ATP-dependent chromatin remodeling protein ATRX is an essential regulator involved in maintenance of DNA structure and chromatin state and regulation of gene expression during development. ATRX was originally identified as the monogenic cause of X-linked α-thalassemia mental retardation (ATR-X) syndrome. Affected individuals display a variety of developmental abnormalities and skeletal deformities.
View Article and Find Full Text PDFOsteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes, in addition to the bone fragility. It is caused by a recurrent, dominant pathogenic variant (c.-14C>T) in interferon-induced transmembrane protein 5 (IFITM5).
View Article and Find Full Text PDFThe Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains a public health concern and a subject of active research effort. Development of pre-clinical animal models is critical to study viral-host interaction, tissue tropism, disease mechanisms, therapeutic approaches, and long-term sequelae of infection. Here, we report two mouse models for studying SARS-CoV-2: A knock-in mAce2 mouse that expresses a mouse-human hybrid form of the angiotensin-converting enzyme 2 (ACE2) receptor under the endogenous mouse Ace2 promoter, and a Rosa26 conditional knock-in mouse carrying the human ACE2 allele (Rosa26).
View Article and Find Full Text PDFInhaled nitric oxide (NO) therapy has been reported to improve lung growth in premature newborns. However, the underlying mechanisms by which NO regulates lung development remain largely unclear. NO is enzymatically produced by three isoforms of nitric oxide synthase (NOS) enzymes.
View Article and Find Full Text PDFNitric oxide (NO) is a critical signaling molecule that has been implicated in the pathogenesis of neurocognitive diseases. Both excessive and insufficient NO production have been linked to pathology. Previously, we have shown that argininosuccinate lyase deficiency (ASLD) is a novel model system to investigate cell-autonomous, nitric oxide synthase-dependent NO deficiency.
View Article and Find Full Text PDFSLC7A7 deficiency, or lysinuric protein intolerance (LPI), causes loss of function of the y+LAT1 transporter critical for efflux of arginine, lysine and ornithine in certain cells. LPI is characterized by urea cycle dysfunction, renal disease, immune dysregulation, growth failure, delayed bone age and osteoporosis. We previously reported that Slc7a7 knockout mice (C57BL/6×129/SvEv F2) recapitulate LPI phenotypes, including growth failure.
View Article and Find Full Text PDFThe residues of cycloxaprid enantiomers and metabolites are investigated by ultraperformance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) during raw and ripen Puer tea processing. A Chiralpak AG column with chiral stationary phase of amylose tris (3-chloro-5-methylphenylcarbamate) is succeed to separate the -cycloxaprid, -cycloxaprid, and their metabolite, which is identified as nitrylene-imidazolidine. It is not conversed cycloxaprid into -cycloxaprid during Puer tea processing.
View Article and Find Full Text PDFLoss-of-function mutations in DDRGK1 have been shown to cause Shohat type spondyloepimetaphyseal dysplasia (SEMD). In zebrafish, loss of function of ddrgk1 leads to defects in early cartilage development. Ddrgk1-/- mice show delayed mesenchymal condensation in the limb buds and early embryonic lethality.
View Article and Find Full Text PDFBACKGROUNDCurrently, there is no disease-specific therapy for osteogenesis imperfecta (OI). Preclinical studies demonstrate that excessive TGF-β signaling is a pathogenic mechanism in OI. Here, we evaluated TGF-β signaling in children with OI and conducted a phase I clinical trial of TGF-β inhibition in adults with OI.
View Article and Find Full Text PDFType V collagen is a regulatory fibrillar collagen essential for type I collagen fibril nucleation and organization and its deficiency leads to structurally abnormal extracellular matrix (ECM). Haploinsufficiency of the Col5a1 gene encoding α(1) chain of type V collagen is the primary cause of classic Ehlers-Danlos syndrome (EDS). The mechanisms by which this initial insult leads to the spectrum of clinical presentation are not fully understood.
View Article and Find Full Text PDFCoatomer complexes function in the sorting and trafficking of proteins between subcellular organelles. Pathogenic variants in coatomer subunits or associated factors have been reported in multi-systemic disorders, i.e.
View Article and Find Full Text PDFGillespie syndrome (GLSP) is characterized by bilateral symmetric partial aplasia of the iris presenting as a fixed and large pupil, cerebellar hypoplasia with ataxia, congenital hypotonia, and varying levels of intellectual disability. GLSP is caused by either biallelic or heterozygous, dominant-negative, pathogenic variants in ITPR1. Here, we present a 5-year-old male with GLSP who was found to have a heterozygous, de novo intronic variant in ITPR1 (NM_001168272.
View Article and Find Full Text PDFThe aims of the study were to assess the contribution of resilience, coping style, and COVID-19 stress on the quality of life (QOL) in frontline health care workers (HCWs). The study was a cross-sectional surveyperformed among 309 HCWs in a tertiaryhospital during the outbreak of COVID-19 in China. Data were collected through an anonymous, self-rated questionnaire, including demographic data, a 10-item COVID-19 stress questionnaire, Generic QOL Inventory-74, Connor-Davidson Resilience Scale, and the Simplified Coping Style Questionnaire.
View Article and Find Full Text PDFPrevious studies have shown that nitric oxide (NO) supplements may prevent bone loss and fractures in preclinical models of estrogen deficiency. However, the mechanisms by which NO modulates bone anabolism remain largely unclear. Argininosuccinate lyase (ASL) is the only mammalian enzyme capable of synthesizing arginine, the sole precursor for nitric oxide synthase-dependent (NOS-dependent) NO synthesis.
View Article and Find Full Text PDFInt J Soc Psychiatry
September 2021
Background: The pandemic of coronavirus disease (Covid-19) seriously impacts the health and well-being of all of us.
Aims: We aim to assess the psychological impact of Covid-19 on frontline health care workers (HCWs), including anxiety, depression and stress of threat of the disease.
Method: The study was a cross-sectional survey among the frontline HCWs in a hospital at Jinan, China.
Food Sci Nutr
September 2020
The stereoisomer behavior of sulfoxaflor was investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) during raw Puer tea, ripen Puer tea, and sun-dry Puer tea processing. The persistence of sulfoxaflor stereoisomers was consistently prolonged with different Puer tea processing from sun-dry Puer tea, ripen Puer tea to raw Puer tea with 4.0-4.
View Article and Find Full Text PDFLysinuric protein intolerance (LPI) is an inborn error of cationic amino acid (arginine, lysine, ornithine) transport caused by biallelic pathogenic variants in SLC7A7, which encodes the light subunit of the y+LAT1 transporter. Treatments for the complications of LPI, including growth failure, renal disease, pulmonary alveolar proteinosis, autoimmune disorders and osteoporosis, are limited. Given the early lethality of the only published global Slc7a7 knockout mouse model, a viable animal model to investigate global SLC7A7 deficiency is needed.
View Article and Find Full Text PDFOsteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by bone deformities and fractures caused by low bone mass and impaired bone quality. OI is a genetically heterogeneous disorder that most commonly arises from dominant mutations in genes encoding type I collagen (COL1A1 and COL1A2). In addition, OI is recessively inherited with the majority of cases resulting from mutations in prolyl-3-hydroxylation complex members, which includes cartilage-associated protein (CRTAP).
View Article and Find Full Text PDFBACKGROUNDLiver disease in urea cycle disorders (UCDs) ranges from hepatomegaly and chronic hepatocellular injury to cirrhosis and end-stage liver disease. However, the prevalence and underlying mechanisms are unclear.METHODSWe estimated the prevalence of chronic hepatocellular injury in UCDs using data from a multicenter, longitudinal, natural history study.
View Article and Find Full Text PDFZhongguo Shi Yan Xue Ye Xue Za Zhi
August 2019
Objective: To investigate the expression and pathogenesis of IL-17 in bone marrow blood of multiple myeloma (MM) patients.
Methods: Expression levels of IL-6, TNF-α and IL-17 in bone marrow serum of 20 MM patients and 20 control subjects were detected by ELISA, and correlation analysis was performed to analyze the correlation IL-17 with IL-6 and TNF-α. The effect of IL-17 on the proliferation of MM cells treated with different concentration of IL-17 was detected by cell prollferation and toxicity tesis.
Five new oxygenated sesquiterpenes, molestins A⁻D (, ⁻) and -gibberodione (), three new cyclopentenone derivatives, -sinulolides C, D, and F ((+)-⁻(+)-), one new butenolide derivative, -sinulolide H ((+)-), and one new cembranolide, molestin E (), together with 14 known related metabolites (⁻, (⁻)-⁻(⁻)-, (±)-, (⁻)-, ⁻) were isolated from the Paracel Islands soft coral cf. . The structures and absolute configurations were elucidated based on comprehensive spectroscopic analyses, quantum chemical calculations, and comparison with the literature data.
View Article and Find Full Text PDFProstate cancer is the most common illness affecting men worldwide. Although much progress has been made in the study of prostate cancer prevention and treatment, less attention has been paid to the molecular mechanism of the disease. The molecular arrangement by which atractylenolide II (ATR II) induces human prostate cancer cytotoxicity was comprehensively examined in the present study.
View Article and Find Full Text PDFThe heritable disorder osteogenesis imperfecta (OI) is characterized by bone fragility and low bone mass. OI type VI is an autosomal recessive form of the disorder with moderate to severe bone fragility. OI type VI is caused by mutations in the serpin peptidase inhibitor, clade F, member 1 (), the gene coding for pigment epithelium-derived factor (PEDF).
View Article and Find Full Text PDFPrimary hypertension is a major risk factor for ischemic heart disease, stroke, and chronic kidney disease. Insights obtained from the study of rare Mendelian forms of hypertension have been invaluable in elucidating the mechanisms causing primary hypertension and development of antihypertensive therapies. Endothelial cells play a key role in the regulation of blood pressure; however, a Mendelian form of hypertension that is primarily due to endothelial dysfunction has not yet been described.
View Article and Find Full Text PDFOsteoarthritis (OA) is a degenerative disease of synovial joints characterized by progressive loss of articular cartilage, subchondral bone remodeling, and intra-articular inflammation with synovitis that results in chronic pain and motor impairment. Despite the economic and health impacts, current medical therapies are targeted at symptomatic relief of OA and fail to alter its progression. Given the complexity of OA pathogenesis, we hypothesized that a combinatorial gene therapy approach, designed to inhibit inflammation with interleukin-1 receptor antagonist (IL-1Ra) while promoting chondroprotection using lubricin (PRG4), would improve preservation of the joint compared to monotherapy alone.
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