المؤلفون: Yuan Fang, Yi-Zhen Wang, Lian Chen, Xin-Bao Xie

المصدر: Frontiers in Genetics, Vol 14 (2023)

مصطلحات موضوعية: ATP6AP2, congenital disorders of glycosylation, X-linked, hereditary, cirrhosis, Genetics, QH426-470

الوصف: Background: A rare X-linked hereditary condition known as ATP6AP2-congenital disorder of glycosylation (ATP6AP2-CDG) is caused by pathogenic variants in ATP6AP2, resulting in autophagic misregulation with reduced siganling of mammalian target of rapamycin (mTOR) that clinically presents with aberrant protein glycosylation, hepatosteatosis, immunodeficiency, cutis laxa, and psychomotor dysfunction. To date, only two missense mutations have been reported in three patients from two unrelated families.Methods: In order to extend the profiles of phenotype and genotype associated with ATP6AP2-CDG, we assessed the clinical history, whole exome sequencing (WES), and liver histology as well as immunohistochemistry in a Chinese patient, and performed quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and untargeted metabolomics in genetic exogenously constructed cells.Results: The 11-month-old Chinese boy presented with recurrent jaundice, cutis laxa, cirrhosis, growth retardation, coagulopathy, anemia, and cardiomegaly, and underwent liver transplantation. A novel mutation, c.185G>A (p.Gly62Glu), was identified in exon 3 of ATP6AP2. The expression of ATP6AP2 was observed to remain unchanged in the liver sample of the patient as well as in HEK293T cells harboring the p.Gly62Glu. This missense mutation was found to dysregulate autophagy and mTOR signaling. Moreover, metabolomics analysis revealed that the exogenously introduced Gly62Glu mutant resulted in the downregulation of numerous metabolites involved in lipid metabolism pathway.Conclusion: This study may enable a more detailed exploration of its precise pathogenesis and potential therapeutic interventions.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fgene.2023.1264237/fullTest; https://doaj.org/toc/1664-8021Test

الوصول الحر: https://doaj.org/article/89ffb5529a334ee39f47c6ebe1c391efTest

المؤلفون: Dong-Dong Wu, Sheng Jin, Ruo-Xiao Cheng, Wen-Jie Cai, Wen-Long Xue, Qing-Qing Zhang, Le-Jie Yang, Qi Zhu, Meng-Yao Li, Ge Lin, Yi-Zhen Wang, Xue-Pan Mu, Yu Wang, Igor Ying Zhang, Qi Zhang, Ying Chen, Sheng-Yang Cai, Bo Tan, Ye Li, Yun-Qian Chen, Pu-Juan Zhang, Chen Sun, Yue Yin, Ming-Jie Wang, Yi-Zhun Zhu, Bei-Bei Tao, Jia-Hai Zhou, Wei-Xue Huang, Yi-Chun Zhu

المصدر: Cell Reports, Vol 42, Iss 7, Pp 112750- (2023)

مصطلحات موضوعية: CP: Molecular biology, Biology (General), QH301-705.5

الوصف: Summary: The present study examines whether there is a mechanism beyond the current concept of post-translational modifications to regulate the function of a protein. A small gas molecule, hydrogen sulfide (H2S), was found to bind at active-site copper of Cu/Zn-SOD using a series of methods including radiolabeled binding assay, X-ray absorption near-edge structure (XANES), and crystallography. Such an H2S binding enhanced the electrostatic forces to guide the negatively charged substrate superoxide radicals to the catalytic copper ion, changed the geometry and energy of the frontier molecular orbitals of the active site, and subsequently facilitated the transfer of an electron from the superoxide radical to the catalytic copper ion and the breakage of the copper-His61 bridge. The physiological relevance of such an H2S effect was also examined in both in vitro and in vivo models where the cardioprotective effects of H2S were dependent on Cu/Zn-SOD.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2211124723007611Test; https://doaj.org/toc/2211-1247Test

الوصول الحر: https://doaj.org/article/4f5a5fbce8904261a2dd86229256dcdbTest

المؤلفون: Xia Wei, Yuan Fang, Jian-She Wang, Yi-Zhen Wang, Yuan Zhang, Kuerbanjiang Abuduxikuer, Lian Chen

المصدر: Frontiers in Pediatrics, Vol 11 (2023)

مصطلحات موضوعية: neonatal sclerosing cholangitis, biliary cirrhosis, DCDC2, ciliopathy, novel mutations, Pediatrics, RJ1-570

الوصف: BackgroundNeonatal sclerosing cholangitis (NSC) is a rare and severe autosomal recessive inherited liver disease with mutations in DCDC2, commonly requiring liver transplantation (LT) for decompensated biliary cirrhosis in childhood.MethodsThe information of four Chinese patients with NSC caused by mutations in DCDC2 from Children's Hospital of Fudan University were gathered. The four patients' clinicopathological and molecular features were summarized by clinical data, liver biopsy, immunohistochemical, and molecular genetic analysis.ResultsAll patients presented with jaundice, hepatosplenomegaly, hyperbilirubinemia and bile embolism, and high serum γ-glutamyl transferase activity (GGT). Liver biopsies revealed varying degrees of bile duct hyperplasia, portal-tract inflammation, and/or fibrosis. Whole-exome sequencing (WES) found novel heterozygous variants of c.1024-1G > T /p.? and c.544G > A /p. Gly182Arg in the DCDC2.ConclusionThis study expands the genetic spectrum of DCDC2 in NSC.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fped.2023.1094895/fullTest; https://doaj.org/toc/2296-2360Test

الوصول الحر: https://doaj.org/article/9792fab641264e9f9ef202f4ca9d8eaaTest

المؤلفون: Yuan Fang, Ye Zhang, Rui Dong, Yi-zhen Wang, Lian Chen, Gong Chen

المصدر: Frontiers in Medicine, Vol 9 (2022)

مصطلحات موضوعية: intestinal ganglioneuromatosis, juvenile polyps, pseudomembranous enteritis, mutation, case series, Medicine (General), R5-920

الوصف: IntroductionIntestinal ganglioneuromatosis (IGN) is a rare condition with enteric involvement. Herein, we report a case series of pediatric IGN with a novel phenotypic and genotypic profile.MethodsThe clinical presentation, histopathology, immunochemistry, molecular features, treatment, and prognosis of 3 cases of IGN were assessed.ResultsThe cases involved 3 boys with an age range of 1 year and 4 months to 8 years, mimicking juvenile polyps or pseudomembranous enteritis. One patient carried a novel germline mutation in RTEL1 (c.296C > T/p.Pro99Leu) along with variants in F11 (c.1489C > T/p.Arg497Xaa), NBAS (c.1514delC/p.Pro505Hisfs*15), and FECH (c.315-48T > C/splicing), who died due to intractable inflammation. The other two patients underwent recurrence without significant signs of systemic syndrome or malignant progression.ConclusionThis case series added to the phenotypic and genotypic spectrum of pediatric IGN, which requires the accumulation of more cases and research for in-depth understanding.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmed.2022.883958/fullTest; https://doaj.org/toc/2296-858XTest

الوصول الحر: https://doaj.org/article/d461be9a07cd4b5f9b73c9d42e56ce91Test

المؤلفون: Yong-Peng Sun, Si-Yu Lei, Ying-Bin Wang, Yi-Zhen Wang, Hong-Sheng Qiang, Yi-Fan Yin, Ze-Min Jiang, Min Zhu, Xiao-Li Chen, Hui-Ming Ye, Zi-Zheng Zheng, Ning-Shao Xia

المصدر: Microbiology Spectrum, Vol 10, Iss 2 (2022)

مصطلحات موضوعية: RSV, hospitalized children, attachment glycoprotein, fusion protein, molecular epidemiology, Microbiology, QR1-502

الوصف: ABSTRACT Monitoring viral transmission and analyzing the genetic diversity of a virus are imperative to better understand its evolutionary history and the mechanism driving its evolution and spread. Especially, effective monitoring of key antigenic mutations and immune escape variants caused by these mutations has great scientific importance. Thus, to further understand the molecular evolutionary dynamics of respiratory syncytial virus (RSV) circulating in China, we analyzed nasopharyngeal swab specimens derived from hospitalized children ≤5 years old with acute respiratory tract infections (ARIs) in Xiamen during 2016 to 2019. We found that infants under 6 months of age (52.0%) were the main population with RSV infection. The prevalent pattern “BBAA” of RSV was observed during the epidemic seasons. RSV ON1 and BA9 genotypes were the dominant circulating strains in Xiamen. Interestingly, we observed four Xiamen-specific amino acid substitution combinations in the G protein and several amino acid mutations primarily occurring at antigenic sites Ø and V in the F protein. Our analyses suggest that introduction of new viruses and local evolution are shaping the diversification of RSV strains in Xiamen. This study provides new insights on the evolution and spread of the ON1 and BA9 genotypes at local and global scales. IMPORTANCE Monitoring the amino acid diversity of the RSV G and F genes helps us to find the novel genotypes, key antigenic mutations affecting antigenicity, or neutralizing antibody-resistant variants produced by natural evolution. In this study, we analyzed the molecular evolution of G and F genes from RSV strains circulating in Xiamen, China. These data provide new insights on local and global transmission and could inform the development of control measures for RSV infections.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2165-0497Test

الوصول الحر: https://doaj.org/article/df99ecb677e64ebc94f36cce055ad323Test

المؤلفون: Yuan Fang, Kuerbanjiang Abuduxikuer, Yi-Zhen Wang, Shao-Mei Li, Lian Chen, Jian-She Wang

المصدر: Frontiers in Genetics, Vol 13 (2022)

مصطلحات موضوعية: congenital disorders of glycosylation, TMEM199-CDG, inherited metabolic disease, liver disease, mutation, Genetics, QH426-470

الوصف: Background: TMEM199-congenital disorder of glycosylation (TMEM199-CDG) is a rare autosomal recessive inherited disease characterized by chronically elevated serum transaminase, decreased serum ceruloplasmin, steatosis and/or fibrosis, TMEM199 mutation, reduced level of TMEM199 protein, and abnormal protein glycosylation.Methods: The information of a Chinese patient with TMEM199-CDG in the Children’s Hospital of Fudan University was reviewed. The patient’s clinical, pathological, and molecular features were obtained by clinical data study, liver biopsy, immunohistochemistry, and molecular genetic analysis.Results: A 4-year-old Chinese boy presented with hypertransaminasemia, hypercholesterolemia, elevated alkaline phosphatase, decreased serum ceruloplasmin and serum copper level, and coagulopathy since birth. To the best of our knowledge, novel findings included strabismus, cirrhosis by liver biopsy, reduced expression of TMEM199 by immunohistochemistry, and a frameshift variant of c.128delA/p.Lys43Argfs*25 in the TMEM199 gene.Conclusion: This case added to the phenotypic and genotypic spectrum of TMEM199-CDG.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fgene.2022.833495/fullTest; https://doaj.org/toc/1664-8021Test

الوصول الحر: https://doaj.org/article/3289d795daf54e239a081431787534c4Test

المؤلفون: Ebenezeri Erasto Ngowi, Yi-Zhen Wang, Lei Qian, Yasmeen Ahmed Saleheldin Hassan Helmy, Bright Anyomi, Tao Li, Meng Zheng, En-She Jiang, Shao-Feng Duan, Jian-She Wei, Dong-Dong Wu, Xin-Ying Ji

المصدر: Frontiers in Bioengineering and Biotechnology, Vol 9 (2021)

مصطلحات موضوعية: nanotechnology, brain diseases and disorders, diagnosis, treatment, nanoparticles, Biotechnology, TP248.13-248.65

الوصف: Brain is by far the most complex organ in the body. It is involved in the regulation of cognitive, behavioral, and emotional activities. The organ is also a target for many diseases and disorders ranging from injuries to cancers and neurodegenerative diseases. Brain diseases are the main causes of disability and one of the leading causes of deaths. Several drugs that have shown potential in improving brain structure and functioning in animal models face many challenges including the delivery, specificity, and toxicity. For many years, researchers have been facing challenge of developing drugs that can cross the physical (blood–brain barrier), electrical, and chemical barriers of the brain and target the desired region with few adverse events. In recent years, nanotechnology emerged as an important technique for modifying and manipulating different objects at the molecular level to obtain desired features. The technique has proven to be useful in diagnosis as well as treatments of brain diseases and disorders by facilitating the delivery of drugs and improving their efficacy. As the subject is still hot, and new research findings are emerging, it is clear that nanotechnology could upgrade health care systems by providing easy and highly efficient diagnostic and treatment methods. In this review, we will focus on the application of nanotechnology in the diagnosis and treatment of brain diseases and disorders by illuminating the potential of nanoparticles.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fbioe.2021.629832/fullTest; https://doaj.org/toc/2296-4185Test

الوصول الحر: https://doaj.org/article/766e54b3fd4b41debdcd0377f3f40299Test

المؤلفون: Saadullah Khattak, Qian-Qian Zhang, Muhammad Sarfraz, Pir Muhammad, Ebenezeri Erasto Ngowi, Nazeer Hussain Khan, Saqib Rauf, Yi-Zhen Wang, Hui-Wen Qi, Di Wang, Attia Afzal, Xin-Ying Ji, Dong-Dong Wu

المصدر: Biomolecules, Vol 11, Iss 5, p 682 (2021)

مصطلحات موضوعية: hydrogen sulfide, respiratory diseases, metabolism processes, signaling pathways, Microbiology, QR1-502

الوصف: Respiratory diseases are leading causes of death and disability around the globe, with a diverse range of health problems. Treatment of respiratory diseases and infections has been verified to be thought-provoking because of the increasing incidence and mortality rate. Hydrogen sulfide (H2S) is one of the recognized gaseous transmitters involved in an extensive range of cellular functions, and physiological and pathological processes in a variety of diseases, including respiratory diseases. Recently, the therapeutic potential of H2S for respiratory diseases has been widely investigated. H2S plays a vital therapeutic role in obstructive respiratory disease, pulmonary fibrosis, emphysema, pancreatic inflammatory/respiratory lung injury, pulmonary inflammation, bronchial asthma and bronchiectasis. Although the therapeutic role of H2S has been extensively studied in various respiratory diseases, a concrete literature review will have an extraordinary impact on future therapeutics. This review provides a comprehensive overview of the effective role of H2S in respiratory diseases. Besides, we also summarized H2S production in the lung and its metabolism processes in respiratory diseases.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2218-273X/11/5/682Test; https://doaj.org/toc/2218-273XTest

الوصول الحر: https://doaj.org/article/2d2eca713ff241ac9de471b3fad6d3d9Test

المؤلفون: Yi-Zhen Wang, Ebenezeri Erasto Ngowi, Di Wang, Hui-Wen Qi, Mi-Rong Jing, Yan-Xia Zhang, Chun-Bo Cai, Qing-Lin He, Saadullah Khattak, Nazeer Hussain Khan, Qi-Ying Jiang, Xin-Ying Ji, Dong-Dong Wu

المصدر: International Journal of Molecular Sciences, Vol 22, Iss 4, p 2194 (2021)

مصطلحات موضوعية: hydrogen sulfide, gas signaling molecule, cardiovascular homeostasis, heart function, cardiac protection, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/22/4/2194Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/c4aa14e49e6a4eceb688ac7bd02c5a8fTest

المؤلفون: Yu‐Sheng Lin, Tzu‐Hao Chang, Chung‐Sheng Shi, Yi‐Zhen Wang, Wan‐Chun Ho, Hsien‐Da Huang, Shih‐Tai Chang, Kuo‐Li Pan, Mien‐Cheng Chen

المصدر: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 8, Iss 1 (2019)

مصطلحات موضوعية: atrioventricular block, cardiomyopathy, liver X receptor/retinoid X receptor pathway, pacing, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Background The molecular mechanisms through which high‐demand pacing induce myocardial dysfunction remain unclear. Methods and Results We created atrioventricular block in pigs using dependent right ventricular septal pacing for 6 months. Echocardiography was performed to evaluate dyssynchrony between pacing (n=6) and sham control (n=6) groups. Microarray and enrichment analyses were used to identify differentially expressed genes (DEGs) in the left ventricular (LV) myocardium between pacing and sham control groups. Histopathological and protein changes were also analyzed and an A cell pacing model was also performed. Pacing significantly increased mechanical dyssynchrony. Enrichment analysis using Ingenuity Pathway Analysis and the activation z‐score analysis method demonstrated that there were 5 DEGs (ABCA1, APOD, CLU, LY96, and SERPINF1) in the LV septum (z‐score=−0.447) and 5 DEGs (APOD, CLU, LY96, MSR1, and SERPINF1) in the LV free wall (z‐score=−1.000) inhibited the liver X receptor/retinoid X receptor (LXR/RXR) pathway, and 4 DEGs (ACTA2, MYL1, PPP2R3A, and SNAI2) activated the integrin‐linked kinase (ILK) pathway in the LV septum (z‐score=1.000). The pacing group had a larger cell size, higher degree of myolysis and fibrosis, and increased expression of intracellular lipid, inflammatory cytokines, and apoptotic markers than the sham control group. The causal relationships between pacing and DEGs related to LXR/RXR and ILK pathways, apoptosis, fibrosis, and lipid expression after pacing were confirmed in the cell pacing model. Luciferase reporter assay in the cell pacing model also supported inhibition of the LXR pathway by pacing. Conclusions Right ventricular septal‐dependent pacing was associated with persistent LV dyssynchrony–induced cardiomyopathy through inhibition of the LXR/RXR pathway.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2047-9980Test

الوصول الحر: https://doaj.org/article/c47cfc4e73094b71b64bf838f57911ccTest