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Diabetes-related brain complications have been reported in clinical patients and experimental models. The objective of the present study was to investigate the neuroprotective mechanisms of Lactobacillus reuteri GMNL-263 in streptozotocin (STZ)-induced diabetic rats. In this study, three different groups, namely control group, STZ-induced (55 mg/kg streptozotocin intraperitoneally) diabetic rats (DM), and DM rats treated with Lactobacillus reuteri GMNL-263 (1 × 10

The functional design of scaffolding biomaterials with potent capabilities of promoting cell adhesion and proliferation is critically important for tissue repair and regeneration. Here, we exploit the effects of oxidation level of aldehyde hyaluronic acid (oHA) on gelatin microcarriers for repairing corneal injuries. Specifically, high oxidation levels can endow the microcarrier surface with large oHA grafting amount, smooth topography, and strong stiffness, consequently formulating biocompatible scaffolding materials with superior affinities for keratocyte attachment and growth. In a rabbit model of corneal alkali burn injury, single intracorneal injection of keratocytes/functionalized microcarriers with an appropriate oxidation level could effectively reduce corneal swelling (~62-fold improvement), recover ~94% collagen production and ~89% keratocan expression, and repair disordered collagenous stromal architecture after 4 weeks. These findings on the oxidation level effects of the aldehyde polysaccharide show a great potential use in the development of advanced scaffolds for efficient tissue engineering.

Oxidative stress-induced brain cell damage is a crucial factor in the pathogenesis of reactive oxygen species (ROS)-associated neurological diseases. Further, studies show that astrocytes are an important immunocompetent cell in the brain and play a potentially significant role in various neurological diseases. Therefore, elimination of ROS overproduction might be a potential strategy for preventing and treating neurological diseases. Accumulating evidence indicates that calycosin, a main active ingredient in the Chinese herbal medicine Huangqi (Radix Astragali Mongolici), is a potential therapeutic candidate with anti-inflammation and/or anticancer effects. Here, we investigated the protective effect of calycosin in brain astrocytes by mimicking in vitro oxidative stress using H

The poor prognosis and chemoresistance of patients with triple-negative breast cancer (TNBC) urge the development of new therapeutic strategies. Snail mucus has shown its ability against inflammation, a process closely related to tumorigenesis, suggesting a potential anti-cancer activity.The effect and mechanisms of snail mucus on cell viability were determined by IncuCyte Live-cell analysis and molecular biological methods. The anti-cancer fractions of snail mucus were isolated and identified by medium pressure liquid chromatography (MPLC) and nuclear magnetic resonance (NMR) spectrometry analysis.Snail mucus significantly decreased the viability of TNBC cells with relatively lower cytotoxicity to normal breast epithelial cells and enhanced their response to chemotherapy through activation of Fas signaling by suppressing nucleolin. Two peptide fractions have been identified as the anti-cancer ingredients of the snail mucus.Snail mucus can induce programmed cell death via the extrinsic apoptotic pathway and has therapeutic potential by achieving a chemo-sensitizing effect in TNBCs.

Our research was designed to evaluate the effect on bone regeneration with 3-dimensional (3D) printed polylactic acid (PLA) and 3D printed polycaprolactone (PCL) scaffolds, determine the more effective option for enhancing bone regeneration, and offer tentative evidence for further research and clinical application. Employing the 3D printing technique, the PLA and PCL scaffolds showed similar morphologies, as confirmed via scanning electron microscopy (SEM). Mechanical strength was significantly higher in the PLA group (63.4 MPa) than in the PCL group (29.1 MPa) (p &lt, 0.01). Average porosity, swelling ratio, and degeneration rate in the PCL scaffold were higher than those in the PLA scaffold. SEM observation after cell coculture showed improved cell attachment and activity in the PCL scaffolds. A functional study revealed the best outcome in the 3D printed PCL-TGF-β1 scaffold compared with the 3D printed PCL and the 3D printed PCL-Polydopamine (PDA) scaffold (p &lt, 0.001). As confirmed via SEM, the 3D printed PCL- transforming growth factor beta 1 (TGF-β1) scaffold also exhibited improved cell adhesion after 6 h of cell coculture. The 3D printed PCL scaffold showed better physical properties and biocompatibility than the 3D printed PLA scaffold. Based on the data of TGF-β1, this study confirms that the 3D printed PCL scaffold may offer stronger osteogenesis.

Aim: Cancer is a major health burden and a leading cause of death worldwide. We sought to discover potential anticancer molecules with novel scaffold for further development of more active agents to address the issue. Methodology: A series of β-carboline-1-one hydantoins were designed according to a conformational restriction strategy, synthesized via a one-pot Knoevenagel condensation−intramolecular cyclization, and tested in cytotoxicity assays. Results: The study culminated in the identification of 6b and 6c, both of which were found to potently inhibit breast and lung cancer cell lines. Of particular interest was 6c, which was 83 times more potent an inhibitor than 5-fluorouracil in inhibiting MCF-7. Conclusion: This work establishes β-carboline-1-one hydantoin as a promising scaffold in the investigation of anticancer agents.

This study aimed to investigate dosimeter characteristics by using a photon beam with and without the flattening filter of intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) by using a 3D N-isopropylacrylamide (NIPAM) polymer gel. A self-developed optical computed tomography scheme was used to measure the dose distribution. Gamma evaluation was performed between the dose distribution calculated by a treatment planning system and the measured dose distribution by using the criteria of 3% dose difference and 3 mm distance to agreement. Under these criteria, the passing rates showed no significant difference between IMRT and VMAT irradiation with and without the flattening filter. All these results revealed that the NIPAM gel dosimeter was for high-dose-rate radiation and clinical-pretreatment verifications.

Previous studies stated that stem cell functions are reduced under high glucose environment, leading to reduce stem cell capability of tissue regeneration. This study aimed to investigate if stem cells preconditioned with resveratrol show better therapeutic effect on the treatment of liver dysfunction in diabetic rats than stem cells without resveratrol precondition. Male Wistar rats were divided into four groups including sham, DM (diabetic rats), DM + ADSC (DM rats receiving autologous transplantation of adipose-derived stem cells), and DM + pre-R-ADSC (DM rats receiving ADSC preconditioned with resveratrol). Compared with sham group, experimental results showed that DM group induced suppression of survival, suppression of Sirt1, activation of apoptotic, and activation of fibrotic pathways, leading to liver dysfunction. Autologous transplantation of ADSC (DM + ADSC) improved above pathways except for fibrotic signaling. By contrast, transplantation of resveratrol preconditioned ADSC (DM + pre-R-ADSC) significantly improved above pathways including fibrosis. Supplemental evidences suggest that resveratrol precondition increases ADSC viability under high glucose stress via Sirt1 and IGF1R expressions. Furthermore, increased secretion of IGF1 via paracrine route also confirmed in ADSC preconditioned with resveratrol. The experimental results imply that ADSC preconditioned with resveratrol shows potential in the treatment of liver dysfunction in DM patients with liver dysfunction.

BackgroundTriple-negative breast cancers (TNBCs) patients showed poor survival outcomes due to chemoresistance, and the development of new therapeutic strategies is urgently needed. The development of cancer is mainly related to chronic inflammation. Therefore, the pharmacological reduction of inflammation by natural extract components may promote anti-cancer activity and increase chemosensitivity. Snail mucus has been reported to possess the ability against inflammation, a process closely related to tumorigenesis, suggesting a potential anti-cancer function. The direct cytotoxic activity of snail mucus in cancer cells was investigated in this study.Methods The effect of snail mucus on cell viability in breast cancer cells and normal epithelial cells were measured by MTT and IncuCyte Live-cell analysis. The active fractions of snail mucus were isolation by performing MPLC and the anti-cancer ingredients were identified by NMR spectrometer analysis.Results Snail mucus significantly decreased the proliferation and viability of TNBC cells with relatively lower cytotoxicity to normal breast epithelial cells and enhanced their response to chemotherapy. Mechanistically, snail mucus induces an extrinsic apoptotic pathway through activation of Fas signaling by suppressing nucleolin. Two possible peptide fractions have also been identified as the anti-cancer ingredients of the snail mucus.ConclusionsIn summary, snail mucus can induce programmed cell death via the extrinsic apoptotic pathway and might have therapeutic potential with chemo-sensitizing effect for TNBCs.

Habitual chewing of the areca nut increases the risk of mortality owing to cardiovascular disease, but few reports have revealed the cardiotoxicity mechanism of the areca nut. Arecoline has been reported to be the primary toxic constituent in the areca nut. In order to study the acute cardiotoxicity of the areca nut in the development of pathologic heart hypertrophy, we induced heart injury in rats using arecoline. Arecoline at a low dosage (5 mg/kg/day) or a high dosage (50 mg/kg/day) was intraperitoneally injected to Sprague-Dawley rats for 21 days. The change of heart function and biochemical pathways were investigated with echocardiography and Western blot. The results were presented that heart functions were weakened by arecoline stimulation, and western blotting analysis revealed an elevation in BNP levels in the heart after arecoline exposure. Arecoline induced IL-6-mediated activation of the MEK5/ERK5 and JAK2/STAT3 pathways, as well as mitogen-activated protein kinase signaling cascades. Further, arecoline increased the calcineurin and NFATc3 levels in the heart. In summary, our results suggest that arecoline causes significantly cardiotoxicity and heart damage by inducing several hypertrophy-related signaling pathways, including IL-6-induced MEK5/ERK5, JAK2/STAT3, mitogen-activated protein kinases, and calcineurin signaling pathways. The study elucidated, for the first time, the possible cardiac hypertrophy mechanisms underlying the cardiotoxicity of the areca nut.

In this study, magnetic nanoparticles composed of a core (doxorubicin&ndash, gelatin) and a shell layer (Fe3O4&ndash, alginate) were developed to function as targeted anticancer drug delivery vehicles. The anticancer drug doxorubicin (DOX) was selected as a model drug and embedded in the inner gelatin core to obtain high encapsulation efficiency. The advantage of the outer magnetic layer is that it targets the drug to the tumor tissue and provides controlled drug release. The physicochemical properties of doxorubicin&ndash, gelatin/Fe3O4&ndash, alginate nanoparticles (DG/FA NPs) were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction. The mean diameter of DG/FA NPs, which was determined using a zeta potential analyzer, was 401.8 &plusmn, 3.6 nm. The encapsulation rate was 64.6 &plusmn, 11.8%. In vitro drug release and accumulation were also studied. It was found that the release of DOX accelerated in an acidic condition. With the manipulation of an external magnetic field, DG/FA NPs efficiently targeted Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and showed in the nucleus after 6 h of incubation. After 12 h of incubation, the relative fluorescence intensity reached 98.4%, and the cell viability of MCF-7 cells decreased to 52.3 &plusmn, 4.64%. Dual-layer DG/FA NPs could efficiently encapsulate and deliver DOX into MCF-7 cells to cause the death of cancer cells. The results show that DG/FA NPs have the potential for use in targeted drug delivery and cancer therapy.

In this study, magnetic nanoparticles composed of a core (doxorubicin–gelatin) and a shell layer (Fe3O4–alginate) were developed to function as targeted anticancer drug delivery vehicles. The anticancer drug doxorubicin (DOX) was selected as a model drug and embedded in the inner gelatin core to obtain high encapsulation efficiency. The advantage of the outer magnetic layer is that it targets the drug to the tumor tissue and provides controlled drug release. The physicochemical properties of doxorubicin–gelatin/Fe3O4–alginate nanoparticles (DG/FA NPs) were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction. The mean diameter of DG/FA NPs, which was determined using a zeta potential analyzer, was 401.8 ± 3.6 nm. The encapsulation rate was 64.6 ± 11.8%. In vitro drug release and accumulation were also studied. It was found that the release of DOX accelerated in an acidic condition. With the manipulation of an external magnetic field, DG/FA NPs efficiently targeted Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and showed in the nucleus after 6 h of incubation. After 12 h of incubation, the relative fluorescence intensity reached 98.4%, and the cell viability of MCF-7 cells decreased to 52.3 ± 4.64%. Dual-layer DG/FA NPs could efficiently encapsulate and deliver DOX into MCF-7 cells to cause the death of cancer cells. The results show that DG/FA NPs have the potential for use in targeted drug delivery and cancer therapy.

Bone scaffold surface characterization is important for improving cell adhesion, migration, and differentiation. In this study, bone morphogenetic protein-2 (BMP-2) was immobilized to the surface of the gelatin/hydroxyapatite composite using avidin–biotin binding system to produce a bone-tissue engineering scaffold. Firstly, hydroxyapatite particles reacted with hexamethylene diisocyanate and then the terminal group was converted into a primary amine group. Avidin was then immobilized on the surfaces of hydroxyapatite particles using N-ethyl-N′-(3-(dimethylamino)propyl) carbodiimide and N-hydroxysuccinimide as coupling agents. Gelatin was blended with avidin-modified hydroxyapatite and pure hydroxyapatite to obtain gelain/hydroxyapatite composite. The composite was then cross-linked with glutaraldehyde. Finally, biotin-conjugated BMP-2 was immobilized on the surface of the composite via avidin–biotin binding. In vitro study indicated that BMP-2-immobilized composite film had a higher ALP activity than that composite film without BMP-2. The composite scaffolds were then implanted into rabbit skulls to check bone-tissue regeneration. Ultrasound and micro-CT scans demonstrated that neovascularization and new bone formation in the BMP-2-immobilized composite scaffolds were higher than those in composite scaffolds without BMP-2. Histological evaluation result was similar to that of the micro-CT. Therefore, the surface immobilization of BMP-2 could effectively improve osteogenesis in the gelatin/hydroxyapatite composite scaffold.

Systemic inflammation induced by bacterial infection is one of several causative agents for cardiovascular disorders in patients with periodontal disease. Experimental results indicate that miRNAs play important roles in systemic inflammation induced by endotoxins. Further evidence states that stem cell based therapy shows potential in the treatment of inflammatory responses induced by sepsis. This study investigates if stem cells show protective effects on cardiomyocyte damage induced by porphyromonas gingivalis-LPS (Pg-LPS) through regulating miRNAs. H9c2 cardiomyoblasts and neonatal rat cardiomyocytes (NRCMs) were damaged using Pg-LPS in this study. Pg-LPS damaged H9c2 or NRCMs were then rescued using adipose-derived stem cells (ADSC). The experimental results reveal that Pg-LPS treatment is capable of inducing TLR4/NFκB axis activation, cell death signaling and IGF1R/PI3 K/Akt axis suppression. miR181b was downregulated in Pg-LPS damaged H9c2/NRCMs. All markers were improved in H9c2/NRCMs cocultured with ADSC. miR181b mimic and inhibitor confirmed that miR181b plays a central role in regulating the cardio protective effect on Pg-LPS damaged H9c2/NRCMs cocultured with ADSC. miR181b acts as potential therapeutic marker in cardiomyopathy induced by Pg-LPS. Transplantation of adipose-derived stem cells show potential in the treatment of cardiomyopathy induced by porphyromonas gingivalis endotoxin via regulation of miR181b.

Treatment of hyperglycemia with drugs that block renal glucose reabsorption via inhibition of sodium-dependent glucose cotransporter 2 (SGLT2) is a novel approach to diabetes management. In this study, twenty-seven aryl C-glycosides bearing a C=N/C−N linkage at the glucosyl C6 position were designed, synthesized and evaluated for their inhibitory activity against human SGLT2 (hSGLT2). Compounds with good hSGLT2 inhibition were further investigated to determine their selectivity over hSGLT1. Of these, five representative aryl C-glycosides were chosen for pharmacokinetic analysis. Oxime 2a was determined to have the most promising pharmacokinetic properties and was selected for in vivo glucosuria and plasma glucose level studies, which found it to exhibit comparable efficacy to dapagliflozin (1). Furthermore, 2a was not found to exhibit either significant cytotoxicity (CC50 > 50 μM) or human ether-a-go-go related gene (hERG) inhibition (2% inhibition at 10 μM). Taken together, these efforts culminated in the discovery of oxime 2a as a potential SGLT2 inhibitor.

Impaired growth factor production, angiogenic response, macrophage function, and collagen accumulation have been shown to delay wound healing. Delayed wound healing is a debilitating complication of diabetes that leads to significant morbidity. In this study, curcumin and Lithospermi radix (LR) extract, which are used in traditional Chinese herbal medicine, were added within nanofibrous membranes to improve wound healing in a streptozotocin (STZ)-induced diabetic rat model. Gelatin-based nanofibers, which were constructed with curcumin and LR extract at a flow rate of 0.1 mL/hour and an applied voltage of 20 kV, were electrospun onto chitosan scaffolds to produce bilayer nanofibrous scaffolds (GC/L/C). The wounds treated with GC/L/C exhibited a higher recovery rate and transforming growth factor-beta (TGF-&beta, ) expression in Western blot assays. The decreased levels of pro-inflammatory markers, interleukin-6 (IL-6) and tumor necrosis factor-&alpha, (TNF-&alpha, ), provided evidence for the anti-inflammatory effects of GC/L/C treatment. Chronic wounds treated with GC/L/C achieved better performance with a 58 &plusmn, 7% increase in recovery rate on the seventh day. Based on its anti-inflammatory and wound-healing effects, the GC/L/C bilayer nanofibrous scaffolds can be potential materials for chronic wound treatment.

PURPOSE Radiotherapy is an effective treatment for many types of cancer in clinical settings. Gel dosimetry has the potential to record three-dimensional (3D) dose distribution compared to a conventional ion chamber. As the elasticity of the gel is altered after irradiation due to gel polymerization, we aim to measure the dose recorded in gel dosimetry with ultrasonic shear wave elasticity imaging (SWEI), a nondestructive and quantitative elasticity imaging tool. METHODS In this study, a cylindrical N-isopropylacrylamide (NIPAM) polymer gel with a diameter of 10 cm and a height of 10 cm and with cellulose as an ultrasonic scatterer was irradiated by a linear accelerator with the irradiation parameters of 6 MV x-ray, dose rate of 100 cGy/min and field size of 10 × 20 mm2 . The six gel phantoms were irradiated with the dose of 0, 1, 3, 5, 8, or 10 Gy. The gel phantoms were measured with SWEI at 24, 36, and 48 h after x-ray irradiation. The two-dimensional (2D) shear wave velocity and Young's modulus maps corresponding to x-ray dose distribution were reconstructed following a time-of-flight reconstruction from a set of time-series displacement maps. The spatial resolution of the reconstructed SWEI image is ~1 mm. RESULTS Our results show that the elastic modulus increases linearly as irradiation dose increases (R2 = 0.94 at 24 h, R2 = 0.98 at 36 h, R2 = 0.98 at 48 h), suggesting that the gel elasticity is highly associated with x-ray irradiation dose at 36 h post irradiation, and the dose resolution was 0.66 kPa/Gy. From the 3D elastic modulus maps, the dose distribution along the depth and lateral direction can be reflected in the NIPAM gel dosimetry using SWEI as well. CONCLUSIONS In this study, the irradiated NIPAM gel phantom was quantitatively measured with SWEI for the first time to read the dose distribution recorded in the gel dosimetry. The results suggest that the gel elasticity is highly associated with x-ray irradiation dose. In the future, 2D/or 3D dose distribution from intensity modulated radiotherapy (IMRT) or other potential particle radiotherapy will be measured and reconstructed with SWEI and compared with the dose map from a treatment planning system (TPS) in the clinic.

Background Cardio-dysfunction is one of the complications in patients with diabetes mellitus (DM). This paper aimed to investigate if oral administration of green tea Epigallocatechin-3-gallate (EGCG, E) and transplantation of adipose-derived stem cells (ADSC) show cross effects on the treatment of cardiomyopathy in rats with type 1 DM. Materials and methods Wistar male rats were divided into four groups (each group contained 8 animals) including sham, DM (diabetic group), DM + ADSC (DM group with ADSC treatment) and DM + ADSC + E (DM + ADSC group with oral administration of EGCG). Results Pathological parameters including hypertrophy, inflammation, and fibrosis were activated in DM group. By contrast, all parameters were significantly improved in treatment group (DM + ADSC group). In addition, improvement of pathological parameters in DM + ADSC + E was significantly better than DM + ADSC. Conclusion We found that EGCG can increase expression of survival marker in ADSC under high glucose environment and reduce serum oxidative stress in DM rats.

Volumetric modulated arc therapy (VMAT) was developed to shorten treatment time and increase target conformance. However, a true three-dimensional (3D) gel dosimeter is needed for dose verification. In this study, two clinic cases were adopted: a simple case of lung cancer and a complex case of larynx cancer. For each clinic case, two treatment plans were generated for the same planning target volume using VMAT and intensity modulated radiation therapy calculation software packages. An N-isopropylacrylamide (NIPAM) polymer gel dosimeter was used for 3D dose verification. In addition, the dose characteristics of the NIPAM gel dosimeter were investigated for the two clinic cases.

Innate immune responses are important for pathogen elimination and adaptive immune response activation. However, excess inflammation may contribute to immunopathology and disease progression (e.g. inflammation-associated hepatocellular carcinoma). Immune modulation resulting from pattern recognition receptor-induced responses is a potential strategy for controlling immunopathology and related diseases. This study demonstrates that the mycotoxin patulin suppresses Toll-like receptor- and RIG-I/MAVS-dependent cytokine production through GSH depletion, mitochondrial dysfunction, the activation of p62-associated mitophagy, and p62-TRAF6 interaction. Blockade of autophagy restored the immunosuppressive activity of patulin, and pharmacological activation of p62-dependent mitophagy directly reduced RIG-I-like receptor-dependent inflammatory cytokine production. These results demonstrated that p62-dependent mitophagy has an immunosuppressive role to innate immune response and might serve as a potential immunomodulatory target for inflammation-associated diseases.

The incidence of osteoporosis has increased among the elderly population. Establishing a model of bone remodeling for screening new drugs is critical to identify safe and effective treatments for osteoporosis. In this study, we established a platform to investigate the therapeutic effects of collagenous peptides extracted from scales of two kinds of fish, namely, sparidae and chanos. These peptides were prepared using seven concentrations of collagenous peptide: 100, 80, 60, 40, 20, 10 and 1 mg/ml. Experimental results indicated that collagenous peptides promoted the proliferation of osteoblasts and inhibited the proliferation of mature osteoclasts; the effective concentration of collagenous peptide-sparidae was 10 mg/ml and that of collagenous peptide-chanos was 40 mg/ml. These findings demonstrate that, to a certain extent, collagenous peptides extracted from fish scales can be used to prevent osteoporosis to assist bone remodeling.

The new flavone-glycoside aciculatin (1), from Chrysopogon aciculatus, has been shown to have cytotoxic, anti-inflammatory, and antiarthritis activity. Further biological studies have been limited because of the limited availability of 1 from natural sources. Herein the first total synthesis of 1 in an overall yield of 8.3% is described. The synthesis involved the regio- and stereoselective glycosylation-Fries-type O-to-C rearrangement to construct the C-aryl glycosidic linkage, followed by a Baker-Venkataraman rearrangement and cyclodehydration to form the flavone scaffold.

Suppression of glucose reabsorption through the inhibition of sodium-dependent glucose co-transporter 2 (SGLT2) is a promising therapeutic approach for the treatment of type 2 diabetes. To investigate the effect of C6-substitution on inhibition of SGLT2 by N-indolylglucosides, a small library of 6-triazole, 6-amide, 6-urea, and 6-thiourea N-indolylglycosides were synthesized and tested. A detailed structure-activity relationship (SAR) study culminated in the identification of 6-amide derivatives 6a and 6o as potent SGLT2 inhibitors, which were further tested for inhibitory activity against SGLT1. The data obtained indicated that 6a and 6o are mildly to moderately selective for SGLT2 over SGLT1. Both compounds were also evaluated in a urinary glucose excretion test and pharmacokinetic study; 6a was found capable of inducing urinary glucose excretion in normal SD rats.

Uneven distribution of pores, lack of connection between holes, low reproducibility, insufficient mechanical strength, and incomplete volatility of organic solvents are some problems associated with traditional tissue engineering methods for bone defect repair. These characteristics reduce the quality and stability of products. This study uses 3D printing (3DP) to fabricate a biocompatible poly(lactic) acid-based scaffold for repairing bone tissue. Hence, three different types of scaffolds are assessed: a freeze-dried polylactic acid (PLA) scaffold constructed using the traditional freeze-extraction method; a 3D-PLA scaffold produced through the 3DP technique; and a 3D-PLA-bone morphogenetic protein-2 (BMP-2) scaffold that is prepared using 3DP technology, with the addition of BMP-2. To enhance biological activity, polydopamine (pDA) is used to graft BMP-2 on the surface of the 3D-PLA-BMP-2 scaffold. Then, the scaffolds are implanted into the bilateral femoral condyles of rabbits, and their ability to repair the bone tissue defects is tested. The results of the experiments reveal that the 3DP scaffolds are more biocompatible than the ones produced through the traditional manufacturing methods because they enhance cell adhesion and differentiation after pDA modification and BMP-2 fixation. In the future, the 3DP products may be applied for the repair of larger bone defects in the clinical setting.

Prolonged healing is a severe problem for elderly and diabetic patients. Impaired angiogenesis, stem cell differentiation, and migration have been shown to delay wound healing. The chemokine stromal cell-derived factor-1 (SDF-1) plays an essential role in recruiting cells to wound sites and is suggested to be a candidate for tissue engineering. In this study, chitosan (CHI) scaffolds were crosslinked with nontoxic genipin (Gp) and further heparinized for SDF-1 immobilization. Then, the structures were evaluated for their physicochemical properties (porosity, swelling ratio, and water vapor transmission rate (WVTR)). The interaction between SDF-1 and heparin could sustain SDF-1 release, which has been shown to enhance human umbilical vein endothelial cell (HUVEC) 2D/3D migration. The investigation of the wound-healing activity of the SDF-1-loaded CHI scaffolds revealed a better wound recovery rate in vivo in healthy and streptozotocin-induced diabetic Sprague-Dawley (SD) rats. The histological analysis illustrated that the local of SDF-1 treatment scaffold at the wound site enhanced neovascularization. The wounds treated with SDF-1 scaffolds also exhibited higher vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) expression in Western blot assays. Based on the wound-healing activity and beneficial characteristics, the SDF-1-loaded CHI scaffold demonstrates potential as a material for treating skin wounds.

A poly(&gamma, &ndash, glutamic acid)/&beta, tricalcium phosphate (&gamma, PGA/&beta, TCP) composite fibrous mat was fabricated using the electrospinning technique as a novel bone substitute. The mat was then cross-linked with cystamine in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide to improve its water-resistant ability. Scanning electron micrographs revealed that the &gamma, TCP fibers had a uniform morphology with diameters ranging from 0.64 &plusmn, 0.07 &micro, m to 1.65 &plusmn, 0.16 &micro, m. The average diameter of the fibers increased with increasing cross-linking time. Moreover, increasing the cross-linking time and decreasing the &gamma, TCP weight ratio decreased the swelling ratio and in vitro degradation rate of the composite fibrous mat. In vitro experiments with osteoblast-like MG-63 cells demonstrated that the mat with a &gamma, TCP weight ratio of 20 and cross-linked time of 24 h had a higher alkaline phosphatase activity and better cell adhesion. Furthermore, the rat cranial bone defect was created and treated with the &gamma, TCP composite fibrous mat to evaluate its potential in bone regeneration. After 8 weeks of implantation, micro computed tomography showed that the &gamma, TCP composite fibrous mat promoted new bone growth. These observations suggest that the &gamma, TCP composite fibrous mat has a potential application in bone tissue engineering.

Exercise is known to be beneficial in controlling aging associated disorders however, the consequence of long-term exercise on cardiac health among aging population is not much clear. In this study the protective effect of exercise on aging associated cardiac disorders was determined using a D-galactose-induced aging model. Eight weeks old Sprague Dawley rats were given intraperitoneal injection of 150 mL/kg D-galactose. Swimming exercise was provided in warm water for 60 min/day for five days per week. Hematoxylin and eosin staining of cardiac tissue sections revealed cardiomyocyte disarrangements in the aging rat hearts but long-term exercise training showed improvements in the cardiac histology. Exercise training also enhanced the expression levels of proteins such as SIRT1, PGC-1α and AMPKα1 that are associated with energy homeostasis and further suppressed aging associated inflammatory cytokines. Our results show that long-term exercise training potentially enhances SIRT1 associated anti-aging signaling and provide cardio-protection against aging.

Staphylococcus aureus (S. aureus) is a leading cause of keratitis worldwide and a significant threat to healthy vision. Pathological manifestations of bacterial keratitis (BK) caused by S. aureus involve stromal opacity, edema and neovascularization of an inflamed cornea, requiring immediate medical attention. Thus, S. aureus-induced keratitis is a devastating ocular infection that can lead to blindness if effective and timely treatment is not initiated. In this study, we demonstrate gelatin-capped silver nanoparticles (G-Ag NPs) as anti-infective therapeutics for the treatment of S. aureus-induced keratitis. G-Ag NPs were prepared by simple mixing of silver nitrate, maltose and gelatin. The gelatin molecules are capped in situ on the Ag NPs (∼14 nm). Compared to uncapped Ag NPs, the G-Ag NPs possess superior stability and antibacterial activity against S. aureus. We further demonstrate that G-Ag NPs possess effective inhibition of the proliferation, migration and tube formation of human umbilical vein endothelial cells, as well as strong disturbance of the angiogenesis in chick chorioallantoic membrane and rabbit corneal neovascularization. Furthermore, intrastromal administration of highly biocompatible G-Ag NPs alleviates S. aureus-induced bacterial keratitis in rabbit eyes and bacterial infection-induced corneal neovascularization. Our results demonstrate G-Ag NPs as a promising dual functional (antimicrobial and antiangiogenic) nanotherapeutic for preclinical treatment of eye-related microbial infections.

Sodium-dependent glucose co-transporter 2 (SGLT2) inhibition has been demonstrated to efficiently control hyperglycemia via an insulin secretion-independent pathway. The unique mode of action eliminates the risk of hypoglycemia and makes SGLT2 inhibitors an attractive option for the treatment of type 2 diabetes. In a continuation of our previous studies on SGLT2 inhibitors bearing different sugar moieties, sixteen new N-glucosyl indole derivatives were designed, synthesized, and evaluated for their inhibitory activity against hSGLT2. Of these sixteen, acethydrazide-containing N-glucosyl indole 9d was found to be the most potent SGLT2 inhibitor, and caused a significant elevation in urine glucose excretion in rats at 50 mg/kg, relative to the vehicle control.

This study examined the in vitro characteristics and in vivo wound healing effect of novel Lithospermi radix (LR) extract-containing bilayer scaffolds in a rat model. LR extract, which has been used as a traditional herbal medicine for treating skin wounds, was added to a biocompatible gelatin solution. After glutaraldehyde vapor was used to modify the surface of chitosan scaffolds, various ratios of mammalian gelatin and fish collagen (GF100, GF91 and GF82) were electrospun onto the chitosan scaffolds to manufacture bilayer scaffolds. The porous chitosan scaffolds with a high swelling ratio showed efficient exudate absorption ability. GF91 gelatin nanofibers electrospun at a constant flow rate at 0.1 mL/h and a voltage of 20 kV displayed the optimal characteristics required for cell attachment and skin tissue regeneration. Moreover, the LR extract was successfully released slowly from the GF91 nanofibers. The investigation of the wound-healing activity of the chitosan/gelatin (CGF) bilayer scaffolds revealed that CGF91L provided the highest wound recovery rate in vivo in Sprague-Dawley (SD) rats. Based on its wound-healing effect and beneficial characteristics, the novel LR extract-containing CGF91 bilayer scaffold demonstrates potential as a material for treating skin wounds.

Several reagents have been studied to overcome the problems encountered with antiseptic use, such as moderate cutaneous wound cytotoxicity and skin thinning. We successfully prepared a gelatin/chitosan/epigallocatechin gallate nanoparticle incorporated in a poly(γ-glutamic acid)/gelatin hydrogel, which comprised activated carbon fibers with gentamicin, to fabricate a sandwiched dressing to enhance wound regeneration. The inner layer of activated carbon fibers with gentamicin was designed to prevent bacterial infection, and the outer layer of gelatin/chitosan/epigallocatechin gallate nanoparticles incorporated in a poly(γ-glutamic acid)/gelatin hydrogel was designed to prevent inflammation and facilitate reepithelialization. An in vitro study demonstrated that the dressing effectively inhibited target microorganisms, and scanning electron microscope and confocal laser scanning microscope indicated that the nanoparticles were homogeneously dispersed and migrated into the hydrogel. The in vivo study reported that the sandwiched dressing, comprising the poly(γ-glutamic acid)/gelatin hydrogel, was easy to remove from the wound and facilitated wound tissue regeneration and accelerated healing process.