Alleviating Severe Cytoskeletal Destruction of Spinal Motor Neurons: Another Effect of Docosahexaenoic Acid in Spinal Cord Injury.

Spinal cord injury (SCI) treatment remains a major challenge. Spinal motor neurons (MNs) are seriously injured in the early stage after SCI, but this has not received sufficient attention. Oxidative stress is known to play a crucial role in SCI pathology. Our studies demonstrated that oxidative stress can cause severe damage to the cytoskeleton of spinal MNs. Docosahexaenoic acid (DHA) has been shown to have beneficial effects on SCI, but the mechanism remains unclear, and no study has investigated the effect of DHA on oxidative stress-induced spinal MN injury. Here, we investigated the effect of DHA on spinal MN injury through in vivo and in vitro experiments, focusing on the cytoskeleton. We found that DHA not only promoted spinal MN survival but, more importantly, alleviated the severe cytoskeletal destruction of these neurons induced by oxidative stress in vitro and in mice with SCI in vivo. In addition, the mechanisms involved were investigated and elucidated. These results not only suggested a beneficial role of DHA in spinal MN cytoskeletal destruction caused by oxidative stress and SCI but also indicated the important role of the spinal MN cytoskeleton in the recovery of motor function after SCI. Our study provides new insights for the formulation of SCI treatment.

Overexpression of cannabinoid receptor 2 is associated with human breast cancer proliferation, apoptosis, chemosensitivity and prognosis via the PI3K/Akt/mTOR signaling pathway.

INTRODUCTION: The cannabinoid receptor 2 (CB2) is mainly involved in the immune system. However, although CB2 has been reported to play an anti-tumor function in breast cancer (BC), its specific mechanism in BC remains unclear. METHODS: We examined the expression and prognostic significance of CB2 in BC tissues by qPCR, second-generation sequencing, western blot, and immunohistochemistry. We assessed the impacts of overexpression and a specific agonist of CB2 on the growth, proliferation, apoptosis, and drug resistance of BC cells in vitro and in vivo using CCK-8, flow cytometry, TUNEL staining, immunofluorescence, tumor xenografts, western blot, and colony formation assays. RESULTS: CB2 expression was significantly lower in BC compared with paracancerous tissues. It was also highly expressed in benign tumors and ductal carcinoma in situ, and its expression was correlated with prognosis in BC patients. CB2 overexpression and treatment of BC cells with a CB2 agonist inhibited proliferation and promoted apoptosis, and these actions were achieved by suppressing the PI3K/Akt/mTOR signaling pathway. Moreover, CB2 expression was increased in MDA-MB-231 cell treated with cisplatin, doxorubicin, and docetaxel, and sensitivity to these anti-tumor drugs was increased in BC cells overexpressing CB2. CONCLUSIONS: These findings reveal that CB2 mediates BC via the PI3K/Akt/mTOR signaling pathway. CB2 could be a novel target for the diagnosis and treatment of BC.

Identification of STAT5B as a biomarker associated with prognosis and immune infiltration in breast cancer.

BACKGROUND: Breast invasive cancer (BRCA) is the most common malignancy and the second leading cause of malignancy death among women. Signal transducers and activators of transcription (STAT) family played a vital role in regulating certain biological processes and could serve as biomarkers for many diseases or cancers. METHODS: The expression, prognostic value, and clinical functions of STAT family in BRCA were evaluated with several bioinformatics web portals. RESULTS: The expression of STAT5A/5B were downregulated in BRCA in subgroup analyses based on race, age, gender, race, subclasses, tumor histology, menopause status, nodal metastasis status, and TP53 mutation. BRCA patients with high STAT5B expression had a better overall survival, relapse free survival, MDFS and post progression survival. STAT5B expression level can impact the prognosis in BRCA patients with positive PR status, negative Her2 status and wild type TP53. Moreover, STAT5B was positively correlated with immune cell infiltration and the level of immune biomarkers. Drug sensitivity revealed that low STAT5B expression was resistant to the many small molecules or drugs. Functional enrichment analysis revealed that STAT5B was involved in adaptive immune response, translational initiation, JAK-STAT signaling pathway, Ribosome, NF-kappa B signaling pathway and Cell adhesion molecules. CONCLUSIONS: STAT5B was a biomarker associated with prognosis and immune infiltration in breast cancer.

Oxidative stress disrupts the cytoskeleton of spinal motor neurons.

BACKGROUND AND AIM: Traumatic spinal cord injury (SCI) is a common and devastating central nervous disease, the treatment of which faces many challenges to the medical community and society as a whole. Treatment measures based on oxidative stress of spinal motor neurons during SCI are expected to help restore biological functions of neurons under injury conditions. However, to date, there are no systematic reports regarding oxidative stress on spinal motor neuron injury. Our aim is to better understand and explain the influences and mechanisms of oxidative stress on spinal motor neurons during SCI. METHODS: We first exposed VSC4.1 motor neurons to hydrogen peroxide (H2 O2 ) and evaluated the effects on cell viability, morphology, cycling, and apoptosis, with an emphasis on the changes to the cytoskeleton and the effect of N-acetyl-l-cysteine (NAC) on these changes. Then, we investigated the effects of NAC on these cytoskeletal changes in vitro and in vivo. RESULTS: We found that H2 O2 caused severe damage to the normal cytoskeleton, leading to a reduction in neurite length and number, rearrangement of the actin cytoskeleton, and disorder of the microtubules and neurofilaments in VSC4.1. Importantly, NAC attenuated the oxidative damage of spinal motor neurons in vitro and in vivo, promoting the recovery of hindlimb motor ability in mice with SCI at the early stage of injury. CONCLUSION: This study shows that oxidative stress plays an important role in the cytoskeleton destruction of spinal motor neurons in SCI, and treatment of SCI on this basis is a promising strategy. These findings will help to elucidate the role of oxidative stress in spinal motor neuron injury in SCI and provide references for further research into the study of the pathology and underlying mechanism of SCI.

Prevalence of Suboptimal Health Status and Its Influencing Factors among Chinese Software Programmers.

BACKGROUND: There is a lack of specific study of the suboptimal health status (SHS) in software programmers. The aims of the present study were to investigate the prevalence of SHS and analyze the influencing factors among Chinese software programmers. METHODS: A cross-sectional survey using a programmer SHS scale was conducted to evaluate the prevalence of SHS, as well chi-square test and multi-factor logistic regression were applied to analyze the relationship between suboptimal health and personal basic information, living and work habits in software programmers. RESULTS: The prevalence of SHS was 18.67% in software programmers. Single factor analysis found that there were differences in suboptimal health prevalence among different work cities (P = 0.031), hours of sleep per day (P = 0.046), overtime days per month (P = 0.010) and exercise frequency per week (P = 0.015). The factors for suboptimal health such as hours of sleep per day (OR = 0.307, 95% CI = 0.096∼0.984) and exercise frequency per week (OR = 0.190, 95% CI = 0.054∼0.671) significantly affected subjects of SHS via multi-factor logistic regression analysis, indicating that adequate sleep and exercise decreased the chance of SHS up to 30.70% and 19.00%, respectively. CONCLUSION: Suboptimal health had become a serious public health challenge in Chinese software programmers. Whilst, the health status of the programmers could be effectively elevated by improving lifestyles.

The Effect of Metformin on Aminotransferase Levels, Metabolic Parameters and Body Mass Index in Nonalcoholic Fatty Liver Disease Patients: A Metaanalysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common reasons for the increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Moreover, liver- associated death is approximately 10 times higher in patients with NAFLD than in common individuals. In theory, NAFLD is a kind of metabolic syndrome that manifests in the liver, and insulin resistance plays an important role in it. Therefore, drugs that improve insulin sensitivity may be effective for NAFLD. OBJECTIVE: The aim of this study was to evaluate the effect of metformin treatment on aminotransferase levels, metabolic parameters and body mass index in NAFLD patients via a meta-analysis of clinical trials. METHODS: A comprehensive search on PubMed, EMBASE, the Web of Science and the Cochrane Central Register of Controlled Trials was performed for randomized controlled trials (RCTs) on the effect of metformin treatment on aminotransferase levels, metabolic parameters and body mass index in NAFLD patients. Serum hepatic enzyme, lipid, glucose and insulin levels, homeostasis model assessment-insulin resistance (HOMA-IR) index and body mass index (BMI) at different follow-up points exhibited desirable outcomes. The final search was performed in January, 2021. RESULTS: In total, 10 RCTs with 459 patients were included. Compared with controls, metformin could effectively reduce serum fasting glucose and insulin levels and the HOMA-IR index in NAFLD patients at the 6-month follow-up. In addition, metformin could clearly reduce the serum ALT and HOMA-IR index at the 12-month follow-up. Although metformin was found to be effective in managing lipid metabolism and controlling BMI in NAFLD patients compared with that at baseline, the effect was similar to that in controls. In addition, the speed of metformin treatment seemed to be slower than that of controls. CONCLUSION: Compared to the controls, metformin could effectively reduce the serum fasting glucose and insulin levels and the HOMA-IR index in NAFLD patients at the 6-month follow-up and ALT and the HOMA-IR index at the 12-month follow-up.

Resveratrol alleviates ethanol-induced neuroinflammation in vivo and in vitro: Involvement of TLR2-MyD88-NF-κB pathway.

Excessive ethanol (EtOH) intake affects cognitive function and leads to permanent learning and memory deficits. EtOH-induced neuroinflammation plays an important role in EtOH neurotoxicity. Studies have shown that EtOH activates microglia and induces an inflammatory response. Resveratrol (Rsv) is a natural polyphenol found in a wide variety of plants and fruits, and produces the neuroprotective and anti-inflammatory effects in the central nervous system. However, effect of Rsv on EtOH-induced neuroinflammation is still unknown. We investigated the anti-inflammatory effect of Rsv in the context of EtOH-induced neurotoxicity and the molecular mechanisms potentially involved in the effect. The results showed that treatment of rats with Rsv prevented the deficits of spatial reference memory induced by EtOH and mitigated EtOH-induced neuroinflammation by inhibiting microglial activation and decreasing the levels of inflammatory cytokines including interleukin-1ß, interleukin-6 and tumor necrosis factor α. The further studies indicated that Rsv reduced TLR2 expression in vivo and in vitro, and downregulated expression of myeloid differentiation primary response 88 (MyD88) and phosphorylation of nuclear factor κB (NF-κB). These data demonstrate that Rsv alleviates the ethanol-induced neuroinflammation via inhibition of TLR2-MyD88-NF-κB signal pathway.

Efficacy and safety of COX-2 inhibitors for advanced non-small-cell lung cancer with chemotherapy: a meta-analysis.

BACKGROUND: The study of cyclooxygenase-2 (COX-2) inhibitors is now mired in controversy. We performed a meta-analysis to assess the efficacy and safety profile of COX-2 inhibitors in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A literature search of PubMed, EMBASE, the Cochrane Central databases, and ClinicalTrials.gov, up until March 26, 2017, identified relevant randomized controlled trials. Data analysis was performed using Stata 12.0. RESULTS: Six eligible trials (1,794 patients) were selected from the 407 studies that were identified initially. A significant difference, favoring COX-2 inhibitors plus chemotherapy over chemotherapy alone, was observed in the overall response rate (relative risk [RR] =1.25, 95% confidence interval [CI]: 1.06-1.48). Further, we conducted two subgroup analyses according to the type of COX-2 inhibitors (celecoxib, rofecoxib, or apricoxib) and treatment line (first or second chemotherapy). The first-line treatment includes: NP (changchun red bean + cisplatin or carboplatin), GP (double fluorine cytidine + cisplatin or carboplatin), or TP (paclitaxel + cisplatin or carboplatin, docetaxel + cisplatin or carboplatin). The second-line treatment includes two internationally recognized compounds, one is docetaxel and the other is the pemetrexed, both of which are individually selected. In subgroup analysis, significantly increased overall response rate (ORR) results were found for rofecoxib plus chemotherapy (RR =1.56, 95% CI: 1.08-2.25) and COX-2 inhibitor given with first-line chemotherapy (RR =1.27, 95% CI: 1.07-1.50). However, there was no difference between COX-2 inhibitors plus chemotherapy and chemotherapy alone in overall survival (hazard ratio [HR] =1.04, 95% CI: 0.91-1.18), progression-free survival (HR =0.97, 95% CI: 0.86-1.10), and 1-year survival rate (RR =1.03, 95% CI: 0.89-1.20). Toxicity did not differ significantly between COX-2 inhibitors plus chemotherapy and chemotherapy alone with the exception of leukopenia (RR =1.21, 95% CI: 1.03-1.42), thrombocytopenia (RR =1.32, 95% CI: 1.04-1.67), and cardiovascular events (RR =2.39, 95% CI: 1.06-5.42). The results of the Egger's test indicated no significant difference in primary outcomes. CONCLUSION: COX-2 inhibitors improved ORR of advanced NSCLC with chemotherapy, but had no effect on survival indices. Moreover, COX-2 inhibitors may lead to higher rates of hematologic toxicities and cardiovascular events.

Addressing Antibiotic Abuse in China: An Experimental Audit Study.

China has high rates of antibiotic abuse and antibiotic resistance but the causes are still a matter for debate. Strong physician financial incentives to prescribe are likely to be an important cause. However, patient demand (or physician beliefs about patient demand) is often cited and may also play a role. We use an audit study to examine the effect of removing financial incentives, and to try to separate out the effects of patient demand. We implement a number of different experimental treatments designed to try to rule out other possible explanations for our findings. Together, our results suggest that financial incentives are the main driver of antibiotic abuse in China, at least in the young and healthy population we draw on in our study.

Social Networks and Externalities from Gift Exchange: Evidence from A Field Experiment.

This paper asks whether gift exchange generates externalities for people outside of the bilateral relationship between the gift giver and recipient, and whether the nature of this relationship is affected by social networks. We examine this question in the context of a field experiment in urban Chinese hospital outpatient clinics. We first show that when patients give a small gift, doctors reciprocate with better service and a fewer unnecessary prescriptions of antibiotics. We then show that gift giving creates externalities for third parties. If two patients, A and B are perceived as unrelated, B receives worse care when A gives a gift. However, if A identifies B as a friend, then both A and B benefit from A's gift giving. Hence, we show that gift giving can create positive or negative externalities, depending on the giver's social distance to the third party.