Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases. In addition, a number of clinical drugs have been identified to modulate NCOA4-mediated ferritinophagy, significantly affecting disease progression and treatment efficacy. This paper aims to review the current research progress on the role of NCOA4-mediated ferritinophagy in related diseases, in order to provide new ideas for targeted clinical therapy.
Humans ; Nuclear Receptor Coactivators/physiology* ; Ferritins/metabolism* ; Animals ; Neurodegenerative Diseases/metabolism* ; Iron/metabolism* ; Autophagy/physiology* ; Liver Cirrhosis/metabolism* ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/physiopathology*

This study investigates the reproductive protective effect and potential mechanism of Cistanches Herba extract(CHE) on a rat model of kidney-Yang deficiency induced by adenine. Rats were randomly divided into five groups: normal, model, low-dose CHE(0.6 g·kg~(-1)·d~(-1)), high-dose CHE(1.2 g·kg~(-1)·d~(-1)), and L-carnitine(100 mg·kg~(-1)·d~(-1)). The rats were administered adenine(200 mg·kg~(-1)·d~(-1)) by gavage for the first 14 days to induce kidney-Yang deficiency, while simultaneously receiving drug treatment. After 14 days, the modeling was discontinued, but drug treatment continued to 49 days. The content of components in CHE was analyzed by high-performance liquid chromatography. The adenine-induced kidney-Yang deficiency model was assessed through symptom characterization and measurement of testosterone(T) levels using an enzyme-linked immunosorbent assay kit. Pathological damage to the testis and epididymis was evaluated based on the wet weight and performing hematoxylin-eosin staining. Sperm density and motility were measured using computer-aided sperm analysis, and sperm viability was assessed using live/dead sperm staining kits, and sperm morphology was evaluated using eosin staining, thereby determining rat sperm quality. Metabolomics was used to analyze changes in serum metabolites, enrich related metabolic pathways, and explore the mechanism of CHE in improving reproductive function damage in rats with kidney-Yang deficiency syndrome. Compared to the normal group, the model group exhibited significant kidney-Yang deficiency symptoms, reduced T levels, decreased testicular and epididymal wet weights, and significant pathological damage to the testis and epididymis. The sperm density, motility, and viability decreased, with an increased rate of sperm abnormalities. In contrast, rats treated with CHE showed marked improvements in kidney-Yang deficiency symptoms, restored T levels, alleviated pathological damage to the testis and epididymis, and improved various sperm parameters. Metabolomics results revealed 286 differential metabolites between the normal and model groups(191 upregulated and 95 downregulated). Seventy-five differential metabolites were identified between the model and low-dose CHE groups(21 upregulated and 54 downregulated). A total of 24 common differential metabolites were identified across the three groups, with 22 of these metabolites exhibiting opposite regulation trends between the two comparison groups. These metabolites were primarily involved in linoleic acid metabolism, ether lipid metabolism, and pantothenic acid and coenzyme A biosynthesis, as well as metabolites including 13-hydroperoxylinoleic acid, lysophosphatidylcholine, and pantethine. CHE can improve kidney-Yang deficiency symptoms in rats, alleviate reproductive organ damage, and enhance sperm quality. The regulation of lipid metabolism may be a potential mechanism through which CHE improves reproductive function in rats with kidney-Yang deficiency. The potential bioactive compounds of CHE include echinacoside, verbascoside, salidroside, betaine, and cistanoside A.
Animals ; Male ; Rats ; Yang Deficiency/physiopathology* ; Metabolomics ; Kidney/physiopathology* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Cistanche/chemistry* ; Kidney Diseases/metabolism* ; Testis/metabolism* ; Humans ; Reproduction/drug effects* ; Testosterone/blood*

Panvascular disease is a complex systemic disorder. Research by our team has established "kidney deficiency-vascular impairment" as its core pathogenesis. Consequently, we developed a three-tiered progressive prevention and treatment strategy: early prevention phase: focuses on tonifying the kidney and reducing turbidity; mid-term control phase: focuses on tonifying the kidney and stabilizing plaque; late recovery phase: focuses on tonifying the kidney and unblocking collaterals. This targeted therapeutic protocol effectively alleviates clinical symptoms, improves biochemical markers, enhances treatment efficacy, and achieves comprehensive management throughout the disease course. This article systematically elaborates on the concept of "kidney deficiency-vascular impairment" in panvascular disease, summarizes the mechanisms of kidney-tonifying Chinese herbal medicines, aiming to provide a beneficial reference for the whole-course management of panvascular diseases.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Kidney/blood supply* ; Vascular Diseases/physiopathology* ; Animals ; Kidney Diseases/physiopathology*

Kidney-Yang deficiency syndrome is a common geriatric disease that underlies chronic conditions such as diabetic nephropathy, chronic kidney disease, and osteoporosis. As age progresses, the kidney-Yang deficiency syndrome showcases increasingly pronounced manifestations, emerging as a key factor in the comorbidities experienced by elderly patients and affecting their quality of life and overall health status. Traditional Chinese medicine(TCM) has been extensively utilized in the treatment of kidney-Yang deficiency syndrome, with Epimedii Folium, Cinnamomi Cortex, and Lycii Fructus widely used in clinical settings. Despite the complexity of the molecular mechanisms involved in treating kidney-Yang deficiency syndrome, the potential therapeutic value of TCM remains compelling. Delving into the mechanisms of TCM treatment of kidney-Yang deficiency syndrome by regulating the neuro-endocrine-immune system can provide a scientific basis for targeted treatments of this syndrome and lay a foundation for the modernization of TCM. The pathophysiology of kidney-Yang deficiency syndrome involves multiple systems, including the interaction of the neuro-endocrine-immune system, the decline in renal function, the intensification of oxidative stress responses, and energy metabolism disorders. Understanding these mechanisms and their interrelationships can help untangle the etiology of kidney-Yang deficiency syndrome, aiding clinicians in making more precise diagnoses and treatments. Furthermore, the research on the specific applications of TCM in research on these pathological mechanisms can enhance the international recognition and status of TCM, enabling it to exert a greater global influence.
Humans ; Yang Deficiency/physiopathology* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/physiopathology* ; Neurosecretory Systems/physiopathology* ; Animals ; Kidney/physiopathology* ; Endocrine System/physiopathology* ; Immune System/physiopathology*

OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min•1.73 m, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min•1.73 m, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min•1.73 m per year. CONCLUSION Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).
Adult ; Disease Progression ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; drug effects ; Humans ; Kidney Diseases ; drug therapy ; physiopathology ; Male ; Middle Aged ; Outcome Assessment (Health Care)

Cardiovascular disease is one of the most common complications and the main cause of death in patients with chronic kidney disease. Uremic toxins are the primary cause of cardiovascular disease in renal insufficiency. In patients with chronic kidney disease, the protein-bound uremic toxins represented by indoxyl sulfate are difficult to be removed by conventional dialysis and are extremely toxic. In recent years, studies have confirmed that the occurrence of cardiovascular disease induced by chronic kidney disease is closely related to the accumulation of indoxyl sulfate. Indoxyl sulfate can induce oxidative stress to cause endothelial injury, smooth muscle cell proliferation and migration, and promote the occurrence of atherosclerosis, thereby affecting multiple systems throughout the body. This article reviews the research progress of uremic toxin indoxyl sulfate in end-stage renal diseases associated cardiovascular diseases.
Cardiovascular Diseases ; complications ; physiopathology ; Humans ; Indican ; toxicity ; Kidney Failure, Chronic ; complications ; physiopathology ; Oxidative Stress ; Toxins, Biological ; toxicity

Kidney diseases are important causes of mortality world widely. Renal microvascular dysfunction plays a pivotal role in the development of kidney diseases. Pharmacological and biochemical tools have been used to conduct detailed studies on the metabolization of arachidonic acid by cytochrome P450 (CYP450) in renal microvasculature. CYP450 epoxygenase metabolites epoxyeicosatrienoic acids (EETs) are mainly produced in renal microvessels. EETs exhibit renoprotective effects through vasodilation, anti-hypertension, anti-apoptosis and anti-inflammation, and were reported as therapeutic targets of renal diseases. However, the ability of the kidney in generating EETs is reduced in renal diseases. Recently, the studies from transgenic animal overexpressing CYP450 epoxygenases and application of soluble epoxide hydrolase inhibitors revealed that increasing of EETs exhibits renoprotective effects in vivo. The present review focuses on the protective mechanisms of EETs in kidney physiology and diseases.
Animals ; Animals, Genetically Modified ; Arachidonic Acid ; metabolism ; Cytochrome P-450 Enzyme System ; physiology ; Disease Models, Animal ; Humans ; Inflammation ; Kidney ; physiology ; Kidney Diseases ; physiopathology ; Vasodilation

Cofilin is a actin-binding protein in eukaryotic cells. It plays a role in maintaining the steady state of the internal environment through regulating actin dynamics, which contributes to the development of various kinds of diseases. In recent 20 years, cofilin has been widely attracted due to its regulatory effect on cell phenotype, gene transcription, apoptosis and inflammation in renal tissue. Cofilin plays a regulatory role in pathological changes in proteinuria diseases such as minimal change nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy. It could be one of the diagnosis index for glomerular podocyte injury. At the same time, cofilin plays a key role in maintaining the polarity and function of proximal tubular epithelial cells and it is involved in the regulation of kidney inflammation in a variety of kidney diseases, such as renal ischemia/reperfusion injury, diabetic nephropathy, and hypertensive nephropathy reaction. In addition, cofilin plays an important role in epithelial-to-mesenchymal transition (EMT) of tumor cells and epithelial cells in various tissues, suggesting that cofilin may be involved in the regulation of peritoneal dialysis-related EMT and fibrosis. Cofilin might turn into the new diagnosis and treatment target of kidney diseases.
Cofilin 1 ; metabolism ; Glomerulosclerosis, Focal Segmental ; physiopathology ; Humans ; Kidney ; physiopathology ; Kidney Diseases ; physiopathology ; Proteinuria ; genetics ; physiopathology

BACKGROUNDAtherosclerosis (AS) is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory factors and risk factors with different target organ damages (TOD) in essential hypertension (EH) patients and to explore its clinical significance.

METHODSA total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty-eight healthy subjects were selected as control. The clinical biochemical parameters, serum amyloid A, serum tryptase, and lipoprotein-associated phospholipase A2 (Lp-PLA2) in each group were detected, and the related risk factors were also statistically analyzed.

RESULTSFibrinogen (Fbg) was the most significant independent risk factor in acute coronary syndrome (ACS) group (odds ratio [OR]: 22.242, 95% confidence interval [CI]: 6.458-76.609, P< 0.001) with the largest absolute value of the standardized partial regression coefficient B' (b': 1.079). Lp-PLA2 was the most significant independent risk factor in stroke group (OR: 13.699, 95% CI: 5.236-35.837, P< 0.001) with b' = 0.708. Uric acid (UA) was the most significant independent risk factor in renal damage group (OR: 15.307, 95% CI: 4.022-58.250, P< 0.001) with b' = 1.026.

CONCLUSIONSFbg, Lp-PLA2, and UA are the strongest independent risk factors toward the occurrence of ACS, ischemic stroke, and renal damage in EH patients, thus exhibiting the greatest impacts on the occurrence of ACS, ischemic stroke, and renal damage in EH patients, respectively.

1-Alkyl-2-acetylglycerophosphocholine Esterase ; Aged ; Antihypertensive Agents ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Essential Hypertension ; blood ; complications ; drug therapy ; physiopathology ; Female ; Humans ; Kidney Diseases ; blood ; etiology ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Renal Insufficiency, Chronic ; blood ; etiology ; physiopathology ; Risk Factors ; Serum Amyloid A Protein ; metabolism ; Stroke ; blood ; etiology ; physiopathology ; Tryptases ; blood

OBJECTIVETo observe the effect of Trichinella spiralis and its worm-derived proteins on cecal ligation and puncture (CLP)-induced sepsis in mice.

METHODSEighty male BALB/c mice were randomly divided into sham-operated group, CLP group, Trichinella spiralis muscle larvae (ML) pre-infection group (ML+CLP group), soluble muscle larvae proteins (SMP) treatment group (SMP+CLP group) and excretory-secretory proteins (MES) treatment group (MES+CLP group). In ML+CLP group, the mice were orally infected with 300 Trichinella spiralis muscle larvae at 28 days before CLP and those in the other groups were intraperitioneally injected with PBS or SMP (25 µg/mice) or MES (25µg/mice) 30 min after CLP. The general condition and 72-h survival after CLP of the mice were observed. The levels of alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), creatinine (Cr), TNF-α, IL-6, IL-1β, IL-10 and TGF-β were measured at 12 h after the operation, and the pathological changes of the liver and kidney were observed.

RESULTSs Compared with the sham-operated mice, the mice in CLP group showed decreased 72-h survival, obviously increased ALT, AST, BUN, Cr, TNF-α, IL-6, IL-1β, IL-10, and TGF-β with hepatic cords disorder, hepatocytes swelling, glomerulus shrinkage, and renal tubular cell edema. Compared with CLP group, the mice in ML+CLP group showed lowered levels of ALT, AST, Cr, TNF-α and IL-1β and increased levels of IL-10 and TGF-β; in SMP+CLP group, the levels of ALT, AST, Cr, TNF-α and IL-1β were decreased and TGF-β increased. In MES+CLP group, the mice showed obviously increased 72-h survival with lowered levels of ALT, AST, BUN, Cr, TNF-α, IL-6 and IL-1β, increased levels of IL-10 and TGF-β, and alleviated liver and kidney damages.

CONCLUSIONTrichinella spiralis and its worm-derived proteins can decrease the levels of pro-inflammatory cytokines and increase immunomodulatory cytokines, and MES has more potent effect to reduce structural and functional damages of the liver and kidney.

Alanine Transaminase ; blood ; Animals ; Antigens, Helminth ; pharmacology ; Aspartate Aminotransferases ; blood ; Blood Urea Nitrogen ; Cecum ; Creatinine ; blood ; Cytokines ; blood ; Helminth Proteins ; pharmacology ; Kidney ; physiopathology ; Kidney Diseases ; therapy ; Ligation ; Liver ; physiopathology ; Liver Diseases ; therapy ; Male ; Mice ; Mice, Inbred BALB C ; Sepsis ; therapy ; Trichinella spiralis