Journal of Biosciences最新文献

{"title":"Are all VapC toxins of Mycobacterium tuberculosis endowed with enigmatic RNase activity?","authors":"Sheeba Zarin, Anwar Alam, Seyed Ehtesham Hasnain, Nasreen Zafar Ehtesham","doi":"10.1007/s12038-024-00420-3","DOIUrl":"https://doi.org/10.1007/s12038-024-00420-3","url":null,"abstract":"<p><i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) employs an extensive network of more than 90 toxin–antitoxin systems, and among them, VapC toxins are the most abundant. While most VapCs function as classical RNases with toxic effects, a significant number of them do not exhibit toxicity. However, these non-toxic VapCs may retain specific RNA binding abilities as seen in case of VapC16, leading to ribosome stalling at specific codons and reprofiling <i>M. tb</i>'s proteome to aid in the bacterium's survival under different stressful conditions within the host. Here, we challenge the conventional classification of all VapC toxins as RNases and highlight the complexity of <i>M. tb</i>'s strategies for survival and adaptation during infection.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"6 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orphan drug development: Challenges, regulation, and success stories","authors":"Narendra Chirmule, Huije Feng, Esha Cyril, Vihang Vivek Ghalsasi, Mohua Chakraborty Choudhury","doi":"10.1007/s12038-024-00425-y","DOIUrl":"https://doi.org/10.1007/s12038-024-00425-y","url":null,"abstract":"<p>Rare diseases, also known as orphan diseases, are diseases with low occurrence in the population. Developing orphan drugs is challenging because of inadequate financial and scientific resources and insufficient subjects to run clinical trials. With advances in genome sequencing technologies, emergence of cell and gene therapies, and the latest developments in regulatory pathways, some orphan drugs that have curative potential have been approved. In India, due to its large population and resource crunch, developing orphan drugs is phenomenally challenging. After adopting the Orphan Drug Act, the US-FDA has continuously made advances in regulatory pathways for orphan drugs. Particularly, n-of-one clinical trials have been successful in some cases. India has recently adopted policies that have impacted the long-neglected rare-disease ecosystem; however, there is no clear regulatory path for orphan drug development in India. We have proposed a multi-pronged approach involving close collaboration between the government, regulatory bodies, industries, and patient advocacy groups to boost orphan drug development in India. We believe that rapidly evolving technologies and business models can enable better and faster development of novel orphan drugs in India and other resource-constrained countries.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"35 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare genetic diseases in India: Steps toward a nationwide mission program","authors":"Anjana Kar, P Sundaravadivel, Ashwin Dalal","doi":"10.1007/s12038-024-00430-1","DOIUrl":"https://doi.org/10.1007/s12038-024-00430-1","url":null,"abstract":"<p>Rare genetic diseases are rare by themselves with prevalence of 1 in 25,000, but collectively they are a significant cause of morbidity and mortality. Till date, collectively there are more than 9,000 rare diseases documented, which impose a devastating impact on patients, their families, and the healthcare system, including enormous societal burden. Obtaining a conclusive diagnosis for a patient with a rare genetic disease can be long and gruelling. For some patients it takes months or years to receive a definite diagnosis, and around 50% of the patients remain undiagnosed even with expert clinical and advanced high-end laboratory investigations. Owing to the large population and practice of consanguinity the Indian population is a pool of indigenous variants and unreported phenotypes or diseases. A mission program on pediatric rare diseases is an unparalleled initiative to study unique clinical conditions via the use of latest state-of-art technologies and with the combination of a mulit-omics approach. Our initiative will not only provide diagnosis to patients with rare disease but also build a platform for translational research for rare disease screening, management, and treatment.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"31 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the mitochondria without a code: mechanistic insights into mitochondrial DNA depletion syndromes","authors":"Ritoprova Sen, Cuckoo Teresa Jetto, Ravi Manjithaya","doi":"10.1007/s12038-024-00428-9","DOIUrl":"https://doi.org/10.1007/s12038-024-00428-9","url":null,"abstract":"<p>Mitochondrial DNA depletion syndromes (MDS) encompass a wide spectrum of rare genetic disorders caused by severe reduction in mitochondrial DNA (mtDNA), and exhibit heterogenous phenotypes classified as myopathic, encephalomyopathic, hepatocerebral, and neurogastrointestinal. Prognosis for such a spectrum of diseases is poor and is majorly dependent on symptomatic treatment and nutritional supplementation. Understanding the mechanistic aspect of mtDNA depletion can help bring forth a new era of medicine, moving beyond symptomatic treatment and focusing more on organelle-targeted therapies. In this review, we highlight some of the proposed mechanistic bases of mtDNA depletion and the latest therapeutic measures used to treat MDS.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"238 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-viral delivery of nucleic acid for treatment of rare diseases of the muscle","authors":"Divya Rao, Munia Ganguli","doi":"10.1007/s12038-023-00411-w","DOIUrl":"https://doi.org/10.1007/s12038-023-00411-w","url":null,"abstract":"<p>Rare muscular disorders (RMDs) are disorders that affect a small percentage of the population. The disorders which are attributed to genetic mutations often manifest in the form of progressive weakness and atrophy of skeletal and heart muscles. RMDs includes disorders such as Duchenne muscular dystrophy (DMD), GNE myopathy, spinal muscular atrophy (SMA), limb girdle muscular dystrophy, and so on. Due to the infrequent occurrence of these disorders, development of therapeutic approaches elicits less attention compared with other more prevalent diseases. However, in recent times, improved understanding of pathogenesis has led to greater advances in developing therapeutic options to treat such diseases. Exon skipping, gene augmentation, and gene editing have taken the spotlight in drug development for rare neuromuscular disorders. The recent innovation in targeting and repairing mutations with the advent of CRISPR technology has in fact opened new possibilities in the development of gene therapy approaches for these disorders. Although these treatments show satisfactory therapeutic effects, the susceptibility to degradation, instability, and toxicity limits their application. So, an appropriate delivery vector is required for the delivery of these cargoes. Viral vectors are considered potential delivery systems for gene therapy; however, the associated concurrent immunogenic response and other limitations have paved the way for the applications of other non-viral systems like lipids, polymers, cell-penetrating peptides (CPPs), and other organic and inorganic materials. This review will focus on non-viral vectors for the delivery of therapeutic cargoes in order to treat muscular dystrophies.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"4 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139756880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges and opportunities for discovering the biology of rare genetic diseases of the brain","authors":"Padinjat Raghu, Yojet Sharma, Aswathy Bhuvanendran Nair Suseela Devi, Harini Krishnan","doi":"10.1007/s12038-023-00408-5","DOIUrl":"https://doi.org/10.1007/s12038-023-00408-5","url":null,"abstract":"<p>Diseases of the human nervous system are an important cause of morbidity and mortality worldwide. These disorders arise out of multiple aetiologies of which rare genetic mutations in genes vital to nervous system development and function are an important cause. The diagnosis of such rare disorders is challenging due to the close overlap of clinical presentations with other diseases that are not of genetic origin. Further, understanding the mechanisms by which mutations lead to altered brain structure and function is also challenging, given that the brain is not readily accessible for tissue biopsy. However, recent developments in modern technologies have opened up new opportunities for the analysis of rare genetic disorders of the brain. In this review, we discuss these developments and strategies by which they can be applied effectively for better understanding of rare diseases of the brain. This will lead to the development of new clinical strategies to manage brain disorders.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"203 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139756930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of quinoa (Chenopodium quinoa Willd.) germplasms under high-SAR saline water on the basis of growth, yield, and multivariate analysis","authors":"","doi":"10.1007/s12038-023-00396-6","DOIUrl":"https://doi.org/10.1007/s12038-023-00396-6","url":null,"abstract":"<h3>Abstract</h3> <p>Increasing soil and underground water salinization with decreasing availability of fresh water has become a potential threat to sustainable crop production in arid and semi-arid areas globally. Introduction and evaluation of salt-tolerant halophytic crops is one of the sustainable ways to preserve productivity in saline ecosystems. This study was aimed to screen quinoa germplasms under high-sodium adsorption ratio (SAR) saline stress. Thirteen quinoa germplasms were evaluated under four levels [best available water (BAW), 8, 16, and 24 dSm⁻¹] of high-SAR saline water irrigation. The evaluation was carried out based on growth, yield, and ionic content parameters along with statistical tools such as multivariate analysis, salt tolerance indices, and correlation. The results showed that the salinity levels of 16 and 24 dSm⁻¹ resulted in increase of chlorophyll content relative to BAW and 8 dSm⁻¹. The germplasm CSQ2 recorded the highest proline content (163.7 mg g⁻¹ FW) at 24 dSm⁻¹. Increasing levels of salinity reduced relative water content in plant leaves, and the germplasm CSQ2 showed minimal reduction of 4% at 24 dSm⁻¹. Na⁺ and K⁺ contents in the plants increased with increasing salinity levels, while the K⁺/Na⁺ ratio decreased. The grain yield of quinoa germplasms ranged between 3.5 and 14.1 g plant⁻¹. The germplasm EC507740 recorded the highest grain yield (7.0 g plant⁻¹) followed by CSQ1 and CSQ2 at a maximum stress of 24 dSm⁻¹. Principal component analysis (PCA) and correlation elucidated that Na⁺ content in plants was negatively correlated with all the studied traits except SPAD, proline content, and K⁺ content. The different salt tolerance indices indicated that the germplasms EC507740, CSQ1, CSQ2, EC507738, and IC411825 were more stable at high-SAR salinity, while PCA showed the germplasms EC507740 and CSQ2 as the most salt-tolerant germplasms.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"1 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139518284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lafora progressive myoclonus epilepsy: Disease mechanism and therapeutic attempts","authors":"Rashmi Parihar, Subramaniam Ganesh","doi":"10.1007/s12038-023-00407-6","DOIUrl":"https://doi.org/10.1007/s12038-023-00407-6","url":null,"abstract":"<p>Lafora disease (LD) is a life-threatening autosomal recessive and progressive neurodegenerative disorder that primarily affects adolescents, resulting in mortality within a decade of onset. The symptoms of LD include epileptic seizures, ataxia, dementia, and psychosis. The underlying pathology involves the presence of abnormal glycogen inclusions in neurons and other tissues, which may contribute to neurodegeneration. LD is caused by loss-of-function mutations in either the <i>EPM2A</i> gene or the <i>NHLRC1</i> gene. These two genes, respectively, code for laforin phosphatase and malin ubiquitin ligase, and are thought to function, as a functional complex, in diverse cellular pathways. One of the major pathways affected in LD is glycogen metabolism; defects here lead to abnormally higher levels of glycogen and its hyperphosphorylation and aggregation, resulting in the formation of Lafora inclusion bodies. Currently, there is no effective therapy for LD. Studies, particularly from animal models, provide distinct insights into the fundamental mechanisms of diseases and potential avenues for therapeutic interventions. The purpose of this review is to present a comprehensive overview of our current knowledge regarding the disease, its genetics, the animal models that have been developed, and the therapeutic strategies that are being developed based on an understanding of the disease mechanism.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"5 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139509635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor immune microenvironment-based clusters in predicting prognosis and guiding immunotherapy in breast cancer","authors":"","doi":"10.1007/s12038-023-00386-8","DOIUrl":"https://doi.org/10.1007/s12038-023-00386-8","url":null,"abstract":"<h3>Abstract</h3> <p>The development and progression of breast cancer (BC) depend heavily on the tumor microenvironment (TME), especially tumor infiltration leukocytes (TILs). TME-based classifications in BC remain largely unknown and need to be clarified. Using the bioinformatic analysis, we attempted to construct a prognostic nomogram based on clinical features and TME-related differentially expressed genes (DEGs). We also tried to investigate the association between the prognostic nomogram and clinical characteristics, TILs, possible signaling pathways, and response to immunotherapy in BC patients. DEGs for BC patients were identified from The Cancer Genome Atlas Breast Invasive Carcinoma database. TME-related genes were downloaded from the Immunology Database and Analysis Portal. After intersecting DEGs and TME-related genes, 3985 overlapping TME-related DEGs were selected for non-negative matrix factorization clustering, microenvironment cell populations-counter (MCP-counter), LASSO Cox regression, tumor immune dysfunction, and exclusion (TIDE) algorithm analyses. BC patients were divided into three clusters based on the TME-related DEGs and survival data, in which cluster 3 had the best overall survival (OS). Of note, cluster 3 exhibited the highest infiltration or lowest infiltration of CD³⁺ T-cells, CD⁸⁺ T-cells, cytotoxic lymphocytes, B-lymphocytes, monocytic lineage, and myeloid dendritic cells (MDCs). A total of 33 TME-related DEGs were identified as a prognostic gene signature by the LASSO regression analysis. The prognostic gene signature separated BC patients into low- and high-risk groups with significant differences in OS (<em>p</em>&lt;0.01) and demonstrated powerful effectiveness (TCGA all group: 1-year area under the curve [AUC] = 0.773, 3-year AUC = 0.770, 5-year AUC = 0.792). By integrating demographic features, tumor-node metastasis (TNM) stages, and prognostic gene signature, we constructed a nomogram with better predictive value than other clinical features alone. TME-related DEGs in the low-risk BC patients (with better OS) were enriched in chemokine, cytokine–cytokine receptor interaction, and JAK-STAT and Toll-like receptor signaling pathways. BC patients in the low-risk group exhibited higher TIDE scores associated with worse immune checkpoint blockade response. A prognostic nomogram based on TME-related DEGs and clinical characteristics could predict prognosis and guide immunotherapy in BC patients.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"168 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139509779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation and characterization of retinal pigment epithelium from patient iPSC line to model oculocutaneous albinism (OCA)1A disease","authors":"Janavi Subramani, Niharika Patlolla, Rajani Battu, Taslimarif Saiyed, Rajarshi Pal","doi":"10.1007/s12038-023-00406-7","DOIUrl":"https://doi.org/10.1007/s12038-023-00406-7","url":null,"abstract":"<p>Oculocutaneous albinism (OCA) is characterized by reduced melanin biosynthesis affecting the retina, thus impairing visual function. The disease pathology of OCA is poorly understood at the cellular level due to unavailability of suitable biological model systems. This study aimed to develop a disease-specific <i>in vitro</i> model for OCA type 1A, the most severe form caused by <i>TYR</i> (tyrosinase) gene mutations, using retinal pigment epithelium (RPE) differentiated from patient-derived human-induced pluripotent stem cells (hiPSCs). A comparative study between healthy and OCA1A RPE cells revealed that while healthy RPE cells exhibited timely onest of pigmentation during differentiation, OCA1A RPE cells failed to pigment even after an extended culture period. This observation was validated by ultrastructural studies using electron microscopy, hinting at melanosome-specific defects. Immunocytochemistry demonstrated abnormal expression patterns of melanogenesis-specific protein markers in OCA1A RPE cells, indicating reduced or absence of melanin synthesis. Next, a quantitative assay was performed to confirm the absence of melanin production in OCA1A RPE cells. Tyrosinase assay showed no activity in OCA1A compared with healthy RPE, suggesting non-functionality of <i>TYR</i>, further corroborated by western blot analysis showing complete absence of the protein. Gene expression by RNA sequencing of healthy and OCA1A RPE cells uncovered differential gene expression associated with lens development, visual perception, transmembrane transporter activity, and key signaling pathways. This disease-in-a-dish model of OCA1A provides an excellent platform to understand disease mechanism, identify potential therapeutic targets, and facilitate gene therapy or gene correction.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"12 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139509624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}