Pub Date : 2024-01-01DOI: 10.2174/1871530323666230518105408
Chaoming Qiu, Xifei Yang, Pei Yu
Sarcopenia is becoming prevalent in older or inactive patients, which is placing a heavy burden on the social health system. Studies on the pathogenesis of sarcopenia mainly focus on adipose tissue, myoglobin autophagy, and mitochondrial dysfunction. Up to now, non-drug treatment has been the main way to treat sarcopenia, and there are no drugs specially approved for the treatment of sarcopenia. Here, the pathophysiology and treatment methods of sarcopenia have been summarized, and new drugs for sarcopenia to be researched and developed in the future have been prospected.
{"title":"Sarcopenia: Pathophysiology and Treatment Strategies.","authors":"Chaoming Qiu, Xifei Yang, Pei Yu","doi":"10.2174/1871530323666230518105408","DOIUrl":"10.2174/1871530323666230518105408","url":null,"abstract":"<p><p>Sarcopenia is becoming prevalent in older or inactive patients, which is placing a heavy burden on the social health system. Studies on the pathogenesis of sarcopenia mainly focus on adipose tissue, myoglobin autophagy, and mitochondrial dysfunction. Up to now, non-drug treatment has been the main way to treat sarcopenia, and there are no drugs specially approved for the treatment of sarcopenia. Here, the pathophysiology and treatment methods of sarcopenia have been summarized, and new drugs for sarcopenia to be researched and developed in the future have been prospected.</p>","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"31-38"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9492282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1871530323666230821102718
Teresa V Jacob, Gaurav M Doshi
Peptic ulcers (PU) are one of the commonest yet problematic diseases found to be existing in the majority of the population. Today, drugs from a wide range of therapeutic classes are available for the management of the disease. Still, the complications of the condition are difficult to tackle and the side effect profile is quite a concern. The literature indicates that Toll-like receptors (TLRs) and Semaphorins (SEMAs) have been under study for their various pharmacological actions over the past few decades. Both these signalling pathways are found to regulate immunological and inflammatory responses. Moreover, receptors and signalling molecules from the family of TLRs and SEMAs are found to have bacterial recognition and antibacterial properties which are essential in eradicating Helicobacter pylori (H. pylori), one of the major causative agents of PU. Our understanding of SEMAs, a class of proteins involved in cell signalling, is relatively less developed compared to TLRs, another class of proteins involved in the immune response. SEMAs and TLRs play different roles in biological processes, with SEMAs primarily involved in guiding cell migration and axon guidance during development, while TLRs are responsible for recognizing pathogens and initiating an immune response. Here, in this review, we will discuss in detail the signalling cascade of TLRs and SEMAs and thereby understand its association with PU for future therapeutic targeting. The review also aims at providing an overview of the study that has been into exploring the role of these signalling pathways in the management of PU.
消化性溃疡(PU)是大多数人最常见的疾病之一,但也是最棘手的疾病之一。如今,治疗该疾病的药物种类繁多。然而,该病的并发症仍然难以解决,其副作用也相当令人担忧。文献表明,在过去几十年中,人们一直在研究 Toll 样受体(TLRs)和 Semaphorins(SEMAs)的各种药理作用。研究发现,这两种信号通路都能调节免疫和炎症反应。此外,还发现 TLRs 和 SEMAs 家族的受体和信号分子具有细菌识别和抗菌特性,这对于根除幽门螺杆菌(H. pylori)至关重要,而幽门螺杆菌是 PU 的主要致病菌之一。与参与免疫反应的另一类蛋白质 TLRs 相比,我们对 SEMA(一类参与细胞信号传递的蛋白质)的了解相对较少。SEMAs和TLRs在生物过程中发挥着不同的作用,SEMAs主要参与发育过程中的细胞迁移和轴突导向,而TLRs则负责识别病原体并启动免疫反应。在本综述中,我们将详细讨论 TLRs 和 SEMAs 的信号级联,从而了解其与 PU 的关联,为今后的治疗提供靶点。本综述还旨在概述探索这些信号通路在治疗 PU 中的作用的研究。
{"title":"New Promising Routes in Peptic Ulcers: Toll-like Receptors and Semaphorins.","authors":"Teresa V Jacob, Gaurav M Doshi","doi":"10.2174/1871530323666230821102718","DOIUrl":"10.2174/1871530323666230821102718","url":null,"abstract":"<p><p>Peptic ulcers (PU) are one of the commonest yet problematic diseases found to be existing in the majority of the population. Today, drugs from a wide range of therapeutic classes are available for the management of the disease. Still, the complications of the condition are difficult to tackle and the side effect profile is quite a concern. The literature indicates that Toll-like receptors (TLRs) and Semaphorins (SEMAs) have been under study for their various pharmacological actions over the past few decades. Both these signalling pathways are found to regulate immunological and inflammatory responses. Moreover, receptors and signalling molecules from the family of TLRs and SEMAs are found to have bacterial recognition and antibacterial properties which are essential in eradicating <i>Helicobacter pylori (H. pylori)</i>, one of the major causative agents of PU. Our understanding of SEMAs, a class of proteins involved in cell signalling, is relatively less developed compared to TLRs, another class of proteins involved in the immune response. SEMAs and TLRs play different roles in biological processes, with SEMAs primarily involved in guiding cell migration and axon guidance during development, while TLRs are responsible for recognizing pathogens and initiating an immune response. Here, in this review, we will discuss in detail the signalling cascade of TLRs and SEMAs and thereby understand its association with PU for future therapeutic targeting. The review also aims at providing an overview of the study that has been into exploring the role of these signalling pathways in the management of PU.</p>","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"865-878"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10042081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Systemic Lupus Erythematosus (SLE) or Lupus is a multifactorial autoimmune disease of multiorgan malfunctioning of extremely heterogeneous and unclear etiology that affects multiple organs and physiological systems. Some racial groups and women of childbearing age are more susceptible to SLE pathogenesis. Impressive progress has been made towards a better understanding of different immune components contributing to SLE pathogenesis. Recent investigations have uncovered the detailed mechanisms of inflammatory responses and organ damage. Various environmental factors, pathogens, and toxicants, including ultraviolet light, drugs, viral pathogens, gut microbiome metabolites, and sex hormones trigger the onset of SLE pathogenesis in genetically susceptible individuals and result in the disruption of immune homeostasis of cytokines, macrophages, T cells, and B cells. Diagnosis and clinical investigations of SLE remain challenging due to its clinical heterogeneity and hitherto only a few approved antimalarials, glucocorticoids, immunosuppressants, and some nonsteroidal anti-inflammatory drugs (NSAIDs) are available for treatment. However, the adverse effects of renal and neuropsychiatric lupus and late diagnosis make therapy challenging. Additionally, SLE is also linked to an increased risk of cardiovascular diseases due to inflammatory responses and the risk of infection from immunosuppressive treatment. Due to the diversity of symptoms and treatment-resistant diseases, SLE management remains a challenging issue. Nevertheless, the use of next-generation therapeutics with stem cell and gene therapy may bring better outcomes to SLE treatment in the future. This review highlights the autoimmune responses as well as potential therapeutic interventions for SLE particularly focusing on the recent therapeutic advancements and challenges.
系统性红斑狼疮(SLE)或狼疮是一种影响多个器官和生理系统的多因素自身免疫性疾病,多器官功能失调,病因极为复杂且不明确。一些种族群体和育龄妇女更容易受到系统性红斑狼疮发病机制的影响。在更好地了解导致系统性红斑狼疮发病的不同免疫成分方面,已经取得了令人瞩目的进展。最近的研究发现了炎症反应和器官损伤的详细机制。各种环境因素、病原体和毒物,包括紫外线、药物、病毒病原体、肠道微生物代谢产物和性激素,都会诱发遗传易感人群的系统性红斑狼疮发病,并导致细胞因子、巨噬细胞、T 细胞和 B 细胞的免疫平衡被破坏。由于其临床异质性,系统性红斑狼疮的诊断和临床研究仍具有挑战性,迄今为止,只有少数几种经批准的抗疟药、糖皮质激素、免疫抑制剂和一些非甾体抗炎药(NSAIDs)可用于治疗。然而,肾性狼疮和神经精神性狼疮的不良反应以及诊断较晚使治疗面临挑战。此外,系统性红斑狼疮还与炎症反应导致的心血管疾病风险增加以及免疫抑制治疗带来的感染风险有关。由于系统性红斑狼疮的症状和耐药性多种多样,其治疗仍然是一个具有挑战性的问题。然而,干细胞和基因疗法等新一代疗法的使用可能会为系统性红斑狼疮的治疗带来更好的结果。本综述重点介绍系统性红斑狼疮的自身免疫反应以及潜在的治疗干预措施,尤其关注近期的治疗进展和面临的挑战。
{"title":"Autoimmune Responses and Therapeutic Interventions for Systemic Lupus Erythematosus: A Comprehensive Review.","authors":"Surya Prakash Pandey, Rakesh Bhaskar, Sung Soo Han, Kannan Badri Narayanan","doi":"10.2174/1871530323666230915112642","DOIUrl":"10.2174/1871530323666230915112642","url":null,"abstract":"<p><p>Systemic Lupus Erythematosus (SLE) or Lupus is a multifactorial autoimmune disease of multiorgan malfunctioning of extremely heterogeneous and unclear etiology that affects multiple organs and physiological systems. Some racial groups and women of childbearing age are more susceptible to SLE pathogenesis. Impressive progress has been made towards a better understanding of different immune components contributing to SLE pathogenesis. Recent investigations have uncovered the detailed mechanisms of inflammatory responses and organ damage. Various environmental factors, pathogens, and toxicants, including ultraviolet light, drugs, viral pathogens, gut microbiome metabolites, and sex hormones trigger the onset of SLE pathogenesis in genetically susceptible individuals and result in the disruption of immune homeostasis of cytokines, macrophages, T cells, and B cells. Diagnosis and clinical investigations of SLE remain challenging due to its clinical heterogeneity and hitherto only a few approved antimalarials, glucocorticoids, immunosuppressants, and some nonsteroidal anti-inflammatory drugs (NSAIDs) are available for treatment. However, the adverse effects of renal and neuropsychiatric lupus and late diagnosis make therapy challenging. Additionally, SLE is also linked to an increased risk of cardiovascular diseases due to inflammatory responses and the risk of infection from immunosuppressive treatment. Due to the diversity of symptoms and treatment-resistant diseases, SLE management remains a challenging issue. Nevertheless, the use of next-generation therapeutics with stem cell and gene therapy may bring better outcomes to SLE treatment in the future. This review highlights the autoimmune responses as well as potential therapeutic interventions for SLE particularly focusing on the recent therapeutic advancements and challenges.</p>","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"499-518"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10651965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Selenium, a significant trace element needed by the human body, is closely related to thyroid. Therefore, this study aimed to explore the status of selenium and thyroid diseases, analyze emerging insights, and predict future trends.
Methods: Literature on selenium and thyroid included in the core database of Web of Science from January 1992 to October 2022 was retrieved. CiteSpace and VOSviewer software were used for visual analysis in terms of publication, author, country, institution, co-citation, and keywords.
Results: A total of 1,142 works of literature were included after the screening, and the annual publication showed a fluctuating upward trend. The country and the institution with the highest publication volume were the United States and Charité Universitätsmedizin Berlin, respectively. In terms of authors, Schomburg L has formed a cooperative network and has published the largest number of papers and made great contributions in this field. The biggest cluster of keywords was trace elements, and the hot keywords in recent years were oxidative stress, Hashimoto's thyroiditis, cadmium, copper, etc. Conclusion: This paper analyzes the current status, insights, and trends of the studies on selenium and thyroid diseases by the method of bibliometrics and delivers ideas and methods for subsequent research in this field. The therapeutic effect of selenium on Hashimoto's thyroiditis is controversial and needs further research, and oxidative stress is also a research hotspot in this field. The crossstudy of multiple trace elements and diseases may be the development trend in the future.
{"title":"Emerging Insights and Global Trends in the Relationship between Selenium and Thyroid Diseases: A Bibliometric Analysis.","authors":"Yuqing Wu, Tiantian Cai, Yuan Tao, Jing Zhao, Jinan Zhang","doi":"10.2174/1871530323666230918121353","DOIUrl":"10.2174/1871530323666230918121353","url":null,"abstract":"<p><strong>Objective: </strong>Selenium, a significant trace element needed by the human body, is closely related to thyroid. Therefore, this study aimed to explore the status of selenium and thyroid diseases, analyze emerging insights, and predict future trends.</p><p><strong>Methods: </strong>Literature on selenium and thyroid included in the core database of Web of Science from January 1992 to October 2022 was retrieved. CiteSpace and VOSviewer software were used for visual analysis in terms of publication, author, country, institution, co-citation, and keywords.</p><p><strong>Results: </strong>A total of 1,142 works of literature were included after the screening, and the annual publication showed a fluctuating upward trend. The country and the institution with the highest publication volume were the United States and Charité Universitätsmedizin Berlin, respectively. In terms of authors, Schomburg L has formed a cooperative network and has published the largest number of papers and made great contributions in this field. The biggest cluster of keywords was trace elements, and the hot keywords in recent years were oxidative stress, Hashimoto's thyroiditis, cadmium, copper, etc. Conclusion: This paper analyzes the current status, insights, and trends of the studies on selenium and thyroid diseases by the method of bibliometrics and delivers ideas and methods for subsequent research in this field. The therapeutic effect of selenium on Hashimoto's thyroiditis is controversial and needs further research, and oxidative stress is also a research hotspot in this field. The crossstudy of multiple trace elements and diseases may be the development trend in the future.</p>","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"808-819"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10308966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-19DOI: 10.2174/0118715303279986231211090830
Ana Miguel Capela, Ana Cunha, Ana Maria Fortuna, Cláudia Falcão Reis
Introduction:: Inborn errors of metabolism (IEM) are genetic diseases involving congenital disorders of enzyme activities. Most follow Mendelian autosomal recessive inheritance and few follow mitochondrial inheritance. In many cases, after the birth of an affected child parents discover that have been the carriers for the condition and worry about the risk of recurrence in future offspring. Preimplantation genetic testing (PGT) can analyze embryos before their transfer to the uterus and prevent the transmission of hereditary conditions to descendants, however this procedure is of limited value in mtDNA conditions. Methods:: The list of diseases currently approved for PGT were reviewed. The process for eligibility, was as for the Comissão Nacional Procriação Medicamente Assistida (CNPMA), of Portugal (PT). Review of international practices for Assisted Reproductive Techniques (ART) in IEM was carried out. Results:: As of 07.2022, 23 IEM diseases associated with deleterious variants in nDNA were approved for PGT in PT. Couples at risk for conditions not included in the list can solicit an evaluation from an expert committee, after a medical genetics consultation. To qualify for approval, diseases must cause significant suffering and/or premature death. Due to a greater number of solicitations many more IEM conditions have been approved for PGT across the world. ART for mtDNA is not available in PT. International expert centers include PGT for specific well documented variants and mitochondrial donation. Conclusion:: PGT is a reliable approach to reduce the risk of transmission of a genetic condition to the offspring. The list of IEM disorders currently accepted for this technique in Portugal are small, but it is expanding, as many more diseases fit the necessary criteria. While appealing in theory, low success rates coupled with limited availability can be discouraging for patients. Genetic counselling is of paramount importance after the diagnosis of IEM diseases. It is important for both clinicians and patients to be made aware of the available reproductive options and their limitations.
{"title":"Pre-implantation Genetic Testing in Inherited Metabolic Diseases? Stateof- the-art and current challenges","authors":"Ana Miguel Capela, Ana Cunha, Ana Maria Fortuna, Cláudia Falcão Reis","doi":"10.2174/0118715303279986231211090830","DOIUrl":"https://doi.org/10.2174/0118715303279986231211090830","url":null,"abstract":"Introduction:: Inborn errors of metabolism (IEM) are genetic diseases involving congenital disorders of enzyme activities. Most follow Mendelian autosomal recessive inheritance and few follow mitochondrial inheritance. In many cases, after the birth of an affected child parents discover that have been the carriers for the condition and worry about the risk of recurrence in future offspring. Preimplantation genetic testing (PGT) can analyze embryos before their transfer to the uterus and prevent the transmission of hereditary conditions to descendants, however this procedure is of limited value in mtDNA conditions. Methods:: The list of diseases currently approved for PGT were reviewed. The process for eligibility, was as for the Comissão Nacional Procriação Medicamente Assistida (CNPMA), of Portugal (PT). Review of international practices for Assisted Reproductive Techniques (ART) in IEM was carried out. Results:: As of 07.2022, 23 IEM diseases associated with deleterious variants in nDNA were approved for PGT in PT. Couples at risk for conditions not included in the list can solicit an evaluation from an expert committee, after a medical genetics consultation. To qualify for approval, diseases must cause significant suffering and/or premature death. Due to a greater number of solicitations many more IEM conditions have been approved for PGT across the world. ART for mtDNA is not available in PT. International expert centers include PGT for specific well documented variants and mitochondrial donation. Conclusion:: PGT is a reliable approach to reduce the risk of transmission of a genetic condition to the offspring. The list of IEM disorders currently accepted for this technique in Portugal are small, but it is expanding, as many more diseases fit the necessary criteria. While appealing in theory, low success rates coupled with limited availability can be discouraging for patients. Genetic counselling is of paramount importance after the diagnosis of IEM diseases. It is important for both clinicians and patients to be made aware of the available reproductive options and their limitations.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"26 2 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138821417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction:: Single Nucleotide Polymorphisms (SNPs) are used as drug susceptibility biomarkers in metabolic diseases. Alterations in the gene encoding triggers the enzyme flavin monooxygenase 3 (FMO3), involved in the Sulindac metabolization, which also is responsible for the inherited metabolic disorder. Trimethylaminuria (TMAu, OMIM: 602079). DPYD gene variants are associated with the enzyme dihydropyrimidine dehydrogenase deficiency (DPD; OMIM: 274270). This autosomal recessive metabolic disorder, ultimately leads to the inability to metabolize fluoropyrimidines, which causes severe toxicity in individuals treated with these drugs. Methods:: Variants in genes responsible for the expression of enzymes that encode transporters or receptors involved in the metabolization pathways of certain drugs may condition the individuals response to certain drugs, compromising the therapeutic response and clinical prognosis. Thus the sequencing and identification of variants become relevant, not only gain knowledge on effects of these variants’ on disease causality but also in terms of its side effects resulting from the coding enzymes responsible for drug metabolization. Results:: It was found that patients with the c.472G>A (p.Glu158Lys) and c.923A>G (p.Glu308Gly) polymorphisms, in homozygosity, in FMO3 gene did not develop polyps, thus have a protective effect in the treatment of Familial Adenomatous Polyposis (PAF). However, in the case of the DPYD gene, c.1905+1G>A (IVS14+1G>A), c.1679T>G (p.Ile560Ser), c.2846A>T (p.Asp949Val) e c.1236G>A/HapB3 variants can be lethal in cancer patients indicated for fluoropyrimidine-based chemotherapy. Conclusion:: Knowledge on the drug mechanisms will affect the therapeutic response of patients treated with a given drug. Thus, pharmacogenetics is an essential tool in personalized medicine, since molecular studies allows the clinician to predict the probability of efficacy and toxicity of certain drugs, resulting higher efficiency in individualizing treatment and also improving the safety of the patient. From a personalized medicine perspective, the study of the characteristics of the drug and its metabolization site, the genes involved in the encoding of enzymes responsible for its metabolization will be of great interest.
{"title":"Pharmacogenetic Variants Can Influence Optical Medication Use","authors":"Diana Alves, Filipa Ferreira, Cristina Pereira, Altina Lopes, Célia Nogueira, Laura Vilarinho","doi":"10.2174/0118715303271934231211085226","DOIUrl":"https://doi.org/10.2174/0118715303271934231211085226","url":null,"abstract":"Introduction:: Single Nucleotide Polymorphisms (SNPs) are used as drug susceptibility biomarkers in metabolic diseases. Alterations in the gene encoding triggers the enzyme flavin monooxygenase 3 (FMO3), involved in the Sulindac metabolization, which also is responsible for the inherited metabolic disorder. Trimethylaminuria (TMAu, OMIM: 602079). DPYD gene variants are associated with the enzyme dihydropyrimidine dehydrogenase deficiency (DPD; OMIM: 274270). This autosomal recessive metabolic disorder, ultimately leads to the inability to metabolize fluoropyrimidines, which causes severe toxicity in individuals treated with these drugs. Methods:: Variants in genes responsible for the expression of enzymes that encode transporters or receptors involved in the metabolization pathways of certain drugs may condition the individuals response to certain drugs, compromising the therapeutic response and clinical prognosis. Thus the sequencing and identification of variants become relevant, not only gain knowledge on effects of these variants’ on disease causality but also in terms of its side effects resulting from the coding enzymes responsible for drug metabolization. Results:: It was found that patients with the c.472G>A (p.Glu158Lys) and c.923A>G (p.Glu308Gly) polymorphisms, in homozygosity, in FMO3 gene did not develop polyps, thus have a protective effect in the treatment of Familial Adenomatous Polyposis (PAF). However, in the case of the DPYD gene, c.1905+1G>A (IVS14+1G>A), c.1679T>G (p.Ile560Ser), c.2846A>T (p.Asp949Val) e c.1236G>A/HapB3 variants can be lethal in cancer patients indicated for fluoropyrimidine-based chemotherapy. Conclusion:: Knowledge on the drug mechanisms will affect the therapeutic response of patients treated with a given drug. Thus, pharmacogenetics is an essential tool in personalized medicine, since molecular studies allows the clinician to predict the probability of efficacy and toxicity of certain drugs, resulting higher efficiency in individualizing treatment and also improving the safety of the patient. From a personalized medicine perspective, the study of the characteristics of the drug and its metabolization site, the genes involved in the encoding of enzymes responsible for its metabolization will be of great interest.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"1 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138818290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: There is an ongoing effort to increase rare disease awareness amongst healthcare providers. This front is important and can help to address several challenges faced by rare disease patients, such as lengthy diagnosis times, difficulty in finding adequate providers of medical services and experts, and adequate treatment if one exists. On another front, there is the need for awareness among citizens and their support in the advocacy for public policies towards rare disease patients and families. Awareness campaigns are prevalent in social networks and fundraising events. In this poster, we present a complementary approach to engage society and promote rare disease awareness through children’s literature and music. A Portuguese teenager wrote a book (‘My Life with my sister’), describing simple and daily moments spent with her teenage sister affected by Sanfilippo syndrome. A professional illustrator designed and illustrated the book. The book is bilingual in Portuguese and English. The author, with the assistance of her music teacher, also composed a song which was recorded with the participation of professional musicians and made into a video clip telling their story and the books. The book and song promote the inclusion and love for people affected by rare diseases and their families. To increase outreach, sister organizations translated the book, adapted the song, and published/ recorded the material in Brazilian Portuguese and French. The proceeds from the sales go towards the Sanfilippo foundations in their respective countries to fund common research projects. The material is being advertised on social media, television, interviews, newspapers, podcasts, libraries, schools, bookshops, book fairs, and others. To date, more than eight hundred books have been sold to individuals and companies. The interviews and video clips add to more than twelve hundred views. The target audience is children, parents, teachers but also companies, and their employees.
{"title":"Increasing Sanfilippo Syndrome Awareness through Children's Literature and Music","authors":"Raquel Marques, Rodrigo Carlson, Guilhain Higonnet","doi":"10.2174/0118715303272345231211094632","DOIUrl":"https://doi.org/10.2174/0118715303272345231211094632","url":null,"abstract":": There is an ongoing effort to increase rare disease awareness amongst healthcare providers. This front is important and can help to address several challenges faced by rare disease patients, such as lengthy diagnosis times, difficulty in finding adequate providers of medical services and experts, and adequate treatment if one exists. On another front, there is the need for awareness among citizens and their support in the advocacy for public policies towards rare disease patients and families. Awareness campaigns are prevalent in social networks and fundraising events. In this poster, we present a complementary approach to engage society and promote rare disease awareness through children’s literature and music. A Portuguese teenager wrote a book (‘My Life with my sister’), describing simple and daily moments spent with her teenage sister affected by Sanfilippo syndrome. A professional illustrator designed and illustrated the book. The book is bilingual in Portuguese and English. The author, with the assistance of her music teacher, also composed a song which was recorded with the participation of professional musicians and made into a video clip telling their story and the books. The book and song promote the inclusion and love for people affected by rare diseases and their families. To increase outreach, sister organizations translated the book, adapted the song, and published/ recorded the material in Brazilian Portuguese and French. The proceeds from the sales go towards the Sanfilippo foundations in their respective countries to fund common research projects. The material is being advertised on social media, television, interviews, newspapers, podcasts, libraries, schools, bookshops, book fairs, and others. To date, more than eight hundred books have been sold to individuals and companies. The interviews and video clips add to more than twelve hundred views. The target audience is children, parents, teachers but also companies, and their employees.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"17 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138818295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-19DOI: 10.2174/0118715303273290231211062420
Marta Simões, Maria João Santos, Sara Martins, Maria do Carmo Macário, João Durães, Luísa Diogo, João Paulo Oliveira, José Carlos Ferreira, Manuela Grazina
Introduction:: Mitochondrial oxidative phosphorylation (OXPHOS) diseases are challenging both from clinical and therapeutic perspectives. The advent of next-generation sequencing (NGS) boosted the discovery of new genetic defects affecting OXPHOS, with pathogenic variants identified in >350 genes to date [1]. However, in many patients, novel variants of unknown clinical significance are found. Subsequent functional studies may clarify its pathogenic consequences and modify the variant’s classification, establishing a genetic diagnosis [2, 3]. Methods:: Analysis of data obtained from patients (P1-P5) with novel genetic causes and functional genomics’ studies performed, namely OXPHOS respiratory/glycolytic rates (Seahorse XF), enzymatic activity and assembly (BN-page), protein levels (SDS-WB), single muscle fiber assay, NGS and bioinformatics. Results/Case Report:: P1-Leigh syndrome (40y, male); Complex IV activity deficiency (full assembly absent), homozygous deletion (c.-11_13del, SURF1), not detected by NGS[2]. P2- Epileptic encephalopathy (8y, male); homozygous c.882-1G>A, FASTKD2; OXPHOS decrease; reduced FASTKD2 expression and abnormal respiratory/glycolytic rates. P3-Cardiomyopathy/ nephropathy (39y, male); c.29G>C, FASTKD2; OXPHOS decrease; reduced FASTKD2 levels. P4-CPEO (62y, female); multiple OXPHOS deficiency; mtDNA alterations (m.7486G>A, MTTS1; 4,977bp del); higher levels of mutant mtDNA alterations in COX-deficient fibers [3]. P5- Polyneuropathy (15y, female); heterozygous c.1437C>A, POLG; combined def. or normal OXPHOS activity/respiratory capacity (tissue variable), raised CI assembly; normal POLG levels. Also, proteins’ expression levels were reduced (P1-4), confirming pathogenicity. In P5, data do not support pathogenicity. Conclusion:: If specific functional results are similar to controls, one might inquire about the pathogenicity of the studied variant and more genetic or bioinformatics analyses and family investigations are needed. There are also limitations of NGS in mutation detection that Sanger sequencing can overcome (P1). When performed first, the OXPHOS activity may guide to genetic screening or interpretation, concordant to later assembly results. All cases were solved and data may be crucial for genetic counseling.
{"title":"Challenges in Genetic Diagnosis of Mitochondrial Diseases: What Can Functional Genomics' Studies Do?","authors":"Marta Simões, Maria João Santos, Sara Martins, Maria do Carmo Macário, João Durães, Luísa Diogo, João Paulo Oliveira, José Carlos Ferreira, Manuela Grazina","doi":"10.2174/0118715303273290231211062420","DOIUrl":"https://doi.org/10.2174/0118715303273290231211062420","url":null,"abstract":"Introduction:: Mitochondrial oxidative phosphorylation (OXPHOS) diseases are challenging both from clinical and therapeutic perspectives. The advent of next-generation sequencing (NGS) boosted the discovery of new genetic defects affecting OXPHOS, with pathogenic variants identified in >350 genes to date [1]. However, in many patients, novel variants of unknown clinical significance are found. Subsequent functional studies may clarify its pathogenic consequences and modify the variant’s classification, establishing a genetic diagnosis [2, 3]. Methods:: Analysis of data obtained from patients (P1-P5) with novel genetic causes and functional genomics’ studies performed, namely OXPHOS respiratory/glycolytic rates (Seahorse XF), enzymatic activity and assembly (BN-page), protein levels (SDS-WB), single muscle fiber assay, NGS and bioinformatics. Results/Case Report:: P1-Leigh syndrome (40y, male); Complex IV activity deficiency (full assembly absent), homozygous deletion (c.-11_13del, SURF1), not detected by NGS[2]. P2- Epileptic encephalopathy (8y, male); homozygous c.882-1G>A, FASTKD2; OXPHOS decrease; reduced FASTKD2 expression and abnormal respiratory/glycolytic rates. P3-Cardiomyopathy/ nephropathy (39y, male); c.29G>C, FASTKD2; OXPHOS decrease; reduced FASTKD2 levels. P4-CPEO (62y, female); multiple OXPHOS deficiency; mtDNA alterations (m.7486G>A, MTTS1; 4,977bp del); higher levels of mutant mtDNA alterations in COX-deficient fibers [3]. P5- Polyneuropathy (15y, female); heterozygous c.1437C>A, POLG; combined def. or normal OXPHOS activity/respiratory capacity (tissue variable), raised CI assembly; normal POLG levels. Also, proteins’ expression levels were reduced (P1-4), confirming pathogenicity. In P5, data do not support pathogenicity. Conclusion:: If specific functional results are similar to controls, one might inquire about the pathogenicity of the studied variant and more genetic or bioinformatics analyses and family investigations are needed. There are also limitations of NGS in mutation detection that Sanger sequencing can overcome (P1). When performed first, the OXPHOS activity may guide to genetic screening or interpretation, concordant to later assembly results. All cases were solved and data may be crucial for genetic counseling.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"35 9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138818386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-15DOI: 10.2174/0118715303260423231122111705
Fabio Vescini, Giorgio Borretta, Iacopo Chiodini, Marco Boniardi, Marina Carotti, Elena Castellano, Cristiana Cipriani, Cristina Eller-Vainicher, Sandro Giannini, Maurizio Iacobone, Antonio Stefano Salcuni, Federica Saponaro, Stefano Spiezia, Annibale Versari, Guido Zavatta, Zuzana Mitrova, Rosella Saulle, Simona Vecchi, Debora Antonini, Michele Basile, Alexia Giovanazzi, Agostino Paoletta, Enrico Papini, Agnese Persichetti, Irene Samperi, Alessandro Scoppola, Roberto Novizio, Giorgio Calò, Filomena Cetani, Luisella Cianferotti, Sabrina Corbetta, Maria Luisa De Rimini, Alberto Falchetti, Giovanni Iannetti, Stefano Laureti, Celestino Pio Lombardi, Bruno Madeo, Claudio Marcocci, Sandro Mazzaferro, Vittorio Miele, Salvatore Minisola, Andrea Palermo, Jessica Pepe, Alfredo Scillitani, Laura Tonzar, Franco Grimaldi, Renato Cozzi, Roberto Attanasio
Aim:: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. Methods:: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell’Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as “critical” and “important” were considered in the systematic review of evidence. Those classified as “critical” were considered for the clinical practice recommendations. Results:: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations. Conclusion:: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient’s preferences and the available resources and.
{"title":"Italian Guidelines for the Management of Sporadic Primary Hyperparathyroidism","authors":"Fabio Vescini, Giorgio Borretta, Iacopo Chiodini, Marco Boniardi, Marina Carotti, Elena Castellano, Cristiana Cipriani, Cristina Eller-Vainicher, Sandro Giannini, Maurizio Iacobone, Antonio Stefano Salcuni, Federica Saponaro, Stefano Spiezia, Annibale Versari, Guido Zavatta, Zuzana Mitrova, Rosella Saulle, Simona Vecchi, Debora Antonini, Michele Basile, Alexia Giovanazzi, Agostino Paoletta, Enrico Papini, Agnese Persichetti, Irene Samperi, Alessandro Scoppola, Roberto Novizio, Giorgio Calò, Filomena Cetani, Luisella Cianferotti, Sabrina Corbetta, Maria Luisa De Rimini, Alberto Falchetti, Giovanni Iannetti, Stefano Laureti, Celestino Pio Lombardi, Bruno Madeo, Claudio Marcocci, Sandro Mazzaferro, Vittorio Miele, Salvatore Minisola, Andrea Palermo, Jessica Pepe, Alfredo Scillitani, Laura Tonzar, Franco Grimaldi, Renato Cozzi, Roberto Attanasio","doi":"10.2174/0118715303260423231122111705","DOIUrl":"https://doi.org/10.2174/0118715303260423231122111705","url":null,"abstract":"Aim:: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. Methods:: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell’Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as “critical” and “important” were considered in the systematic review of evidence. Those classified as “critical” were considered for the clinical practice recommendations. Results:: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations. Conclusion:: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient’s preferences and the available resources and.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"23 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138680260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-14DOI: 10.2174/0118715303279681231122104925
Helena Santos, Ana Vieira, Joana Tenente, Ana Carriço, Esmeralda Rodrigues
Introduction:: Long-chain fatty acid oxidation disorders (LC-FAOD) are inborn errors of metabolism, also identified in newborn screening in Portugal. They interfere with adequate energy utilization, namely by muscles, heart, and liver. Treatment aims to maintain patients in an anabolic state, with increased caloric intake, using carbohydrates and medium-chain fatty acids. Treatment with triheptanoin (THP), a synthetic seven-carbon fatty acid triglyceride compound with an anaplerotic effect that increases energy availability to the cell, has been advocated as an efficacious and safe therapy in LC-FAOD. Methods:: Retrospective revision of clinical records of 2 LC-FAOD patients comparing number, severity and admissions for rhabdomyolysis crises, maximum CK values and weight gain in a period of 18 months before and after treatment with THP. Results/Case Report:: Patient 1 is a 12 year old male with VLCADD, with main manifestation being rhabdomyolysis crises. After he started THP we found a decrease in admissions (6 to 2), less rhabdomyolysis crises treated at home (5 to 3), and lower maximum CK values (72352 U/L to 13.000U/L). He had a large increase in weight - 13kg in 18 months. He was able to start pool exercises with no rhabdomyolysis associated. Patient 2 is an 8 year old male with LCAHDD, with main manifestations being rhabdomyolysis crises and retinopathy. After he started THP we found a decrease in admissions (4 to 1), no rhabdomyolysis crises treated at home, and lower maximum CK values (100.000U/L to 19848 U/L). He also increased his weight - 7kg in 18 months. He plays football in school and swims with no rhabdomyolysis associated. In both patients, no major side effects were observed. Conclusion:: In our patients, we could observe a reduction in the number of admissions, and less severe rhabdomyolysis crises after THP use. The weight gain was significant. There were no major side effects. Despite regarding only two patients, our findings are in line with the latest literature on THP and LC-FAOD, reinforcing the utility of THP as one more tool in the treatment of these disorders with rhabdomyolysis as the main manifestation. The weight increase is an issue to be aware of and to address from the start of the treatment.
{"title":"18 Months of Treatment with Triheptanoin in 2 Patients with Long Chain Fatty Acid Oxidation Disorders","authors":"Helena Santos, Ana Vieira, Joana Tenente, Ana Carriço, Esmeralda Rodrigues","doi":"10.2174/0118715303279681231122104925","DOIUrl":"https://doi.org/10.2174/0118715303279681231122104925","url":null,"abstract":"Introduction:: Long-chain fatty acid oxidation disorders (LC-FAOD) are inborn errors of metabolism, also identified in newborn screening in Portugal. They interfere with adequate energy utilization, namely by muscles, heart, and liver. Treatment aims to maintain patients in an anabolic state, with increased caloric intake, using carbohydrates and medium-chain fatty acids. Treatment with triheptanoin (THP), a synthetic seven-carbon fatty acid triglyceride compound with an anaplerotic effect that increases energy availability to the cell, has been advocated as an efficacious and safe therapy in LC-FAOD. Methods:: Retrospective revision of clinical records of 2 LC-FAOD patients comparing number, severity and admissions for rhabdomyolysis crises, maximum CK values and weight gain in a period of 18 months before and after treatment with THP. Results/Case Report:: Patient 1 is a 12 year old male with VLCADD, with main manifestation being rhabdomyolysis crises. After he started THP we found a decrease in admissions (6 to 2), less rhabdomyolysis crises treated at home (5 to 3), and lower maximum CK values (72352 U/L to 13.000U/L). He had a large increase in weight - 13kg in 18 months. He was able to start pool exercises with no rhabdomyolysis associated. Patient 2 is an 8 year old male with LCAHDD, with main manifestations being rhabdomyolysis crises and retinopathy. After he started THP we found a decrease in admissions (4 to 1), no rhabdomyolysis crises treated at home, and lower maximum CK values (100.000U/L to 19848 U/L). He also increased his weight - 7kg in 18 months. He plays football in school and swims with no rhabdomyolysis associated. In both patients, no major side effects were observed. Conclusion:: In our patients, we could observe a reduction in the number of admissions, and less severe rhabdomyolysis crises after THP use. The weight gain was significant. There were no major side effects. Despite regarding only two patients, our findings are in line with the latest literature on THP and LC-FAOD, reinforcing the utility of THP as one more tool in the treatment of these disorders with rhabdomyolysis as the main manifestation. The weight increase is an issue to be aware of and to address from the start of the treatment.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"26 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138689807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}