Revitalizing gut barrier integrity: miR-192-5p's role in enhancing autophagy via Rictor in enteritis.

BACKGROUND: Intestinal inflammation and compromised barrier function are critical factors in the pathogenesis of gastrointestinal disorders. This study aimed to investigate the role of miR-192-5p in modulating intestinal epithelial barrier (IEB) integrity and its association with autophagy. METHODS: A DSS-induced colitis model was used to assess the effects of miR-192-5p on intestinal inflammation. In vitro experiments involved cell culture and transient transfection techniques. Various assays, including dual-luciferase reporter gene assays, quantitative real-time PCR, western blotting, and measurements of transepithelial electrical resistance, were performed to evaluate changes in miR-192-5p expression, Rictor levels, and autophagy flux. Immunofluorescence staining, H&E staining, TEER measurements, and FITC-dextran analysis were also employed. RESULTS: Our findings revealed a reduced expression of miR-192-5p in inflamed intestinal tissues, correlating with impaired IEB function. Overexpression of miR-192-5p alleviated TNF-induced IEB dysfunction by targeting Rictor, resulting in enhanced autophagy flux in enterocytes (ECs). Moreover, the therapeutic potential of miR-192-5p was substantiated in colitis mice, wherein increased miR-192-5p expression ameliorated intestinal inflammatory injury by enhancing autophagy flux in ECs through the modulation of Rictor. CONCLUSION: Our study highlights the therapeutic potential of miR-192-5p in enteritis by demonstrating its role in regulating autophagy and preserving IEB function. Targeting the miR-192-5p/Rictor axis is a promising approach for mitigating gut inflammatory injury and improving barrier integrity in enteritis patients.

Comprehensive analyses of solute carrier family members identify SLC12A2 as a novel therapy target for colorectal cancer.

As the largest transporter family impacting on tumor genesis and development, the prognostic value of solute carrier (SLC) members has not been elucidated in colorectal cancer (CRC). We aimed to identify a prognostic signature from the SLC members and comprehensively analyze their roles in CRC. Firstly, we downloaded transcriptome data and clinical information of CRC samples from GEO (GSE39582) and TCGA as training and testing dataset, respectively. We extracted the expression matrix of SLC genes and established a prognostic model by univariate and multivariate Cox regression. Afterwards, the low-risk and high-risk group were identified. Then, the differences of prognosis traits, transcriptome features, clinical characteristics, immune infiltration and drug sensitivity between the two groups were explored. Furthermore, molecular subtyping was also implemented by non-negative matrix factorization (NMF). Finally, we studied the expression of the screened SLC genes in CRC tumor tissues and normal tissues as well as investigated the role of SLC12A2 by loss of function and gain of function. As a result, we developed a prognostic risk model based on the screened 6-SLC genes (SLC39A8, SLC2A3, SLC39A13, SLC35B1, SLC4A3, SLC12A2). Both in the training and testing sets, CRC patients in the high-risk group had the poorer prognosis and were in the more advanced pathological stage. What's more, the high-risk group were enriched with CRC progression signatures and immune infiltration. Two groups showed different drug sensitivity. On the other hand, two distinct subclasses (C1 and C2) were identified based on the 6 SLC genes. CRC patients in the high-risk group and C1 subtype had a worse prognosis. Furthermore, we found and validated that SLC12A2 was steadily upregulated in CRC. A loss-of-function study showed that knockdown of SLC12A2 expression restrained proliferation and stemness of CRC cells while a gain-of-function study showed the contrary results. Hence, we provided a 6-SLC gene signature for prognosis prediction of CRC patients. At the same time, we identified that SLC12A2 could promote tumor progression in CRC, which may serve as a potential therapeutic target.

The Eph/ephrin system symphony of gut inflammation.

The extent of gut inflammation depends largely on the gut barrier's integrity and enteric neuroimmune interactions. However, the factors and molecular mechanisms that regulate inflammation-related changes in the enteric nervous system (ENS) remain largely unexplored. Eph/ephrin signaling is critical for inflammatory response, neuronal activation, and synaptic plasticity in the brain, but its presence and function in the ENS have been largely unknown to date. This review discusses the critical role of Eph/ephrin in regulating gut homeostasis, inflammation, neuroimmune interactions, and pain pathways. Targeting the Eph/ephrin system offers innovative treatments for gut inflammation disorders, offering hope for enhanced patient prognosis, pain management, and overall quality of life.

Comprehensive analysis of the relationship between cuproptosis-related gene GCSH and prognosis, tumor microenvironment infiltration, and therapy response in endometrial cancer.

BACKGROUND: Cuproptosis, a novel form of cell death regulated by protein lipoylation and implicated in mitochondrial metabolism. However, the impact of the cuproptosis-related gene γ-glutamylcysteine synthetase (GCSH) on endometrial cancer (EC) prognosis, tumor immune microenvironment, and therapeutic response remains to be further researched. METHODS: The differential expression of GCSH between endometrial cancer and normal tissues was analyzed using multiple public databases. Additionally, cancer and adjacent tissues were prospectively collected from 17 EC patients, and immunohistochemical analysis was performed to further investigate GCSH expression differences. The relationship between GCSH and the prognosis and clinicopathological characteristics of EC patients was evaluated, and a nomogram was constructed to predict patient survival based on GCSH expression. Then, Gene set variation analysis (GSVA) was utilized to explore the potential biological functions of GCSH in EC. The impact of GCSH on the tumor microenvironment (TME) was estimated. Finally, the effect of GCSH on the response to immunotherapy and chemotherapeutic drugs in EC was investigated. RESULTS: The expression of GCSH was significantly upregulated in EC. High GCSH expression was associated with poor prognosis in EC patients. Enrichment analysis showed that high GCSH was associated with immune suppression. Furthermore, high GCSH was found to be associated with a non-inflamed TME, leading to decreased infiltration levels of immune cells. Finally, it was observed that patients with high GCSH were insensitive to both immunotherapy and chemotherapeutic drugs. CONCLUSION: This study revealed the role of GCSH in TME, response to therapy, and clinical prognosis in EC, which provided novel insights for the therapeutic application in EC.

Guanylate-binding proteins signature predicts favorable prognosis, immune-hot microenvironment, and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: The role of guanylate-binding proteins (GBPs) in various cancers has been elucidated recently. However, our knowledge of the clinical relevance and biological characteristics of GBPs in hepatocellular carcinoma (HCC) remains limited. METHODS: A total of 955 HCC patients were enrolled from five independent public HCC cohorts. The role of GBP molecules in HCC was preliminarily investigated, and a GBP family signature, termed GBPs-score, was constructed by principal component analysis to combine the GBP molecule values. We revealed the effects of GBP genes and GBPs-score in HCC via well-established bioinformatics methods and validated GBP1-5 experimentally in a tissue microarray (TMA) cohort. RESULTS: GBPs molecules were closely associated with the prognosis of patients with HCC, and a high GBPs-score highly inferred a favorable survival outcome. We also revealed high GBPs-score was related to anti-tumor immunity, the immune-hot tumor microenvironment (TME), and immunotherapy response. Among the GBPs members, GBP1-5 rather than GBP6/7 may be dominant in these fields. The TMA analysis based on immunohistochemistry showed positive correlations between GBP1-5 and the immune-hot TME with abundant infiltration of CD8+ T cells in HCC. CONCLUSIONS: Our integrative study revealed the genetic and immunologic characterizations of GBPs in HCC and highlighted their potential values as promising biomarkers for prognosis and immunotherapy.

Emerging glyco-risk prediction model to forecast response to immune checkpoint inhibitors in colorectal cancer.

BACKGROUND: Aberrant glycosylation is one of the most common post-translational modifications leading to heterogeneity in colorectal cancer (CRC). This study aims to construct a risk prediction model based on glycosyltransferase to forecast the response to immune checkpoint inhibitors in CRC patients. METHODS: Based on the TCGA dataset and glycosyltransferase genes, the NMF algorithm and WGCNA were used to identify molecular subtypes and co-expressed genes, respectively. Lasso and multivariate COX regression were used to identify prognostic glycosyltransferase genes and construct a glyco-risk prediction model in CRC patients. Univariate and multivariate Cox regression, Kaplan-Meier, and ROC curves were applied to further verify the prognostic performance of the model in CRC patients in the training and validation sets. We compared the responsiveness of immunotherapy and chemotherapy between the two groups. In vitro experiments and clinical specimens verified the specific function of the key glycosyltransferase genes in CRC. RESULTS: The CRC cohort was divided into two subtypes with prominent differences in survival based on the well-robust seven-gene glyco-risk prediction model (composed of ALG1L2, HAS1, PYGL, COLGALT2, B3GNT4, POFUT2, and GALNT7). The nomograms based on the risk model could predict the prognosis of CRC patients independently of other clinicopathologic characteristics. Our prediction model showed a better overall prediction performance than other models. Compared with the low-risk group, the high-risk CRC patients showed a lower immune infiltration state, but a higher TMB and a lower response to anti-PD-1, anti-PD-L1, and anti-CTLA-4 therapy. Clinical specimen validation showed an obvious difference in the expression of seven glycosyltransferase genes between the low- and high-risk groups. Significant reduction in POFUT2 expression in high-risk groups was associated with reduced N-glycans production. CONCLUSION: Our study constructed a robust glyco-risk prediction model that could provide direction for immunotherapy and chemotherapy in CRC patients, which could help clinicians make personalized treatment decisions.

DNMT3A facilitates colorectal cancer progression via regulating DAB2IP mediated MEK/ERK activation.

The inactivation of tumor suppressor DOC-2/DAB2 interactive protein (DAB2IP) by epigenetic and post-transcriptional modification has been reported in multiple human malignancies. DNA methyltransferase 3A (DNMT3A) is involved in de novo establishment of DNA methylation and plays a vital role in tumorigenesis. However, whether DNMT3A can regulate colorectal cancer (CRC) progression via modulation of DAB2IP remains unclear. In this study, we revealed that DNMT3A was significantly increased in CRC, predicting a poor overall survival. Functionally, ectopic expression of DNMT3A in CRC cells enhanced cell proliferation, whereas DNMT3A knockdown had the opposite effect by inducing cell cycle arrest. Mechanistically, methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) proved that the expression of DAB2IP was epigenetically suppressed by DNMT3A-mediated promoter methylation in CRC cells. Using dual-luciferase reporter assay and ChIP-PCR assay, we further confirmed that DNMT3A restrained the transcriptional activity of DAB2IP promoter through directly binging to it. In addition, DNMT3A could activate the MEK/ERK signaling pathway via efficiently downregulating DAB2IP. Inhibition of the MEK/ERK cascade abrogated the oncogenic effects of DNMT3A on CRC cells. In conclusion, our study demonstrates that DNMT3A facilitates CRC progression by regulating DAB2IP mediated MEK/ERK activation, providing promising targets for CRC treatment.

Identification of Pharmacological Autophagy Regulators of Active Ulcerative Colitis.

Background: Ulcerative colitis (UC) is a chronic recurrent disease of unknown etiology. Recently, it has been reported that autophagy-related gene polymorphism is closely associated with increased risk of UC, and the therapeutic effect of some UC drugs is mediated by regulating autophagy pathways. This study aims to identify pivotal autophagy-related regulators in UC pathogenesis and provide novel molecular targets for the treatment of active UC. Methods: Gene expression profiles and clinical information of active UC patients were obtained from GEO databases. CIBERSORT was adopted to evaluate the immune cell infiltration. We used weighted gene co-expression network analysis (WGCNA) and differential expression analysis to identify the pivotal modules and genes associated with active UC. Subsequently, we conducted validation in the validation set and explored its relationship with commonly used UC therapeutics. Results: 36 healthy controls and 46 active UC patients have been obtained from the training set of GSE53306, GSE87466, and GSE134025. There were 423 differentially expressed genes (DEGs) found, which dramatically enriched in autophagy-related pathways. And more infiltration of mast cells, activated T cells, dendritic cells, and M1 macrophages were observed in the intestinal mucosa of active UC, while more infiltration of resting immune cells and M2 macrophages in healthy controls. WGCNA indicated that the turquoise and blue modules were the critical modules. CASP1, SERPINA1, and CCL2 have been identified as the hub autophagy-related genes of active UC, after combining DEGs and 232 autophagy-related genes from HADb with the genes of turquoise and blue modules, respectively. We further verified that CASP1, SERPINA1, and CCL2 were positively associated with active UC and served as an autophagy-related biomarker for active UC. Moreover, increased SERPINA1 in the involved intestinal mucosa was reduced in patients with active UC who responded to golimumab or glucocorticoid therapy. But, neither CASP1, SERPINA1, and CCL2 were changed by treatment of 5-aminosalicylic acid (5-ASA) and azathioprine. Conclusion: CASP1, SERPINA1, and CCL2 are autophagy-related hub genes of active UC. And SERPINA1 may serve as a new pharmacological autophagy regulator of UC, which provides a new target for the use of small molecules targeting autophagy in the treatment of active UC.

DOC-2/DAB2 interactive protein destabilizes c-Myc to impair the growth and self-renewal of colon tumor-repopulating cells.

Colorectal carcinoma (CRC) remains a huge challenge in clinical treatment due to tumor metastasis and recurrence. Stem cell-like colon tumor-repopulating cells (TRCs) are a subpopulation of cancer cells with highly tumorigenic and chemotherapy resistant properties. The core transcription factor c-Myc is essential for maintaining cancer stem-like cell phenotypes, yet its roles and regulatory mechanisms remain unclear in colon TRCs. We report that elevated c-Myc protein supported formation and growth of TRC spheroids. The tumor suppressor DOC-2/DAB2 interactive protein (DAB2IP) suppressed c-Myc expression to inhibit TRC expansion and self-renewal. Particularly, DAB2IP disrupted c-Myc stability through glycogen synthase kinase 3ß/protein phosphatase 2A-B56α-mediated phosphorylation and dephosphorylation cascade on c-Myc protein, leading to its eventual degradation through the ubiquitin-proteasome pathway. The expression of DAB2IP was negatively correlated with c-Myc in CRC specimens. Overall, our results improved mechanistic insight into how DAB2IP suppressed TRC growth and self-renewal.

Identification of microRNA-16-5p and microRNA-21-5p in feces as potential noninvasive biomarkers for inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic idiopathic gastrointestinal disease. Increasing evidence suggests that microRNAs (miRNAs) may participate in the pathophysiology of IBD. METHODS: A miRCURY™ LNA Array and in situ hybridization were employed to screen for differentially expressed miRNAs (DEMs) in fecal specimens from 41 IBD patients (22 ulcerative colitis (UC), 19 Crohn's disease (CD)) and 23 healthy controls (HC). RT-qPCR was performed to confirm the findings. The DEMs target genes and corresponding biological functions were predicted by bioinformatics analysis. RESULTS: Compared with HC, miR-16-5p in the feces was up-regulated both in UC and CD patients (p < 0.01), while miR-21-5p was up-regulated only in UC patients (p < 0.01). TargetScan 7.2, miRWalk, and miRDB were used to predict 216 public target genes of miR-16-5p and miR-21-5p, and six hub genes (PIK3R1, GRB2, SUZ12, NTRK2, Smurf2, and WWP1) were analyzed using the STRING database and Cytoscape. All the hub genes promote the occurrence and development of IBD-related colorectal cancer. CONCLUSIONS: The elevated levels of miR-16-5p and miR-21-5p in feces of IBD patients have to guide significance for the noninvasive clinical diagnosis of IBD and have a warning effect on the occurrence of IBD-related colorectal cancer.

Risk factors and characteristics associated with nonalcoholic fatty liver disease in patients with ischemic colitis.

BACKGROUND: Ischemic colitis (IC) was investigated to be associated with dyslipidemia and subcutaneous adipose tissue. Nonalcoholic fatty liver disease (NAFLD) is associated with ischemic diseases such as coronary heart disease, ischemic stroke. But there is a paucity of data regarding the association between NAFLD and IC. NAFLD may be associated with the treatment and prognosis of IC. We investigated risk factors and characteristics associated with NAFLD in patients with IC. METHODS: Patients with IC (NAFLD: 34 and controls: 81) from Zhongnan Hospital were investigated retrospectively from January 2012 to December 2018. Clinical data were compared by chi-square tests or independent samples T-tests. Binary logistic regressions and Kaplan-Meier analysis were performed to evaluate risk factors and prognosis, respectively. RESULTS: NAFLD was diagnosed in 28.19% patients with IC. In the logistic regression analysis, hypertension [odds ratio (OR) 3.523; P = 0.019], elevated alanine aminotransferase (ALT) (OR 6.278; P = 0.048), elevated triglyceride (OR 4.667; P = 0.003) and increased weight (OR 1.055; P = 0.039) were risk factors of NAFLD in patients with IC. Patients with NAFLD were more likely to require the vasodilators (P = 0.011) and get a relapse of IC (P = 0.011). CONCLUSION: NAFLD was found in 28.19% of patients with IC. Hypertension, increased weight, elevated ALT and triglyceride are independent predictors of NAFLD in patients with IC. NAFLD in patients with IC is associated with a greater probability of requiring for the vasodilators. NAFLD in IC and period of bowel rest are risk factors for the recurrence of IC.

COVID-19: gastrointestinal symptoms from the view of gut-lung axis.

The main symptoms of coronavirus disease 2019 (COVID-19) are respiratory manifestations, while some confirmed patients developed gastrointestinal symptoms or even initially presented digestive symptoms. The link between pneumonia and gastrointestinal symptoms caused by severe acute respiratory symptoms coronavirus 2 focused our attention on the concept of 'gut-lung axis'. In this review, we discuss the inevitability and possible mechanisms of the occurrence of intestinal symptoms or intestinal dysfunction in COVID-19 from the perspective of the gut-lung axis, as well as the influence of the imbalance of intestinal homeostasis on the respiratory symptoms of COVID-19. The interaction between lung and intestine might lead to a vicious cycle of pulmonary and intestinal inflammation which may be a potential factor leading to the death of patients with COVID-19.

FATP2-targeted therapies - A role beyond fatty liver disease.

Fatty acid transport protein 2 (FATP2) is a multifunctional protein whose specific function is determined by the type of located cell, its intracellular location, or organelle-specific interactions. In the different diseases setting, a newfound appreciation for the biological function of FATP2 has come into view. Two main functions of FATP2 are to activate long-chain fatty acids (LCFAs) as a very long-chain acyl-coenzyme A (CoA) synthetase (ACSVL) and to transport LCFAs as a fatty acid transporter. FATP2 is not only involved in the occurrence of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), but also plays an important role in lithogenic diet-induced cholelithiasis, the formation of cancer tumor immunity, the progression of chronic kidney disease (CKD), and the regulation of zoledronate-induced nephrotoxicity. Herein, we review the updated information on the role of FATP2 in related diseases. In particular, we discuss the new functions of FATP2 and propose that FATP2 is a potential clinical biomarker and therapeutic target. In conclusion, regulatory strategies for FATP2 may bring new treatment options for cancer and lipid metabolism-related disorders.

Identification of NEO1 as a prognostic biomarker and its effects on the progression of colorectal cancer.

BACKGROUND: Due to the high morbidity and poor clinical outcomes, early predictive and prognostic biomarker identification is desiderated in colorectal cancer (CRC). As a homologue of the Deleted in Colorectal Cancer (DCC) gene, the role of Neogenin-1 (NEO1) in CRC remained unveiled. This study was designed to probe into the effects and potential function of NEO1 in CRC. METHODS: Online databases, Gene Set Enrichment Analysis (GSEA), quantitative real-time PCR and western blotting were used to evaluate NEO1 expression in colorectal cancer tissues. Survival analysis was performed to predict the prognosis of CRC patients based on NEO1 expression level. Then, cell proliferation was detected by colony formation and Cell Counting Kit 8 (CCK-8) assays. CRC cell migration and invasion were examined by transwell assays. Finally, we utilized the Gene Set Variation Analysis (GSVA) and GSEA to dig the potential mechanisms of NEO1 in CRC. RESULTS: Oncomine database and The Cancer Genome Atlas (TCGA) database showed that NEO1 was down-regulated in CRC. Further results validated that NEO1 mRNA and protein expression were both significantly lower in CRC tumor tissues than in the adjacent tissues in our clinical samples. NEO1 expression was decreased with the progression of CRC. Survival and other clinical characteristic analyses exhibited that low NEO1 expression was related with poor prognosis. A gain-of-function study showed that overexpression of NEO1 restrained proliferation, migration and invasion of CRC cells while a loss-of-function showed the opposite effects. Finally, functional pathway enrichment analysis revealed that NEO1 low expression samples were enriched in inflammation-related signaling pathways, EMT and angiogenesis. CONCLUSION: A tumor suppressor gene NEO1 was identified and verified to be correlated with the prognosis and progression of CRC, which could serve as a prognostic biomarker for CRC patients.

Consumption of ultra-processed foods and health outcomes: a systematic review of epidemiological studies.

BACKGROUND: Consumption of ultra-processed foods (UPFs) plays a potential role in the development of obesity and other diet-related noncommunicable diseases (NCDs), but no studies have systematically focused on this. This study aimed to summarize the evidence for the association between UPFs consumption and health outcomes. METHODS: A comprehensive search was conducted in PubMed, Embase, and Web of Science to identify all relevant studies. Epidemiological studies were included, and identified studies were evaluated for risk of bias.A narrative review of the synthesized findings was provided to assess the association between UPFs consumption and health outcomes. RESULTS: 20 studies (12 cohort and 8 cross-sectional studies) were included in the analysis, with a total of 334,114 participants and 10 health outcomes. In a narrative review, high UPFs consumption was obviously associated with an increased risk of all-cause mortality, overall cardiovascular diseases, coronary heart diseases, cerebrovascular diseases, hypertension, metabolic syndrome, overweight and obesity, depression, irritable bowel syndrome, overall cancer, postmenopausal breast cancer, gestational obesity, adolescent asthma and wheezing, and frailty. It showed no significant association with cardiovascular disease mortality, prostate and colorectal cancers, gestational diabetes mellitus and gestational overweight. CONCLUSIONS: This study indicated a positive association between UPFs consumption and risk of several health outcomes. Large-scale prospective designed studies are needed to confirm our findings.

Clinical characteristics, laboratory outcome characteristics, comorbidities, and complications of related COVID-19 deceased: a systematic review and meta-analysis.

BACKGROUND: At present, novel coronavirus disease 2019 (COVID-19) has become a serious global public health problem. The current meta-analysis aimed to find risk factors for the COVID-19-related death, helping to enhance the efficacy and reduce the mortality of COVID-19. METHODS: We searched PubMed, Embase, medRxiv, and Cochrane Library for articles published between January 1, 2020, and April 13, 2020. We statistically analyzed the risk factors of the COVID-19 deceased with meta-analysis. RESULTS: A total of 2401 patients in 15 articles were included in this study. Meta-analysis showed that 66.6% of COVID-19 deceased were male, with a median age of 69.9 years. Common symptoms of deceased included fever (70.6-100%), dyspnea (38.89-85.7%), cough (22.4-78%), and fatigue (22-61.9%). The incidence of hypertension, chronic cardiovascular disease, diabetes, and chronic cerebrovascular disease among the COVID-19 deceased were 38.56% (95% confidence interval (CI) 25.84 ~ 52.12%), 17.54% (95% CI 13.38 ~ 21.69%), 22.2% (95% CI 19.30 ~ 25.10%), and 15.58% (95% CI 10.05 ~ 21.12%), respectively. Compared with the surviving COVID-19 patients, the deceased had lower platelet levels (mean difference (MD) = - 39.35, 95% CI - 55.78 ~ - 22.93) and higher C-reactive protein (CRP) (MD = 80.85, 95% CI 62.53 ~ 99.18) and lactate dehydrogenase (LDH) (MD = 246.65, 95% CI 157.43 ~ 335.88) at admission. The most common complications of the deceased were acute respiratory distress syndrome (ARDS) (OR = 100.36, 95% CI 64.44 ~ 156.32) and shock (OR = 96.60, 95% CI 23.80 ~ 392.14). CONCLUSION: Most of the COVID-19 deceased were elderly males. Fever, dyspnea, dry cough, fatigue, hypertension, chronic cardiovascular and cerebrovascular disease, diabetes, and laboratory examinations showed low levels of platelet content, increased CRP and LDH were associated with the risk of dying. ARDS and shock were risk factors for death in COVID-19 patients.

Crosstalk Between Liver Macrophages and Surrounding Cells in Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH), the advanced stage of nonalcoholic fatty liver disease (NAFLD), is emerging as a leading cause of progressive liver fibrosis and end-stage liver disease. Liver macrophages, mainly composed of Kupffer cells (KCs) and monocyte-derived macrophages (MoMFs), play a vital role in NASH progression and regression. Recent advances suggest that cell-cell communication is a fundamental feature of hepatic microenvironment. The reprogramming of cell-cell signaling between macrophages and surrounding cells contributes to the pathogenesis of NASH. In this review, we summarize the current knowledge of NASH regarding the composition of liver macrophages and their communication with surrounding cells, which are composed of hepatocytes, hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs) and other immune cells. We also discuss the potential therapeutic strategies based on the level of macrophages.

The liver injury and gastrointestinal symptoms in patients with Coronavirus Disease 19: A systematic review and meta-analysis.

Backgrounds: Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. Our study aimed to evaluate the association of liver injury and gastrointestinal symptoms (GIS) with the progression of COVID-19. Methods: A comprehensive search was performed on the PubMed to identify eligible studies that summarized the liver injury and GIS in COVID-19. Results: A total of 21 studies with 3024 patients were included. Up to 53% patients had liver dysfunctions and the degree of liver damage was associated the severity of the disease. The prevalence of diarrhoea, nausea/vomiting or abdominal pain in patients with COVID-19 were 9.1%, 5.2% and 3.5%, respectively. No significant was found in the prevalence of diarrhoea (OR, 1.24; 95%CI, 0.90 to 1.72; I2 = 0%, P = 0.19) and nausea/vomiting (OR, 1.24; 95%CI, 0.57 to 2.69; I2 = 61%, P = 0.58) between severe and non-severe patients. In addition, diarrhoea (OR, 1.22; 95%CI, 0.50 to 2.98; I2 = 0%, P = 0.66) and nausea/vomiting (OR, 1.09; 95%CI, 0.46 to 2.62; I2 = 0%, P = 0.84) were not associated with the prognosis of COVID-19 patients. Conclusions: The incidences of GIS in patients with COVID-19 is relatively low and are not associated with the COVID-19 progression. Gastroenterologists should pay more attention to the liver injury induced by SARS-CoV-2 during the course of infection.