Alcohol and opioid abuse have pervasive and detrimental consequences from the individual to societal level. The extent of genetic contribution to alcoholism has been studied for decades, yielding speculative and often inconsistent results since the previous discovery of two pharmacokinetic variants strongly protective against alcoholism. The neurobiology of addiction involves innumerate genes with combinatorial and epistatic interactions, creating a difficult landscape for concrete conclusions. In contrast, pharmacogenomic variation in the treatment of alcoholism yields more immediate clinical utility, while also emphasizing pathways crucial to the progression of addiction. An improved understanding of genetic predisposition to alcohol abuse has inherent significance for opioid addiction and treatment, as the two drugs induce the same reward pathway. This review outlines current knowledge, treatments, and research regarding genetic predisposition to alcoholism, focusing on pharmacodynamic variation within the dopaminergic system and shared implications for opioid abuse. Multifaceted and highly polygenic, the phenotype of addiction seems to grow more complex as new research extends the scope of its impact on the brain, body, and progeny.
{"title":"Genetic variation in alcoholism and opioid addiction susceptibility and treatment: a pharmacogenomic approach","authors":"Catherine Demery-Poulos, Joseph M Chambers","doi":"10.3934/molsci.2021016","DOIUrl":"https://doi.org/10.3934/molsci.2021016","url":null,"abstract":"Alcohol and opioid abuse have pervasive and detrimental consequences from the individual to societal level. The extent of genetic contribution to alcoholism has been studied for decades, yielding speculative and often inconsistent results since the previous discovery of two pharmacokinetic variants strongly protective against alcoholism. The neurobiology of addiction involves innumerate genes with combinatorial and epistatic interactions, creating a difficult landscape for concrete conclusions. In contrast, pharmacogenomic variation in the treatment of alcoholism yields more immediate clinical utility, while also emphasizing pathways crucial to the progression of addiction. An improved understanding of genetic predisposition to alcohol abuse has inherent significance for opioid addiction and treatment, as the two drugs induce the same reward pathway. This review outlines current knowledge, treatments, and research regarding genetic predisposition to alcoholism, focusing on pharmacodynamic variation within the dopaminergic system and shared implications for opioid abuse. Multifaceted and highly polygenic, the phenotype of addiction seems to grow more complex as new research extends the scope of its impact on the brain, body, and progeny.","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70226064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Afreen Bhatty, Z. Rubab, Hafiz Syed Mohammad Osama Jafri, Sheh Zano
Objective
The aim of the current study was to explore the gene enrichment and dysregulated pathways on the basis of interaction network analysis of SLC30A8 in type 1 diabetes mellitus (T1DM). SLC30A8 polymorphism could be characterized as a beneficial tool to identify the interacting gene in developing T1DM.
Materials and methods
SLC30A8 interacting protein interaction network was obtained by String Interaction network Version 11.0. Ten proteins were identified interacting with SLC30A8 and were analysed by protein-protein interaction and enrichment network analysis along with Functional Enrichment analysis tool (FunRich 3.1.3) to map the gene data sets. In entire analysis, FunRich database was used as background against all annotated gene/protein list. Protein-protein interaction (PPI) and enrichment network analysis of the selected protein: SLC30A8 gene along with gene mapping and pathway enrichment were performed using FunRich 3.1.3 and String Interaction network Version 11.0.
Results
Biological pathway grouping displayed enriched proteins in TRAIL signalling pathway (p < 0.001). PTPRN, GAD2 and TCF7L2 were enriched in TRAIL Signalling pathway when INS was made focused gene and directly interacting with SLC30A8.
Conclusions
TRAIL signalling pathways were enriched in T1DM. Therefore, SLC30A8 along with PTPRN, GAD2 and TCF7L2 involved in TRAIL pathway must be further explored to understand their in vivo role in T1DM.
目的通过相互作用网络分析SLC30A8基因在1型糖尿病(T1DM)中的富集和失调途径。SLC30A8多态性可作为鉴定T1DM发生过程中相互作用基因的有益工具。材料与方法通过String interaction network Version 11.0获得sslc30a8相互作用蛋白相互作用网络。鉴定出10个与SLC30A8相互作用的蛋白，并利用功能富集分析工具(FunRich 3.1.3)进行蛋白相互作用和富集网络分析，绘制基因数据集。在整个分析中，FunRich数据库作为所有注释基因/蛋白列表的背景。利用FunRich 3.1.3和String interaction network Version 11.0对选取的SLC30A8基因进行蛋白-蛋白相互作用(protein -protein interaction, PPI)和富集网络分析，并进行基因定位和通路富集。结果生物通路分组显示TRAIL信号通路蛋白富集(p < 0.001)。当INS成为聚焦基因并与SLC30A8直接相互作用时，TRAIL信号通路中PTPRN、GAD2和TCF7L2富集。结论T1DM中strail信号通路丰富。因此，SLC30A8与PTPRN、GAD2和TCF7L2参与TRAIL通路还需进一步探索，以了解它们在T1DM中的体内作用。
{"title":"Identification of dysregulated pathways through SLC30A8 protein interaction in type 1 diabetes mellitus","authors":"Afreen Bhatty, Z. Rubab, Hafiz Syed Mohammad Osama Jafri, Sheh Zano","doi":"10.3934/molsci.2021023","DOIUrl":"https://doi.org/10.3934/molsci.2021023","url":null,"abstract":"<abstract><sec> <title>Objective</title> <p>The aim of the current study was to explore the gene enrichment and dysregulated pathways on the basis of interaction network analysis of <italic>SLC30A8</italic> in type 1 diabetes mellitus (T1DM). <italic>SLC30A8</italic> polymorphism could be characterized as a beneficial tool to identify the interacting gene in developing T1DM.</p> </sec><sec> <title>Materials and methods</title> <p><italic>SLC30A8</italic> interacting protein interaction network was obtained by String Interaction network Version 11.0. Ten proteins were identified interacting with <italic>SLC30A8</italic> and were analysed by protein-protein interaction and enrichment network analysis along with Functional Enrichment analysis tool (FunRich 3.1.3) to map the gene data sets. In entire analysis, FunRich database was used as background against all annotated gene/protein list. Protein-protein interaction (PPI) and enrichment network analysis of the selected protein: <italic>SLC30A8</italic> gene along with gene mapping and pathway enrichment were performed using FunRich 3.1.3 and String Interaction network Version 11.0.</p> </sec><sec> <title>Results</title> <p>Biological pathway grouping displayed enriched proteins in TRAIL signalling pathway (<italic>p</italic> < 0.001). <italic>PTPRN, GAD2</italic> and <italic>TCF7L2</italic> were enriched in TRAIL Signalling pathway when <italic>INS</italic> was made focused gene and directly interacting with <italic>SLC30A8</italic>.</p> </sec><sec> <title>Conclusions</title> <p>TRAIL signalling pathways were enriched in T1DM. Therefore, <italic>SLC30A8</italic> along with <italic>PTPRN, GAD2</italic> and <italic>TCF7L2</italic> involved in TRAIL pathway must be further explored to understand their in vivo role in T1DM.</p> </sec></abstract>","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70226416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cartilage tissue is avascular and resistant to tumor invasion, but the basis for these properties is still unclear. Here we report that the NH2-propeptide of type IIB procollagen (PIIBNP), a product of collagen biosynthesis, is capable of inhibiting angiogenesis both in vitro and in vivo. PIIBNP inhibits tube formation in human umbilical vein cells (HUVEC), inhibits endogenous endothelial cell outgrowth in mouse aortic ring angiogenesis bioassay and is anti-angiogenic in the mouse cornea angiogenesis assay. As αVß3 and αVß5 integrins are expressed primarily in endothelial cells, cancer cells and osteoclasts, but not in normal chondrocytes and PIIBNP binds to cell surface integrin αVß3 and αVß5, we propose that natural occurring PIIBNP protects cartilage by targeting endothelial cells during chondrogenesis, thus inhibiting angiogenesis, and rendering the tissue avascular.
{"title":"Cartilage type IIB procollagen NH2-propeptide, PIIBNP, inhibits angiogenesis","authors":"Zhepeng Wang, Aiwu Lu","doi":"10.3934/molsci.2021022","DOIUrl":"https://doi.org/10.3934/molsci.2021022","url":null,"abstract":"<abstract> <p>Cartilage tissue is avascular and resistant to tumor invasion, but the basis for these properties is still unclear. Here we report that the NH<sub>2</sub>-propeptide of type IIB procollagen (PIIBNP), a product of collagen biosynthesis, is capable of inhibiting angiogenesis both <italic>in vitro</italic> and <italic>in vivo</italic>. PIIBNP inhibits tube formation in human umbilical vein cells (HUVEC), inhibits endogenous endothelial cell outgrowth in mouse aortic ring angiogenesis bioassay and is anti-angiogenic in the mouse cornea angiogenesis assay. As α<sub>V</sub>ß<sub>3</sub> and α<sub>V</sub>ß<sub>5</sub> integrins are expressed primarily in endothelial cells, cancer cells and osteoclasts, but not in normal chondrocytes and PIIBNP binds to cell surface integrin α<sub>V</sub>ß<sub>3</sub> and αVß<sub>5</sub>, we propose that natural occurring PIIBNP protects cartilage by targeting endothelial cells during chondrogenesis, thus inhibiting angiogenesis, and rendering the tissue avascular.</p> </abstract>","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70226208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aliya Irshad Sani, Zil-e-Rubab, S. Usman, Syed Zaryab Ahmed, M. Hosein
Body‟s defence mechanism has ability to combat tumour cells but tumour cells can circumvent immune system in order to flourish. Therefore, current research focuses on reinvigorating immune system to combat against extensive range of human malignancies through immunotherapy. Recently, immuno-therapy has demonstrated beneficial outcomes in cancers treatment but the main drawbacks are primary and acquired resistance to the therapeutic agents and immune-related toxicities. Therefore, novel immune therapies are direly required. Co-stimulatory molecules such as TNF Receptor Superfamily Member 4 (OX40, CD134) and its ligand TNF Superfamily Member 4 (CD252, OX40L) are expressed on different immune cells. The mutual interaction between OX40 and its ligand (OX40/OX40L) decreases the functional capacity of immunosuppression offered by regulatory T cells (Tregs) and induces the proliferation of T cells against specific antigen enhancing the immune response. Many clinical trials are focusing on OX40/OX40L therapeutic agents to find out whether they have therapeutic effect on cancer treatment. The initial phase trials result of OX40 and its ligands focusing therapeutic agents are encouraging but still not sufficient. This review will concentrate on the cellular and molecular pathways of OX40-mediated T-cell co-stimulation, the expression of OX40 and OX40L in tumours, the implications of their interactions and their under-or over-expression patterns, with particular focus on the function of OX40 in tumours of different origins. Finally, we discuss results of clinical trials of OX40 and OX40L directed pharmacotherapy and the lacunae that need to be filled.
{"title":"Role of OX40 and its ligand as costimulatory modulators in cancer immunotherapy","authors":"Aliya Irshad Sani, Zil-e-Rubab, S. Usman, Syed Zaryab Ahmed, M. Hosein","doi":"10.3934/molsci.2021012","DOIUrl":"https://doi.org/10.3934/molsci.2021012","url":null,"abstract":"Body‟s defence mechanism has ability to combat tumour cells but tumour cells can circumvent immune system in order to flourish. Therefore, current research focuses on reinvigorating immune system to combat against extensive range of human malignancies through immunotherapy. Recently, immuno-therapy has demonstrated beneficial outcomes in cancers treatment but the main drawbacks are primary and acquired resistance to the therapeutic agents and immune-related toxicities. Therefore, novel immune therapies are direly required. Co-stimulatory molecules such as TNF Receptor Superfamily Member 4 (OX40, CD134) and its ligand TNF Superfamily Member 4 (CD252, OX40L) are expressed on different immune cells. The mutual interaction between OX40 and its ligand (OX40/OX40L) decreases the functional capacity of immunosuppression offered by regulatory T cells (Tregs) and induces the proliferation of T cells against specific antigen enhancing the immune response. Many clinical trials are focusing on OX40/OX40L therapeutic agents to find out whether they have therapeutic effect on cancer treatment. The initial phase trials result of OX40 and its ligands focusing therapeutic agents are encouraging but still not sufficient. This review will concentrate on the cellular and molecular pathways of OX40-mediated T-cell co-stimulation, the expression of OX40 and OX40L in tumours, the implications of their interactions and their under-or over-expression patterns, with particular focus on the function of OX40 in tumours of different origins. Finally, we discuss results of clinical trials of OX40 and OX40L directed pharmacotherapy and the lacunae that need to be filled.","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70225751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cervical cancer is the sequel of a multi-factorial, long-term unresolved disease that includes genetic, epigenetic, and viral components responsible for its development and progression. It is the second most common cancer of females in India. Human papillomavirus (HPV) is considered the primary causative agent of pre-neoplastic and cancerous lesions and 90% of all cervical carcinomas are linked to high-risk HPV type 16 and type 18. Although most HR-HPV infections are asymptomatic, transient, and self-limiting, the persistent infection with a high risk (HR-HPV) may cause precancerous lesions that can progress to cervical cancer. HPV type 16 is the most common HPV in India associated with more than 75% of cervical cancer, followed by HPV type 18 and other high-risk types. Infection with HPV alone is not sufficient for the development of cervical cancer but there is the involvement of some host genetic factors also that are responsible for the development and progression of cervical cancer. This article briefly reviews molecular pathogenesis, viral load, and the interaction of HPV oncoprotein E6 and E7 with host cellular markers in the progression of cervical cancer.
{"title":"Viral load and interaction of HPV oncoprotein E6 and E7 with host cellular markers in the progression of cervical cancer","authors":"B. Mir, P. F. Rahaman, Arif Ahmad","doi":"10.3934/molsci.2021014","DOIUrl":"https://doi.org/10.3934/molsci.2021014","url":null,"abstract":"Cervical cancer is the sequel of a multi-factorial, long-term unresolved disease that includes genetic, epigenetic, and viral components responsible for its development and progression. It is the second most common cancer of females in India. Human papillomavirus (HPV) is considered the primary causative agent of pre-neoplastic and cancerous lesions and 90% of all cervical carcinomas are linked to high-risk HPV type 16 and type 18. Although most HR-HPV infections are asymptomatic, transient, and self-limiting, the persistent infection with a high risk (HR-HPV) may cause precancerous lesions that can progress to cervical cancer. HPV type 16 is the most common HPV in India associated with more than 75% of cervical cancer, followed by HPV type 18 and other high-risk types. Infection with HPV alone is not sufficient for the development of cervical cancer but there is the involvement of some host genetic factors also that are responsible for the development and progression of cervical cancer. This article briefly reviews molecular pathogenesis, viral load, and the interaction of HPV oncoprotein E6 and E7 with host cellular markers in the progression of cervical cancer.","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70225903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aging is the strongest contributor to the development and severity of many chronic and infectious diseases, primarily through age-related increases in low-grade inflammation (inflammaging) and decreases in immune function (immunosenescence). Metabolic reprogramming in immune cells is a significant contributor to functional and phenotypic changes in these cells, but little is known about the direct effect of aging on immunometabolism. This review highlights several recent advances in this field, focusing on mitochondrial dysfunction, NAD+ metabolism, and therapeutic reprogramming in aged monocytes and macrophages. Perspectives on opportunities for future research in this area are also provided. Targeting immunometabolism is a promising strategy for designing therapeutics for a wide variety of age-related diseases.
{"title":"Recent developments and future perspectives in aging and macrophage immunometabolism","authors":"B. Pence","doi":"10.3934/molsci.2021015","DOIUrl":"https://doi.org/10.3934/molsci.2021015","url":null,"abstract":"Aging is the strongest contributor to the development and severity of many chronic and infectious diseases, primarily through age-related increases in low-grade inflammation (inflammaging) and decreases in immune function (immunosenescence). Metabolic reprogramming in immune cells is a significant contributor to functional and phenotypic changes in these cells, but little is known about the direct effect of aging on immunometabolism. This review highlights several recent advances in this field, focusing on mitochondrial dysfunction, NAD+ metabolism, and therapeutic reprogramming in aged monocytes and macrophages. Perspectives on opportunities for future research in this area are also provided. Targeting immunometabolism is a promising strategy for designing therapeutics for a wide variety of age-related diseases.","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70226010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amal Farouk, Areez Shafqat, Shameel Shafqat, J. Kashir, K. Alkattan, A. Yaqinuddin
The COVID-19 pandemic has driven an upheaval of new research, providing key insights into the pathogenesis of this disease. Lymphocytopenia, hyper-inflammation and cardiac involvement are prominent features of the disease and have prognostic value. However, the mechanistic links among these phenomena are not well understood. Likewise, some COVID-19 patients exhibit multi-organ failure with diseases affecting the cardiac system, appearing to be an emerging feature of the COVID-19 pandemic. Neutrophil extracellular traps (NETs) have been frequently correlated with larger infarct sizes and can predict major adverse cardiac events. However, the exact mechanism behind this remains unknown. Although the excessive NET formation can drive inflammation, particularly endothelial and promote thrombosis, it is essential to normal immunity. In this paper, we postulate the role of NETs in cardiac disease by providing an overview of the relationship between NET and inflammasome activities in lung and liver diseases, speculating a link between these entities in cardiac diseases as well. Future research is required to specify the role of NETs in COVID-19, since this carries potential therapeutic significance, as inhibition of NETosis could alleviate symptoms of this disease. Knowledge gained from this could serve to inform the assessment and therapeutics of other hyper inflammatory diseases affecting the heart and vasculature alike.
{"title":"COVID-19 associated cardiac disease: Is there a role of neutrophil extracellular traps in pathogenesis?","authors":"Amal Farouk, Areez Shafqat, Shameel Shafqat, J. Kashir, K. Alkattan, A. Yaqinuddin","doi":"10.3934/molsci.2021021","DOIUrl":"https://doi.org/10.3934/molsci.2021021","url":null,"abstract":"The COVID-19 pandemic has driven an upheaval of new research, providing key insights into the pathogenesis of this disease. Lymphocytopenia, hyper-inflammation and cardiac involvement are prominent features of the disease and have prognostic value. However, the mechanistic links among these phenomena are not well understood. Likewise, some COVID-19 patients exhibit multi-organ failure with diseases affecting the cardiac system, appearing to be an emerging feature of the COVID-19 pandemic. Neutrophil extracellular traps (NETs) have been frequently correlated with larger infarct sizes and can predict major adverse cardiac events. However, the exact mechanism behind this remains unknown. Although the excessive NET formation can drive inflammation, particularly endothelial and promote thrombosis, it is essential to normal immunity. In this paper, we postulate the role of NETs in cardiac disease by providing an overview of the relationship between NET and inflammasome activities in lung and liver diseases, speculating a link between these entities in cardiac diseases as well. Future research is required to specify the role of NETs in COVID-19, since this carries potential therapeutic significance, as inhibition of NETosis could alleviate symptoms of this disease. Knowledge gained from this could serve to inform the assessment and therapeutics of other hyper inflammatory diseases affecting the heart and vasculature alike.","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70225860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Shboul, H. Sassi, H. Jilani, I. Rejeb, Y. Elaribi, S. Hizem, L. B. Jemaa, Marwa Hilmi, S. Kircher, A. Kaissi, Kurgan Russia Ortopedics n.a. G.A. Ilizarov
Objective: Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Mutations in the COL2A1 gene cause a spectrum of rare autosomal-dominant type II collagenopathies characterized by skeletal dysplasia, short stature, and with vision and auditory defects. In this study, we have investigated in more detail the phenotypic and genotypic characterization resulting from glycine to serine mutations in the COL2A1 gene in a 2-year-old boy. Materials and methods: Detailed clinical and radiological phenotypic characterization was the baseline tool to guide the geneticists toward proper genotypic confirmation. Results: Genetic analysis revealed a de novo mutation, c.1681G>A (p.Gly561Ser), in the collagen type II alpha-1 gene (COL2A1). The identified variant showed impaired protein stability, and lead to dysfunction of type II collagen. In addition to pre and postnatal growth retardation, remarkable retardation of gross motor development and intellectual disability were noted. The latter was connected to cerebral malformations. The overall clinical phenotype of our current patient resembles spondyloepiphyseal dysplasia congenita (SEDC), but with extra phenotypic criteria. Conclusions: The aim of this paper is twofold; firstly, raising awareness among orthopaedic surgeons when dealing with children
目的:骨软骨发育不良是一种异质性的遗传性骨骼发育不良。COL2A1基因突变导致罕见的常染色体显性II型胶原病，其特征是骨骼发育不良、身材矮小、视力和听觉缺陷。在这项研究中，我们更详细地研究了一名2岁男孩COL2A1基因中甘氨酸到丝氨酸突变的表型和基因型特征。材料和方法:详细的临床和放射学表型表征是指导遗传学家进行适当基因型确认的基线工具。结果:遗传分析显示胶原II型α -1基因(COL2A1)中有一个新的突变，c.1681G> a (p.Gly561Ser)。鉴定的变异显示蛋白质稳定性受损，并导致II型胶原功能障碍。除了产前和产后生长迟缓外，还注意到明显的大运动发育迟缓和智力残疾。后者与大脑畸形有关。我们当前患者的整体临床表型类似于先天性脊柱骨骺发育不良(SEDC)，但具有额外的表型标准。结论:本文的目的是双重的;首先，提高骨科医生在处理儿童问题时的意识
{"title":"The phenotypic spectrum in a patient with Glycine to Serine mutation in the COL2A1 gene: overview study","authors":"M. Shboul, H. Sassi, H. Jilani, I. Rejeb, Y. Elaribi, S. Hizem, L. B. Jemaa, Marwa Hilmi, S. Kircher, A. Kaissi, Kurgan Russia Ortopedics n.a. G.A. Ilizarov","doi":"10.3934/MOLSCI.2021006","DOIUrl":"https://doi.org/10.3934/MOLSCI.2021006","url":null,"abstract":"Objective: Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Mutations in the COL2A1 gene cause a spectrum of rare autosomal-dominant type II collagenopathies characterized by skeletal dysplasia, short stature, and with vision and auditory defects. In this study, we have investigated in more detail the phenotypic and genotypic characterization resulting from glycine to serine mutations in the COL2A1 gene in a 2-year-old boy. Materials and methods: Detailed clinical and radiological phenotypic characterization was the baseline tool to guide the geneticists toward proper genotypic confirmation. Results: Genetic analysis revealed a de novo mutation, c.1681G>A (p.Gly561Ser), in the collagen type II alpha-1 gene (COL2A1). The identified variant showed impaired protein stability, and lead to dysfunction of type II collagen. In addition to pre and postnatal growth retardation, remarkable retardation of gross motor development and intellectual disability were noted. The latter was connected to cerebral malformations. The overall clinical phenotype of our current patient resembles spondyloepiphyseal dysplasia congenita (SEDC), but with extra phenotypic criteria. Conclusions: The aim of this paper is twofold; firstly, raising awareness among orthopaedic surgeons when dealing with children","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70225877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. P. Priyanka, R. S. Nair, Sanjana Kumaraguru, K. Saravanaraj, Vasantharekha Ramasamy
Neuroendocrine-immune homeostasis in health and disease is a tightly regulated bidirectional network that influences predisposition, onset and progression of age-associated disorders. The complexity of interactions among the nervous, endocrine and immune systems necessitates a complete review of all the likely mechanisms by which each individual system can alter neuroendocrine-immune homeostasis and influence the outcome in age and disease. Dysfunctions in this network with age or external/internal stimuli are implicated in the development of several disorders including autoimmunity and cancer. The existence of sympathetic noradrenergic innervations on lymphoid organs in synaptic association with immune cells that express receptors for endocrine mediators such as hormones, neural mediators such as neurotransmitters and immune effector molecules such as cytokines explains the complicated nature of the regulatory pathways that must always maintain homeostatic equilibrium within and among the nervous, endocrine and immune systems. The incidence, development and progression of cancer, affects each of the three systems by disrupting regulatory pathways and tipping the scales away from homeostasis to favour pathways that enable it to evade, override and thrive by using the network to its advantage. In this review, we have explained how the neuroendocrine-immune network is altered in female reproductive aging and cancer, and how these modulations contribute to incidence and progression of cancer and hence prove to be valuable targets from a therapeutic standpoint. Reproductive aging, stress-associated central pathways, sympathetic immunomodulation in the periphery, inflammatory and immunomodulatory changes in central, peripheral and tumor-microenvironment, and neuro-neoplastic associations are all likely candidates that influence the onset, incidence and progression of cancer.
{"title":"Insights on neuroendocrine regulation of immune mediators in female reproductive aging and cancer","authors":"H. P. Priyanka, R. S. Nair, Sanjana Kumaraguru, K. Saravanaraj, Vasantharekha Ramasamy","doi":"10.3934/molsci.2021010","DOIUrl":"https://doi.org/10.3934/molsci.2021010","url":null,"abstract":"Neuroendocrine-immune homeostasis in health and disease is a tightly regulated bidirectional network that influences predisposition, onset and progression of age-associated disorders. The complexity of interactions among the nervous, endocrine and immune systems necessitates a complete review of all the likely mechanisms by which each individual system can alter neuroendocrine-immune homeostasis and influence the outcome in age and disease. Dysfunctions in this network with age or external/internal stimuli are implicated in the development of several disorders including autoimmunity and cancer. The existence of sympathetic noradrenergic innervations on lymphoid organs in synaptic association with immune cells that express receptors for endocrine mediators such as hormones, neural mediators such as neurotransmitters and immune effector molecules such as cytokines explains the complicated nature of the regulatory pathways that must always maintain homeostatic equilibrium within and among the nervous, endocrine and immune systems. The incidence, development and progression of cancer, affects each of the three systems by disrupting regulatory pathways and tipping the scales away from homeostasis to favour pathways that enable it to evade, override and thrive by using the network to its advantage. In this review, we have explained how the neuroendocrine-immune network is altered in female reproductive aging and cancer, and how these modulations contribute to incidence and progression of cancer and hence prove to be valuable targets from a therapeutic standpoint. Reproductive aging, stress-associated central pathways, sympathetic immunomodulation in the periphery, inflammatory and immunomodulatory changes in central, peripheral and tumor-microenvironment, and neuro-neoplastic associations are all likely candidates that influence the onset, incidence and progression of cancer.","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70225952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Srinivasamurthy, Nagaraj Kakanahalli, Shreeshail V. Benakanal
Hydrocephalus is a neurodevelopmental, X-linked recessive disorder caused by mutations in the L1CAM gene. The L1CAM gene encodes for L1CAM protein which is essential for the nervous system development including adhesion between neurons, Myelination, Synaptogenesis etc. Herein, the present study has reported mutations in L1 syndrome patient with Hydrocephalus and Adducted thumb. Genomic DNA was extracted from patients whole blood (n = 18). The 11 exons of the L1CAM gene were amplified using specific PCR primers. The sequenced data was analysed and the pathogenicity of the mutation was predicted using the various bioinformatics programs: PROVEAN, PolyPhen2, and MUpro. The results revealed that the proband described here had nonsense mutation G1120→T at position 1120 in exon 9 which is in extracellular immunoglobulin domain (Ig4) of the L1CAM gene. This nonsense mutation is found to be truncated with a deleterious effect on developing brain of the child, and this is the first report of this novel mutation in patient with X-linked Hydrocephalus in India.
{"title":"A truncation mutation in the L1CAM gene in a child with hydrocephalus","authors":"M. Srinivasamurthy, Nagaraj Kakanahalli, Shreeshail V. Benakanal","doi":"10.3934/molsci.2021017","DOIUrl":"https://doi.org/10.3934/molsci.2021017","url":null,"abstract":"Hydrocephalus is a neurodevelopmental, X-linked recessive disorder caused by mutations in the L1CAM gene. The L1CAM gene encodes for L1CAM protein which is essential for the nervous system development including adhesion between neurons, Myelination, Synaptogenesis etc. Herein, the present study has reported mutations in L1 syndrome patient with Hydrocephalus and Adducted thumb. Genomic DNA was extracted from patients whole blood (n = 18). The 11 exons of the L1CAM gene were amplified using specific PCR primers. The sequenced data was analysed and the pathogenicity of the mutation was predicted using the various bioinformatics programs: PROVEAN, PolyPhen2, and MUpro. The results revealed that the proband described here had nonsense mutation G1120→T at position 1120 in exon 9 which is in extracellular immunoglobulin domain (Ig4) of the L1CAM gene. This nonsense mutation is found to be truncated with a deleterious effect on developing brain of the child, and this is the first report of this novel mutation in patient with X-linked Hydrocephalus in India.","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70226087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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