Rationale: Renal fibrosis is the terminal manifestation of chronic and irreversible renal disease. Effective therapies other than dialysis are extremely limited. In this study, we investigated the potential effects of targeting elevated interleukin-6 (IL-6) levels in the treatment of renal fibrosis. Methods: Fc-gp130 was used to specifically block IL-6 trans-signaling. Unilateral ureteral occlusion (UUO) and ischemia reperfusion (IR) mouse models were constructed to investigate the therapeutic effect of Fc-gp130 on renal fibrosis. The role of IL-6 trans-signaling and phosphorylation of signal transducer and activator of transcription (STAT) 3 in regulating fibroblast accumulation and extracellular matrix protein deposition were evaluated in cell experiments and mouse models. Results: The kidneys of mice with UUO were found to have elevated soluble IL-6 receptor (sIL-6R) levels in the progression of fibrosis. Fc-gp130 attenuated renal fibrosis in mice, as evidenced by reductions in tubular atrophy and the production of extracellular matrix protein. Blockade of IL-6 trans-signaling with Fc-gp130 also reduced inflammation levels, immune cell infiltration, and profibrotic cytokines expression in renal tissue, with decreased STAT3 phosphorylation and reduced fibroblast accumulation in the renal tissue. In vitro, Fc-gp130 also reduced the phosphorylation of STAT3 induced by transforming growth factor (TGF)-β1 in fibroblasts. Furthermore, the therapeutic effect of Fc-gp130 was confirmed in a model of acute kidney injury-chronic kidney disease. Conclusion: Overall, IL-6 trans-signaling may contribute to crucial events in the development of renal fibrosis, and the targeting of IL-6 trans-signaling by Fc-gp130 may provide a novel therapeutic strategy for the treatment of renal fibrosis.

C1q/TNF-related protein 4 (CTRP4) is generally thought to be released extracellularly and plays a critical role in energy metabolism and protecting against sepsis. However, its physiological functions in autoimmune diseases have not been thoroughly explored. In this study, we demonstrate that Th17 cell-associated experimental autoimmune encephalomyelitis was greatly exacerbated in Ctrp4-/- mice compared with WT mice due to increased Th17 cell infiltration. The absence of Ctrp4 promoted the differentiation of naive CD4+ T cells into Th17 cells in vitro. Mechanistically, CTRP4 interfered with the interaction between IL-6 and the IL-6 receptor (IL-6R) by directly competing to bind with IL-6R, leading to suppression of IL-6-induced activation of the STAT3 pathway. Furthermore, the administration of recombinant CTRP4 protein ameliorated disease symptoms. In conclusion, our results indicate that CTRP4, as an endogenous regulator of the IL-6 receptor-signaling pathway, may be a potential therapeutic intervention for Th17-driven autoimmune diseases.

Immune cell trafficking constitutes a fundamental component of immunological response to tissue injury, but the contribution of intrinsic RNA nucleotide modifications to this response remains elusive. We report that RNA editor ADAR2 exerts a tissue- and stress-specific regulation of endothelial responses to interleukin-6 (IL-6), which tightly controls leukocyte trafficking in IL-6-inflamed and ischemic tissues. Genetic ablation of ADAR2 from vascular endothelial cells diminished myeloid cell rolling and adhesion on vascular walls and reduced immune cell infiltration within ischemic tissues. ADAR2 was required in the endothelium for the expression of the IL-6 receptor subunit, IL-6 signal transducer (IL6ST; gp130), and subsequently, for IL-6 trans-signaling responses. ADAR2-induced adenosine-to-inosine RNA editing suppressed the Drosha-dependent primary microRNA processing, thereby overwriting the default endothelial transcriptional program to safeguard gp130 expression. This work demonstrates a role for ADAR2 epitranscriptional activity as a checkpoint in IL-6 trans-signaling and immune cell trafficking to sites of tissue injury.

Pulmonary hypertension (PH) is a critical and dangerous disease in cardiovascular system. Pulmonary vascular remodeling is an important pathophysiological mechanism for the development of pulmonary arterial hypertension. Pulmonary artery smooth muscle cell (PASMC) proliferation, hypertrophy, and enhancing secretory activity are the main causes of pulmonary vascular remodeling. Previous studies have proven that various active substances and inflammatory factors, such as interleukin 6 (IL-6), IL-8, chemotactic factor for monocyte 1, etc., are involved in pulmonary vascular remodeling in PH. However, the underlying mechanisms of these active substances to promote the PASMC proliferation remain to be elucidated. In our study, we demonstrated that PASMC senescence, as a physiopathologic mechanism, played an essential role in hypoxia-induced PASMC proliferation. In the progression of PH, senescence PASMCs could contribute to PASMC proliferation via increasing the expression of paracrine IL-6 (senescence-associated secretory phenotype). In addition, we found that activated mTOR/S6K1 pathway can promote PASMC senescence and elevate hypoxia-induced PASMC proliferation. Further study revealed that the activation of mTOR/S6K1 pathway was responsible for senescence PASMCs inducing PASMC proliferation via paracrine IL-6. Targeted inhibition of PASMC senescence could effectively suppress PASMC proliferation and relieve pulmonary vascular remodeling in PH, indicating a potential for the exploration of novel anti-PH strategies.

The outbreak of coronavirus disease 2019 (COVID-19) initially occurred in December 2019 and triggered a public health emergency. The increasing number of deaths due to this disease was of great concern. Therefore, our study aimed to explore risk factors associated with COVID-19 deaths. After having searched the PubMed, EMBASE, and CNKI for studies published as of August 10, 2020, we selected articles and extracted data. The meta-analysis was performed using Stata 16.0 software. Nineteen studies were used in our meta-analysis. The proportions of comorbidities such as diabetes, hypertension, malignancies, chronic obstructive pulmonary disease, cardio-cerebrovascular disease, and chronic liver disease were statistically significantly higher in mortal COVID-19 cases. Coagulation and inflammatory markers, such as platelet count, D-dimer, prothrombin time, C-reactive protein, procalcitonin, and interleukin 6, predicted the deterioration of the disease. In addition, extracorporeal membrane oxygenation and mechanical ventilation predicted the poor prognosis during its progression. The COVID-19 pandemic is still evolving, placing a huge burden on healthcare facilities. Certain coagulation indicators, inflammatory indicators, and comorbidities contribute to the prognosis of patients. Our study results may help clinicians optimize the treatment and ultimately reduce the mortality rate.

Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by the excess accumulation of fat in the hepatocytes. It is commonly associated with severe obesity and inflammation. Free fatty acids (FFAs) are the key to regulate lipid metabolism and immune response in hepatocyte cells. This study examined the effects of AEN (alcohol extract of nutmeg, the seed of Myristica fragrans Houtt.) on the inhibition of lipid synthesis and inflammation in vitro and in vivo and on high-fat diet-induced obesity in NAFLD mice. Our results showed that AEN treatment could downregulate the expression of lipid synthesis-related genes fatty acid synthase (FASN) and sterol regulatory element-binding protein 1c (SREBP-1c) and lower the lipid content of cells. AEN also inhibited FFAs-mediated inflammation-related cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) expression in cells. In a mouse model, AEN reduced the bodyweight of obese mice and improved NAFLD without affecting food intake. Further analysis revealed that AEN significantly reduced inflammation level, cholesterol and lipid accumulation, blood glucose, and other liver function indexes in mice fed with a high-fat diet. In conclusion, AEN inhibited the aggravation of obesity and inflammation by downregulating lipid-gene expression in the liver to ameliorate NAFLD.

Acute liver injury has multiple causes and can result in liver failure. In this study, we evaluated the hepatoprotective ability of cyanidin (Cy) and investigated its associated mechanisms. Cy administration significantly and dose-dependently ameliorated acute liver injury induced by carbon tetrachloride (CCl4). High-dose Cy showed effects comparable to those achieved by the positive control (silymarin). Severe oxidative stress and inflammatory responses in the liver tissue induced by CCl4 were significantly mitigated by Cy supplementation. The total antioxidant capacity and the activity of superoxide dismutase, catalase, and glutathione peroxidase were increased and the content of malondialdehyde, lipid peroxide, tumor necrosis factor α, interleukin-1β, and interleukin-6 were decreased. Additionally, the Nrf2 and NF-κB signaling pathways, which regulate antioxidative and inflammatory responses, were analyzed using quantitative real-time polymerase chain reaction and western blot assay. Cy treatment not only increased Nrf2 transcription and expression but also decreased NF-κB signaling. Moreover, molecular docking simulation indicated that Cy had high affinity for Keap1 and NF-κB/p65, which may promote nuclear translocation of Nrf2 and inhibit that of NF-κB. In summary, Cy treatment exerted antioxidative and anti-inflammatory effects and ameliorated liver injury by increasing Nrf2 and inhibiting the NF-κB pathway, demonstrating the potential of Cy as a therapeutic agent in liver injury.

Irritable bowel syndrome with diarrhea and functional diarrhea are both functional bowel disorders that cause chronic diarrhea. Chronic diarrhea is closely related to daily life and the psychological condition of diarrhea in patients, and probiotics can play a significant role in alleviating chronic diarrhea in some research. Lactobaccilus plantarum CCFM1143 can relieve diarrhea in mice caused by enterotoxigenic Escherichia coli (ETEC); however, its clinical effects remain unclear. This study aimed to assess the effects of CCFM1143 as a therapy for chronic diarrhea patients. Fifty-five patients with chronic diarrhea were randomly assigned into the probiotic group (n = 28) and the placebo group (n = 27), receiving the routine regimen with or without probiotics for 4 weeks, respectively. CCFM1143 can mitigate the apparent clinical symptoms and improve the health status and quality of life of patients. In addition, it could inhibit the increase in interleukin 6 (IL-6) and the decrease in motilin; modulate the short-chain fatty acids, especially acetic and propionic acids; and regulate the gut microbiota, particularly reducing the abundance of Bacteroides and Eggerthella and enriching the abundance of Akkermansia, Anaerostipes, and Terrisporobacter. In addition, treatment with probiotics showed clinical effectiveness in managing chronic diarrhea when compared with the placebo group. The findings could help to develop and further the application of probiotics for chronic diarrhea.

Mesenchymal stem cell (MSC) transplantation has demonstrated its potential in repairing infarct heart tissue and recovering heart function after myocardial infarction (MI). However, its therapeutic effect is still limited due to poor MSC engraftment at the injury site whose tissue stiffness and local inflammation both dynamically and rapidly change after MI. Whether and how inflammatory cytokines could couple with stiffness change to affect MSC engraftment in the infarct zone still remain unclear. In this study, we characterized dynamic stiffness changes of and inflammatory cytokine expression in the infarct region of rat heart within a month after MI. We found that the tissue stiffness of the heart tissue gradually increased and peaked 21 days after MI along with the rapid upregulation of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the first 3 days, followed by a sharp decline. We further demonstrated in vitro that immobilized inflammatory cytokine IL-6 performed better than the soluble form in enhancing MSC adhesion to stiffened substrate through IL-6/src homology 2 (SH2) domain-containing tyrosine phosphatase-2 (SHP2)/integrin signaling axis. We also confirmed such mechano-immune coupling of tissue stiffness and inflammatory cytokines in modulating MSC engraftment in the rat heart after MI in vivo. Our study provides new mechanistic insights of mechanical-inflammation coupling to improve MSC mechanosensing and adhesion, potentially benefiting MSC engraftment and its clinical therapy for MI.

Osteoporosis is a clinically prevalent comorbidity in patients with hemophilia. A preventive effect of kefir peptides (KPs) on postmenopausal osteoporosis has been proved. The aim of this study was to evaluate the therapeutic effect of KPs for the treatment of osteoporosis in coagulation factor VIII (FVIII) gene knockout mice (F8KO), a model of hemophilia A. In this study, male F8KO mice at 20 weeks of age were orally administered different doses of KPs for 8 weeks. The therapeutic effects of KPs were shown in the femoral trabeculae and the 4th lumbar vertebrae, which increased the trabecular bone mineral density (BMD), bone volume (Tb.BV/TV), and trabecular number (Tb.N) and decreased the trabecular separation (Tb.Sp), and they were also observed in the femoral cortical bones, in which the mechanical properties were enhanced in a dose-dependent manner. Characterization of receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and interleukin 6 (IL-6) demonstrated that the serum RANKL/OPG ratio and IL-6 levels were significantly decreased in the F8KO mice after the KP treatment. Tartrate-resistant acid phosphatase (TRAP) staining of mature osteoclasts indicated that the therapeutic effect of KPs in F8KO mice was associated with the functions of KPs to inhibit RANKL-induced osteoclastogenesis by reducing serum RANKL/OPG ratio and IL-6 secretion. The present study is the first to address the potentials of KPs for the treatment of hemophilia-induced osteoporosis in mice and it also provides useful information for the application of KPs as a complementary therapy for the treatment of osteoporosis in hemophilic patients.

Constipation is currently one of the most common gastrointestinal disorders, and its causes are diverse. Multi-strain probiotics are often considered a more effective treatment than single-strain probiotics. In this study, a constipation model was constructed using loperamide hydrochloride to evaluate the ability of a multi-strain probiotic combination of four different ratios of Bifidobacterium and Lactobacillus to regulate intestinal flora, relieve constipation, and explore the initial mechanism in mice. After four weeks of probiotic intervention, BM1, BM2, and PB2 effectively relieved constipation; however, the pathways involved were different. The Bifidobacteria-dominated formulations BM1 and BM2 mainly changed the composition and structure of the intestinal flora and significantly decreased the relative abundance of Tyzzerella, Enterorhabdus, Faecalibaculum, Gordonibacter, and Mucispirillum in stool; increased the relative abundance of Parabacteroides and the content of short-chain fatty acids (SCFAs) in stool; restored motilin (MTL) and vasoactive intestinal peptide (VIP) levels; and downregulated interleukin 6 (IL-6) and IL-8 levels in serum. This repaired the inflammatory response caused by constipation. Finally, it promoted peristalsis of the gastrointestinal tract, increasing stool water content, and relieving constipation. While Lactobacillus-dominated formula PB2 mainly restored the levels of serum neurotransmitters (MTL, SP (substance P), VIP and PYY (Peptide YY)) and inflammatory factors (IL-1, IL-6 and IL-8), it significantly decreased the relative abundance of Tyzzerella, Enterorhabdus, Faecalibaculum, Gordonibacter and Mucispirillum in stool; it then increased acetic acid content, thereby reducing the level of inflammation and changing stool properties and gastrointestinal motility.

Here, we aimed to investigate the role of long noncoding RNA (lncRNA) THRIL in septic-induced acute lung injury. C57BL/6 mice were injected with Adenoviruses (Ad)-shTHRIL or negative control (NC) before caecal ligation and puncture (CLP) operation. MPVECs were transfected with Ad-shTHRIL or NC, followed by lipopolysaccharide (LPS) treatment. MiR-424 and Rho-associated kinase 2 (ROCK2) were predicted and verified as direct targets of THRIL and miR-424, respectively, by using dual-luciferase reporter assay. ROCK2 overexpression vector and shTHRIL were co-transfected into mouse pulmonary microvascular endothelial cells for 24 h before LPS treatment. Our results showed that THRIL was highly expressed in the lung of sepsis mice. CLP triggered severe lung injury and apoptosis in mice, which was abolished by THRIL knockdown. Moreover, CLP treatment visibly increased protein concentration, the number of total cell of neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF). Besides, elevated protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 were observed in both lung and BALF. However, inhibition of THRIL reduced the number of inflammatory cells and the production of pro-inflammatory cytokines in sepsis mouse model. The effect of THRIL on inflammatory response and apoptosis in the lung was confirmed in sepsis cell model. Moreover, mechanistic studies have shown that THRIL up-regulated ROCK2 level through sponging miR-424. Furthermore, ROCK2 overexpression reversed the inhibitory effects of THRIL knockdown on LPS-induced inflammatory response and apoptosis. Overall, in vivo and in vitro results suggested that THRIL accelerates sepsis-induced lung injury by sponging miR-424 and further restoring ROCK2.

Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is closely related to the gut microbiome. Myristica fragrans is widely used as a traditional seasoning and has a therapeutic effect on gastrointestinal diseases. Although previous studies have shown that M. fragrans extracts have anti-obesity and anti-diabetes effects in mice fed a high-fat diet, few studies have determined the active components or the corresponding mechanism in vivo. In this study, for the first time, an M. fragrans extract (MFE) was shown to be a prebiotic that regulates gut microbes and metabolites in mice fed a high-fat diet. Bioinformatics, network pharmacology, microbiome, and metabolomics analyses were used to analyze the nutrient-target pathway interactions in mice with NAFLD. The National Center for Biotechnology Information Gene Expression Omnibus database was used to analyze NAFLD-related clinical data sets to predict potential targets. The drug database and disease database were then integrated to perform microbiome and metabolomics analyses to predict the target pathways. The concentrations of inflammatory factors in the serum and liver, such as interleukin-6 and tumor necrosis factor-α, were downregulated by MFE. We also found that the hepatic concentrations of low-density lipoprotein cholesterol, total cholesterol, and triglycerides were decreased after MFE treatment. Inhibition of the nuclear factor kappa B (NF-κB) pathway and downregulation of the fatty acid synthase (FAS)-sterol regulatory element-binding protein 1c pathway resulted in the regulation of inflammation and lipid metabolism by activating tryptophan metabolite-mediated aryl hydrocarbon receptors (AhR). In summary, MFE effectively attenuated inflammation and lipid metabolism disorders in mice with NAFLD through the NF-κB and AhR-FAS pathways.

Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran) after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis.

Colorectal cancer (CRC) is a prevalent malignant tumour type arising from the colon and rectum. The present study aimed to explore the molecular mechanisms of the development and progression of CRC. Initially, differentially expressed genes (DEGs) between CRC tissues and corresponding non-cancerous tissues were obtained by analysing the GSE15781 microarray dataset. The Database for Annotation, Visualization and Integrated Discovery was then utilized for functional and pathway enrichment analysis of the DEGs. Subsequently, a protein-protein interaction (PPI) network was created using the Search Tool for the Retrieval of Interacting Genes and Proteins database and visualized by Cytoscape software. Furthermore, CytoNCA, a Cytoscape plugin, was used for centrality analysis of the PPI network to identify crucial genes. Finally, UALCAN was employed to validate the expression of the crucial genes and to estimate their effect on the survival of patients with colon cancer by Kaplan-Meier curves and log-rank tests. A total of 1,085 DEGs, including 496 upregulated and 589 downregulated genes, were screened out. The DEGs identified were enriched in various pathways, including 'metabolic pathway', 'cell cycle', 'DNA replication', 'nitrogen metabolism', 'p53 signalling' and 'fatty acid degradation'. PPI network analysis suggested that interleukin-6, MYC, NOTCH1, inhibin subunit βA (INHBA), CDK1, cyclin (CCN)B1 and CCNA2 were crucial genes, and their expression levels were markedly upregulated. Survival analysis suggested that upregulated INHBA significantly decreased the survival probability of patients with CRC. Conversely, upregulation of CCNB1 and CCNA2 expression levels were associated with increased survival probabalities. The identified DEGs, particularly the crucial genes, may enhance the current understanding of the genesis and progression of CRC, and certain genes, including INHBA, CCNB1 and CCNA2, may be candidate diagnostic and prognostic markers, as well as targets for the treatment of CRC.

Pro-inflammatory cytokines and anti-inflammatory cytokines are important mediators that regulate the inflammatory response in inflammation-related diseases. The aim of this study is to evaluate different New Zealand (NZ)-grown ginseng fractions on the productions of pro-inflammatory and anti-inflammatory cytokines in human monocytic THP-1 cells. Four NZ-grown ginseng fractions, including total ginseng extract (TGE), non-ginsenoside fraction extract (NGE), high-polar ginsenoside fraction extract (HPG), and less-polar ginsenoside fraction extract (LPG), were prepared and the ginsenoside compositions of extracts were analyzed by HPLC using 19 ginsenoside reference standards. The THP-1 cells were pre-treated with different concentrations of TGE, NGE, HPG, and LPG, and were then stimulated with lipopolysaccharide (LPS). The levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and anti-inflammatory cytokines, such as interleukin-10 (IL-10), and transforming growth factor beta-1 (TGF-β1), were determined by enzyme-linked immunosorbent assay (ELISA). TGE at 400 µg/mL significantly inhibited LPS-induced TNF-α and IL-6 productions. NGE did not show any effects on inflammatory secretion except inhibited IL-6 production at a high dose. Furthermore, LPG displayed a stronger effect than HPG on inhibiting pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) productions. Particularly, 100 µg/mL LPG not only significantly inhibited the production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, but also remarkably enhanced the production of anti-inflammatory cytokine IL-10. NZ-grown ginseng exhibited anti-inflammatory effects in vitro, which is mainly attributed to ginsenoside fractions (particularly less-polar ginsenosides) rather than non-saponin fractions.

Obesity has become a global epidemic disease as it is closely associated with a chronic low-grade inflammatory state that results in metabolic dysfunction. Ramulus Mori (Sangzhi) alkaloids (SZ-A) derived from Morus alba L. were licensed to treat type 2 diabetes (T2DM) in 2020. In this study, we explored the effect of SZ-A on adipose tissue metabolism and inflammation using an obesity model induced by a high-fat diet (HFD). C57BL/6J mice were fed high fat for 14 weeks and followed by SZ-A 400 mg/kg treatment via gavage for another six weeks, during which they were still given the high-fat diet. The results showed that SZ-A notably reduced body weight and serum levels of lipid metabolism-related factors, such as triglycerides (TG) and total cholesterol (TC); and inflammation-related factors, namely tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), fibrinogen activator inhibitor-1 (PAI-1), angiopoietin-2 (Ang-2), and leptin (LEP), in the HFD-induced mice. SZ-A increased the protein and mRNA expression of lipid metabolism-related factors, including phosphorylated acetyl coenzyme A carboxylase (p-ACC), phosphorylated hormone-sensitive triglyceride lipase (p-HSL), adipose triglyceride lipase (ATGL), and peroxisome proliferator-activated receptor-alpha (PPARα), in adipose tissue. Immunohistochemistry results demonstrated that SZ-A significantly reduced the infiltration of pro-inflammatory M1-type macrophages in epididymal fat. The data also suggested that SZ-A down-regulates the transcriptional levels of inflammatory factors Il6, Tnfα, monocyte chemoattractant protein-1 (Mcp1), and F4/80, and up-regulates interleukin 4 (Il4), interleukin 10 (Il10), and interleukin 13 (Il13) in adipose tissue. Overall, the results indicate that SZ-A exhibits potential in regulating lipid metabolism and ameliorating obesity-linked adipose inflammation.

The interleukin 6 receptor (IL6R) gene has been shown to locate in the chromosome 1q21 associated with metabolic syndrome (MetS), a condition related to the augmented risk of ischaemic stroke (IS), cardiovascular diseases and all-cause mortality. The aim of this study was to assess the relationship between IL6R gene polymorphisms and IS in patients with MetS in the Chinese Han population. We designed a case-control study enrolling 447 patients with MetS plus IS and 438 patients with MetS alone. Tag single nucleotide polymorphisms (SNPs) of the IL6R gene were determined by a fine-mapping strategy and genotyped using SNPscan technology. A logistic regression model was used to analzse the associations between the genetic variations in IL6R and the risk of IS in MetS patients. The linkage disequilibrium (LD) analysis was performed and four gamete rules were used to define the block. The haplotypes was reconstructed by the SNPstats software. Two SNPs were significantly related to the risk of IS in MetS patients after adjusting for potential confounders as follows: regarding rs12083537, the GG genotype and the GA genotype decreased the risk of IS in the MetS patients compared with the IS risk in the patients with the AA genotype (multivariate-adjusted, P = 0.005); and regarding rs8192284, the CC genotype and the AC genotype decreased the risk of IS compared with the IS risk in the patients with the AA genotype (multivariate-adjusted, P = 0.004). Strong LD was existed in block 2 and the haplotype analysis showed that compared with the ACCG haplotype, the ATCT haplotype (adjusted OR 1.700; 95% CI 1.246-2.319; P = 0.001) increased the risk of IS in the MetS patients. The analysis of the SNP-SNP interactions showed that rs8192284 was the most influential contributor to the risk of IS in the MetS patients. Our results indicate that rs12083537 and rs8192284 in the IL6R gene might be related to the risk of IS in MetS patients.