TMT quantitative proteomics and network pharmacology reveal the mechanism by which asiaticoside regulates the JAK2/STAT3 signaling pathway to inhibit peritoneal fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine, Centella asiatica (L.) Urb., has been extensively utilized in clinics to treat a variety of fibrotic disorders. Asiaticoside (ASI), as an important active ingredient, has attracted much attention in this field. However, the effect of ASI on peritoneal fibrosis (PF) is still unclear. Therefore, we evaluated the benefits of ASI for PF and mesothelial-mesenchymal transition (MMT) and revealed the underlying mechanisms. AIM OF STUDY: The objective of this investigation was to anticipate the potential molecular mechanism of ASI against peritoneal mesothelial cells (PMCs) MMT employing proteomics and network pharmacology, and to confirm it using in vivo and in vitro studies. MATERIALS AND METHODS: The mesentery of peritoneal fibrosis mice and normal mice were analyzed quantitatively for proteins that were differentially expressed using a technique tandem mass tag (TMT). Next, the core target genes of ASI against PF were screened through network pharmacology analysis, and PPI and C-P‒T networks were constructed by Cytoscape Version 3.7.2. According to the findings of a GO and KEGG enrichment analysis of differential proteins and core target genes, the signaling pathway with a high correlation degree was selected as the key signaling pathway of ASI inhibiting the PMCs MMT for further molecular docking analysis and experimental verification. RESULTS: TMT-based quantitative proteome analysis revealed the identification of 5727 proteins, of which 70 were downregulated and 178 were upregulated. Among them, the levels of STAT1, STAT2, and STAT3 in the mesentery of mice with peritoneal fibrosis were considerably lower than in the control group, indicating a role for the STAT family in the pathogenesis of peritoneal fibrosis. Then, a total of 98 ASI-PF-related targets were identified by network pharmacology analysis. JAK2 is one of the top 10 core target genes representing a potential therapeutic target. JAK/STAT signaling may represent a core pathway mediating PF effects by ASI. Molecular docking studies showed that ASI had the potential to interact favorably with target genes involved in the JAK/STAT signaling pathway, such as JAK2 and STAT3. The experimental results showed that ASI could significantly alleviate Chlorhexidine Gluconate (CG)-induced peritoneal histopathological changes and increase JAK2 and STAT3 phosphorylation levels. In TGF-ß1-stimulated HMrSV5 cells, E-cadherin expression levels were dramatically reduced whereas Vimentin, p-JAK2, α-SMA, and p-STAT3 expression levels were considerably increased. ASI inhibited the TGF-ß1-induced HMrSV5 cell MMT, decreased the activation of JAK2/STAT3 signaling, and increased the nuclear translocation of p-STAT3, which was consistent with the effect of the JAK2/STAT3 pathway inhibitor AG490. CONCLUSION: ASI can inhibit PMCs MMT and alleviate PF by regulating the JAK2/STAT3 signaling pathway.

Meta-analysis on the effect of combining Lianhua Qingwen with Western medicine to treat coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a worldwide life-threatening pandemic. Lianhua Qingwen is believed to possess the ability to treat or significantly improve the symptoms of COVID-19. These claims make it important to systematically evaluate the effects of using Lianhua Qingwen with Western medicine to treat COVID-19. OBJECTIVE: To evaluate the safety and efficacy of combination therapy, employing Lianhua Qingwen with Western medicine, to treat COVID-19, using a meta-analysis approach. SEARCH STRATEGY: China National Knowledge Infrastructure, Wanfang Database, VIP Database, PubMed, Embase, and Cochrane Library databases were searched for studies evaluating the effect of Lianhua Qingwen-Western medicine combination therapy in the treatment of COVID-19. INCLUSION CRITERIA: (1) Research object: hospitalized patients meeting the diagnostic criteria of COVID-19 were included. (2) Intervention measures: patients in the treatment group received Lianhua Qingwen treatment combined with Western medicine, while the control group received either Western medicine or Chinese medicine treatment. (3) Research type: randomized controlled trials and retrospective study were included. DATA EXTRACTION AND ANALYSIS: Two researchers extracted the first author, the proportion of males and females, age, body temperature, course of treatment, rate of disappearance of main symptoms, duration of fever, adverse reactions, and total effectiveness from the literature. Odds ratio (OR) and 95% confidence interval (CI) were used as the effect value for count data, and mean difference (MD) and 95% CI were used as the effect value for measurement data. RESULTS: Six articles met the inclusion criteria, including a total of 856 COVID-19 patients. The meta-analysis showed that Lianhua Qingwen combination therapy achieved higher rates of fever reduction (OR = 3.43, 95% CI [1.78, 6.59], P = 0.0002), cough reduction (OR = 3.39, 95% CI [1.85, 6.23], P < 0.0001), recovery from shortness of breath (OR = 10.62, 95% CI [3.71, 30.40], P < 0.0001) and recovery from fatigue (OR = 2.82, 95% CI [1.44, 5.53], P = 0.003), higher total effectiveness rate (OR = 2.51, 95% CI [1.73, 3.64], P < 0.00001), and shorter time to recovery from fever (MD = -1.00, 95% CI [-1.04, 0.96], P < 0.00001), and did not increase the adverse reaction rate (OR = 0.65, 95% CI [0.42, 1.01], P = 0.06), compared to the single medication control. CONCLUSION: The Lianhua Qingwen and Western medicine combination therapy is highly effective for COVID-19 patients and has good clinical safety. As only a small number of studies and patients were included in this review, more high-quality, multicenter, large-sample-size, randomized, double-blind, controlled trials are still needed for verification.

Knowledge, attitude and practice level of women at the periconceptional period: a cross-sectional study in Shaanxi China.

BACKGROUND: Identifying and understanding the knowledge, attitude and practice (KAP) level of women at the periconceptional period has implications for formulating and measuring the adverse pregnancy outcomes for primary prevention. METHODS: A cross-sectional study among pregestational and pregnant women was conducted in Shaanxi during 2016-2017. RESULTS: Among 791 participants, the average score of periconceptional healthcare knowledge awareness was 6.32 ± 1.78, whereas 28.8% of women have failed. Women who planned to or had undergone premarital and pre-pregnancy examinations accounted for 50.2, and 62.5%, respectively. Less than half (42.0%) of the women started taking folic acid (FA) before pregnancy, and only 37.9% of them took FA regularly at the right time. Multivariate analysis showed that age was the main factor influencing the Attitude and Practice level of women at the periconceptional period, and demonstrated a positive effect on the awareness of right timing of folic acid supplementation, and high rates of premarital and pre-pregnancy examinations. Also, the knowledge pass rate was increased with education level. Fewer women who have birth experience were willing to take FA consistently at the right time compared to those women without birth. CONCLUSIONS: The women at the periconceptional period in Shaanxi lacked the total KAP level of periconceptional healthcare, especially those who live in rural areas and have less education. Government agencies should reinforce more effective primary preventive measures and policies for the prevention of adverse pregnancy outcomes.

A cupin domain is involved in α-amylase inhibitory activity.

Proteinaceous α-amylase inhibitors have specialized activities that make some strong inhibition of α-amylases. New α-amylase inhibitors continue to be discovered so far. A proteinaceous α-amylase inhibitor CL-AI was isolated and identified from chickpea seeds. CL-AI, encoded by Q9SMJ4, was a storage legumin precursor containing one α-chain and one ß-chain, and each chain possessed a same conserved cupin domain. Amino acid mutation and deficiency of cupin domain would lead to loss of α-amylase inhibitory activity, indicating that it was essential for inhibitory activity. CL-AI(α + ß) in its single stranded state in vivo had inhibitory activity. After it was processed into one α-chain and one ß-chain, the two chains were connected to each other via disulfide bond, which would cover the cupin domains and lead to the loss of inhibitory activity. The CL-AI(α + ß), α-chain and ß-chain could inhibit various α-amylases and delay the seed germination of wheat, rice and maize as well as the growth and development of potato beetle larva. Two cupin proteins, Glycinin G1 in soybean and Glutelinin in rice were also found to have inhibitory activity. Our results indicated that the cupin domain is involved in α-amylase inhibitory activity and the proteins with a cupin domain may be a new kind of proteinaceous α-amylase inhibitor.