Smad1 Promotes Tumorigenicity and Chemoresistance of Glioblastoma by Sequestering p300 From p53.

Acetylation is critically required for p53 activation, though it remains poorly understood how p53 acetylation is regulated in glioblastoma (GBM). This study reveals that p53 acetylation is a favorable prognostic marker for GBM, regardless of p53 status, and that Smad1, a key negative regulator of p53 acetylation, is involved in this process. Smad1 forms a complex with p53 and p300, inhibiting p300's interaction with p53 and leading to reduced p53 acetylation and increased Smad1 acetylation in GBM.

Evaluation of the Clinical Safety of the Low-Cost Warburg Therapy for the Treatment of Patients With Advanced Cancers.

Background: Rising cancer care costs are becoming cost prohibitive for lower income people worldwide. We developed the Warburg protocol as a low-cost option for the treatment of cancer that was inspired. It was developed to exploit an Achilles heel which is a hallmark of cancer cells; the metabolic requirement for higher levels of glucose than normal cells.

Gut microbiota metabolism of branched-chain amino acids and their metabolites can improve the physiological function of aging mice.

The metabolism of branched-chain amino acids by gut microbiota can improve overall health and may reverse aging. In this study, we investigated Parabacteroides merdae, a gut microbe that is known to catabolise branched-chain amino acids (BCAAs). Three metabolites of BCAAs isovalerate, 2-methylbutyrate, and isobutyrate were used to treat D-gal induced aging mice.

Peli1 Deficiency in Macrophages Attenuates Pulmonary Hypertension by Enhancing Foxp1-Mediated Transcriptional Inhibition of IL-6.

Background: The infiltration of macrophages into the lungs is a common characteristic of perivascular inflammation, contributing to vascular remodeling in pulmonary hypertension (PH). Peli1 (pellino E3 ubiquitin-protein ligase 1) plays a critical role in regulating the production of proinflammatory cytokines and the polarization of macrophages in various diseases. However, the role of Peli1 in PH remains to be investigated.

Slow Metabolism-Driven Amplification of Hepatic PPARγ Agonism Mediates Benzbromarone-Induced Obesity-Specific Liver Injury.

Obesity and nonalcoholic fatty liver disease (NAFLD) are established risk factors for drug-induced liver injury (DILI). The previous study demonstrates that benzbromarone (BBR), a commonly prescribed pharmaceutical agent for managing gout and hyperuricemia, exacerbates hepatic steatosis and liver injury specifically in obese individuals. However, the precise mechanism underpinning this adverse effect remains incompletely elucidated.

Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice.

The prevalent itching condition associated with aging, historically referred to as senile pruritus, diminishes quality of life. Despite its impact, effective treatments remain elusive, largely due to an incomplete understanding of its pathological cause. In this study, we reveal a subset of dorsal root ganglion neurons enriched with Zn2+ that express the vesicular Zn2+ transporter TMEM163.

Multi-omic molecular characterization and diagnostic biomarkers for occult hepatitis B infection and HBsAg-positive hepatitis B infection.

Background: The pathological and physiological characteristics between HBsAg-positive HBV infection and occult hepatitis B infection (OBI) are currently unclear. This study aimed to explore the immune microenvironment in the peripheral circulation of OBI patients through integration of proteomic and metabolomic sequencing, and to identify molecular biomarkers for clinical diagnosis of HBsAg-positive HBV and OBI.

Methods: This research involved collection of plasma from 20 patients with OBI (negative for HBsAg but positive for HBV DNA, with HBV DNA levels < 200 IU/mL), 20 patients with HBsAg-positive HBV infection, and 10 healthy individuals.

Novel Approach for Biosensor-Based Imaging of Cysteine Levels in Ischemeic Heart Disease: Insights from Preclinical Models and Human Samples.

Cardiovascular diseases (CVDs) pose a serious threat to human health, with atherosclerosis being a leading cause of heart disease and stroke. Elevated cysteine (Cys) levels have been closely linked to an increased risk of cardiovascular diseases, underscoring its significance in cardiovascular health. However, current detection methods for cysteine in serum and atherosclerotic plaques present challenges in sensitivity, specificity, dynamic monitoring, and invasiveness.

Interaction Between DHCR24 and hsa_circ_0015335 Facilitates Cognitive Impairment in Cerebral Small Vessel Disease Patients.

Aims: The study attempted to determine the underlying role and regulation mechanism of 3β-hydroxysterol-Δ24 reductase (DHCR24) in the pathophysiology of cerebral small vessel disease-associated cognitive impairment (CSVD-CI). An RNA high-throughput sequencing and independent verification were conducted to identify potential circRNAs becoming the upstream regulator.

Methods: RNA sequencing was performed in whole-blood samples in cohort 1 (10 CSVD-CI and 8 CSVD with cognitively normal [CSVD-CN] patients).

The role and mechanism of P2X7R in cirrhotic cardiomyopathy.

In the context of liver cirrhosis, the incidence of myocardial inflammation and apoptosis escalates, contributing to the development and progression of cirrhotic cardiomyopathy. The P2X7 receptor, a purinergic receptor linked to inflammatory processes, has been identified in the etiology of a range of autoinflammatory, autoimmune, chronic inflammatory, and metabolic disorders. Despite this, the specific role of the P2X7 receptor in the etiology of cirrhotic cardiomyopathy remains to be elucidated.

Circular RNA HIPK3 mediates epithelial-mesenchymal transition of retinal pigment epithelial cells by sponging multiple microRNAs.

Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells plays key roles in the pathogenesis of multiple vitreoretinal diseases, leading to profound and permanent vision loss. Circular RNAs (circRNAs) are widespread and functional endogenous RNAs that could regulate gene expression in eukaryotes. The functions of circRNAs in mediating EMT has been reported in several diseases.

Lovastatin-mediated pharmacological inhibition of Formin protein DIAPH1 suppresses tumor immune escape and boosts immunotherapy response.

Background: The immunosuppressive tumor microenvironment (TME) is a key characteristic of human cancer. Immunotherapy has emerged as a promising treatment strategy to overcome immune escape and has gained widespread use in recent years. In particular, the blockade of PD-1/PD-L1 interaction holds significant importance in oncotherapy.

Pulrodemstat, a selective inhibitor of KDM1A, suppresses head and neck squamous cell carcinoma growth by triggering apoptosis.

Background: Chemotherapy is often ineffective as a first-line treatment for head and neck squamous cell carcinoma (HNSCC), and a more precise and effective therapeutic option is urgently needed.

Methods: High-throughput screening of a histone demethylase inhibitor library was performed to identify potential drugs for treating HNSCC. The Cancer Genome Atlas (TCGA) and single-cell sequencing were used to evaluate the potential diagnostic value and expression distribution of candidate drug targets.

Nonlinear association of alkaline phosphatase-to-albumin ratio with all-cause and cancer mortality: Evidence from NHANES 2005 to 2016.

The relationship between the alkaline phosphatase-to-albumin ratio (APAR) and mortality remains unclear. This research looked into the association between APAR levels and cause-specific mortality in US adults. A cohort of 7561 participants from National Health and Nutrition Examination Survey (2005-2016) was analyzed, with mortality outcomes collected from National Death Index records.

Aberrant hippocampal intrinsic morphological connectivity patterns in Neuromyelitis optica spectrum disorder with cognitive impairment: Insights from an individual-based morphological brain network.

Background: Although several clinical studies have demonstrated that hippocampus volume loss in neuromyelitis optica spectrum disorder (NMOSD) may be a significant predictor of cognition, no consensus has been reached. To investigate the alterations of the intrinsic ,hippocampal morphological networks in cognitively impaired NMOSD patients and their correlations with cognitive performance.

Methods: 38 NMOSD patients and 39 healthy controls (HC) were enrolled.

LncRNA MYOSLID contributes to PH via targeting BMPR2 signaling in pulmonary artery smooth muscle cell.

Background/objective: The pathogenesis and vascular remodeling during pulmonary hypertension (PH) have been associated with dysregulation of bone morphogenetic protein receptor type 2 (BMPR2) and transforming growth factor-β (TGF-β) signaling in pulmonary artery smooth muscle cells (PASMCs). Evidence suggests that the human-specific lncRNA MYOSLID is a transcriptional target of the TGF-β/SMAD pathway. In this study, we investigated the involvement of MYOSLID in the pathogenesis of PH.

Comprehensive analysis and validation of TP73 as a biomarker for calcium oxalate nephrolithiasis using machine learning and in vivo and in vitro experiments.

Calcium oxalate (CaOx) nephrolithiasis constitutes approximately 75% of nephrolithiasis cases, resulting from the supersaturation and deposition of CaOx crystals in renal tissues. Despite their prevalence, precise biomarkers for CaOx nephrolithiasis are lacking. With advances in high-throughput sequencing, we aimed to identify biomarkers of CaOx nephrolithiasis by combining two CaOx nephrolithiasis datasets (GSE73680 and GSE117518).

Triglyceride-lowering therapies in hypertriglyceridemia-associated acute pancreatitis in China: a multicentre prospective cohort study.

Background: No specific triglyceride-lowering therapy is recommended in patients with hypertriglyceridemia-associated acute pancreatitis (HTG-AP), primarily because of the lack of quality evidence. This study aimed to describe practice variations in triglyceride-lowering therapies for early HTG-AP patients and assess whether more rapid triglyceride decline is associated with improving organ failure.

Methods: This is a multicentre, prospective cohort study recruiting HTG-AP patients with elevated plasma triglyceride (> 11.

Multimodal ultrasound plus tumor markers demonstrates a high value in enhanced diagnosis of breast cancer.

Objective: To determine the diagnostic value of multimodal ultrasound combined with tumor markers in breast cancer (BC).

Methods: A retrospective analysis was conducted on 198 patients with breast lesions treated at the Affiliated Wuxi People's Hospital of Nanjing Medical University between May 2020 and May 2023. All patients underwent multimodal ultrasound and tumor marker testing.

Mitophagy drives maldifferentiation of tissue-resident memory T cells in patients with rheumatoid arthritis.

Objective: To investigate the function of mitophagy in instructing T-cell differentiation of patients with rheumatoid arthritis (RA).

Method: The mRNA and protein levels of optic atrophy protein-1 were detected in T cells from 94 RA patients and 37 age- and sex-matched healthy individuals by quantitative polymerase chain reaction and Western blotting. The impact of mitophagy on the differentiation of T cells was determined by flow cytometry.