Rett syndrome: Pathogenicity and regulation of MECP2 (human) and Mecp2 (mouse) genes and their protein products through various molecular mechanisms.

Rett syndrome was first described over 50 years ago as an unusual clinical entity. Mutations in the X-linked MECP2 gene are the primary causes of Rett syndrome. The unstructured MeCP2 protein adopts various functional conformations, complicating its study.

Identification of therapeutic targets for chronic kidney disease through Mendelian randomization analysis of druggable genes.

Chronic Kidney Disease (CKD) is a multifaceted and gradually advancing condition characterized by a complex pathogenesis. The current therapeutic options for CKD remain limited in efficacy. Consequently, the identification and exploration of novel drug targets for CKD are of paramount importance.

The microbial metabolite trimethylamine N-oxide and the kidney diseases.

Trimethylamine N-oxide (TMAO), a metabolite, is a co-metabolite produced by both gut microbiota and livers, originating from foods rich in choline or carnitine. Emerging evidence suggests that TMAO may play a role in the pathogenesis of various kidney diseases, including acute kidney injury and chronic kidney disease. Research has demonstrated that heightened levels of TMAO are correlated with a heightened likelihood of kidney disease advancement and cardiovascular incidents among individuals with chronic kidney disease.

Evaluation of GFM1 mutations pathogenicity through in silico tools, RNA sequencing and mitophagy pahtway in GFM1 knockout cells.

GFM1 is a nuclear gene that plays a role in mitochondrial function. In recent decades, various homozygous and compound heterozygous mutations have been identified, leading to significant health issues in patients and often resulting in early death. There is a few experimental research on this gene, particularly regarding its pathogenicity through in silico methods and RNA sequencing and experimental validation in GFM1 knockout cells.

The essential role of CCT2 in the regulation of aggrephagy.

Protein aggregation, a defining characteristic of numerous human diseases, poses a significant challenge to cellular health. Autophagy, an essential cellular recycling process, specifically targets and degrades these harmful protein aggregates through a specialized mechanism known as aggrephagy. However, the precise mechanisms underlying the exquisite selectivity of aggrephagy in identifying and eliminating only aggregated proteins while sparing healthy cellular components have remained enigmatic.

Macrophage autophagy protects against acute kidney injury by inhibiting renal inflammation through the degradation of TARM1.

Macroautophagy/autophagy activation in renal tubular epithelial cells protects against acute kidney injury (AKI). However, the role of immune cell autophagy, such as that involving macrophages, in AKI remains unclear. In this study, we discovered that macrophage autophagy was an adaptive response during AKI as mice with macrophage-specific autophagy deficiency () exhibited higher serum creatinine, more severe renal tubule injury, increased infiltration of ADGRE1/F4/80 macrophages, and elevated expression of inflammatory factors compared to WT mice during AKI induced by either LPS or unilateral ischemia-reperfusion.

Glutaminolysis is a Potential Therapeutic Target for Kidney Diseases.

Metabolic reprogramming contributes to the progression and prognosis of various kidney diseases. Glutamine is the most abundant free amino acid in the body and participates in more metabolic processes than other amino acids. Altered glutamine metabolism is a prominent feature in different kidney diseases.

Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease.

Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages.

Endoplasmic Reticulum Stress in Systemic Lupus Erythematosus and Lupus Nephritis: Potential Therapeutic Target.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Approximately one-third to two-thirds of the patients with SLE progress to lupus nephritis (LN). The pathogenesis of SLE and LN has not yet been fully elucidated, and effective treatment for both conditions is lacking.

The Therapeutic Potential of CDK4/6 Inhibitors, Novel Cancer Drugs, in Kidney Diseases.

Inflammation is a crucial pathological feature in cancers and kidney diseases, playing a significant role in disease progression. Cyclin-dependent kinases CDK4 and CDK6 not only contribute to cell cycle progression but also participate in cell metabolism, immunogenicity and anti-tumor immune responses. Recently, CDK4/6 inhibitors have gained approval for investigational treatment of breast cancer and various other tumors.

Research progress on endoplasmic reticulum homeostasis in kidney diseases.

The endoplasmic reticulum (ER) plays important roles in biosynthetic and metabolic processes, including protein and lipid synthesis, Ca homeostasis regulation, and subcellular organelle crosstalk. Dysregulation of ER homeostasis can cause toxic protein accumulation, lipid accumulation, and Ca homeostasis disturbance, leading to cell injury and even death. Accumulating evidence indicates that the dysregulation of ER homeostasis promotes the onset and progression of kidney diseases.

Asiatic acid alleviates cisplatin-induced renal fibrosis in tumor-bearing mice by improving the TFEB-mediated autophagy-lysosome pathway.

Nephrotoxicity is a major side effect of cisplatin treatment of solid tumors in the clinical setting. Long-term low-dose cisplatin administration causes renal fibrosis and inflammation. However, few specific medicines with clinical application value have been developed to reduce or treat the nephrotoxic side effects of cisplatin without affecting its tumor-killing effect.

Cellular Protein Aggregates: Formation, Biological Effects, and Ways of Elimination.

The accumulation of protein aggregates is the hallmark of many neurodegenerative diseases. The dysregulation of protein homeostasis (or proteostasis) caused by acute proteotoxic stresses or chronic expression of mutant proteins can lead to protein aggregation. Protein aggregates can interfere with a variety of cellular biological processes and consume factors essential for maintaining proteostasis, leading to a further imbalance of proteostasis and further accumulation of protein aggregates, creating a vicious cycle that ultimately leads to aging and the progression of age-related neurodegenerative diseases.

Effect of Lacking ZKSCAN3 on Autophagy, Lysosomal Biogenesis and Senescence.

Transcription factors can affect autophagy activity by promoting or inhibiting the expression of autophagic and lysosomal genes. As a member of the zinc finger family DNA-binding proteins, ZKSCAN3 has been reported to function as a transcriptional repressor of autophagy, silencing of which can induce autophagy and promote lysosomal biogenesis in cancer cells. However, studies in knockout mice showed that the deficiency of ZKSCAN3 did not induce autophagy or increase lysosomal biogenesis.

Macrophage autophagy in macrophage polarization, chronic inflammation and organ fibrosis.

As the essential regulators of organ fibrosis, macrophages undergo marked phenotypic and functional changes after organ injury. These changes in macrophage phenotype and function can result in maladaptive repair, causing chronic inflammation and the development of pathological fibrosis. Autophagy, a highly conserved lysosomal degradation pathway, is one of the major players to maintain the homeostasis of macrophages through clearing protein aggregates, damaged organelles, and invading pathogens.

Autophagy and Renal Fibrosis.

Renal fibrosis is a common process of almost all the chronic kidney diseases progressing to end-stage kidney disease. As a highly conserved lysosomal protein degradation pathway, autophagy is responsible for degrading protein aggregates, damaged organelles, or invading pathogens to maintain intracellular homeostasis. Growing evidence reveals that autophagy is involved in the progression of renal fibrosis, both in the tubulointerstitial compartment and in the glomeruli.

Extracellular HSPs: The Potential Target for Human Disease Therapy.

Heat shock proteins (HSPs) are highly conserved stress proteins known as molecular chaperones, which are considered to be cytoplasmic proteins with functions restricted to the intracellular compartment, such as the cytoplasm or cellular organelles. However, an increasing number of observations have shown that HSPs can also be released into the extracellular matrix and can play important roles in the modulation of inflammation and immune responses. Recent studies have demonstrated that extracellular HSPs (eHSPs) were involved in many human diseases, such as cancers, neurodegenerative diseases, and kidney diseases, which are all diseases that are closely linked to inflammation and immunity.

Cell Cycle Dysregulation and Renal Fibrosis.

Precise regulation of cell cycle is essential for tissue homeostasis and development, while cell cycle dysregulation is associated with many human diseases including renal fibrosis, a common process of various chronic kidney diseases progressing to end-stage renal disease. Under normal physiological conditions, most of the renal cells are post-mitotic quiescent cells arrested in the G0 phase of cell cycle and renal cells turnover is very low. Injuries induced by toxins, hypoxia, and metabolic disorders can stimulate renal cells to enter the cell cycle, which is essential for kidney regeneration and renal function restoration.

Autophagy in Viral Infection and Pathogenesis.

As an evolutionarily conserved cellular process, autophagy plays an essential role in the cellular metabolism of eukaryotes as well as in viral infection and pathogenesis. Under physiological conditions, autophagy is able to meet cellular energy needs and maintain cellular homeostasis through degrading long-lived cellular proteins and recycling damaged organelles. Upon viral infection, host autophagy could degrade invading viruses and initial innate immune response and facilitate viral antigen presentation, all of which contribute to preventing viral infection and pathogenesis.