PCSK9 with a gain of function D374Y mutation aggravates atherosclerosis by inhibiting PPARα expression.

The preprotein convertase, Bacillus subtilis protease/kexin type 9 serine protease (PCSK9), has garnered significant attention as a potential lipid lowering and therapeutic drug target for atherosclerosis (AS). Peroxisome proliferator-activated receptor alpha (PPARα) is expressed in various tissues and has crucial roles in lipid metabolism and the inflammatory response; however, the precise impact of PCSK9 on AS progression through its regulation of PPARα remains uncertain. The present study aimed to examine the impact of introducing stable liver transduction of human derived PCSK9 with a gain of function D374Y mutation (PCSK9) into systemic PPARα knockout mice (PPARα) on plasma lipid levels and AS.

Recombinant dsAAV9-mediated Endogenous Overexpression of Macrophage Migration Inhibitory Factor Alleviates Myocardial Ischemia-Reperfusion Injury via Activating AMPK and ERK1/2 Signaling Pathways.

Purpose: To investigate the protective effect and mechanism of enhanced expression of endogenous macrophage migration inhibitory factor (MIF) on cardiac ischemia-reperfusion (I/R) injury.

Methods: A recombinant double-stranded adeno-associated virus serotype 9 with MIF or green fluorescent protein (GFP) genes (dsAAV9-MIF/GFP) was transduced into mice and neonatal rat ventricular myocytes (NRVMs). The models of cardiac 60 min ischemia and 24 h reperfusion and 12 h hypoxia/12 h reoxygenation (H/R) were established in mice and NRVMs, respectively.

Research Progress of Drug Delivery Systems Targeting the Kidneys.

Chronic kidney disease (CKD) affects more than 10% of the global population, and its incidence is increasing, partially due to an increase in the prevalence of disease risk factors. Acute kidney injury (AKI) is an independent risk factor for CKD and end-stage renal disease (ESRD). The pathogenic mechanisms of CKD provide several potential targets for its treatment.

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.

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.

Autophagy in peritoneal fibrosis.

Peritoneal dialysis (PD) is a widely accepted renal replacement therapy for patients with end-stage renal disease (ESRD). Morphological and functional changes occur in the peritoneal membranes (PMs) of patients undergoing long-term PD. Peritoneal fibrosis (PF) is a common PD-related complication that ultimately leads to PM injury and peritoneal ultrafiltration failure.

AMP-activated protein kinase α2 contributes to acute and chronic hyperuricemic nephropathy via renal urate deposition in a mouse model.

Hyperuricemia can induce acute and chronic kidney damage, but the pathological mechanism remains unclear. The potential role of AMP-activated protein kinase (AMPK) α2 in hyperuricemia-induced renal injury was investigated in this study. Acute and chronic hyperuricemic nephropathy was induced by administering intraperitoneal injections of uric acid and oxonic acid to AMPK α2 knockout and wild-type mice.

Metformin improves renal injury of MRL/lpr lupus-prone mice via the AMPK/STAT3 pathway.

Objective: Lupus nephritis (LN) is a major complication and cause of death among patients with SLE. This research used in vivo and in vitro experiments to explore the therapeutic potential of metformin in kidney injury from LN-induced inflammation.

Methods: In vivo study, 8-week-old MRL/MpJ-Faslpr/J (MRL/lpr) mice were randomly divided into two groups (n=12 each): daily administration of 0.

Characteristics and health risks of personal exposure to particle-bound PAHs for Hong Kong adult residents: From ambient pollution to indoor exposure.

Research on individual level polycyclic aromatic hydrocarbons (PAHs) exposure is scarce. Moreover, the independent contribution of ambient- and indoor-origin PAHs to personal exposure remains poorly studied. We performed simultaneous ambient, residential indoor, and personal exposure measurements in a panel of healthy adults to investigate particle-bound PAHs, focusing on their carcinogenic congeners (cPAHs).

A prediction model based on platelet parameters, lipid levels, and angiographic characteristics to predict in-stent restenosis in coronary artery disease patients implanted with drug-eluting stents.

Background: The present study was aimed to establish a prediction model for in-stent restenosis (ISR) in subjects who had undergone percutaneous coronary intervention (PCI) with drug-eluting stents (DESs).

Materials And Methods: A retrospective cohort study was conducted. From September 2010 to September 2013, we included 968 subjects who had received coronary follow-up angiography after primary PCI.

Lysosome Depletion-Triggered Autophagy Impairment in Progressive Kidney Injury.

Background: Macroautophagy (autophagy) is a cellular recycling process involving the destruction of damaged organelles and proteins in intracellular lysosomes for efficient nutrient reuse.

Summary: Impairment of the autophagy-lysosome pathway is tightly associated with multiple kidney diseases, such as diabetic nephropathy, proteinuric kidney disease, acute kidney injury, crystalline nephropathy, and drug- and heavy metal-induced renal injury. The impairment in the process of autophagic clearance may induce injury in renal intrinsic cells by activating the inflammasome, inducing cell cycle arrest, and cell death.

Polymorphisms of rs2483205 and rs562556 in the PCSK9 gene are associated with coronary artery disease and cardiovascular risk factors.

PCSK9 plays a crucial role in lipid metabolism. This case-control study explored the associations of novel single nucleotide polymorphisms (SNPs) of the PCSK9 gene with coronary artery disease (CAD) (≥ 1 coronary artery stenosis ≥ 50%) and its risk factors in the Han population in Xinjiang, China. Four tag SNPs (rs11583680, rs2483205, rs2495477 and rs562556) of the PCSK9 gene were genotyped in 950 CAD patients and 1082 healthy controls.

Cyclosporine A blocks autophagic flux in tubular epithelial cells by impairing TFEB-mediated lysosomal function.

Cyclosporine A (CsA) is an immunosuppressor widely used for the prevention of acute rejection during solid organ transplantation. However, severe nephrotoxicity has substantially limited its long-term usage. Recently, an impaired autophagy pathway was suggested to be involved in the pathogenesis of chronic CsA nephrotoxicity.

Toxicological effects of personal exposure to fine particles in adult residents of Hong Kong.

Toxicological studies have demonstrated the associations between fine particle (PM) components and various cytotoxic endpoints. However, few studies have investigated the toxicological effects of source-specific PM at the individual level. To investigate the potential impact of source-specific PM on cytotoxic effects, we performed repeated personal PM monitoring of 48 adult participants in Hong Kong during the winter and summer of 2014-2015.

SMAD3 promotes autophagy dysregulation by triggering lysosome depletion in tubular epithelial cells in diabetic nephropathy.

Macroautophagy/autophagy dysregulation has been noted in diabetic nephropathy; however, the regulatory mechanisms controlling this process remain unclear. In this study, we showed that SMAD3 (SMAD family member 3), the key effector of TGFB (transforming growth factor beta)-SMAD signaling, induces lysosome depletion via the inhibition of TFEB-dependent lysosome biogenesis. The pharmacological inhibition or genetic deletion of SMAD3 restored lysosome biogenesis activity by alleviating the suppression of , thereby protecting lysosomes from depletion and improving autophagic flux in renal tubular epithelial cells in diabetic nephropathy.

Characteristics and toxicological effects of commuter exposure to black carbon and metal components of fine particles (PM) in Hong Kong.

Epidemiological studies have demonstrated significant associations between traffic-related air pollution and adverse health outcomes. Personal exposure to fine particles (PM) in transport microenvironments and their toxicological properties remain to be investigated. Commuter exposures were investigated in public transport systems (including the buses and Mass Transit Railway (MTR)) along two sampling routes in Hong Kong.

Overexpression of IκBα in cardiomyocytes alleviates hydrogen peroxide-induced apoptosis and autophagy by inhibiting NF-κB activation.

Background: Inflammation and oxidative stress play predominant roles in the initiation and progression of ischaemia/reperfusion (I/R) injury, with nuclear factor kappa B (NF-κB) serving as a crucial mediator. Overexpression of the inhibitor of κB alpha (IκBα) gene is hypothesized to have protective effects against apoptosis and autophagy in cardiomyocytes subjected to hydrogen peroxide (HO) by inhibiting the NF-κB pathway.

Methods: The IκBα gene was transfected via adeno-associated virus serotype 9 (AAV9) delivery into neonatal rat ventricular cardiomyocytes (NRVMs) prior to HO treatment.

Autophagy Inhibition Sensitizes Renal Tubular Epithelial Cell to G1 Arrest Induced by Transforming Growth Factor beta (TGF-β).

BACKGROUND Cell cycle arrest and autophagy have been demonstrated to be involved in various transforming growth factor (TGF)-ß-mediated phenotype alterations of tubular epithelial cells (TECs) and tubulointerstitial fibrosis. But the relationship between cell cycle arrest and the autophagy induced by TGF-ß has not been explored well. MATERIAL AND METHODS The effects of autophagy inhibition on TGF-ß-induced cell cycle arrest in TECs were explored in vitro.

Indoor, outdoor, and personal exposure to PM and their bioreactivity among healthy residents of Hong Kong.

Direct evidence about associations between fine particles (PM) components and the corresponding PM bioreactivity at the individual level is limited. We conducted a panel study with repeated personal measurements involving 56 healthy residents in Hong Kong. Fractional exhaled nitric oxide (FeNO) levels were measured from these subjects.

Apolipoprotein A1 is associated with SYNTAX score in patients with a non-ST segment elevation myocardial infarction.

Background: The study was designed to investigate lipid profile and SYNTAX score in patients with non-ST segment elevation myocardial infarction (NSTEMI).

Methods: 311 patients with NSTEMI were enrolled. The demographic, clinical data, blood samples and SYNTAX score were documented.

Cardioprotective effects of constitutively active MEK1 against HO-induced apoptosis and autophagy in cardiomyocytes via the ERK1/2 signaling pathway.

Oxidative stress injury is one of the main mechanisms of ischemia-reperfusion (I/R) injury. The extracellular signal-regulated kinase (ERK1/2) pathway plays an important role in cardioprotective during acute myocardial infarction. In this study, we used constitutively active MEK1 gene (CaMEK) transfection strategy to investigate whether CaMEK provides a protective effect against apoptosis and autophagy induced by Hydrogen peroxide (HO) in neonatal rat cardiac ventricular cardiomyocytes (NCMs) and the underlying mechanisms.

Macrophage migration inhibitory factor plays an essential role in ischemic preconditioning-mediated cardioprotection.

Ischemic preconditioning (IPC) is an endogenous protection strategy against myocardial ischemia-reperfusion (I/R) injury. Macrophage migration inhibitory factor (MIF) released from the myocardium subjected to brief periods of ischemia confers cardioprotection. We hypothesized that MIF plays an essential role in IPC-induced cardioprotection.

Estimation of personal exposure to fine particles (PM) of ambient origin for healthy adults in Hong Kong.

Personal exposure and ambient fine particles (PM) measurements for 13 adult subjects (ages 19-57) were conducted in Hong Kong between April 2014 and June 2015. Six to 21 personal samples (mean = 19) per subject were obtained throughout the study period. Samples were analyzed for mass by gravimetric analysis, and 19 elements (from Na to Pb) were analyzed using X-Ray Fluorescence.