Molecular mechanism of regulating tat protein expression of pingganjiedu TCM in the treatment of AIDS based on network pharmacology.

AIDS is a serious disease with impaired immune function caused by human immunodeficiency virus (HIV) infection. The treatment of AIDS has always been the focus of global scientific research, and Tat protein is a key regulatory protein in the process of HIV infection. Its high expression is closely related to virus replication, disease progression, etc. The aim of this study is to explore the molecular mechanism of regulating Tat protein expression by using network pharmacology based traditional Chinese medicine for calming the liver and detoxifying. 129 AIDS patients were enrolled in the study and randomly divided into HAART combined with PGJDP treatment and HAART alone treatment groups. The virological response rate, immunological response status (CD4 + T cell level, CD4/CD8) and incidence of abnormal liver function were observed before and 48 weeks after treatment. Using the TCMSP database to obtain the chemical components and targets of the main traditional Chinese medicine components in PGJDP, clinical results indicate that the combination of HAART and PGJDP treatment can improve the virological response rate (P > 0.05); Increase the number of CD4 + T lymphocytes (P > 0.05); Significantly increased CD4/CD8 ratio (P < 0.01); Simultaneously, it significantly reduced the incidence of liver dysfunction (P < 0.01). After screening and analysis, the Chinese herbal medicine for calming liver and detoxifying has the potential to significantly regulate the expression of Tat protein. These Chinese herbal compounds can reduce the expression of Tat protein by affecting key pathways and regulating the expression of related genes, which has potential therapeutic effects on the treatment of AIDS.

Metallothionein III Decreases the Proliferation of Astrocytes and Enhances Pathological Improvements in a Mouse Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) affects the brain and causes difficulties with cognition and emotions. At present, there are no viable therapies to halt or slow down the advancement of AD. Metallothionein III (MT-III) exhibits antioxidant and anti-inflammatory characteristics, indicating possible therapeutic benefits. This study aimed to explore the influence of MT-III on AD pathological alterations and cognitive abilities. METHODS: In this research, we employed the universally accepted AD mouse models (3xTg-AD) as test subjects and administrated vehicle or MT-III. The mice were subjected to the Morris water maze test to assess their spatial learning and memory capabilities. Moreover, to evaluate the consequent effects on neuronal groups in the hippocampus, the Nissl staining and neuronal nuclear antigen (NeuN) immunohistochemistry were used to identify the cellular morphology changes and density. Immunohistochemistry was also used to detect ß-amyloid (Aß) and glial fibrillary acidic protein (GFAP) to measure Aß accumulation and astrocyte growth. Western blot was also used to measure Tau pathology-related PHD finger protein 1 (PHF-1), phosphorylated Tau (AT-8), and total Tau protein. RESULTS: The administration of MT-III notably enhanced spatial learning and memory function in 3xTg-AD mice, as evidenced by the Morris water maze test (p < 0.01). According to immunohistochemistry and the obtained findings, it was observed that brain tissues of mice treated with MT-III showed a notable increase of Nissl bodies and NeuN intensity (p < 0.01) while a remarkable decrease in Aß accumulation and GFAP (p < 0.01). Additionally, MT-III largely decreased levels of Tau phosphorylation-related PHF-1 and AT-8 (p < 0.01) and slightly reduced the level of Tau 5 (p < 0.05). CONCLUSION: In summary, our research indicates that MT-III has the capacity to ameliorate pathological alterations in AD mouse models and safeguard their cognitive and emotional abilities. By decreasing ß-amyloid accumulation and reducing the intensity of Tau pathology, MT-III protected hippocampal subfield neurons against pathological harm. Furthermore, MT-III reduced inflammation by inhibiting abnormal proliferation of astrocytes. Of utmost importance, MT-III greatly enhanced the cognitive abilities related to spatial learning and memory in mice, suggesting its promising therapeutic properties for AD.

Predictive model and risk analysis for coronary heart disease in people living with HIV using machine learning.

OBJECTIVE: This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs). METHODS: Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model. RESULTS: The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814-0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD. CONCLUSION: This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.

CagA-positive Helicobacter pylori may promote and aggravate scrub typhus.

Helicobacter pylori (H. pylori) infection may alter the host's resistance to tsutsugamushi disease pathogens through the Th1 immune response, leading to potential synergistic pathogenic effects. A total of 117 scrub typhus cases at Beihai People's Hospital and affiliated hospitals of Youjiang University for Nationalities and Medical Sciences were studied from January to December 2022, alongside 130 healthy individuals forming the control group. All participants underwent serum H. pylori antibody testing. The prevalence of H. pylori infection was significantly higher among scrub typhus patients (89.7%) compared to healthy individuals (54.6%) (p < 0.05). Moreover, type I H. pylori infection was notably more prevalent in scrub typhus cases (67.5%) compared to healthy individuals (30%) (p < 0.05). Multifactorial analysis demonstrated type I H. pylori infection as an independent risk factor for scrub typhus (adjusted odds ratio: 2.407, 95% confidence interval: 1.249-4.64, p = 0.009). Among scrub typhus patients with multiple organ damage, the prevalence of type I H. pylori infection was significantly higher (50.6%) than type II H. pylori infection (15.4%) (χ2 = 4.735, p = 0.030). These results highlight a higher incidence of H. pylori infection in scrub typhus patients compared to the healthy population. Additionally, type I H. pylori strain emerged as an independent risk factor for scrub typhus development. Moreover, individuals infected with type I H. pylori are more susceptible to multiple organ damage. These findings suggest a potential role of H. pylori carrying the CagA gene in promoting and exacerbating scrub typhus.