Urolithin A exerts a protective effect on lipopolysaccharide-induced acute lung injury by regulating HMGB1-mediated MAPK and NF-κB signaling pathways.

Acute lung injury (ALI) is a severe inflammatory disorder that has a high morbidity and mortality rate. Urolithin A (UA) is reported to have anti-inflammatory and anti-oxidative effects in ALI. However, its molecular mechanisms in ALI remain to be explored. Mice and BEAS-2B cells were administrated with lipopolysaccharide (LPS) to mimic the ALI model in vivo and in vitro. Hematoxylin-eosin (HE) staining was used to detect the pathological injury of lung tissues. The levels of proinflammatory cytokines in bronchoalveolar lavage fluid (BALF) and culture supernatant and the levels of oxidative stress markers in lung tissues were measured using ELISA. DCFH-DA probe was used to assess the reactive oxygen species (ROS) level. TUNEL staining and flow cytometry were performed to determine cell apoptosis. The key targets and pathways were confirmed by immunohistochemistry (IHC) and western blot. UA suppressed the pathologic damage, wet/dry weight ratio, and total protein and inflammatory cells in BALF. UA decreased neutrophil infiltration and proinflammatory cytokines production. UA reduced the level of malondialdehyde (MDA) and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in pulmonary tissues. UA also inhibited cell apoptosis in lung tissues by decreasing Bax expression and increasing Bcl-2 expression. In addition, UA suppressed LPS-induced inflammatory factor production, ROS level, and cell apoptosis in BEAS-2B. Importantly, UA decreased the expression of HMGB1 in LPS-treated mice and BEAS-2B cells. HMGB1 overexpression greatly abrogated the inhibition of UA on inflammation, ROS, and cell apoptosis in LPS-administrated BEAS-2B. Furthermore, UA treatment suppressed the phosphorylated levels of p38, JNK, ERK, and p65 in LPS-administrated mice and BEAS-2B cells. UA alleviated lung inflammation, oxidative stress, and apoptosis in ALI by targeting HMGB1 to inactivate the MAPK/NF-κB signaling, suggesting the potential of UA to treat ALI.

Integrating Network Pharmacology and Experimental Validation to Elucidate the Mechanism of Yiqi Yangyin Decoction in Suppressing Non-Small-Cell Lung Cancer.

Yiqi Yangyin Decoction (YYD) is a classic traditional Chinese medicine (TCM) formulation to treat lung cancer in clinic. Nevertheless, the active ingredients, key targets, and molecular mechanisms for YYD are still poorly understood. This study is focused on elucidating the pharmacological mechanism of YYD in non-small-cell lung cancer (NSCLC) by using a combined network pharmacology approach and biological experiment validation. Online bioinformatics tools showed that 40 bioactive compounds and 229 putative targets of YYD were associated with anti-NSCLC activity. Protein-Protein Interaction (PPI) network demonstrated AKT1, SRC, JUN, TP53, and EGFR as the top five key targets for YYD against NSCLC. Through enrichment analysis, YYD was found to affect cell proliferation and apoptosis in NSCLC possibly by PI3K-AKT signaling. Molecular docking confirmed a strong binding between the main compounds (quercetin or luteolin) and EGFR. As demonstrated by CCK-8, EdU, and colony formation assays, we found a significant inhibition of YYD on cell proliferation. Moreover, YYD treatment induced cell cycle arrest by affecting p53, p21, and cyclin D1 expression. YYD administration enhanced apoptosis by changing the expression of cleaved caspase-3, Bax, and Bcl-2. Mechanistically, YYD resulted in a significant inactivation of EGFR-PI3K-AKT signaling. Furthermore, EGFR activator significantly reversed YYD-mediated proliferation inhibition and apoptosis. YYD also showed an inhibitory effect on tumor growth in mice. Together, YYD might target the EGFR-PI3K-AKT pathway to repress NSCLC progression.

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Bushen Hugu Decoction in the Treatment of Malignant Tumor Bone Metastases.

Purpose: To explore the active compounds of the Chinese medicine prescriptions of Bushen Hugu Decoction (BHD) and demonstrate its mechanisms against malignant tumor bone metastasis (BM) through network pharmacology and molecular docking analysis. Methods: The main components and targets of BHD were retrieved from the TCMSP database, and the targets were normalized by UniProt. The Herbs-Components-Targets network of BHD was established by Cytoscape. The main BM targets were obtained from GeneCards, TTD, DrugBank, and OMIM. STRING and Cytoscape were used to construct a PPI network and obtain hub genes. DAVID and Metascape were used for GO and KEGG enrichment analyses. According to the network topology parameters, the top 4 components were selected for molecular docking verification with the core targets. Results: Compound-target network of BHD mainly contained 51 compounds and 259 corresponding targets including 107 BHD-BM targets. PPI interaction network and subnetworks identified ten hub genes. GO enrichment analysis found 1970 terms (p < 0.05), and 164 signaling pathways (p < 0.05) were found in KEGG, including PI3K-Akt signaling pathway, proteoglycans in cancer, prostate cancer, MAPK signaling pathway, and IL-17 signaling pathway. Molecular docking analysis showed that the active components of BHD, quercetin, luteolin, kaempferol, and aureusidin have good binding activity to the core targets. Conclusion: The potential molecular target and signaling pathways were found for BHD major active components. It provides guidance for the future mechanism research of the BHD in malignant tumor bone metastasis. This study also established the foundation for the new strategy for the pharmacology study of Chinese medicine.

Wenzi Jiedu Recipe ameliorates colorectal cancer by remodeling the gut microbiota and tumor microenvironment.

Introduction: Wenzi Jiedu Recipe (WJR), traditional Chinese medicine (TCM) formula, has been proven to be clinically useful in the treatment of colorectal cancer (CRC). However, its underlying mechanisms are still elusive, which limits its wider application. Thus, we aimed to evaluate the effect of WJR on CRC and elucidate mechanisms underlying its action. Methods: Network pharmacology was employed to clarify the "herb-active ingredient-target" network of WJR. The 16S rDNA sequencing method was used to analyze the changes of gut microbes mediated by WJR in tumor-bearing mice with CRC. The proportions of CD4+ T cell and CD8+ T cell were measured by flow cytometry. Levels of the cytokines interleukin (IL)-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were assessed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Results: WJR showed significant anti-CRC effects both in vitro and in vivo. Network pharmacology revealed that WJR exerts anti-CRC therapeutic effect on multiple targets and signaling pathways. Gut microbiota analysis revealed that WJR therapy significantly enriched for Oscillibacter and Bacteroides_acidifacien. In particular, we found that WJR significantly increased the proportion of CD8+ T cells and the expression of immune-associated cytokines IL-10, IFN-γ, and TNF-α. Conclusion: The regulation of gut microbiota by WJR may be the breakthrough point to clarify its mechanism of action in the treatment of CRC, and it has a good prospect of clinical application.

Molecular mechanism of betulin palliative therapy for chronic obstructive pulmonary disease (COPD) based on P2X7 receptor target of gated ion channel.

Background: The aim of this study was to discover the molecular mechanism of betulin palliative therapy for chronic obstructive pulmonary disease (COPD) based on the P2X7 receptor target of gated ion channel. Methods: A COPD mouse model was developed. Changes in pulmonary ventilation function, pulmonary airway and vascular remodeling indicators, inflammatory cells, and inflammatory factors were determined after betulin intervention, and the pathological alterations of lung tissues were detected. An in vitro experimental model was constructed to observe the influence of betulin at varying concentrations on the proliferation of human bronchial epidermal cell line (16-HBE) cells and changes in inflammatory factors in cell supernatant. The expression levels of key proteins in 16-HBE cells transfected with overexpressed or silenced P2X7 genes were determined through quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. Results: After betulin intervention, pulmonary ventilation function in the 20 mg/kg betulin and 40 mg/kg betulin groups was improved. Levels of white blood cells (WBCs), neutrophils (Ns), tumor necrosis factor (TNF), TNF-ɑ, interleukin (IL)-1ß, and IL-6 in the 2 groups also decreased significantly (all P<0.05). The pathological changes in COPD mice were detected. After betulin intervention, the pathological injury of the lung was reduced, the pathological score decreased significantly, and the remodeling indicators of pulmonary airway and pulmonary vessels diminished remarkably (all P<0.05). Betulin had no effect on the proliferation of 16-HBE cells in vitro. After cigarette smoke extract (CSE) stimulation, the rate of survival for 16-HBE cells decreased significantly. After betulin treatment, the survival rate of 16-HBE cells augmented remarkably, and the levels of TNF-ɑ, IL-6, and IL-1ß in cell supernatant reduced substantially (all P<0.05). 16-HBE with overexpression and knockdown of P2X7 was constructed. After being treated with betulin, the relative expression levels of messenger RNA (mRNA) of ERK, JNK, rho-associated protein kinase (ROCK), nuclear factor-κB (NF-κB), and p38 in 16-HBE cells with P2X7 overexpression or knockdown were decreased significantly (all P<0.05), but the above indicators were largely unchanged (all P>0.05). Conclusions: Betulin relieved lung pathological injury, ameliorated lung ventilation function, and diminished the level of inflammatory factors in COPD mice, playing a therapeutic role via the P2X7 signaling pathway.

Efficacy and Safety of Qili Qiangxin Capsule on Dilated Cardiomyopathy: A Systematic Review and Meta-Analysis of 35 Randomized Controlled Trials.

Objective: Qili Qiangxin Capsule (QQC), a Chinese patent medicine, is clinically effective in treating dilated cardiomyopathy (DCM). However, the meta-analysis of QCC combined with conventional western medicine (CWM) on DCM remains unexplored. This study aimed to systematically evaluate the efficacy and safety of QCC in the treatment of DCM. Methods: Searched the studies of the combination of QQC and CWM in the treatment of DCM, from databases like PubMed, Cochrane Library, Web of Science, Wan Fang Databases, Chinese Biomedical Literature Database, China Science and Technology Journal Database, China National Knowledge Infrastructure, prior to 15 January 2022. Two reviewers respectively regulated research selection, data extraction, and risk of bias assessment. Review Manager Software 5.4 was used for meta-analysis. Furthermore, GRADE pro3.6.1 software was selected to grade the current evidence in our findings. This meta-analysis has been registered in PROSPERO (CRD42022297906). Results: There were 35 studies pertaining to 3,334 patients included. The meta-analysis showed compared with CWM alone, the combination therapy had significant advantages in improving the clinical efficiency rate (RR = 1.24, 95% CI: 1.19 to 1.29, p < 0.00001), 6 min walking distance (6MWD) (MD = 41.93, 95%CI: 39.82 to 44.04, p < 0.00001), superior in ameliorating the left ventricular ejection fraction (LVEF) (MD = 5.73, 95%CI: 4.70 to 6.77, p < 0.00001), left ventricular end-diastolic dimension (LVEDD) (MD = -4.09, 95%CI: -4.91 to -3.27), p < 0.00001), left ventricular end-systolic diameter (LVESD) (MD = -4.73, 95%CI: -5.63 to -3.84), p < 0.00001) and BNP (MD = -101.09, 95%CI: -132.99 to -69.18), p < 0.00001), and also superior in reducing hypersensitive-C-Reactive Protein (hs-CRP) (MD = -3.78, 95%CI: -4.35 to -3.21), p < 0.00001), Interleukin- 6 (IL-6) (MD = -25.92, 95%CI: -31.35 to -20.50), p < 0.00001), tumor necrosis factor-α (TNF-α) (MD = -5.04, 95%CI: -6.13 to -3.95), p < 0.00001), high mobility group protein B1 (HMGB1) (MD = -4.34, 95%CI: -5.22 to -3.46), p < 0.00001), and adverse reactions (ARs) (RR = 0.70, 95%CI: 0.51-0.97), p = 0.03). The GRADE evidence quality rating presented with moderate or low quality of evidence for the available data. Conclusion: Compared with the control group, QQC combined with CWM may be effective in treating DCM. However, the conclusion of this study must be interpreted carefully due to the inferior quality and ambiguity of bias in the included trials. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier [CRD42022297906].

Investigation of the differences between the medical personnel's and general population's view on the doctor-patient relationship in China by a cross-sectional survey.

BACKGROUND: Due to economic development and an increase in the aging population, the demand for medical resources is increasing. A good doctor-patient relationship (DPR) can optimize patients' medical experience and improve treatment efficiency. The DPR, however, is currently in crisis in China. To explore ways to improve DPR, this study assessed the views on the status of the DPR, medical services, and the general situation of medical work among medical personnel (MP) and the general population (GP). METHODS: This cross-sectional study, conducted between December 2019 and March 2020, targeted the MP and the GP in Nanjing City, Jiangsu Province, and Zhengzhou City, Henan Province. A total of 154 MP and 329 GP answered a self-administered questionnaire through Questionnaire Star and WeChat apps. Wilcoxon's Sign Rank Test, Chi-square test, and frequency distributions and percentages were used to process the data. RESULTS: Only 11.04% of the MP and 14.89% of the GP believed that the current DPR was harmonious. Moreover, 54.55% of the MP and 71.12% of the GP believed that the medical industry was a service industry. While 14.29% of the MP and 64.44% of the GP thought medical staff earned high salaries, 19.48% of the MP and 47.11% of the GP wanted their children to be in the medical industry. The recognition of the current status of the DPR did not affect the GP's preference for their children's practice (p < 0.05). Most MPs hoped to improve salaries (40.26%), followed by safety (17.53%) and social status (12.99%); only 8.44% of the MP wanted to improve the DPR. CONCLUSION: The MP's and GP's views on the current status of DPR, the importance of medical service attitudes, and the general sense of the medical industry were similar. However, there was a significant difference in the perception of the nature of medical services and the income of the people employed in the medical industry between the two groups. Balancing the expectations of patients in the medical industry and increasing public awareness of the actual situation in the medical industry may be a feasible way to improve the DPR.

The Relationship between Prevention and Treatment of Colorectal Cancer and Cancerous Toxin Pathogenesis Theory Basing on Gut Microbiota.

Gut microbiota is a diverse consortium of bacteria, fungi, protozoa, and viruses in the gut of all mammals. Gut microbiota remains in steady state under normal conditions. Changes in the internal and external environment may cause gut Microbiota to be out of tune. Malignant tumors are one of the major diseases currently endangering human health. CRC (colorectal cancer) has a significant upward trend in morbidity and mortality in many parts of the world. Technological advances have not yet brought about a breakthrough in the efficacy of CRC. The development of colon cancer is closely related to gut microbiota imbalance. According to more than 60 years of clinical practice, Professor Zhongying Zhou first proposed the pathogenesis theory of "cancerous toxin" in the 1990s and believed that cancerous toxin was a key pathogenesis of tumor development. Under the guidance of the theory of cancerous toxin, combined with clinical practice, Professor Zhou created an effective anticancer Chinese herbal compound, Jiedu Xiaoai Prescription. This paper summarizes recent hotspots related to gut microbiota and the occurrence, development, and prevention of colon cancer at home and abroad. The relationship between gut microbiota and cancerous toxin theory is proposed, and the feasibility of further studying the biological basis of cancerous toxin pathogenesis theory from the perspective of gut microbiota is pointed out.

A Survey on Perceptions of Complementary and Alternative Medicine among Undergraduates in China.

In recent years, complementary and alternative medicine (CAM) is more widely known and used globally. This study was the first to investigate undergraduates' attitude toward CAM, and influencing factors and barriers for students to use CAM. Students of five different grades in six universities of China were selected for this study from February to May 2019. First, the participants were divided into two groups based on their majors and fulfilled a previously validated 10-item CAM Health Belief Questionnaire (CHBQ) to evaluate their attitudes toward CAM. Second, the chi-square test was used to analyze the differences between the groups, and correlation analysis was conducted to investigate the relationship of the data between the two groups. Third, we used frequency analysis to identify the types that students wanted to study and the barriers to use CAM. The overall mean score of the CHBQ was 48.87 ± 8.594, which was higher than that in other countries. The students in lower grades had a stronger desire to learn CAM than those in higher grades (89% vs 83%, p < 0.05). "Too time-consuming and bad tastes," "Western medicine was enough," and "lack of relevant knowledge" were found to be the main interruptions for students to use CAM. 82.3% of students wanted CAM to be incorporated into the curriculum and desired to learn more about CAM. 72.3% of the students who had never learned CAM wanted to know more about CAM. 55.5% of the students were willing to recommend CAM. Most undergraduates desired to learn more about CAM. It is necessary to introduce or integrate CAM courses into the present curriculum, and it should be started in the lower grades. We hope this study can provide evidence for the authority in China to make appropriate changes and integrate CAM into the college curriculum.