Mutations in PARKIN, pten-induced putative kinase 1 (PINK1), and DJ-1 are individually linked to autosomal recessive early-onset familial forms of Parkinson disease (PD). Although mutations these genes lead the same state, functional relationships between them how their respective disease-associated cause PD largely unknown. Here, we show that Parkin, PINK1, formed a complex (termed PPD complex) promote ubiquitination degradation Parkin substrates, including itself Synphilin-1 neuroblastoma...

Oxidative stress is a key contributor in chronic obstructive pulmonary disease (COPD) pathogenesis caused by cigarette smoking. NRF2, redox-sensitive transcription factor, dissociates from its inhibitor, KEAP1, to induce antioxidant expression that inhibits oxidative stress.To determine the link between severity of COPD, stress, and NRF2-dependent levels peripheral lung tissue patients with COPD.We assessed antioxidants, regulators NRF2 activity, damage non-COPD (smokers former smokers)...

Mitochondrial dysfunction has been reported in both familial and sporadic Parkinson's disease (PD). However, effective therapy targeting this pathway is currently inadequate. Recent studies suggest that manipulating the processes of mitochondrial fission fusion considerable potential for treating human diseases. To determine therapeutic impact these pathways on PD, we used two complementary mouse models impairments as seen PD. We show here blocking neuroprotective PTEN-induced putative...

Mutations in the DJ-1 gene were recently identified an autosomal recessive form of early-onset familial Parkinson disease. Structural biology, biochemistry, and cell biology studies have suggested potential functions oxidative stress, protein folding, degradation pathways. However, animal models are needed to determine whether how loss function leads We generated null mice with a mutation that resembles large deletion reported patients. Our behavioral analyses indicated deficiency led...

The role of dopamine as a vulnerability factor and toxic agent in Parkinson's disease (PD) is still controversial, yet the presumed toxicity partly responsible for “DOPA-sparing” clinical practice that avoids using l -3,4-dihydroxyphenylalanine ( -DOPA), precursor, early PD. There lack studies on animal models directly isolate one determining causing neurodegeneration. To address this, we have generated novel transgenic mouse model which striatal neurons are engineered to take up...

In vitro evidence suggests that the inefficient removal of damaged mitochondria by macroautophagy contributes to Parkinson's disease (PD). Using a tissue-specific gene amplification strategy, we generated transgenic mouse line with human α-synuclein A53T overexpression specifically in dopamine (DA) neurons. Transgenic mice showed profound early-onset abnormalities, characterized marker-positive cytoplasmic inclusions containing mainly mitochondrial remnants, which preceded degeneration DA...

The association between systolic blood pressure and all-cause mortality differs frail nonfrail individuals, highlighting uncertainties about the effectiveness of antihypertensive treatments in populations. Using data from SHEP trial (Systolic Hypertension Elderly Program), a baseline frailty index (FI), including 55 variables, was constructed. Fine-Gray subdistribution hazard models Cox proportional hazards regression were used to explore FI risks stroke, cardiovascular disease, death, as...

Parkinson's disease (PD) has multiple proposed etiologies with implication of abnormalities in cellular homeostasis ranging from proteostasis to mitochondrial dynamics energy metabolism. PINK1 mutations are associated familial PD and here we discover a novel mechanism stress response. Using hypoxia as physiological trigger oxidative disruption metabolism, demonstrate that PINK1(-/-) mouse cells exhibited significantly reduced induction HIF-1α protein, transcriptional activity,...

Although elevated uric acid is associated with obesity and considered a predictor of hypertension, the causal linkage between three metabolic conditions not very clear. We aim to examine whether mediates effects on hypertension development.A total 1984 participants (mean aged 53 years, 62.10% female) repeated measurements obesity, blood pressure, 4 years apart in Gusu cohort were included. first applied cross-lagged panel analysis bidirectional association delineate temporal hyperuricemia....

As a key enzyme of the natriuretic peptides system, corin may participate in development cardiovascular disease (CVD). Its level circulation predicted CVD recurrence patients with myocardial infarction and heart failure, but no study examined this prediction general populations.This sought to examine prospective association between community-based population Chinese adults.The Gusu cohort included 2,498 participants (mean age 53 years, 39% men) who were free at baseline. Serum was measured...

Poor sleep quality is becoming very common in a developed society and relates to many health disorders. However, the association between hypertension has not been well studied Chinese adults.Blood pressure was measured assessed by Pittsburgh Sleep Quality Index (PSQI) for 5167 participants (mean aged 51±15 years, 41.5% males) Tianning Cohort. A logistic regression model constructed examine quality, as its components, hypertension, adjusting age, sex, education level, current smoking,...

Furin has been associated with glucose metabolic phenotypes in small sampled clinical studies. However, this association not yet studied Chinese. Here, we aimed to examine the between serum furin and fasting Chinese adults.Serum plasma were assayed for 2,172 participants (mean aged 53 years, 38% men) Gusu cohort. A median regression model was applied glucose, adjusting age, sex, education level, cigarette smoking, alcohol drinking, obesity, blood pressure, lipids. To facilitate data...

<strong>Background:</strong> Atrial natriuretic peptide (ANP) has been associated with cardiovascular disease (CVD) and related risk factors, but the clinical application is limited underlying mechanisms are not very clear. Here, we aimed to examine whether proANP its coding gene methylation were CVD in Chinese population. <strong>Methods: </strong>Serum peripheral blood DNA of A (<em>NPPA</em>) promoter was quantified at baseline for 2,498 community members (mean aged 53 years, 38% men)...

As the physical activator of natriuretic peptides, corin has been associated with stroke, but underlying mechanism is not very clear. Here, we examined whether CORIN promoter's methylation, an epigenetic DNA modification, was risk stroke in two independent samples.A total 1771 participants including 853 cases and 918 healthy controls were included as a discovery sample 2,498 community members 10 years follow-up replication sample. methylation promoter quantified by target bisulfite...

Furin has been associated with diabetes but the underlying mechanisms are unclear. As a mediator linking fixed genome and dynamic environment, DNA methylation of its coding gene FURIN may be involved. Here, we aimed to examine prospective association between in promoter incident during 4 years follow-up Chinese adults. levels were quantified by target bisulfite sequencing using peripheral blood from 1836 participants Gusu cohort who free at baseline. To diabetes, constructed logistic...

Background Serum corin has been associated with stroke in observational studies, but the underlying causality is uncertain. This study examined causal association between and through Mendelian randomization study. Methods Results In Gusu cohort, serum was assayed at baseline, incidents were prospectively obtained during 10 years of follow‐up. Single‐nucleotide polymorphisms (SNPs) CORIN genotyped by MassArray for 2310 participants (mean age, 53 years; 39% men). Seventeen SNPs passed...

Atrial natriuretic peptide (ANP) has been associated with ischemic stroke (IS), but the underlying molecular mechanisms are not clear. The objective of this study was to examine whether DNA methylation and hydroxymethylation in coding gene ANP (NPPA) were IS, as well its functional outcome. NPPA promoter region quantified by targeted bisulfite sequencing APOBEC-coupled epigenetic sequencing, respectively, 615 IS patients 610 age- sex-matched healthy controls. True calculated level minus...

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Atrial natriuretic peptide plays a potential role in obesity with unclear molecular mechanisms. The objective of this study was to examine the association between its coding gene (&lt;i&gt;natriuretic A&lt;/i&gt; [&lt;i&gt;NPPA&lt;/i&gt;]) methylation and obesity. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Peripheral blood DNA &lt;i&gt;NPPA&lt;/i&gt; promoter quantified at baseline by targeted bisulfite sequencing for 2,497 community...

Rapid identification is critical for ischemic stroke due to the very narrow therapeutic time window. The objective of this study was construct a diagnostic model rapid stroke.A mixture population constituted patients with (n = 481), hemorrhagic 116), and healthy individuals from communities 2498) were randomly resampled into training 1547, mean age: 55 years, 44% males) testing 1548, 54 43% samples. Serum corin assayed using commercial ELISA kits. Potential risk factors including age, sex,...