Complement system is overactivated in patients with IgA nephropathy after COVID-19.

IgA nephropathy (IgAN), which has been confirmed as a complement mediated autoimmune disease, is also one form of glomerulonephritis associated with COVID-19. Here, we aim to investigate the clinical and immunological characteristics of patients with IgAN after COVID-19. The level of plasma level of C5a (p < 0.001), soluble C5b-9 (p = 0.018), FHR5 (p < 0.001) were all significantly higher in Group CoV (33 patients with renal biopsy-proven IgAN experienced COVID-19) compared with Group non-CoV (44 patients with IgAN without COVID-19), respectively. Compared with Group non-CoV, the intensity of glomerular C4d (p = 0.017) and MAC deposition (p < 0.001) and Gd-IgA1 deposition (p = 0.005) were much stronger in Group CoV. Our finding revealed that for IgAN after COVID-19, mucosal immune responses to SARS-CoV-2 infection may result in the overactivation of systemic and renal local complement system, and increased glomerular deposition of Gd-IgA1, which may lead to renal dysfunction and promote renal progression in IgAN patients.

BCR-Associated Protein 31 Regulates Macrophages Polarization and Wound Healing Function via Early Growth Response 2/C/EBPß and IL-4Rα/C/EBPß Pathways.

The BCR-associated protein 31 (BAP31), a transmembrane protein in the endoplasmic reticulum, participates in the regulation of immune cells, such as microglia and T cells, and has potential functions in macrophages that remain to be unexplored. In this study, we designed and bred macrophage-specific BAP31 knockdown mice to detect the polarization and functions of macrophages. The results revealed that M2 macrophage-associated genes were suppressed in mouse bone marrow-derived macrophages of Lyz2 Cre-BAP31flox/flox mice. Multiple macrophage-associated transcription factors were demonstrated to be able to be regulated by BAP31. Among these factors, C/EBPß was the most significantly decreased and was regulated by early growth response 2. BAP31 could also affect C/EBPß via modulating IL-4Rα ubiquitination and proteasome degradation in IL-4-stimulated macrophages. Furthermore, we found that BAP31 affects macrophages functions, including angiogenesis and skin fibrosis, during the wound healing process through IL-4Rα, as confirmed by infection with adeno-associated virus-short hairpin (sh)-IL-4Rα in Lyz2 Cre-BAP31flox/flox mice. Our findings indicate a novel mechanism of BAP31 in regulating macrophages and provide potential solutions for the prevention and treatment of chronic wounds.

The heterophilicic epitopes in conserved HA regions of human and avian influenza viruses can produce antibodies that bound to kidney tissue.

Influenza virus infection can cause kidney damage. However, the link between influenza infection and disease is still unclear. The purpose of this study was to analyze the relationship between heterophilic epitopes on H5N1 hemagglutinin (HA) and disease. The monoclonal antibody (mAb) against H5N1 was prepared, mAbs binding to human kidney tissue were screened, and the reactivities of mAbs with five different subtypes of influenza virus were detected. Design and synthesize the peptides according to the common amino acid sequence of these antigens, and analyze the distribution of the epitope on the crystal structure of HA. Immunological methods were used to detect whether the heterophilic epitopes could induce the production of antibodies that cross-react with kidney tissue. The results showed that H5-30 mA b binding to human kidney tissue recognized the heterophilic epitope 191-LVLWGIHHP-199 on the head of HA. The key amino acid were V192, L193, W194 and I196, which were highly conserved in human and avian influenza virus HA. The heterophilic epitope could induce mice to produce different mAbs binding to kidney tissue. Such heterophilic antibodies were also detected in the serum of the patients. It can provide materials for the mechanism of renal diseases caused by influenza virus infection.

Characteristics of blood immune cell profile and their correlation with disease progression in patients infected with HIV-1.

BACKGROUND: Antiretroviral therapy (ART) can reduce viral load in individuals infected with human immunodeficiency virus (HIV); however, some HIV-infected individuals still cannot achieve optimal immune recovery even after ART. Hence, we described the profile of peripheral immune cells and explored the association with disease progression in patients infected with HIV-1. METHODS: Mass cytometry analysis was used to characterize the circulating immune cells of 20 treatment-naïve (TNs), 20 immunological non-responders (INRs), 20 immunological responders (IRs), and 10 healthy controls (HCs). Correlation analysis was conducted between cell subpopulation percentages and indicators including HIV-1 cell-associated (CA)-RNA, DNA, CD4+ T cell count, and CD4/CD8 ratio. RESULTS: Global activation, immunosenescence, and exhaustion phenotypes were observed in myeloid cells and T cells from individuals with HIV-1 infection. We also found that specific subsets or clusters of myeloid, CD4+ T, and CD8+ T cells were significantly lost or increased in TN individuals, which could be partially restored after receiving ART. The percentages of several subpopulations correlated with HIV-1 CA-RNA, DNA, CD4+ T cell count, and CD4/CD8 ratio, suggesting that changes in immune cell composition were associated with therapeutic efficacy. CONCLUSION: These data provide a complete profile of immune cell subpopulations or clusters that are associated with disease progression during chronic HIV-1 infection, which will improve understanding regarding the mechanism of incomplete immune recovery in INRs.

Identification of Heterophilic Epitopes of H1N1 Influenza Virus Hemagglutinin.

Our previous studies found that the H1-50 monoclonal antibody (mAb) of influenza A virus hemagglutinin (HA) cross-reacted with pancreatic tissue and islet ß-cells, and further studies showed that H1-50 mAb binds to prohibitin (PHB) protein of islet ß-cells. These suggest that there are heterophilic epitopes between influenza virus HA and pancreatic tissue, which may be involved in the pathogenesis of type 1 diabetes. To further investigate these heterophilic epitopes, we screened binding epitopes of H1-50 mAb using a phage 12-peptide library. DNA sequencing and comparative analysis were performed on specific positive phage clones, and the sequence of 12-peptide binding to H1-50 mAb was obtained. The binding epitopes of H1-50 mAb in influenza virus HA were determined by sequence analysis and experimental verification, and their distribution within the three-dimensional structure was assessed by PyMOL. The results showed that H1-50 mAb specifically binds to polypeptides (306-SLPFQNIHPITIGK-319) of influenza A virus HA, located in the stem of the HA protein. However, there is no specific binding sequence between H1-50 mAb and the PHB protein of islet ß-cells in the primary structure, and we speculate that the binding of H1-50 mAb to islet ß-cells may depend on the spatial conformation. The identification of the heterophilic epitopes of H1N1 influenza virus hemagglutinin provides a new perspective on type 1 diabetes that may be caused by influenza virus infection, which may contribute to the prevention and control of influenza.

Identification and analysis of B cell epitopes of hemagglutinin of H1N1 influenza virus.

The frequent variation of influenza virus hemagglutinin (HA) antigen is the main cause of influenza pandemic. Therefore, the study of B cell epitopes of HA is of great significance in the prevention and control of influenza virus. In this study, the split vaccine of 2009 H1N1 influenza virus was used as immunogen, and the monoclonal antibodies (mAbs) were prepared by conventional hybridoma fusion and screening techniques. The characteristics of mAbs were identified by ELISA method, Western-blot test and hemagglutination inhibition test (HI). Using the obtained mAbs as a tool, the B cell epitopes of HA were predicted by ELISA blocking test, sandwich ELISA method and computer simulation method. Finally, four mAbs against HA antigen of H1N1 influenza virus were obtained. The results of ELISA and computer prediction showed that there were at least two types of epitopes on HA of influenza virus. The results of this study complemented the existing methods for predicting HA epitopes, and also provided a new method for predicting other pathogenic microorganisms.

Long-term exposure to copper induces mitochondria-mediated apoptosis in mouse hearts.

Copper is a trace element necessary for the normal functioning of organisms, but excessive copper contents may be toxic to the heart. The goal of this study was to investigate the role of excessive copper accumulation in mitochondrial damage and cell apoptosis inhibition. In vivo, the heart copper concentration and cardiac troponin I (c-TnI) and N-terminal forebrain natriuretic peptide (NT-pro-BNP) levels increased in the copper-laden model group compared to those of the control group. Histopathological and ultrastructural observations revealed that the myocardial collagen volume fraction (CVF), perivascular collagen area (PVCA) and cardiomyocyte cross-sectional area (CSA) were markedly elevated in the copper-laden model group compared with the control group. Furthermore, transmission electron microscopy (TEM) showed that the mitochondrial double-layer membrane was incomplete in the copper-laden model groups. Furthermore, cytochrome C (Cyt-C) expression was downregulated in mitochondria but upregulated in the cytoplasm in response to copper accumulation. In addition, Bcl-2 expression decreased, while Bax and cleaved caspase-3 levels increased. These results indicate that copper accumulation in cardiomyocyte mitochondria induces mitochondrial injury, and Cyt-C exposure and induces apoptosis, further resulting in heart damage.

Investigation on the effect of three isoflavones on the fibrillation of hen egg-white lysozyme.

In this paper, the effects of three isoflavones including daidzein, genistein, and puerarin on fibrillation of hen egg-white lysozyme were investigated by various analytical methods. The results demonstrated that all isoflavones could effectively inhibit the fibrillogenesis of hen egg-white lysozyme and destabilized the preformed fibrils of hen egg-white lysozyme in a dose-dependent manner. To further understand the inhibition mechanism, molecular modeling was carried out. The docking results demonstrated that the isoflavones could bind to two key fibrogenic sites in hen egg-white lysozyme through van der Waals force, electrostatic forces, and hydrogen bonding, as well as σ-π stacking. By these means, isoflavones could not only obviously enhance the hydrophobicity of the binding sites, but also greatly stabilize the native state of HEWL, which was able to postpone the fibrosis process of hen egg-white lysozyme.

Monoclonal Antibody Targeting the HA191/199 Region of H1N1 Influenza Virus Mediates the Damage of Neural Cells.

Vaccination is the most effective mean of preventing influenza virus infections. However, vaccination-induced adverse reactions of the nervous system, the causes of which are unknown, lead to concerns on the safety of influenza A vaccine. In this study, we used flow cytometry, cell ELISA, and immunofluorescence to find that H1-84 monoclonal antibody (mAb) against the191/199 region of the H1N1 influenza virus hemagglutinin (HA) protein binds to neural cells and mediates cell damage. Using molecular simulation software, such as PyMOL and PDB viewer, we demonstrated that the HA191/199 region maintains the overall structure of the HA head. Since the HA191/199 region cannot be removed from the HA structure, it has to be altered via introducing point mutations by site-directed mutagenesis. This will provide an innovative theoretical support for the subsequent modification the influenza A vaccine for increasing its safety.

Two kinds of rare light chain cast nephropathy caused by multiple myeloma: case reports and literature review.

BACKGROUND: Light chain cast nephropathy (LCCN) is the most common renal disease caused by multiple myeloma (MM). In addition to ordinary light chain protein casts, there are a few rare casts with unique shapes, including light chain amyloid casts (LCAC) and light chain crystal casts (LCCC). CASE PRESENTATIONS: Here, we report two patients. Patient 1 is a 72-year-old man who was clinically diagnosed with MM and acute kidney injury (AKI). Pathological examination of a renal biopsy revealed that there were many amyloid casts in the distal tubules that had a lightly-stained central area and a deeply-stained burr-like edge. The marginal zone of the cast was positive for Congo red staining and contained numerous amyloid fibers, as observed by electron microscopy. No systemic amyloidosis was found. The patient received 4 courses of bortezomib-based chemotherapy, and then, his MM achieved partial remission. Patient 2 is a 57-year-old man who was also clinically diagnosed with MM and AKI. Pathological examination of a renal biopsy showed that there were many crystalline casts in the distal tubules that were fully or partially composed of crystals with different shapes, including rhomboid, needle, triangle, rectangle and other geometric shapes. Congo red staining was negative. Crystals were also detected in the urine of this patient. After 9 courses of treatment with a bortezomib-based regimen, his MM obtained complete remission and his renal function returned to normal. CONCLUSIONS: LCAC and LCCC nephropathy caused by MM are two rare types of LCCN, and both have their own unique morphological manifestations. LCAC nephropathy may not be accompanied by systemic amyloidosis. The diagnosis of these two unique LCCNs must rely on renal biopsy pathology, and the discovery of urine crystals is of great significance for indicating LCCC nephropathy.

Ultralow-Content Palladium Dispersed in Covalent Organic Framework for Highly Efficient and Selective Semihydrogenation of Alkynes.

Developing noble-metal-based catalysts with ultralow loading to achieve excellent performance for selective hydrogenation of alkynes under mild reaction conditions is highly desirable but still faces huge challenges. To this end, a SO3H-anchored covalent organic framework (COF-SO3H) as the support was deliberately designed, and then ultralow-content Pd (0.38 wt %) was loaded by a wet-chemistry immersion dispersion method. The resulting Pd0.38/COF-SO3H composite exhibits outstanding performance for the selective hydrogenation of phenylacetylene with 97.06% conversion and 93.15% selectivity to styrene under mild reaction conditions (1 bar of H2, 25 °C). Noticeably, the turnover frequency value reaches as high as 3888 h-1, which outperforms most of reported catalysts for such use. Moreover, such a catalyst also exhibits excellent activity for a series of other alkynes and high stability without obvious loss of catalytic performance after five consecutive cycles.

The faster-onset antidepressant effects of hypidone hydrochloride (YL-0919).

Hypidone hydrochloride (YL-0919), is a novel structural antidepressant candidate as a triple selective serotonin re-uptake inhibitor (SSRI), 5-HT1A partial agonist and 5-HT6 agonist. Here, we investigated the rapid onset antidepressant-like effects of YL-0919 and the possible mechanism in rats exposed to a chronic unpredictable stress (CUS) paradigm. In the CUS rats, it was found that fluoxetine (FLX, 10 mg/kg) treatment exerted antidepressant actions on 20-22d, while YL-0919 or vilazodone (VLZ, a dual 5-HT1A partial agonist and SSRI) administrated once daily exerted faster antidepressant-like behaviors [4 days in the sucrose preference test (SPT) and 6 days in the novelty suppressed feeding test (NSF)]. Thereafter, the serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels were reversed by treatment with YL-0919 for 7 days. Furthermore, YL-0919 treatment for 5 days reversed the brain derived neurotrophic factor (BDNF)-mammalian target of rapamycin (mTOR) signaling and the key synaptic proteins, such as post-synaptic density (PSD95), GluR1 and presynaptic protein synapsin1. Meanwhile, the dendritic complexity of pyramidal neurons in prefrontal cortex (PFC) were also increased in the CUS rats. These data suggest that YL-0919 exerts a faster antidepressant-like effect on behaviors and this effect maybe at least partially mediated by the BDNF-mTOR signaling related dendritic complexity increase in the PFC.

Corrigendum to "CD36-Mediated Lipid Accumulation and Activation of NLRP3 Inflammasome Lead to Podocyte Injury in Obesity-Related Glomerulopathy".

[This corrects the article DOI: 10.1155/2019/3172647.].

CD36-Mediated Lipid Accumulation and Activation of NLRP3 Inflammasome Lead to Podocyte Injury in Obesity-Related Glomerulopathy.

Podocyte injury critically contributes to the pathogenesis of obesity-related glomerulopathy (ORG). Recently, lipid accumulation and inflammatory responses have been found to be involved in podocyte injury. This study is to explore their role and relationship in podocyte injury of ORG. In animal experiments, the ORG mice developed proteinuria, podocyte injury, and hypertriglyceridemia, accompanied with deregulated lipid metabolism, renal ectopic lipid deposition, activation of NOD-like receptor protein 3 (NLRP3) inflammasome, and secretion of IL-1ß of the kidney. The expression of adipose differentiation-related protein (ADRP), CD36, sterol regulatory element-binding protein 1 (SREBP-1), and peroxisome proliferator-activated receptor α (PPARα) in renal tissue were increased. In in vitro cell experiments, after cultured podocytes were stimulated with leptin, similar to ORG mice, we found aggravated podocyte injury, formatted lipid droplet, increased expression of ADRP and CD36, activated NLRP3 inflammasome, and released IL-1ß. In addition, after blocking CD36 with inhibitor sulfo-N-succinimidyl oleate (SSO) or CD36 siRNA, activation of NLRP3 inflammasome and release of IL-1ß are downregulated, and podocyte injury was alleviated. However, after blocking NLRP3 with MCC950, although podocyte injury was alleviated and release of IL-1ß was decreased, there was no change in the expression of CD36, ADRP, and intracellular lipid droplets. Taken together, our study suggests that CD36-mediated lipid accumulation and activation of NLRP3 inflammasome may be one of the potential pathogeneses of ORG podocyte injury.

[Learning and Memory Capacity and NMDA Receptor Expression in Shen Deficiency Constitution Rats].

OBJECTIVE: To explore material bases and neurobiological mechanisms of "Shen storing will" by observing learning and memory capacities and N-methyl-D-aspartic acid (NMDA) receptor expressions in Shen deficiency constitution (SDC) rats. METHODS: Totally 40 SD rats were randomly divided into the model group, the Zuogui Pill (ZP) group, the Yougui Pill (YP) group, the blank control group (consisting of normal pregnant rats), 10 in each group. SDC young rat model (inherent deficiency and postnatal malnutrition) was prepared by the classic way of "cat scaring rat". Medication started when they were scared by cat. Rats in the ZP group and the YP group were administered by gastrogavage with ZP suspension 0.1875 g/mL and YP suspension 0.0938 g/mL respectively. Equal volume of normal saline was administered to rats in the blank control group and the model group by gastrogavage. All medication was given once per day, 5 days in a week for 2 consecutive months. Learning and memory capacities were detected by Morris water maze test. Expressions of NMDA receptor subunits NR2A and NR2B in hippocamus were detected by immunohistochemical method. RESULTS: Compared with the blank control group, the latency period, total distance in Morris water maze test were longer in the model group (P < 0.05). All the aforesaid indices all decreased in the ZP group and the YP group, with statistical difference when compared with the model group (P < 0.05). The protein expressions of NR2A and NR2B in hippocamus were lower in the model group than in the blank control group (P < 0.05). But when compared with the model group, they were obviously higher in the ZP group and the YP group (P < 0.05). CONCLUSIONS: SDC rats had degenerated learning and memory capacities and lowered NMDA receptor expressions. ZP and YP could up-regulate learning and memory capacities and NMDA receptor expressions, thereby improving deterioration of brain functions in SDC rats.

[Application of Immunohistochemistry and Immunofluorescence Staining in Detection of Phospholipase A2 Receptor on Paraffin Section of Renal Biopsy Tissue].

OBJECTIVE: To evaluate the application of immunohistochemistry and fluorescence staining method in the detection of phospholipase A2 receptor (PLA2R) on paraffin section of renal biopsy tissue,and to find an accurate and fast method for the detection of PLA2R in renal tissue. METHODS: The PLA2R of 193 cases were detected by immunohistochemical staining,and the antigen was repaired by the method of high pressure cooker (HPC) hot repair plus trypsin repair. The 193 samples including 139 cases of idiopathic membranous nephropathy (IMN), 15 cases of membranous lupus nephritis, 8 cases of hepatitis B virus associated membranous nephropathy, 18 cases of IgA nephropathy, and 13 cases of minimal change diseases. To compare the dyeing effects, 22 paraffin sections of renal biopsy tissue of IMN cases with positive PLA2R were stained by using 4 different. METHODS: of antigen repairing,which included HPC hot repair, HPC hot repair plus trypsin repair, water bath heat repair, and water bath heat repair plus trypsin repair. To compare the dyeing effects, 15 paraffin sections of renal biopsy tissue of IMN cases with positive PLA2R were stained by using 3 different. METHODS: of antigen repairing,which included water bath heat repair plus trypsin repair, protease K digestion repair, and pepsin digestion repair. RESULTS: In 193 cases, the positive rate of PLA2R in IMN cases was 90.6% (126/139), and the other 54 patients without IMN were negative. Twenty-two IMN patients were positive for PLA2R by using the HPC heat repair plus trypsin repaire or the water bath heat repair plus trypsin repair;while only a few cases of 22 IMN cases were positive by using the HPC hot repair alone or water bath heat repair alone. Fifteen IMN patients were positive for PLA2R by using water bath heat repair plus trypsin repair,protease K digestion repair,and pepsin digestion repair, but the distribution of positive deposits and the background were different. CONCLUSIONS: PLA2R immunohistochemical staining can effectively identify IMN and secondary MN. For immunohistochemical staining and immunofluorescence staining, the preferred method of antigen repair is water bath heat repair plus trypsin repair.

Addition of optically pure H-phosphinate to ketones: selectivity, stereochemistry and mechanism.

Aromatic methyl ketones and cyclic asymmetric ketones underwent hydrophosphorylation with P-stereogenic H-P species in the presence of potassium carbonate to produce P,C-stereogenic tertiary α-hydroxyl phosphinates in excellent yields with up to 99 : 1 dr. The diastereoselectivity was induced by a reversible conversion of less stable stereomer of product to that of a more stable one via an equilibrium, which was confirmed by aldehyde/ketone exchanging reaction. Toward the exchange, aliphatic or aldehyde carbonyl were more active than aromatic or ketone carbonyls, respectively. The stability difference between the two diastereomers was controlled by the sizes of substituents linking to phosphorus or α-carbon.

Effects of endothelial nitric oxide synthase gene on end stage renal disease progression in autosomal dominant polycystic kidney disease.

AIM: To investigate whether endothelial nitric oxide synthase (eNOS) gene associate with the progression of autosomal dominant polycystic kidney disease (ADPKD). METHODS: Databases of EMBASE, Pubmed, ISI, Ovid Database, Cochrane library and China National Knowledge Infrastructure were all searched. Associated studies about eNOS polymorphisms and ADPKD were analyzed by meta-analysis. RESULTS: A total of 11 studies with Glu298Asp and 4b/a polymorphisms were included. A allele of the 4b/a polymorphism increased the risk of end stage renal disease (ESRD) in ADPKD (odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.17-2.94, P = 0.009). However, GG phenotype of Glu298Asp polymorphism neither decreased the ESRD risk (OR = 0.77, 95% CI 0.55-1.08, P = 0.13) nor affected the hypertension risk (OR = 1.04, 95% CI 0.66-1.66, P = 0.86). The GG phenotype carriers had later ESRD age compared with the T allele of Glu298Asp polymorphism (WMD = 2.39; 95% CI 1.32-3.46; P < 0.0001). Significant association was also found in Caucasians (WMD = 2.41; 95% CI 1.18-3.64; P = 0.0001). Subgroup analysis by gender indicated GG genotype carriers had older age of ESRD than T allele carriers in males (WMD = 4.51; 95% CI 3.95-5.08; P = 0.00001), but not in females. CONCLUSIONS: GG genotype of the Glu298Asp variant slowed the ESRD progression in ADPKD, while a allele carriers of the 4b/a variant increased the risk of ESRD. Variants of eNOS gene might play different roles in the ESRD progression in ADPKD.

Human papillomavirus-related psychosocial impact of patients with genital warts in China: a hospital-based cross-sectional study.

BACKGROUND: Genital warts (GW) are the most common sexually transmitted infections. To date, few studies using a human papillomavirus (HPV)-specific questionnaire have focused on the impact of quality of life (QoL) among patients with GW in developing countries. The origins of GW related psychosocial burdens and variations between genders were poorly characterized as well. METHODS: A hospital-based survey was conducted in Beijing and Nanjing of China in 2008. Eligible patients aged 18-65 who had a diagnosis of GW within 3 months were recruited. Demographic information, HPV knowledge, and assessment of psychosocial burden were collected by the HPV Impact Profile (HIP). The HIP examined 7 specific psychosocial domains by 29 items: (1) worries and concerns, (2) emotional impact, (3) sexual impact, (4) self-image, (5) partner and transmission, (6) interactions with physicians, and (7) control/life impact. HIP scores are reversely relates to the subjects' QoL, by which a higher score indicating a heavier psychosocial burden. RESULTS: Patients with GW experienced heavier psychosocial burdens than those of the general population, and females experienced heavier burdens than males (male vs. female: 49.20 vs.51.38, P < 0.001). "Self Image" and "Sexual Impact" were the two domains that affected patients the most, with mean HIP scores of 63.09 and 61.64, respectively. Women suffered heavier psychosocial burdens than men in the domain of "Worries and Concerns" (female vs. male: 54.57 vs. 42.62, P < 0.001), but lower psychosocial burdens in the domains of "Sexual Impact" (female vs. male: 59.16 vs. 65.26, P < 0.001) and "Interactions with Doctors" (female vs. male: 34.40 vs. 41.97, P < 0.001). Patients from Nanjing suffered a higher psychosocial burden than those of Beijing, especially in domains of "Emotional Impact", "Sexual Impact", "Partner and Transmission", and "Interactions with Doctors". CONCLUSIONS: Patients with GW suffered heavy psychological burden, and self-image and sexual-related concern were the primary cause of burdens. It's important to change the current biomedical model to bio-psycho-social model, and establish psychosocial support systems. The distinctions of origins of psychosocial burden between genders identified will be informative for prevention of GW and control efforts in China and other similar settings.

A prepared anti-MSTN polyclonal antibody reverses insulin resistance of diet-induced obese rats via regulation of PI3K/Akt/mTOR&FoxO1 signal pathways.

Suppression of myostatin (MSTN) is associated with skeletal muscle atrophy and insulin resistance. However, the mechanisms by which MSTN regulates insulin resistance are not well known. We have explored the signaling pathways through which MSTN regulates insulin resistance in diet-induced obese rats using a polyclonal antibody for MSTN. The anti-MSTN polyclonal antibody significantly improved insulin resistance and whole-body insulin sensitivity, decreased MSTN protein expression in muscle samples by 39% in diet-induced obese rats. Furthermore, the anti-MSTN polyclonal antibody significantly enhanced PI3K activity (140%), Akt phosphorylation (86%), GLUT4 protein expression (23%), the phosphorylation of mTOR (21%), and inhibited the phosphorylation of FoxO1 (57%), but did not affect the phosphorylation of GSK-3ß. Thus, suppression of MSTN by the anti-MSTN polyclonal antibody reverses insulin resistance of diet-induced obesity via MSTN/PI3K/Akt/mTOR and MSTN/PI3K/Akt/FoxO1 signaling pathways.