Babaodan overcomes cisplatin resistance in cholangiocarcinoma via inhibiting YAP1.

CONTEXT: Cholangiocarcinoma with highly heterogeneous, aggressive, and multidrug resistance has a poor prognosis. Although babaodan (BBD) combined with cisplatin improved non-small cell lung cancer efficacy, its impact on overcoming resistance in cholangiocarcinoma remains unexplored. OBJECTIVE: This study explored the role and mechanism of BBD on cisplatin resistance in cholangiocarcinoma cells (CCAs). MATERIALS AND METHODS: Cisplatin-resistant CCAs were exposed to varying concentrations of cisplatin (25-400 µg/mL) or BBD (0.25-1.00 mg/mL) for 48 h. IC50 values, inhibition ratios, apoptosis levels, DNA damage, glutathione (GSH) levels, oxidized forms of GSH, total GSH content, and glutaminase relative activity were evaluated using the cell counting kit 8, flow cytometry, comet assay, and relevant assay kits. RESULTS: BBD-reduced the cisplatin IC50 in CCAs from 118.8 to 61.83 µg/mL, leading to increased inhibition rate, apoptosis, and DNA damage, and decreased expression of B-cell lymphoma-2, p-Yes-associated protein 1/Yes-associated protein 1, solute carrier family 1 member 5, activating transcription factor 4, and ERCC excision repair 1 in a dose-dependent manner with maximum reductions of 78.97%, 51.98%, 54.03%, 56.59%, and 63.22%, respectively; bcl2-associated X and gamma histone levels were increased by 0.43-115.77% and 22.15-53.39%. The impact of YAP1 knockdown on cisplatin-resistant CCAs resembled BBD. GSH, oxidized GSH species, total GSH content, and glutaminase activity in cisplatin-resistant CCAs with BBD treatment also decreased, while YAP1 overexpression countered BBD's effects. DISCUSSION AND CONCLUSION: This study provides a scientific basis for BBD clinical application and provides a new direction for BBD biological mechanism research.

Binary classification of non-specific low back pain condition based on the combination of B-mode ultrasound and shear wave elastography at multiple sites.

Introduction: Low back pain (LBP) is a prevalent and complex condition that poses significant medical, social, and economic burdens worldwide. The accurate and timely assessment and diagnosis of LBP, particularly non-specific LBP (NSLBP), are crucial to developing effective interventions and treatments for LBP patients. In this study, we aimed to investigate the potential of combining B-mode ultrasound image features with shear wave elastography (SWE) features to improve the classification of NSLBP patients. Methods: We recruited 52 subjects with NSLBP from the University of Hong Kong-Shenzhen Hospital and collected B-mode ultrasound images and SWE data from multiple sites. The Visual Analogue Scale (VAS) was used as the ground truth to classify NSLBP patients. We extracted and selected features from the data and employed a support vector machine (SVM) model to classify NSLBP patients. The performance of the SVM model was evaluated using five-fold cross-validation and the accuracy, precision, and sensitivity were calculated. Results: We obtained an optimal feature set of 48 features, among which the SWE elasticity feature had the most significant contribution to the classification task. The SVM model achieved an accuracy, precision, and sensitivity of 0.85, 0.89, and 0.86, respectively, which were higher than the previously reported values of MRI. Discussion: In this study, we aimed to investigate the potential of combining B-mode ultrasound image features with shear wave elastography (SWE) features to improve the classification of non-specific low back pain (NSLBP) patients. Our results showed that combining B-mode ultrasound image features with SWE features and employing an SVM model can improve the automatic classification of NSLBP patients. Our findings also suggest that the SWE elasticity feature is a crucial factor in classifying NSLBP patients, and the proposed method can identify the important site and position of the muscle in the NSLBP classification task.

Secondary Metabolites of Osmanthus fragrans: Metabolism and Medicinal Value.

Osmanthus fragrans (scientific name: Osmanthus fragrans (Thunb.) Lour.) is a species of the Osmanthus genus in the family Oleaceae, and it has a long history of cultivation in China. O. fragrans is edible and is well known for conferring a natural fragrance to desserts. This flowering plant has long been cultivated for ornamental purposes. Most contemporary literature related to O. fragrans focuses on its edible value and new species discovery, but the functional use of O. fragrans is often neglected. O, fragrans has many properties that are beneficial to human health, and its roots, stems, leaves, flowers and fruits have medicinal value. These characteristics are recorded in the classics of traditional Chinese medicine. Studies on the metabolites and medicinal value of O. fragrans published in recent years were used in this study to evaluate the medicinal value of O. fragrans. Using keywords such as metabolites and Osmanthus fragrans, a systematic and nonexhaustive search of articles, papers and books related to the medicinal use of Osmanthus fragrans metabolites was conducted. Fifteen metabolites were identified through this literature search and classified into three categories according to their properties and structure: flavonoids, terpenes and phenolic acids. It was found that the pharmacological activities of these secondary metabolites mainly include antioxidant, anticancer, anti-inflammatory and antibacterial activities and that these metabolites can be used to treat many human diseases, such as cancer, skin diseases, cardiovascular diseases, and neurological diseases. Most of the reports that are currently available and concern the secondary metabolites of Osmanthus fragrans have limitations. Some reports introduce only the general classification of compounds in Osmanthus fragrans, and some reports introduce only a single compound. In contrast, the introduction section of this paper includes both the category and the functional value of each compound. While reviewing the data for this study, the authors found that the specific action sites of these compounds and their mechanisms of action in plants are relatively weak, and in the future, additional research should be conducted to investigate this topic further.

Tanshinone IIA improves degranulation of mast cells and allergic rhinitis induced by ovalbumin by inhibiting the PLCγ1/PKC/IP3R pathway.

Allergic rhinitis (AR) is a common allergic inflammatory and chronic reactive disease caused by allergen-induced immunoglobulin E (IgE). Tanshinone IIA (Tan IIA) is one of the active ingredients in Salvia miltiorrhiza Bunge (Danshen) and plays a vital role in inhibiting inflammation. Thus, we hypothesized that Tan IIA has anti-allergic effects and studied the function of Tan IIA in mast cells and an AR animal model. We induced RBL-2H3 cell sensitization with monoclonal anti-2,4,6-dinitrophenyl-immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA) and constructed an ovalbumin (OVA)-induced AR model in mice. The role of Tan IIA in AR progression was studied using the MTT assay, ELISA, western blot, toluidine blue staining, HE staining, and Alcian blue and safranin O (A&S) staining. Tan IIA treatment significantly increased IgE/HSA-induced cell viability. However, Tan IIA treatment markedly downregulated the expression levels of ß-hexosaminidase, histamine, tumor necrosis factor (TNF-α), interleukin 1ß (IL-1ß), IL-4, and IL-5 in IgE/HSA-induced cells. Furthermore, Tan IIA improved typical symptoms in the OVA-induced AR model mice by inhibiting the phospholipase Cγ1 (PLCγ1)/protein kinase C (PKC)/IP3R pathway. Additionally, Tan IIA effectively improved the degranulation of RBL-2H3 cells and OVA-induced AR in mice. Together, these results suggest that Tan IIA may be a potential drug for the treatment of AR in the future.

Salvinorin A inhibits ovalbumin-stimulated allergic rhinitis and RBL-2H3 cells degranulation.

Allergic rhinitis (AR) is a long-term noncommunicable inflammatory disease of the nasal mucosa mediated by immunoglobulin E and is mainly caused by exposure of genetically susceptible individuals to environmental allergens. Mast cells contribute to the pathogenesis of allergic and nonallergic inflammatory diseases. Salvinorin A has been previously shown to inhibit leukotriene production and mast cell degranulation to suppress airway hyperresponsiveness caused by sensitization; thus, we hypothesized that salvinorin A has an anti-AR effect. We tested this hypothesis using monoclonal anti-2,4,6-dinitrophenyl immunoglobulin E/human serum albumin-induced rat basophilic leukemia cells (RBL-2H3 cells) and ovalbumin (OVA)-induced AR in mice as in vivo and in vitro AR models, respectively. The expression levels of histamine, ß-hexosaminidase, interleukin-4 and tumor necrosis factor-α were decreased by salvinorin A in vitro. Granule release and F-actin organization were also suppressed by salvinorin A. Furthermore, salvinorin A inhibited OVA-induced features of AR in mice, including nasal rubbing and sneezing, as well as increased OVA-specific immunoglobulin E, histamine, tumor necrosis factor-α and interleukin-4 levels. In addition, salvinorin A decreased the phosphorylation of phosphoinositide 3-kinase/Akt in vitro and in vivo. Our work suggests that salvinorin A suppresses AR caused by sensitization by inhibiting the inflammatory responses of mast cells; thus, salvinorin A may have potential for treatment of AR.

Wnt signaling in breast cancer: biological mechanisms, challenges and opportunities.

Wnt signaling is a highly conserved signaling pathway that plays a critical role in controlling embryonic and organ development, as well as cancer progression. Genome-wide sequencing and gene expression profile analyses have demonstrated that Wnt signaling is involved mainly in the processes of breast cancer proliferation and metastasis. The most recent studies have indicated that Wnt signaling is also crucial in breast cancer immune microenvironment regulation, stemness maintenance, therapeutic resistance, phenotype shaping, etc. Wnt/ß-Catenin, Wnt-planar cell polarity (PCP), and Wnt-Ca2+ signaling are three well-established Wnt signaling pathways that share overlapping components and play different roles in breast cancer progression. In this review, we summarize the main findings concerning the relationship between Wnt signaling and breast cancer and provide an overview of existing mechanisms, challenges, and potential opportunities for advancing the therapy and diagnosis of breast cancer.