Cerebral white matter damage in patients with end-stage kidney disease associates with cognitive impairment.

Background: Damage to brain white matter often occurs in individuals with chronic kidney disease, which might be related to their cognitive decline. This study aims to investigate tract-specific white matter damage in patients with end-stage kidney disease by using fixel-based analysis.

Methods: Images of 31 end-stage kidney disease patients and 16 normal controls (aged: 61.

The positive feedback loop between SP1 and MAP2K2 significantly drives resistance to VEGFR inhibitors in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common and aggressive malignancies of the urinary system. Despite being the first-line treatment for advanced ccRCC, vascular endothelial growth factor receptor inhibitors (VEGFRis) face significant limitations due to both initial and acquired resistance, which impede complete tumor eradication. Using a CRISPR/Cas9 library screening approach, was identified as a resistance-associated gene for three prevalent VEGFRis (Sunitinib, Axitinib, and Sorafenib).

The Dual Role of Cellular Senescence in Macrophages: Unveiling the Hidden Driver of Age-Related Inflammation in Kidney Disease.

Aging is a complex biological process that involves the gradual decline of cellular, tissue, and organ functions. In kidney, aging manifests as tubular atrophy, glomerulosclerosis, and progressive renal function decline. The critical role of senescence-associated macrophage in diseases, particularly kidney diseases, is increasingly recognized.

Regulation of INPP5E in Ciliogenesis, Development, and Disease.

Inositol polyphosphate-5-phosphatase E (INPP5E) is a 5-phosphatase critically involved in diverse physiological processes, including embryonic development, neurological function, immune regulation, hemopoietic cell dynamics, and macrophage proliferation, differentiation, and phagocytosis. Mutations in cause Joubert and Meckel-Gruber syndromes in humans; these are characterized by brain malformations, microphthalmia, situs inversus, skeletal abnormalities, and polydactyly. Recent studies have demonstrated the key role of INPP5E in governing intracellular processes like endocytosis, exocytosis, vesicular trafficking, and membrane dynamics.

Downregulated CCND3 Is a Key Event Driving Lung Adenocarcinoma Metastasis during Acquired Cisplatin Resistance.

Cyclin D3 (CCND3), a member of the cyclin D family, is known to promote cell cycle transition. In this study, we found that CCND3 was downregulated in cisplatin-resistant (-diamminedichloroplatinum, DDP) lung adenocarcinoma (LUAD) cells. The loss of CCND3 indeed impeded cell cycle transition.

Tubulointerstitial nephritis antigen-like 1 promotes the progression of liver fibrosis after HCV eradication with direct-acting antivirals.

Although therapies based on direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus (HCV) in patients, there is still a high risk of liver fibrosis even after a sustained virological response. Therefore, it is of great clinical importance to understand the mechanism of potential factors that promote liver fibrosis after virological cure by treatment with DAAs. Here, we found that tubulointerstitial nephritis antigen-like 1 (TINAGL1) is significantly increased in HCV-infected hepatocytes and in the liver of patients with liver fibrosis, and that higher TINAGL1 expression persists in HCV-eradicated hepatocytes after treatment with DAAs.

Involvement of Tim-3 in Maternal-fetal Tolerance: A Review of Current Understanding.

As the first T cell immunoglobulin mucin (Tim) family member to be identified, Tim-3 is a powerful immune checkpoint that functions in immunoregulation and induction of tolerance. Conventionally, Tim-3 is considered to play a role in adaptive immunity, especially in helper T cell-mediated immune responses. As researches progress, Tim-3 has been detected in a wider range of cell types, modulating cell function through ligand-receptor interactions and other pathways.

S6K1 is a Targetable Vulnerability in Tumors Exhibiting Plasticity and Therapy Resistance.

Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms associated with cancer cell plasticity and heterogeneity. We used a chemical biology approach to identify protein targets in cancer cells exhibiting diverse driver mutations and representing models of tumor lineage plasticity and therapy resistance. An unbiased screen of a drug library was performed against cancer cells followed by synthesis of chemical analogs of the most effective drug.

Glycine Decarboxylase Regulates Renal Carcinoma Progression via Interferon Stimulated Gene Factor 3-Mediated Pathway.

Renal cell carcinoma (RCC) is considered as a "metabolic disease" due to various perturbations in metabolic pathways that could drive cancer development. Glycine decarboxylase (GLDC) is a mitochondrial enzyme that takes part in the oxidation of glycine to support nucleotide biosynthesis via transfer of one-carbon units. Herein, we aimed to investigate the potential role of GLDC in RCC development.

Mitochondrial SIRT2-mediated CPT2 deacetylation prevents diabetic cardiomyopathy by impeding cardiac fatty acid oxidation.

Dysregulated energy metabolism, particularly lipid metabolism disorders, has been identified as a key factor in the development of diabetic cardiomyopathy (DCM). Sirtuin 2 (SIRT2) is a deacetylase involved in the regulation of metabolism and cellular energy homeostasis, yet its role in the progression of DCM remains unclear. We observed significantly reduced SIRT2 expression in DCM model mice.

Lingo1 in the hippocampus contributes to cognitive dysfunction after anesthesia and surgery in aged mice.

Cognitive impairment caused by anesthesia and surgery is one of the most common complications with multiple etiologies that occurs in elderly patients. The underlying mechanisms are not fully understood, and there is a lack of therapeutic strategies. Increasing evidence has demonstrated that myelin loss, abnormal phosphorylation of the tau protein and neuronal apoptosis are substantial driving factors of cognitive deficits.

TAGLN-RhoA/ROCK2-SLC2A3-mediated Mechano-metabolic Axis Promotes Skin Fibrosis.

Skin fibrotic diseases are characterized by abnormal fibroblast function and excessive deposition of extracellular matrix. Our previous single-cell sequencing results identified an enriched fibroblast subcluster in skin fibrotic tissues that highly expresses the actin cross-linking cytoskeletal protein Transgelin (TAGLN), which bridges the mechanical environment of tissues and cellular metabolism. Therefore, we aimed to investigate the role of TAGLN in the pathogenesis of skin fibrosis.

Caveolin-1 mitigates the advancement of metabolic dysfunction-associated steatotic liver disease by reducing endoplasmic reticulum stress and pyroptosis through the restoration of cholesterol homeostasis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, which has the potential to advance to fibrosis. CAV1 has the effects of improving liver lipid deposition in MASLD, however, the potential mechanism is largely unknown. Here, we establish a MASLD mouse model in CAV1 knockout (KO) mice and perform transcriptome analysis on livers from mice to investigate the effects of CAV1 in MASLD progression.

FKBP10 Promotes the Muscle Invasion of Bladder Cancer via Lamin A Dysregulation.

Bladder cancer (BC) is a prevalent urinary malignancy and muscle-invasive bladder cancer (MIBC) is particularly aggressive and associated with poor prognosis. One of MIBC features is the nuclear atypia. However, the molecular mechanism underlying MIBC remains unclear.

New insights into mitochondrial quality control in anthracycline-induced cardiotoxicity: molecular mechanisms, therapeutic targets, and natural products.

Anthracyclines (ANTs) are widely used in cancer therapy, particularly for lymphoma, sarcoma, breast cancer, and childhood leukemia, and have become the cornerstone of chemotherapy for various malignancies. However, it is associated with fatal and dose-dependent cardiovascular complications, especially cardiotoxicity. Mitochondrial quality control mechanisms, encompassing mitophagy, mitochondrial dynamics, and mitochondrial biogenesis, maintain mitochondrial homeostasis in the cardiovascular system.

FAT1 knockdown enhances the CSC properties of HNSCC through p-CaMKII-mediated inactivation of the IFN pathway.

FAT atypical cadherin 1 (), which encodes an atypical cadherin-coding protein, has a high mutation rate and is commonly regarded as a tumor suppressor gene in head and neck squamous cell carcinoma (HNSCC). Nonetheless, the potential regulatory mechanisms by which FAT1 influences the progression of HNSCC remain unresolved. In this context, we reported that FAT1 was downregulated in tumor tissues/cells compared with normal tissues/cells and that it was correlated with the clinicopathological features and prognosis of HNSCC.

The Cyclin-Dependent Kinase 8 Inhibitor E966-0530-45418 Attenuates Pulmonary Fibrosis and .

Pulmonary fibrosis (PF) is a high-mortality lung disease with limited treatment options, highlighting the need for new therapies. Cyclin-dependent kinase 8 (CDK8) is a promising target due to its role in regulating transcription via the TGF-β/Smad pathway, though CDK8 inhibitors have not been thoroughly studied for PF. This study aims to evaluate the potential of E966-0530-45418, a novel CDK8 inhibitor, in mitigating PF progression and explores its underlying mechanisms.

Cold atmospheric plasma potentiates ferroptosis via EGFR(Y1068)-mediated dual axes on GPX4 among triple negative breast cancer cells.

Cold atmospheric plasma (CAP) has been proposed as an emerging onco-therapeutics that can specifically kill cancer cells without harming healthy cells. Here we explore its potency in triggering ferroptosis in transformed cells using triple negative breast cancer as the disease model. Through the whole transcriptome sequencing, mass spectrometry analysis, point mutation, and a series of and molecular assays, we identified two signaling axes centered at EGFR(Y1068), i.

HIF-2α/LPCAT1 orchestrates the reprogramming of lipid metabolism in ccRCC by modulating the FBXW7-mediated ubiquitination of ACLY.

The current research revealed a strong link between lipid reprogramming and dysregulated lipid metabolism to the genesis and development of clear cell renal cell carcinoma (ccRCC). Pathologically, ccRCC exhibits a high concentration of lipid droplets within the cytoplasm. HIF-2α expression has previously been demonstrated to be elevated in ccRCC caused by mutations in the von Hippel-Lindau (VHL) gene, which plays a vital role in the development of renal cell carcinoma.

Deficiency of Epithelial PIEZO1 Alleviates Liver Steatosis Induced by High-Fat Diet in Mice.

PIEZO1 has been found to play a vital role in regulating intestinal epithelial cells (IEC) function and maintaining intestinal barrier in recent years. Therefore, IEC PIEZO1 might exert a significant impact on liver metabolism through the gut-liver axis, but there is no research on this topic currently. Classic high-fat diet (HFD) model and mice with IEC-specific deficiency of PIEZO1 ( ) were used to explore the problem.

TEAD1 Prevents Necroptosis and Inflammation in Cisplatin-Induced Acute Kidney Injury Through Maintaining Mitochondrial Function.

Cisplatin is widely used for the treatment of solid tumors and its antitumor effects are well established. However, a known complication of cisplatin administration is acute kidney injury (AKI). In this study, we examined the role of TEA domain family member 1 (TEAD1) in the pathogenesis of cisplatin-induced AKI.

BMSCs-derived small extracellular vesicles antagonize cerebral endothelial Caveolin-1 driven autophagic degradation of tight-junction proteins to protect blood-brain barrier post-stroke.

Bone marrow mesenchymal stem cells (BMSCs) -derived extracellular vesicles (EVs), especially small EVs (sEVs), were vastly reported to enable multiple restorative effects on ischemic stroke, yet the protective mechanism of blood-brain barrier (BBB) has not been fully illustrated. In the present study, we investigated the therapeutic effects and mechanism of BMSCs-derived sEVs on BBB injury after ischemic stroke. In-vivo, administering sEVs to transient middle cerebral artery occlusion (tMCAo) mice mitigated the brain infarct volume, BBB permeability and neural apoptosis, and improved the cerebral blood flow perfusion and neurological function.

USP25 stabilizes STAT6 to promote IL-4-induced macrophage M2 polarization and fibrosis.

As a leading cause of morbidity and mortality, fibrosis is the common pathway of various chronic inflammatory diseases in organs and causes death in a large number of patients. It can destroy the structure and function of organs and ultimately lead to organ failure, which is a major cause of disability and death in many diseases. However, the regulatory mechanism of organ fibrosis is not well clear and the lack of effective drugs and treatments, which seriously endangers human health and safety.

Fibroblasts in heterotopic ossification: mechanisms and therapeutic targets.

Heterotopic ossification (HO) refers to the abnormal formation of bone in non-skeletal tissues. Fibroblasts have traditionally been viewed as stationary cells primarily responsible for producing extracellular matrix during tissue repair and fibrosis. However, recent discoveries regarding their plasticity-encompassing roles in inflammation, extracellular matrix remodeling, and osteogenesis-highlight their potential as key contributors to the development of HO.

Toll-like receptor adaptor protein TIRAP has specialized roles in signaling, metabolic control and leukocyte migration upon wounding in zebrafish larvae.

The TIRAP protein is an adaptor protein in TLR signaling which links TLR2 and TLR4 to the adaptor protein Myd88. The transcriptomic profiles of zebrafish larvae from a , and mutant and the corresponding wild type controls under unchallenged developmental conditions revealed a specific involvement of in calcium homeostasis and myosin regulation. Metabolomic profiling showed that the mutation results in lower glucose levels, whereas a mutation leads to higher glucose levels.