellitus. METHODS: Passage 3 hUC-MSCs were differentiated into islet-like cells after 7, 14, 21, 28 days of oriented induction. Eighty male healthy Wistar rats, clean grade, were used in the study. Except eight rats in normal control group, all the rats were injected with streptozotocin at a dose of 70 mg/kg to establish diabetic models. The rats at 10 days after successful modeling were randomly divided into model control group, non-induced group, 7-day induction group, 14-day induction group, 21-day induction group and 28-day induction group. Rats in the normal control group and model control group were given 2 mL of culture medium without any cells and rats in the other groups were implanted with corresponding cell suspension (2×106 cells) via tail vein for two sessions with an interval of 2 weeks. The blood glucose level, body mass and serum insulin level were detected during the treatment process. The rats were executed to observe the structure changes of each organ at 4 weeks after the second cell transplantation. RESULTS AND CONCLUSION: (1) Compared with the model control group, the body mass and the serum insulin level significantly increased and the blood glucose levels significantly decreased in all the transplantation groups (P < 0.05), and the therapeutic effect was best in the 28-day induction group. (2) Compared with the model control group and normal control group, the frozen sections in all the transplantation groups showed that the morphological structures of the liver and kidney were clear with no abnormal changes, such as necrosis and fibrosis, after transplantation. These experimental results show that it is relatively safe and effective to transplant the different induced stages of islet-like cells induced by hUC-MSCs in the treatment of diabetes mellitus, and the therapeutic effect of islet-like cells at 28 days of in vitro induction is most obvious. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pioglitazone is a common hypoglycemic drug capable of improving proliferation and activation, and inhibiting apoptosis of endothelial progenitor cells (EPCs). We speculated that the combined use of pioglitazone and EPCs transplantation could have significant improving effects on hyperglycemia and kidney function after diabetes mellitus. OBJECTIVE: To investigate the improving effect of EPCs transplantation combined with pioglitazone treatment on the kidney function of diabetic rat models. METHODS: The 15 of 75 Wistar rats were randomly selected and served as normal control group (no treatment). Animal models of type 1 diabetes mellitus were made in the rest 60 rats through the intraperitoneal injection of 40 mg/kg streptozotocin for continuous 5 days. The human EPCs (labeled by CM-Dil) were recovered, cultured and preserved until transplantation. After 4 weeks of modeling, the 60 rat models were randomly divided into model group (PBS injection), pioglitazone group, EPCs transplantation group and combined treatment group, followed by tail vein injection of EPCs suspension and/or intragastric administration of 20 mg/kg pioglitazone for continuous 4 days. After 8 weeks of treatment, the levels of glucose, insulin and creatinine in serum, urea nitrogen and urine protein during 24 hours were determined. The number and distribution of EPCs labeled by CM-Dil were detected by fluorescence microscope, the apoptosis in kidney cells was tested by TUNEL method, and the kidney weight/body weight ratio in rats was calculated. RESULTS AND CONCLUSION: Compared with the model group, the blood glucose and serum creatinine levels and the urea nitrogen and urine protein concentrations during 24 hours were significantly decreased (P < 0.05), and the serum insulin level was significantly increased (P < 0.05) in the pioglitazone and EPCs transplantation groups. These biochemical indexes in the combined treatment group were more significantly altered compared with the model group (P < 0.01). The kidney weight to the body weight ratio was lowest in the combined treatment group and lower in the pioglitazone and EPCs transplantation groups followed by the model group (P < 0.05). The order of apoptotic kidney cells labeled by TUNEL was as follows: model group > pioglitazone group > EPCs transplantation group > combined treatment group (P < 0.05). To conclude, the EPCs transplantation combined with pioglitazone treatment can decrease the blood glucose and serum creatinine levels and urea nitrogen and urine protein concentrations, improve the serum insulin level, reduce cell apoptosis in the kidney, and remit the kidney dysfunction of diabetic rats to a certain extent. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recent studies have shown that adipose-derived mesenchymal stem cells (ADMSCs) not only have multilineage differentiation potential, but also exert an important role in blood sugar balance and hormone production. OBJECTIVE: To observe the differentiation potential of human ADMSCs (hADMSCs) into functional islet-like cells and the therapeutic effect of hADMSCs transplantation in diabetic rats. METHODS: PDX-1 gene was transfected into hADMSCs by adenovirus. Cell differentiation and insulin secretion were identified and detected by dithizone staining and ELISA, respectively. Twenty male Sprague-Dawley rats were randomly divided into control group (n=4), diabetes group (n=8) and transplantation group (n=8). Rats in the latter two groups were subjected to making diabetic models by 65 mg/kg streptozotocin injection. Afterwards, rats in the transplantation group were given PDX-1 transfected ADMSCs via the tail vein. RESULTS AND CONCLUSION: At 15 days after transfection, the number of insulin positive cells and insulin secretion were both increased significantly (P < 0.05). Fasting glucose levels in the transplantation group decreased significantly (P < 0.05), while the body weight increased significantly (P < 0.05). In the diabetic group, the fasting glucose level still maintained at a high level, and the body weight of rats was significantly decreased. These results implicated that PDX-1 gene could induce hADMSCs differentiating into functional islet-like cells. PDX-1 transfected ADMSCs transplantation is effective in treating diabetic rats, but the mechanism needs further study. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tranexamic acid has been used to reduce bleeding after total knee arthroplasty in patients for the reason of big trauma and blood loss. Diabetes mellitus patients may have the poor ability to resist infection and heal tissue and vascular lesions. There are still no relevant literature reports about whether the application of tranexamic acid will achieve hemostasis and does not increase the risk of venous thrombosis of lower limbs. OBJECTIVE: To evaluate the efficacy and safety of tranexamic acid on perioperative blood loss in osteoarthritis or rheumatoid arthritis patients complicated with type 2 diabetes mellitus during total knee arthroplasty. METHODS: One hundred patients with the diagnosis of osteoarthritis or rheumatoid arthritis patients complicated with type 2 diabetes mellitus were selected between January 2013 and January 2015. Among all the subjects, 46 patients who received the operation before January 2014 served as the control group and 54 patients who received the operation after January 2014 were selected as the treatment group. Patients in the treatment group received 15 mg/kg tranexamic acid dissolved in 250 mL normal saline by fast intravenous infusion before the end of the operation. The patients in the control group just received 250 mL normal saline. Perioperative bleeding, blood transfusion, hemoglobin, hematocrit and coagulation index level were compared between the two groups, and deep venous thrombosis of lower limbs was observed. RESULTS AND CONCLUSION: (1) The postoperative drainage, hidden blood loss, total blood loss, transfusion volume, and transfusion rate in the treatment group were lower than that in control group (P < 0.05). (2) The levels of hemoglobin and hematokrit in the two groups were not significantly different, but decreased at 3 hours, 1 and 3 days after the surgery, and increased at 5 days postoperatively, but still lower than preoperatively. The levels of hemoglobin and hematokrit in the treatment group were significantly higher than that in the control group at different time points postoperatively (P < 0.05). (3) Prothrombin time, activated partial thromboplastin time, and fibrinogen were not significantly different preoperatively, during tourniquet removal, at 3 hours, 1 and 5 days postoperatively between the two groups. D-dimer levels were not significantly different preoperatively and during tourniquet removal in both groups, but increased at 3 hours, 1 and 5 days postoperatively; moreover, D-dimer levels were significantly lower in the treatment group than in the control group (P < 0.05). D-dimer levels were not significantly different between the two groups at 5 days after surgery. (4) Deep venous thrombosis of lower limbs was not visible in double lower limb venous ultrasonography in both groups at 5 days and 1 month postoperatively. (5) To decrease the blood loss, intravenous infusion of 15 mg/kg of tranexamic acid during total knee arthroplasty before tourniquet removel is effective and safe in osteoarthritis or rheumatoid arthritis patients complicated with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]