Vol 27, No 3 (2024)

Rheumatoid Arthritis (RA) is an autoimmune disorder that generally causes joint synovial inflammation as well as gradual cartilage and degenerative changes, resulting in progressive immobility. Cartilage destruction induces synovial inflammation, including synovial cell hyperplasia, increased synovial fluid, and synovial pane development. This phenomenon causes articular cartilage damage and joint alkalosis. Traditional medicinal system exerts their effect through several cellular mechanisms, including inhibition of inflammatory mediators, oxidative stress suppression, cartilage degradation inhibition, increasing antioxidants and decreasing rheumatic biomarkers. The medicinal plants have yielded a variety of active constituents from various chemical categories, including alkaloids, triterpenoids, steroids, glycosides, volatile oils, flavonoids, lignans, coumarins, terpenes, sesquiterpene lactones, anthocyanins, and anthraquinones. This review sheds light on the utilization of medicinal plants in the treatment of RA. It explains various phytoconstituents present in medicinal plants and their mechanism of action against RA. It also briefs about the uses of polyherbal formulations (PHF), which are currently in the market and the toxicity associated with the use of medicinal plants and PHF, along with the limitations and research gaps in the field of PHF. This review paper is an attempt to understand various mechanistic approaches employed by several medicinal plants, their possible drug delivery systems and synergistic effects for curing RA with minimum side effects.

Introduction:To understand the risk factors of asthma, we combined genome-wide association study (GWAS) risk loci and clinical data in predicting asthma using machine-learning approaches.

Methods:A case-control study with 123 asthmatics and 100 controls was conducted in the Zhuang population in Guangxi. GWAS risk loci were detected using polymerase chain reaction, and clinical data were collected. Machine-learning approaches were used to identify the major factors that contribute to asthma.

Results:A total of 14 GWAS risk loci with clinical data were analyzed on the basis of 10 times the 10-fold cross-validation for all machine-learning models. Using GWAS risk loci or clinical data, the best performances exhibited area under the curve (AUC) values of 64.3% and 71.4%, respectively. Combining GWAS risk loci and clinical data, the XGBoost established the best model with an AUC of 79.7%, indicating that the combination of genetics and clinical data can enable improved performance. We then sorted the importance of features and found the top six risk factors for predicting asthma to be rs3117098, rs7775228, family history, rs2305480, rs4833095, and body mass index.

Conclusion:Asthma-prediction models based on GWAS risk loci and clinical data can accurately predict asthma, and thus provide insights into the disease pathogenesis.

Aims:We aim to explore new potential therapeutic targets and markers in human glioma

Background:Gliomas are the most common malignant primary tumor in the brain.

Objective:In the present research, we evaluated the effect of CAI2, a long non-coding RNA, on the biological behaviors of glioma and explored the related molecular mechanism.

Methods:The expression of CAI2 was analyzed using qRT-PCR in 65 cases of glioma patients. The cell proliferation was determined with MTT and colony formation assays, and the PI3K-AKt signaling pathway was analyzed using western blot.

Results:CAI2 was upregulated in human glioma tissue compared with the matched, adjacent nontumor tissue and was correlated with WHO grade. Survival analyses proved that the overall survival of patients with high CAI2 expression was poor compared to that of patients with low CAI2 expression. High CAI2 expression was an independent prognostic factor in glioma. The absorbance values in the MTT assay after 96 h were .712 ± .031 for the si-control and .465 ± .018 for the si- CAI2-transfected cells, and si-CAI2 inhibited colony formation in U251 cells by approximately 80%. The levels of PI3K, p-AKt, and AKt in si-CAI2-treated cells were decreased.

Conclusion:CAI2 may promote glioma growth through the PI3K-AKt signaling pathway. This research provided a novel potential diagnostic marker for human glioma.

Background:The improvements in the treatment of colorectal cancer (CRC) and prolongation of survival time have improved the incidence of bone metastasis. Forkhead box D3 (FOXD3) is involved in the development of CRC. However, the role and mechanism of FOXD3 in CRC bone metastases development are unknown.

Objective:Using the combined bioinformatics and cytology experimental analyses, this study aimed to explore the mechanistic role of FOXD3 in the bone metastasis of colon cancer, thereby aiding in the treatment of colon cancer bone metastasis and identification of drug-targeting markers.

Methods:First, the changes in the expression levels of the FOXD3 gene and differentially expressed genes (DEGs) between the colon cancer samples and colon cancer metastases were obtained from The Cancer Genome Atlas (TCGA) database. Then, the correlations of the FOXD3 gene with the DEGs were identified. Next, the effects of the FOXD3 on the proliferation and invasion abilities of colon cancer bone metastatic cells were identified using Cell Counting Kit-8 (CCK8) and Transwell cell migration assays, respectively. In addition, Western blot analysis was used to identify the expression levels of the proteins related to the EGFR/Ras/Raf/MEK/ERK (EGFR/ERK) signaling pathway and epithelial-to-mesenchymal transition (EMT).

Results:FOXD3 was downregulated in colon cancer and could interact with multiple DEGs in colon cancer bone metastases. FOXD3 gene knockdown could increase the proliferation of human colon cancer bone metastatic cells and their invasive ability. FOXD3 gene knockdown could activate the expression of EGFR/ERK signaling pathway-related proteins and inhibit/promote the expression of EMT-related proteins, which in turn promoted the proliferation and metastasis of LoVo cells from colon cancer bone metastases.

Conclusion:Overall, this study demonstrated that the downregulation of the FOXD3 gene might promote the proliferation of colon cancer bone metastatic cell lines through the EGFR/ERK pathway and promote their migration through EMT, thereby serving as a promising therapeutic target.

Background:Recent research indicates that clopidogrel resistance is connected with a patient's future ischemia risk, hence increasing the likelihood of recurrent ischemic cerebrovascular disease. Thromboelastographic and clopidogrel gene polymorphism testing can be used to see how a person responds to antiplatelet therapy and change the treatment plan accordingly. This may be a good way to make antiplatelet aggregation therapy more effective and safer

Objective:The objective of this study was to investigate the efficacy of dual antiplatelet aggregation therapy in patients with symptomatic intracranial large artery stenosis being resistant to clopidogrel tablets. The thromboelastographic and gene polymorphism bimodality detection techniques were used to analyze the clopidogrel resistance influencing factors.

Methods:89 patients with symptomatic intracranial large arterial stenosis who were admitted to our hospital from February 2021 to February 2022 were selected, classified as large artery atherosclerotic type by TOAST, and confirmed as having severe intracranial large arterial stenosis (70 % to 99 %) by magnetic resonance angiography (MRA), computed tomographic angiography (CTA), and digital subtraction angiography (DSA). All patients were treated with dual antiplatelet therapy with aspirin and clopidogrel, and thromboelastography and clopidogrel gene polymorphism were monitored 1 week later.

Results:44 of 89 patients were clopidogrel-resistant. Among 44 patients, 20 were ticagrelorresistant and 24 were cilostazol-resistant. Clopidogrel had a resistance rate of 49.4%. The recurrence of ischemic cerebrovascular disease in the three groups was statistically significant (P(<0.05) after 3 months of follow-up treatment, but bleeding (intracranial, gastrointestinal, respiratory, urinary, and mucocutaneous) and dyspnea were not. The clopidogrel-resistant group had a higher number of females, as well as higher levels of hypertension, diabetes, and platelet count than the sensitive group (P(<0.05), but there was no significant difference in age, smoking, alcohol consumption, previous stroke, glycosylated haemoglobin, creatinine, or low-density cholesterol.

Conclusion:Using thromboelastographic and gene polymorphism bimodality detection, we found switching to ticagrelor antiplatelet aggregation therapy as better than switching to cilostazol in patients with symptomatic intracranial large artery stenosis being resistant to clopidogrel tablets. The results may be biased due to the study being a single-centre study and having a limited sample size.

Aim:This study investigated the molecular action mechanism of a compound herb, also known as the Dendrobium officinale throat-clearing formula (QYF), by using network pharmacology and animal experimental validation methods to treat chronic pharyngitis (CP).

Methods:The active ingredients and disease targets of QYF were determined by searching the Batman-TCM and GeneCards databases. Subsequently, the drug-active ingredient-target and protein-protein interaction networks were constructed, and the core targets were obtained through network topology. The Metascape database was screened, and the core targets were enriched with Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes.

Results:In total, 1403 and 241 potential targets for drugs and diseases, respectively, and 81 intersecting targets were yielded. The core targets included TNF, IL-6, and IL-1β, and the core pathways included PI3K-Akt. The QYF treatment group exhibited effectively improved general signs, enhanced anti-inflammatory ability in vitro, reduced serum and tissue expressions of TNF- α, IL-6, and IL-1β inflammatory factors, and decreased blood LPS levels and Myd88, TLR4, PI3K, Akt, and NF-κB p65 protein expression in the tissues.

Conclusion:QYF could inhibit LPS production, which regulated the expression of the TLR4/PI3K/Akt/NF-κB signaling pathway to suppress the expression of the related inflammatory factors (i.e., TNF-α, IL-6, and IL-1β), thereby alleviating the CP process.