Mitochondrial metabolism (MM)-mediated ferroptosis plays a critical role in breast cancer (BC). However, the potential targets based on ferroptosis and MM in BC remain poorly understood. This study aimed to explore the prognostic role of ferroptosis- and MM-related genes (FPMMs) in BC. Differentially expressed FPMMs were identified, and functional analyses were performed. Univariate Cox, LASSO, and multivariate Cox regression analyses were used to screen hub genes, and a prognostic risk model was then constructed and validated in external datasets. Gene set variation analysis was conducted to investigate their regulatory functions. Furthermore, immune infiltration analysis was performed using the "quantiseq" algorithm. We identified 206 differentially expressed FPMMs. A prognostic risk model consisting of 6 genes (BRD4, FLT3, SIAH2, CS, EMC2, and PI3KCA) was constructed, exhibiting good predictive capability and stability. These 6 prognostic genes were dysregulated in BC, with PI3KCA exhibiting the highest mutation frequency. Gene set variation analysis further revealed that the PI3K-AKT-mTOR signaling was suppressed in BC. In addition, the risk score based on the prognostic model was associated with immune infiltration, particularly with B cells, T cells, CD4, and dendritic cells. Our study highlights the potential of the prognostic model based on FPMMs as a valuable tool for BC prognosis prediction.

Lung cancer is one of the most prevalent malignancies worldwide, and the metastasis of nonsmall cell lung cancer often leads to rapid deterioration of patient conditions, with brain metastasis (BM) being the most detrimental. The mechanisms underlying lung cancer brain metastasis remain incompletely understood.

This study aimed to elucidate the molecular mechanisms of lung cancer brain metastasis and identify potential biomarkers and therapeutic targets.

The high invasiveness of H1975-BM51 cells was verified using Western blotting, cell invasion assays, and the establishment of an nonsmall cell lung cancer brain metastasis mouse model. Transcriptome sequencing of H1975 and H1975-BM51 cells was conducted, followed by Least Absolute Shrinkage and Selection Operator regression and single-gene Gene Set Enrichment Analysis to screen key genes. Quantitative real-time PCR and Western blotting were employed to detect the expression levels of the AGO3 gene in H1975-BM51 cells.

Transcriptomic analysis revealed that the AGO3 gene contributes to lung cancer brain metastasis by negatively regulating hormone metabolic processes. Compared with parental H1975 cells, both mRNA and protein expression levels of AGO3 were significantly upregulated in highly invasive H1975-BM51 cells.

This study identifies AGO3 as a potential biomarker and therapeutic target for lung cancer brain metastasis.

Background: Orphan class A G protein-coupled receptors (GPCRs) are a large and diverse family with broad tissue expression, and their roles in tumors are increasingly recognized. However, their involvement in gastric cancer (GC) remains unclear. Methods: We performed survival and differential expression analyses to characterize orphan class A GPCR expression patterns in stomach adenocarcinoma (STAD). A prognostic risk model was developed using univariate Cox and LASSO regression analysis and validated in the GEO database. Drug sensitivity and immune infiltration were evaluated across different risk groups. The role of GPR176 in GC and its relationship with tumor immunity were further explored using cellular assays. Results: A model incorporating nine orphan class A GPCRs (GPR15, GPR150, GPR176, GPR4, GPR26, GPR78, GPR101, GPR34, and GPR87) was constructed, showing a positive correlation with M2 macrophages and naive B cells. Low-risk patients showed higher sensitivity to AZD6482, BX.795, GDC0941, and pazopanib. GPR176 was found to be upregulated in GC, and functional assays demonstrated that its knockdown suppressed proliferation and migration in the GC cell lines SGC-7901 and HGC-27. GPR176 also modulated the Wnt/β-catenin pathway and M2 macrophage polarization. Conclusion: These findings may provide new insights into the role of orphan class A GPR genes in STAD and identify GPR176 as a new therapeutic target for GC.

Pancreatic cancer (PC) is marked by extensive heterogeneity, posing significant challenges to effective treatment. The tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), plays a critical role in driving PC progression. However, the prognostic and functional contributions of distinct CAF subtypes remain inadequately understood. Here, we introduce a novel 7-gene risk model that not only robustly stratifies PC patients but also unveils the unique role of PHLDA1 as a key mediator in tumor-stroma crosstalk.

By integrating single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and bulk RNA sequencing data, we comprehensively characterized the heterogeneity of CAFs in PC. We identified five CAF subtypes and focused on matrix CAFs (mCAFs), which were strongly associated with poor prognosis. A 7-gene mCAF-associated risk model was constructed using advanced machine learning algorithms, and the biological significance of PHLDA1 was validated through co-culture experiments and pan-cancer analyses.

Our multiomics analysis revealed that the novel 7-gene model (comprising USP36, KLF5, MT2A, KDM6B, PHLDA1, REL, and DDIT4) accurately predicts patient survival, immunotherapy response, and TME status. Notably, PHLDA1 was uniquely overexpressed in CAFs and correlated with the activation of key protumorigenic pathways, including EMT, KRAS, and TGF-β, underscoring its central role in modulating the crosstalk between CAFs and malignant ductal cells. Pan-cancer analysis further supported PHLDA1's prognostic and immunomodulatory significance across multiple tumor types.

Our study presents a novel 7-gene prognostic model that significantly enhances risk stratification in PC and identifies PHLDA1+ CAFs as promising prognostic biomarkers and therapeutic targets. These findings provide new insights into the TME of PC and open avenues for personalized treatment strategies.

Tyrosine kinase inhibitors (TKIs) are a class of therapies used to target specific genetic mutations such as epidermal growth factor receptor (EGFR) mutations in cancer treatment. This study investigates the function of epithelial membrane protein 3 (EMP3) in EGFR-TKI resistance in lung adenocarcinoma (LUAD). Human LUAD cells HCC827 and H1975 were exposed to different doses of osimertinib or erlotinib to generate TKI-resistant cell lines. These cells exhibited increased expression of EMP3. EMP3 overexpression in parental cells significantly increased TKI resistance, as well as promoted proliferation, migration, and stem cell characteristics. Epithelial-mesenchymal transition (EMT) is a major cause for EMP3 upregulation, as overexpression of ZEB1 increased EMP3 expression. By contrast, inhibition of the TGF/β signaling with LY2109761 reduced EMP3 expression in cells. In vivo, EMP3-overexpressing mouse 3LL cells exhibited strengthened tumorigenic activity in C57BL/6 mice in the presence of osimertinib treatment, accompanied by increased stem cell markers. Notably, the LY2109761 treatment reduced TKI resistance and diminished expansion, migration, and stemness in cancer cells induced by EMP3 overexpression. In conclusion, this study indicates that EMP3, upregulated upon EMT, contributes to EGFR-TKI resistance in LUAD cells.

To identify and characterize non-profit organizations (NPOs) from English-speaking countries providing advocacy to individuals with head and neck cancer (HNC) and critically analyze the multifaceted roles played by these NPOs for patients, caregivers, healthcare professionals, and researchers.

A scoping review was conducted through PubMed, Scopus, EMBASE, Web of Science, Google Scholar, ProQuest, and open databases. The data collected on the NPOs were: information on origin, founder background, cancer types addressed, mission, and information and services offered.

Twenty-five NPOs were identified, predominantly from the US (n = 10/40%) and UK (n = 10/40%). Most NPOs (n = 16/64%) were founded by survivors and/or their families. The websites provided diverse information, with over 84% (n = 21) covering risk factors, signs, symptoms, and screening/diagnosis. Common services included educational resources, newsletters, and patient support groups. Legal advice was also provided but less frequently. All NPOs promoted fundraising; the majority promoted awareness events, and 40% (n = 10) offered research grant opportunities.

NPOs are vital advocates for HNC patients, offering community support and empowerment. Healthcare professionals, by being aware of NPOs and their work, can enhance patient support. Additionally, researchers should view NPOs as essential sources for patient and public engagement, which is increasingly valued by funding agencies.

Recent observational studies show a correlation between serum uric acid (SUA) levels and colorectal and gastric cancers (CRC and GC). It is unclear, nevertheless, what the biological mechanisms and causation of these connections are. Using summary data from the genome-wide association study, we analyzed 2-sample Mendelian randomization (MR). Inverse-variance weighted (IVW) was the main technique for determining causality. The weighted median, weighted mode, MR-Egger, Wald ratio, and IVW were employed to investigate the causal link between SUA and GC/CRC. To evaluate weak instrumental variable (IV) bias, F-statistics were computed. Using MR-PRESSO, outliers were found and removed. Cochran Q test, MR-Egger test, and leave-one-out approach were employed to find heterogeneity and stability in MR results. Ultimately, bioinformatics investigations were carried out to investigate plausible biological pathways linking GC/CRC and SUA. According to IVW data, SUA dramatically lowered the chance of GC (OR = 0.804, 95% Cl: 0.700-0.922, P = .002). There was no discernible cause-and-effect connection between SUA and CRC (OR = 0.999, 95% Cl: 0.997-1.000, P = .080). Furthermore, the reliability of the multiple validity and heterogeneity tests demonstrated the validity of the MR data. A total of 10 hub genes were found, with the majority of them being enriched in the AMPK signaling pathway, lipid metabolism, glucose metabolism, and cholesterol metabolism. This study indicates that SUA lowers the chance of developing GC, regardless of the risk of acquiring CRC. The link between SUA and GC could be due to several metabolic processes.

Fatigue is a common sequela of SARS-CoV-2 infection, with many COVID-19 patients subsequently developing chronic fatigue syndrome and myalgic encephalomyelitis (CFS/ME). Long-term associations between COVID-19, new-onset CFS/ME, and other independent predictors such as vaccination for SARS-CoV-2, re-infection, and blood biomarkers at time of infection remain unclear. This study investigated the incidence and independent predictors of developing new-onset CFS/ME up to 4 years post SARS-CoV-2 infection in comparison to COVID- controls.

This retrospective analysis conducted within the Montefiore Health System from February 1, 2020, to January 12, 2024 included adults without a prior diagnosis of fatigue or CFS/ME who were hospitalized for COVID-19 (n = 10,667), not hospitalized for COVID-19 (n = 25,409), and non-COVID-19 controls (n = 111,301). The observation time was between 30 days and 4 years post index date. The outcome was new-onset CFS/ME. Multivariate adjusted hazard ratios (HR) with 95% confidence intervals were calculated, assessing risk posed by SARS-CoV-2 infection, re-infection, and vaccination. Whether abnormal levels of aspartate aminotransferase, creatinine, D-dimer, lactate dehydrogenase, ferritin, hemoglobin, platelets, neutrophil/lymphocyte ratio, and temperature during hospitalization were associated with future CFS/ME risk was examined.

Compared to COVID- controls, the risk of developing new-onset CFS/ME was higher among both COVID-19 hospitalized (adjusted HR = 1.46 [1.07, 1.99]) and non-hospitalized patients (1.56 [1.25, 1.93]). Females (1.54 [1.27, 1.89]), patients with liver disease (1.61 [1.29, 2.00]), autoimmune disorders (1.57 [1.18, 2.08]), and anxiety disorders (1.35 [1.04, 1.74]) were more likely to develop CFS/ME (p < 0.05). Re-infection with SARS-CoV-2 was not associated with increased risk of incident CFS/ME. COVID-19 vaccination status during the initial phase of the rollout (prior to 2022) was associated with an increased risk of new-onset CFS/ME (p < 0.05). None of the blood biomarkers during acute COVID-19 were associated with new-onset CFS/ME risk (p > 0.05).

SARS-CoV-2 infection is associated with an increased risk of new-onset CFS/ME, independent of hospitalization status. Females, and individuals with autoimmune and anxiety disorders were more susceptible. These findings highlight the need for ongoing surveillance and management of fatigue-related symptoms in COVID-19 survivors.

With the persistence of global challenges related to the COVID-19 pandemic, it has become essential to explore the dynamics of physical activity in adolescents. Although knowledge exists on the importance of physical activity for overall health, understanding the factors influencing adolescent physical activity patterns remains a less explored terrain. This study aims to determine the prevalence and factors associated with physical activity in adolescents in Lambayeque, Peru.

An analytical cross-sectional study with secondary data analysis was conducted in adolescents from five secondary schools. Physical activity was assessed using the PAQ-A questionnaire. Its association with various factors was investigated, such as bullying (EBIPQ questionnaire), self-esteem (Rosenberg questionnaire), family dysfunctionality (APGAR Family questionnaire), resilience (abbreviated CD-RISC questionnaire), insomnia (ISI questionnaire), depressive-anxious symptoms and stress (DASS21 questionnaire), suicidal risk (Plutchik Suicide Risk Scale), eating disorder (SCOFF questionnaire), acne (Spanish Acne Severity Scale-EGAE), and quality of life (DLQI questionnaire).

Of 1266 adolescents, the mean age was 14.6 years, and 54.6% were male. The prevalence of active physical activity was 33.8% (95% CI: 31.20-36.49). In multiple regression analysis, factors associated with physical activity included male sex (PR: 1.51), having a very frequent family approach (PR: 1.26), a high level of resilience (PR: 1.15), having a crush (PR: 1.19), and mild anxious symptoms (PR: 1.30). In contrast, frequent use of social networks (PR: 0.72), moderate (PR: 0.64) or severe (PR: 0.66) family dysfunctionality, medium (PR: 0.85) and low (PR: 0.80) levels of self-esteem, and an extreme effect on quality of life due to acne (PR: 0.66) were negatively associated with physical activity.

The findings reveal a relatively low prevalence of active physical activity among adolescents. The positive association with resilience, family closeness, and mild anxious symptoms highlights the importance of strengthening protective factors to encourage physical activity in this vulnerable group. Conversely, the negative influence of family dysfunctionality, low self-esteem, and the impact of acne on quality of life underscores the need to address these psychosocial aspects to promote a healthy lifestyle in adolescents in the post-COVID era. These findings inform more effective intervention strategies, thus contributing to the holistic well-being of youth in the current global health landscape.

Chronic Obstructive Pulmonary Disease (COPD) exacerbations are associated with increased mortality and cardiovascular events. However, there is limited evidence on the relationship between COPD exacerbations and mortality and cardiovascular outcomes in China.

This retrospective cohort study included Chinese patients with COPD aged ≥ 40 years from the Yinzhou regional electronic health records database. Patients were screened for eligibility between 1 Jan 2014 and 1 Mar 2022, with the index date being the first identified COPD diagnosis within this timeframe. Patient characteristics and frequency and severity of COPD exacerbations were collected during the 24-month baseline period prior to the index date. Outcomes included all-cause mortality and severe cardiovascular events. The incidence of death and first severe cardiovascular event was reported overall, and by baseline exacerbation history. Cox proportional hazards models were employed to identify the association between baseline COPD exacerbation history and all-cause death.

A total of 14,713 patients with COPD were included, with a median follow-up duration of 41.3 months. During the follow-up period, 20.1% of patients died, with a crude incidence rate of 5.17 (95% CI: 4.98, 5.36) per 100 person-years. Additionally, 20.1% of patients experienced severe cardiovascular events. The incidence of severe cardiovascular events numerically increased with higher frequency and severity of baseline COPD exacerbations. Patients with history of severe COPD exacerbations exhibited an increased risk (adjusted HR: 1.26, 95%CI: 1.14, 1.38) of all-cause death compared with patients with no exacerbations.

This study found that severe COPD exacerbations significantly increased mortality risk in Chinese patients with COPD. Patients with a history of severe exacerbations also reported a higher incidence rate of severe cardiovascular events. These findings emphasize the need for improved exacerbation prevention strategies in COPD management.