Wu-Mei-Wan (WMW), a traditional Chinese medicine, has been applied in the treatment of gastrointestinal diseases with long-term diarrhea and mucopurulent bloody stool as the main symptoms since ancient times. Studies have shown that WMW inhibits intestinal inflammation, repairs damaged intestinal mucosa, resists colon necrosis, and resists intestinal fibrosis. However, the specific mechanism of action is not yet clear. Ulcerative colitis (UC), an intestinal disease with intestinal inflammation and injury as the main pathological manifestations, is one of the high-risk factors for colon cancer. Inhibiting the inflammatory response and promoting colonic epithelial repair are critical to the treatment of UC. However, there is still a lack of remedies with satisfactory curative effects. In this study, the role of WMW in dextran sulfate sodium (DSS)-induced colitis in mice and its related mechanisms are discussed from two aspects: intestinal inflammation and tissue repair. DSS was used to induce colitis in mice and the therapeutic effect of WMW was analyzed by disease activity score, histopathological score, colon length measurement, serum cytokine detection, and flow cytometry. Macrophage activation and colonic stem cell proliferation were observed by immunohistochemistry. The expression of critical molecules in macrophage activation and colonic stem cell proliferation signaling pathways in colon tissue was detected with immunohistochemistry, immunofluorescence staining, RT-qPCR, and Western blot. WMW could significantly alleviate DSS-induced colitis. We showed that WMW could reduce disease activity, reduce pathological scores, limit weight loss, inhibit colon shortening, inhibit inflammatory factor secretion, attenuate inflammatory response, and promote the repair of damaged colonic epithelium. WMW inhibited the activation of colonic macrophages, and its mechanism might be inhibiting the Notch/NF-κB/NLRP3 pathway; WMW promoted the proliferation of colonic stem cells, and its mechanism was associated with the regulation of the Hippo/YAP signaling pathway. The results of this study suggested that WMW could treat UC via a mechanism that inhibited the intestinal inflammatory response and repaired damaged intestinal mucosa.

Previous circular RNA (circRNA) microarray analyses have uncovered an abnormal expression of hsa_circ_0070963 in hepatic stellate cells (HSCs). However, the specific role of hsa_circ_0070963 in liver fibrosis remains unknown. Here, we show that hsa_circ_0070963 inhibits liver fibrosis via regulation of miR-223-3p and LEMD3. Moreover, we demonstrated that hsa_circ_0070963 levels were reduced during liver fibrosis while restoring hsa_circ_0070963 levels abolished HSC activation, with a reduction in α-SMA and type I collagen levels both in vitro and in vivo. Furthermore, hsa_circ_0070963 overexpression suppressed both cell proliferation and the cell cycle of HSCs. MiR-223-3p was confirmed as a target of hsa_circ_0070963 and was shown to be involved in the effects of hsa_circ_0070963 on HSC activation. Furthermore, LEMD3 was confirmed as a target of miR-223-3p and was shown to be responsible for the activation of HSCs. The interactions between hsa_circ_0070963, miR-223-3p, and LEMD3 were validated via bioinformatic analysis, luciferase reporter assays, and rescue experiments. Collectively, hsa_circ_0070963 appeared to function as a miR-223-3p sponge that inhibited HSC activation in liver fibrosis via regulation of miR-223-3p and LEMD3. Therefore, hsa_circ_0070963 may serve as a potential therapeutic target for liver fibrosis.

Pulmonary fibrosis (PF) is a chronic, progressive, fibrotic interstitial disease of the lung with poor prognosis and without effective treatment currently. Data from previous coronavirus infections, such as the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome, as well as current clinical evidence from the Coronavirus disease 2019 (COVID-19), support that SARS-CoV-2 infection may lead to PF, seriously impacting patient prognosis and quality of life. Therefore, effective prevention and treatment of PF will improve patient prognosis and reduce the overall social and economic burdens. Stem cells, especially mesenchymal stem cells (MSCs) have many great advantages, including migration to damaged lung tissue and secretion of various paracrine factors, thereby regulating the permeability of endothelial and epithelial cells, reducing inflammatory response, promoting tissue repair and inhibiting bacterial growth. Clinical trials of MSCs for the treatment of acute lung injury, PF and severe and critically ill COVID-19 are ongoing. The purpose of this study is to systematically review preclinical studies, explored the effectiveness of MSCs in the treatment of bleomycin (BLM)-induced pulmonary fibrosis and analyze the potential mechanism, combined with clinical trials of current MSCs for idiopathic pulmonary fibrosis (IPF) and COVID-19, so as to provide support for clinical research and transformation of MSCs. Searching PubMed and Embase (− 2021.4) identified a total of 36 preclinical studies of MSCs as treatment of BLM-induced acute lung injury and PF in rodent models. Most of the studies showed the MSCs treatment to reduce BLM-induced lung tissue inflammatory response, inflammatory cell infiltration, inflammatory cytokine expression, extracellular matrix production and collagen deposition, and to improve Ashcroft score. The results of present studies indicate that MSCs may serve as a potential therapeutic modality for the treatment of PF, including viral-induced PF and IPF.

Gastric mucosal injury is a chronic and progressive stomach disease that can be caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, there is an urgent need to find safe and effective drugs to prevent gastric mucosal injury due to NSAIDs. Cinnamaldehyde (CA) is a bioactive compound extracted from the rhizome of cinnamon and has various pharmacological functions, including anti-inflammatory, analgesic, antiapoptotic, and antioxidant activities. However, the potential pharmacological effect of CA on gastric mucosal injury remains unknown. The aim of this study was to investigate the protective effects of CA on aspirin-induced gastric mucosal injury and to explore its mechanism of action METHODS: The effect of CA on gastric mucosal injury was investigated in vitro and in vivo, in vitro mouse model of gastric mucosal injury induced by aspirin, in vitro model of GES-1 cell injury by aspirin and Erastin. The mechanism of action of CA was determined using Transcriptomics and bioinformatics. CA exerted its protective effects against gastric mucosal injury by modulating the downstream targets, including mTOR, GSK3β, and NRF2, via the PI3K/AKT signaling pathway to inhibit autophagy, apoptosis, and ferroptosis in the gastric epithelial cells. Further cellular experiments confirmed that the PI3K/AKT pathway was a key target for CA against gastric mucosal injury. This study provides the first evidence of CA, an active compound in cinnamon, possessing therapeutic potential in preventing and treating gastric mucosal injury, with its mechanism involving the regulation of apoptosis, autophagy, and ferroptosis in gastric epithelial cells mediated by the PI3K/AKT signaling pathway.

As newly found non‐coding RNAs, circular RNAs (circRNAs) are involved in multiple biological processes. Emerging evidence has illustrated the pivotal roles of circRNAs in various human cancers. However, the function of circFAT1 in hepatocellular carcinoma (HCC) remains largely unclear. In the present study, we found that circFAT1 expression is up‐regulated in HCC tissues and cells. In addition, circFAT1 level is positively correlated with TNM stage and tumour size. To further explore the function of circFAT1 in HCC, in vitro and in vivo experiments were performed. The results show that circFAT1 inhibition reduces the proliferation and invasion of HCC cells and tumorigenesis in vivo, whereas REEP3 overexpression reverses these processes. In conclusion, circFAT1 sponges miR‐30a‐5p to regulate the expression of REEP3, thus promoting hepatocarcinogenesis. New HCC diagnosis or treatment strategies may be developed from circFAT1 as a target.

An increasing body of evidence shows that macrophages play an important role in the pathogenesis of ulcerative colitis (UC). Macrophage polarization and changes in related signaling pathways are reported to have a protective effect on intestinal inflammation. The well-known Chinese medicine Wumeiwan (WMW) has been used to treat diarrhea, one of the main symptoms of colitis, for more than 2,000 years. Increasing evidence shows that WMW can inhibit intestinal inflammation and repair damaged intestinal mucosa, but its effector mechanisms are unknown. Therefore, we studied the prophylactic effects of WMW in dextran sulfate sodium (DSS)-induced UC and its effects on macrophage mechanisms and polarization. The results show that colitis was significantly alleviated in mice in the WMW group, and the secretion and expression of pro-inflammatory factors TNF-α, IL-1, and IL-6 were inhibited in the serum and colonic tissues of mice with WMW-treated colitis, whereas anti-inflammatory factors IL-10, Arg-1, and TGF-β1 were increased. Subsequent studies found that WMW could inhibit M1 polarization and promote M2 polarization in colonic macrophages in DSS-induced colitis mice. Network pharmacology was used to predict potential targets and pathways, and further studies confirmed the related targets The results showed that WMW gradually inhibits the activation of the P38MAPK and NF-κB signaling pathways and further activates the STAT6 signaling pathway. In summary, WMW interferes with the p38MAPK, NF-κB and STAT6 signaling pathways to regulate M1/M2 polarization in macrophages, thereby protecting mice against DSS-induced colitis.