Genetically predicted major depression causally increases the risk of temporomandibular joint disorders.

Objective: Observational studies have reported that mental disorders are comorbid with temporomandibular joint disorder (TMD). However, the causal relationship remains uncertain. To clarify the causal relationship between three common mental illnesses and TMD, we conduct this Mendelian Randomization (MR) study. Methods: The large-scale genome-wide association studies data of major depression, bipolar disorder and schizophrenia were retrieved from the Psychiatric Genomics Consortium. The summary data of TMD was obtained from the Finn-Gen consortium, including 211,023 subjects of European descent (5,668 cases and 205,355 controls). The main approach utilized was inverse variance weighting (IVW) to evaluate the causal association between the three mental disorders and TMD. Five sensitivity analyses including MR-Egger, Maximum Likelihood, Weighted median, MR. RAPS and MR-PRESSO were used as supplements. We conducted heterogeneity tests and pleiotropic tests to ensure the robustness. Results: As shown by the IVW method, genetically determined major depression was associated with a 1.65-fold risk of TMD (95% CI = 1.10-2.47, p < 0.05). The direction and effect size remained consistent with sensitivity analyses. The odds ratios (ORs) were 1.51 (95% CI = 0.24-9.41, p > 0.05) for MR-Egger, 1.60 (95% CI = 0.98-2.61, p > 0.05) for Weighted median, 1.68 (95% CI = 1.19-2.38, p < 0.05) for Maximum likelihood, 1.56 (95% CI = 1.05-2.33, p < 0.05) for MR. RAPS, and 1.65 (95% CI = 1.10-2.47, p < 0.05) for MR-PRESSO, respectively. No pleiotropy was observed (both P for MR-Egger intercept and Global test >0.05). In addition, the IVW method identified no significant correlation between bipolar disorder, schizophrenia and TMD. Conclusion: Genetic evidence supports a causal relationship between major depression and TMD, instead of bipolar disorder and schizophrenia. These findings emphasize the importance of assessing a patient's depressive status in clinical settings.

Effects of Glutathione Tablets on Ferroptosis Pathway and Oxidative Stress-Related Indexes in Serum of Patients Undergoing Sevoflurane Inhalation General Anesthesia and Its Clinical Significance.

Objective: To explore the effect of glutathione on serum oxidative stress, inflammatory reaction, and brain injury in patients with Sevoflurane inhalation general anesthesia based on iron metabolism pathway. Methods: From January 2018 to January 2023, 120 patients undergoing Sevoflurane inhalation anesthesia in Xingtai Third Hospital were divided into a control group and an observation group. The control group was given routine treatment, and the observation group patients were given oral glutathione tablets 2 weeks before anesthesia based on the control group. Relevant basic data of patients were collected 3 days before operation (T0), 1 day after the operation (T1), 3 days (T2), and 7 days (T3) respectively, and the serum oxidative stress indicators of patients in each group were measured by ELISA: SOD, MDA, GSH, Hif-1α, ferroptosis related indicators: SIRT3, GPX4; related inflammatory indicators: IL-1ß, TGF-ß, IL-33; neuronal injury related proteins: MBP, NGF, and statistical analysis of the data. Results: There was no significant difference in general conditions and operation time between the two groups (P > .05). Compared with the control group, the observation group showed significant differences in oxidative stress indicators: SOD in the observation group at T1, SOD, and Hif-1α in the observation group at T2, and SOD, MDA, GSH and Hif-1α in the observation group at T3. 1α, there were significant differences compared with the indicators of the control group at the same time (P < .001). In terms of inflammatory factor indicators, compared with the control group, there were significant differences in IL-1ß at T1, TGF-ß, and IL-33 at T2, and IL-1ß, TGF-ß and IL-33 at T3. (P < .001). In terms of ferroptosis indicators, compared with the control group, there were significant differences in SIRT3 at T1, SIRT3, and GPX4 at T2, and SIRT3 and GPX4 at T3 (P < .001). In terms of nerve injury-related proteins, in patients, MBP levels were negatively correlated with SIRT3 (r=-0.8979, P < .0001), MBP levels were positively correlated with GPX4 (r=0.528, P < .0001), and NGF levels were positively correlated with SIRT3 (r=0.8979, P < .0001), NGF level was negatively correlated with GPX4 (r=0.528, P < .0001). Conclusion: Glutathione tablets can alleviate sevoflurane-induced ferroptosis and oxidative stress by elevating GPX4 protein levels, and glutathione tablets have an ameliorative effect on brain injury in patients with sevoflurane inhalation anesthesia.

A Review of Metamaterials in Wireless Power Transfer.

Wireless power transfer (WPT) is a technology that enables energy transmission without physical contact, utilizing magnetic and electric fields as soft media. While WPT has numerous applications, the increasing power transfer distance often results in a decrease in transmission efficiency, as well as the urgent need for addressing safety concerns. Metamaterials offer a promising way for improving efficiency and reducing the flux density in WPT systems. This paper provides an overview of the current status and technical challenges of metamaterial-based WPT systems. The basic principles of magnetic coupling resonant wireless power transfer (MCR-WPT) are presented, followed by a detailed description of the metamaterial design theory and its application in WPT. The paper then reviews the metamaterial-based wireless energy transmission system from three perspectives: transmission efficiency, misalignment tolerance, and electromagnetic shielding. Finally, the paper summarizes the development trends and technical challenges of metamaterial-based WPT systems.

Seasonal variations of cave dripwater hydrogeochemical parameters and δ13CDIC in the subtropical monsoon region and links to regional hydroclimate.

Stalagmites are considered natural archives of climate proxies. However, under the combined effects of atmospheric circulation patterns, precipitation, and karst environments, drip hydrogeochemical processes can be coupled and linked to each other to control cave sediment record information. Therefore, the evolution of chemistry and factors controlling the isotopic composition of the dripwater during regional precipitation migration from the surface to caves need to be evaluated. In this study, hydrogeochemical characteristics and the isotopic composition of the dripwater in the Mahuang Cave in Guizhou Province, Southwest China, including stable isotope (δ13CDIC) and trace element ratios, were monitored from August 2018 to December 2020. The results showed seasonal variations in the δ13CDIC, Mg/Ca, and Sr/Ca values of the dripwater in dry and wet seasons under the control of water-gas-rock reactions, such as soil CO2 concentrations and carbonate rock dissolution. In addition, the five monitored dripwater points in the Mahuang Cave showed fast and slow seepage due to the complex cave fractures and stratigraphy, reflecting the effects of precipitation variations to different degrees. Indeed, the δ13CDIC were more sensitive to the recharge changes from extreme precipitation and drought events. Therefore, dripwater δ13CDIC is a reliable indicator of the recorded hydrological signal in the southwest monsoon region.

Efficacy of Adjunctive Chlorhexidine in non-surgical treatment of Peri-Implantitis/Peri-Implant Mucositis: An updated systematic review and meta-analysis.

Objective: The current review aimed to assess the efficacy of adjunctive chlorhexidine (CHX) in the non-surgical treatment of peri-implantitis/peri-implant mucositis. Methods: PubMed, Embase, Science Direct, CENTRAL, and Google Scholar databases were searched up to 10th March 2022 for relevant randomized controlled trials or controlled clinical trials. Results: Fourteen studies were included. Meta-analysis revealed significantly lower probing depths in peri-implant mucositis patients using CHX adjuncts as compared to controls (SMD: -1.49 95% CI: -2.56, -0.42 I2=95% p=0.006). However, the same effect was not noted in peri-implantitis (SMD: -1.18 95% CI: -0.04, 2.40 I2=96% p=0.06). CHX was not found to improve bleeding of probing in peri-implant mucositis while sufficient data was unavailable for peri-implantitis. Results on other outcome variables were conflicting. Conclusion: Evidence on the efficacy of adjunctive CHX for peri-implant mucositis is conflicting. Similarly, strong conclusions on the effect of CHX for peri-implantitis cannot be drawn due to limited number of studies. Overall, there seems to be a trend of non-significant impact of CHX on outcomes of peri-implant mucositis as well as peri-implantitis.

Immediate vs Conventional Loading of Mandibular Overdentures: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Clinicians treating overdenture patients need to know if immediate loading and conventional loading results in similar outcomes. This study aimed to perform a systematic literature search of studies comparing immediate and conventional loading of mandibular overdentures irrespective of the number of implants and conduct a meta-analysis of implant failure and marginal bone loss (MBL). A literature search of PubMed, ScienceDirect, Ovoid, Springer, and Google Scholar databases was performed for randomized controlled trials (RCTs) comparing immediate vs conventional loading of mandibular overdentures. The primary outcome was implant failure and the secondary outcome was marginal bine loss (MBL). A descriptive analysis was performed for other outcomes. Thirteen trials were included. Only one trial compared the immediate and delayed loading of single implant-supported overdenture. Seven trials used 2 implants, 1 trial used 3 implants while 4 trials used 4 implants. Meta-analysis indicated no statistically significant difference in implant failure and MBL between immediate and conventional loading of 2- and 4-implant supported overdentures. Descriptive analysis indicated no difference in peri-implant tissue indices, implant stability, and quality of life outcomes between the 2 loading protocols. There may be no difference in implant failure and MBL with immediate loading or conventional loading of 2- and 4-implant supported mandibular overdentures. Literature review indicates that there may be no difference in peri-implant tissue indices, implant stability, and quality of life outcomes between the 2 loading protocols. The overall quality of evidence is moderate. Further, adequately powered RCTs are required to strengthen the evidence.

MicroRNA-132-3p alleviates neuron apoptosis and impairments of learning and memory abilities in Alzheimer's disease by downregulation of HNRNPU stabilized BACE1.

Alzheimer's disease (AD) is a progressive neuro-degenerative disease characterized by dementia. MicroRNAs (miRNAs) are involved in many diseases, including AD. MiR-132-3p has been identified to be downregulated in AD. In this study, we explored the effects of miR-132-3p on neuron apoptosis and impairments of learning and memory abilities. Aß1-42-stimulated SH-SY5Y cells were used as in vitro models of AD. An AD-like homocysteine (Hcy) rat model was established to evaluate the effects of miR-132-3p on AD pathogenesis in vivo. RIP, RNA pull down and luciferase reporter assays were conducted to investigate the relationship between miR-132-3p and its downstream target genes. The viability and apoptosis of SH-SY5Y cells were measured by CCK-8 and TUNEL assays. The rat spatial learning and memory abilities were accessed using Morris water maze test. Results indicated that miR-132-3p was downregulated in SH-SY5Y cells after Aß1-42 treatment and promoted cell apoptosis. Mechanistically, miR-132-3p targeted heterogeneous nuclear ribonucleoprotein U (HNRNPU). HNRNPU acted as an RNA binding protein (RBP) to regulate the mRNA stability of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1). Overexpression of HNRNPU or BACE1 reversed the effects of miR-132-3p overexpression on the viability and apoptosis of Aß1-42-treated SH-SY5Y cells. In vivo experiments revealed the downregulation of miR-132-3p in the hippocampus of Hcy-treated rats. MiR-132-3p suppressed levels of apoptotic genes in hippocampus and reduced impairments of learning and memory abilities in Hcy-treated rats. In conclusion, miR-132-3p reduces apoptosis of SH-SY5Y cells and alleviates impairments of learning and memory abilities in AD rats by modulating the HNRNPU/BACE1 axis.

Study of TCM Syndrome Identification Modes for Patients with Type 2 Diabetes Mellitus Based on Data Mining.

OBJECTIVE: To establish the diagnosis model for syndromes of type 2 diabetes mellitus (T2-DM) and explore symptoms, the pulse and tongue signs, and laboratory indexes related to syndromes of T2-DM. METHODS: A syndromatologic and laboratory investigation was conducted in 554 T2-DM patients with 58 symptoms, 14 tongue signs, 6 pulse signs, and 12 laboratory indexes. The clinical data on the syndrome were collected and analyzed by using logistic regression analysis, decision tree, and K-nearest neighbor to establish a diagnostic model for effectively distinguishing the typical syndromes in T2-DM patients. RESULTS: The most typical syndromes revealed in T2-DM were stomach heat flourishing (SHF) syndrome (261 patients, accounting for 47.1%) and Qi-Yin deficiency (QYD) syndrome (293 patients, 52.9%). According to the clinical data of the patients with these two syndromes, variables including 6 symptoms and signs, 2 pulse signs, 1 tongue sign, and 2 laboratory indicators were introduced into the logistic regression model. All of them were statistically significant. Then, a diagnostic model constructed by QUEST and CHAID algorithms of the decision tree for identifying the two syndromes was proved to have an accurate diagnostic rate of 85.2%. It was found that the following sign and symptoms were effective to differentiate these two syndromes: odor in the mouth, polyphagia, vulnerability to starvation, burning sensation in the stomach, fatigue, limb weakness, slippery and replete pulse, weak pulse, pink tongue, oral glucose tolerance test, and hemoglobin A1C. A classification model constructed by the K-nearest neighbor method to identify the two syndromes showed an accurate diagnostic rate of 88.3%. Three major statistically significant predictors included in the model were slippery and replete pulse, polyphagia, and weak pulse (P < 0.05). CONCLUSION: A model for distinguishing the two typical syndromes (SHF syndrome and QYD syndrome) in T2-DM patients was effectively established. This model could help to provide methodological support for the standardization of traditional Chinese medicine (TCM) syndrome differentiation methods.

Outcomes of implants placed after osteotome sinus floor elevation without bone grafts: a systematic review and meta-analysis of single-arm studies.

BACKGROUND: The aim of this study is to evaluate the implant survival/success rate, gain in alveolar bone height, crestal bone loss, and complications associated with implants placed in the posterior maxilla after osteotome sinus floor elevation without bone substitutes. METHODS: The electronic databases, such as MEDLINE, EMBASE, CENTRAL, and SCOPUS were systematically and manually searched for publications in peer-reviewed journals. The included articles were subjected to qualitative and quantitative analyses, and the meta-analysis was carried out for single-arm studies. Methodological quality assessment was made for all the included studies. RESULTS: The included studies were of moderate quality, with the overall implant success and survival rates of 98.3% and 97.9% respectively. The most frequent intra-surgical complication was sinus membrane perforation, accounting for 3.08% of the total implants with reported perforations. The overall crestal bone loss in patients with immediate implants placed with OSFE after a 5-year follow-up was 0.957 mm 95%CI (0.538, 1.377). CONCLUSION: Within the limitations of this review, it can be concluded that the survival and success rates of implants placed immediately along with OSFE without any bone substitutes are acceptable and show adequate implant stability with less crestal bone loss over 5 years.

3D­printed Ti6Al4V scaffolds combined with pulse electromagnetic fields enhance osseointegration in osteoporosis.

The loosening and displacement of prostheses after dental implantation and arthroplasty is a substantial medical burden due to the complex correction surgery. Three­dimensional (3D)­printed porous titanium (pTi) alloy scaffolds are characterized by low stiffness, are beneficial to bone ingrowth, and may be used in orthopedic applications. However, for the bio­inert nature between host bone and implants, titanium alloy remains poorly compatible with osseointegration, especially in disease conditions, such as osteoporosis. In the present study, 3D­printed pTi scaffolds with ideal pore size and porosity matching the bone tissue, were combined with pulse electromagnetic fields (PEMF), an exogenous osteogenic induction stimulation, to evaluate osseointegration in osteoporosis. In vitro, external PEMF significantly improved osteoporosis­derived bone marrow mesenchymal stem cell proliferation and osteogenic differentiation on the surface of pTi scaffolds by enhancing the expression of alkaline phosphatase, runt­related transcription factor­2, osteocalcin, and bone morphogenetic protein­2. In vivo, Microcomputed tomography analysis and histological evaluation indicated the external PEMF markedly enhanced bone regeneration and osseointegration. This novel therapeutic strategy has potential to promote osseointegration of dental implants or artificial prostheses for patients with osteoporosis.

Gabapentin for phantom limb pain after amputation in pediatric oncology: a systematic review protocol.

BACKGROUND: Phantom limb pain (PLP) is a prevalent problem for children after amputation because of the chemotherapy treatment. Gabapentin is a potential option to manage PLP after amputation in pediatric oncology. However, no systematic review specifically investigated this topic. Thus, this study aims to appraise the efficacy and safety of gabapentin for post-amputation PLP in pediatric oncology. METHODS: Electronic databases (Cochrane Library, MEDLINE, EMBASE, Web of Science, CINAHL, PsychINFO, Scopus, WANGFANG, and Chinese Biomedical Literature Database) will be systematically searched from the beginning to the present without limitations to publication status and language. Primary outcome is pain intensity. Secondary outcomes are analgesic drug consumption, sleep quality, depression, anxiety, health-related quality of life, and adverse events. The treatment effect of all dichotomous outcome data will be estimated as risk ratio and 95% confidence intervals (CIs) and that of continuous outcome data will be calculated as mean difference or standardized mean difference and 95% CIs. Methodological quality of randomized controlled trials (RCTs) will be assessed using Cochrane risk of bias tool and that of case-controlled studies (CCSs) will be appraised using Newcastle-Ottawa Tool. Statistical analysis will be conducted using RevMan 5.3 software. DISCUSSION: This study will summarize up-to-date high-quality RCTs and CCSs to assess the efficacy and safety of gabapentin for PLP after amputation in pediatric oncology. The findings of this study will help to determine whether or not gabapentin is effective and safe for children with PLP after amputation. SYSTEMATIC REVIEW REGISTRATION: INPLASY202060090.

Home-based exercise is associated with improved cardiac functional performance in patients after acute myocardial infarction.

OBJECTIVE: To evaluate the effects of home-based exercise and physical activity on cardiac functional performance in patients after acute myocardial infarction (MI) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This retrospective study enrolled patients that received treatment of acute ST-segment elevation MI between and were followed-up 6 months later. The patients were divided into physically active and inactive groups based on their levels of home exercise after hospital discharge. RESULTS: A total of 78 patients were enrolled in the study: 32 were physically active and 46 were physically inactive. The baseline characteristics were comparable between the two groups. At the 6-month visit, left ventricular ejection fraction and six-minute walking test (6MWT) were significantly improved while the proportion of patients with a New York Heart Association (NYHA) functional III classification was decreased in the active patients, whereas these parameters were not significantly changed in the inactive patients. In addition, the 6MWT was greater while the proportion of patients with an NYHA III classification was lower in the active group than the inactive group at the 6-month visit. CONCLUSION: Maintaining physical activity at home was associated with improved cardiac functional performance in patients after acute MI during the COVID-19 pandemic.

Passive medialization of the inferior alveolar nerve to facilitate implant placements in a patient with severe atrophic posterior mandible.

Placing implants in the edentulous jaw of an individual with severe posterior mandibular atrophy is challenging due to the insufficient bone height above the inferior alveolar nerve canal. The different reconstruction techniques available cause extensive morbidity, are costly, and require prolonged treatments. In here we report a case series of patients treated with a new minimally invasive technique to facilitate implant placement in patients with severely atrophied posterior mandible.

Association between small intestinal bacterial overgrowth and beta-cell function of type 2 diabetes.

AIMS: Previous studies suggest that small intestinal bacterial overgrowth (SIBO) is associated with type 2 diabetes. However, few studies have evaluated the association between SIBO and beta-cell function in type 2 diabetes. The aim of this study was to evaluate whether beta-cell function was associated with SIBO. MATERIALS AND METHODS: One hundred four patients with type 2 diabetes were included in this study. Based on the presence of SIBO, the patients were divided into SIBO-positive and SIBO-negative groups. Oral glucose tolerance tests were performed. Insulin sensitivity was measured using 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and the insulin sensitivity index (ISIM). Insulin release was calculated by HOMA-ß, early-phase insulin secretion index InsAUC30/GluAUC30, and total-phase insulin secretion index InsAUC120/GluAUC120. RESULTS: Compared with the SIBO-negative group, patients in the SIBO-positive group showed a higher glucose level at 120 minutes, HbA1c, 1/HOMA-IR, and ISIM and a lower HOMA-ß level, early-phase InsAUC30/GluAUC30, and total-phase InsAUC120/GluAUC120. Multiple linear regression analysis showed that body mass index, glucose at 0 minutes, and SIBO were independently associated with the early-phase and total-phase insulin secretion. CONCLUSION: SIBO may be involved in lower levels of insulin release and worse glycemic control.

Compound Danshen Dripping Pills Prevented Leptin Deficiency-Induced Hepatic ER Stress, Stimulated Autophagy, and Improved Insulin Resistance of ob/ob Mice.

Compound Danshen dripping pills (CDDP) is widely used for the treatment of coronary arteriosclerosis and ischemic heart diseases for decades of years. In our study, we interestingly discovered the effects and mechanism of CDDP on insulin resistance that increase the risk factor of cardiovascular diseases. Effects of CDDP on fasting blood glucose, the insulin tolerance test (ITT), the oral glucose tolerance test (OGTT), hepatic function, and underlying mechanism were analyzed in ob/ob mice. CDDP was found improving the impaired insulin signal sensitivity of ob/ob mice by ameliorating insulin and glucose tolerance, improving hepatic phosphorylation of the insulin receptor substrate-1 on Ser 307 (pIRS1) of ob/ob mice, and restoring hepatic function by decreasing serum ALT and AST, which increased in ob/ob mice serum. Decreasing hepatic phosphorylation of pancreatic ER kinase (PERK) and inositol-requiring enzyme-1 (IRE1) regulating hepatic ER stress in the liver of ob/ob mice were increased by CDDP. Furthermore, CDDP was also found stimulating ob/ob mice hepatic autophagy by increasing the expression of Beclin1 and LC3B, while decreasing P62 expression. Our study discovered an important role of CDDP on improving ob/ob mice insulin resistance and liver function probably through relieving hepatic ER stress and stimulating hepatic autophagy, which would broaden the application value and provide more benefits for treating cardiovascular patients. This trial is registered with NCT01659580.

Salvianolic acid B improved insulin resistance through suppression of hepatic ER stress in ob/ob mice.

Impaired insulin sensitivity of insulin-sensitive tissues plays a major role in the pathogenesis of type 2 diabetes, salvianolic acid B (SalB), a natural antioxidant usually treated various cardiovascular diseases was also reported potential utility on diabetes and dyslipidemia. Based on these, we aimed to explored whether the antioxidant effect of SalB play a pivotal role in the molecular mechanisms leading to insulin resistance. We found that SalB improved glucose tolerance and insulin sensitivity, decreased serum ALT, AST and ALP levels of ob/ob mice. Also, transcription of Bip and CHOP, phosphorylation of PERK and IRE1 for endoplasmic reticulum stress (ER) and phosphorylation of IRS-1 for insulin sensitivity in the liver of ob/ob mice were relieved by SalB. Further, SalB decreased phosphorylation of PERK, IRE1 and IRS1 and transcription of Bip and CHOP stimulated by palmitate of hepatic cells HL7702, but did not reversed phosphorylation of JNK and IRS1 and transcription of Bip and CHOP when ER stress was stimulated by tunicamycin. These data shows that SalB improved insulin resistance of ob/ob mice through suppression of hepatic ER stress.

miR-183-5p acts as a potential prognostic biomarker in gastric cancer and regulates cell functions by modulating EEF2.

BACKGROUND: Gastric cancer (GC) is the fourth most prevalent malignant tumor and the second leading cause of cancer-related death around the world. Aberrant proliferation and metastasis are the mainspring of death in patients with GC. However, the specific mechanism of gastric cancer is far from being fully elucidated. Accumulating evidence revealed that miRNA played a significant role in the tumorigenesis and development. METHODS: The level of miR-183-5p was detected in 102 GC patients by using qRT-PCR. The prognostic value of miR-183-5p in GC was evaluated. Cell function assays (CCK-8 and transwell assays) were conducted to assess the role of miR-183-5p in proliferation and metastasis in GC. Dual luciferase report assay and western blot were performed to validate this potential target regulated by miR-183-5p in GC. RESULTS: miR-183-5p was down-regulated in GC tissues and cell lines. Remarkable pertinence was obtained between miR-183-5p level and TNM stage, tumor size, invasion depth, and lymph node metastasis. TNM stage, differentiation and miR-183-5p level were independent causes impacting on the overall survival in GC in multivariate analysis. GC individuals with high miR-183-5p level would experience a relatively better survival prognosis. Upregulation of miR-183-5p restrained GC cell proliferation and migration. EEF2 may be a potential target gene regulated by miR-183-5p in GC. CONCLUSION: miR-183-5p acts as a potential prognostic biomarker in gastric cancer and regulates cell functions by modulating EEF2.

Inhibition of MicroRNA-204 Conducts Neuroprotection Against Spinal Cord Ischemia.

BACKGROUND: MicroRNA(miR)-204 is an autophagy- and apoptosis-related gene. Neuroprotection by the inhibition of miR-204 against spinal cord ischemia was evaluated, and the roles of neuronal autophagy and apoptosis were investigated. METHODS: Spinal cord ischemia was conducted in rats by cross-clamping the descending aorta for 14 minutes. Inhibition of miR-204 was induced by intrathecal injection of lentivirus vectors containing antagomiR-204. Hind-limb motor function was assessed with the motor deficit index. Lumbar spinal cords were harvested for histologic examinations and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining. Autophagy was evaluated by the LC3-II/LC3-I ratio and beclin-1 expression. Expressions of LC3-I, LC3-II, beclin-1, B-cell lymphoma-2 (BCL-2), caspase-3, and miR-204 were measured by Western blot and quantitative real-time polymerase chain reaction. Autophagy was blocked by 3-methyladenine. RESULTS: Transient ischemia enhanced miR-204 expression and the LC3-II/LC3-I ratio and downregulated BCL-2 expression in spinal cords in a time-dependent manner. AntagomiR-204 significantly reduced expressions of miR-204 and caspase-3, dramatically upregulated expressions of beclin-1 and BCL-2 and the LC3-II/LC3-I ratio in spinal cords after reperfusion. Compared with controls, inhibition of miR-204 markedly decreased the motor deficit index scores at 6, 12, 24, and 48 hours after reperfusion; increased the number of viable motor neurons; and decreased the number of apoptotic neurons. 3-Methyladenine completely abolished enhancements of the LC3-II/LC3-I ratio and beclin-1 expression induced by antagomiR-204 and inhibited the protective effect on hind-limb motor function. CONCLUSIONS: Inhibition of miR-204 exerts spinal cord protection against ischemia-reperfusion injury, possibly via promotion of autophagy and antiapoptotic effects.

Inhibition of SphK2 Stimulated Hepatic Gluconeogenesis Associated with Dephosphorylation and Deacetylation of STAT3.

BACKGROUND: Sphingosine kinase (SphK) is considered as a potential target for developing novel therapeutics of cancer and other diseases including diabetes. As the major SphK isoform in the liver, much less is known the role of SphK2 involved in regulating hepatic glucose metabolism. METHOD: In this study, RNA interference, real time RT-PCR, western blot and immunoprecipitation method was used to investigate the regulation of SphK2 in hepatic glucose metabolism. RESULTS: Both siRNA and SphK2 inhibitor ABC294640 stimulated expression of gluconeogenetic gene PEPCK and G6Pase but not enzymes of hepatic glycogenolysis, glycolysis and glycogen synthesis. Inhibition of SphK2 also prevented insulin repressed PEPCK and G6Pase expression as well as glucose production levels. Furtherly, inhibition of SphK2 inactivated STAT3 by decreasing both phosphorylation on Tyr705 and acetylation on lysine residue, and led to stimulation of PEPCK and G6Pase expression. Inhibition of SphK2 also prevented IL-6 dependent activation of STAT3 and suppression of PEPCK and G6pase expression both in vitro and in vivo. CONCLUSION: Our study suggests that SphK2 participates in hepatic glucose metabolism related to activation of STAT3.