The integrated analysis and underlying mechanisms of FNDC5 on diabetic induced cognitive deficits.

OBJECTIVES: Chronic hyperglycemia is considered as an important factor to promote the neurodegenerative process of brain, and the synaptic plasticity as well as heterogeneity of hippocampal cells are thought to be associated with cognitive dysfunction in the early process of neurodegeneration. To date, fibronectin type III domain-containing protein 5 (FNDC5) has been highlighted its protective role in multiple neurodegenerative diseases. However, the potential molecular and cellular mechanisms of FNDC5 on synaptic plasticity regulation in cognitive impairment (CI) induced by diabetics are still need to known. METHODS/DESIGN: To investigate the heterogeneity and synaptic plasticity of hippocampus in animals with CI state induced by hyperglycemia, and explore the potential role of FNDC5 involved in this process. Firstly, the single cell sequencing was performed based on the hippocampal tissue from db diabetic mice induced CI and normal health control mice by ex vivo experiments; and then the integrated analysis and observations validation using Quantitative Real-time PCR, western blot as well as other in vitro studies. RESULTS: We observed and clarified the sub-cluster of type IC spiral ganglion neurons expressed marker genes as Trmp3 and sub-cluster of astrocytes with marker gene as Atp1a2 in hippocampal cells from diabetic animals induced CI and the effect of those on neuron-glial communication. We also found that FNDC5\BDNF-Trk axis was involved in the synaptic plasticity regulation of hippocampus. In high glucose induced brain injury model in vitro, we investigated that FNDC5 significantly regulates BDNF expression and that over-expression of FNDC5 up-regulated BDNF expression (p < 0.05) and can also significantly increase the expression of synapsin-1 (p < 0.05), which is related to synaptic plasticity, In addition, the unbalanced methylation level between H3K4 and H3K9 in Fndc5 gene promoter correlated with significantly down-regulated expression of FNDC5 (p < 0.05) in the hyperglycemia state. CONCLUSION: The current study revealed that the synaptic plasticity of hippocampal cells in hyperglycemia might be regulated by FNDC5\BDNF-Trk axis, playing the protective role in the process of CI induced by hyperglycemia and providing a target for the early treatment of hyperglycemia induced cognitive dysfunction in clinic.

A Review of Gap Junction Protein and its Potential Role in Nervous System-Related Disease.

Gap junction (GJ) is a special cell membrane structure composed of connexin. Connexin is widely distributed and expressed in all tissues except differentiated skeletal muscle, red blood cells, and mature sperm cells, which is related to the occurrence of many genetic diseases due to its mutation. Its function of regulating immune response, cell proliferation, migration, apoptosis, and carcinogenesis makes it a therapeutic target for a variety of diseases. In this paper, the possible mechanism of its action in nervous system-related diseases and treatment are reviewed.

The METS-IR is independently related to bone mineral density, FRAX score, and bone fracture among U.S. non-diabetic adults: a cross-sectional study based on NHANES.

AIM: The purpose of this study was to investigate the association between the metabolic score for insulin resistance (METS-IR) and bone mineral density (BMD) in American non-diabetic adults. METHODS: We conducted a cross-sectional study with 1114 non-diabetic adults from the National Health and Nutrition Examination Survey cycle (2013-2014). The associations between METS-IR and BMD of total femur and spine were assessed by the multiple linear regression and verified the non-linear relationship with a smooth curve fit and threshold effect model. Furthermore, we evaluated the relationship between METS-IR, FRAX score, and history of bone fractures. RESULTS: We found that BMD of the total femur and spine increased by 0.005 g/cm3 and 0.005 g/cm3, respectively, for a one-unit increase of METS-IR in all participants. This positive association was more pronounced among higher METS-IR participants, and there was a non-linear relationship, which was more significant when the MTTS-IRfemur was < 41.62 or the METS-IRspine was < 41.39 (ßfemur = 0.008, ßspine = 0.011, all P < 0.05). We also found that METS-IR was positively correlated with both FRAX scores in all female participants. However, METS-IR was positively correlated only with the 10-year hip fracture risk score in male participants with fractures. No significant association between METS-IR and a history of bone fractures. CONCLUSIONS: In American non-diabetic adults, there is a correlation between elevated levels of METS-IR within the lower range and increased BMD as well as decreased risk of fractures, suggesting that METS-IR holds promise as a novel biomarker for guiding osteoporosis (OP) prevention. However, it is important to carefully balance the potential benefits and risks of METS-IR in OP.

The metabolic score of insulin resistance is positively correlated with bone mineral density in postmenopausal patients with type 2 diabetes mellitus.

The prevalence of type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP) is increasing yearly. Early prevention, detection and treatment of OP are important in postmenopausal patients with T2DM. This study aimed to explore the correlation between insulin resistance and bone mineral density (BMD), and OP in postmenopausal patients with T2DM. In this study, postmenopausal patients with T2DM who visited our hospital from January 2021 to March 2022 were divided into the OP group (n = 91) and non-OP group (n = 119) according to whether they were complicated with OP or not. The general data of patients, BMD, blood routine, glucose metabolism, lipid metabolism, liver and kidney function indexes were collected, and the homeostatic model assessment for IR (HOMA-IR), the triglyceride-glucose (TyG) index and the metabolic score for IR (METS-IR) were calculated. A weighted multivariate linear regression model assessed the correlation between insulin resistance (IR) related indexes and lumbar spine, femoral neck, and hip BMD. A weighted logistic regression model assessed the odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between the IR-related indexes and OP risk. The nonlinear relationship was also evaluated by smooth curve fitting (SCF) and a weighted generalized additive model (GAM). Moreover, the Receiver-operating characteristics (ROC) curve was used to analyze the predictive efficiency of METS-IR in postmenopausal patients with T2DM with OP. HOMA-IR, TyG, and METS-IR in the OP group were lower than those in the non-OP group (all P < 0.05). Weighted multiple linear regression after adjusting covariates showed that METS-IR was positively correlated with the lumbar spine, femoral neck, and hip BMD (ßMETS-IR = 0.006,0.005,0.005, all P < 0.001). The results of weighted Logistic regression and GAM showed that when METS-IR < 44.5, each unit of increased METS-IR value was associated with a decreased OP risk of 12% (P = 0.002). When METS-IR ≥ 44.5, there was no significant correlation between METS-IR and the risk of OP (OR = 1.00, P = 0.934). Similar trends were not observed in HOMA-IR and TyG. The ROC suggested helpful discriminative power of the METS-IR index for T2DM. We confirmed that METS-IR, as a novel alternative marker of IR, had a positive association with BMD in postmenopausal patients with T2DM, and METS-IR was a protective factor for OP in a specific range.

Seropositive for hepatitis B and C viruses is associated with the risk of decreased bone mineral density in adults: An analysis of studies from the NHANES database.

Background: Some studies had reported that patients with viral hepatitis are at increased risk of reduced bone mineral density and even osteoporosis. However, the interaction between reduced bone mineral density (BMD) and viral hepatitis remains inconclusive. Therefore, our study collected hepatitis test results and bone mineral density from respondents in the NHANES database. The aim of this study was to investigate whether there is an association between hepatitis and a decrease in bone mineral density. Methods: The respondents with both hepatitis- and BMD-related indicators from the NHANES database in the United States from 2005-2010, 2013-2014, to 2017-2020 were collected for this study. BMD were compared between respondents who were positive and negative for respondents related to hepatitis B and C. BMD was measured using dual-energy X-ray absorptiometry of the femur and lumbar spine. Finally, multiple regression analysis was performed between hepatitis B surface antigen (HBsAg) and hepatitis C RNA (HCV-RNA) and BMD in the respondents. Results: A total of 15,642 respondents were included in the hepatitis B surface antigen-related survey. Of these, 1,217 respondents were positive for hepatitis B surface antigen. A total of 5111 hepatitis C RNA-related responders were included. Hepatitis C RNA-positive had 268 respondents. According to the results of the multiple regression analysis, the femoral BMD was significantly lower in HBsAg (+) respondents compared to HBsAg (-) respondents: -0.018 (-0.026, -0.009) (P < 0.01). Moreover, spinal BMD was significantly lower in HBsAg (+) respondents compared to HBsAg (-) respondents: -0.020 (-0.030, -0.010) (P < 0.01). According to the results of multiple regression analysis for hepatitis C RNA, HCV-RNA (+) respondents had significantly lower BMD compared to HCV-RNA (-) respondents: -0.043 (-0.059, -0.026) (P < 0.01). Conclusion: During the analysis of respondents in the NHANES database in the United States, positive tests for hepatitis B surface antigen and hepatitis C RNA were found to be associated with a reduction in BMD. Positive serology for these hepatitis indicators may increase the risk of reduced BMD. Of course, this conclusion still needs to be further confirmed by more large clinical trials.

Association of bone mineral density with trichlorophenol: a population-based study.

BACKGROUND: Trichlorophenols (TCPs) are metabolites of several organochlorine chemicals, including chlorobenzene, hexachlorocyclohexane, and chlorophenoxy acid, present in air, surface water, soil, and sediment. Many studies have shown that endocrine disruptors (EDs)may contribute to decreased bone mass and the increased risk of osteoporosis. However, the relationship between TCP and bone mineral density (BMD) has not been studied yet. METHODS: We conducted a cross-sectional study by using data from the 2005-2010 National Health and Nutrition Examination Survey (NHANES). TCP levels were measured in urine samples from 3385 participants and bone mineral density was obtained by dual X-ray absorptiometry (DXA) lumbar spine and femur scanning. Multiple regression analysis, stratified analysis, curve fitting analysis, and trend tests were used to assess the relationship between TCP and BMD. RESULT: After adjusting for confounding factors, the results of multiple regression analysis only showed that ln-2,4,5-TCP was negatively associated with BMD of lumbar spine. In stratified analyses, Male, Menstruating Female and Menopausal Female were divided into three groups for analysis. The results showed that ln-2,4,5-TCP and ln-2,4,6-TCP were not statistically associated with BMD in total femur, femoral neck, femoral tuberosity, intertrochanteric femur and lumbar spine, which was also confirmed by curve fitting analyses and trend tests. CONCLUSION: This study demonstrated that 2,4,5-TCP and 2,4,6-TCP in urine samples were not significantly associated with BMD in the US population. Therefore, 2,4,5-TCP and 2,4,6-TCP may not be detrimental to BMD.

Enhanced Recovery after Surgery Rehabilitation Protocol in the Perioperative Period of Orthopedics: A Systematic Review.

PURPOSE: Enhanced recovery after surgery (ERAS) is a surgical rehabilitation protocol of increasing interest to clinicians in recent years, with the aim of faster and better recovery of patients after surgery. Our main focus in this review is to analyze the effectiveness of ERAS rehabilitation protocols in orthopedic surgery. By comparing the post-operative recovery of patients receiving the ERAS rehabilitation program with that of patients receiving the conventional rehabilitation program, we observed whether the patients who have received the ERAS rehabilitation program could recover better and faster, thereby achieving the aim of a shorter hospital stay and reducing the incidence of complications. METHODS: We conducted the literature searches in PubMed, MEDLINE, Web of Science, Cochrane Reviews, EMBASE and other databases on clinical studies related to orthopedic surgery regarding the effectiveness of rehabilitation using ERAS rehabilitation protocols compared with conventional rehabilitation protocols. A systematic review was performed in accordance with the Preferred Reporting Items of Systematic Reviews and Meta-analysis (PRISMA) statement. If there was variability in the rehabilitation data of the patients between the two subgroups, it was considered that there was a difference in the rehabilitation effect of the ERAS rehabilitation protocol and the conventional rehabilitation protocol on the patients. CONCLUSION: The application of ERAS rehabilitation protocols can shorten patients' hospital stay and reduce their expenses. In addition, patients with ERAS rehabilitation protocols will have fewer postoperative complications, while patients will have less postoperative pain than those with conventional rehabilitation, facilitating better postoperative recovery.

What is the role of Von Willebrand factor in chronic hepatitis B virus infection to hepatocellular carcinoma: a review article.

Von Willebrand factor (VWF) is a glycoprotein synthesized and secreted by vascular endothelial cells and megakaryocytes, found on plasma surface, endothelial cells, and α-granule of platelets. VWF can be interacted with collagen and platelet membrane glycoproteins GPIb and GPIb-IIa and play an important role in platelet adhesion and aggregation. Growing research evidence suggests that VWF also mediates the prevention or protesting of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients from several clinical studies. While the mechanism of VWF in HCC protection or protest is still unclear, further study is required. This article aims to rationalize the role of VWF in the development of HCC, and the functional domain of VWF in cancer as well as cross-talking with platelets and miRNAs. This article also looks forward to the future development and challenges of VWF research.

Comparison of dynamic and static spacers for the treatment of infections following total knee replacement: a systematic review and meta-analysis.

BACKGROUND: Revision surgery is the most common treatment for patients who develop infection after total knee arthroplasty (TKA). Two types of spacers are often used in revision surgery: dynamic spacers and static spacers. The comparative efficacy of these two types of spacers on knee prosthesis infections is not well established. Therefore, we carried out a systematic evaluation and meta-analysis with the aim of comparing the difference in efficacy between dynamic and static spacers. METHODS: We conducted the literature search in PubMed, Web of Science, Cochrane Library, and Embase databases. The articles searched were clinical study comparing the difference in efficacy between dynamic spacers and static spacers for the treatment of prosthetic infections occurring after total knee arthroplasty. RESULTS: We conducted a literature search and screening based on the principles of PICOS. Ultimately, 14 relevant clinical studies were included in our current study. We use infection control rate as the primary evaluation indicator. The KSS knee scores (KSSs), KSS functional scores, bone loss and range of motion (ROM) are secondary indicators of evaluation. Thirteen of these included studies reported the infection control rates, with no significant difference between dynamic and static shims (RR: 1.03; 95% Cl 0.98, 1.09; P = 0.179 > 0.05). The KSSs were reported in 10 articles (RR: 5.98; 95% CI 0.52, 11.43; P = 0.032 < 0.05). Six articles reported the KSS functional scores (RR: 13.90; 95% CI 4.95, 22.85; P = 0.02 < 0.05). Twelve articles reported the ROM (RR: 17.23. 95% CI 10.18, 24.27; P < 0.0001). Six articles reported the bone loss (RR: 2.04; 95% CI 1.11, 3.77; P = 0.022 < 0.05). CONCLUSION: Current evidence demonstrates that dynamic spacers are comparable to static spacers in controlling prosthetic joint infection. In terms of improving the functional prognosis of the knee joint, dynamic spacers are more effective than static spacers.

Changes in dorsal root ganglion CGRP expression in mouse pinch nerve injury model: Modulation by Somatostatin type-2 receptor.

INTRODUCTION: Our previous work has shown that somatostatin effectively inhibits neuropathic pain by activating its type 2 receptor (SSTR2) in the dorsal root ganglion (DRG) and spinal cord of mice. However, the underlying mechanism of this activation has not been elucidated. METHODS: To explore further mechanisms, we examined pain behavior and the expression of neuropeptides such as calcitonin gene-related peptide (CGRP) in dorsal root ganglion neurons(DRGs) as well as the changes of the number of CGRP-IR DRGs in the mouse model of sciatic pinch nerve injury. RESULTS: In this model, the number of medium and small DRG neurons in ipsilateral CGRP-IR was slightly increased, but not significantly, compared with sham animals at 3, 7, and 9 days after pinch nerve injury. This correlated with the behavioral readouts of hypersensitivity at the same time points. However, the magnitude of the painful behavior (Autotomy) was observed after application of SSTR2 antagonist (CYN154806, 5 mg/kg) in the injured nerve groups compared to the saline-treated injured group as well as the sham-operated group. Following pinch nerve injury, there was a significant decrease in the number of ipsilateral CGRP-IR small and medium DRG neurons in SSTR2 antagonist (anti-SSTR2)- but not saline-treated mice. These data also correlated with painful behavioral readouts where hypersensitivity was significantly increased by anti-SSTR2 but not saline treatment. DISCUSSION/CONCLUSION: In all, application of the SSTR2 antagonist to the pinched sciatic nerve suppressed CGRP expression and aggravated painful behavior, suggesting that CGRP expression in DRG neurons can be an important component of the pain mechanism and an indicator of pain behavior.

Fabrication and Simulation of a Layered Ultrahigh Thermally Conductive Material of Lamellar Stacking Graphene and Polydopamine on an Aluminum Substrate.

As technology continues to develop, electronic devices are becoming ever more integrated. The high level of integration results in a higher volume of calculations and higher heat generation. Metal materials have always been good conductors of heat and are commonly used in thermally conductive devices. However, the thermal conductivity of metallic materials decreases at elevated temperatures. Therefore, it is reasonable to develop new composite materials as thermal conductivity materials. In the experiments, a novel composite material with a sandwich structure has been designed. The material uses metallic aluminum (Al) as a substrate. Then, the metallic aluminum was soaked in a polydopamine (PDA) solution. Graphene (G) on the surface of the material was then enriched using an electrophoretic method. The material was removed and annealed to form the G-PDA-Al composite. According to the measurement, the thermal conductivity of the material is 492 W·m-1·K-1, which means ultrahigh thermal conductivity. Elongation experiments were carried out, and they increased the strength of the material by 12.4%. The formation of the material was then analyzed. The construction of the material was then carefully examined. The surface morphology, elemental composition, and structures were investigated by using scanning electron microscopy equipped by a scanning electron microscope, X-ray diffraction, infrared spectroscopy, and X-ray photoelectron spectroscopy. Differences from ordinary thermal materials were obtained based on calculations. A flexible thermal conductor was fabricated by using this material. The device can reduce the spontaneous combustion of ternary lithium batteries.

Fabrication and simulation of a layered ultrahigh thermal conductive material made of self-assembled graphene and polydopamine on a copper substrate.

A composite material of graphene (G) and polydopamine (PDA) on a copper (Cu) substrate (G/PDA@Cu) was fabricated successfully by sequential immersion deposition in a dopamine solution and an aqueous graphene oxide suspension before annealing. Optimum preparation conditions were explored by the orthogonal experimental method. The morphology and chemical composition of G/PDA@Cu were studied systematically by a series of characterization techniques. The thermal-conductive performance was evaluated by a laser flash thermal analyser. The thermal conductivity of G/PDA@Cu was 519.43 W m-1 K-1, which is ultrahigh and 30.50% higher than that of the Cu substrate. The adhesion force between G/PDA and the Cu substrate was 4.18 mN, which means that G bonds to the Cu substrate tightly. The model simulation also showed that G/PDA@Cu exhibits excellent thermal conductivity, allowing it to play a significant role in the thermal management of advanced electronic chips. The thermal-conductive devices using this material were prepared for practical applications.