Xiaoer niuhuang qingxin powder alleviates influenza a virus infection by inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoer Niuhuang Qingxin Powder (XNQP) is a classic traditional Chinese medicine formula with significant clinical efficacy for treating febrile convulsions and influenza. AIM OF THE STUDY: This study aims to explore the potential mechanisms of XNQP in combating combating the influenza A virus, providing a theoretical basis for its clinical application. MATERIALS AND METHODS: The present investigation employed network pharmacology and bioinformatics analysis to determine the TLR4/MyD88/NF-κB signaling pathway as a viable target for XNQP intervention in IAV infection.Subsequently, a mouse model of influenza A virus infection was established, and different doses of XNQP were used for intervention. The protein expression levels of TLR4/MyD88/NF-κB were detected using HE staining, Elisa, immunohistochemistry, immunofluorescence, and western blot. RESULTS: The results showed that treatment with XNQP after IAV infection reduced the mortality and prolonged the survival time of infected mice. It reduced the release of TNF-α and IFN-γ in the serum and alleviated pathological damage in the lung tissue following infection. Additionally, the levels of TLR4, MyD88, NF-κB, and p-NF-κB P65 proteins were significantly reduced in lung tissue by XNQP. The inhibitory effect of XNQP on the expression of MyD88 and NF-κB was antagonized when TLR4 signaling was overexpressed. Consequently, the expression levels of MyD88, NF-κB, and p-NF-κB P65 were increased in lung tissue. Conversely, the expression levels of the proteins MyD88, NF-κB, and p-NF-κB P65 were downregulated when TLR4 signaling was inhibited. CONCLUSIONS: XNQP alleviated lung pathological changes, reduced serum levels of inflammatory factors, reduced mortality, and prolonged survival time in mice by inhibiting the overexpression of the TLR4/MyD88/NF-κB signaling pathway in lung tissues after IAV infection.

Research progress on the mechanism of traditional Chinese medicine regulating intestinal microbiota to combat influenza a virus infection.

Influenza A viruses (IAV) are a prevalent respiratory pathogen that can cause seasonal flu and global pandemics, posing a significant global public health threat. Emerging research suggests that IAV infections may disrupt the balance of gut microbiota, while gut dysbiosis can affect disease progression in IAV patients. Therefore, restoring gut microbiota balance may represent a promising therapeutic target for IAV infections. Traditional Chinese medicine, with its ability to regulate gut microbiota, offers significant potential in preventing and treating IAV. This article provides a comprehensive review of the relationship between IAV and gut microbiota, highlighting the impact of gut microbiota on IAV infections. It also explores the mechanisms and role of traditional Chinese medicine in regulating gut microbiota for the prevention and treatment of IAV, presenting novel research avenues for traditional Chinese medicine-based IAV treatments.

Identification of bioactive compounds and potential mechanisms of scutellariae radix-coptidis rhizoma in the treatment of atherosclerosis by integrating network pharmacology and experimental validation.

OBJECTIVE: This study aims at investigating the potential targets and functional mechanisms of Scutellariae Radix-Coptidis Rhizoma (QLYD) against atherosclerosis (AS) through network pharmacology, molecular docking, bioinformatic analysis and experimental validation. METHODS: The compositions of QLYD were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature, where the main active components of QLYD and corresponding targets were identified. The potential therapeutic targets of AS were excavated using the OMIM database, DrugBank database, DisGeNET database, CTD database and GEO datasets. The protein-protein interaction (PPI) network of common targets was constructed and visualized by Cytoscape 3.7.2 software. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to analyze the function of core targets in the PPI network. Molecular docking was carried out using AutoDockTools, AutoDock Vina, and PyMOL software to verify the correlation between the main components of QLYD and the core targets. Mouse AS model was established and the results of network pharmacology were verified by in vivo experiments. RESULTS: Totally 49 active components and 225 corresponding targets of QLYD were obtained, where 68 common targets were identified by intersecting with AS-related targets. Five hub genes including IL6, VEGFA, AKT1, TNF, and IL1B were screened from the PPI network. GO functional analysis reported that these targets had associations mainly with cellular response to oxidative stress, regulation of inflammatory response, epithelial cell apoptotic process, and blood coagulation. KEGG pathway analysis demonstrated that these targets were correlated to AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, and NF-kappa B signaling pathway. Results of molecular docking indicated good binding affinity of QLYD to FOS, AKT1, and TNF. Animal experiments showed that QLYD could inhibit inflammation, improve blood lipid levels and reduce plaque area in AS mice to prevent and treat AS. CONCLUSION: QLYD may exert anti-inflammatory and anti-oxidative stress effects through multi-component, multi-target and multi-pathway to treat AS.

Inhibition of Non-small Cell Lung Cancer by Ferroptosis and Apoptosis Induction through P53 and GSK-3ß/Nrf2 Signal Pathways using Qingrehuoxue Formula.

This study aimed to elucidate the effects of Qingrehuoxue Formula (QRHXF) on NSCLC and its underlying mechanisms. Nude mouse model of subcutaneous tumors was established. QRHXF and erastin were administered orally and intraperitoneally, respectively. Mice's body weight and subcutaneous tumor volumes were measured. The effects of QRHXF on epithelial-mesenchymal transition (EMT), tumor-associated angiogenesis and matrix metalloproteinases (MMPs) were assessed. Importantly, we also analysed the anti-NSCLC of QRHXF form the aspect of ferroptosis and apoptosis and investigate its underlying mechanisms. The safety of QRHXF in mice was also evaluated. QRHXF slowed down the speed of tumor growth and visibly inhibited tumor growth. The expression levels of CD31, VEGFA, MMP2 and MMP9 were prominently suppressed by QRHXF. Furthermore, QRHXF appeared to remarkably inhibite cell proliferation and EMT by decreasing Ki67, N-cadherin and vimentin expression but elevating E-cadherin expression. There were more apoptotic cells in QRHXF group's tumor tissues, and QRHXF treatment increased BAX and cleaved-caspased 3 levels but decreased Bcl-2 levels. QRHXF significantly increased the accumulation of ROS, Fe2+, H2O2, and MDA while reduced GSH levels. SLC7A11 and GPX4 protein levels were considerably suppressed by QRHXF treatment. Moreover, QRHXF triggered ultrastructural changes in the mitochondria of tumor cells. The levels of p53 and p-GSK-3ß were upregulated, whereas that of Nrf2 was downregulated in the groups treated with QRHXF. QRHXF displayed no toxicity in mice. QRHXF activated ferroptosis and apoptosis to suppress NSCLC cell progression via p53 and GSK-3ß/Nrf2 signaling pathways.

Active Surveillance for Prostate Cancer: Are We Failing Latino Patients at a Large Safety Net Hospital?

INTRODUCTION: Active surveillance (AS) is one recommended option for low-risk prostate cancer and involves close follow-up and monitoring. Our objective was to determine whether non-clinical trial patients adhere to AS protocols and how many are lost to follow-up (LTFU). PATIENTS AND METHODS: Retrospective chart review was performed for patients with nonmetastatic prostate cancer who initiated AS at Los Angeles County Hospital (LAC) and University of Southern California Norris Comprehensive Cancer Center (Norris) between January 1, 2008, and January 1, 2015. Competing-risks regression analyses examined the difference in LTFU rates of AS patients in the 2 institutions and examined the association between LTFU and patient characteristics. We used California Cancer Registry data to verify if patients LTFU were monitored and/or treated at other LAC medical facilities. RESULTS: We found 116 patients at LAC and 98 at Norris who met the AS criteria for this study. Patients at LAC and Norris had similar tumor characteristics but differed in median income, race, primary language spoken, distance residing from hospital, and socioeconomic status (SES). LTFU was significantly different between the institutions: 57 ± 7% at LAC and 32 ± 6% at Norris at 5 years (P < .001). By multivariable analysis, the main determinant of LTFU was SES (P = .045). By 5 years, the chance of an LAC patient remaining on AS was 8 ± 6% compared to 20 ± 6% for a Norris patient (P < .001). CONCLUSION: Successful AS implementation relies on patient follow-up. We found that patients on AS from lower SES strata are more often LTFU. Identifying barriers to follow-up and compliance among low SES patients is critical to ensure optimal AS.

Thyroid and hepatic function after high-dose 131 I-metaiodobenzylguanidine (131 I-MIBG) therapy for neuroblastoma.

BACKGROUND: (131) I-Metaiodobenzylguanidine ((131) I-MIBG) provides targeted radiotherapy for children with neuroblastoma, a malignancy of the sympathetic nervous system. Dissociated radioactive iodide may concentrate in the thyroid, and (131) I-MIBG is concentrated in the liver after (131) I-MIBG therapy. The aim of our study was to analyze the effects of (131) I-MIBG therapy on thyroid and liver function. PROCEDURE: Pre- and post-therapy thyroid and liver functions were reviewed in a total of 194 neuroblastoma patients treated with (131) I-MIBG therapy. The cumulative incidence over time was estimated for both thyroid and liver toxicities. The relationship to cumulative dose/kg, number of treatments, time from treatment to follow-up, sex, and patient age was examined. RESULTS: In patients who presented with Grade 0 or 1 thyroid toxicity at baseline, 12 ± 4% experienced onset of or worsening to Grade 2 hypothyroidism and one patient developed Grade 2 hyperthyroidism by 2 years after (131) I-MIBG therapy. At 2 years post-(131) I-MIBG therapy, 76 ± 4% patients experienced onset or worsening of hepatic toxicity to any grade, and 23 ± 5% experienced onset of or worsening to Grade 3 or 4 liver toxicity. Liver toxicity was usually transient asymptomatic transaminase elevation, frequently confounded by disease progression and other therapies. CONCLUSION: The prophylactic regimen of potassium iodide and potassium perchlorate with (131) I-MIBG therapy resulted in a low rate of significant hypothyroidism. Liver abnormalities following (131) I-MIBG therapy were primarily reversible and did not result in late toxicity. (131) I-MIBG therapy is a promising treatment for children with relapsed neuroblastoma with a relatively low rate of symptomatic thyroid or hepatic dysfunction.