Molecular mechanisms of hepatic insulin resistance in nonalcoholic fatty liver disease and potential treatment strategies.

The prevalence of nonalcoholic fatty liver disease (NAFLD) in the general population is estimated at 25 %, and there is currently no effective treatment of NAFLD. Although insulin resistance (IR) is not the only factor causing the pathogenesis of NAFLD, hepatic IR has a cause-effective relationship with NAFLD. Improving hepatic IR is a potential therapeutic strategy to treat NAFLD. This review highlights the molecular mechanisms of hepatic IR in the development of NAFLD. Available data on potential drugs including glucagon-like peptide 1 receptor (GLP-1) agonists, peroxisome proliferator-activated receptor (PPAR-γ/α/δ) agonists, farnesoid X receptor (FXR) agonists, etc. are carefully discussed.

Binary mixtures of active and passive particles on a sphere.

We study the cooperation and segregation dynamics of binary mixtures of active and passive particles on a sphere. According to the competition between rotational diffusion and polar alignment, we find three distinct phases: a mixed phase and two different demixed phases. When rotational diffusion dominates the dynamics, the demixing is due to the aggregation of passive particles, where active and passive particles respectively occupy two hemispheres. When polar alignment is dominated, the demixing is caused by the aggregation of active particles, where active particles occupy the equator of the sphere and passive particles occupy the two poles of the sphere. In this case, there exist a circulating band cluster and two cambered surface clusters, which is a purely curvature-driven effect with no equivalent in the planar model. When rotational diffusion and polar alignment are comparable, particles are completely mixed. Our findings are relevant to the experimental pursuit of segregation dynamics of binary mixtures on curved surfaces.

Latitudinal pronounced variations in tintinnid (Ciliophora) community at surface waters from the South China Sea to the Yellow Sea: Oceanic-to-neritic species shift, biotic-abiotic interaction and future prediction.

The oceanic-to-neritic species shift of microzooplanktonic tintinnids and their interaction with relevant abiotic variables are two crucial processes in the marine ecosystem. However, these processes remain poorly documented in China's marginal seas. In the summer of 2022, we investigated the community structure of pelagic tintinnids in surface waters from the South China Sea (SCS) to the Yellow Sea (YS), passing through the East China Sea (ECS). A number of 58 species from 23 genera were identified, with 36 and 22 species belonging to oceanic and neritic genera, respectively. The abundance proportion of oceanic and neritic genera exhibited a decreasing and increasing trend, respectively, from the SCS to YS. Furthermore, four distinctive tintinnid community groups were classified based on cluster analysis using tintinnid species and abundance data, and the position of southern Taiwan Strait was identified as the "Shift Point" for oceanic-to-neritic species dominance. The top two tintinnid species in each group showed distinct variations in body size. Additionally, multivariate biotic-abiotic statistical analyses revealed that temperature determined tintinnid species richness, while temperature, salinity, Si(OH)4, and Chl a determined tintinnid abundance. Our study provides a substantial foundation for recognizing the oceanic-to-neritic species shift of tintinnids in the China's marginal seas, and highlights the role of biotic-abiotic factors in driving biogeochemical fluxes and the potential response of microzooplankton to future climate change.

Thymopentin (TP-5) prevents lipopolysaccharide-induced neuroinflammation and dopaminergic neuron injury by inhibiting the NF-κB/NLRP3 signaling pathway.

Neuroinflammation plays a pivotal role in neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and stroke, and is accompanied by excessive release of inflammatory cytokines and mediators by activated microglia. Microglial inflammatory response inhibition may be an effective strategy for preventing inflammatory disorders. However, the reciprocal connections between the central nervous system (CNS) and immune system have not been elucidated. Thus far, these links have been proven to mainly involve immuno- and neuropeptides. The pentapeptide thymopentin (TP-5) exerts a significant immunomodulatory effect; however, its antineuroinflammatory effects and underlying mechanism are still unclear. In this study, lipopolysaccharide (LPS) was used to establish an inflammation model, and the therapeutic effect of TP-5 was evaluated. Behavioral tests showed that TP-5 treatment could improve the performance of LPS-treated mice in the open field and pole test, but not hanging wire test. TP-5 also attenuated neuronal lesions in the brains of LPS-treated mice. TP-5 reduced cytotoxicity and morphological changes in activated microglia. Label-free quantitative analysis indicated that the expression of multiple proteins and the activation of associated signaling pathways were altered by TP-5. Moreover, TP-5 could inhibit LPS-induced neuroinflammation in the brain and BV2 microglia and the expression of major genes in the NF-κB/NLRP3 signaling pathway. Additionally, tyrosine hydroxylase (TH) expression downregulation was rescued in the LPS + TP-5 group compared with the LPS group. We conclude that TP-5 exerts neuroprotection by alleviating LPS-induced inflammatory damage and dopaminergic neurodegeneration. The protective effect of TP-5 may involve the NF-κB/NLRP3 signaling pathway.

Curcumin alleviated dextran sulfate sodium-induced colitis by recovering memory Th/Tfh subset balance.

BACKGROUND: Restoration of immune homeostasis by targeting the balance between memory T helper (mTh) cells and memory follicular T helper (mTfh) cells is a potential therapeutic strategy against ulcerative colitis (UC). Because of its anti-inflammatory and immunomodulatory properties, curcumin (Cur) is a promising drug for UC treatment. However, fewer studies have demonstrated whether Cur can modulate the mTh/mTfh subset balance in mice with colitis. AIM: To explore the potential mechanism underlying Cur-mediated alleviation of colitis induced by dextran sulfate sodium (DSS) in mice by regulating the mTh and mTfh immune homeostasis. METHODS: Balb/c mice were administered 3% and 2% DSS to establish the UC model and treated with Cur (200 mg/kg/d) by gavage on days 11-17. On the 18th d, all mice were anesthetized and euthanized, and the colonic length, colonic weight, and colonic weight index were evaluated. Histomorphological changes in the mouse colon were observed through hematoxylin-eosin staining. Levels of Th/mTh and Tfh/mTfh cell subsets in the spleen were detected through flow cytometry. Western blotting was performed to detect SOCS-1, SOCS-3, STAT3, p-STAT3, JAK1, p-JAK1, and NF-κB p65 protein expression levels in colon tissues. RESULTS: Cur effectively mitigates DSS-induced colitis, facilitates the restoration of mouse weight and colonic length, and diminishes the colonic weight and colonic weight index. Simultaneously, it hinders ulcer development and inflammatory cell infiltration in the colonic mucous membrane. While the percentage of Th1, mTh1, Th7, mTh7, Th17, mTh17, Tfh1, mTfh1, Tfh7, mTfh7, Tfh17, and mTfh17 cells decreased after Cur treatment of the mice for 7 d, and the frequency of mTh10, Th10, mTfh10, and Tfh10 cells in the mouse spleen increased. Further studies revealed that Cur administration prominently decreased the SOCS-1, SOCS-3, STAT3, p-STAT3, JAK1, p-JAK1, and NF-κB p65 protein expression levels in the colon tissue. CONCLUSION: Cur regulated the mTh/mTfh cell homeostasis to reduce DSS-induced colonic pathological damage, potentially by suppressing the JAK1/STAT3/SOCS signaling pathway.

Pien Tze Huang alleviates Concanavalin A-induced autoimmune hepatitis by regulating intestinal microbiota and memory regulatory T cells.

BACKGROUND: Traditional Chinese medicine has used the drug Pien Tze Huang (PTH), a classic prescription, to treat autoimmune hepatitis (AIH). However, the precise mode of action is still unknown. AIM: To investigate the mechanism of PTH in an AIH mouse model by determining the changes in gut microbiota structure and memory regulatory T (mTreg) cells functional levels. METHODS: Following induction of the AIH mouse model induced by Concanavalin A (Con A), prophylactic administration of PTH was given for 10 d. The levels of mTreg cells were measured by flow cytometry, and intestinal microbiota was analyzed by 16S rRNA analysis, while western blotting was used to identify activation of the toll-like receptor (TLR)2, TLR4/nuclear factor-κB (NF-κB), and CXCL16/CXCR6 signaling pathways. RESULTS: In the liver of mice with AIH, PTH relieved the pathological damage and reduced the numbers of T helper type 17 cells and interferon-γ, tumor necrosis factor-alpha, interleukin (IL)-1ß, IL-2, IL-6, and IL-21 expression. Simultaneously, PTH stimulated the abundance of helpful bacteria, promoted activation of the TLR2 signal, which may enhance Treg/mTreg cells quantity to produce IL-10, and suppressed activation of the TLR4/NF-κB and CXCL16/CXCR6 signaling pathways. CONCLUSION: PTH regulates intestinal microbiota balance and restores mTreg cells to alleviate experimental AIH, which is closely related to the TLR/CXCL16/CXCR6/NF-κB signaling pathway.

Curcumin alleviates experimental colitis via a potential mechanism involving memory B cells and Bcl-6-Syk-BLNK signaling.

BACKGROUND: Immune dysfunction is the crucial cause in the pathogenesis of inflammatory bowel disease (IBD), which is mainly related to lymphocytes (T or B cells, incl-uding memory B cells), mast cells, activated neutrophils, and macrophages. As the precursor of B cells, the activation of memory B cells can trigger and differentiate B cells to produce a giant variety of inducible B cells and tolerant B cells, whose dysfunction can easily lead to autoimmune diseases, including IBD. AIM: To investigate whether or not curcumin (Cur) can alleviate experimental colitis by regulating memory B cells and Bcl-6-Syk-BLNK signaling. METHODS: Colitis was induced in mice with a dextran sulphate sodium (DSS) solution in drinking water. Colitis mice were given Cur (100 mg/kg/d) orally for 14 con-secutive days. The colonic weight, colonic length, intestinal weight index, occult blood scores, and histological scores of mice were examined to evaluate the curative effect. The levels of memory B cells in peripheral blood of mice were measured by flow cytometry, and IL-1ß, IL-6, IL-10, IL-7A, and TNF-α expression in colonic tissue homogenates were analyzed by enzyme-linked immunosorbent assay. Western blot was used to measure the expression of Bcl-6, BLNK, Syk, and other signaling pathway related proteins. RESULTS: After Cur treatment for 14 d, the body weight, colonic weight, colonic length, colonic weight index, and colonic pathological injury of mice with colitis were ameliorated. The secretion of IL-1ß, IL-6, TNF-α, and IL-7A was statistically decreased, while the IL-35 and IL-10 levels were considerably increased. Activation of memory B cell subsets in colitis mice was confirmed by a remarkable reduction in the expression of IgM, IgG, IgA, FCRL5, CD103, FasL, PD-1, CD38, and CXCR3 on the surface of CD19+ CD27+ B cells, while the number of CD19+ CD27+ IL-10+ and CD19+ CD27+ Tim-3+ B cells increased significantly. In addition, Cur significantly inhibited the protein levels of Syk, p-Syk, Bcl-6, and CIN85, and increased BLNK and p-BLNK expression in colitis mice. CONCLUSION: Cur could effectively alleviate DSS-induced colitis in mice by regulating memory B cells and the Bcl-6-Syk-BLNK signaling pathway.

Sishen Pill Ameliorates Dextran Sulfate Sodium (DSS)-Induced Colitis with Spleen-Kidney Yang Deficiency Syndromes: Role of Gut Microbiota, Fecal Metabolites, Inflammatory Dendritic Cells, and TLR4/NF-κB Pathway.

Sishen pill (SSP) is an old Chinese medicine used to treat colitis with spleen-kidney-yang deficiency (SKYD) syndromes. However, its exact mechanism of action has not yet been fully elucidated. The aim of this study was to evaluate the effects and potential mechanisms of SSP on colitis with SKYD syndromes in mice. Colitis with SKYD syndromes was induced by rhubarb, hydrocortisone, and dextran sulfate sodium (DSS), and treatment was provided with SSP. Flow cytometry was performed to examine the inflammatory dendritic cell (infDC) regulations of SSP. The changes in the gut microbiota (GM) and fecal metabolites post-SSP treatment were investigated using the combination of 16S rRNA sequencing and untargeted metabolomics. Additionally, we also examined whether SSPs could regulate the infDCs by modifying TLR4/NF-κB signaling pathways. Compared with the DSS group, the disease activity index, colonic weight, index of colonic weight, and colonic injury scores, as well as the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-12p70 decreased significantly in the DSS + SSP group, while free triiodothyronine (FT3), free tetraiodothyronine (FT4), testosterone (TESTO), body weight change, colonic length, and the levels of IL-10 increased. Also, SSP decreased the amounts of CD103+CD11c+iNOS+, CD103+CD11c+TNF-α +, CD11c+CD103+CD324+, CD103+CD11c+MHC-II+, and CD103+CD11c+CD115+. Interestingly, 16S rRNA sequencing and untargeted metabolomics showed that SSP treatment restored the dysbiosis of GM and improved the dysfunction in fecal metabolism in colitis mice with SKYD syndromes. Correlation analysis indicated that the modulatory effects of SSP on FT3, FT4, IL-10, colonic weight index, CD103+CD11c+TNF-α +, CD103+CD11c+MHC-II+, and 13 common differential metabolites were related to alterations in the abundance of Parvibacter, Aerococcus, norank_f_Lachnospiraceae, Lachnospiraceae_UCG-006, Akkermansia, and Rhodococcus in the GM. In addition, SSP markedly inhibited the activation of the TLR4, MyD88, TRAF6, TAB2, and NF-κBp65 proteins and activated IκB. These results indicate that SSP can effectively alleviate colitis mice with SKYD syndrome by regulating infDCs, GM, fecal metabolites, and TLR4/NF-κB signaling pathways.

Whole-genome resequencing reveals molecular imprints of anthropogenic and natural selection in wild and domesticated sheep.

The abundance of domesticated sheep varieties and phenotypes is largely the result of long-term natural and artificial selection. However, there is limited information regarding the genetic mechanisms underlying phenotypic variation induced by the domestication and improvement of sheep. In this study, to explore genomic diversity and selective regions at the genome level, we sequenced the genomes of 100 sheep across 10 breeds and combined these results with publicly available genomic data from 225 individuals, including improved breeds, Chinese indigenous breeds, African indigenous breeds, and their Asian mouflon ancestor. Based on population structure, the domesticated sheep formed a monophyletic group, while the Chinese indigenous sheep showed a clear geographical distribution trend. Comparative genomic analysis of domestication identified several selective signatures, including IFI44 and IFI44L genes and PANK2 and RNF24 genes, associated with immune response and visual function. Population genomic analysis of improvement demonstrated that candidate genes of selected regions were mainly associated with pigmentation, energy metabolism, and growth development. Furthermore, the IFI44 and IFI44L genes showed a common selection signature in the genomes of 30 domesticated sheep breeds. The IFI44 c. 54413058 C>G mutation was selected for genotyping and population genetic validation. Results showed that the IFI44 polymorphism was significantly associated with partial immune traits. Our findings identified the population genetic basis of domesticated sheep at the whole-genome level, providing theoretical insights into the molecular mechanism underlying breed characteristics and phenotypic changes during sheep domestication and improvement.

Regulatory effect of Zuojin Pill on correlation with gut microbiota and Treg cells in DSS-induced colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: As a classic prescription and commercial Chinese patent medicine, Zuojin Pill (ZJP) has been used to treat ulcerative colitis (UC) effectively for many years. However, its mechanism of action remains unclear. AIM OF THE STUDY: METHODS: Mice with dextran-sulfate-sodium-induced colitis were treated with ZJP for 7 d. In the present study, the therapeutic effect of ZJP was evaluated by macroscopic and microscopic observation; regulatory T (Treg) cells and their subsets were analyzed by flow cytometry; and the composition of gut microbiota was tested by 16S rRNA analysis. Activation of the phosphoinostide 3-kinase (PI3K)/Akt signaling pathway was observed by western blotting. RESULTS: The pathological damage was attenuated and expression of proinflammatory cytokines was decreased. While the diversity of intestinal microflora was regulated, the relative abundance of Actinobacteria, and Sphingobacteriia was modified. Meanwhile, the level of CD4+CD25+Foxp3+ and PD-L1+ Treg cells improved. These changes maintained a positive correlation which was analyzed statistically. Our results also showed that ZJP inhibited activation of the PI3K/Akt signaling pathway. CONCLUSIONS: ZJP regulates crosstalk between intestinal microflora and Treg cells to attenuate experimental colitis via the PI3K/Akt signaling pathway.

Curcumin Regulated the Homeostasis of Memory T Cell and Ameliorated Dextran Sulfate Sodium-Induced Experimental Colitis.

Immune memory is protective against reinvasion by pathogens in the homeostatic state, while immune memory disorders can cause autoimmune disease, including inflammatory bowel disease. Curcumin is a natural compound shown to be effective against human inflammatory bowel disease and experimental colitis, but the underlying mechanism is unclear. Here, experimental colitis was induced by dextran sulfate sodium (DSS) in this study. Significant changes in the percentages of naïve, central memory T (TCM), and effector memory (TEM) cells and their CD4+ and CD8+ subsets were found in the peripheral blood of mice with colitis using flow cytometry. After 7 days of continuous curcumin (100 mg/kg/day) administration, the DSS-induced experimental colitis was effectively relieved, with significant decreases in the ratio of day weight to initial body weight, colonic weight, pathological injury score, levels of proinflammatory cytokines IL-7, IL-15, and IL-21, colonic mucosal ulceration, and amount of inflammatory infiltrate. Importantly, curcumin significantly restored the percentages of naïve, TCM, and TEM cells and their CD4+ and CD8+ subpopulations. In addition, curcumin significantly inhibited the activation of the JAK1/STAT5 signaling pathway, downregulation of JAK1, STAT5, and p-STAT5 proteins in colon tissue, and upregulation of PIAS1 proteins. These results suggested that curcumin effectively regulated the differentiation of naïve, TCM, and TEM cells in the peripheral blood to alleviate DSS-induced experimental colitis, which might be related to the inhibition of JAK1/STAT5 signaling activity.

Dynamics and diagenesis of trace metals in sediments of the Changjiang Estuary.

The seasonal dynamics and diagenesis of trace metals at two contrasting coastal sites were studied to determine the mechanism that drove the diffusive release of trace metals from sediments in the Changjiang Estuary. Porewater trace metal concentrations were 53.4-4829 nM for Zn, 11.0-344 nM for Cu, 7.75-221 nM for Cr, 2.71-61.1 nM for Co, 0.822-42.7 nM for Pb and 0.037-4.22 nM for Cd. The concentrations and profiles of trace metals in the porewater and solid phase displayed obvious regional and seasonal variations. This variation was mainly reflected in the surface layer and the depth of the suboxic and anoxic layers. Regionally, surface porewater trace metal concentrations in the seasonal hypoxic region were higher than those in the aerobic region due to changes in the redox conditions being beneficial to the release of trace metals. Seasonally, surface porewater trace metal concentrations decreased in summer compared to spring due to their removal by forming metal sulfides in summer. Solid profiles of the trace metals supported their dynamic variations in the porewater. The partition coefficient suggested that the formation of Fe/Mn (hydr)oxides was effective for the removal of trace metal in oxidizing condition, while the formation of sulfides was conducive to the removal of trace metals in reducing condition. The combination of porewater with solid phase data suggested that the dynamics of Cu, Zn, Cr and Co were mainly controlled by Fe and Mn diagenesis, the dynamics of Cd were affected by S cycling, and the dynamics of Pb were disturbed by anthropogenic inputs and benthic organism activities. Estimation of benthic fluxes indicated that sediments were an important source of trace metals in the water column. The contributions of trace metals by sediments to the water column of the Changjiang Estuary were only one order of magnitude lower than those by riverine fluxes.

CYP3A4*1B Polymorphism and Cancer Risk: A Meta-Analysis Based on 55 Case-control Studies.

Published data on the association between CYP3A4*1B polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the association, we conducted a meta-analysis. A systematic search of the PubMed database was performed. A total of 55 separate studies including 22072 cancer cases and 25433 controls were involved in this meta-analysis. We found a significant association between CYP3A4*1B and cancer risk in the overall population in dominant model (AG+GG vs. AA: OR=1.142, 95% CI=1.006-1.295). No significant association was found in recessive model (GG vs. AG+AA: OR=1.156, 95% CI=0.941-1.419), heterozygous model (AG vs. AA: OR=1.109, 95% CI=0.977-1.259), or homozygous model (GG vs. AA: OR=1.213, 95% CI=0.950-1.549). We performed subgroup meta-analysis based on the difference of ethnicity and cancer type. Ethnic subgroup analyses revealed no significant associations of African or Caucasian ethnicities in any genetic models. In the subgroup analysis by Cancer types, we observed an increased risk for leukemia in dominant model and heterozygous model. Excluding studies with controls not in HWE, a significant association was found in dominant model and heterozygous model. In summary, this meta-analysis suggests that the CYP3A4*1B polymorphism might play a modest role in susceptibility to cancer, especially for leukemia.

[Amino acids in marine particulate matters and sediments and their role as indicators for organic matter degradation.] / 海洋颗粒物/æ²‰ç§¯ç‰©ä¸­çš„æ°¨åŸºé ¸åŠå ¶å¯¹æœ‰æœºè´¨é™è§£çš„æŒ‡ç¤ºä½œç”¨.

As important components of marine organic matters especially of organic nitrogen, amino acids play an important role in organic matter cycles owing to their lability. The concentration, composition, and distribution of amino acids have been widely used to indicate the degradation state of organic matters in particulates and sediments of marine. Here, the distribution, influencing factors of amino acids and their role in indicating degradation of organic matters were systematically summarized. Gly, Glu, Ala, and Asp were the major components of amino acids in marine particulates and sediments. The contents of amino acids in the particles and sediments showed a decreasing tendency from the coastal waters to the open sea, and adecreased with the water depth. The lower value of %AA-C/TOC, %AA-N/TN and degradation index (DI) based on changes in the composition of amino acids indicated the higher degradation degrees of organic matters. The reactivity index (RI) and ratios of D-AA and L-AA (D/L) based on non-protein amino acids and D-AA were used to indicate the degradation of organic matter according to the bacterial transformation of amino acids, in which RI value closer to 0, higher D/L, and lower ratios of protein amino acids to non-protein amino acids (Asp/ß-Ala and Glu/γ-Aba) indicated the higher degree of degradation in organic matters. The migration and transformation of amino acid were mainly affected by dissolved oxygen, nutrient concentrations, sources of organic matter, depositional environments and microbial activities. Further studies should focus on the synergistic effects of particles and sediments, and also the effects and the specific regulatory roles of microorganisms on amino acids.

Erzhi Pill® Protected Experimental Liver Injury Against Apoptosis via the PI3K/Akt/Raptor/Rictor Pathway.

Erzhi Pill (EZP) is one of the basic prescriptions for treating liver diseases in traditional Chinese medicine. However, its mechanism of action is still undefined. The PI3K/AKT/Raptor/Rictor signaling pathway is closely related to apoptosis and plays a significant role in the pathogenesis of liver disease. To define the mechanism of the hepatoprotective effect of EZP in the treatment of liver disease, hepatic injury induced by 2-acetylaminofluorene/partial hepatectomy was treated by EZP for 14 days. The therapeutic effect of EZP was confirmed by the decreased production of aspartate aminotransferase and alanine aminotransferase, recovery of pathological liver injury, followed by inhibition of pro-inflammatory cytokines and transforming growth factor-ß1. Bromodeoxyuridine assay and TUNEL staining indicated that apoptosis was suppressed and the numbers of cells in S phase and G0/G1phase were decreased. The crucial proteins in the PI3K/AKT/Raptor/Rictor signaling pathway were deactivated in rats with experimental liver injury treated by EZP. These results indicated that the hepatoprotective effect of EZP via inhibition of hepatocyte apoptosis was closely related to repression of the PI3K/Akt/Raptor/Rictor signaling pathway.

Effect of Puerarin Regulated mTOR Signaling Pathway in Experimental Liver Injury.

It is known that excessive hepatocellular apoptosis is a typical characteristic of hepatic disease, and is regulated by the mammalian target of rapamycin (mTOR) signaling pathway. As the main active component of Kudzu (Pueraria lobata) roots, which is frequently used to treat hepatic diseases, Puerarin (Pue) has been reported to alleviate and protect against hepatic injury. However, it is unclear whether Pue can inhibit mTOR signaling to prevent excessive apoptosis in the treatment of hepatic diseases. In the present study, Pue effectively ameliorated pathological injury of the liver, decreased serum enzyme (ALT, AST, γ-GT, AKP, DBIL, and TBIL) levels, regulated the balance between pro-inflammatory (TNF-α, IL-1ß, IL-4, IL-6, and TGF-ß1) and anti-inflammatory cytokines (IL-10), restored the cell cycle and inhibited hepatocellular apoptosis and caspase-3 expression in rats with liver injury induced by 2-AAF/PH. Pue inhibited p-mTOR, p-AKT and Raptor activity, and increased Rictor expression in the liver tissues of rats with experimental liver injury. These results indicated that Pue effectively regulated the activation of mTOR signaling pathway in the therapeutic and prophylactic process of Pue on experimental liver injury.

Persistence of immune responses to vaccine against haemorrhagic fever with renal syndrome in healthy adults aged 16-60 years: results from an open-label2-year follow-up study.

BACKGROUND: Approximately 2 million doses of vaccine against haemorrhagic fever with renal syndrome (HFRS) have been used annually in China. However, there were limited studies focused on persistence of immune responses to HFRS vaccine in healthy adults. A phase 4, multicentre, open trial has been undertaken to assess antibody persistence after HFRS vaccination of healthy adolescents and adults aged 16-60 years. METHODS: The vaccine was administered as a three-dose series at 0, 2 weeks and 6 months, including two primary doses and one booster dose. Anti-hantavirus IgG antibodies were measured by enzyme-linked immunosorbent test (ELISA) pre-vaccination and 1.5, 7 and 24 months after the initial vaccination. RESULTS: A total of 143 individuals aged 16-60 years were included. The median OD (range) values of IgG antibody were 0.005 (0.004-0.016), 0.116 (0.036-0.620), 0.320 (0.065-0.848) and 0.128 (0.011-0.649) pre-vaccination and at 1 month after the two primary doses, 1 month after the booster dose and 18 months after the booster dose. The positivity rate was 7.7%, 40.6%, 62.2% and 48.2%, respectively. CONCLUSIONS: The two primary doses could help healthy individuals to generate an immune response, and this three-dose series may be better than a two-dose regimen.

Erzhi Pill® Repairs Experimental Liver Injury via TSC/mTOR Signaling Pathway Inhibiting Excessive Apoptosis.

The present study aimed to investigate the mechanism of hepatoprotective effect of Erzhi Pill (EZP) on the liver injury via observing TSC/mTOR signaling pathway activation. The experimental liver injury was induced by 2-acetylaminofluorene (2-AAF) treatment combined with partial hepatectomy (PH). EZP treated 2-AAF/PH-induced liver injury by the therapeutic and prophylactic administration. After the administration of EZP, the activities of aspartic transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AKP), and gamma-glutamyl transpeptidase (γ-GT) were decreased, followed by the decreased levels of hepatocyte apoptosis and caspase-3 expression. However, the secretion of albumin, liver weight, and index of liver weight were elevated. Microscopic examination showed that EZP restored pathological liver injury. Meanwhile, Rheb and mammalian target of rapamycin (mTOR) activation were suppressed, and tuberous sclerosis complex (TSC) expression was elevated in liver tissues induced by 2-AAF/PHx and accompanied with lower-expression of Bax, Notch1, p70S6K, and 4E-EIF and upregulated levels of Bcl-2 and Cyclin D. Hepatoprotective effect of EZP was possibly realized via inhibiting TSC/mTOR signaling pathway to suppress excessive apoptosis of hepatocyte.

Long-term persistence of anti-hantavirus antibodies in sera of patients undergoing hemorrhagic fever with renal syndrome and subjects vaccinated against the disease.

Background China has the highest prevalence of hemorrhagic fever with renal syndrome (HFRS) and accounts for 90% of the total cases worldwide. However, the long-term persistence of anti-hantavirus antibodies in sera of patients with HFRS and subjects vaccinated against the disease remains unclear. The aim of the present study was to investigate the prevalence of anti-hantavirus IgG antibodies in sera of patients with prior HFRS, versus subjects vaccinated against the disease and controls in Shaanxi, China. Methods Six hundred individuals were included in this study. We quantified anti-hantavirus IgG antibodies in HFRS patients (n = 100), vaccinees (n = 200), controls from endemic regions (n = 200), and controls from non-endemic regions (n = 100) in China. Results The median optical density (OD) values (range) were 0.803 (0.008-1.813), 0.075 (0.004-1.565), 0.026 (0-1.179), and 0.015 (0.009-0.118) for HFRS patients, vaccinated subjects, endemic controls, and non-endemic controls, respectively. There was a strikingly significant difference between the HFRS group and each non-HFRS group (p < 0.001). The vaccinated subjects were also significantly different from the endemic controls. The time since the acute phase was correlated with the OD values of the HFRS patients. Conclusions Our study suggests that HFRS patients gain long-lasting protection and that vaccination may be an effective way to stimulate antibody production.

Astragalus polysaccharide attenuates rat experimental colitis by inducing regulatory T cells in intestinal Peyer's patches.

AIM: To explore probable mechanism underlying the therapeutic effect of Astragalus polysaccharide (APS) against experimental colitis. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four groups. Colitis was induced with 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The rats with colitis were treated with 400 mg/kg of APS for 7 d. The therapeutic effect was evaluated by colonic weight, weight index of the colon, colonic length, and macroscopic and histological scores. The levels of regulatory T (Treg) cells in Peyer's patches were measured by flow cytometry, and cytokines in colonic tissue homogenates were analyzed using enzyme-linked immunosorbent assay. The expression of related orphan receptor-γt (ROR-γt), IL-23 and STAT-5a was measured by Western blot. RESULTS: After 7-d treatment with APS, the weight index of the colon, colonic weight, macroscopical and histological scores were decreased, while the colonic length was increased compared with the model group. The expression of interleukin (IL)-2, IL-6, IL-17, IL-23 and ROR-γt in the colonic tissues was down-regulated, but Treg cells in Peyer's patches, TGF-ß and STAT5a in the colonic tissues were up-regulated. CONCLUSION: APS effectively ameliorates TNBS-induced experimental colitis in rats, probably through restoring the number of Treg cells, and inhibiting IL-17 levels in Peyer's patches.