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.

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.

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.

Smad2 Cooperating with TGIF2 Contributes to EMT and Cancer Stem Cells Properties in Pancreatic Cancer via Co-Targeting SOX2.

The underlying mechanisms between cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) remain unclear. In this study, we identified TGIF2 as a target gene of CSC using sncRNA and machine learning. TGIF2 is closely related to the expression of SOX2, EGFR, and E-cadherin, indicating poor prognosis.

Fluorescent identification of axons, dendrites and soma of neuronal retinal ganglion cells with a genetic marker as a tool for facilitating the study of neurodegeneration.

This study characterizes a fluorescent -tdTomato neuronal reporter mouse line with strong labeling of axons throughout the optic nerve, of retinal ganglion cell (RGC) soma in the ganglion cell layer (GCL), and of RGC dendrites in the inner plexiform layer (IPL). The model facilitated assessment of RGC loss in models of degeneration and of RGC detection in mixed neural/glial cultures. The tdTomato signal showed strong overlap with >98% cells immunolabeled with RGC markers RBPMS or BRN3A, consistent with the ubiquitous presence of the vesicular glutamate transporter 2 (VGUT2, SLC17A6) in all RGC subtypes.

Orofacial Cleft and Its Association with Consanguineous Marriage and Other Risk Factors: A Case-control Study from a Tertiary Care Hospital in Jammu Province.

Background: Orofacial cleft is among the most common craniofacial malformations. It presents a complex and multifactorial etiology that involves genetic and environmental factors. One of the etiological factors is consanguinity (marriage between blood relatives).

Anti-Mesothelin CAR-NK cells as a novel targeted therapy against cervical cancer.

Resistance to the currently available treatment paradigms is one of the main factors that contributes to poor outcomes in patients with advanced cervical cancer. Novel targeted therapy approaches might enhance the patient's treatment outcome and are urgently needed for this malignancy. While chimeric-antigen receptor (CAR)-based adoptive immunotherapy displays a promising treatment strategy for liquid cancers, their use against cervical cancer is largely unexplored.

Elucidating the Role of Estrogen Effects in Leukemia: Insights from Single-Cell RNA Sequencing and Mendelian Randomization.

Epidemiological studies have confirmed the potential role of estrogen effects in influencing the development and outcome of leukemia. Estrogen effects are increasingly attracting research interest for their potential antitumor effects beyond gynecological tumors. However, their causal relationship remains unclear.

Uncovering the Role of in Prostate Cancer: Insights from Genetic and Expression Analyses.

Biochemical recurrence (BCR) is a critical concern in prostate cancer management; however, its underlying genetic determinants remain poorly understood. The () gene family is involved in cellular detoxification and biosynthetic processes and has been implicated in various cancers. This study investigated the association between the family members and prostate cancer recurrence.

Colorectal Cancer and Its Microenvironment: A Brief Review.

Background: The narrative review aims to explore CRC pathogenesis by deciphering genetic-environmental interactions, analyzing the tumor microenvironment's role, and assessing treatment responses. These objectives seek to enhance clinical decision-making and improve CRC patient care through a comprehensive understanding of the disease.

Methods: A narrative review from 2019 to 2024 on colorectal cancer (CRC) pathogenesis and treatment strategies was conducted.

A missense mutation in the gene in a patient with autism spectrum disorder and epilepsy.

The gene (OMIM: 608271) encodes the Microtubule-Actin Cross-Linking Factor 1 protein. Existing medical research shows that genetic mutations in the gene have been associated with neurodevelopmental and neurodegenerative disorders, with variants of unknown significance also linked to autism spectrum disorder (ASD). However, the number of reported autism disorder or epilepsy cases associated with mutations remains limited.

Insulin-Like Growth Factor-1 (IGF-1) Deficiency and Metabolic-Dysfunction-Associated Steatotic Liver Disease in a Young Patient.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in the Western world. MASLD-associated cirrhosis prevalence is on the rise along with the obesity and metabolic syndrome epidemic. Genetic factors are included in the multi-hit model of MASLD pathogenesis and insulin-like growth factor-1 (IGF-1) has an important role.

Genomics Reveal Population Structure and Intergeneric Hybridization in an Endangered South American Bird: Implications for Management and Conservation.

Genomics is an invaluable tool for conservation, particularly for endangered species impacted by wildlife trafficking. This study uses genomic data to provide new insights to aid conservation and management of endangered species, using as a case study the Yellow cardinal (), a bird endemic to southern South America severely affected by illegal trade and the transformation of its natural habitat. We explore population structure within the Yellow cardinal, delimiting management units and describing connectivity among them.

An expanded substrate scope for cross-chiral ligation enables efficient synthesis of long l-RNAs.

Despite the growing interest in mirror-image l-oligonucleotides, both as a robust nucleic acid analogue and as an artificial genetic polymer, their broader adoption in biochemical research and medicine remains hindered by challenges associated with the synthesis of long sequences, especially for l-RNA. Herein, we present a novel strategy for assembling long l-RNAs the joining of two or more shorter fragments using cross-chiral ligase ribozymes together with new substrate activation chemistry. We show that 5'-monophosphorylated l-RNA, which is readily prepared by solid-phase synthesis, can be activated by chemical attachment of a 5'-adenosine monophosphate (AMP) or diphosphate (ADP), yielding 5'-adenosyl(di- or tri-)phosphate l-RNA.