Loss of Type 2 Bone Morphogenetic Protein Receptor Activates NOD-Like Receptor Family Protein 3/Gasdermin E-Mediated Pyroptosis in Pulmonary Arterial Hypertension.

Background: Pulmonary arterial hypertension (PAH) is an incurable disease initiated by endothelial dysfunction, secondary to vascular inflammation and occlusive pulmonary arterial vascular remodeling, resulting in elevated pulmonary arterial pressure and right heart failure. Previous research has reported that dysfunction of type 2 bone morphogenetic protein receptor (BMPR2) signaling pathway in endothelium is inclined to prompt inflammation in PAH models, but the underlying mechanism of BMPR2 deficiency-mediated inflammation needs further investigation. This study was designed to investigate whether BMPR2 deficiency contributes to pulmonary arterial hypertension via the NLRP3 (NOD-like receptor family protein 3)/GSDME (gasdermin E)-mediated pyroptosis pathway.

Association Between Sugar-Sweetened Beverage Consumption and Frailty Among Older Adults With Hypertension: Evidence From the National Health and Nutrition Examination Survey 1999-2020.

Frailty is a condition characterized by increased vulnerability to adverse health outcomes, particularly among older adults. With the significant prevalence of hypertension and the consumption of sugar-sweetened beverages (SSBs) in this demographic, it is essential to explore their potential combined effects on frailty. This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2020, involving 13,465 hypertensive adults aged 60 and above.

Single-cell transcriptomic analysis of glioblastoma reveals pericytes contributing to the blood-brain-tumor barrier and tumor progression.

The blood-brain barrier is often altered in glioblastoma (GBM) creating a blood-brain-tumor barrier (BBTB) composed of pericytes. The BBTB affects chemotherapy efficacy. However, the expression signatures of BBTB-associated pericytes remain unclear.

Programmed cell death: molecular mechanisms, biological functions, diseases, and therapeutic targets.

Programmed cell death represents a precisely regulated and active cellular demise, governed by a complex network of specific genes and proteins. The identification of multiple forms of programmed cell death has significantly advanced the understanding of its intricate mechanisms, as demonstrated in recent studies. A thorough grasp of these processes is essential across various biological disciplines and in the study of diseases.

Spatiotemporal evolutionary process of osteosarcoma immune microenvironment remodeling and C1QBP-driven drug resistance deciphered through single-cell multi-dimensional analysis.

The tumor immune microenvironment has manifested a crucial correlation with tumor occurrence, development, recurrence, and metastasis. To explore the mechanisms intrinsic to osteosarcoma (OS) initiation and progression, this study synthesizes multiple single-cell RNA sequencing data sets, constructing a comprehensive landscape of the OS microenvironment. Integrating single-cell RNA sequencing with bulk RNA sequencing data has enabled the identification of a significant correlation between heightened expression of the fatty acid metabolism-associated gene () and patient survival in OS.

Anoikis in cell fate, physiopathology, and therapeutic interventions.

The extracellular matrix (ECM) governs a wide spectrum of cellular fate processes, with a particular emphasis on anoikis, an integrin-dependent form of cell death. Currently, anoikis is defined as an intrinsic apoptosis. In contrast to traditional apoptosis and necroptosis, integrin correlates ECM signaling with intracellular signaling cascades, describing the full process of anoikis.

There Is No Direct Causal Relationship Between Coronary Artery Disease and Alzheimer Disease: A Bidirectional Mendelian Randomization Study.

Background: The association between poor cardiovascular health and cognitive decline as well as dementia progression has been inconsistent across studies. This study used Mendelian randomization (MR) to investigate the causal relationship between Alzheimer disease (AD), circulating levels of total-tau, and coronary artery disease (CAD).

Methods And Results: This study used MR to investigate the causal relationship between AD or circulating levels of total-tau and CAD, including ischemic heart disease, myocardial infarction, coronary heart disease, coronary atherosclerosis, and heart failure.

Causal role of vitamin E in atopic dermatitis risk: A Mendelian randomization study.

Prior studies suggested that vitamin E might be beneficial in alleviating atopic dermatitis, but confirming a causal link was hindered by limitations such as sample sizes and unaccounted confounders. The present study aimed to clarify this through Mendelian randomization (MR) analysis. GWAS summary statistics was obtained from public databases encompassing a study on vitamin E and two studies related to atopic dermatitis.

Extracellular vesicles and endothelial dysfunction in infectious diseases.

Cardiovascular diseases (CVDs) remain the leading cause of mortality and morbidity globally. Studies have shown that infections especially bacteraemia and sepsis are associated with increased risks for endothelial dysfunction and related CVDs including atherosclerosis. Extracellular vesicles (EVs) are small, sealed membrane-derived structures that are released into body fluids and blood from cells and/or microbes and are critically involved in a variety of important cell functions and disease development, including intercellular communications, immune responses and inflammation.

Airway epithelial-derived exosomes induce acute asthma exacerbation after respiratory syncytial virus infection.

Acute asthma exacerbation refers to the progressive deterioration of asthma symptoms that is always triggered by virus infection represented by respiratory syncytial virus (RSV). After RSV infection, exaggerated Th2-mediated pulmonary inflammation is the critical pathological response of asthmatic patients with acute exacerbation. Significantly, airway epithelial cells, being the primary targets of RSV infection, play a crucial role in controlling the pulmonary inflammatory response by releasing airway epithelial cell-derived exosomes (AEC-Exos), which potentially influence the development of asthma.

New insights into immune cells in cancer immunotherapy: from epigenetic modification, metabolic modulation to cell communication.

Cancer is one of the leading causes of death worldwide, and more effective ways of attacking cancer are being sought. Cancer immunotherapy is a new and effective therapeutic method after surgery, radiotherapy, chemotherapy, and targeted therapy. Cancer immunotherapy aims to kill tumor cells by stimulating or rebuilding the body's immune system, with specific efficiency and high safety.

Epigenetic modifications in obesity-associated diseases.

The global prevalence of obesity has reached epidemic levels, significantly elevating the susceptibility to various cardiometabolic conditions and certain types of cancer. In addition to causing metabolic abnormalities such as insulin resistance (IR), elevated blood glucose and lipids, and ectopic fat deposition, obesity can also damage pancreatic islet cells, endothelial cells, and cardiomyocytes through chronic inflammation, and even promote the development of a microenvironment conducive to cancer initiation. Improper dietary habits and lack of physical exercise are important behavioral factors that increase the risk of obesity, which can affect gene expression through epigenetic modifications.

Inhibition of 15-hydroxyprostaglandin dehydrogenase protects neurons from ferroptosis in ischemic stroke.

Ischemic stroke is an acute serious cerebrovascular disease with high mortality and disability. Ferroptosis is an important regulated cell death (RCD) in ischemic stroke. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH), a degrading enzyme of prostaglandin E2 (PGE2), is shown to regulate RCD such as autophagy and apoptosis.

ATR-dependent ubiquitin-specific protease 20 phosphorylation confers oxaliplatin and ferroptosis resistance.

Oxaliplatin (OXA) resistance is a major clinic challenge in hepatocellular carcinoma (HCC). Ferroptosis is a kind of iron-dependent cell death. Triggering ferroptosis is considered to restore sensitivity to chemotherapy.

Targeted therapies in bladder cancer: signaling pathways, applications, and challenges.

Bladder cancer (BC) is one of the most prevalent malignancies in men. Understanding molecular characteristics via studying signaling pathways has made tremendous breakthroughs in BC therapies. Thus, targeted therapies including immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitor (TKI) have markedly improved advanced BC outcomes over the last few years.

Deep learning in precision medicine and focus on glioma.

Deep learning (DL) has been successfully applied to different fields for a range of tasks. In medicine, DL methods have been also used to improve the efficiency of disease diagnosis. In this review, we first summarize the history of the development of artificial intelligence models, demonstrate the features of the subtypes of machine learning and different DL networks, and then explore their application in the different fields of precision medicine, such as cardiology, gastroenterology, ophthalmology, dermatology, and oncology.

Flourishing tumor organoids: History, emerging technology, and application.

Malignant tumors are one of the leading causes of death which impose an increasingly heavy burden on all countries. Therefore, the establishment of research models that closely resemble original tumor characteristics is crucial to further understanding the mechanisms of malignant tumor development, developing safer and more effective drugs, and formulating personalized treatment plans. Recently, organoids have been widely used in tumor research owing to their advantages including preserving the structure, heterogeneity, and cellular functions of the original tumor, together with the ease of manipulation.

The ubiquitin-specific protease 5 mediated deubiquitination of LSH links metabolic regulation of ferroptosis to hepatocellular carcinoma progression.

Epigenetic regulators and posttranslational modifications of proteins play important roles in various kinds of cancer cell death, including ferroptosis, a non-apoptotic form of cell death. However, the interplay of chromatin modifiers and deubiquitinase (DUB) in ferroptosis remains unclear. Here, we found that ubiquitin-specific protease 5 (USP5) is regarded as a bona fide DUB of lymphoid-specific helicase (LSH), a DNA methylation repressor, in hepatocellular carcinoma (HCC).

Development and validation of a prognostic model incorporating tumor thrombus grading for nonmetastatic clear cell renal cell carcinoma with tumor thrombus: A multicohort study.

There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole-exome sequencing on normal-tumor-thrombus-metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs).

The reconfiguration pattern of individual brain metabolic connectome for Parkinson's disease identification.

F-Fluorodeoxyglucose positron emission tomography (F-FDG PET) is widely employed to reveal metabolic abnormalities linked to Parkinson's disease (PD) at a systemic level. However, the individual metabolic connectome details with PD based on F-FDG PET remain largely unknown. To alleviate this issue, we derived a novel brain network estimation method for individual metabolic connectome, that is, Jensen-Shannon Divergence Similarity Estimation (JSSE).

TXNL4B regulates radioresistance by controlling the PRP3-mediated alternative splicing of FANCI.

Ionizing radiation (IR) has been extensively used for cancer therapy, but the radioresistance hinders and undermines the radiotherapy efficacy in clinics greatly. Here, we reported that the spliceosomal protein thioredoxin-like 4B (TXNL4B) is highly expressed in lung tissues from lung cancer patients with radiotherapy. Lung cancer cells with TXNL4B knockdown illustrate increased sensitivity to IR.

Pan-cancer analyses reveal molecular and clinical characteristics of cuproptosis regulators.

Imbalance in copper homeostasis can be lethal. A recent study found that excess copper induces cell death in a way that has never been characterized before, which is dependent on mitochondrial stress and is referred to as "cuproptosis." The role of cuproptosis in tumors has not yet been elucidated.

ATF4/TXNIP/REDD1/mTOR signaling mediates the antitumor activities of liver X receptor in pancreatic cancers.

Background: Limited by difficulties in early detection and availabilities of effective treatments, pancreatic cancer is a highly malignant disease with poor prognosis. Nuclear receptors are a family of ligand-dependent transcription factors that are highly druggable therapeutic targets playing critical roles in human physiological and pathological development, including cancer. In this study, we explored the therapeutic potential as well as the molecular mechanisms of liver X receptor (LXR) agonist GW3965 in pancreatic cancer.