Background: Lung cancer (LC) is the second most lethal cancer and efficient treatments are missing. Our understanding of the underlying pathogenic mechanisms remains limited. Oridonin is a compound extracted from the Chinese herb Rabdosia rubescens with anticancer properties. Nevertheless, its effects on LC and the underlying mechanisms remain unknown.
Methods: In the current research, A549 and Hcc1833 cells were treated with different doses of oridonin, and cell proliferation and migration were detected using CCK8, EdU, Transwell, and wound healing assays. A subcutaneous tumor and caudal vein metastasis model was generated to verify the inhibitory effects of oridonin on Hcc1833 tumor growth and metastasis in vivo. Proteomics analyses then were performed to examine the regulatory mechanism. LiP-SMap combined with microscale thermophoresis and molecular docking analyses were used to validate the relationship between oridonin and S100A11.
Result: Data showed that oridonin suppressed cell proliferation and migration depending on dose and suppressed tumor growth and invasion. LiP-SMap and molecular docking analyses confirmed that oridonin interacted with the Asn-53 residue of S100A11, which inhibited the activation of oridonin. S100A11 overexpression reversed the inhibitory effects of oridonin on cell proliferation and migration.
Conclusion: In conclusion, the data indicate that oridonin suppresses LC malignant progression by targeting S100A11.
Alzheimer's disease (AD) remains a significant challenge in neurology, marked by progressive cognitive decline and neurodegeneration. Despite extensive research efforts, effective treatments are still lacking. Traditional drug discovery is often slow and costly, frequently resulting in limited success. Drug repurposing, which identifies new therapeutic uses for existing medications, has emerged as a promising approach to expedite AD treatment development. This review examines the potential of drug repurposing to transform AD therapy by utilizing the established safety profiles and known mechanisms of current drugs. We explore various repurposed drugs under investigation for AD, originally intended for cardiovascular, metabolic, and psychiatric conditions. Detailed discussions include how these drugs provide neuroprotective benefits by inhibiting amyloid-beta aggregation, reducing tau phosphorylation, and modulating neuroinflammation. Additionally, we emphasize the benefits of drug repurposing, such as shortened development timelines, lower costs, and increased chances of clinical success. By integrating current research findings, this review offers a thorough overview of the most promising repurposed drug candidates and their potential impact on AD treatment strategies. It stresses the importance of innovative approaches in AD research and calls for greater investment in drug repurposing initiatives. Through these strategies, we aim to accelerate the availability of effective treatments, providing renewed hope and a brighter future for those affected by this devastating disease.
Cervical cancer remains a significant global health concern, making it essential to investigate new treatment options continuously. This page provides an overview of the latest advancements and best practices in detection and intervention, including Pap smears, colposcopy, biopsy, immunotherapy, targeted therapies, chemotherapy, radiation therapy, and surgery. Surgical techniques such as radical hysterectomy and minimally invasive procedures have advanced to enhance patient outcomes and quality of life. Simultaneously, radiation therapy methods have been refined to maximize tumour control while reducing adverse effects. Chemotherapy remains vital, with new drugs and combination regimens demonstrating improved tolerance and efficacy. Immunotherapy, notably immune checkpoint inhibitors, has shown promise in advanced stages of cervical cancer. Additionally, targeted therapies that focus on specific biochemical pathways offer the potential for personalized treatment approaches. This review critically assesses ongoing research, evaluates existing data, and emphasizes the opportunities and challenges of each therapeutic approach. Ultimately, integrating these diverse treatment strategies is the key to enhancing patient outcomes.
Background: Necroptosis is a modifiable form of cell death mainly dependent on RIPK3 and MLKL. The association between necroptosis and inflammation has been a key focus of research. An increasing number of studies have shown that necroptosis plays an important role in inflammatory diseases, such as inflammatory bowel disease.
Methods: Articles published up to 2023 were searched on the Web of Science. VOSviewer, CiteSpace, Gephi, and Microsoft Office Excel were used for bibliometric analysis and visualisation. In addition, journal impact factors and journal partitions were obtained through the Web of Science.
Results: A total of 3011 articles were included in this study. The number of publications and citations in the field increased year by year. China had the highest number of publications. Cell Death & Disease published the most papers in the field. P. Vandenabeele is one of the most important scholars in this field. The most cited reference was "Molecular Mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death".We found substantial evidence that acute kidney injury, sepsis, cancer, and other diseases are closely related to necroptosis. In addition, we found that inhibitors of necroptosis have great potential in the treatment of inflammatory diseases.
Conclusion: This is the first bibliometric analysis of studies related to necroptosis in inflammatory diseases. Our results provide an overview of basic and influential research, providing a basis for the identification of valuable research directions. Furthermore, this work offers general insight into the role of necroptosis in inflammatory human diseases.
Introduction: Copine-3 (CPNE3) is a conservative calcium-dependent phospholipid-binding protein belonging to the copines protein family. CPNE3 has been implicated in the development and progression of several diseases, including cancer.
Method: Herein, we investigated the molecular mechanisms through which CPNE3 regulates the migration of lung adenocarcinoma (LUAD) cells in vitro. Western blotting and immunohistochemical assays showed that CPNE3 is widely distributed in LUAD tissues and cell lines and that CPNE3 downregulation promotes the migration of human LUAD A549 cells.
Results: Stable isotope labelling with amino acids in cell culture, which is a quantitative proteomics approach coupled with bioinformatic analyses, revealed that CPNE3 regulates SQSTM1/p62 and vimentin expression, indicating that CPNE3 may mediate epithelial-mesenchymal transition (EMT). CPNE3 silencing by siRNA upregulated vimentin levels but downregulated E-cadherin levels in the A549 cells.
Conclusion: Furthermore, SQSTM1/p62 knockdown enhanced migratory ability and EMT progression in CPNE3-silenced A549 cells. Overall, CPNE3 knockdown was found to promote EMT by inhibiting SQSTM1/p62 signalling and facilitating cell migration. Our findings highlight the role of CPNE3 as a tumour suppressor, providing deeper insights into its carcinogenic roles in LUAD.
Background: Metabolic Syndrome (MS) is a cluster of conditions that significantly increase the risk of infertility in women. Granulosa cells are crucial for ovarian folliculogenesis and fertility. Understanding molecular alterations in these cells can provide insights into MS-associated infertility.
Objective: This study aimed to investigate Differentially Expressed Genes (DEGs) and Proteins (DEPs) in granulosa cells from female patients with MS-associated infertility.
Method: Transcriptome and proteome analyses were integrated to compare granulosa cells from three MS patients with infertility to three control subjects. RNA sequencing and quantitative proteomics analyses were conducted, followed by differential expression analysis, Gene Set Enrichment Analysis (GSEA), and Protein-protein Interaction (PPI) network construction. Functional enrichment of overlapping DEGs and DEPs and potential drug-protein interactions were also explored. Hub genes identified by PPI were validated via quantitative Polymerase Chain Reaction (qPCR) and western blot assays.
Results: Principal Component Analysis (PCA) demonstrated a distinct separation between MS and control groups, indicating significant differences in gene and protein expression. A total of 1,046 upregulated and 23 downregulated DEGs, along with 222 upregulated and 412 downregulated DEPs, were identified in the MS group. GSEA highlighted enrichment in processes, like the cell cycle and immune response. Venn diagram revealed 71 overlapping DEGs and DEPs, mainly related to immune regulation. Key hub proteins and potential therapeutic candidates were identified, with hub genes upregulated at the mRNA level, but downregulated at the protein level in granulosa cells of MS patients.
Conclusion: The integrative analyses revealed significant molecular alterations in granulosa cells from MS patients with infertility. Identified DEGs, DEPs, and hub proteins suggested potential therapeutic targets and pathways for addressing MS-associated infertility.
Background: Resistance to lenvatinib poses a serious threat to the therapy of patients with Hepatocellular Carcinoma (HCC). The mechanism by which HCC develops resistance to lenvatinib is currently unknown.
Objective: The aim of this study was to identify key genes and pathways involved in lenvatinib resistance in HCC using bioinformatic analysis and experimental validation.
Methods: Differentially expressed genes (DEGs) were identified from the GSE186191 gene expression profile, comparing HCC cell lines with lenvatinib-resistant HCC cell lines. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were then carried out using DAVID. A protein-protein interaction network was constructed to visualize DEGs and identify hub genes. The expression and prognostic significance of these hub genes were further examined. Additionally, genomic enrichment analysis (GSEA) was utilized to investigate the potential functions of key genes. Following this, the presence of AHSG was validated in both the original Huh7 cells and the lenvatinib-resistant Huh7 (Huh7LR) cells resistant to lenvatinib through the utilization of quantitative real-time PCR (qRT-PCR).
Results: A total of 232 DEGs were identified between HCC cell lines and those that are resistant to lenvatinib. These DEGs were significantly associated with arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, dilated cardiomyopathy, and mucin-type O-glycan biosynthesis. Three hub genes, including AHSG, C6, and ORM1, were identified. The low expression of AHSG showed a poorer prognosis in HCC. GSEA demonstrated a significant correlation between low AHSG expression and pathways involving fatty acid metabolism, ribosome function, glycine, serine, and threonine metabolism, peroxisome activity, and bile acid biosynthesis. The expression of AHSG was notably reduced in Huh7LR cells (p = 0.006) compared to Huh7 cells.
Conclusion: Diminished AHSG expression is strongly associated with lenvatinib resistance in HCC, suggesting that it may have implications for developing effective strategies to overcome this resistance.
Objective: This study aims to investigate the effect of Gallic Acid (GA) on the alleviation of chemotherapy-induced bone marrow suppression, with a comparison to Diyu sheng bai tablets (DYSB) and RhG-CSF.
Methods: A mouse model of bone marrow suppression was established in BALB/c mice using intraperitoneal injections of cyclophosphamide (CTX). All procedures were performed after obtaining ethical clearance from the institutional animal ethics committee. Mice were treated with low (100 mg/kg/d), medium (200 mg/kg/d), and high (400 mg/kg/d) doses of Gallic Acid (GA) to mitigate CTX-induced bone marrow suppression. In parallel, mice in the positive control group were also treated with DYSB and RhG-CSF at their respective standard doses (DYSB: 100 mg/kg/day, RhG-CSF: 125 mg/kg/day). The efficacy of GA in alleviating chemotherapy-induced bone marrow suppression was evaluated through blood cell counts, immune organ (thymus and spleen) indices, bone marrow nucleated cell (BMNC) counts, cell cycle analysis, apoptosis, histopathology of bone marrow and spleen, and analysis of splenic hematopoietic factors.
Results: CTX induced a decrease in peripheral blood cells and BMNC counts, reduced spleen and thymus indices, and diminished abnormal pathology of bone marrow and spleen, as well as decreasing disturbances in hematopoietic factors. GA was able to alleviate these abnormalities in the bone marrow. It modulated cell proliferation and apoptosis, adjusted the proportion of cells in the G0/G1 phase, and reduced apoptosis in femoral bone marrow.
Conclusion: Gallic Acid (GA) alleviates chemotherapy-induced bone marrow suppression by improving immune organ function, promoting bone marrow cell recovery, and inhibiting apoptosis. These findings support GA as a potential adjunct therapy for chemotherapy, with promising clinical applications.
Background: This study investigates the potential effects of elemene injection on pancreatic cancer using network pharmacology and experimental validation.
Methods: GEO database were used to acquire genes which are differentially expressed between pancreatic cancer tissue and normal tissue. The vigorous energetic ingredients were identified in research and the object genes were obtained from BATMAN-TCM. The key targets and signaling pathways of elemene injection were identified using compound- target network analysis, protein-protein interaction network analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. in vitro experiments were carried out to confirm the accuracy of the network pharmacology predictions.
Results: Two hundred and eleven target genes that may be involved in Elemene's impact on pancreatic cancer were identified. Bioinformatics analysis was conducted to determine the two active mixtures and one key target. GO and KEGG enrichment analyses indicated that elemene injection exerts therapeutic effects on pancreatic cancer, regulating the cell adhesion by ECM-receptor interaction pathway. The experiments verified that elemene injection suppressed the growth and movement of pancreatic cancer cell lines Panc02 and MiaPaca-2 and the mechanism is related to regulating ECM-receptor interaction pathway-related genes. FN1 was identified as core targets by bioinformatics analysis. The FN1 was downregulated by elemene injection and was validated by QPCR and Western Blot.
Conclusion: The findings of the current study emphasized that elemene injection might control cell attachment, decrease metastasis, and suppresses pancreatic cancer progress. FN1 might be a therapeutic target for pancreatic cancer.
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