Lentinus edodes Polysaccharides Alleviate Acute Lung Injury by Inhibiting Oxidative Stress and Inflammation.

Acute lung injury (ALI) is a kind of lung disease with acute dyspnea, pulmonary inflammation, respiratory distress, and non-cardiogenic pulmonary edema, accompanied by the mid- and end-stage characteristics of COVID-19, clinically. It is imperative to find non-toxic natural substances on preventing ALI and its complications. The animal experiments demonstrated that Lentinus edodes polysaccharides (PLE) had a potential role in alleviating ALI by inhibiting oxidative stress and inflammation, which was manifested by reducing the levels of serum lung injury indicators (C3, hs-CRP, and GGT), reducing the levels of inflammatory factors (TNF-α, IL-1ß, and IL-6), and increasing the activities of antioxidant enzymes (SOD and CAT) in the lung. Furthermore, PLE had the typical characteristics of pyran-type linked by ß-type glycosidic linkages. The conclusions indicated that PLE could be used as functional foods and natural drugs in preventing ALI.

Stropharia rugoso-annulata acetylated polysaccharides alleviate NAFLD via Nrf2/JNK1/AMPK signaling pathways.

The acetylated Stropharia rugoso-annulata polysaccharides (ASRP) was successfully characterized, and the effects and mechanism on alleviating NAFLD were investigated in HFD-induced mice models. The characterization showed that ASRP was successfully acetylated and rich in galactose. The animal studies demonstrated that ASRP at the dose of 400 mg/kg possessed hepatoprotective effects by potential antioxidation, anti-inflammation and improving hepatocellular histopathology, with the possible mechanisms on regulating the JNK1/AP-1 and activating the Nrf2 signaling pathways. Besides, ASRP could improve the fat metabolism by activating the AMPK/SREBP-1c signaling pathways. The results provided basal theories for the development of ASRP on treating the NAFLD and its complications.

hECA: The cell-centric assembly of a cell atlas.

The accumulation of massive single-cell omics data provides growing resources for building biomolecular atlases of all cells of human organs or the whole body. The true assembly of a cell atlas should be cell-centric rather than file-centric. We developed a unified informatics framework for seamless cell-centric data assembly and built the human Ensemble Cell Atlas (hECA) from scattered data. hECA v1.0 assembled 1,093,299 labeled human cells from 116 published datasets, covering 38 organs and 11 systems. We invented three new methods of atlas applications based on the cell-centric assembly: "in data" cell sorting for targeted data retrieval with customizable logic expressions, "quantitative portraiture" for multi-view representations of biological entities, and customizable reference creation for generating references for automatic annotations. Case studies on agile construction of user-defined sub-atlases and "in data" investigation of CAR-T off-targets in multiple organs showed the great potential enabled by the cell-centric ensemble atlas.

Efficacy and Safety of Zuojin Pill for the Treatment of Chronic Nonatrophic Gastritis: A Randomized Active-Controlled Clinical Trial.

Objective: Zuojin pill (ZJP) is used as the classical prescription for a wide variety of digestive diseases. However, there is a lack of direct evidence for its use in the treatment of chronic nonatrophic gastritis (CNG). In particular, there is a lack of rigorous trials of randomized controlled designs. In this study, a randomized active-controlled clinical trial was performed to verify the efficacy and safety of ZJP in detail. Methods: Patients with CNG were divided into the ZJP group and the Marzulene-S granule group. Patients were enrolled from September 2019 to February 2021 (ChiCTR2000040549). Endoscopy and histology scores were evaluated as the primary outcome measure. The Helicobacter pylori positive rate and the disappearance rate of symptoms were also measured to reflect the outcomes. Finally, adverse events were also calculated as the index of safety. Results: A total of 68 eligible patients were enrolled in this trial and randomly divided into two groups with baseline comparability. ZJP was able to improve the red plaques as well as bile reflux scores compared with Marzulene-S granule (P=0.043 and P=0.019, respectively). Moreover, it also remarkably alleviated the active chronic inflammation score (P=0.043). However, there was no difference between the Helicobacter pylori positivity rate (P=0.752). The symptom scores of abdominal distension (P=0.004), belching (P=0.010), and loss of appetite (P=0.019) were alleviated by ZJP, but nausea and vomiting were not (P=0.616). ZJP can also be considered safe with no obvious adverse effects. Conclusion: ZJP might decrease mucosal injury and alleviate symptoms in CNG. In addition, more large-scale clinical trials should be carried out to further confirm its clinical efficacy and safety.

Circ_0001667 knockdown blocks cancer progression and attenuates adriamycin resistance by depleting NCOA3 via releasing miR-4458 in breast cancer.

Accumulating evidence suggests that developmental chemoresistance in cancers is closely associated with the dysregulation of circular RNA transcriptions. The objective of this study is to disclose the role of circ_0001667 and provide a potential functional mechanism in breast cancer. Quantitative real-time PCR was applied for the analysis of circ_0001667, microRNA-4458 (miR-4458) and nuclear receptor coactivator 3 (NCOA3) expression. In adriamycin (ADM)-resistant cell lines, we investigated cell proliferation using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and colony formation assay. Cell migration and cell invasion were determined by transwell assay. The protein levels of multi-drug resistance-1, matrix metalloproteinases-9, cleaved-caspase3, cleaved-caspase9 and NCOA3 were detected by western blot. ADM resistance was ascertained by IC50 value using MTT assay. Cell apoptosis was checked by flow cytometry assay. The putative relationship between miR-4458 and circ_0001667 and NCOA3 was validated by pull-down assay, dual-luciferase reporter assay or RNA Immunoprecipitation assay. Circ_0001667 knockdown inhibited MCF-7/ADM and MDA-MB-231/ADM cell proliferation, migration, invasion and ADM resistance. MiR-4458 was a target of circ_0001667, and its expression was decreased in ADM-resistant tumor tissues and cells. MiR-4458 inhibition reversed the effects of circ_0001667 knockdown. In depth, NCOA3 was a target of circ_0001667, and circ_0001667 knockdown weakened NCOA3 expression by releasing miR-4458. MCF-7/ADM and MDA-MB-231/ADM cell proliferation, migration, invasion, and ADM resistance inhibited by miR-4458 restoration were recovered by NCOA3 overexpression. Circ_0001667 knockdown also repressed tumor growth and ADM resistance in vivo. Circ_0001667 knockdown blocks cancer progression and attenuates ADM resistance by depleting NCOA3 via releasing miR-4458 in breast cancer.

Dehydroevodiamine ameliorates indomethacin-induced gastric injury via inhibition of ERK and p38 signaling pathway.

BACKGROUND: Dehydroevodiamine (DHE), a pivotal quinazoline alkaloid isolated from Fructus Evodiae (Tetradium ruticarpum (A. Juss.) Hartley), has various pharmacological effects. However, the effect of DHE on gastric injury is still uncharted. PURPOSE: To clarify the pharmacological effect and mechanism of DHE on gastric injury (GI) induced by indomethacin (IDO). STUDY DESIGN: The gastric injury was induced in rat by oral administration of 5 mg/kg IDO for 7 days. Then the rats were treated with DHE (10, 20, 40 mg/kg, ig) for 7 days. METHODS: The changes of food intake, body weight, gastric pH and general state observation were determined. And HE staining and AB-PAS staining was analyzed. Then, the inflammatory infiltration of gastric tissue was observed through MPO immunohistochemical approach, and the expression of TNF-α, IL-6 and IL-10 were measured. Furthermore, the levels of proteins ERK, p-ERK, P38, p-P38, JNK and p-JNK were determined to elucidate the molecular mechanism of DHE. RESULTS: DHE alleviated food intake reduction, weight loss and gastric injury induced by IDO and made gastric pH and mucosal thickness return to normal. In addition, DHE could down regulate the expression of MPO, TNF-α and IL-6 and up regulate the expression of IL-10 to reduce the damage induced by inflammatory, and create a healing environment. Furthermore, DHE could significantly inhibit the phosphorylation of ERK and p38 not JNK. CONCLUSION: DHE ameliorated dyspepsia, inflammatory infiltration and tissue damage induced by IDO through ERK and p38 signaling pathways rather than JNK pathway.

Zuojin Pill ameliorates chronic atrophic gastritis induced by MNNG through TGF-ß1/PI3K/Akt axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Zuojin Pill (ZJP) is a classic prescription composed of Coptis chinensis and Tetradium ruticarpum (A.Juss.) T.G.Hartley, which is often used in the treatment of digestive system diseases. AIM OF THIS STUDY: The purpose of this study was to explore the therapeutic effect and potential mechanism of ZJP on chronic atrophic gastritis (CAG) induced by MNNG. MATERIALS AND METHODS: The GES-1 and rat model of CAG was established by MNNG. Detection of cell viability, morphological changes and proliferation of GES-1 by CCK-8 and high content screening (HCS) assay. G-17, IL-8 and TNF-α in rat serum were detected by ELISA kit. The expression of related mRNA and protein on TGF-ß1/PI3K/Akt signal axis were detected by RT-PCR and Western blot. RESULTS: The results showed that ZJP could significantly improve the GES-1 damage induced by MNNG and improve the gastric histomorphology of CAG rats. The intervention of ZJP could significantly reduce the content of G-17 and inflammatory factors IL-8, TNF- α, IL-6 and IL-1ß, inhibit the expression of TGF-ß1, PI3K and their downstream signals p-Akt, p-mTOR, P70S6K, and promote the expression level of PTEN, LC3-II and Beclin-1. CONCLUSION: ZJP has a good therapeutic effect on CAG induced by MNNG, which may be closely related to the inhibition of TGF-ß1/PI3K/Akt signal pathway.

Metabolomic profiles of breath odor compounds for prognostic prediction in patients with acute-on-chronic liver failure: A pilot study.

AIM: The aim of this study was to use a metabonomics approach to identify potential biomarkers of exhaled breath condensate (EBC) for predicting the prognosis of acute-on-chronic liver failure (ACLF). METHODS: Using liquid chromatography mass spectrometry, EBC metabolites of ACLF patients surviving without liver transplantation (n = 57) and those with worse outcomes (n = 45), and controls (n = 15) were profiled from a specialized liver disease center in Beijing. The metabolites were used to identify candidate biomarkers, and the predicted performance of potential biomarkers was tested. RESULTS: Forty-one metabolites, involving glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, and amino acid metabolism, as candidate biomarkers for discriminating the different outcomes of ACLF were selected. A prognostic model was constructed by a panel of four metabolites including phosphatidylinositol [20:4(5Z,8Z,11Z,14Z)/13:0], phosphatidyl ethanolamine (12:0/22:0), L-metanephrine and ethylbenzene, which could predict the worse prognosis in ACLF patients with sensitivity (84.4%) and specificity (89.5%) (area under the receiver operating characteristic curve [AUC] = 0.859, 95% confidence interval [CI] = 0.787-0.931). Compared with Model for End-Stage Liver Disease (MELD) score (AUC = 0.639, 95% CI = 0.526-0.753) and MELD-sodium (MELD-Na) score (AUC = 0.692, 95% CI = 0.582-0.803), EBC-associated metabolite signature model could better predict worse outcomes in patients with ACLF (p < 0.05). Using the MELD-Na score and EBC metabolite signatures, a decision tree model was built for predicting the prognosis of ACLF identified on logistic regression analyses (AUC = 0.906, 95% CI = 0.846-0.965). CONCLUSION: EBC metabolic signatures show promise as potential biomarkers for predicting worse prognosis of ACLF.

MicroRNA-212 suppresses cell proliferation in nasopharyngeal carcinoma by targeting ELF3.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy of the head and neck that is prevalent in China. The present study investigated the molecular mechanisms of microRNA-212 (miR-212) and E74-like factor 3 (ELF3) in NPC cell lines and tissues. Using reverse transcription-quantitative PCR, the present study identified that miR-212 expression was downregulated in NPC cell lines and tissues. Furthermore, an elevated expression level of miR-212 was revealed to inhibit NPC cell proliferation, as determined using a cell counting kit-8 assay in vitro. ELF3 was identified as a direct target of miR-212 in NPC cells by a luciferase reporter assay. Additionally, the expression levels of miR-212 and ELF3 were negatively correlated in NPC tissues. The expression levels of ELF3 and miR-212 were associated with metastasis and TNM stage in patients with NPC. In summary, the present study indicated that miR-212 was downregulated in NPC and suppressed cell proliferation. This suggested that the miR-212/ELF3 axis may serve as a novel target for the diagnosis and treatment of NPC.

Overexpression of Annexin A1 protects against benzo[a]pyrene­induced bronchial epithelium injury.

The incidence of asthma is increasing worldwide. Bronchial epithelium injury is common in asthma. The regulatory role of Annexin A1 (ANXA1) in bronchial epithelium injury is currently not well understood. The aim of the present study was to evaluate the role of ANXA1 on bronchial epithelium injury. The cell viability and levels of apoptosis were respectively tested by Cell Counting Kit­8 and flow cytometry. Reactive oxygen species (ROS) content and the activity of oxidative indicators were assessed by commercial kits. Enzyme linked immunosorbent assay was performed to detect the activity of active caspase­3. Reverse transcription­quantitative polymerase chain reaction and western blot assays were used to determine the expression levels of the target factors. The results demonstrated that ANXA1 improved the viability of benzo[a]pyrene (Bap)­treated bronchial epithelial cells. The Bap­induced oxidative stress was mitigated by the reduction in ROS generation, and the regulation of the activity of superoxide dismutase, glutathione peroxidases, malondialdehyde and lactic dehydrogenase. In addition, apoptosis was decreased by ANXA1 via the reduction of the expression of B­cell lymphoma 2 (Bcl­2), and the increase in the expression of Bcl­2­associated X protein and cyclin D1. Furthermore, the expression of phosphatase and tensin homolog (PTEN) and focal adhesion kinase (FAK) was rescued and the phosphorylation of phosphatidylinositol 3­kinase (PI3K)/protein kinase B (Akt) was depressed by ANXA1, when compared with the Bap group. SF1670 treatment reversed the anti­apoptotic effect of ANXA1. In conclusion, the results highlighted the protective effects of ANXA1 on bronchial epithelium injury, which most likely occurred via the PTEN/FAK/PI3K/Akt signaling pathway. Thus, the present study contributes to a potential therapeutic strategy for asthma patients.

Latent variable analysis on Chinese medicine syndrome in patients with antituberculosis drug-induced liver injury.

OBJECTIVE: To explore the Chinese medicine (CM) syndrome discipline in patients with antituberculosis drug (ATBD)-induced liver injury to provide the basis of the standard Chinese medicine treatment for the disease with latent variable analysis. METHODS: Epidemiological investigation method was adopted. Two hundred and sixty-one patients with ATBD-induced liver injury were investigated using CM syndrome questionnaire. The syndrome types were determined with exploratory factor analysis (EFA), and the latent variables were analyzed by confirmatory factor analysis (CFA). RESULTS: Totally 26 indexes related to CM syndrome differentiation were obtained from the 261 eligible cases, among them, 5 were as the latent dependent variables, which corresponded to 5 common syndrome types, including dampness encumbering the Spleen (Pi), Liver (Gan)-qi stagnation, Spleen and Stomach (Wei) deficiency, stasis-toxin accumulation, and qi-yin deficiency. CFA indicated that the indexes with loading coefficient [Symbol: see text]0.6 exactly reflected the connotation of its corresponding syndrome type. CONCLUSIONS: Five CM syndrome types are the most common in patients with ATBD-induced liver injury, which relate to their corresponding indexes for differentiation. It is feasible to apply combined EFA and CFA for explaination and measurement of the existence of CM syndrome under specific diseases.