المؤلفون: Huawei Mao, Mengyue Deng

المصدر: BMJ Paediatrics Open, Vol 7, Iss 1 (2023)

مصطلحات موضوعية: Pediatrics, RJ1-570

الوصف: Inborn errors of immunity (IEI), also known as primary immunodeficiency diseases, comprise a group of rare genetic disorders that affect the development or/and function of the immune system. These disorders predispose individuals to recurrent infections, autoimmunity, cancer and immune dysregulations. The field of IEI diagnosis and treatment in mainland China has made significant strides in recent years due to advances in genome sequencing, genetics, immunology and treatment strategies. However, the accessibility and affordability of diagnostic facilities and precision treatments remain variable among different regions. With the increasing government emphasis on rare disease prevention, diagnosis, and treatment, the field of IEI is expected to progress further in mainland China. Herein, we reviewed the development and current state of IEI in mainland China, highlighting the achievements made, as well as opportunities and challenges that lie ahead.

وصف الملف: electronic resource

العلاقة: https://bmjpaedsopen.bmj.com/content/7/1/e002002.fullTest; https://doaj.org/toc/2399-9772Test

الوصول الحر: https://doaj.org/article/8a991f6942444f39b63d9ee00fa642a3Test

المؤلفون: Yue Li, Mengyue Deng, Yulu Li, Xiaolan Mao, Shi Yan, Xuemei Tang, Huawei Mao

المصدر: Genes and Diseases, Vol 10, Iss 3, Pp 1090-1100 (2023)

مصطلحات موضوعية: Autoinflammatory diseases, Familial cold autoinflammatory syndrome type 2 (FCAS2), NLRP12-Associated autoinflammatory disease (NLRP12-AID), Nod-like receptor family pyrin domain-containing protein 12 (NLRP12), Nuclear factor-Kappa B (NF-κB), Medicine (General), R5-920, Genetics, QH426-470

الوصف: Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is one of the critical pattern recognition receptors which participates in the regulation of multiple inflammatory responses. Mutations in NLRP12 cause exceptionally rare NLRP12-associated autoinflammatory disease (NLRP12-AID). So far, very few patients with NLRP12-AID have been identified worldwide; therefore, data on the clinical phenotype and genetic profile are limited. In this study, we reported 10 patients who presented mainly with periodic fever syndrome or arthritis. Next-generation sequencing (NGS) identified 6 heterozygous mutations of NLRP12, including 2 novel null mutations. Of the patients, some with same mutations showed different clinical features. Compared to healthy controls, the increased levels of cytokines were revealed in the patients' plasmas, as well as in the supernatants of patients’ cells stimulated with lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α). The missense mutations did not change the protein expression; but decreased level of NLRP12 protein was shown in the null mutations. And in vitro expression assay demonstrated a truncating protein induced by the frameshift mutation. Further functional studies revealed the deleterious effect of mutations on nuclear factor-kappa B (NF-κB) signaling. Both the null and missense mutations impaired their inhibition of NF-κB activation induced by p65. Collectively, this study reported a relatively large NLRP12-AID case series. Our findings expand the clinical spectrum, and reinforce the diversity of genetic mutations and clinical phenotypes. The NLRP12-associated disorder should be considered when autoinflammatory diseases are encountered in the clinical practice, especially for patients presenting with periodic fever but no other genetic cause identified.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2352304222001465Test; https://doaj.org/toc/2352-3042Test

الوصول الحر: https://doaj.org/article/e807c748f74b4bcc81b7d06afa033122Test

المؤلفون: Wen Wen, Li Wang, Mengyue Deng, Yue Li, Xuemei Tang, Huawei Mao, Xiaodong Zhao

المصدر: Genes and Diseases, Vol 9, Iss 1, Pp 176-186 (2022)

مصطلحات موضوعية: AD-EDA-ID, HSCT, IκBα, NF-κB activation, NFKBIA, Medicine (General), R5-920, Genetics, QH426-470

الوصف: Germline heterozygous gain-of-function (GOF) mutation of NFKBIA, encoding IκBα, would affect the activation of NF-κB pathway and cause an autosomal dominant (AD) form of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). Here we reported a Chinese patient with a heterozygous N-terminal truncation mutation of NFKBIA/IκBα. She presented recurrent fever, infectious pneumonia and chronic diarrhea with EDA-ID. Impaired NF-κB translocation and IL1R and TLR4 pathway activation were revealed in this patient. The findings suggested that the truncation mutation of IκBα caused medium impaired of activation of NF-κB but the early death. Furthermore, we reviewed all the reported patients with NFKBIA mutation to learn more about this disease.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2352304221000441Test; https://doaj.org/toc/2352-3042Test

الوصول الحر: https://doaj.org/article/262667ad5aa04a3d9ed31e56350459b6Test

المؤلفون: Mengyue Deng, Yue Li, Yulu Li, Xiaolan Mao, Han Ke, Weiling Liang, Xiaoguang Lei, Yu-Lung Lau, Huawei Mao

المصدر: Frontiers in Immunology, Vol 13 (2022)

مصطلحات موضوعية: STAT3, gain-of-function mutation, interstitial lung disease, autoimmune disease, STAT3 inhibitor, JAK inhibitor, Immunologic diseases. Allergy, RC581-607

الوصف: Signal transducer and activator of transcription 3 (STAT3) gain-of-function (GOF) mutations cause early-onset immune dysregulation syndrome, characterized by multi-organ autoimmunity and lymphoproliferation. Of them, interstitial lung disease (ILD) usually develops after the involvement of other organs, and the onset time is childhood and beyond rather than infancy. Here, we reported a patient who presented with fatal infancy-onset ILD, finally succumbing to death. Next-generation sequencing identified a novel heterozygous mutation in STAT3 (c.989C>G, p.P330R). Functional experiments revealed it was a gain-of-function mutation. Upon interleukin 6 stimulation, this mutation caused a much higher activation of STAT3 than the wild-type control. In addition, the mutation also activated STAT3 under the steady state. The T helper 17 cell level in the patient was significantly higher than that in normal controls, which may contribute to the autoimmune pathology caused by the STAT3P330R mutation. Apart from Janus kinase (JAK) inhibitors, we also provided experimental evidence of a STAT3 selective inhibitor (Stattic) effectively suppressing the activation of mutant STAT3 in vitro. Collectively, our study expanded the clinical spectrum of STAT3 GOF syndrome. STAT3 GOF mutation appears as a new etiology of ILD and should be considered in patients with early-onset ILDs. In addition to JAK inhibitors, the specific STAT3 inhibitor would be an appealing option for the targeted treatment.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.866638/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/be2f51b57b7845a6814f0b8a171108a1Test

المؤلفون: Zijun Yan, Kun Yang, Xiang Tang, Yunfeng Bi, Yuzhen Ding, Mengyue Deng, Die Xia, Yunqi Zhao, Tong Chen

المصدر: Journal of Immunology Research, Vol 2022 (2022)

مصطلحات موضوعية: Immunologic diseases. Allergy, RC581-607

الوصف: Malignant tumors have become the main cause of harm to human life and health. Development for new antitumor drugs and the exploration to drug carriers are becoming the concerned focus. In this study, we exploited our experiments to explore the effect of NCTD-NLC on liver cancer cells: the HepG2 cells cultured in vitro were given with NCTD-NLC administration; then, the estimation on cellular proliferation and apoptosis was accomplished through MTT and flow cytometry. Six hours after the administration, we performed the High Performance Liquid Chromatography (HPLC) detection to estimate the NCTD content in the heart, liver, spleen, lung, kidney and plasma of rats. Then, our outcomes showed that NCTD-NLC had a notable inhibitory effect on HepG2 cells, leading to a gradually decreased cellular viability. Cell viability was negatively correlated with NCTD-NLC concentration. Along with the concentration increasing, significantly increasing cellular apoptosis and gradually decreasing cellular viability were observed. The apoptosis rate was positively correlated with the concentration of NCTD-NLC. On the basis of the data we obtained, we found that the group with NCTD-NLC tail vein injection had an obvious advantage in drug delivery when compared with other groups. Through the tumorigenesis test to nude mice, we found that the tumor inhibition rate of the NCTD-NLC tail vein injection group had a 27.48% elevation in contrast to the NCTD gavage group, and it was also the group with the best tumor inhibition efficiency. In conclusion, the NCTD-NLC prepared in this study had a mighty inhibitory effect towards HepG2 cellular viability and an accelerating work on apoptosis. Tail vein injection of NCTD-NLC has the best drug delivery effect.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2314-7156Test

الوصول الحر: https://doaj.org/article/1dc1bbd5486c43029ded1e39c43bf7caTest

المؤلفون: Mengyue Deng, Yue Li, Yulu Li, Xiaolan Mao, Ke Han, Weiling Liang, Xiaoguang Lei, Yu Lung Lau, Huawei Mao

مصطلحات موضوعية: Genetic Basis of Primary Immunodeficiency Disorders, Immunology, FOS Clinical medicine, Immunology and Microbiology, Life Sciences, Idiopathic Pulmonary Fibrosis Diagnosis and Management, Pulmonary and Respiratory Medicine, Medicine, Health Sciences, Neonatal Lung Development and Respiratory Morbidity, Interstitial Lung Disease, STAT3, Mutation, STAT protein, Interstitial lung disease, Janus kinase, Autoimmunity, Cancer research, Immune system, Biology, Lung, Signal transduction, Cytokine, Internal medicine, Genetics, FOS Biological sciences, Gene

الوصف: Signal transducer and activator of transcription 3 (STAT3) gain-of-function (GOF) mutations cause early-onset immune dysregulation syndrome, characterized by multi-organ autoimmunity and lymphoproliferation. Of them, interstitial lung disease (ILD) usually develops after the involvement of other organs, and the onset time is childhood and beyond rather than infancy. Here, we reported a patient who presented with fatal infancy-onset ILD, finally succumbing to death. Next-generation sequencing identified a novel heterozygous mutation in STAT3 (c.989C>G, p.P330R). Functional experiments revealed it was a gain-of-function mutation. Upon interleukin 6 stimulation, this mutation caused a much higher activation of STAT3 than the wild-type control. In addition, the mutation also activated STAT3 under the steady state. The T helper 17 cell level in the patient was significantly higher than that in normal controls, which may contribute to the autoimmune pathology caused by the STAT3P330R mutation. Apart from Janus ... : محول الإشارة ومنشط النسخ 3 (STAT3) تؤدي طفرات اكتساب الوظيفة (GOF) إلى متلازمة خلل التنظيم المناعي المبكر، والتي تتميز بالمناعة الذاتية متعددة الأعضاء والتكاثر اللمفاوي. من بينها، عادة ما يتطور مرض الرئة الخلالي (ILD) بعد إشراك الأعضاء الأخرى، ووقت البداية هو الطفولة وما بعدها بدلاً من الطفولة المبكرة. هنا، أبلغنا عن مريض قدم مع مرض العقم الدماغي المميت في مرحلة الطفولة، واستسلم أخيرًا حتى الموت. حدد تسلسل الجيل التالي طفرة جديدة متغايرة الزيجوت في STAT3 (c.989C>G, p.P330R). كشفت التجارب الوظيفية أنها كانت طفرة مكسب وظيفي. عند تحفيز الإنترلوكين 6، تسببت هذه الطفرة في تنشيط STAT3 أعلى بكثير من التحكم من النوع البري. بالإضافة إلى ذلك، نشطت الطفرة أيضًا STAT3 في ظل الحالة المستقرة. كان مستوى الخلايا التائية 17 في المريض أعلى بكثير من ذلك في الضوابط العادية، والتي قد تسهم في أمراض المناعة الذاتية الناجمة عن طفرة STAT3P330R. بصرف النظر عن مثبطات جانوس كيناز (JAK)، قدمنا أيضًا دليلًا تجريبيًا على مثبط انتقائي STAT3 (STATIC) يمنع بشكل فعال تنشيط STAT3 المتحول في المختبر. بشكل جماعي، وسعت دراستنا الطيف السريري ...

العلاقة: https://dx.doi.org/10.60692/h4pyq-6cc04Test

الإتاحة: https://doi.org/10.60692/sqakj-f1w2410.60692/h4pyq-6cc04Test

المؤلفون: Kun Wang, Lichen Liu, Mengyue Deng, Yaxian Feng

المصدر: Sustainability; Volume 15; Issue 1; Pages: 736

مصطلحات موضوعية: internal control, total factor productivity, environmental uncertainty, moderating effect

جغرافية الموضوع: agris

الوصف: Based on the data of China’s A-share listed companies from 2009 to 2019, this paper empirically examines the relationship between internal control and total factor productivity of enterprises in the presence of environmental uncertainty. The research shows that high quality internal control can effectively improve the total factor productivity of enterprises. Environmental uncertainty negatively moderates the relationship between internal control quality and total factor productivity. Further research in this paper shows that there are heterogeneous effects on the adjusting effects of different life cycles, property rights and regional distribution of enterprises, that is, when enterprises are in the growth stage, the quality of internal control has a significant effect on the improvement of total factor productivity of enterprises. For enterprises and non-state-owned enterprises located in the eastern region, the inhibition and adjustment effect of environmental uncertainty is more significant. At the same time, the supplementary research finds that internal control directly affects the total factor productivity of enterprises through the intermediary role of promoting enterprise development and innovation and easing financing constraints. The research conclusions enrich the literature on the mechanism of internal control affecting enterprises’ total factor productivity and provide a new reference and basis for enterprises to effectively manage the internal environment, strengthen the risk control management mechanism and improve the enterprise value.

وصف الملف: application/pdf

العلاقة: https://dx.doi.org/10.3390/su15010736Test

الإتاحة: https://doi.org/10.3390/su15010736Test

المؤلفون: Li Wang, Wen Wen, Mengyue Deng, Yue Li, Gan Sun, Xiaodong Zhao, Xuemei Tang, Huawei Mao

المصدر: Frontiers in Immunology, Vol 12 (2021)

مصطلحات موضوعية: NLRC4, novel mutation, autoinflammatory disease, mild phenotype, urticaria, Immunologic diseases. Allergy, RC581-607

الوصف: BackgroundNOD-like receptor family CARD-containing 4 protein (NLRC4) is a cytosolic protein that forms an inflammasome in response to flagellin and type 3 secretion system (T3SS) proteins from invading Gram-negative bacteria. NLRC4 mutations have been recently identified in early-onset severe autoinflammatory disorders. In this study, we reported a novel mutation in NLRC4 in two Chinese patients, who manifested with recurrent urticaria and arthralgia.MethodsWe summarized the clinical data of the two patients. Gene mutations were identified by whole-exome sequencing (WES). Swiss-PdbViewer was used to predict the pathogenicity of the identified mutations. Cytokine levels and caspase-1 activation were detected in the patient PBMCs with lipopolysaccharide (LPS) stimulation. All previously published cases with NLRC4 mutations were reviewed.ResultsWe identified a missense heterozygous mutation (c.514G>A, p.Gly172Ser), which was located in the highly conserved residue of nucleotide-binding domain (NBD) of NLRC4. The mutation did not alter the expression of NLRC4 protein, but induced considerably much higher production of IL-1β and IL-6 in patient PBMCs than in healthy controls after LPS stimulation. Four NLRC4 inflammasomopathy phenotypes have been described, with severe inflammatory diseases including macrophage activation syndrome, enterocolitis and NOMID in patients with mutations in the NBD and HD1 domains, whereas a mild clinical phenotype was associated with two mutations in the WHD domain of NLRC4.ConclusionWe identified a novel mutation in the NBD domain, and the patients just presented with a mild inflammatory phenotype. Thus, our findings reinforce the diversity of NLRC4 mutations and expand the clinical spectrum of associated diseases.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2021.674808/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/efe3a148512a47e98b34d55fddb5ed3eTest

المؤلفون: Yan Li, Mengyue Deng, Tongxin Han, Wenxiu Mo, Huawei Mao

المصدر: Journal of Clinical Immunology. 43:780-793

مصطلحات موضوعية: Immunology, Immunology and Allergy

الوصف: Purpose Sideroblastic anemia, immunodeficiency, periodic fevers, and developmental delay (SIFD) is an autosomal recessive syndrome caused by biallelic loss-of-function variant of tRNA nucleotidyl transferase 1 (TRNT1). Efficacious methods to treat SIFD are lacking. We identified two novel mutations in TRNT1 and an efficacious and novel therapy for SIFD. Methods We retrospectively summarized the clinical records of two patients with SIFD from different families and reviewed all published cases of SIFD. Results Both patients had periodic fever, developmental delay, rash, microcytic anemia, and B cell lymphopenia with infections. Whole-exome sequencing of patient 1 identified a previously unreported homozygous mutation of TRNT1 (c.706G > A/p.Glu236Lys). He received intravenous immunoglobulin (IVIG) replacement and antibiotics, but died at 1 year of age. Gene testing in patient 2 revealed compound heterozygous mutations (c.907C > G/p.Gln303Glu and c.88A > G/p.Met30Val) in TRNT1, the former of which is a novel mutation. Periodic fever was controlled in the first month after adalimumab therapy and IVIG replacement, but recurred in the second month. Adalimumab was discontinued and replaced with thalidomide, which controlled the periodic fever and normalized inflammatory markers effectively. A retrospective analysis of reported cases revealed 69 patients with SIFD carrying 46 mutations. The male: female ratio was 1: 1, and the mean age of onset was 3.0 months. The most common clinical manifestations in patients with SIFD were microcytic anemia (82.6%), hypogammaglobulinemia/B cell lymphopenia (75.4%), periodic fever (66.7%), and developmental delay (60.0%). In addition to the typical tetralogy, SIFD features several heterogeneous symptoms involving multiple systems. Corticosteroids, immunosuppressants, and anakinra have low efficacy, whereas etanercept suppressed fever and improved anemia in reports. Bone-marrow transplantation can be used to treat severe SIFD, but carries a high risk. In total, 28.2% (20/71) of reported patients died, mainly because of multi-organ failure. Biallelic mutations located in exon1-intron5 lead to more severe phenotypes and higher mortality. Furthermore, 15.5% (11/71) patients survived to adulthood. The symptoms could be resolved spontaneously in five patients. Conclusions Thalidomide can control the inflammation of SIFD and represents a new treatment for SIFD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::06150f667f29d1eb87566a456f4b4548Test
https://doi.org/10.1007/s10875-023-01441-7Test

المؤلفون: PANPAN WEI, MENGYUE DENG, YUZHEN DING, DIE XIA, ZIJUN YAN, TONG CHEN

المصدر: Acta Poloniae Pharmaceutica; Sep/Oct2023, Vol. 80 Issue 5, p705-716, 12p

مصطلحات موضوعية: POLYSACCHARIDES, NATURAL resources, ANTIOXIDANTS, MEDICAL care, MEDICAL databases, PREVENTIVE medicine

مستخلص: Oxidative stress is associated with the development of many diseases, such as chronic inflammation, cardiovascular disease, and cancer. Antioxidants can scavenge free radicals in the body, reduce the production of reactive oxygen species (ROS), and effectively prevent oxidative stress. Polysaccharides--a kind of high molecular polymer with antioxidant activity--are antioxidants that are widely found in natural sources. They can prevent oxidative stress and play a role in disease prevention through various mechanisms. In this paper, the different types of polysaccharides were summarized, such as plant, algal, microbial and animal polysaccharides, and their antioxidant mechanism and application in the treatment of disease were also discussed. We hope this review can offer some theoretical basis and inspiration for the antioxidant activity study and application of polysaccharides from natural sources. [ABSTRACT FROM AUTHOR]

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