Novel insights into macrophage immunometabolism in nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH), an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis, and has been becoming the leading cause of liver-related morbidity and mortality worldwide. Unfortunately, the pathogenesis of NASH has not been completely clarified, and there are no approved therapeutic drugs. Recent accumulated evidences have revealed the involvement of macrophage in the regulation of host liver steatosis, inflammation and fibrosis, and different phenotypes of macrophages have different metabolic characteristics. Therefore, targeted regulation of macrophage immunometabolism may contribute to the treatment and prognosis of NASH. In this review, we summarized the current evidences of the role of macrophage immunometabolism in NASH, especially focused on the related function conversion, as well as the strategies to promote its polarization balance in the liver, and hold promise for macrophage immunometabolism-targeted therapies in the treatment of NASH.

Enhanced natural degradation of cyanide tailings: Integrated application of solar drying system and UV irradiation.

Cyanide tailings are the bulk solid waste generated by the production processes of gold mines. Since the highly toxicity of cyanide affects its disposal and comprehensive utilization, a decyanation treatment is needed. However, wide-ranging industrial uses of the current decyanation methods are restricted due to the treatment effects and costs. Based on the natural degradation method, the cyanide treatment effect was enhanced by raising the treatment temperature, increasing the ultraviolet (UV) irradiation and turning the pile periodically. Using the Arrhenius equation, the activation energies of the cyanide hydrolysis reactions were calculated as 52.22 kJ/mol and 34.59 kJ/mol for heating alone and for heating combined with UV irradiation, respectively. At 60 â„ƒ, the cyanide tailings reached the discharge standard (leachate, total cyanide (CNt)< 5 mg/L) after 8 h of treatment. Moreover, after adding UV irradiation (with an intensity of 120 µW/cm2) and a hydrogen peroxide spray (spraying intensity, 2 mL/kg) to the above conditions and shortening the treatment time to 7 h, the cyanide tailings reached the standard for use in building materials (leachate, CNt <0.5 mg/L). Based on these results, UV irradiation, ventilation, spraying and pile-turning were integrated into the solar drying room to form an enhanced natural degradation system, which was applied in the semi-industrial scale treatment of the cyanide tailings. The results showed that the cyanide tailings consistently met the standards for discharge and use in building materials, successfully verified the conditions and effects of the laboratory treatment, and reduced the treatment cost by more than 50 %.

Yinchen Linggui Zhugan decoction ameliorates high fat diet-induced nonalcoholic fatty liver disease by modulation of SIRT1/Nrf2 signaling pathway and gut microbiota.

Yinchen Linggui Zhugan decoction (YLZD) is an effective and classical traditional herbal prescription for treating the nonalcoholic fatty liver disease (NAFLD) and has been proven to be effective in the regulation of lipid metabolism disorder and attenuate inflammation for a NAFLD rat model. However, the exact underlying mechanism has not been elucidated. In the current study, a NAFLD rat model was established using a high-fat diet (HFD) for 10 weeks, followed by YLZD treatment with 1.92 g/kg/day for 4 weeks to explore the mechanisms of YLZD. Our results showed that YLZD decreased the hepatic lipid deposition, restored the liver tissue pathological lesions, inhibited the expression of oxidative stress, and decreased the inflammatory cytokines levels. Meanwhile, the genes and proteins expressions of SIRT1/Nrf2 signaling pathway together with downstream factors including HO-1 and NQO1 were elevated in the YLZD treated NAFLD rats. For further elaborating the upstream mechanism, short-chain fatty acids (SCFAs) in serum and feces were measured by liquid chromatograph mass spectrometer and gas chromatograph mass spectrometer, and the differences in gut microbiota of rats in each group were analyzed through high-throughput sequencing of 16S rRNA. The results demonstrated that the contents of butyric acid (BA) and total SCFAs in YLZD-treated NAFLD rats were significantly increased in serum and feces. 16S rRNA sequencing analysis illustrated that YLZD intervention led to a modification of the gut microbiota composition, with a decrease of Oribacterium, Lactobacillus and the ratio of Firmicutes/Bacteroides, as well as the increase in SCFAs-producing bacteria such as Christensenellaceae, Clostridia, Muribaculaceae, and Prevotellaceae. Spearman rank correlation analysis indicated that BA and total SCFAs were negatively co-related with oxidative stress-related factors and inflammatory cytokines, while they were positively co-related with SIRT1/Nrf2 pathway related genes and proteins. Furthermore, in vitro study confirmed that BA effectively reduced oxidative stress by activating SIRT1/Nrf2 signaling pathway in L02 cells. Together, the present data revealed YLZD could ameliorate HFD-induced NAFLD in rats by the modulation of SIRT1/Nrf2 signaling pathway and gut microbiota.

How to improve the diagnosis of neoplastic transformation of gastric hyperplastic polyps in the context of autoimmune gastritis?: A case report and lierature review.

RATIONALE: Gastric hyperplastic polyp (GHP) commonly arises in the abnormal background mucosa, which makes it easy to be misdiagnosed and missed, and has a potential risk of malignant transformation over time. Here, we present a case of neoplastic transformation of GHP in a context of autoimmune gastritis (AIG). PATIENT CONCERNS: In 2020, a 67-year-old woman was admitted for endoscopic review 6 years after gastric polyp resection, the histological diagnosis of gastric polyp was neoplastic transformation of GHP as before. The patient had undergone multiple polypectomies at the same part. Then histological examination revealed that partial epithelial hyperplasia and dysplasia, and the neoplastic areas were interlaced with normal mucosa. DIAGNOSES AND INTERVENTIONS: We further found that the background diagnosis was AIG. These results supported the diagnosis of neoplastic transformation of GHP in a context of AIG. With the doubt of missed diagnose, we retrospectively analyzed the medical history in 2014, 2015 and 2016, confirmed the presence of AIG. Unfortunately, serological tests and special treatment were not performed. OUTCOMES: The correct diagnosis was eventually confirmed in 2020, which enables patients to receive normal treatment and monitoring, and avoids further deterioration of the disease. LESSONS: The purpose of this case report is to increase clinical awareness of neoplastic transformation of GHP in a context of AIG, and hope promise for early diagnosis and treatment.

Qingchang Wenzhong Decoction Alleviates DSS-Induced Inflammatory Bowel Disease by Inhibiting M1 Macrophage Polarization In Vitro and In Vivo.

Background: An imbalance of macrophage M1/M2 polarization significantly influences the pathogenesis of inflammatory bowel disease. Qingchang Wenzhong decoction (QCWZD) has a proven therapeutic effect on patients with inflammatory bowel disease (IBD) and can significantly inhibit the inflammatory response in mice with colitis. However, its effect on macrophages during IBD treatment remains nebulous. Aim of the Study. Explore the mechanism underlying QCWZD effects in a dextran sulfate sodium (DSS)-induced colitis mouse model in vivo and RAW264.7 cell in vitro by observing macrophage polarization dynamics. Methods: The main active components of QCWZD were determined using high-performance liquid chromatography. Surface marker expression on M1-type macrophages was analyzed using flow cytometry and immunofluorescence. The effect on inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) released by M1 type macrophages was determined using ELSA and RT-PCR. The expression of key proteins in the JAK2/STAT3 signaling pathway was analyzed using western blotting. QCWZD cytotoxicity in macrophages was measured using CCK8 and Annexin V-FITC/PI assays. Results: The main active components of QCWZD were berberine chloride, coptisine chloride, epiberberine chloride, gallic acid, ginsenoside Rg1, ginsenoside Rb1, indigo, indirubin, notoginsenoside R1, palmatine chloride, and 6-curcumin. QCWZD markedly alleviated DSS-induced colitis in mice, as revealed by the rescued weight loss and disease activity index, attenuated the colonic shortening and mucosal injury associated with the inhibition of M1 macrophage polarization and expression of related cytokines, such as IL-6 and TNF-α, in vivo and in vitro. Furthermore, QCWZD decreased the iNOS, JAK2, and STAT3 levels in vivo and in vitro, regulating the JAK2/STAT3 signaling pathway. Conclusion: QCWZD administration improves intestinal inflammation by inhibiting M1 macrophage polarization. The JAK2/STAT3 signaling pathway may mediate the effects of QCWZD on M1 macrophage polarization in colitis treatment. This study presents a novel macrophage-mediated therapeutic strategy for the treatment of IBD.

Protective Effects and Mechanisms of Yinchen Linggui Zhugan Decoction in HFD-Induced Nonalcoholic Fatty Liver Disease Rats Based on Network Pharmacology and Experimental Verification.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, characterized by excessive accumulation of hepatocyte fat. However, there is no exact and effective pharmacotherapy for NAFLD. Yinchen linggui zhugan decoction (YLZD) has been widely used to treat NAFLD. Nevertheless, its pharmacological and molecular mechanisms have not been clearly elucidated. This study was carried out to investigate the active components of YLZD and explore its potential mechanisms for treating NAFLD by network pharmacology and experimental verification. The results showed that a total of 120 active components of YLZD and 365 targets were retrieved through databases, and the main active ingredients of YLZD consisted of chlorogenic acid, emodin, aloe-emodin, rhein, and geniposide. KEGG enrichment analysis revealed fundamental roles of TNF, PI3K/AKT, HIF-1α, and insulin resistance signaling pathways in the treatment of NAFLD by YLZD. Moreover, our experimental verification results showed that YLZD improved the liver pathological and cholesterol level, and reduced the expressions of TNF-α, IL-1ß, IL-6, NF-κB, CCL2, and CXCL10 in NAFLD rats, which all belonged to TNF signaling pathway. The molecular docking confirmed the correlation between the four core components (chlorogenic acid, emodin, rhein, and geniposide) and key factors (TNF-α, IL-6, and NF-κB) in TNF signaling pathway. In conclusion, the present study systematically clarified the protective mechanisms of YLZD against NAFLD through targeting the TNF signaling pathway, and provided new ideas for the drug research of this disease.

The role of Akkermansia muciniphila in inflammatory bowel disease: Current knowledge and perspectives.

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, is a chronic relapsing gastrointestinal inflammatory disease mediated by dysregulated immune responses to resident intestinal microbiota. Current conventional approaches including aminosalicylates, corticosteroids, immunosuppressive agents, and biological therapies are focused on reducing intestinal inflammation besides inducing and maintaining disease remission, and managing complications. However, these therapies are not curative and are associated with various limitations, such as drug resistance, low responsiveness and adverse events. Recent accumulated evidence has revealed the involvement of mucin-degrading bacterium Akkermansia muciniphila (A. muciniphila) in the regulation of host barrier function and immune response, and how reduced intestinal colonisation of probiotic A. muciniphila can contribute to the process and development of inflammatory bowel diseases, suggesting that it may be a potential target and promising strategy for the therapy of inflammatory bowel disease. In this review, we summarise the current knowledge of the role of A. muciniphila in IBD, especially focusing on the related mechanisms, as well as the strategies based on supplementation with A. muciniphila, probiotics and prebiotics, natural diets, drugs, and herbs to promote its colonisation in the gut, and holds promise for A. muciniphila-targeted and -based therapies in the treatment of inflammatory bowel disease.

Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice.

Inflammatory bowel disease (IBD), a group of multifactorial and inflammatory infirmities, is closely associated with dysregulation of gut microbiota and host metabolome, but effective treatments are currently limited. Qingchang Wenzhong Decoction (QCWZD) is an effective and classical traditional herbal prescription for the treatment of IBD and has been proved to attenuate intestinal inflammation in a model of acute colitis. However, the role of QCWZD in recovery phase of colitis is unclear. Here, we demonstrated that mice treated with QCWZD showed a faster recovery from dextran sulfate sodium (DSS)-induced epithelial injury, accompanied by reduced mucosal inflammation and attenuated intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing compared to those receiving sterile water. The protective effects of QCWZD are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Gut microbes transferred from QCWZD-treated mice displayed a similar role in mucosal protection and epithelial regeneration as QCWZD on colitis in mice, and depletion of the gut microbiota through antibiotics treatments diminished the beneficial effects of QCWZD on colitis mice. Moreover, metabolomic analysis revealed metabolic profiles alternations in response to the gut microbiota reprogrammed by QCWZD intervention, especially enhanced tryptophan metabolism, which may further accelerate intestinal stem cells-mediated epithelial regeneration to protect the integrity of intestinal mucosa through activation of Wnt/ß-catenin signals. Collectively, our results suggested that orally administrated QCWZD accelerates intestinal mucosal healing through the modulation of dysregulated gut microbiota and metabolism, thus regulating intestinal stem cells-mediated epithelial proliferation, and hold promise for novel microbial-based therapies in the treatment of IBD.

Tongxie Anchang Decoction Relieves Visceral Hypersensitivity in Diarrhea-Predominant Irritable Bowel Syndrome Rats by Regulating the NGF/TrkA Signaling Pathway.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease characterized by visceral hypersensitivity-related abdominal pain, in which diarrhea-predominant IBS (IBS-D) is the main subtype and has a high clinical incidence. Tongxie Anchang Decoction (TXACD) has been proved to significantly improve abdominal pain in patients with IBS-D, but its underlying therapeutic mechanism still remains unclear. In the present study, IBS-D model rats were induced by neonatal maternal separation (NMS) combined with restraint stress (RS). The therapeutic effect of TXACD was evaluated by fecal characteristics and abdominal withdrawal reflex (AWR) scores. After 14 days of intragastric administration, the colonic tissues of rats were collected to detect the protein and gene level of the NGF, TrkA, and TRPV1 using Western blotting and real-time polymerase chain reaction, respectively, and detect mast cells infiltration using toluidine blue staining. The abdominal aorta blood centrifuged was collected for detecting serum levels of SP, 5-HT, and CGRP with ELISA. The results revealed that TXACD could significantly improve visceral hypersensitivity in IBS-D rats, reflected in the decrease of AWR score and the serum levels of SP, 5-HT, and CGRP. In addition, TXACD treatment could alleviate mast cells infiltration. Moreover, the expression levels of the NGF, TrkA, and TRPV1 were repressed by TXACD. The findings of the present study indicated that the therapeutic effect of TXACD on visceral hypersensitivity might be closely related to the downregulation of the NGF/TrkA signaling pathway, the reversal of TRPV1 expression and mast cells infiltration, and the decreased release of neuroendocrine factors SP, 5-HT, and CGRP.

Arterial Stiffness in Inflammatory Bowel Disease: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis were carried out on well-conducted and adequately powered studies to explore whether arterial stiffness was associated with inflammatory bowel disease (IBD). METHODS: The search for potential literature was conducted on PubMed, MEDLINE, Cochrane Library, and Embase from inception to February 15, 2020. The studies assessing arterial stiffness in IBD were reviewed and included. RESULTS: Conclusively, 17 eligible trials with a total of 2188 participants were in compliance with the inclusion criteria. Of the included 2188 participants, the cases for ulcerative colitis (UC) and Crohn's disease (CD) were 558 and 693, respectively. Altogether 10 studies were conducted to evaluate the carotid-femoral pulse wave velocity (CPWV) in overall IBD patients, which was significantly increased with the mean difference (MD) and 95% CI as 0.70 (0.48-0.92, P < .01). The pooled results for CPWV in patients with CD and UC were also faster than that of control groups with MD and 95% CI as 1.09 (0.45-1.72) and 0.57 (0.57-1.24), respectively. The CPWV in CD and UC groups was comparable with a MD of 0.07 (P = .74, 95% CI: -0.32 to 0.45). CONCLUSION: Arterial stiffness had associations with the overall IBD, UC, and CD with a similar strength of association between UC and CD.

Network Pharmacology Identifies the Mechanisms of Action of Tongxie Anchang Decoction in the Treatment of Irritable Bowel Syndrome with Diarrhea Predominant.

AIM: This study aims to uncover the pharmacological mechanism of Tongxie Anchang Decoction (TXACD), a new and effective traditional Chinese medicine (TCM) prescription, for treating irritable bowel syndrome with diarrhea predominant (IBS-D) using network pharmacology. METHODS: The active compounds and putative targets of TXACD were retrieved from TCMSP database and published literature; related target genes of IBS-D were retrieved from GeneCards; PPI network of the common target hub gene was constructed by STRING. Furthermore, these hub genes were analyzed using gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: A total of 54 active compounds and 639 targets were identified through a database search. The compound-target network was constructed, and the key compounds were screened out according to the degree. By using the PPI and GO and KEGG enrichment analyses, the pharmacological mechanism network of TXACD in the treatment of IBS-D was constructed. CONCLUSIONS: This study revealed the possible mechanisms by which TXACD treatment alleviated IBS-D involvement in the modulation of multiple targets and multiple pathways, including the immune regulation, inflammatory response, and oxidative stress. These findings provide novel insights into the regulatory role of TXACD in the prevention and treatment of IBS-D and hold promise for herb-based complementary and alternative therapy.

Clinical efficacy of Qi Di laxative decoction in the treatment of functional constipation: A protocol for systematic review and meta-analysis.

BACKGROUND: Functional constipation (FC) is a common gastrointestinal disorder characterized by slow bowel movement and defecation difficulties, significantly impacting patients' quality of life and exerting heavy financial burden to whole society. However, more than 50% FC patients are not completely satisfied with current therapies and alternative therapies are urgently required. Increasing evidences have demonstrated that traditional Chinese medicine has a good therapeutic effect on FC, which is well known for its multitarget and multimode effects on diverse diseases as well as less side effects. Furthermore, studies proved that Qi Di Laxative Decoction was an effective treatment for FC. Its safety and effectiveness should be verified by further studies. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the clinical efficacy of Qi Di Laxative Decoction in treating FC: Wanfang and Pubmed Database, China National Knowledge Infrastructure Database, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica database. Each database will be searched from inception to November 2020. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses. RESULTS: This proposed study will evaluate the clinical efficacy of Qi Di Laxative Decoction for patients with FC. The outcomes will include changes in FC relief and adverse effect. CONCLUSION: This proposed systematic review will evaluate the existing evidence on the clinical efficacy of Qi Di Laxative Decoction in treating FC. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/M2ESR.

Identification of differentially expressed genes in ulcerative colitis and verification in a colitis mouse model by bioinformatics analyses.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease that is difficult to diagnose and treat. To date, the degree of inflammation in patients with UC has mainly been determined by measuring the levels of nonspecific indicators, such as C-reactive protein and the erythrocyte sedimentation rate, but these indicators have an unsatisfactory specificity. In this study, we performed bioinformatics analysis using data from the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) databases and verified the selected core genes in a mouse model of dextran sulfate sodium (DSS)-induced colitis. AIM: To identify UC-related differentially expressed genes (DEGs) using a bioinformatics analysis and verify them in vivo and to identify novel biomarkers and the underlying mechanisms of UC. METHODS: Two microarray datasets from the NCBI-GEO database were used, and DEGs between patients with UC and healthy controls were analyzed using GEO2R and Venn diagrams. We annotated these genes based on their functions and signaling pathways, and then protein-protein interactions (PPIs) were identified using the Search Tool for the Retrieval of Interacting Genes. The data were further analyzed with Cytoscape software and the Molecular Complex Detection (MCODE) app. The core genes were selected and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed. Finally, colitis model mice were established by administering DSS, and the top three core genes were verified in colitis mice using real-time polymerase chain reaction (PCR). RESULTS: One hundred and seventy-seven DEGs, 118 upregulated and 59 downregulated, were initially identified from the GEO2R analysis and predominantly participated in inflammation-related pathways. Seven clusters with close interactions in UC formed: Seventeen core genes were upregulated [C-X-C motif chemokine ligand 13 (CXCL13), C-X-C motif chemokine receptor 2 (CXCR2), CXCL9, CXCL5, C-C motif chemokine ligand 18, interleukin 1 beta, matrix metallopeptidase 9, CXCL3, formyl peptide receptor 1, complement component 3, CXCL8, CXCL1, CXCL10, CXCL2, CXCL6, CXCL11 and hydroxycarboxylic acid receptor 3] and one was downregulated [neuropeptide Y receptor Y1 (NYP1R)] in the top cluster according to the PPI and MCODE analyses. These genes were substantially enriched in the cytokine-cytokine receptor interaction and chemokine signaling pathways. The top three core genes (CXCL13, NYP1R, and CXCR2) were selected and verified in a mouse model of colitis using real-time PCR Increased expression was observed compared with the control mice, but only CXCR2 expression was significantly different. CONCLUSION: Core DEGs identified in UC are related to inflammation and immunity inflammation, indicating that these reactions are core features of the pathogenesis of UC. CXCR2 may reflect the degree of inflammation in patients with UC.

Indigo Naturalis Alleviates Dextran Sulfate Sodium-Induced Colitis in Rats via Altering Gut Microbiota.

Ulcerative colitis is a gastrointestinal disorder intricately associated with intestinal dysbiosis, but effective treatments are currently limited. Indigo naturalis, a traditional Chinese medicine derived from indigo plants, has been widely used in the treatment of ulcerative colitis. However, the specific mechanisms have not yet been identified. Accordingly, in this study, we evaluated the effects and mechanisms of indigo naturalis on dextran sulfate sodium (DSS)-induced colitis in rats. Our results showed that indigo naturalis potently alleviated DSS-induced colitis in rats, and reversed DSS-induced intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing. The protective effects of indigo naturalis were gut microbiota dependent, as demonstrated by antibiotic treatments and fecal microbiota transplantation. Depletion of the gut microbiota through a combination of antibiotic treatments blocked the anti-inflammatory effect of indigo naturalis on the DSS-induced colitis, and the recipients of the gut microbiota from indigo naturalis-treated rats displayed a significantly attenuated intestinal inflammation, which was actively responsive to therapeutic interventions with indigo naturalis. Notably, supplement with indigo naturalis greatly increased the levels of feces butyrate, which was positively correlated with the relative abundances of Ruminococcus_1 and Butyricicoccus. We further showed that indigo naturalis-dependent attenuation of colitis was associated with elevated expression of short-chain fatty acid-associated receptors GPR41 and GPR43. Collectively, these results suggested that indigo naturalis alleviates DSS-induced colitis in rats through a mechanism of the microbiota-butyrate axis, particularly alterations in Ruminococcus_1 and Butyricicoccus abundances, and target-specific microbial species may have unique therapeutic promise for ulcerative colitis.

Combined use of salivary biomarkers and carcinoembryonic antigen for lung cancer detection in a Chinese population.

Blood-based biomarkers, such as carcinoembryonic antigen (CEA), and saliva-based biomarkers, such as mRNA, have emerged as potential liquid biopsies for non-invasive detection of many cancers. However, current tests typically use single type of biomarkers, and their sensitivity and specificity is often unsatisfactory.In this study, we developed a novel biomarker panel that measures both CEA level in blood and GREB1 and FRS2 levels in saliva to achieve high sensitivity and high specificity in detecting Non-Small Cell Lung Cancer (NSCLC).In the discovery phase, we achieved sensitivity of 96.67% and specificity of 93.33% for 30 NSCLC patients and 30 healthy controls. To further evaluate the prediction performance of our biomarker panel, we applied it to an independent set of 15 NSCLC cancer patients and 25 healthy controls. The sensitivity and specificity of our test reached 93.33% and 80.00% respectively.Our study discovered that the combined analysis of CEA and mRNA can be a novel liquid-biopsy technology for non-invasive detection of NSCLC.

The effect of Heweijiangni-decoction on esophageal morphology in a rat model of OVA-induced visceral hypersensitivity followed by acid exposure.

Heweijiangni decoction (HWJND) is an effective traditional Chinese medicine prescription in clinical treatment of nonerosive reflux disease (NERD). Esophageal hypersensitivity and acid contribute to the disease. However, the exact underlying mechanism of action remains unclear. In this study, we observed the effect of HWJND on esophageal morphology in a rat model of ovalbumin (OVA)-induced visceral hypersensitivity followed by acid exposure. Esophageal morphology was assessed by measuring the extent of dilated intercellular spaces (DIS), desmosome disruption, and mitochondrial fragmentation. HWJND in low, moderate, and high doses relieved DIS and desmosome disruption in esophageal epithelium compared with model group (P<0.05 for all doses). In addition, HWJND in high dose protected mitochondria from fragmentation (P<0.05). Other findings suggest that DIS and mitochondrial fragmentation are independent events, and that omeprazole protects mitochondria. Overall, HWJND significantly resists esophageal morphology changes in OVA-induced and acid exposure rat model.

Gut Microbiota-Mediated NLRP12 Expression Drives the Attenuation of Dextran Sulphate Sodium-Induced Ulcerative Colitis by Qingchang Wenzhong Decoction.

Qingchang Wenzhong Decoction (QCWZD) is a newly developed, effective traditional Chinese herbal formulation for ulcerative colitis (UC). In earlier studies, we found that QCWZD could relieve the clinical symptoms of UC patients, reduce inflammation, and improve the intestinal barrier function in dextran sulphate sodium (DSS)-induced UC rats. However, the relationship between QCWZD and the gut microbiota in colitis was not clarified. In this study, we established a rat model of DSS-induced UC and then investigated the regulatory effects of QCWZD on the gut microbiota using 16S rRNA analysis. We also determined the expression of NLRP12 after QCWZD administration. Our findings suggested that QCWZD administration could modulate gut microbiota composition and selectively promote the protective strains such as Butyricimonas, Blautia, and Odoribacter, whereas the enteric pathogens including Clostridium and Dorea were significantly reduced after QCWZD treatment. It is noteworthy that QCWZD administration was identified to promote gut microbiota-mediated NLRP12 expression by inhibiting the activity of the TLR4/Blimp-1 axis. In conclusion, our study supports the potential of QCWZD administration as a beneficial therapeutic strategy for UC.

MiR-139-5p inhibits proliferation and promoted apoptosis of human airway smooth muscle cells by downregulating the Brg1 gene.

MicroRNAs have emerged as critical regulators in the pathogenesis of asthma. However, the role of microRNAs in asthma needs to be further elucidated. In this study, we found that miR-139-5p was greatly decreased in airway smooth muscle (ASM) cells from asthmatic humans as well as ASM cells stimulated with cytokines. Overexpression of miR-139-5p markedly suppressed ASM cell proliferation and promoted cell apoptosis, whereas knockdown of miR-139-5p had the opposite effect. Further study verified that Brg1, a chromatin remodeling factor, was upregulated in ASM cells treated with cytokines and acted as a direct target of miR-139-5p. Ectopic expression of Brg1 partially reversed the effect of miR-139-5p on cell proliferation and apoptosis. Moreover, overexpression of Brg1 restored miR-139-5p-induced downregulation of Akt and p70S6K phosphorylation. Together, these data indicate that miR-139-5p may function as a key regulator of ASM cell proliferation and apoptosis, potentially by targeting the Brg1 gene, and thus suggesting a potential role of miR-139-5p in the pathogenesis of asthma.