Cycle Migration Research Articles

Silencing of APEX1 triggers ferroptosis in clear cell renal cell carcinoma via APP-mediated activation of p53/xCT signaling.

Apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) is involved in regulating the proliferation, invasion, migration, and other malignant progression of various cancer cells. However, its mechanism in clear cell renal cell carcinoma (ccRCC) remains unclear. UALCAN database was performed to predict APEX1 expression in ccRCC. CCK-8, colony formation, EdU, wound healing, transwell, and flow cytometry assays were used to assess cell proliferation, migration, invasion, and cell cycle. Expressions of cell cycle proteins and ferroptosis biomarkers were detected by western blot. The levels of Fe2+, ROS, MDA, SOD, and GSH in cells were detected by assay kits. Fluorescent probe was used to monitor the intracellular lipid peroxidation level. The binding of APEX1 and amyloid precursor protein (APP) was validated by Co-IP. The expressions of p53/xCT pathway proteins were examined by western blot. The results showed that APEX1 was highly expressed in ccRCC tissues and positively correlated with poor prognosis. Silencing of APEX1 inhibited the proliferation, invasion, migration of Caki-1 cells and induced cell cycle arrest. This silencing also led to increased levels of intracellular Fe2+, lipid peroxidation, and ROS, thereby inducing cell ferroptosis. APEX1 could bind to APP, and their expressions were negatively correlated. Silencing of APP reversed the inhibition effects of APEX1 silencing on proliferation, invasion, migration, and cell cycle in Caki-1 cells. Moreover, APEX1 up-regulated the p53/xCT signaling by binding to APP, thereby promoting ferroptosis. In summary, silencing of APEX1 promotes ferroptosis and inhibits the malignant progression of ccRCC, potentially through APP-mediated activation of p53/AKT signaling, providing a novel therapeutic strategy for ccRCC treatment.

Silencing PADI-2 induces antitumor effects by downregulating NF-κB, Nrf2/HO-1 and AKT1 in A549 lung cancer cells.

This study aimed to investigate the tumorigenic role and regulatory pathways of peptidyl arginine deiminase 2 (PAD-2) in A549 lung cancer cells following treatment with small interfering RNA (PADI-2 siRNA) or the pharmacological pan-PAD inhibitor BB-Cl amidine. A549 lung cancer cells were treated with PADI-2 siRNA to knock down PADI-2 expression or with BB-Cl amidine to inhibit PAD2 activity. The effects on cell proliferation, migration, invasion, and cell cycle phases were assessed. Additionally, the expression levels of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), AKT serine/threonine kinase 1 (AKT), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin 6 (IL6), and p53 were analyzed to elucidate the underlying mechanisms involved. The manipulation of PAD-2 expression or activity significantly influenced tumor cell behavior. Knockdown of PADI-2 in A549 cells reduced cell proliferation by inhibiting the S and G2 phases and decreasing cell migration and invasion. Inhibition of PADI-2 expression also suppressed the protein levels of Nrf2 and HO-1 via suppression of the AKT/NF-κB pathway. Furthermore, this inhibition enhanced the senescence-associated secretory phenotype (SASP) through the regulation of IL6 and p53, resulted in significant upregulation of SASP factors mainly, p21, Lamin B1 and HMGB1. Downregulation of PADI-2 attenuated the proliferation, migration, and invasion of A549 lung cancer cells by modulating the Nrf2/HO-1/AKT signaling pathway. It also increased senescence in A549 lung cancer cells via IL6 and p53 key regulators. These findings highlight the potential of PADI-2 as a therapeutic target in lung cancer treatment.

Knockdown of IGF2BP2 overcomes cisplatin-resistance in lung cancer through downregulating Spon2 gene

BackgroundCisplatin (DDP) resistance has long posed a challenge in the clinical treatment of lung cancer (LC). Insulin-like growth factor 2 binding protein 2 (IGF2BP2) has been identified as an oncogenic factor in LC, whereas its specific role in DDP resistance in LC remains unclear.ResultsIn this study, we investigated the role of IGF2BP2 on DDP resistance in DDP-resistant A549 cells (A549/DDP) in vitro and in a DDP-resistant lung tumor-bearing mouse model in vivo. Additionally, methylated RNA immunoprecipitation sequencing (MeRIP-seq) was conducted to identify the potential mRNAs regulated by IGF2BP2, an N6-methyladenosine (m6A) regulator, in the tumor tissues of mice. Compared to normal tissues, IGF2BP2 levels were increased in LC tissues and in relapsed/resistant LC tissues. Most importantly, IGF2BP2 levels were significantly higher in relapsed/resistant LC tissues than in LC tissues. Significantly, knockdown of IGF2BP2 or DDP treatment inhibited A549 cell viability, migration, and cell cycle progression. Consistently, DDP treatment suppressed the viability and migration and triggered cell cycle arrest in A549/DDP cells in vitro, as well as reduced tumor volume and weight of A549/DDP tumor-bearing mice; meanwhile, the combination of DDP and IGF2BP2 siRNA further significantly inhibited A549/DDP cell growth in vitro and in vivo compared to DDP treatment alone. Furthermore, MeRIP-seq data showed that IGF2BP2 downregulation remarkably elevated m6A levels of spondin 2 (Spon2) and reduced mRNA levels of Spon2 in tumor tissues from A549 tumor-bearing mice. Meanwhile, the combination of DDP and IGF2BP2 siRNA notably reduced Spon2 levels, as well as inhibited the viability and induced apoptosis in A549/DDP cells; however, these effects were reversed by Spon2 overexpression.ConclusionCollectively, downregulation of IGF2BP2 could overcome DDP resistance in LC through declining the Spon2 gene expression in an m6A-dependent manner. These results may provide a new strategy for overcoming DDP resistance in LC.

CYBC1 Drives Glioblastoma Progression via ROS and NF-κB Pathways.

This study aims to investigate the role of Cytochrome b-245 chaperone 1 (CYBC1) in glioblastoma (GBM) progression, focusing on its involvement in reactive oxygen species (ROS) production and associated signaling pathways. Understanding the molecular mechanisms driven by CYBC1 could provide new therapeutic targets and prognostic markers for GBM. Publicly available datasets were analyzed to assess CYBC1 expression in GBM and its correlation with patient survival. GBM cell lines were genetically manipulated using the CRISPR/Cas9 system to deplete CYBC1. The effects of CYBC1 deficiency on cell proliferation, migration, invasion, and cell cycle dynamics were experimentally evaluated. Additionally, the impact of CYBC1 on the expression of NOXA1, a subunit of NADPH oxidase, and downstream signaling pathways such as NF-κB was explored. CYBC1 expression was significantly elevated in GBM tissues and correlated with poor patient survival. CYBC1 deficiency in GBM cells resulted in reduced cell viability, migration, and invasion. Mechanistically, CYBC1 positively regulated NOXA1 expression, which in turn enhanced ROS production and activated the ERK·AKT/NF-κB pathways. The suppression of CYBC1 led to decreased ROS levels, reduced phosphorylation of NF-κB, and downregulation of genes involved in epithelial-mesenchymal transition. CYBC1 is implicated in GBM progression by regulating NOXA1-mediated ROS production and activating the ERK·AKT/NF-κB pathways. This study suggests that CYBC1 could serve as a potential therapeutic target and prognostic marker in GBM, warranting further investigation into its molecular mechanisms and therapeutic potential.

Disrupted Lipid Metabolism, Cytokine Signaling, and Dormancy: Hallmarks of Doxorubicin-Resistant Triple-Negative Breast Cancer Models.

Chemoresistance in triple-negative breast cancer (TNBC) presents a significant clinical hurdle, limiting the efficacy of treatments like doxorubicin. This study aimed to explore the molecular changes associated with doxorubicin resistance and identify potential therapeutic targets to overcome this resistance, thereby improving treatment outcomes for TNBC patients. Doxorubicin-resistant (DoxR) TNBC models (MDA-MB-231 and BT-549) were generated by exposing cells to increasing concentrations of doxorubicin. RNA sequencing (RNA-Seq) was performed using the Illumina platform, followed by bioinformatics analysis with CLC Genomics Workbench and iDEP. Functional assays assessed proliferation, sphere formation, migration, and cell cycle changes. Protein expression and phosphorylation were confirmed via Western blotting. Pathway and network analyses were conducted using Ingenuity Pathway Analysis (IPA) and STRING, while survival analysis was performed using Kaplan-Meier Plotter database. DoxR cells exhibited reduced proliferation, sphere formation, and migration, but showed enhanced tolerance to doxorubicin. Increased CHK2 and p53 phosphorylation indicated cellular dormancy as a resistance mechanism. RNA-Seq analysis revealed upregulation of cytokine signaling and stress-response pathways, while cholesterol and lipid biosynthesis were suppressed. Activation of the IL1β cytokine network was prominent in DoxR cells, and CRISPR-Cas9 screens data identified dependencies on genes involved in rRNA biogenesis and metabolism. A 27-gene signature associated with doxorubicin resistance was linked to worse clinical outcomes in a large breast cancer cohort (HR = 1.76, FDR p < 2.0 × 10-13). This study uncovers potential therapeutic strategies for overcoming TNBC resistance, including dormancy reversal and targeting onco-ribosomal pathways and cytokine signaling networks, to improve the efficacy of doxorubicin-based treatments.

The regulation of the cell cycle and epithelial-mesenchymal transition through FUCA2/GGH signaling promotes the progression of lung adenocarcinoma.

The development of lung adenocarcinoma (LUAD) is intricately linked with cell cycle regulation and epithelial-mesenchymal transition (EMT). Our study, leveraging bioinformatics and database analysis, identified FUCA2 as a key gene influencing the prognosis and progression of LUAD. We observed that FUCA2 is highly expressed in LUAD and correlates with poor outcomes. Functionally, we assessed the role of this gene through cell cloning, scratch assays, transwell migration, and western blotting, revealing that FUCA2 knockdown significantly inhibits tumor cell proliferation and migration, downregulates the expression of cell cycle and EMT-related proteins, and markedly reduces tumor burden. Mechanistically, pathway enrichment analysis identified GGH as a downstream target of FUCA2. Knockdown of GGH similarly inhibits the proliferation, migration, and cell cycle progression of LUAD cells. FUCA2 upregulates GGH to modulate cell cycle and EMT in LUAD. Collectively, our findings indicate that the FUCA2/GGH axis promotes LUAD progression by regulating cell cycle and EMT.

Silencing LY6K Suppresses CD44+ EpCAM+ HCT116 Human Colon Cancer Stem Cells Growth: Insights from In Vitro and In Vivo Evidence.

Lymphocyte antigen 6 complex, locus K (LY6K) is a putative oncogene in various human cancers, including colorectal cancer, where elevated expression is associated with poor prognosis. This study investigates the antitumor effects of LY6K in colon cancer stem cells (CCSCs) both in vitro and in vivo. EpCAM and CD44 surface markers were used to isolate CCSCs from HCT116 cells, and the expression of LY6K in CCSCs was analyzed by real-time PCR. RNA interference was used to silence LY6K to evaluate its potential role of LY6K on the proliferation, migration, invasion, and cell cycle of CCSCs. Functional assays, including MTS assays, flow cytometric analyses, Transwell migration and invasion assays, and a xenograft model, were used for analysis. The results revealed that LY6K was highly expressed in CCSCs. siRNA-mediated LY6K-silencing in CCSCs inhibited cell proliferation by inducing G1 phase cell cycle arrest and suppressed migration and invasion. In vivo, LY6K silencing effectively reduced tumor growth and extended survival in a mouse model. These findings suggest LY6K as a promising therapeutic target for eradicating CCSCs in colorectal cancer treatment.

Plasma-Activated Medium Inhibited the Proliferation and Migration of Non-Small Cell Lung Cancer A549 Cells in 3D Culture.

Lung cancer is the most common type of malignant tumor worldwide. Plasma-activated medium (PAM) is an innovative cancer treatment method that has received considerable scientific attention. The objective of this study is to evaluate the effects of PAM on the anti-tumor characteristics of non-small cell lung cancer (NSCLC) cells in two-dimensional (2D) and three-dimensional (3D) cultures. The effects of PAM treatment on the proliferative and migratory capabilities of A549 cells in 2D and 3D cultures were assessed using MTT, migration, invasion assays, and cell cycle, respectively. The study also investigated the impact of PAM treatment on the changes in the content of intracellular and extracellular reactive species and analyzed protein expression using the Western Blot method. PAM treatment inhibited the viability, migration, and invasion abilities of A549 cells in both 2D and 3D cultures, suppressed the epithelial-mesenchymal transition (EMT) process, and downregulated the expression of the RAS/ERK signaling pathway, which effectively inhibited tumor spheroid formation. Additionally, the effect of PAM on A549 cells was mediated through ROS-induced oxidative reactions, and PAM treatment exhibited greater cytotoxicity in 2D culture compared to 3D culture. As compared to 2D, the 3D cell culture model provides a viable in vitro cell model for studying the mechanisms of PAM treatment in lung cancer. PAM represents an effective new treatment for NSCLC.

SSBP1 positively regulates RRM2, affecting epithelial mesenchymal transition and cell cycle arrest in human lung adenocarcinoma cells

Progression of lung adenocarcinoma (LUAD) is frequently associated with alterations in epithelial-mesenchymal transition (EMT) and cell cycle. Our study analyzed the Cancer Genome Atlas (TCGA) database and identified a positive correlation between high expression of SSBP1 in LUAD tumor tissues and poor prognosis (p < 0.05), with an AUC of 0.853, suggesting that SSBP1 could serve as a prognostic biomarker. In vitro experiments, including siRNA-mediated SSBP1 knockdown and subsequent cell cloning and Transwell assays, revealed significant inhibition of proliferation, migration, and cell cycle progression in LUAD cells (p < 0.05). In vivo mouse model experiments further confirmed that SSBP1 knockdown inhibits tumor burden (p < 0.05). Mechanistic investigations, integrating pathway enrichment analysis with molecular biology techniques, identified RRM2 as a downstream target of SSBP1, and RRM2 knockdown similarly suppressed LUAD cell proliferation, migration, and cell cycle progression (p < 0.05). These findings indicate that SSBP1 promotes EMT and cell cycle progression in LUAD cells by positively regulating RRM2, thereby accelerating disease progression. Collectively, our study not only confirms the potential role of SSBP1 in LUAD but also provides a theoretical foundation for therapeutic strategies targeting the SSBP1/RRM2 axis, potentially offering new therapeutic targets for LUAD patients.

A comprehensive assessment of the antiproliferative effects of Cymbopogon winterianus essential oil, citronellal, and citronellal complexed with β-cyclodextrin on cervical cancer cell line (HeLa)

Cymbopogon winterianus. Jowitt (syn. Cymbopogon nardus. (L.) W. Watson var. mahapengiri. Winter) (Poaceae family) is native to tropical and semitropical areas of Asia, India, and Indonesia, and is cultivated in South and Central America. In this work, the antiproliferative potential of the essential oil of C. winterianus, its major compound against the HeLa cervical cancer lineage, as well as the major compound Citronellal complexed with β-cyclodextrin (β-CO) was evaluated. By gas chromatography coupled with mass spectrometry, it was possible to identify that Citronellal (38.89 %) is the major compound in C. winterianus. In vitro assays with cervical cancer cells (HeLa), it was possible to observe the antiproliferative activity of C. winterianus essential oil (CW), with IC50 of 1.86 μg/mL, as well as of the compound Citronellal (CO), IC50 4.44 μg/mL and citronellal complexed β-cyclodextrin (β-CO), IC50 2.59 μg/mL, as well as the evaluation of cell migration and cell cycle. NIH-3T3 non-tumor cells were also used to evaluate the selectivity of these compounds in tumor cells. All tested samples showed SI > 3, confirming the highest toxicity in tumor cells. All samples tested were able to decrease cell migration and when the proportion of cells in the Sub-G0 Phase was observed, all samples increased the proportion of cells with fragmented DNA, an indication of cell death, except for CW. Thus, it can be concluded that there is a potential to be explored in the C. winterianus essential oil, Citronellal, and Citronellal complexed with β-cyclodextrin.

Highly Pathogenic H5N1 Influenza A Virus (IAV) in Blue-Winged Teal in the Mississippi Flyway Is Following the Historic Seasonal Pattern of Low-Pathogenicity IAV in Ducks.

Highly pathogenic H5N1 (HP H5N1) influenza A virus (IAV) has been detected annually in North American ducks since its introduction during 2021, but it is unknown if this virus will follow the same seasonal and geographic patterns that have been observed with low-pathogenicity (LP) IAV in this reservoir. We monitored blue-winged teal in the Mississippi flyway prior to the detection of HP H5N1 and during two post-introduction migration cycles from spring 2022 to spring 2024, testing birds for infection and antibodies to IAV nucleoprotein (NP), hemagglutinin subtype H5, and neuraminidase subtype N1. Antigens representing clade 2.3.4.4b HP H5 and LP North American H5 were used for hemagglutination inhibition (HI) and virus neutralization (VN) tests for H5 antibodies. Virologic results were consistent with historic seasonal and geographic patterns reported for LP IAV with peak infections occurring in pre-migration staging areas in Minnesota during fall 2022. However, the high prevalence of the H5 subtype was exceptional compared to historic prevalence estimates at this same site and for the Mississippi flyway. HP H5N1 was detected on wintering areas in Louisiana and Texas during the fall of that same year and this was followed by an increase in estimated antibody prevalence to NP, H5, and N1 with no HP H5N1 detections during the wintering or spring migration periods of 2022/2023. HP H5N1 was not detected in Minnesota during fall 2023 but was detected from a single bird in Louisiana. However, a similar increase in antibody prevalence was observed during the winter and spring period of 2023 and 2024. Over the two migration cycles, there was a temporal shift in observed prevalence and relative titers against the H5 antigens with a higher proportion of ducks testing positive to the 2.3.4.4b H5 antigen and higher relative titer to that antigen compared to the representative LP North American H5 antigen. The seasonal and geographic patterns observed appear to be driven by population immunity during the migration cycle. Results support an initial high infection rate of HP H5N1 in blue-winged teal in the Mississippi flyway followed by a high prevalence of antibodies to NP, H5, and N1. Although prevalence was much reduced in the second migration cycle following introduction, it is not known if this pattern will persist in the longer term or affect historic patterns of subtype diversity in this reservoir.

Fatty acid dehydratase HACD3 poses protein kinase activity and promotes the malignant progression of colorectal cancer

HACD3 is a member belonging to the very long-chain fatty acid dehydratase family. However, little is known about HACD3's function besides its weak dehydratase activity. The current study aims to investigate the potential role of HACD3 in Colorectal Cancer (CRC).The study evaluates HACD3 expression in CRC patient samples. Moreover, the study investigates in vitro cell proliferation, colony formation, invasion, migration, and cell cycle progression on HACD3 knockdown and overexpressing CRC cells, along with in vivo tumorigenesis within NSG mice, Hacd3−/−; ApcMin/+ mice and Hacd3ΔIEC; ApcMin/+mice. The study identifies the molecular target(s) of HACD3 via phosphoproteomics, followed by biological assay verification.The study identifies that HACD3 is highly expressed in CRC tissues and promotes the malignant progression of cancer cells. Additionally, HACD3 interacts with CDK2, leading to CDK2 T160 phosphorylation via a domain between amino acids 298–324 of HACD3.Thus, fatty acid dehydratase HACD3 possesses protein kinase activity and stimulates tumorigenesis, partly by activating the CDK2 pathway. Therefore, inhibiting HACD3 could facilitate CRC treatment.

Upregulation of LncRNA WT1-AS Inhibits Tumor Growth and Promotes Autophagy in Gastric Cancer via Suppression of PI3K/Akt/mTOR Pathway.

Increasing evidence has highlighted the involvement of the imbalance of long non-coding RNAs in the development of gastric cancer (GC), which is one of the most common malignancies in the world. This study aimed to determine the role of lncRNA WT1-AS in the progression of GC and explore its underlying mechanism. The expression of lncRNA WT1-AS in gastric cancer tissues was detected using RT-qPCR. We knocked down the expression of WT1-AS in GC cells or treated them with rapamycin or both. Then, transwell assay and scratch assay were carried out to determine the migration of GC cells, and flow cytometry was carried out to determine the cell cycle. The immunofluorescence technique was used to determine the autophagy, and a tumor formation experiment was carried out to determine tumor growth in vivo. The expression of factors related to the PI3K/Akt/mTOR pathway was also measured by Western Blotting. In GC tissues and cells, lncRNA WT1-AS was underexpressed. Moreover, overexpression of lncRNA WT1-AS blocked the PI3K/Akt/mTOR pathway. Upregulation of lncRNA WT1-AS or inhibition of the PI3K/Akt/mTOR pathway suppressed cancer cell migration in vitro, leading to cell cycle arrest, and promoted autophagy while inhibiting tumor growth in vivo. It also reduced the expression levels of Ki-67, MMP2, MMP9, and VEGF. The WT1-AS+rapamycin group was the most prominent in all experiments. The upregulation of lncRNA WT1-AS could suppress the PI3K/Akt/mTOR pathway, which inhibits cell migration and cell cycle arrest while promoting autophagy in gastric cancer cells.

Cyclanoline Reverses Cisplatin Resistance in Bladder Cancer Cells by Inhibiting the JAK2/STAT3 Pathway.

Cisplatin is a key therapeutic agent for bladder cancer, yet the emergence of cisplatin resistance presents a significant clinical challenge. This study aims to investigate the potential and mechanisms of cyclanoline (Cyc) in overcoming cisplatin resistance. Cisplatin-resistant T24 and BIU-87 cell models (T24/DR and BIU-87/DR) were established by increasing gradual concentration. Western Blot (WB) assessed the phosphorylation of STAT3, JAK2, and JAK3. T24/DR and BIU-87/DR cell lines were treated with selective STAT3 phosphorylation modulators, and cell viability was evaluated by CCK-8. Cells were subjected to cisplatin, Cyc, or their combination. Immunofluorescence (IHC) examined p-STAT3 expression. Protein and mRNA levels of apoptosis-related and cell cycle-related factors were measured. Changes in proliferation, invasion, migration, apoptosis, and cell cycle were monitored. In vivo, subcutaneous tumor transplantation models in nude mice were established, assessing tumor volume and weight. Changes in bladder cancer tissues were observed through HE staining, and the p-STAT3 was assessed via WB and IHC. Cisplatin-resistant cell lines were successfully established, demonstrating increased phosphorylation of STAT3, JAK2, and JAK3. Cisplatin or Cyc treatment decreased p-STAT3, inhibited invasion and migration, and induced apoptosis and cell cycle arrest in the G0/G1 phase in vitro. In vivo, tumor growth was significantly suppressed, with extensive tumor cell death. IHC and WB consistently showed a substantial downregulation of STAT3 phosphorylation. These changes were more pronounced when cisplatin and Cyc were administered in combination. Cyc reverses cisplatin resistance via JAK/STAT3 inhibition in bladder cancer, offering a potential clinical strategy to enhance cisplatin efficacy in treating bladder cancer.

Carbonic anhydrase 2 is important for articular chondrocyte function and metabolic homeostasis

ObjectivesAberrant chondrocyte metabolism significantly contributes to cartilage degeneration and osteoarthritis (OA) genesis. However, the mechanisms driving the metabolic shift in OA chondrocytes remain unclear. Interestingly, carbonic anhydrase 2 (CA2) is implicated in metabolic regulation, and its expression dramatically increases in OA chondrocytes, but its exact role and mechanism are poorly understood. This study investigates the mechanistic role of CA2 in chondrocyte metabolic homeostasis under hypoxic and inflammatory conditions. MethodsRNA-seq was performed on CA2-deficient C28/I2 cells to identify pathways affected by the loss of CA2 function. We examined CA2’s impact on chondrocyte metabolism, anabolism, and catabolism using C28/I2 cells and primary chondrocytes under normoxia and hypoxia and in a model of inflammatory OA. ResultsRNA-seq revealed enrichment of glycolysis, apoptosis, and TNF signaling pathways in CA2-deficient cells. Under hypoxia, CA2 expression increased 10-fold in a HIF-1α-independent manner. Knockdown of CA2 reduced extracellular lactate production, increased ADP/ATP ratio, impaired glycolysis, reduced glycolytic capacity, and lowered expression of glycolysis rate-limiting enzymes but did not disrupt pHi and ROS production. CA2 deficiency altered chondrocyte anabolic and catabolic equilibrium by affecting PI3K/AKT and RELA/p65 signaling. CA2-deficient chondrocytes displayed impeded migration, suppressed proliferation, and cell cycle arrest at the G0/G1 phase. Forced expression of CA2 stabilized chondrocyte metabolism and restored cellular functions. ConclusionsOur research uncovered a hitherto unknown mechanistic role for CA2 in regulating chondrocyte energy metabolism and inflammation, underscoring its potential as a critical mediator in OA pathogenesis. Further research using a murine model of experimental OA is warranted to capture the functional implications of CA2.

Oncogenic role of lncRNA SBF2-AS1 in bladder cancer

IntroductionBladder cancer is a malignant neoplasm with increasing incidence rates. LncRNAs play an important role in cancer, including development, prognosis, and response to therapies. It is known that lncRNA SBF2-AS1 was associated with cell proliferation and worse prognosis in various tumor types, but its role remains incompletely understood in bladder cancer. In this context, our objective was to evaluate the effect of lncRNA SBF2-AS1 silencing on bladder cancer cells. MethodsJ82 and UM-UC-3 high-grade bladder tumor cells were treated with two siRNAs specific for SBF2-AS1 to evaluate cytotoxicity, clonogenic survival, morphology, cell migration, and cell cycle progression. ResultsExpression inhibition of SBF2-AS1 resulted in cytotoxicity, morphological changes, and decreased clone formation and cell migration. Cell cycle alterations were not observed. ConclusionOur study revealed that SBF2-AS1 plays an oncogenic role and holds promise as a potential target for the treatment of bladder cancer.

Expression and role of methyltransferase 3 in oral malignant transformation

ObjectiveTo investigate the expression and role of methyltransferase 3 (METTL3) in oral malignant transformation. Materials and methodsImmunohistochemical method was used to investigate the expression of METTL3 in the human oral malignant transformation. Bioinformatics analysis was used to explore the role of METTL3 in oral malignant transformation. Oral cancer animal model was used to verify the expression trend of METTL3 in oral malignant transformation. Knockdown of METTL3 expression in human oral mucosal precancerous lesion cells was performed to explore the METTL3 effect on proliferation, migration, apoptosis, and cell cycle. ResultsMETTL3 expression was significantly up-regulated in the human oral malignant transformation. Moreover, METTL3 was related to the pathway of “Neuroactive ligand-receptor interaction.” In addition, METTL3 expression was also significantly up-regulated in the hamster oral malignant transformation. Finally, the proliferation and migration abilities of human oral mucosal precancerous lesion cells were inhibited after METTL3 knockdown. ConclusionsIn conclusion, we found that METTL3 was up-regulated in oral malignant transformation, and the role may relate to the pathway of “Neuroactive ligand-receptor interaction.”

Marine Staurosporine Analogues: Activity and Target Identification in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and drug resistance and no targeted drug available at present. Compound 4, a staurosporine alkaloid derived from Streptomyces sp. NBU3142 in a marine sponge, exhibits potent anti-TNBC activity. This research investigated its impact on MDA-MB-231 cells and their drug-resistant variants. The findings highlighted that compound 4 inhibits breast cancer cell migration, induces apoptosis, arrests the cell cycle, and promotes cellular senescence in both regular and paclitaxel-resistant MDA-MB-231 cells. Additionally, this study identified mitogen-activated protein kinase kinase kinase 11 (MAP3K11) as a target of compound 4, implicating its role in breast tumorigenesis by affecting cell proliferation, migration, and cell cycle progression.

Access to medicines among asylum seekers, refugees and undocumented migrants across the migratory cycle in Europe: a scoping review

IntroductionAccess to essential medicines is a critical element of health systems and an important measure of their performance. Migrants may face barriers in accessing healthcare, including essential medicines, throughout the...

β-Cyclodextrin as an elicitor of polyphenolic contents of barley (Hurdeum vulgare) callus with antioxidant and anti-aging properties on human skin fibroblast cells (HFF2)

The skin, as the largest organ of body, plays a crucial role in human beauty, yet is vulnerable to aging due to ultraviolet radiation (UV) exposure. Various methods, including intradermal injection, surgery, laser therapy, stem cell applications, and cosmetic treatments, are employed to combat skin aging. Phytochemicals, known for their antioxidant properties, are extensively studied for skincare. Barley (Hurdeum vulgare) contains diverse phenolic compounds, exhibiting strong antioxidant activity, potentially reducing cellular aging. Here, we examined the anti-aging properties of barley callus extract enriched with polyphenols in human skin fibroblast cells (HFF2) exposed to UVB radiation. β-cyclodextrin was used as an elicitor at concentrations of 2.5 and 5 ppm to enhance the production of polyphenolic compounds in the callus of black and yellow barley. A concentration of 5 ppm significantly increased the phenolic and flavonoid content in both black and yellow barley callus. Analysis of the extracts obtained from the callus showed that aqueous and ethanolic extracts of black barley callus, at a concentration of 0.1 μg/mL, enhanced cell viability and decreased matrix metalloproteinase-1 (MMP-1) levels while increasing sirtuin (SIRT1) production in UVB-exposed HFF2 cells. These extracts also exhibited high antioxidant effects and promoted cell migration, DNA integrity, and cell cycle advancement. The findings suggest the potential use of black barley callus extract in cosmetics to mitigate UV radiation effects and premature skin aging. Additionally, β-cyclodextrin is highlighted as a valuable elicitor for enhancing polyphenol content, contributing to the antioxidant and anti-aging properties of black barley callus for skincare applications.