• The ANXA2P1-hnRNP F-HK2/c-Myc Positive Feedback Loop Promotes Proliferation and Glycolytic Metabolism in Gastric Cancer.
    2 days ago
    Pseudogene-derived long non-coding RNAs (lncRNAs) contribute to carcinogenesis. However, the role of the pseudogene ANXA2P1 in gastric cancer (GC) growth and glucose metabolism remains unknown. Analysis of microarray and RNA sequencing (RNA-seq) reveals that ANXA2P1 is increased upon glucose starvation in GC cells and displays elevated expression in GC. Moreover, ANXA2P1 overexpression promotes proliferation and metastasis by enhancing aerobic glycolysis in GC. Mechanistically, ANXA2P1 binds to the RNA-binding protein hnRNP F and promotes proximal polyadenylation site usage of HK2, thereby generating a short 3'UTR isoform with enhanced stability. Consequently, elevated HK2 expression accelerates GC proliferation and metabolic reprogramming. Interestingly, HK2 exerts a non-metabolic role by serving as a co-activator of transcription factor c-Myc to collaboratively drive ANXA2P1 expression. Clinically, ANXA2P1, hnRNP F, HK2, and c-Myc were augmented in specimens from GC patients compared to matched normal gastric mucosa. This study illustrates that ANXA2P1 is considered an oncogene, and the ANXA2P1-hnRNP F-HK2/c-Myc positive feedback loop may act as a potential therapeutic target for GC.
    Cancer
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  • Polycystin-1 Orchestrates Tumor Context-Dependent Mechanotransduction Programs Driving Epithelial-to-Mesenchymal Transition and Invasion in Solid Cancers.
    2 days ago
    Mechanotransduction critically shapes tumor progression by regulating cytoskeletal remodeling, epithelial-to-mesenchymal transition (EMT), invasion, and immune evasion. Polycystin-1 (PC1) and polycystin-2 (PC2), established mechanosensitive proteins in epithelial systems, have recently been implicated in tumor biology; however, their roles across diverse solid malignancies remain insufficiently defined. We assessed PC1 and PC2 expression patterns and their associations with clinicopathological features in human lung, breast, prostate, and brain tumors. PC1 functional modulation was performed in xenograft models using an extracellular mechanosensitivity-blocking antibody, and in cancer cell lines via polycystic kidney disease 1 (PKD1) siRNA. We evaluated consequences on EMT, tumor growth, migration, and the mechanotransduction effector TAZ. PC1 and PC2 exhibited strong positive correlation across multiple tumor types, indicating coordinated mechanobiological regulation in cancer. Their expression associated with clinically aggressive features, including PD-L1 expression in lung cancer, adverse pathological characteristics in prostate cancer, and poorer survival in HER2⁺ breast cancer with elevated PC2 levels. In vivo, inhibition of PC1 mechanosensing consistently attenuated EMT programs across tumor types, accompanied by reductions in tumor growth. In vitro, PKD1 silencing reduced cell migration and induced context-dependent modulation of EMT markers. Notably, PC1 suppression induced TAZ activation in breast cancer and glioma cells, indicating a cell type-specific regulatory interaction between PC1 and Hippo-mechanotransduction signaling. Our data suggest that polycystins, PC1 in particular, exert conserved yet context-dependent mechanoregulatory functions in solid tumors. By influencing EMT, migration, tumor progression, and TAZ-mediated mechanotransduction, PC1 emerges as a potential biomarker and mechanotherapeutic target in mechanically responsive cancers.
    Cancer
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  • Corrigendum to: Effects of SVEP1 on Lung Squamous Cell Carcinoma and its Association with Tumor Mutation Burden, Prognosis, and Immune Regulation.
    2 days ago
    It has come to our notice that in the published version of this article [1], the asterisk denoting the corresponding author was inadvertently omitted. The corrected author list is provided below. The original article can be found online at https://benthamscience.com/public/article/144076 Details of the correction: • Original: Yu Luo1,*, Min Zhang2,*, Zhibo Wang1,*, Zhihua Li1, Xiru Chen1, Juan Cao1, Jun Que1, Liang Chen1,# and Xiaheng Deng1,# • Corrected: Yu Luo1,*, Min Zhang2,*, Zhibo Wang1,*, Zhihua Li1, Xiru Chen1, Juan Cao1, Jun Que1, Liang Chen1,# and Xiaheng Deng1,* We apologize for any inconvenience caused.
    Cancer
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  • Toxicological Implications of m6A Dysregulation: SH3PXD2A-AS1-Driven PD-L1 Overexpression Promotes Immune Evasion in NSCLC.
    2 days ago
    The lncRNA SH3PXD2A-AS1 drives therapy resistance in non-small cell lung cancer (NSCLC) through m6A-mediated PD-L1 overexpression, representing a novel molecular toxicology paradigm. In the present work, the functional significance of SH3PXD2A-AS1 in orchestrating immune escape and malignant progression of NSCLC was systematically examined. Integrating TCGA analyses with cell and mouse studies, we found that SH3PXD2A-AS1 was elevated in NSCLC and associated with features of an immunosuppressive tumor microenvironment. Multi-omics profiling, RNA pull-down/RIP, and promoter-reporter assays revealed that SH3PXD2A-AS1 interacts with the transcription factor MYBL2 to drive transcriptional activation of WTAP, a core component of the m6A writer complex. This axis enhanced m6A modification of PD-L1 mRNA, stabilizing PD-L1 and dampening CD8+ T-cell responses. Silencing SH3PXD2A-AS1 reduced MYBL2/WTAP/PD-L1 signaling, decreased malignant phenotypes in vitro, and restored antitumor T-cell activity in humanized mouse models, whereas enforced MYBL2 or WTAP expression counteracted these effects. Collectively, these findings define an lncRNA-transcription factor-epitranscriptomic checkpoint that sustains PD-L1-mediated immune escape in NSCLC, and nominate SH3PXD2A-AS1 and its MYBL2/WTAP partners as potential biomarkers and therapeutic targets to improve responses to immune checkpoint inhibition.
    Cancer
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  • Meox1 promotes hepatocellular carcinoma progression potentially via regulation of cell cycle and p21 expression.
    2 days ago
    Meox1 is aberrantly expressed in several malignancies, but its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate the effects of Meox1 on HCC cells and explore the underlying molecular mechanisms. Cell proliferation, colony formation, migration, invasion, and cell cycle distribution were assessed by CCK-8, clonogenic, Transwell, and flow cytometry assays, respectively. Protein expression was examined by Western blotting. Meox1 silencing significantly inhibited proliferation, clonogenic capacity, migration and invasion of HCC cells. Cell cycle analysis showed a reduction in G1-phase cells with a marked accumulation in the G2 phase following Meox1 knockdown. Western blot analysis revealed that suppression of Meox1 reduced p21CIP1/WAF1 expression. Meox1 contributest to HCC progression and may represent a potential therapeutic target.
    Cancer
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  • Reliability of the Amharic Version of the Medication Adherence Report Scale and Beliefs about Medicines Questionnaire in Patients with Asthma in Ethiopia.
    2 days ago
    Non-adherence to asthma medications is often associated with poor health outcomes, necessitating a reliable measurement of its extent. Thus, the aim of this study is to assess the reliability of the Medication Adherence Report Scale for asthma (MARS-A) and the Beliefs about Medicines Questionnaire-Specific (BMQ-Specific) adherence measures among patients with asthma in Ethiopia.

    A hospital-based cross-sectional study was conducted among adult patients with asthma at a tertiary hospital in Ethiopia from January to May 2024. The MARS-A and BMQ-Specific tools were used to assess adherence and patients' beliefs about medicines, respectively, while sociodemographic and clinical characteristics, as well as reasons for non-adherence, were obtained through patient interviews and electronic medical records. Descriptive statistics were used to present patient characteristics, and Cronbach's alpha was calculated to evaluate internal consistency.

    The study included 250 patients with a mean age of 53.82 (SD = 13.79) years, of whom 57.2% had well-controlled asthma, and 24.8% were non-adherent to prescribed medications according to MARS-A. According to patient reports, the primary reasons for non-adherence were unaffordability and unavailability of medications. The overall mean (SD) MARS-A score was 4.60 (0.43). The MARS-A and BMQ-Specific instruments were found to be reliable, with Cronbach's alphas of 0.904 and 0.961, respectively.

    Our findings indicate that the Amharic versions of the MARS-A and BMQ-Specific are reliable instruments for assessing medication adherence and beliefs about medicines among Ethiopian patients with asthma.
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  • Lung T1-MRI and Multi-Breath Washout Detect Longitudinal Changes in Children 6-11 Years Old After Beginning Elexacaftor/Tezacaftor/Ivacaftor (ETI) Therapy.
    2 days ago
    Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy was approved in 2021 for clinical use in children with CF (cwCF) age 6-11 years, depending on their genetic variants. Our prior multi-center study showed that lung T1-MRI and multi-breath washout (MBW) provided complementary pathobiological information on CF lung disease in cwCF 6-11 years of age. In this study, we hypothesized that lung T1-MRI and MBW will sensitively detect lung improvements in cwCF after starting ETI therapy. To test this hypothesis, we obtained longitudinal lung T1-MRI, MBW, and spirometry assessments in a cohort of cwCF 6-11 years of age before and after starting ETI therapy.

    CwCF (n = 48, mean age = 8.6 years) were recruited from 3 cystic fibrosis (CF) centers (Riley Hospital for Children (Indianapolis, IN), University of Michigan, Michigan Medicine (Ann Arbor, MI), and Rainbow Babies and Children's Hospital (Cleveland, OH) for longitudinal lung T1-MRI, MBW, and spirometry assessments before initiating ETI (baseline) as well as at 3-months and 6-months after initiating ETI. MBW and spirometry were performed according to published guidelines to obtain measurements of the lung clearance index (LCI) and percent predicted forced expiratory volume at 1 s (ppFEV1), and percent predicted forced expiratory flow at 25%-75% (FEF25 %-75%), respectively. Lung T1-MRI was used to obtain assessments of % normal lung perfusion (%NLP). An ANOVA analysis and descriptive statistics were used to compare the longitudinal changes in the lung T1-MRI, MBW, and spirometry findings.

    Across all subjects, significant improvements in both spirometry (ppFEV1, FEF25 %-75%) and MBW (LCI 2.5) were observed at 3-months, and 6-months post treatment (p < 0.001). As a group, the lung T1-MRI findings showed no significant changes despite a trend for improved lung perfusion. However, lung T1-MRI did show a significant improvement in both 3-months and 6-months after starting ETI therapy (p < 0.03) when evaluating only those subjects with mild-moderate lung disease (ppFEV1 90 % ) $\le 90 \% )$ at baseline.

    MBW, spirometry, and lung T1-MRI are all capable of detecting lung airway and perfusion changes in cwCF 6-11 years of age following the start of ETI therapy. MBW and spirometry assessments were able to detect a sustained improvement in pulmonary function testing regardless of baseline lung status, while lung T1-MRI was able to detect significant improvements in lung perfusion in patients with more advanced lung disease. These findings, in combination with our prior cross-sectional findings, suggest that MBW and lung T1-MRI may provide complementary alternatives to chest CT and can be used to assess disease progression and/or response to therapy.
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  • Coronary arterial age for mortality prediction and risk reclassification in SCORE COVID-19 registry: When vascular age runs faster or slower than chronological age.
    2 days ago
    Coronary arterial age (CAA), derived from coronary artery calcium (CAC) percentiles from the Multi-Ethnic Study of Atherosclerosis (MESA), reflects vascular biological ageing. Its prognostic role in acute settings such as COVID-19 remains unclear.

    We analysed 1482 hospitalized patients from the multicentre SCORE-COVID registry undergoing chest CT. CAA was estimated from CAC percentiles; ΔAge was defined as CAA minus chronological age. A calcium-adjusted biological age (BioAge) was also assessed. The primary endpoint was 30-day all-cause mortality.

    Chronological age and CAA showed similar discrimination (AUC 0.76 vs 0.74; P = .466) and were independently associated with mortality and increased stepwise across ΔAge strata. CAA mainly improved specificity by down-classifying survivors. While no significant interaction was observed between CAA and the 4C score, ΔAge significantly re-stratified mortality risk among patients at high 4C risk.

    CAA demonstrated prognostic performance comparable to chronological age for short-term mortality in COVID-19 and added clinically relevant information on vascular ageing. BioAge meaningfully refined risk stratification among patients at high clinical risk, supporting its use as an adjunctive biomarker whenever chest CT imaging is available.
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    Education
  • Perceptions of Improved Wellbeing and Social Isolation Among Medical Students During Rural Clinical School (RCS) Placements: A Six-Year Analysis.
    2 days ago
    To investigate the trends in the perceived social isolation and improved wellbeing of Australian medical students over a 6-year period (2017-2022) during their rural clinical school (RCS) placements.

    Data were analysed using descriptive statistics and multinomial logistic regressions to identify the trends and factors contributing to perceived social isolation and improved wellbeing during RCS placements.

    This is a retrospective, cross-sectional study of the 2017-2022 FRAME (Federation of Rural Australian Medical Educators) dataset.

    Data were collected from 2915 Australian medical students who completed RCS placements.

    Respondents were located at RCS placements across 19 Australian universities.

    The main outcomes were self-reported social isolation and improvement in wellbeing.

    Over 30% of respondents reported experiencing social isolation. Factors contributing to social isolation were preference to practice in a capital city and lack of financial or overall support from the RCS, while lack of academic isolation was protective. More than 80% of respondents perceived the RCS placement had a positive impact on their wellbeing. Positive influences on wellbeing were associated with active role-modelling of self-care, support services and mentorship by a rural-based clinician. The COVID-19 years did not significantly impact perceived social isolation or improved wellbeing.

    Most medical students on RCS placements reported positive impacts on their wellbeing, while over 30% experienced social isolation. Targeted support strategies that reduce social isolation and enhance student wellbeing on rural placements may help improve rural workforce retention and address healthcare shortages.
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  • Indian Expert Consensus on Allergic Rhinitis in Women: A Modified Delphi Survey.
    2 days ago
    At present, there are many significant gaps in understanding the clinical needs of Indian women with allergic rhinitis. To address a critical gap in clinical practice, the consensus group created an innovative questionnaire tailored to assist Indian clinicians in the diagnosis and management of allergic rhinitis among female patients.

    The modified Delphi survey utilized a systematic approach to group communication in addressing research questions and resolving conflicting viewpoints through detailed evaluation of various arguments. In total, 80 statements were developed focusing on disease burden, risk factors, clinical presentation, comorbidities, symptoms, and treatment of allergic rhinitis.

    Out of 61 statements reviewed by the expert panel, around 38 statements received over 80% agreement, leading to a consensus.

    Allergic conditions are more common among Indian women, impacting them disproportionately. A high level of consensus indicates that many Indian women spend most of their time indoors, which can result in heightened exposure to indoor allergens and pollutants, consequently increasing their vulnerability to allergies. The experts also offered real-world clinical recommendations while assessing and managing modifiable and nonmodifiable allergens in Indian women with allergic rhinitis.
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