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Whole barley (WB) consumption is the subject of renewed interest because of its health benefits. However, there are still controversies regarding the mechanisms of the anti-obesity effects of WB. The gut microbiota has recently become a focus of research into obesity-related disorders. Therefore, the aim of this study was to investigate the contribution of the gut microbiota to the anti-obesity effects of WB. Germ-free (GF) C57BL/6J mice underwent gastric inoculation with human feces to obtain human flora-associated (HFA) mice, and then both the GF and HFA mice were fed a high fat diet (HFD) containing 46% WB or refined barley for 9 weeks. Features of obesity and dyslipidemia were compared between the GF and HFA mice and the cecal microbiota was analyzed using next-generation sequencing of microbial 16S rRNA. WB prevents obesity and hypercholesterolemia in the GF and HFA mice. The mechanism may include the inhibition of cholesterol synthesis, because sterol regulatory element-binding protein-1c (SREBP-1c) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) expression was downregulated, and a reduction in cholesterol accumulation, because cholesterol 7α-hydroxylase (CYP7A1) expression was upregulated, independent of the gut microbiota. Furthermore, WB intake enriched a variety of bacterial genera that are negatively associated with obesity, including Bacteroides, Parabacteroides, and Clostridium cluster XIVa, suggesting that WB counteracted gut dysbiosis in obese mice. Thus, WB helps prevent obesity and dyslipidemia via both gut microbiota-dependent and independent mechanisms.

Objective: Endoscopic therapy can reduce the risks of rebleeding, continued bleeding, need for surgery, and mortality. The objective of this systematic review was to compare the different modalities of endoscopic therapy for GI bleeding. Methods: Studies were identified by searching electronic databases MEDLINE. We selected all available clinical studies published after 2000 that assessed efficacy and/or safety of different endoscopic hemostatic techniques in treating GI bleeding. The outcomes evaluated included initial hemostasis, rebleeding rate, and 30-day all-cause mortality. Network meta-analyses were performed to summarize the treatment effects. Results: Total 20 studies involving 1845 patients were evaluated. Ten different treatment categories including mechanic, ablative, injection, and combined therapy were compared in our analysis in terms of their efficacy in stopping bleeding and complications. Band ligation [rate: 0.757; 95% Credible Interval (0.565, 0.887)] and injection therapy [rate: 0.891; 95% CI (0.791, 0.944)] had inferior efficacy in attaining initial hemostasis compared to others. Combined therapy of band ligation and HPC and hemoclip may represent the best options for preventing rebleeding and mortality respectively. No significant difference was found among other treatments in terms of complications. Conclusions: We recommend the application of hemoclips in treating GI bleeding due to its high hemostasis efficacy and low risk of 30-day mortality. How to cite this:Wang TX, Zhang J, Cui LH, Tian JJ Wei R. Efficacy of Therapeutic Endoscopy for Gastrointestinal Lesion (GI): A network meta-analysis. Pak J Med Sci. 2019;35(2):561-568. doi: https://doi.org/10.12669/pjms.35.2.636 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gastric carcinoma is a common type of gastrointestinal tumor with high morbidity and mortality rates. IL-17 is a newly discovered cytokine that has been reported to serve an important role in the development of gastric carcinoma. The potential effect of apatinib on IL-17 expression levels in the development of gastric carcinoma has been rarely reported. The present study aimed to investigate the potential mechanism of IL-17 and apatinib in the development of gastric carcinoma. A total of 30 tumor and para-carcinoma tissues were collected from 30 patients with gastric carcinoma between January 2019 and December 2019 and the expression levels of IL-17 in the tissues were analyzed by reverse transcription-quantitative PCR and western blotting. An in vitro model of gastric carcinoma was also established using the HGC-27 cell line, in which the cells were divided into control, IL-17, IL-17-apatinib and apatinib groups. The expression levels of IL-17, Bax, Bcl-2 and caspase-3 were analyzed using reverse transcription-quantitative PCR and western blotting. An MTT assay and flow cytometry were used to analyze the proliferation and apoptosis of HGC-27 cells, respectively, and a Transwell assay was used to analyze the invasive ability of HGC-27 cells. The results revealed that the expression levels of IL-17 were significantly upregulated in the gastric carcinoma tissues compared with the para-carcinoma tissues. In vitro, IL-17 treatment promoted the proliferation and invasive ability of HGC-27 cells, but inhibited the apoptosis with the significantly downregulated expression levels of Bax and caspase-3 and the upregulated expression levels of Bcl-2 than control group. Conversely, apatinib treatment significantly inhibited the proliferative and invasive abilities of HGC-27 cells, but promoted cell apoptosis in the IL-17 and IL-17-apatinib groups.. Collectively, the present results suggested that the upregulation of IL-17 may be associated with the occurrence and development of gastric carcinoma. The findings indicated that apatinib may inhibit gastric carcinoma development by regulating IL-17 expression via the Bax/Bcl-2 signaling pathway. Therefore, the present findings may enhance the current knowledge of the effect of apatinib on gastric carcinoma cells.

Background: Pathological neovascularization in neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly. Increasing evidence shows that cells of myeloid lineage play important roles in controlling pathological endothelium formation. Suppressor of cytokine signaling 3 (SOCS3) pathway has been linked to neovascularization. Methods: We utilised a laser-induced choroidal neovascularization (CNV) mouse model to investigate the neovascular aspect of human AMD. In several cell lineage reporter mice, bone marrow chimeric mice and Socs3 loss-of-function (knockout) and gain-of-function (overexpression) mice, immunohistochemistry, confocal, and choroidal explant co-culture with bone marrow-derived macrophage medium were used to study the mechanisms underlying pathological CNV formation via myeloid SOCS3. Findings: SOCS3 was significantly induced in myeloid lineage cells, which were recruited into the CNV lesion area. Myeloid Socs3 overexpression inhibited laser-induced CNV, reduced myeloid lineage-derived macrophage/microglia recruitment onsite, and attenuated pro-inflammatory factor expression. Moreover, SOCS3 in myeloid regulated vascular sprouting ex vivo in choroid explants and SOCS3 agonist reduced in vivo CNV. Interpretation: These findings suggest that myeloid lineage cells contributed to pathological CNV formation regulated by SOCS3. Funding: This project was funded by NIH/NEI (R01EY030140, R01EY029238), BrightFocus Foundation, American Health Assistance Foundation (AHAF), and Boston Children's Hospital Ophthalmology Foundation for YS and the National Institutes of Health/National Heart, Lung and Blood Institute (U01HL098166) for PZ.

Retinal blood vessels provide the necessary energy, nutrients and oxygen in order to support visual function and remove harmful particles from blood, thus acting to protect neuronal cells. The homeostasis of the retinal vessels is important for the maintenance of retinal visual function. Neovascularization is the most common cause of blindness in patients with retinopathy. Previous studies have shown that inflammatory mediators are known key regulators in retinopathy, but their causal link has been elusive. Although inflammation is often thought to arise from inflammatory cells like macrophages, neutrophils, and resident microglia, retinal neurons have also been reported to contribute to inflammation, through inflammatory signals, which mediate blood vessel growth. Therefore, it is important to explore the detailed mechanisms of neuroinflammation's effects on retinal neovascularization. This review looks to summarize current research on the relationship between retinal angiogenesis and neuroinflammation in retinopathy, as well as the potential effects of neuroinflammation on retinal neovascularization in different animal models.

Background: MicroRNA-21 (miR-21) is one of the oncogenic miRNAs which may be a potential diagnostic biomarker for hepatocellular carcinoma (HCC). Methods: We systematically searched Medline, Embase, the Cochrane Library, ISI Web of Knowledge, Scopus from inception to August 15, 2018, and reference lists of identified primary studies. Two independent investigators extracted patient and study characteristics. The sensitivity and specificity of microRNA-21 for HCC detection and were analyzed with a random effect model. The area under summary receiver operating characteristic curve (AUC) was used to estimate overall test performance. Results: A total of 515 HCC patients, and 338 healthy or chronic hepatitis controls from six published studies were enrolled in this meta-analysis. All articles were published in English with moderate-to-high quality. The overall pooled sensitivity and specificity were 85.2% (73.3% to 88.4%) and 79.2% (68.4% to 87.0%), respectively. The AUC area was 0.89 (95% CI: 0.85-0.91). The studies had moderate heterogeneity (I2=70.11%). None of the subgroups investigated-ethnicity, controls, sample source-could account for the heterogeneity. Conclusion: MiR-21 is a helpful biomarker for early diagnosis of HCC. Nevertheless, the results of the test must be interpreted carefully in the context of medical history, erological tests and imaging examinations for HCC surveillance. doi: https://doi.org/10.12669/pjms.35.5.685 How to cite this:Qu J, Yang J, Chen M, Cui L, Wang T, Gao W, et al. MicroRNA-21 as a diagnostic marker for hepatocellular carcinoma: A systematic review and meta-analysis. Pak J Med Sci. 2019;35(5):1466-1471. doi: https://doi.org/10.12669/pjms.35.5.685 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

MicroRNAs (miRNAs/miRs) offer great potential as biomarkers for the early detection and prognosis of cancer, and the discovery of miRNAs associated with gastric cancer is required. In the present study, the differences in the plasma expression levels of miR-141 between patients with gastric cancer and healthy controls, and the role of miR-141 in gastric cancer cell oncogenesis were investigated. A follow-up study of 164 patients with gastric cancer who underwent tumor resection was conducted, and comparisons with healthy control subjects were drawn. To investigate the biological functions of miR-141, a series of in vitro and in vivo assays were conducted, including proliferation, wound-healing and Transwell assays, and a xenograft tumor model. The results demonstrated that miR-141 expression was significantly decreased in tumor tissues compared with in healthy tissues (P

Damage to pancreatic β‑cells is closely associated with diabetes. However, the mechanism underlying injury to pancreatic β‑cells remains unclear, although hypoxia is considered as one of the leading causes. Appoptosin is a mitochondrial protein that promotes neuronal apoptosis. Studies conducted on appoptosin thus far have primarily focused on Alzheimer's disease, and have demonstrated that the expression of appoptosin is significantly increased in ischemic‑reperfused rat brains, which indicates its close association with hypoxia. However, the role of appoptosin in pancreatic β‑cells, which are sensitive to hypoxia, remains unknown. Therefore, the current study aimed to investigate the function of appoptosin in pancreatic β‑cells in a hypoxic environment. Cobalt chloride (CoCl2) was used to mimic the hypoxic status of the cells. The results of a terminal deoxynucleotidyl transferase dUTP nick‑end labeling assay demonstrated that CoCl2 promoted apoptosis in MIN6 mouse insulinoma cells, and western blotting and reverse transcription‑quantitative polymerase chain reaction results demonstrated that the activation of appoptosin was induced, promoting mitochondrial damage and caspase 3 activation. Silencing of appoptosin using short hairpin RNA significantly reduced CoCl2‑induced apoptosis in MIN6 cells. In conclusion, CoCl2 increased the expression of appoptosin, which aggravated mitochondrial damage in MIN6 cells. Therefore, inhibiting the expression of appoptosin may benefit pancreatic β-cells survival during islet transplantation.

Type 1 diabetes is caused by destruction of the pancreatic β‑cells and, to date, no cure has been developed. Promoting the survival of pancreatic β‑cells may be beneficial for patients with type 1 diabetes. Puerarin is an estrogen analogue that been demonstrated in previous studies to be able to decreased blood glucose in patients with type 1 diabetes. Similar results were demonstrated in previous studies which additionally demonstrated that puerarin was able to decreased blood glucose in type 1 diabetic mice by protecting pancreatic β‑cells. However, the mechanism underlying the function of puerarin in pancreatic β‑cells remains unclear. Therefore, the present study sought to investigate the detailed function of puerarin in pancreatic β‑cells. In the present study, H2O2 was used to induce apoptosis. It was observed that puerarin significantly decreased H2O2‑induced apoptosis in mouse insulinoma MIN6 cells. It was additionally observed that puerarin decreased the levels of intracellular reactive oxygen species and mitochondrial superoxide in MIN6 cells. The protective effect of puerarin was markedly decreased by 6‑aminonicotinamide, an inhibitor of glucose‑6‑phosphate dehydrogenase (G6PD). In conclusion, the results of the present study suggested that puerarin may increase the activity of G6PD, decreased the level of oxidative stress in MIN6 cells, protect mitochondria and promote MIN6 cell survival. Investigating the mechanism underlying the effect of puerarin in MIN6 cells may provide a novel approach for development of a cure for type 1 diabetes.

Lipopolysaccharide/d-Galactosamine (LPS/d-Gal)-induced acute liver injury is characterized by significant inflammatory responses including TNF-α and interleukin-6 (IL-6) and is a widely applied experimental model for inflammation research. TNF-α is critical in the progression of LPS/d-Gal-induced liver injury. However, the role of IL-6 in this model is still unknown. In the present study, we aim to elucidate the involvement of IL-6 in the pathogenesis of acute liver injury induced by LPS/d-Gal in mice and its underlying mechanism. To induce acute liver injury, LPS (50μg/kg body weight) and d-Gal (400mg/kg body weight) were injected intraperitoneally in the C57BL/6 mice. The vehicle (saline) or a single dose of recombinant IL-6 (200μg/kg body weight) was administered 2h prior to LPS/d-Gal injection. Mice were sacrificed 2h and 6h after LPS/d-Gal injection. The results indicated that IL-6 treatment could protect mice from LPS/d-Gal-induced tissue damage, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation, as well as hepatocyte apoptosis and inflammation. Furthermore, in vitro study showed that IL-6 treatment could significantly suppress LPS-triggered expression of proinflammatory cytokines and chemokines, TNF-α, RANTES and MCP-1 in macrophages while promoting the expression of M2 markers, such as Arg-1 and Mrc-1 in macrophages. Taken together, these findings revealed a novel and unexpected role of IL-6 in ameliorating LPS/d-Gal-induced acute liver injury via regulating inflammatory responses in hepatic macrophages.

The effects of wheat bran feruloylated oligosaccharides (FOs) on the gut microbiota were studied. Furthermore, xylo-oligosaccharides (XOs) and ferulic acid (FA) as the two major moieties were used to demonstrate the structural influence of FOs on microbiota modulation effects. FOs promoted the phylum Firmicutes and Actinobacteria and decreased the relative abundance of Bacteroidetes and Proteobacteria. FA significantly increased the phylum Bacteroidetes. At the genus level, FOs promoted beneficial microorganism such as Bifidobacterium and Faecalibacterium, and inhibit the growth of disease-related bacteria such as Alistipes, Bilophila, Dorea, Enterobacteriaceae, and Oscillopira. FA significantly increased Bacteroides, Dialister and decreased Coprococcus, Enterobacteriaceae, Megamonas, Oscillospira. In terms of metabolites, FOs and XOs increased the content of short-chain fatty acids (SCFAs) but inhibited the production of branched-chain fatty acids (BCFAs). However, FA inhibited the production of both SCFAs and BCFAs. In conclusion, wheat bran FOs showed the prebiotic effects and further promoted the production of SCFAs due to the combined actions of oligosaccharides and FA moieties. Our findings highlighted that composition and structure should be taken into consideration for selecting FOs as prebiotics.