Gallbladder cancer, the most prevalent malignant neoplasm of the biliary tract, has garnered significant attention due to its dismal prognosis and high degree of malignancy. Identifying key regulatory genes is crucial for the development of effective therapeutic strategies. The differential gene expression in biliary tract malignancies was identified using the Gene Expression Omnibus (GEO) database. Subsequently, the interactions among these differentially expressed genes were analyzed employing the STRING database, and the resultant regulatory network was visualized using Cytoscape software. Utilizing the Cytoscape plugin CytoHubba, the core genes within the network were identified, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Ultimately, the overexpression of THBS1 in the gallbladder cancer cell line (NOZ) was achieved through lentiviral transfection and both in vivo and in vitro experiments were conducted to evaluate its effects. We found that thrombospondin-1 (THBS1) was the core gene of gallbladder cancer and its expression was low in gallbladder cancer. Experimental data, both in vivo and in vitro, indicate that the up-regulation of THBS1 exerts an inhibitory effect on the proliferation, migration, and invasion of gallbladder cancer cells. Furthermore, it facilitates the process of apoptosis and suppresses tumor growth and angiogenesis. The expression of THBS1 is low in gallbladder cancer. Up-regulation of THBS1 can effectively inhibit the occurrence and development of gallbladder cancer and can be used as a biomarker for the diagnosis and treatment of gallbladder cancer.

The majority of lung cancer cases are non-small cell lung cancer (NSCLC) which continues to be a serious global health concern. Hypoxia-inducible factor (HIF-α) pathway is a promising therapeutic target because it has a vital function in advanced non-small cell lung carcinoma. Antiangiogenic multi-kinase inhibitor, sorafenib may have a part in regulating HIF signaling in cancer. As a result, there is now more interest in employing it to target hypoxia-driven pathways in non-small cell lung cancer, especially when paired with natural bioactive products such as dauricine which is a naturally occurring alkaloid molecule targets multiple cellular pathways to provide strong anticancer effects. To examine molecular impacts of combining dauricine with sorafenib on HIF-mediated signaling pathways in human lung cancer cell lines. Cell viability was assessed using MTT assay in A549 and H1975 lung tumor cell lines. Levels of key proteins (AKT, mTORC1, HIF-1 α, ERK, VEGF, Cyclin-D1, BCL2, and E-Cadherin) were measured by ELISA.A colorimetric test was utilized to assess the activity of caspase-3, as a marker of apoptosis. qRT-PCR was employed to identify PI3K and VEGFR2 genes expression. Combination of sorafenib and dauricine significantly enhanced cytotoxicity compared to either agent alone. This combination also led to a marked reduction in VEGFR2, PI3K expression and VEGF, AKT, mTOR, HIF-1α, BCL2, ERK and E-Cadherin, and Cyclin-D1 levels. In addition, there was a significant increase in caspase-3 activity. Dauricine potentiates antitumor effects of sorafenib in human NSCLC by modulating HIF-1α-mediated pathways that are involved in several cancer hallmarks. This combination shows promise as a potential lung cancer treatment approach.

Lung and colon cancer are among the most commonly diagnosed and fatal cancer types in the world. Due to their metastatic properties, they complicate the treatment process and pose a great threat to human health. These aggressive types of cancer are resistant to chemotherapy drugs. Therefore, it is extremely important to investigate the therapeutic effects of natural compounds. In our previous study, effective doses of Royal Jelly (RJ) (100 mg/mL) and Aloe vera (AVE) (20 µg/mL) were determined and tested separately and in combination on lung and colorectal cancer cells. Glycolytic capacities were determined using the Seahorse XFe24 Analyzer, total transcriptome profiles were sequenced using NovaSeq 6000, and BAX and BCL-2 gene levels were determined using RT-qPCR. It was seen that RJ and RJ + AVE affected glycolytic capacity and more genes in lung cancer cells. In HT29, AVE alone was seen to reduce glycolytic capacity and RJ + AVE combination was seen to reduce the expression level of genes related to cell proliferation and cycle. After RJ + AVE treatments, the apoptotic process which is triggered via MAPK pathway was found in lung cancer. Moreover, BAX levels increased and BCL-2 levels decreased both lung and colorectal cancer cells. It was observed that the combination of RJ and AVE affected the glycolysis process, cell cycle, proliferation and apoptosis on lung and colorectal cancer. In particular, the combination of RJ + AVE was found to be more effective on lung cancer.

Limited advancements in managing malignant brain tumors have resulted in poor prognoses for glioblastoma (GBM) patients. Standard treatment involves surgery, radiotherapy, and chemotherapy, which lack specificity and damage healthy brain tissue. Boron-containing compounds, such as boric acid (BA), exhibit diverse biological effects, including anticancer properties. This study aimed to examine whether boron supplementation, as BA, can inhibit glioblastoma growth in a xenograft animal model. Using MRI-based tumor size measurement, survival rates, hematological, clinical biochemistry analyses, and genotoxicity parameters, we assessed the impact of BA. Histopathological, immunohistochemical, and immunofluorescence examinations were also conducted. All BA doses (3.25, 6.5, and 13 mg kg−1 b.w.) extended survival compared to GBM controls after 14 days, with a dose-dependent anti-GBM effect observed in MRI analyses. BA treatment improved hematological (WBC and PLT counts) and biochemical parameters (LDL-C, CREA, and ALP). Histopathological examination revealed a significant reduction in tumor diameter with 6.5 and 13 mg kg−1 BA. Immunohistochemical and immunofluorescence staining showed modulation of intracytoplasmic Ki67, cytoplasmic CMPK2, and GFAP expressions in tumor cells post-BA treatment. Additionally, BA did not increase micronuclei formations, indicating its non-genotoxic nature. In conclusion, targeting tumor suppressor networks with boron demonstrates significant therapeutic potential for GBM treatment.

Lymphedema is a chronic condition caused by the accumulation of protein-rich fluid in the interstitial tissue, resulting in edema and a diminished quality of life. When first-line treatments like complete decongestive therapy (CDT) fail, surgical options are considered. These include physiological procedures like lymphaticovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT), which aim to restore lymphatic function, as well as reductive procedures such as liposuction and excisional techniques, which reduce limb volume. Previous studies have evaluated these surgeries, but the literature remains scattered. This rapid review consolidates current research on surgical treatments for lymphedema. We reviewed the PubMed database and included systematic reviews, meta-analyses, randomized clinical trials, and literature reviews published between 2014 and 2024. Studies were selected if they reported outcomes such as objective volume reduction, patient-reported quality of life (QOL), or infection rates. Nineteen publications were selected for review. The most common procedures represented were LVA (N = 12) and VLNT (N = 10), though reductive operations such as liposuction and radical excision were also represented. Both LVA and VLNT, either alone or combined, demonstrated positive outcomes in terms of volume reduction, QOL, and infection prevention. Reductive surgeries were effective in reducing long-term volume but had less favorable cosmetic outcomes and variable infection rates. Overall, while surgical approaches have proven beneficial, the variability in outcome measures and inconsistent follow-up periods limit comparability across studies. Further research is needed to better guide patients in selecting the most appropriate surgical option based on their lymphedema characteristics and personal goals.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense, fibrotic, immunosuppressive, and desmoplastic extracellular matrix. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have emerged as a novel therapeutic strategy. Nonetheless, the potential dual effects of MSC-EVs on tumor cells warrant careful consideration. This study aimed to evaluate the mechanistic effects of MSC-EVs on PDAC. Wharton’s Jelly (WJ) MSC-derived small EVs were isolated using ultracentrifugation method and analyzed through nanoparticle tracking analysis (NTA) and flow cytometry. EVs were added to Panc-1 cells at concentrations of 4000–10,000 EVs per cell, and a preliminary MTT assay was performed. In subsequent experiments, EVs were added to Panc-1 cells at concentrations of only 4000, 8000 and 12,000 EVs per cell. After 24 h, apoptosis and cell cycle analyses were performed. The expression of epithelial-mesenchymal transition (EMT)-related and immune-related genes was analyzed. Cell cycle analysis showed higher G1 phase percentage in the control group (31%) compared to MSC EV-treated groups (35–36%). Apoptosis analysis revealed similar viable and necrotic cell percentages among the control (80% viable) and treated groups (approximately 78–79% viable). The CD44, VIM, MMP9, TIMP1, and ZEB1 genes were downregulated in treated groups compared to the control. Although CLDN1 and CDH1 genes were upregulated at the lowest EV concentration, they were downregulated at higher EV concentrations. Immune gene analysis showed downregulation of pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ, IL-1α, IL-1β) and upregulation of the anti-inflammatory cytokine IL-10 in treated groups. This study revealed the dual role of WJ-MSC small EVs in PDAC. While they suppressed cell proliferation and modulated EMT markers, indicating their antitumor potential, they also exhibited an immunosuppressive profile. These findings highlight both the promise and challenges of using WJ-MSC small EVs as therapeutic agents, necessitating further studies to optimize their application and balance their effects.

BackgroundThis study investigated the protective effects of verbascoside (VER) against 5-fluorouracil (5-FU)-induced gastrointestinal mucositis in Wistar albino rats.Methods and resultsThe study involved 30 female rats that were equally divided into five groups as follows: Control group, 5-FU group (400 mg/kg, IP), VER-only group (0.2 mg/kg, IP), 5-FU (400 mg/kg, IP) + VER (0.2 mg/kg, IP) group, and 5-FU (400 mg/kg, IP) + VER (0.4 mg/kg, IP) group. All animals were euthanized four days after 5-FU administration. Gastrointestinal tissues (esophagus, stomach, duodenum, jejunum, ileum, and colon) and blood sera were collected for histopathological and biochemical analyses. Tissue and sera analyses showed that 5-FU caused significant alterations marked by increases in matrix metalloproteinases (MMP-1, -2, -8), alkaline phosphatase (ALP), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) levels and decreases in tissue inhibitor of metalloproteinases-1 (TIMP-1), albumin, and total protein levels. VER treatment effectively attenuated these 5-FU-induced changes, with trends toward improved histological outcomes at higher doses.ConclusionThe findings strongly suggest that VER offers significant protection, and these results warrant further investigation into its potential clinical application as an adjunct therapy to mitigate gastrointestinal and other toxicities associated with 5-FU chemotherapy.

Curcumin, a natural polyphenol with established anti-tumor properties, has shown therapeutic potential in ovarian cancer. However, its mechanisms, particularly through modulation of tumor-associated macrophages (TAMs) in the tumor microenvironment, remain unexplored. This study aimed to elucidate how curcumin suppresses ovarian cancer progression by regulating TAM polarization. Primary TAMs isolated from ascites of ovarian cancer patients were co-cultured with SKOV3/OVCAR-3 cancer cells. Curcumin was administered at varying doses (5–80 μM) to assess its direct effects on cancer cell viability and its indirect effects via TAM modulation. Epithelial-mesenchymal transition (EMT), migration, invasion, and cytokine profiles were analyzed using CCK-8, flow cytometry, RT-PCR, Western blot, and functional assays. High-dose curcumin (40–80 μM) directly inhibited cancer cell proliferation. In contrast, low-dose curcumin (5–20 μM) suppressed TAM-induced malignant behaviors: it reduced M2 polarization (CD206⁺ TAMs decreased by 54.89% to 32.14%, p < 0.01) while increasing M1-associated cytokines (IL-12↑, IL-1β↑) and decreasing M2 markers (IL-10↓, TGF-β↓). TAM-conditioned medium primed with 20 μM curcumin significantly attenuated cancer cell migration (scratch closure: 65% vs. 85% in TAM-only group, p < 0.01), invasion, and EMT (E-cadherin↑, N-cadherin↓, Vimentin↓). Our study uncovered the mechanism of the anti-tumor effect of curcumin in low doses related to the regulation of TAMs, which might provide novel insight into the treatment of ovarian cancer.

Colorectal cancer (CRC) is a prevalent and lethal malignancy, with ubiquitination significantly influencing cellular processes involved in cancer progression. However, the contributions of ubiquitination-related genes in CRC remain unclear. This study conducted a detailed analysis of gene expression profiles associated with ubiquitination in CRC, evaluating 1006 genes across 46 pathways. By comparing CRC tissues to adjacent normal tissues, we identified differentially expressed genes and developed a ubiquitination-related pathway gene signature (URPGS) using LASSO regression analysis on genes with prognostic significance. The prognostic capability of the URPGS was validated in independent cohorts, and its associations with clinical characteristics, including post-chemotherapy survival outcomes, were examined. Machine learning techniques identified HSPA1A as a key gene relevant to CRC both in vitro and in vivo. Our analysis revealed 307 differentially expressed ubiquitination-related genes, with 24 significantly associated with patient prognosis. The developed 14-gene URPGS exhibited strong prognostic value, effectively stratifying patients into high-risk and low-risk groups for overall survival. The URPGS correlated with advanced clinical stages, lymph node metastasis, and recurrence, with higher scores linked to poorer post-chemotherapy survival outcomes. Knockdown of HSPA1A significantly inhibited CRC cell proliferation, migration, and invasion in vitro, as well as tumor growth and metastasis in vivo. This research establishes a novel URPGS that effectively predicts prognosis and chemotherapy outcomes in CRC, enhancing our understanding of ubiquitination's role and suggesting personalized treatment strategies.