Parkinson's disease (PD) is a disorder of movement, cognition, and emotion, it characterized pathologically by neuronal degeneration with Lewy bodies, which are cytoplasmic inclusion bodies containing deposits aggregated proteins. Most PD cases appear to be sporadic, but genetic forms the disease, caused mutations in α-synuclein, parkin, other genes, have helped elucidate pathogenesis. Mutations leucine-rich repeat kinase 2 ( LRRK2 ) cause autosomal-dominant Parkinsonism clinical features...

Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by selective loss of dopaminergic neurons and the presence Lewy bodies. Alpha-synuclein major component bodies in sporadic PD, mutations alpha-synuclein cause autosomal-dominant hereditary PD. Here, we generated A53T mutant alpha-synuclein-inducible PC12 cell lines using Tet-off regulatory system. Inducing expression differentiated cells decreased proteasome activity, increased intracellular ROS level caused up...

Mutations in the leucine-rich repeat kinase ( LRRK2 ) gene cause late-onset autosomal dominant Parkinson's disease (PD) with pleiomorphic pathology. Previously, we and others found that expression of mutant causes neuronal degeneration cell culture. Here used GAL4 / UAS system to generate transgenic Drosophila expressing either wild-type human or LRRK2-G2019S, most common mutation associated PD. Expression LRRK2-G2019S photoreceptor cells caused retinal degeneration. neurons produced...

Mutation in leucine-rich repeat kinase-2 ( LRRK2 ) is the most common cause of late-onset Parkinson's disease (PD). Although cases PD are sporadic, some inherited, including those caused by mutations. Because these mutations may be associated with a toxic gain function, controlling expression decrease its cytotoxicity. Here we show that carboxyl terminus HSP70-interacting protein (CHIP) binds, ubiquitinates, and promotes ubiquitin proteasomal degradation LRRK2. Overexpression CHIP protects...

Huntingtin proteolysis is implicated in Huntington disease pathogenesis, yet, the nature of huntingtin toxic fragments remains unclear. undergoes by calpains and caspases within an N-terminal region between amino acids 460 600. We have focused on proteolytic steps producing shorter fragments, which we term cp-1 cp-2 (distinct from previously described cp-A/cp-B). used HEK293 cells to express first 511 residues further define cleavage sites. Based epitope mapping with huntingtin-specific...

Huntington's Disease belongs to the CAG repeat family of neurodegenerative diseases and is characterized by presence an expanded polyglutamine (polyQ) in huntingtin (htt) gene product. PolyQ-expanded htt accumulates within large aggregates that are found various subcellular compartments, but more often localized nucleus. It has been suggested sequestration proteins essential cell viability may be one mechanism accounts for toxicity generated polyQ-expanded proteins. Nuclear inclusions...

Excessive accumulation of amyloid β-peptide (Aβ) plays an early and critical role in synapse neuronal loss Alzheimer's Disease (AD). Increased oxidative stress is one the mechanisms whereby Aβ induces death. Given lessened susceptibility to exhibited by mice lacking p66Shc, we investigated p66Shc toxicity. Treatment cells primary cultures with caused apoptotic death induced phosphorylation at Ser36. Ectopic expression a dominant-negative SEK1 mutant or chemical JNK inhibition reduced...

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant Parkinsonism with pleomorphic pathology including deposits of aggregated protein and neuronal degeneration. The pathogenesis LRRK2-linked Parkinson's disease (PD) is not fully understood. Here, using co-immunoprecipitation, we found that LRRK2 interacted synphilin-1 (SP1), a cytoplasmic interacts α-synuclein has implications PD pathogenesis. the N-terminus SP1 whereas predominantly C-terminus LRRK2, domain....

Abstract Background Inflammation is involved in the pathogenesis and progression of coronary artery diseases (CADs), including acute syndrome. The neutrophil-to-lymphocyte ratio (NLR) has been identified as a novel marker pro-inflammatory state. We aimed to evaluate predictive efficacy NLR for prognosis patients with new-onset ACS. Methods retrospectively included consecutive ACS treated emergency angiography. was measured at baseline analyzed by tertiles. severity lesions evaluated Gensini...

Yoga demonstrates systemic physiological benefits, but its molecular mechanisms remain unclear. This multi-omics study explores transcriptomic and immune dynamics following yoga intervention. Analyzing the GSE44777 dataset, we identified 1,260 differentially expressed genes enriched in lipid metabolism, atherosclerosis, cancer pathways. Protein-protein interaction networks revealed HBEGF, SQLE, BCL6 as immune-metabolic hubs. A nomogram incorporating HBEGF/SQLE predicted neuropathic pain with...

TIG3 is a tumor suppressor protein that limits keratinocyte survival during normal differentiation. It also important in cancer, as level reduced tumors and skin cancer cell lines, suggesting loss of expression may be required for survival. An goal identifying how In the present study we show epidermal squamous carcinoma SCC-13 cells reduces proliferation promotes morphological biochemical apoptosis. To identify mechanism drives these changes, demonstrate localizes near centrosome...

There were always strong expectations for suitable biomaterials used bone regeneration. In this study, to improve the biocompatiblity of titanium alloy, calcium phosphate bioceramic coating was obtained by laser cladding technology. The microstructure, phases, bioactivity, cell differentiation, morphology and resorption lacunae investigated optical microscope (OM), x-ray diffraction (XRD), methyl thiazolyl tetrazolium (MTT) assay, tartrate-resistant acid phosphatase (TRAP) staining scanning...

Background . Heart failure (HF) is one of the most common diagnoses associated with hospital readmission. We designed this prospective study to evaluate whether Kansas City Cardiomyopathy Questionnaire (KCCQ) score 30-day readmission in patients hospitalized decompensated HF. Methods and Results enrolled 240 who met criteria. Forty-eight (20%) were readmitted for HF within thirty days discharge, 192 (80%) not readmitted. Compared patients, nonreadmitted had a higher average KCCQ (40.8 versus...

The potential prognostic role of total bilirubin (TBIL) in patients with new-onset non-ST elevation myocardial infarction (NSTEMI) is not fully understood. This study aims to evaluate the predictive value TBIL for long-term prognosis NSTEMI.Patients NSTEMI that underwent emergency coronary angiography our department from June 2015 March 2020 were included. Baseline was measured at admission. SYNTAX scores used indicate severity lesions. association between and analyzed using multivariate...

TIG3 is an importantpro-differentiation regulator that expressed in the suprabasal epidermis. We have shown activates select keratinocyte differentiation-associated processesleading to cornified envelop formation. However, also suppresses cell proliferation by unknown mechanism. Our present studies suggest growth cessation may be mediated via impact of on centrosome and microtubules. The regulates microtubule function interphase cells spindle formation mitotic cells. show co-localizes with...

Recent evidence indicates that a large proportion of deaths from coronavirus disease 2019 (COVID-19) can be attributed to cardiovascular disease, including acute myocardial infarction, arrhythmias and heart failure. Indeed, severe infection increases the risk failure among patients with COVID-19. In most patients, arises complex interactions between pre-existing conditions, cardiac injury, renin-angiotensin system activation, effects systemic inflammation on system. this review, we summarize...

Non-coding RNA (ncRNA) plays a vital part in the regulation of immune responses, growth, and development plants animals. Here, identification, characteristic analysis, molecular verification circRNAs Apis cerana worker larval guts were conducted, followed by in-depth investigation expression pattern during Ascosphaera apis infection exploration potential regulatory differentially expressed (DEcircRNAs) host responses. A total 3178 A. c. identified, with length distribution ranging from 15 to...

Type I transglutaminase (TG1) is an enzyme that responsible for assembly of the keratinocyte cornified envelope. Although TG1 mutation underlying cause autosomal recessive congenital ichthyosis, a debilitating skin disease, pathogenic mechanism not completely understood. In present study we show endoplasmic reticulum (ER) membrane-associated protein trafficked through ER ultimate delivery to plasma membrane. Mutation severely attenuates this processing and catalytically inactive point...

Parathyroid hormone (PTH) levels are useful as a prognostic factor of chronic heart failure (HF) and can predict hospitalization for HF. It is unknown whether serum PTH in hospitalized patients with HF discharge if admission, discharge, or change from admission to measure the most important predictor readmission and/or death.A total 125 consecutive were enrolled into this study. The receiver operating characteristic (ROC) curves indicated predicted values due optimal cutoff points discharge....