Radiation-induced hemorrhagic gastroduodenitis is an intractable and potentially life-threatening condition. This study reports the case of a 57-year-old male with radiation-induced hemorrhagic gastroduodenitis. The patient had previously received radiotherapy for metastatic tumors involving the liver and adrenal gland. Following this treatment, he presented with melena and anemia, necessitating hospital admission. Prior therapeutic efforts included epinephrine spraying in the gastric antrum and embolization of the gastroduodenal artery. Despite these measures, along with multiple transfusions of packed red blood cells, the hemorrhage persisted. Ultimately, oral administration of thalidomide successfully controlled the bleeding. This case indicates that oral thalidomide may represent a potential treatment option for severe radiation-induced hemorrhagic gastroduodenitis.

Background and aims:Primary sclerosing cholangitis (PSC) is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options. The mechanisms underlying the development and progression of PSCs remain unclear. Liver X receptor beta (LXR-β) is recognized to modulate lipid metabolism and immune response, but its specific involvement in the PSC has not been elucidated. Here, we explored the role and mechanism of LXR-β in PSC induced by 3, 5-diethoxycarbonyl-1, 4-dihydro-2, 4, 6-collidine (DDC). Methods:CRISPR-Cas9 technology was applied to generate Abcb4 (coding MDR2, next named as Mdr2), Nr1h2 (coding LXR-β, next named as Lxrβ), and Rag2 (coding RAG2) knockout mice. DDC was used to induce PSC. Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis. Flow cytometry was used to observe immune cell subsets. Results:We observed a declining trend in hepatic Lxrβ in the PSC model. Unexpectedly, Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis. Concomitantly, assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2 -/- DDC mice. However, Lxrβ depletion intensified DDC-induced PSC in the Rag2 -/- mice, with more abundant infiltrative inflammatory cells and more severe liver fibrosis. Compared with Rag2 -/- DDC mice, Lxrβ -/- Rag2 -/- DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes. Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells. Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Background and AimsPrevious studies have suggested that cholecystectomy may lead to an elevated risk of metabolic dysfunction-associated fatty liver disease (MAFLD). However, there is a dearth of knowledge concerning the precise effects and underlying mechanisms through which cholecystectomy influences hepatic lipid metabolism, necessitating further investigation.MethodsPost-cholecystectomy (PC) model mice were established under both normal and high-fat diet conditions. Liver lipid metabolism, inflammation, bile acid profiles, and immune cell alterations were evaluated. Hepatocytes mimicking a high-fat state were exposed to distinctive bile acids to investigate the chemotactic effect on neutrophils. Co-culture experiments of hepatocytes and neutrophils evaluated lipid accumulation in hepatocytes and the expression levels of lipid metabolism-related genes.ResultsCholecystectomy under a high-fat diet markedly disrupted hepatic lipid metabolism and exacerbated inflammation, while cholecystectomy under a normal diet did not. The bile acid profiles in the ileum and liver of PC mice underwent notable changes, along with modifications in bile acid receptors and transporters associated with enterohepatic circulation. Notably, deoxycholic acid (DCA) and tauroursodeoxycholic acid (TDCA) were identified as distinctive bile acids. Furthermore, hepatocytes in PC mice with a high-fat diet showed an elevated level of neutrophil infiltration. Hepatocytes showed a significant increase in releasing CXCL1 and CXCL2 when administered with DCA or TDCA, suggesting an intensified chemotactic response for neutrophils. Co-culturing neutrophils and hepatocytes exacerbated hepatocyte lipid deposition and reduced the expression of genes associated with lipid oxidative degradation.ConclusionsCholecystectomy alongside a high-fat diet aggravates hepatic lipid metabolism disorders and inflammation by modulating hepatic bile acid profiles and promoting neutrophil recruitment.

By analyzing the hairpin structure of miR-486, it was found that the mature sequences of miR-486-5p and miR-486-3p are complementary. For this reason, it is probably the greatest challenge to express miR-486-5p using a lentiviral expression vector in C2C12 cells. Thus, we constructed shRNA/siRNA lentiviral expression vectors for microRNA-486-5p based on miR-30/451 and miRNA sponges. Oligonucleotide sequences (miR-486-5p TuD (tough decoy RNAs), miR-486-5p sponge, miR-486-5p-shRNA30 and miR-486-5p-shRNA451) were digested and cloned into the PLV-U6-MCS vector to generate U6-driven expression cassettes for mmu-miR-486-5p, and these vectors, including anti-miR-486-5p TuD, anti-miR-486-5p sponge, miR-486-5p-shRNA30 and miR-486-5p-shRNA451, were assessed by sequencing. The lentivirus vector was packaged in 293T cells according to the manufacturer’s instructions. Subsequently, C2C12 cells were infected using a lentivirus for the expression of miR-486-5p, and this lentivirus of PLV-U6-MCS served as a control. qRT-PCR analysis showed that anti-miR-486-5p TuD and the anti-miR-486-5p sponge decreased the expression level of miR-486-5p in C2C12 cells by 0.5-fold and 0.7-fold, respectively. Additionally, miR-486-5p-shRNA30 and miR-486-5p-shRNA451 upregulated the expression level of miR-486-5p in C2C12 cells by 15-fold and 3-fold, respectively. However, the expression level of miR-486-3p was increased up to 1000-fold in C2C12 cells containing the miR-486-5p-shRNA30 lentivirus, while other lentiviruses only led to 3-fold increases compared with the miR-486–5p-shRNA30 lentivirus in C2C12 cells. Additionally, western blot and gray density analysis demonstrated that the expression levels of AKT, and pAKT, ERK1/2 and pERK1/2, and Snail were upregulated (approximately 1.20-fold to 1.33-fold and 1.05-fold to 1.20-fold, respectively) in C2C12 cells infected with the anti-miR-486-5p TuD lentivirus and anti-miR-486-5p sponge lentivirus and downregulated (approximately 0.63–0.96 times and 0.72–0.92 times, respectively) in C2C12 cells infected with the miR-486-5p-shRNA30 lentivirus and miR-486-5p-shRNA451 lentivirus. In summary, anti-miR-486-5p TuD, which dramatically reduced the expression level of miR-486-5p and upregulated endogenous protein levels in C2C12 cells, was superior to the anti-miR-486-5p sponge in terms of interference expression of miR-486-5p. miR-486-5p-shRNA451, which did not lead to substantial expression of miR-486-3p and remarkably downregulated endogenous protein levels in C2C12 cells, was better than miR-486-5p-shRNA30 for overexpression of miR-486-5p. These results suggested that anti-miR-486-5p TuD and miR-486-5p-shRNA451 provide a simple way to build long-term effective overexpression or interference of miR-486-5p, to study miRNA function in C2C12 and mice, and to create a potential diagnostic method based on materials for diseases caused by miRNA deregulation.

Myocardial work (MW) is a novel indicator measured by noninvasive echocardiography, which could detect subclinical myocardial dysfunction before reduction of left ventricular ejection fraction (LVEF). The study aimed to evaluate subclinical myocardial dysfunction in patients with systemic sclerosis (SSc) with normal LVEF, using left ventricular MW through two-dimensional speckle-tracking imaging (2D-STI). Eighty patients with SSc, which included 40 diffuse skin type SSc (dcSSc) and 40 limited skin type SSc (lcSSc) according to LeRoy’s criteria, and 40 gender and age matched health subjects were enrolled. The images were collected using standard transthoracic echocardiography. Global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were obtained. Our study showed that there were no significant differences in LVEF and GLS between the SSc group and the control group. Both the lcSSc group and the dcSSc group had lower GWI, GCW, and GWE and higher GWW than the control group (P < 0.05). GWI, GCW, and GWE were lower in the dcSSc group than those in the lcSSc group, while GWW was higher in the dcSSc group (P < 0.05). GWI and GCW were positively correlated with LVEF (P < 0.001). GWI, GCW, and GWE were negatively correlated with GLS (P < 0.001), and GWW was positively correlated with GLS (P < 0.05). Elevated CRP was associated with reduced GWI and GCW (P < 0.05). Our study demonstrates the presence of subclinical myocardial dysfunction in SSc patients. The dcSSc patients may be more prone to have subclinical myocardial dysfunction than the lcSSc patients. Noninvasive left ventricular myocardial work may be a promising novel tool for detection of subclinical myocardial dysfunction.

Background: The intrinsic healing ability of articular cartilage is poor after injury or illness, and untreated injury could lead to cartilage degeneration and ultimately osteoarthritis. iMSCs are derived from embryonic induced pluripotent stem cells and have strong therapeutic capabilities in the repair of cartilage defects, while the mechanism of action is unclear. The aim of this study is to clarify the repair mode of iMSCs on cartilage defects in rat knee joints, elucidate the chemotactic effect of iMSCs on autologous BMSCs in rats, and provide a basis for the treatment of cartilage defects and endogenous regeneration with iMSCs. Methods: Based on the establishment of the rat cartilage defect model, the reparative effect of iMSCs on the rat cartilage defect was evaluated. The cartilage repair was evaluated by quantitative score, H&E staining, Masson staining and Safranin-O staining, and the metabolic changes of iMSCs in the joint cavity were detected in vivo. The expression of SOX9, CD29, CD90, ColⅠ, ColⅡ, PCNA, SDF-1, and CXCR4 was detected by immunohistochemistry (IHC), IF, flow cytometry, respectively. After co-culturing iMSCs with BMSCs in vitro, the expression of CXCR4/SDF-1 on the cell membrane surface of BMSCs was detected by western blotting.; The level of p-Akt and p-Erk1/2 in total protein of BMSCs were detected by western blotting. Significance: Our research results provide experimental evidence for the treatment of cartilage defects and endogenous regeneration with iMSCs; This also provides new ideas for the clinical treatment of cartilage defects using iMSCs.

Non-alcoholic steatohepatitis (NASH) has no effective treatment drug. Our previous study initially found that artemether (Art) treatment significantly attenuates NSAH by regulating liver lipid metabolism. This study further elucidates new mechanisms of Art in improving liver inflammation and provides evidence for drug repurposing. Herein, we utilized HFHF diet-induced animal model and macrophage models to detect the mechanisms of Art in NASH. We confirmed that Art significantly reduced hepatic steatosis, injury, and fibrosis in a high-fat high-fructose (HFHF) diet-induced animal model. Art significantly suppressed the activation of inflammatory macrophages and secretion of pro-inflammatory cytokine (IL-1β) by reducing serum double-stranded DNA (dsDNA) levels and triggering the AIM2/Caspase-1/GSDMD signaling in vivo. dsDNA-induced Caspase-1 and PI-positive cells pyroptosis, AIM2 inflammasome activation, IL-1β, and IL-18 secretion increase were inhibited by Art in vitro. Furthermore, we found Art effectively suppressed mitochondrial DNA (mtDNA), a typical form of dsDNA, released from free fatty acid (FFA)-stressed hepatocytes, which further inhibited AIM2 inflammasome mediated-pyroptosis through decreasing the cleavage of Caspase-1/GSDMD/IL-1β. Moreover, inhibition of the AIM2 gene partly reversed the inhibitory effect of Art on macrophage pyroptosis. Impaired mitochondrial structure and function were confirmed in FFA-stressed hepatocytes and the HFHF-diet-induced NASH mouse model, which was reversed by Art treatment. The present study provides evidence for Art as a potential anti-pyroptosis therapeutic agent for NASH treatment.

Macrophages play an important role in the pathogenesis of atherosclerosis (AS) by mediating oxidative stress, inflammation and lipid metabolism, which can lead to the formation of vascular plaque. The Rac family isoforms of small molecules GTPase are active by binding to GTPase, but are inactivated by binding to GDP, and play a role in the switch of cell information conduction. This experiment adopts shRNA interference THP-1 cells respectively each subtype expression and inhibiting Rac1, Rac2, Rac3 activity, each subtype of Rac family on lipid metabolism, inflammatory reaction and oxidative stress. THP-1 cells were stimulated with Ox-LDL to establish AS cell models including lipid loading, adhesion, migration and chemotaxis. Oil Red O staining, cell immunofluorescence, scratching test, transwell, Western blot and other experiments were performed. To observe the different effects of three subtypes of Rac family on multiple links in the foaming process of THP-1 cells. ApoE-/- mice on a high-fat diet were used as animal models to examine the effects of Rac subtypes in vivo. The results showed that the activation of immune cells induced by ox-LDL was inhibited when Rac1, Rac2 and Rac3 in THP-1 were decreased, respectively. Thus, Rac1 and Rac3 act in combination with ox-LDL and are associated with cellular oxidative stress and inflammation. This study provides new means and ideas for finding potential intervention targets that have important regulatory effects on atherosclerosis, and provides a new direction for the development of clinical drugs.

目的 探索非酒精性脂肪性肝病(NAFLD)小鼠肠道B细胞的变化.方法 将12只雄性C57BL/6J小鼠随机分为实验组和对照组,每组6只.实验组喂以45％高脂肪饮食诱导发生NAFLD,对照组喂以正常饮食.16周后处死小鼠,留取两组肝脏、小肠黏膜、结肠黏膜、肠系膜淋巴结(MLN)、派氏结(PP)及小肠内容物.采用苏木精-伊红染色法确认实验组发生NAFLD,采用免疫组织化学染色法及实时定量PCR法检测小肠及结肠黏膜中B细胞的分布和含量.采用流式细胞术分析MLN和PP中B细胞比例.采用酶联免疫法检测小肠内容物sIgA的水平.采用免疫磁珠法分选MLN中的B细胞进行体外培养,加入脂多糖(LPS)或抗CD40和抗IgM(BCR)刺激,采用细胞因子流式技术法检测培养液上清白介素-6、白介素-10及肿瘤坏死因子-α的水平.结果 实验组和对照组小肠及结肠的B细胞散在分布于固有层中.与对照组相比,实验组MLN和PP中B细胞比例增多(PMLN-B细胞=0.025,PPP-B细胞=0.004).实验组小肠内容物中sIgA的含量较对照组明显升高(P=0.042),并且其PP中IgA+B细胞比例升高(P=0.023).体外实验显示,实验组MLN中的B细胞接受刺激后分泌IL-6增多(PLPS<0.001,PBCR=0.003).结论 NAFLD小鼠PP及MLN中B细胞比例增多,不仅小肠内sIgA含量增多,并且其MLN中B细胞接受刺激后分泌促炎性IL-6增多.

Background Breast cancer patients with metabolic syndrome have an increased risk of cardiovascular disease. These patients are more prone to suffer from cardiotoxicity after anticancer therapy. Patients after completion of cancer-related comprehensive therapy, who show normal myocardial function, may already have subclinical myocardial dysfunction. We sought to evaluate the subclinical myocardial dysfunction in breast cancer patients with metabolic syndrome after cancer-related comprehensive therapy. Methods. In this study, 45 breast cancer patients with metabolic syndrome after completion of cancer-related comprehensive therapy, 45 non-breast cancer patients with metabolic syndrome, and 30 breast cancer patients without metabolic syndrome after therapy were enrolled. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were measured using echocardiogram. Results All the patients had normal LVEF. However, nine breast cancer patients with metabolic syndrome (20%) had GLS that was lower than –17%, while all the noncancer patients had normal GLS. Breast cancer patients with metabolic syndrome had a decrease of GLS and LVEF, compared with noncancer patients with metabolic syndrome. Furthermore, we found that decrease of age was associated with reduction of LVEF and that use of trastuzumab for 1 year was a significant factor associated with reduction of GLS. In addition, breast cancer patients with metabolic syndrome had a decrease of GLS, compared with breast cancer patients without metabolic syndrome after cancer-related therapy. Conclusions Breast cancer patients with metabolic syndrome after completion of cancer-related comprehensive therapy suffered from subclinical myocardial dysfunction. GLS should be routinely performed to early identify subclinical myocardial damage of patients, in order to prevent the cardiotoxicity of cancer-related comprehensive therapy.

Angiogenesis is an essential pathological feature of vulnerable atherosclerotic plaque. Exosome-derived microRNAs (miRNAs or miRs) have been proven to be important regulators of angiogenesis. However, the role of exosomes, which are secreted by endothelial cells (ECs) under conditions of oxidative stress, in angiogenesis remain unclear. The present study aimed to investigate the effects and mechanism of oxidative stress-activated endothelial-derived exosomes in angiogenesis. Exosomes were isolated from H2O2-stimulated human umbilical vein ECs (HUVECs; termed Exo(-H2O2)) by differential centrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis and western blot analysis. Exo(-H2O2) enhanced HUVEC proliferation, migration and tube formation, as determined by EdU incorporation assay, scratch wound migration assay and tube formation assay, respectively. miR-92a-3p was identified as the predominantly downregulated miRNA in the Exo(-H2O2)-treated HUVECs by small RNA sequencing, and the expression of primary miR-92a (pri-miR-92a-1) was also decreased, as shown by RT-qPCR. Similarly, the inhibition of miR-92a-3p promoted angiogenesis in vitro and in vivo. miR-92a-3p overexpression blocked the pro-angiogenic effects of Exo(-H2O2) on target ECs. Tissue factor (TF), a molecule involved in angiogenesis, was increased in HUVECs in which miR-92a-3p expression was downregulated, as shown by mRNA sequencing. TF was also predicted as a target of miR-92a-3p by using the RNA-hybrid program. The overexpression or suppression of miR-92a-3p modified TF expression at both the mRNA and protein level, as measured by RT-qPCR and western blot analysis, respectively. Luciferase reporter assays suggested that miR-92a-3p inhibited TF expression by binding to the 3' untranslated region of TF. On the whole, the findings of the present study demonstrate that exosomes released from oxidative stress-activated ECs stimulate angiogenesis by inhibiting miR-92a-3p expression in recipient ECs, and TF may be involved in the regulatory effects of miR-92a-3p on angiogenesis.

Pyroptosis is a programmed and inflammatory cell death initiated by inflammasome. During pyroptosis, cytosolic pattern recognition receptors, apoptosis-associated speck-like protein and pro-Caspase-1 form activated inflammasome together. Caspase-1 activated by inflammasome results in generating an N-terminal cleavage product of gasdermin D (GSDMD), which is a major executor of pyroptosis. As a consequence of pyroptosis, a large number of pro-inflammatory cytokines are released including IL-1β and IL-18. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and absent in melanoma 2 (AIM2)-like receptors (ALRs) belong to cytosolic pattern recognition receptors and assemble inflammasomes by detecting host cell damage signals. Pyroptosis pathways are divided into canonical and non-canonical pathways according to the identification of damage signals by cytoplasmic protein sensors. Pyroptosis not only plays an important role in infection, but also plays a vital role in inflammatory immune diseases. This article reviews the advances research of pyroptosis initiated by inflammasome in inflammatory and immune diseases.

Epicardial adipose tissue (EAT) is associated with the pathogenesis of atrial fibrillation (AF). The role of local inflammation in persistent AF is unclear. The purpose of this study was to assess the relationship between regional interleukin-1 beta (IL-1 beta) and persistent AF. Thirty-seven persistent AF patients underwent coronary artery bypass grafting surgery were enrolled. Patients without a history of AF (n = 37), but received the same surgery matched by age, gender, and body mass index, were enrolled in the control group. EAT thickness was measured by echocardiography. We obtained blood and EAT samples at open-heart surgery. In each patient, serum and EAT levels of IL-1 beta and adiponectin were measured. The EAT thickness in patients with persistent AF was significantly greater than that in the control group (5.6 +/- 1.1 versus 5.0 +/- 1.3 mm, P = 0.02). The mRNA level of IL-1 beta was higher in persistent AF group than the control group (4.94 +/- 1.69 versus 2.93 +/- 0.91, P < 0.01). Adiponectin expression decreased in persistent AF patients (7.04 +/- 2.21 versus 8.63 +/- 2.95, P = 0.01). There were no significant differences in plasma levels of IL-1 beta and adiponectin between the 2 groups. Multiple logistic regression analysis showed that IL-1 beta was an independent risk factor of persistent AF. These findings suggested that regional IL-1 beta in EAT was an independent risk factor of persistent AF, which may promote the persistence of AF. [GRAPHICS] .

BackgroundThe incidence of premature myocardial infarction (PMI) has gradually increased in recent years. Genetics plays a central role in the development of PMI. Familial hypercholesterolemia (FH) is one of the most common genetic disorders of cholesterol metabolism leading to PMI.ObjectiveThis study investigated the relationship between FH-associated genes and the phenotype of PMI to clarify the genetic spectrum of PMI diseases.MethodThis study enrolled PMI patients (n=225) and detected the mutations in their FH-associated genes (LDLR, APOB, PCSK9, LDLRAP1) by Sanger sequencing. At the same time, patients free of PMI (non-FH patients, n=56) were enrolled as control, and a logistic regression analysis was used to identify risk factors associated with PMI. The diagnosis of FH was confirmed using 2018 Chinese expert consensus of FH screening and diagnosis before the prevalence and clinical features of FH were analyzed.ResultsPathogenic mutations in LDLR, APOB, PCSK9 and LDLRAP1 genes were found in 17 of 225 subjects (7.6%), and all mutations were loss of function (LOF) and heterozygous. The genotype-phenotype relationship of patients carrying FH-associated mutations showed high heterogeneity. The logistic regression analysis showed that the smoking history, obesity and the family history of premature CHD were independent risk factors of PMI. In this study, a total of 19 patients (8.4%) were diagnosed as FH, and the proportion of smoking subjects in FH patients was higher than that in non-FH patients.ConclusionsFH-associated gene mutations were present in about 7.6% of Chinese patients with PMI. In addition to genetic factors, smoking history, lifestyle and other environmental factors may play a synergistic role in determining the phenotype of PMI.Trial registrationEssential gene mutation of cholesterol metabolism in patients with premature myocardial infarction. ChiCTR-OCH-12002349.Registered 26 December 2014, http://www.chictr.org.cn/showproj.aspx?proj=7201.

Epidemiological studies showed that there was an inverse relationship between Helicobacter pylori (H. pylori) infection and the incidence of inflammatory bowel diseases (IBD). Our previous research indicated that the regulatory immune responses induced by H. pylori infection were not limited to gastric mucosa, and the balance of intestinal mucosal immunity was influenced. In this study, mice were infected with H. pylori SS1, and then colitis was induced by 3% dextran sulphate sodium (DSS), to investigate the role of the regulatory B cells in the effects of H. pylori infection on acute and chronic colitis. In acute and chronic colitis groups, DAI and colonic histological scores reduced significantly and colon length shorted less, the proinflammatory cytokines mRNA expression downregulated in colonic mucosa, and the percentages of CD19(+)IL-10(+)Breg cells were higher in the H. pylori/DSS co-treated groups compared with the DSS-treated groups. Our study suggests that H. pylori infection can alleviate the acute and chronic colitis induced by DSS, and CD19(+)IL-10(+)Breg cells may play a critical role in the alleviation of acute and chronic colitis following H. pylori infection.

Mesenteric adipose tissue (MAT) inflammation is associated with non‐alcoholic fatty liver disease (NAFLD), and immune cells play pivotal roles in the inflammation of adipose tissue. Here, we investigated the roles of MAT B lymphocytes in NAFLD. Mice fed with high‐fat diet (HFD) and normal diet (ND) were killed in time gradients (4, 8 and 12 weeks). Compared with ND‐fed mice, intra‐hepatic CD45+CD19+ B lymphocytes increased after 4 weeks (P < 0.01) of HFD feeding, and lasted until the 12th week, infiltrated earlier than CD45+CD3+ T lymphocytes and CD45+F4/80+ macrophages. The mRNA expression of tumour necrosis factor (TNF)‐α, interleukin (IL)‐6 and monocyte chemotactic protein (MCP)‐1 decreased in MAT of Bnull HFD‐fed mice compared to that in wild‐type HFD‐fed mice, along with lesser macrophages. Mesenteric adipose tissue B cells from HFD‐fed mice promoted macrophage differentiation to type‐Ι macrophages and expression of pro‐inflammatory cytokines in vitro. Macrophages pre‐treated with MAT B cells from HFD‐fed mice showed elevated mRNA expression of IL‐6 and TNF‐α and declined IL‐10 levels in adipocytes compared to ND MAT B cell pre‐treated macrophages. Besides, internal near‐infrared scanning and external transwell assay showed that HFD MAT B cells migrated to the liver more than ND MAT B cells. High‐fat diet MAT B cells induced higher MCP‐1 and lower IL‐10 expression in primary hepatocytes compared to ND MAT B cells in co‐culture experiment. These data indicate that B lymphocytes infiltrate early in MAT during the development of NAFLD, which may not only promote MAT inflammation by regulating macrophages but also migrate to the liver and induce hepatocytes inflammation.

Visceral adipose tissue (VAT) is related to nonalcoholic fatty liver disease (NAFLD). However, the role of mesenteric adipose tissue (MAT), part of the VAT, in NAFLD is unclear. In the present study, we monitored the liver and four depots of the VAT in high-fat diet (HFD)-feeding mice at multiple time points (4, 8, and 12 wk). The MAT had become inflamed by the eighth week of HFD feeding, earlier than other depots of VAT. Furthermore, MAT removal after 8 wk of HFD resulted in more severe steatosis and more foci of inflammation infiltration, as well as higher NAFLD activity scores. Consistent with these findings, the mRNA expression of proinflammatory cytokines and lipid anabolism genes was increased in the livers of inflamed MAT-removal mice. MAT removal also injured the intestinal barrier and promoted intestinal inflammation. The bacterial load translocated to the liver and circulating levels of lipopolysaccharide were also evaluated in inflamed MAT-removal mice. In a coculture experiment involving adipocytes and intestinal epithelial cells, mRNA expression of zonula occludens-1 (ZO-1), and occludin in CT-26 cells was upregulated and permeability of monolayer Caco-2 cells was elevated under stimulation from adipocytes or inflamed adipocytes. Taken together, these results demonstrated that MAT removal damaged the intestinal barrier and aggravated NAFLD and that MAT inflammation may be a compensatory response to protect the liver by maintaining the intestinal barrier. NEW & NOTEWORTHY The mesenteric adipose tissue (MAT) lies between the gut and liver and plays a critical role in hepatic metabolic diseases. In the present study, we found that the MAT was prone to inflammation in high-fat diet-fed mice. Removal of the inflamed MAT resulted in more hepatic inflammation, lipid accumulation, and decreased glucose tolerance. Furthermore, we showed that the MAT contributed to intestinal barrier integrity, thus clarifying why MAT removal aggravated nonalcoholic fatty liver disease.

We aimed to investigate the distinctive miRNA profiles in the plasma of elderly patients with unstable angina (UA) and stable angina (SA), and to find more effective markers of UA in elderly people. We compared miRNA expression levels in plasma samples from 10 elderly patients with UA and 10 elderly patients with SA by using microarray-based miRNA chip, and then performed validation with Real-time PCR. Mir-1202, mir-1207-5p, and mir-1225-5p showed a statistically significant down-regulation (P < 0.05), while mir-3162-3p showed an up-regulation (P < 0.05) during validation. Among all single miRNAs, miR-3162-3p showed the highest discriminatory power in the diagnosis of elderly patients with UA (AUC: 0.79, 95% CI: 0.675-0.905). The discriminatory power of a panel of three miRNAs (mir-3162-3p/mir-1225-5p/mir-1207-5p) was highest with an AUC of 0.91 (95% CI: 0.84-0.98), followed by mir-3162-3p/mir-1225-5p (AUC: 0.833, 95% CI: 0.732-0.934) and mir-3162-3p/mir-1207-5p (AUC: 0.817, 95% CI: 0.712-0.922). In conclusion, multi-miRNA panel could provide higher diagnostic value for the diagnosis of elderly patients with UA.