The role of COPD in survival of NSCLC patients receiving immune checkpoint inhibitors: A meta-analysis

The impact of chronic obstructive pulmonary disease (COPD) on the survival of patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs) remains unclear. Given the growing use of ICIs in NSCLC treatment and the high prevalence of COPD among these patients, understanding this relationship is essential. This meta-analysis aims to evaluate the association between COPD and survival outcomes in NSCLC patients treated with ICIs. A systematic search was conducted in PubMed, Embase, and Web of Science from inception to February 10, 2025. Observational studies reporting survival outcomes in NSCLC patients with and without COPD undergoing ICI therapy were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a random-effects model to account for heterogeneity. Thirteen retrospective cohort studies involving 5,564 patients were included. COPD was associated with improved progression-free survival (PFS) (HR: 0.68, 95% CI: 0.54–0.85, p < 0.001) and overall survival (OS) (HR: 0.80, 95% CI: 0.68–0.95, p = 0.01) in NSCLC patients receiving ICIs. Heterogeneity was moderate (I² = 46% for PFS, I² = 43% for OS). Subgroup analyses indicated that the association between COPD and survival outcomes was consistent across study regions (Asian vs. Western countries), patient age, sex distribution, COPD diagnostic criteria (spirometry, clinical diagnosis, or CT-diagnosed emphysema), follow-up duration, analytic models (univariate vs. multivariate), and study quality scores (p for subgroup differences > 0.05). Furthermore, univariate meta-regression analysis showed no significant modification of results by sample size, mean age, sex distribution, follow-up duration, or study quality scores (all p > 0.05)

Erratum: Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain

In the article “Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain” (Xiao et al., DOI: https://doi.org/10.17305/bb.2024.10441), published on 6 September 2024, an incorrect version of Figure 2 was inadvertently published due to an editorial oversight. The article has been corrected online to include the accurate figure. This correction does not affect the study’s results, interpretations, or conclusions. We apologize for the error and thank the authors for bringing it to our attention

Integrins and pulmonary fibrosis: Pathogenic roles and therapeutic opportunities

Characterized by the formation of fibrotic scars, pulmonary fibrosis (PF) involves a complex pathogenesis, limited treatment options, and a high mortality rate. Integrins—heterodimeric transmembrane proteins composed of α and β subunits—mediate extracellular matrix remodeling and regulate the physiological functions of epithelial, mesenchymal, and immune cells through "inside-out" and "outside-in" signaling pathways. These molecules play a critical role in the initiation and progression of PF. Due to their central regulatory functions, a range of integrin-targeted therapies has been developed. However, the complex pathophysiology of PF and the structural diversity of integrins pose significant challenges to targeted treatment. In this study, we systematically delineated the signaling networks mediated by the full spectrum of integrin family members and uncovered the molecular mechanisms by which they contribute to PF through immunoregulatory pathways. We also reviewed the development of integrin-based therapies from preclinical studies to clinical trials and discussed current priorities in clinical, basic, and translational research. These insights may provide new perspectives for the diagnosis and treatment of PF.

Inhibition of RUNX1 slows the progression of pulmonary hypertension by targeting CBX5

Pulmonary artery smooth muscle cell (PASMC) dysfunction is the central pathogenic mechanism in pulmonary hypertension (PH). This study explored the mechanism of action of RUNX1, a potential therapeutic target for PH, in PASMCs. A PH mouse model was used to investigate the impacts of RUNX1 knockdown on hemodynamics, right ventricular hypertrophy (RVH), and pulmonary artery remodeling (hematoxylin–eosin [H&E] staining). Isolated PASMCs were transfected with RUNX1- or chromobox 5 (CBX5)-related vectors and then subjected to cell function assays. Immunoprecipitation was used to detect molecular binding and ubiquitination. RUNX1 knockdown reduced right ventricular systolic pressure (RVSP), RVH, and pulmonary artery remodeling in mice with PH. Knockdown of RUNX1 or CBX5 suppressed proliferation, invasion, and migration and stimulated apoptosis in PASMCs under hypoxia. RUNX1 enhanced ubiquitin-specific protease 15 (USP15) promoter activity. USP15 bound to CBX5 and reduced CBX5 ubiquitination, thereby promoting CBX5 expression. CBX5 overexpression promoted the proliferation and movement of hypoxic PASMCs with reduced RUNX1 expression and decreased their apoptosis. In conclusion, RUNX1 knockdown inhibits USP15 transcription to promote the ubiquitination and degradation of CBX5, thereby alleviating PH in mice and reducing hypoxia-induced PASMC dysfunction

APOC1 knockdown induces apoptosis and decreases angiogenesis in diffuse large B-cell lymphoma cells through blocking the PI3K/AKT/mTOR pathway

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous metastatic lymphoma that can be treated by targeting angiogenesis. Apolipoprotein C1 (APOC1) plays a significant role in the proliferation and metastasis of various malignant tumors; however, its role in DLBCL—particularly its effects on angiogenesis—remains largely unexplored. This study investigates the correlation between APOC1 expression and patient prognosis in DLBCL. Using APOC1 gene knockdown, apoptosis, migration, and invasion were assessed through flow cytometry, the EDU assay, wound healing, and Transwell assays. Additionally, human umbilical vein endothelial cells (HUVEC) angiogenesis was evaluated. Advanced techniques, such as immunofluorescence, TUNEL assay, and immunohistochemical labeling were employed to analyze the effects of APOC1 knockdown on the PI3K/AKT/mTOR signaling pathway and tumor formation in nude mice. Results showed that APOC1 is overexpressed in DLBCL tissues and cells, with high APOC1 levels associated with poor patient prognosis. In vitro experiments revealed that APOC1 knockdown increased apoptosis and inhibited cell proliferation, migration, invasion, HUVEC angiogenesis, and PI3K/AKT/mTOR signaling pathway protein expression in DLBCL cells. Similarly, in vivo studies demonstrated that APOC1 knockdown significantly reduced tumor growth, angiogenesis-related proteins, and phosphorylated PI3K/AKT/mTOR pathway proteins in nude mice. APOC1 knockdown promotes apoptosis and suppresses angiogenesis in DLBCL cells by inhibiting the PI3K/AKT/mTOR pathway

Plasma extracellular vesicle neurofilament light chain as the biomarkers of the progression of Parkinson’s disease

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by progressive symptoms, underscoring the urgent need for predictive blood biomarkers. Plasma extracellular vesicles (EVs) offer a promising platform for biomarker development, with neurofilament light chain (NfL) emerging as a potential candidate for neurological diseases. This study evaluated plasma EV NfL as a biomarker for disease progression in a PD cohort.A total of 55 patients with PD (PwP) and 58 healthy controls (HCs) were followed, with PwP completing an average of 3.96 visits and HCs 2.25 visits. Plasma EVs were isolated and validated, and EV NfL levels were measured using an immunomagnetic reduction assay. Generalized estimating equations and Spearman correlations assessed relationships between clinical symptom progression and biomarkers. Although no significant differences in plasma EV NfL levels were observed between PwP and HCs over time, changes in plasma EV NfL significantly correlated with motor symptom progression, specifically with adjusted-total and akinetic-rigidity subscores of the Unified PD Rating Scale (UPDRS) Part III. Additionally, changes in UPDRS Part II scores were significantly associated with plasma EV NfL levels. These findings suggest that plasma EV NfL reflects motor symptom progression in PwP, highlighting its potential as a valuable biomarker for monitoring disease progression and guiding clinical trials in PD

Skin pathology in ALS: Diagnostic implications and biomarker potential

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain, resulting in motor deficits and muscle atrophy. Approximately 5–10% of ALS patients are familial (fALS), while the rest are sporadic (sALS). Currently, early diagnosis of ALS cannot be achieved based on clinical manifestations and electromyography due to the lack of effective and easily available biomarkers. The skin and central nervous system (CNS) share the same embryonic origin. Several skin biomarkers have been found in many neurodegenerative diseases, such as abnormal deposition of pathological α-synuclein (α-Syn) in Parkinson\u27s disease. Thus, molecular changes in the skin associated with ALS-specific pathological events could readily be detected and become biomarkers for ALS through skin testing. Here, we summarize the literature on pathological changes in the skin of ALS patients and animal models, including structural abnormalities of the skin, reduced density of skin nerve fibers, abnormal protein aggregation, altered mitochondrial morphology and function, and dysregulation of skin inflammation, which may be useful for early diagnosis and monitoring of ALS progression

Epidemiology, prognostic factors, and survival analysis in small cell esophageal carcinoma: A population-based study with external validation

Small cell esophageal carcinoma (SCEC) is a poorly differentiated esophageal neuroendocrine neoplasm with a poor prognosis. This study aimed to explore the factors and treatment approaches influencing the prognosis of SCEC. In this retrospective study, we collected data from the 18 Surveillance, Epidemiology, and End Results (SEER) registries cohort between 2004 and 2019, as well as from a Chinese institutional registry covering the period from 2012 to 2022. We assessed the annual percentage change (APC) in incidence of SCEC. Kaplan-Meier and Cox regression analyses were conducted to evaluate survival outcomes. Additionally, nomograms were developed for overall survival (OS) and cancer-specific survival (CSS) in the SEER cohort for SCEC and validated in an independent Chinese cohort. This analysis included 299 SCEC patients from the SEER cohort and 66 cases from the Chinese cohort. During the period of 2004–2019, the incidence of SCEC reached a plateau, with an APC of -1.40 (95% confidence interval [CI]: -4.3 to 1.40, P > 0.05). Multivariable Cox regression analysis revealed that age, distant metastasis, and chemotherapy were independent factors for OS, while distant metastasis and chemotherapy were independent factors for CSS. The nomograms developed for OS and CSS in SCEC exhibited remarkable accuracy and reliable predictive capacity in estimating 1-year, 3-year, and 5-year OS and CSS. SCEC is a rare malignancy with aggressive behavior. Distant metastasis is significantly associated with worse OS and CSS in patients with SCEC. Currently, chemotherapy remains the primary treatment approach for SCEC

TBRG4 as a prognostic biomarker and key regulator of cell cycle and EMT in lung cancer

Transforming growth factor β regulator 4 (TBRG4) is upregulated in lung cancer, but its biological role and underlying mechanisms remain poorly understood. In this study, we analyzed pancancer gene expression profiles and clinical data from University of California, Santa Cruz Xena (UCSC Xena) to evaluate the prognostic significance of TBRG4 using univariate and multivariate Cox regression analyses. Genes with a Pearson correlation coefficient above 0.4 with TBRG4 in lung cancer were identified via UALCAN, followed by pathway enrichment analyses to explore their functional associations. To investigate TBRG4’s role in lung cancer progression, we assessed cell proliferation, colony formation, and cell cycle alterations in lung cancer cells following TBRG4 knockdown. Western blot analysis was performed to examine the effects of TBRG4 depletion on key cell cycle regulators and epithelial-mesenchymal transition (EMT) markers. Additionally, the biological significance of TBRG4 was evaluated in vivo using a mouse xenograft model. TBRG4 knockdown significantly inhibited cell proliferation and colony formation while inducing cell cycle arrest and apoptosis in lung cancer cells. Analysis of co-expressed genes in the The Cancer Genome Atlas - Lung Adenocarcinoma (TCGA-LUAD) cohort revealed enrichment in cell cycle-related pathways, aligning with our experimental findings. Furthermore, TBRG4 depletion reduced EMT marker expression and suppressed tumor growth in vivo. Collectively, these findings suggest that TBRG4 may serve as a promising prognostic biomarker and therapeutic target in lung cancer

TCF12 enhances angiogenesis and affects sorafenib response in liver cancer via HIF-1α interaction

Transcription factor 12 (TCF12), a member of the basic Helix-Loop-Helix (bHLH) protein family, plays a crucial role in regulating cell growth and differentiation. It has been implicated in the development and progression of malignant tumors; however, its specific mechanisms in vascularization and drug resistance in liver cancer remain poorly understood. This study aims to explore how the interaction between TCF12 and Hypoxia-Inducible Factor 1-alpha (HIF-1α) affects vascularization and drug sensitivity in liver cancer. Using bioinformatics analysis (n = 374 TCGA samples and n = 50 clinical specimens), we assessed TCF12 expression levels in liver cancer and evaluated their association with patient prognosis. Gene Set Enrichment Analysis (GSEA) was employed to identify related signaling pathways. The expression of TCF12 in liver cancer tissues was examined via Western blotting and immunohistochemistry, while Kaplan-Meier survival analysis was used to analyze the relationship between TCF12 expression and overall survival. Functional assays—including scratch wound repair, tube formation, and endothelial cell permeability tests—were conducted to assess TCF12’s role in angiogenesis. Cell viability assays were performed to evaluate the impact of TCF12 on sorafenib sensitivity, and co-immunoprecipitation experiments were carried out to investigate the interaction between TCF12 and HIF-1α. Our bioinformatics analysis revealed that both TCF12 and HIF-1α are significantly overexpressed in liver cancer and are associated with poor prognosis. Immunohistochemical staining showed a positive correlation between TCF12 expression and the vascularization marker CD31. Furthermore, survival analysis demonstrated that patients with elevated TCF12 expression had significantly shorter overall survival. Functional assays indicated that TCF12 knockdown suppressed blood vessel formation and reduced endothelial cell permeability. Moreover, reducing TCF12 expression increased the sensitivity of liver cancer cells to sorafenib. Notably, overexpression of HIF-1α reversed these effects, and co-immunoprecipitation experiments confirmed a direct interaction between TCF12 and HIF-1α. In summary, this study demonstrates that TCF12 is highly expressed in liver cancer and is associated with poor prognosis. TCF12 promotes angiogenesis by stabilizing HIF-1α and modulates tumor sensitivity to sorafenib, highlighting its potential as a therapeutic target in liver cancer