PRDM16 acts as a therapeutic downstream target of TGF-β signaling in chronic kidney disease.

Transforming growth factor beta (TGF-β) signaling is the master modulator of renal fibrosis. However, targeting drugs have failed to prevent the progression of chronic kidney disease (CKD) in clinical trials due to the extensive biological regulation of TGF-β signaling. It is necessary to investigate the precise downstream mechanisms of TGF-β signaling that regulate renal fibrosis.

Enhancing clinical problem-solving skills in cardiology nursing interns: A randomized controlled study of case-based learning and task-driven learning.

Aim: To assess the effectiveness of integrating Case-Based Learning (CBL) with Task-Driven Learning (TDL) in the clinical education of nursing interns specializing in cardiology.

Background: Traditional lecture-based learning (LBL) may not adequately prepare nursing interns for clinical problem-solving in cardiovascular specialties. Combining CBL with TDL methodologies could potentially enhance theoretical understanding and practical application skills.

Fibroblast activation and heterogeneity in fibrotic disease.

Fibroblasts are a special type of interstitial cell that has an essential role in maintaining the structural framework of tissues and organs. In response to injury, fibroblasts are activated and produce large amounts of extracellular matrix proteins. Fibroblast activation has a crucial role in tissue repair and wound healing.

Matrix metalloproteinase-10 promotes kidney fibrosis by transactivating β-catenin signaling.

Kidney fibrosis is characterized by excessive accumulation of extracellular matrix (ECM) and serves as a hallmark of chronic kidney disease (CKD). The turnover of ECM is controlled by a family of matrix metalloproteinases (MMPs), endopeptidases that play a crucial role in ECM remodeling and other cellular processes. In this study, we demonstrate that MMP-10 was upregulated in a variety of animal models of kidney fibrosis and human kidney biopsies from CKD patients.

Extracellular vesicles play a central role in linking podocyte injury to mesangial activation in glomerular disease.

Podocyte injury leading to proteinuria is the primary feature of a vast majority of glomerular diseases, while mesangial cell activation is the hallmark of glomerulosclerosis. Whether and how these two events are connected remains elusive. In this study, we investigated the role of extracellular vesicles (EVs) in linking podocyte injury to mesangial activation in glomerular disease.

Podocyte aging and diabetic kidney disease.

Podocyte injury causes a series of cellular changes, including hypertrophy, dedifferentiation, senescence, apoptosis, and detachment. Although evidence suggests a pivotal role of podocyte senescence in diabetic kidney disease, the exact triggers and underlying mechanism remain elusive. In this study, Li et al.

Short-term and long-term high-fat diet promote metabolic disorder through reprogramming mRNA mA in white adipose tissue by gut microbiota.

Background: Although short-term high-fat diet (S-HFD) and long-term high-fat diet (L-HFD) induce metabolic disorder, the underlying epigenetic mechanism is still unclear.

Results: Here, we found that both 4 days of S-HFD and 10 weeks of L-HFD increased mRNA mA level in epididymal white adipose tissue (eWAT) and impaired metabolic health. Interestingly, S-HFD activated transposable elements (TEs), especially endogenous retroviruses (ERVs) in eWAT, while L-HFD activated long interspersed elements (LINEs).

PRDM16 deficiency promotes podocyte injury by impairing insulin receptor signaling.

Impaired glucose uptake regulated by suppressed insulin receptor signaling is a key driving force of podocytopathies. The identification of potential therapeutic targets that mediate podocyte insulin receptor signaling holds significant clinical importance. Here, we observed a substantial reduction in PR domain-containing 16 (PRDM16) expression within damaged podocytes in both humans and mice.

DNA hypermethylation-induced suppression of ALKBH5 is required for folic acid to alleviate hepatic lipid deposition by enhancing autophagy in an ATG12-dependent manner.

Nonalcoholic fatty liver disease (NAFLD) occurs when too much fat builds up in the liver. As a growing worldwide epidemic, NAFLD is strongly linked with multiple metabolic diseases including obesity, insulin resistance, and dyslipidemia. However, very few effective treatments are currently available.

Quercetin-Driven Akkermansia Muciniphila Alleviates Obesity by Modulating Bile Acid Metabolism via an ILA/mA/CYP8B1 Signaling.

Global health is increasingly challenged by the growing prevalence of obesity and its associated complications. Quercetin, one of the most important dietary flavonoids, is being explored as an effective therapy for obesity with its mechanism remains understudied. Here in this study, it is demonstrated that quercetin intervention significantly reverses obesity-related phenotypes through reshaping the overall structure of microbiota, especially boosting colonization of the beneficial gut commensal Akkermansia muciniphila (A.

1,3,4-Oxadiazole Sulfonamide Derivatives Containing Pyrazole Structures: Design, Synthesis, Biological Activity Studies, and Mechanism Study.

Sulfonamide derivatives have been widely used for pesticide research in recent years. Herein, 1,3,4-oxadiazole sulfonamide derivatives containing a pyrazole structure were synthesized, and their structure-activity relationship was studied. Bioactivity tests showed the remarkable efficacy of most synthesized compounds.

Cochliomycin H, a new 12-membered resorcylic acid lactone from sponge-derived fungus sp. ZYX-Z-4.

A new 12-membered resorcylic acid lactone, cochliomycin H (), and one known resorcylic acid lactone, -demethylated-zeaenol (), were isolated from sponge-derived fungus sp. ZYX-Z-4. The structure of was elucidated by 1D and 2D NMR spectroscopic as well as HR-ESI-MS analysis.

β-catenin-inhibited Sumoylation modification of LKB1 and fatty acid metabolism is critical in renal fibrosis.

Liver kinase B1 (LKB1) is a serine/threonine kinase controlling cell homeostasis. Among post-translational modification, Sumoylation is vital for LKB1 activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), the key regulator in energy metabolism. Of note, AMPK-regulated fatty acid metabolism is highly involved in maintaining normal renal function.

Betaine alleviates nonalcoholic fatty liver disease (NAFLD) via a manner involving BHMT/FTO/mA/ PGC1α signaling.

Nonalcoholic fatty liver disease (NAFLD) has emerged as a major public health crisis with significant health threats and economic burdens worldwide in the past decades. Betaine, a naturally occurring alkaloid compound present in various dietary sources including spinach and beets, has been shown to ameliorate hepatic lipid metabolism and attenuate (NAFLD), while the underlying mechanism remains elusive. Here, we propose a novel mechanism through which betaine exerts its protective effects against hepatic lipid accumulation and (NAFLD) from an epigenetics perspective.

Cannabinoid receptor 2 plays a key role in renal fibrosis through inhibiting lipid metabolism in renal tubular cells.

Aims: Renal fibrosis is a common feature in various chronic kidney diseases (CKD). Tubular cell damage is a main characterization which results from dysregulated fatty acid oxidation (FAO) and lipid accumulation. Cannabinoid Receptor 2 (CB2) contributes to renal fibrosis, however, its role in FAO dysregulation in tubular cells is not clarified.

mA RNA methylation drives kidney fibrosis by upregulating β-catenin signaling.

N-methyladenosine (mA) methylation plays a crucial role in various biological processes and the pathogenesis of human diseases. However, its role and mechanism in kidney fibrosis remain elusive. In this study, we show that the overall level of mA methylated RNA was upregulated and the mA methyltransferase METTL3 was induced in kidney tubular epithelial cells in mouse models and human kidney biopsies of chronic kidney disease (CKD).

FAM3A plays a key role in protecting against tubular cell pyroptosis and acute kidney injury.

Acute kidney injury (AKI) is in high prevalence worldwide but with no therapeutic strategies. Programmed cell death in tubular epithelial cells has been reported to accelerate a variety of AKI, but the major pathways and underlying mechanisms are not defined. Herein, we identified that pyroptosis was responsible for AKI progression and related to ATP depletion in renal tubular cells.

Urinary cytokeratin 20 as a predictor for chronic kidney disease following acute kidney injury.

BACKGROUNDIdentifying patients with acute kidney injury (AKI) at high risk of chronic kidney disease (CKD) progression remains a challenge.METHODSKidney transcriptome sequencing was applied to identify the top upregulated genes in mice with AKI. The product of the top-ranking gene was identified in tubular cells and urine in mouse and human AKI.

Fibroblast expression of transmembrane protein smoothened governs microenvironment characteristics after acute kidney injury.

The smoothened (Smo) receptor facilitates hedgehog signaling between kidney fibroblasts and tubules during acute kidney injury (AKI). Tubule-derived hedgehog is protective in AKI, but the role of fibroblast-selective Smo is unclear. Here, we report that Smo-specific ablation in fibroblasts reduced tubular cell apoptosis and inflammation, enhanced perivascular mesenchymal cell activities, and preserved kidney function after AKI.

Myeloid-derived Wnts play an indispensible role in macrophage and fibroblast activation and kidney fibrosis.

Wnt/β-catenin signaling plays a pivotal role in the pathogenesis of chronic kidney diseases (CKD), which is associated with macrophage activation and polarization. However, the relative contribution of macrophage-derived Wnts in the evolution of CKD is poorly understood. Here we demonstrate a critical role of Wnts secreted by macrophages in regulating renal inflammation and fibrosis after various injuries.

Sulfonate derivatives bearing an amide unit: design, synthesis and biological activity studies.

Pest disasters which occurs on crops is a serious problem that not only cause crop yield loss or even crop failure but can also spread a number of plant diseases.Sulfonate derivatives have been widely used in insecticide and fungicide research in recent years. On this basis, a series of sulfonate derivatives bearing an amide unit are synthesized and the biological activities are evaluated.