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In this study, we assessed the effects of MFG-E8 on the biological characteristics of ovarian cancer cells and explored the underlying mechanisms. Human ovarian cancer SKOV3 cells were transfected with MFG-E8 siRNA or NC siRNA. CCK-8, cell adhesion, scratch-wound, and Transwell assays were used to detect changes in cell metastatic processes. Effects of MFG-E8 silencing on the proteins involved in AKT/mTOR/S6K signalling pathway were assessed using qRT-PCR and Western blotting. Transient silencing of MFG-E8 in SKOV3 cells decreased cell proliferation and downregulated the expression of CDK4, cyclin D1, and caspase-3 proteins. Cell adhesion, migration, and invasion were also suppressed. p-AKT, p-mTORC1, and p-p70S6K levels decreased following MFG-E8 knockdown. Hence, MFG-E8 enhances carcinogenesis and affects the AKT/mTOR/S6K signalling pathway in ovarian cancer cells. In conclusion, our results suggested that MFG-E8 could promote ovarian cancer via AKT/mTOR/S6K signalling pathway which improved our understanding of the molecular mechanisms involved in ovarian cancer.IMPACT STATEMENT What is already known on this subject? Milk fat globule-epidermal growth factor 8 (MFG-E8) is expressed in several types of cancers such as oesophageal, breast, and liver. However, the mechanism of MFG-E8 involving in EOC remains unknown. We previously found that MFG-E8 expression was related to pathological staging, tissue differentiation, platinum sensitivity, ascites state, and other clinicopathological characteristics. What the results of this study add? Due to a series of in vitro studies, we confirmed that MFG-E8 is involved in the process of proliferation, invasion and metastasis. Our results show that silencing MFG-E8 can significantly inhibit the expression of cyclin D1 and CDK4 in EOC SKOV3 cells. MFG-E8 enhances carcinogenesis and affects the AKT/mTOR/S6K signaling pathway in ovarian cancer. What the implications are of these findings for clinical practice and/or further research? Taken together, our findings suggest that MFG-E8 may be an oncogene in EOC and provide new insights into the mechanism of MFG-E8 in the progression of EOC.

Purpose: This study evaluated the retrospective outcomes of implant-borne dental rehabilitation in patients with mandibular defects reconstructed with a fibula free flap. Materials and Methods: Patients with segmental mandibular defects were enrolled in this cohort study. Defects in these patients were caused by oral neoplasm, trauma, and osteoradionecrosis. The patients were treated with a fibula free flap procedure and dental implant–borne prostheses between 1988 and 2010. Clinical and radiographic data were evaluated; Kaplan-Meier survival analysis and Poisson regression analysis were used to evaluate implant survival parameters. The statistical significance (α = .05) of the results was determined. Results: Seventy-four patients were selected in this study. All patients were available for continuous follow-up. Nine patients (12.1%) developed fibular graft complications postoperatively: 3 in donor sites and 6 in recipient sites. One hundred ninety-two implants were inserted, and 18 implants failed (9.3%). Overall implant survival in patients was 90.1%, 83.1%, and 69.3% after 5, 10, and 20 years, respectively. In 152 implants, probing depth (PD) ranged from 2 to 3 mm. In 31 implants, PD was greater than 5 mm. In 9 implants, PD was greater than 7 mm. The highest implant failure rates were expected for men (odds ratio [OR] = 2.948; 95% confidence interval [CI], 1.10 to 7.85; P = .031), patients receiving primary fibula free flap reconstruction (OR = 3.696; 95% CI, 1.16 to 11.73; P = .027), and patients receiving radiotherapy (OR = 5.269; 95% CI, 1.40 to 19.7; P = .014). Conclusion: Fibula free flap procedures and implant-borne prostheses proved to be reliable approaches for rehabilitation of mandibular defects and oral function. The overall postoperative fibula free flap and peri-implant complication rates proved to be low. Regular follow-up visits and proper oral hygiene maintenance contributed to the long-term successful treatments. [ABSTRACT FROM AUTHOR]

Objectives: Lumbosacral fusion through either an anterior or a posterior approach to achieve good lordosis and stability is always a challenging surgical operation and is often accompanied by a higher rate of pseudarthrosis than when other lumbar segments are involved. This study evaluated the clinical and radiological results of lumbosacral fusions achieved through a combined anterior and posterior approach. Materials and Methods: From June 2008 to 2012, 20 patients who had L5-S1 instability and stenosis were consecutively treated, first by anterior interbody fusion using an allogenous strut bone graft through the pararectus approach and then by posterior pedicle screw fixation. A minimum of 1-year of clinical and radiological follow-up was conducted. Intraoperative blood loss, surgical time, and any surgery-related complications were recorded. Clinical outcomes were assessed using a visual analog scale (VAS) and the patient's Oswestry Disability Index (ODI) score. After 1 year, radiological outcomes were assessed by analyzing pelvic incidence, lumbar lordosis, and segmental lordosis using static plain films, while fusion stability was assessed using dynamic plain films. Results: The mean operative time and blood loss were 215 min and 325 cc, respectively. After 1 year, the VAS and ODI scores had significantly improved, and stable fusion with good lordotic curvature was obtained in all cases. Conclusion: The surgical results of the combined procedure are satisfactory in terms of the functional and radiological outcomes. Our method offers advantages regarding both anterior fusion and posterior fixation. [ABSTRACT FROM AUTHOR]

Importance: The increased social and economic burdens for osteoporosis-related fractures worldwide make the prevention of such injuries a major public health goal. Previous studies have reached mixed conclusions regarding the association between calcium, vitamin D, or combined calcium and vitamin D supplements and fracture incidence in older adults.Objective: To investigate whether calcium, vitamin D, or combined calcium and vitamin D supplements are associated with a lower fracture incidence in community-dwelling older adults.Data Sources: The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to December 24, 2016, using the keywords calcium, vitamin D, and fracture to identify systematic reviews or meta-analyses. The primary randomized clinical trials included in systematic reviews or meta-analyses were identified, and an additional search for recently published randomized trials was performed from July 16, 2012, to July 16, 2017.Study Selection: Randomized clinical trials comparing calcium, vitamin D, or combined calcium and vitamin D supplements with a placebo or no treatment for fracture incidence in community-dwelling adults older than 50 years.Data Extraction and Synthesis: Two independent reviewers performed the data extraction and assessed study quality. A meta-analysis was performed to calculate risk ratios (RRs), absolute risk differences (ARDs), and 95% CIs using random-effects models.Main Outcomes and Measures: Hip fracture was defined as the primary outcome. Secondary outcomes were nonvertebral fracture, vertebral fracture, and total fracture.Results: A total of 33 randomized trials involving 51 145 participants fulfilled the inclusion criteria. There was no significant association of calcium or vitamin D with risk of hip fracture compared with placebo or no treatment (calcium: RR, 1.53 [95% CI, 0.97 to 2.42]; ARD, 0.01 [95% CI, 0.00 to 0.01]; vitamin D: RR, 1.21 [95% CI, 0.99 to 1.47]; ARD, 0.00 [95% CI, -0.00 to 0.01]. There was no significant association of combined calcium and vitamin D with hip fracture compared with placebo or no treatment (RR, 1.09 [95% CI, 0.85 to 1.39]; ARD, 0.00 [95% CI, -0.00 to 0.00]). No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of nonvertebral, vertebral, or total fractures. Subgroup analyses showed that these results were generally consistent regardless of the calcium or vitamin D dose, sex, fracture history, dietary calcium intake, and baseline serum 25-hydroxyvitamin D concentration.Conclusions and Relevance: In this meta-analysis of randomized clinical trials, the use of supplements that included calcium, vitamin D, or both compared with placebo or no treatment was not associated with a lower risk of fractures among community-dwelling older adults. These findings do not support the routine use of these supplements in community-dwelling older people. [ABSTRACT FROM AUTHOR]

Background: Abundant reports indicated that depression was often comorbid with type 2 diabetes and even metabolic syndrome. Considering they might share common biological origins, it was tentatively attributed to the chronic cytokine-mediated inflammatory response which was induced by dysregulation of HPA axis and overactivation of innate immunity. However, the exact mechanisms remain obscure. Herein, we mainly focused on the function of the NLRP3 inflammasome to investigate this issue.Methods: Male C57BL/6 mice were subjected to 12 weeks of chronic unpredictable mild stress (CUMS), some of which were injected with glyburide or fluoxetine. After CUMS procedure, behavioral and metabolic tests were carried out. In order to evaluate the systemic inflammation associated with inflammasome activation, IL-1β and inflammasome components in hippocampi and pancreases, as well as corticosterone and IL-1β in serum were detected separately. Moreover, immunostaining was performed to assess morphologic characteristics of pancreases.Results: In the present study, we found that 12 weeks' chronic stress resulted in depressive-like behavior comorbid with insulin resistance. Furthermore, antidiabetic drug glyburide, an inhibitor of the NLRP3 inflammasome, was discovered to be effective in preventing the experimental comorbidity. In brief, it improved behavioral performance, ameliorated insulin intolerance as well as insulin signaling in the hippocampus possibly through inhibiting NLRP3 inflammasome activation by suppressing the expression of TXNIP.Conclusions: All these evidence supported our hypothesis that chronic stress led to comorbidity of depressive-like behavior and insulin resistance via long-term mild inflammation. More importantly, based on the beneficial effects of blocking the activation of the NLRP3 inflammasome, we provided a potential therapeutic target for clinical comorbidity and a new strategy for management of both diabetes and depression. [ABSTRACT FROM AUTHOR]

Painful peripheral neuropathy is a severe side effect in oxaliplatin therapy that compromises cancer patients' quality of life. However, its underlying pathogenic mechanisms remain largely unknown. Here, we found that intraperitoneal consecutive administration of oxaliplatin significantly increased excitability of small diameter dorsal root ganglion neurons and induced thermal hyperalgesia in rats. Furthermore, the CX3CL1 expression was significantly increased after oxaliplatin treatment, and intrathecal injection of a neutralizing antibody against CX3CL1 markedly attenuated the enhanced excitability of dorsal root ganglion neurons and thermal hyperalgesia. Importantly, the upregulated CX3CL1 is mediated by the NF-κB signaling pathway, as inhibition of NF-κB p65 activation with pyrrolidine dithiocarbamate or p65 siRNA inhibited the upregulation of CX3CL1, the enhanced excitability of dorsal root ganglion neurons, and thermal hyperalgesia induced by oxaliplatin. Further studies with chromatin immunoprecipitation found that oxaliplatin treatment increased the recruitment of NF-κB p65 to the CX3Cl1 promoter region. Our results suggest that upregulation of CX3CL1 in dorsal root ganglion mediated by NF-κB activation contributes to the peripheral sensitization and chronic pain induced by oxaliplatin administration. [ABSTRACT FROM AUTHOR]

Background: Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure in many countries. The aim of the study was to describe the profiling of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the plasma and liver of Acetaminophen -induced liver injured mice. Methods: A time course study was carried out using C57BL/6 mice after intraperitoneal administration of 300 mg/kg Acetaminophen 1 h, 3 h, 6 h, 12 h and 24 h. A high-throughput liquid chromatography mass spectrometry (LC-MS) lipidomic method was utilized to detect phosphatidylcholine and phosphatidylethanolamine species in the plasma and liver. The expressions of phosphatidylcholine and phosphatidylethanolamine metabolism related genes in liver were detected by quantitative Reverse transcription polymerase chain reaction (qRT-PCR) and Western-blot. Results: Following Acetaminophen treatment, the content of many PC and PE species in plasma increased from 1 h time point, peaked at 3 h or 6 h, and tended to return to baseline at 24 h time point. The relative contents of almost all PC species in liver decreased from 1 h, appeared to be lowest at 6 h, and then return to normality at 24 h, which might be partly explained by the suppression of phospholipases mRNA expressions and the induction of choline kinase (Chka) expression. Inconsistent with PC profile, the relative contents of many PE species in liver increased upon Acetaminophen treatment, which might be caused by the down-regulation of phosphatidylethanolamine N-methyltransferase (Pemt). Conclusions: Acetaminophen overdose induced dramatic change of many PC and PE species in plasma and liver, which might be caused by damaging hepatocytes and interfering the phospholipid metabolism in Acetaminophen -injured liver. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases. Enterodiol (END) and enterolactone (ENL) are mammalian lignans, which can reduce the risk of various cancers. However, the effects of END and ENL on ovarian cancer are not adequately documented. Methods: We used in vitro assays on the ES-2 cell line to evaluate the inhibiting effects of END and ENL on ovarian cancer cell proliferation, invasion and migration ability and in vivo xenograft experiments on nude mice to validate the anticancer effects of END and ENL. Results: The in vitro assays demonstrated that high-dose END and ENL could obviously inhibit ovarian malignant properties, including cancerous proliferation, invasion, and metastasis. Compared to END, ENL behaved in a better time-dose dependent manner on the cancer cells. The in vivo experiments showed that END (1 mg/kg), ENL (1 mg/kg) and ENL (0.1 mg/kg) suppressed tumor markedly, and there were statistically significant differences between the experimental and control groups in tumor weight and volume. Compared to END, which have serious side effects to the animals at high concentration such as 1 mg/kg, ENL had higher anticancer activities and less side effects in the animals than END at the same concentrations, so it would be a better candidate for drug development. Conclusion: END and ENL both have potent inhibitory effects on ovarian cancer but ENL possesses a more effective anti-cancer capability and less side effects than END. Findings in this work provide novel insights into ovarian cancer therapeutics with phytoestrogens and encourage their clinical applications. [ABSTRACT FROM AUTHOR]

Purpose: This meta-analysis aimed to compare the efficacy and safety of teriparatide vs. bisphosphonates in the management of osteoporosis.Methods: A total of 1,967 patients from eight randomized controlled trials were analyzed; outcomes included bone mineral density (BMD) of the femoral neck, total hip and lumbar spine, vertebral and nonvertebral fractures and any adverse event. A subgroup analysis of treatment effectiveness was performed according to the etiology of osteoporosis; i.e., glucocorticoid-induced osteoporosis (GIO) vs. post-menopausal osteoporosis (PO).Results: Teriparatide increased the BMD of the lumbar spine, femoral neck and total hip to a greater extent than bisphosphonates. Patients treated with teriparatide also had a lower risk of vertebral fractures compared with bisphosphonates; however, no difference in risk of nonvertebral fractures (or adverse events) was found. GIO subgroups showed larger increases in BMD of the lumbar spine, total hip and femoral neck in patients treated with teriparatide compared with bisphosphonates. The PO subgroup showed larger increases in BMD of the lumbar spine in patients treated with teriparatide compared with bisphosphonates. Patients in the GIO subgroup (but not the PO subgroup) were less likely to suffer a vertebral fracture on teriparatide as compared with bisphosphonates. In contrast, no significant difference in the percentage of nonvertebral fractures was noted between the two types of treatment for either subgroup.Conclusion: Teriparatide significantly increased the BMD of lumbar spine, total hip and femoral neck, particularly in GIO-induced osteoporosis. Teriparatide did not lower the risk of nonvertebral fractures when compared with bisphosphonates. [ABSTRACT FROM AUTHOR]

Uveitis, defined as inflammation of the uveal tract, may cause blindness in both young and middle-aged people. Approximately 10–15% of blindness in the West is caused by uveitis. Therefore, a comprehensive investigation to determine the disease pathogenesis is urgent, as it will thus be possible to design effective treatments. Identification of the disease genes that cause uveitis is an important requirement to achieve this goal. To begin to answer this question, in this study, a computational method was proposed to identify novel uveitis-related genes. This method was executed on a large protein–protein interaction network and employed a popular ranking algorithm, the RandomWalk with Restart (RWR) algorithm. To improve the utility of the method, a permutation test and a procedure for selecting core genes were added, which helped to exclude false discoveries and select the most important candidate genes. The five-fold cross-validation was adopted to evaluate the method, yielding the average F1-measure of 0.189. In addition, we compared our method with a classic GBA-based method to further indicate its utility. Based on our method, 56 putative genes were chosen for further assessment. We have determined that several of these genes (e.g., CCL4, Jun, and MMP9) are likely to be important for the pathogenesis of uveitis. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported that eEF-2 kinase is associated with tumour cell sensitivity to certain therapies. In the present study, we investigated the relationship between eEF-2 kinase and lapatinib, a dual inhibitor of EGFR and HER-2, in nasopharyngeal carcinoma (NPC) cells. Methods: The effect of treatment on the growth and proliferation of NPC cells was measured by three methods: cell counting, crystal violet staining and colony counting. Apoptosis was evaluated by flow cytometry to determine Annexin V-APC/7-AAD and cleaved PARP levels, and the results were further confirmed by Western blot analysis. The expression of eEF-2 kinase and the impacts of different treatments on different signalling pathways were analysed by Western blot analysis. Results: The expression of eEF-2 kinase was significantly associated with NPC cell sensitivity to lapatinib. Therefore, suppression of this kinase could increase the cytocidal effect of lapatinib, as well as reduce cell viability and colony formation. Furthermore, inhibition of eEF-2 kinase, by either RNA interference (eEF-2 kinase siRNA or shRNA) or pharmacological inhibition (NH125), enhanced lapatinib-induced apoptosis of NPC cells. The results also showed that lapatinib combined with NH125 had a synergistic effect in NPC cells. In addition, mechanistic analyses revealed that downregulation of the ERK1/2 and Src pathways, but not the AKT pathway, was involved in this sensitizing effect. Conclusions: The results of this study suggest that targeting eEF-2 kinase may improve the efficacy of therapeutic interventions such as lapatinib in NPC cells. [ABSTRACT FROM AUTHOR]

Background: No systemic evaluation of asthma control in Jilin Province has been reported. Asthma control might provide the basis for asthma management in this region. A multicenter hospital-based cross-sectional study was performed to investigate the asthma control and related factors for severe asthma exacerbations in patients with moderate or severe asthma in Jilin Province, China.Methods: The study enrolled 1546 patients in five grade one general hospitals from January to December 2013. Asthma medication, patient self-management, asthma control test (ACT) scores and frequency of severe asthma exacerbations during the follow-up (12 months) were collected via a follow-up questionnaire.Results: In the study, 889 patients provided a complete follow-up questionnaire. Severe asthma exacerbations occurred in 54.89 % of patients. ACT score ≤15, asthma medication ≤ 3 months, severe asthma, income level lower than average Per Capita Disposable Income (PCDI) and a lower educational level were risk factors of a severe exacerbation.Conclusions: Poor adherence to asthma medication, poor asthma symptom control, lower income, a low educational level might be possible reasons for the high incidence of severe asthma exacerbations and poor asthma control in Jilin Province of China. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) is a complex illness with high rates of morbidity and mortality. In embryonic development, the heart is the first formed organ, which is strictly controlled by gene regulatory networks, including transcription factors, signaling pathways, epigenetic factors and microRNAs. Bone morphogenetic protein (BMP)-2 and - 4 are essential in cardiogenesis as they can induce the expression of transcription factors, NKX2-5 and GATA binding protein 4, which are important in the development of the heart. The inhibition of BMP-2 and -4 inhibits the late expression of NKX2-5 and affects cardiac differentiation. The aim of the present study was to investigate whether BMP-2 and -4 variations may be associated with CHD in Chinese Han populations. The rs1049007, rs235768 and rs17563 single nucleotide polymorphisms (SNPs), which are genetic variations located within the translated region of the BMP-2 and -4, were evaluated in 230 patients with CHD from the Chinese Han population and 160 non-CHD control individuals. Statistical analyses were performed using the χ² test, implemented using SPSS software (version 13.0). The Hardy-Weinberg equilibrium test was performed on the population using online Online Encyclopedia for Genetic Epidemiology studies software, and multiple-sequence alignments of the BMP proteins were performed using Vector NTI software. No statistically significant associations were identified between these genetic variations and the risk of CHD (rs1049007, P-value=0.560; rs235768, P-value=0.972; rs17563, P-value=0.787). In addition, no correlation was found between the patients with CHD and the non-CHD control individuals. Therefore, the rs1049007, rs235768 and rs17563 genetic variations of BMP-2 were not associated with CHD in the Chinese Han population. [ABSTRACT FROM AUTHOR]

The medicinal value of hydrogen (H2) was ignored prior to research illustrating that inhalation of 2% H2 can significantly decrease the damage of cerebral ischemia/reperfusion caused by oxidative stress via selective elimination of hydroxyl freebase (OH) and peroxynitrite anion (ONOO-). Subsequently, there have been numerous experiments on H2. Most research and trials involving the mechanisms underlying H2 therapy show the effects of antioxygenation, anti-inflammation, and anti-apoptosis. Among quantities of diseases related with H2 therapy, the brain disease is a hotspot as brain tissue and cell damage are easier to be induced by oxidative stress and other stimulations. In this review, emphasis is on stroke, traumatic brain injuries, and degenerative diseases, such as Alzheimer's disease and Parkinson's disease. Taking into account the blood-brain barrier, penetrability, possible side effects, and the molecular properties of H2 within a single comprehensive review should contribute to advancing both clinical and non-clinical research and therapies. A systematic introduction of H2 therapy with regards to mechanisms and cerebral diseases both in animal and human subjects can make it easier to comprehend H2 therapy and therefore provide the basis for further clinical strategy. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are transcribed RNAs with more than 200 nucleotides in length. A growing body of evidence supports the notion that lncRNAs act as competitive endogenous RNAs for microRNAs and play roles in physiological and pathological processes. Several studies have demonstrated the roles of microRNAs in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, it is unknown whether lncRNAs are involved in IPF. To investigate the roles of lncRNAs in IPF, we determined the interaction of lncRNAs and microRNAs by motif search and manual comparison. The sequences of the dysregulated microRNAs in IPF including miR-21, miR-31, miR-101, miR- 29, miR-199, and let-7d were used to search NONCODE database containing 33,829 human lncRNAs. A total of 34 lncRNAs with potential binding sites to these microRNAs were identified. We then examined the expression levels of the identified lncRNAs in the lungs of IPF patients by real-time PCR. Of 34 lncRNAs, nine lncRNAs were dysregulated in the IPF lungs. Four of them were inversely correlated to the microRNA expression in IPF. Further studies revealed that silencing the lncRNA CD99 molecule pseudogene 1 (CD99P1) inhibited proliferation and α-smooth muscle actin expression of lung fibroblasts, while knockdown of the lncRNA n341773 increased collagen expression in lung fibroblasts. These results suggest that CD99P1 and n341773 may be involved in the regulation of lung fibroblast proliferation and differentiation. The identification of regulatory functions of lncRNAs in lung fibroblasts may provide new research directions for the therapy of IPF. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is characterized by progressive and inexorable β-cell dysfunction, leading to insulin deficiency. Novel strategies to preserve the remaining β-cells and restore β-cell function for the treatment of diabetes are urgently required. Mesenchymal stem cells (MSCs) have been exploited in a variety of clinical trials aimed at reducing the burden of immune-mediated disease. The aim of the present clinical trial was to assess the safety and efficacy of umbilical cord-derived MSC (UCMSC) transplantation for patients with T2D. The safety and efficacy of UCMSC application were evaluated in six patients with T2D during a minimum of a 24-month follow-up period. Following transplantation, the levels of fasting C-peptide, the peak value and the area under the C-peptide release curve increased significantly within one month and remained high during the follow-up period (P<0.05). Three of the six patients became insulin free for varying lengths of time between 25 and 43 months, while the additional three patients continued to require insulin injections, although with a reduced insulin requirement. Fasting plasma glucose and 2-h postprandial blood glucose levels were relatively stable in all the patients following transplantation. There was no immediate or delayed toxicity associated with the cell administration within the follow-up period. Therefore, the results indicated that transplantation of allogeneic UCMSCs may be an approach to improve islet function in patients with T2D. There were no safety issues observed during infusion and the long-term monitoring period. [ABSTRACT FROM AUTHOR]

The effects of medicine on the biomolecular interaction have been given increasing attention in biochemistry and affinity-based analytics since the environment in vivo is complex especially for the patients. Herein, myoglobin, a biomarker of acute myocardial infarction, was used as a model, and the medicine effects on the interactions of myoglobin/aptamer and myoglobin/antibody were systematically investigated using atomic force microscopy (AFM) for the first time. The results showed that the average binding force and the binding probability of myoglobin/aptamer almost remained unchanged after myoglobin-modified gold substrate was incubated with promazine, amoxicillin, aspirin, and sodium penicillin, respectively. These parameters were changed for myoglobin/antibody after the myoglobin-modified gold substrate was treated with these medicines. For promazine and amoxicillin, they resulted in the change of binding force distribution of myoglobin/antibody (i.e., from unimodal distribution to bimodal distribution) and the increase of binding probability; for aspirin, it only resulted in the change of the binding force distribution, and for sodium penicillin, it resulted in the increase of the average binding force and the binding probability. These results may be attributed to the different interaction modes and binding sites between myoglobin/aptamer and myoglobin/antibody, the different structures between aptamer and antibody, and the effects of medicines on the conformations of myoglobin. These findings could enrich our understanding of medicine effects on the interactions of aptamer and antibody to their target proteins. Moreover, this work will lay a good foundation for better research and extensive applications of biomolecular interaction, especially in the design of biosensors in complex systems. [ABSTRACT FROM AUTHOR]

Optic nerve trauma is a common occurrence that results in irreversible blindness. Currently, no effective strategies are known to prevent optic nerve degeneration. We assessed the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) after optic nerve crush in the adult rat. Our results showed that BMSCs significantly promoted the regeneration of injured axons compared with phosphate buffered saline alone. Therefore, BMSC transplantation may be effective for the treatment of central nervous system disorders. [ABSTRACT FROM AUTHOR]

Etanercept (ETN) has been widely applied in the treatment of ankylosing spondylitis (AS). As the use of ETN has increased, associated adverse effects have been reported frequently. Previous meta-analyses have focused on comparing the differences in clinical outcomes between ETN and placebo (PBO). The present meta-analysis evaluated randomised controlled trials (RCTs) to compare the effects of ETN and a PBO or sulfasalazine (SSZ) in patients with AS. The study population characteristics and the main results, including the Assessment in AS 20% response (ASAS 20), the Bath AS Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI), were extracted. The pooled odds ratios (ORs) or weighted mean differences (MDs) were calculated using a fixed or random effects model. Fifteen randomised controlled trials (RCTs) involving 2,194 subjects were included. Compared with a PBO, ETN significantly improved the ASAS 20 [P<0.00001; OR, 8.25; 95% confidence interval (CI), 5.92-11.50], BASDAI (P<0.00001; MD, -18.81; 95% CI, -24.47 to -13.15) and BASFI (P<0.00001; standard MD, -0.68; 95% CI, -0.85 to -0.50). In comparison with SSZ, ETN significantly decreased the BASDAI (P<0.00001; MD, -2.40; 95% CI, -2.89 to -1.90) and C-reactive protein (CRP) levels (P<0.0001; MD, -8.01; 95% CI, -11.73 to -4.29). The most common adverse effect of ETN was an injection site reaction. This meta-analysis shows that ETN monotherapy is effective in improving physical function and reducing disease activity in patients with AS. Compared with SSZ, ETN markedly decreased the BASDAI and CRP levels. However, the efficacy of ETN in treating AS requires further evaluation by more RCTs in a larger population of patients prior to recommending ETN as a substitute for synthetic disease-modifying antirheumatic drug (DMARD) monotherapy, or combinations of synthetic DMARDs. [ABSTRACT FROM AUTHOR]

Background The local recurrence rate after surgical excision of intramuscular hemangioma reported is between 18% and 61%. The aim of this study was to review the clinical outcome and local recurrence rate after surgical excision of nonpalpable intramuscular hemangioma using preoperative ultrasound-guided hookwire localization. Methods We performed ultrasound-guided hookwire localization before excision surgery for nonpalpable intramuscular hemangioma in 37 cases between January 1997 and 2011. There were 20 females and 17 males, with a mean age of 30.2 years (range, 17-49 years). The mean localization procedure time was 10.6 minutes (range, 3-20 minutes). Results The average operation time was 48.6 minutes (range, 30-80 minutes). The average length of the excision wound was 5 cm (range, 4-11 cm), and the average hospital stay was 2.5 days (range, 2-4 days). The postoperative therapeutic report confirmed the diagnosis of intramuscular hemangioma. The average tumor size was 2.11 cm and all excision margins were free in all specimens. After the mean follow-up of 92.9 months (range, 14-179 months), one of the 37 patients had local recurrence (recurrence rate 2.7%). Conclusion The use of ultrasound-guided hookwire localization before excision surgery is safe and effective in treating nonpalpable intramuscular hemangioma and could provide a better cosmetic result and functional recovery. [ABSTRACT FROM AUTHOR]

An abstract of the article "Idiopathic Hypereosinophilic Syndrome With Pulmonary Arterial Hypertension: A Case Report and Literature Review" is presented.

Pulmonary neutrophils are the initial inflammatory cells that are recruited during lung injury and are crucial for innate immunity. However, pathological recruitment of neutrophils results in lung injury. The objective of this study is to determine whether the novel neutrophil chemoattractant, soluble VCAM-1 (sVCAM-1), recruits pathological levels of neutrophils to injury sites and amplifies lung inflammation during acute lung injury. The mice with P2X7 receptor deficiency, or treated with a P2X7 receptor inhibitor or anti–VCAM-1 Abs, were subjected to a clinically relevant two-hit LPS and mechanical ventilation–induced acute lung injury. Neutrophil infiltration and lung inflammation were measured. Neutrophil chemotactic activities were determined by a chemotaxis assay. VCAM-1 shedding and signaling pathways were assessed in isolated lung epithelial cells. Ab neutralization of sVCAM-1 or deficiency or antagonism of P2X7R reduced neutrophil infiltration and proinflammatory cytokine levels. The ligands for sVCAM-1 were increased during acute lung injury. sVCAM-1 had neutrophil chemotactic activities and activated alveolar macrophages. VCAM-1 is released into the alveolar airspace from alveolar epithelial type I cells through P2X7 receptor–mediated activation of the metalloproteinase ADAM-17. In conclusion, sVCAM-1 is a novel chemoattractant for neutrophils and an activator for alveolar macrophages. Targeting sVCAM-1 provides a therapeutic intervention that could block pathological neutrophil recruitment, without interfering with the physiological recruitment of neutrophils, thus avoiding the impairment of host defenses. [ABSTRACT FROM AUTHOR]

Capecitabine, an oral prodrug of 5-fluorouracil, inhibits DNA synthesis and has received FDA approval for treatment of metastatic colorectal and breast cancers. Hand-foot syndrome (HFS) is a serious dose-limiting toxicity and the most frequently reported side effect of capecitabine. Because of the lack of knowledge about the causative mechanism of HFS, scarce information is available for effective treatment or prevention. Data are based on published literatures and reports available from the HFS development program database. The purpose of this Review is to provide information regarding definition, clinical manifestation, and the possible mechanisms of HFS induced by capecitabine. Ethnic variations in the clinical presentation of HFS warrant further attention. Several physiological and pharmacological mechanisms have been investigated, such as cyclooxygenase (COX) inflammatory-type reaction, accumulation of capecitabine metabolites, and enzymes and transporters involved in the metabolism and absorption. Although current studies describe the possible mechanisms of HFS induced by capecitabine, much remains to be determined. It appears from this scientific evidence that additional study is needed to determine the effect of skin-mediated metabolism in the possible mechanism of HFS induced by capecitabine. [ABSTRACT FROM AUTHOR]