scholarly journals Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Bartter and Gitelman Syndromes: A Primer for Clinicians

2021 ◽  
Vol 22 (21) ◽  
pp. 11414
Author(s):  
Laura Nuñez-Gonzalez ◽  
Noa Carrera ◽  
Miguel A. Garcia-Gonzalez
Keyword(s):  
Molecular Basis ◽  
Clinical Symptoms ◽  
Bartter Syndrome ◽  
Transport Proteins ◽  
Therapeutic Approaches ◽  
Salt Wasting ◽  
Molecular Etiology ◽  
Inflammatory Drugs ◽  
Main Basis

Gitelman and Bartter syndromes are rare inherited diseases that belong to the category of renal tubulopathies. The genes associated with these pathologies encode electrolyte transport proteins located in the nephron, particularly in the Distal Convoluted Tubule and Ascending Loop of Henle. Therefore, both syndromes are characterized by alterations in the secretion and reabsorption processes that occur in these regions. Patients suffer from deficiencies in the concentration of electrolytes in the blood and urine, which leads to different systemic consequences related to these salt-wasting processes. The main clinical features of both syndromes are hypokalemia, hypochloremia, metabolic alkalosis, hyperreninemia and hyperaldosteronism. Despite having a different molecular etiology, Gitelman and Bartter syndromes share a relevant number of clinical symptoms, and they have similar therapeutic approaches. The main basis of their treatment consists of electrolytes supplements accompanied by dietary changes. Specifically for Bartter syndrome, the use of non-steroidal anti-inflammatory drugs is also strongly supported. This review aims to address the latest diagnostic challenges and therapeutic approaches, as well as relevant recent research on the biology of the proteins involved in disease. Finally, we highlight several objectives to continue advancing in the characterization of both etiologies.

scholarly journals Lysosomal Storage Disorders: Molecular Basis and Therapeutic Approaches

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 964
Author(s):  
Enrico Moro
Keyword(s):  
Intellectual Disabilities ◽  
Molecular Basis ◽  
Clinical Symptoms ◽  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Therapeutic Approaches ◽  
Progressive Muscle Weakness ◽  
Corneal Clouding ◽  
Storage Disorders ◽  
Bone Deformities

Lysosomal storage disorders (LSDs) are a group of 60 rare inherited diseases characterized by a heterogeneous spectrum of clinical symptoms, ranging from severe intellectual disabilities, cardiac abnormalities, visceromegaly, and bone deformities to slowly progressive muscle weakness, respiratory insufficiency, eye defects (corneal clouding and retinal degeneration), and skin alterations [...]

scholarly journals Structural Characterization of SARS-CoV-2: Where We Are, and Where We Need to Be

2020 ◽  
Vol 7 ◽  
Author(s):  
Giuseppina Mariano ◽  
Rebecca J. Farthing ◽  
Shamar L. M. Lale-Farjat ◽  
Julien R. C. Bergeron
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Structural Characterization ◽  
Molecular Basis ◽  
Structural Studies ◽  
Rapid Progress ◽  
Full Understanding ◽  
Therapeutic Approaches ◽  
Vaccination Strategies

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread in humans in almost every country, causing the disease COVID-19. Since the start of the COVID-19 pandemic, research efforts have been strongly directed towards obtaining a full understanding of the biology of the viral infection, in order to develop a vaccine and therapeutic approaches. In particular, structural studies have allowed to comprehend the molecular basis underlying the role of many of the SARS-CoV-2 proteins, and to make rapid progress towards treatment and preventive therapeutics. Despite the great advances that have been provided by these studies, many knowledge gaps on the biology and molecular basis of SARS-CoV-2 infection still remain. Filling these gaps will be the key to tackle this pandemic, through development of effective treatments and specific vaccination strategies.

scholarly journals Two centuries of meningococcal infection: from Vieusseux to the cellular and molecular basis of disease

2008 ◽  
Vol 57 (11) ◽  
pp. 1313-1321 ◽  
Author(s):  
Alexandre Leite de Souza ◽  
Antonio Carlos Seguro
Keyword(s):  
Molecular Basis ◽  
Diagnostic Procedures ◽  
Meningococcal Infection ◽  
Recent Developments ◽  
History Of ◽  
Inflammatory Drugs ◽  
Therapeutic Tools ◽  
Inflammatory Molecules ◽  
Made In

Scientific knowledge of meningococcal infection has increased greatly since the epidemic nature of the illness was first described by Vieusseux at the dawn of the nineteenth century. In fact, revolutionary advances have been made in public-health measures, antimicrobial therapy, diagnostic procedures, anti-inflammatory drugs and supportive care facilities. Based on the knowledge accumulated to date, it is generally accepted that the pathogenesis of meningococcal infection involves multiple links that interconnect in a complex web of phenomena from Neisseria meningitidis attachment to meningococcal sepsis or meningitis. In fact, a myriad of strongly interacting inflammatory molecules and cells have been implicated in neisserial infection, illustrating the complexity of meningococcal pathogenesis. In addition, many of these signallers are critically involved in outcomes in the human host. Deciphering the pathogenesis of meningococcal infection could expand our knowledge and provide important clues to the host–pathogen interaction, as well as leading to the development of new therapeutic tools. Herein, we review the history of the discovery and characterization of meningococcal disease, epidemiological features of the disease with an emphasis on recent developments in Brazil, the cellular and molecular basis of disease, and discuss diagnosis and therapy.

Molecular basis of therapeutic approaches to gastric cancer

2009 ◽  
Vol 24 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Kaichun Wu ◽  
Yongzhan Nie ◽  
Changcun Guo ◽  
Yu Chen ◽  
Jie Ding ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Basis ◽  
Therapeutic Approaches

scholarly journals Molecular characterization of Polychromophilus parasites of Scotophilus kuhlii bats in Thailand

Parasitology ◽  
2020 ◽  
pp. 1-5
Author(s):  
Chatree Chumnandee ◽  
Nawarat Pha-obnga ◽  
Oskar Werb ◽  
Kai Matuschewski ◽  
Juliane Schaer
Keyword(s):  
Blood Cells ◽  
Clinical Symptoms ◽  
Temperate Climate ◽  
Diverse Group ◽  
Malaria Parasites ◽  
Climate Zones ◽  
Haemosporidian Parasites ◽  
South And Southeast Asia ◽  
Molecular Investigation

Abstract Parasites of the haemosporidian genus Polychromophilus have exclusively been described in bats. These parasites belong to the diverse group of malaria parasites, and Polychromophilus presents the only haemosporidian taxon that infects mammalian hosts in tropical as well as in temperate climate zones. This study provides the first information of Polychromophilus parasites in the lesser Asiatic yellow bat (Scotophilus kuhlii) in Thailand, a common vespertilionid bat species distributed in South and Southeast Asia. The gametocyte blood stages of the parasites could not be assigned to a described morphospecies and molecular analysis revealed that these parasites might represent a distinct Polychromophilus species. In contrast to Plasmodium species, Polychromophilus parasites do not multiply in red blood cells and, thus, do not cause the clinical symptoms of malaria. Parasitological and molecular investigation of haemosporidian parasites of wildlife, such as the neglected genus Polychromophilus, will contribute to a better understanding of the evolution of malaria parasites.

Characterization of class II fumarase from Schistosoma mansoni provides the molecular basis for selective inhibition

2021 ◽  
Vol 175 ◽  
pp. 406-421
Author(s):  
Iara Aimê Cardoso ◽  
Aline Kusumota Luiz de Souza ◽  
Adam Muslem George Burgess ◽  
Iain Wyllie Chalmers ◽  
Karl Francis Hoffmann ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Molecular Basis ◽  
Selective Inhibition ◽  
Class Ii

scholarly journals Practical classification of triple-negative breast cancer: intratumoral heterogeneity, mechanisms of drug resistance, and novel therapies

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Antonio Marra ◽  
Dario Trapani ◽  
Giulia Viale ◽  
Carmen Criscitiello ◽  
Giuseppe Curigliano
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Residual Disease ◽  
Therapeutic Approaches ◽  
Minimal Residual Disease Monitoring ◽  
Anticancer Treatment ◽  
Immune Contexture

Abstract Triple-negative breast cancer (TNBC) is not a unique disease, encompassing multiple entities with marked histopathological, transcriptomic and genomic heterogeneity. Despite several efforts, transcriptomic and genomic classifications have remained merely theoretic and most of the patients are being treated with chemotherapy. Driver alterations in potentially targetable genes, including PIK3CA and AKT, have been identified across TNBC subtypes, prompting the implementation of biomarker-driven therapeutic approaches. However, biomarker-based treatments as well as immune checkpoint inhibitor-based immunotherapy have provided contrasting and limited results so far. Accordingly, a better characterization of the genomic and immune contexture underpinning TNBC, as well as the translation of the lessons learnt in the metastatic disease to the early setting would improve patients’ outcomes. The application of multi-omics technologies, biocomputational algorithms, assays for minimal residual disease monitoring and novel clinical trial designs are strongly warranted to pave the way toward personalized anticancer treatment for patients with TNBC.

scholarly journals Lipid Related Genes Altered in NASH Connect Inflammation in Liver Pathogenesis Progression to HCC: A Canonical Pathway

2019 ◽  
Vol 20 (22) ◽  
pp. 5594 ◽  
Author(s):  
Desterke ◽  
Chiappini
Keyword(s):  
Molecular Basis ◽  
Public Health Problem ◽  
Gene Expression Omnibus ◽  
Canonical Pathway ◽  
Therapeutic Approaches ◽  
Database Querying ◽  
New Therapeutic Approaches ◽  
Data Mining Approach ◽  
Pubmed Database ◽  
Genome Alteration

Nonalcoholic steatohepatitis (NASH) is becoming a public health problem worldwide. While the number of research studies on NASH progression rises every year, sometime their findings are controversial. To identify the most important and commonly described findings related to NASH progression, we used an original bioinformatics, integrative, text-mining approach that combines PubMed database querying and available gene expression omnibus dataset. We have identified a signature of 25 genes that are commonly found to be dysregulated during steatosis progression to NASH and cancer. These genes are implicated in lipid metabolism, insulin resistance, inflammation, and cancer. They are functionally connected, forming the basis necessary for steatosis progression to NASH and further progression to hepatocellular carcinoma (HCC). We also show that five of the identified genes have genome alterations present in HCC patients. The patients with these genes associated to genome alteration are associated with a poor prognosis. In conclusion, using an integrative literature- and data-mining approach, we have identified and described a canonical pathway underlying progression of NASH. Other parameters (e.g. polymorphisms) can be added to this pathway that also contribute to the progression of the disease to cancer. This work improved our understanding of the molecular basis of NASH progression and will help to develop new therapeutic approaches.

scholarly journals Epigenetic events in medulloblastoma development

2005 ◽  
Vol 19 (5) ◽  
pp. 1-13 ◽  
Author(s):  
Janet C. Lindsey ◽  
Jennifer A. Anderton ◽  
Meryl E. Lusher ◽  
Steven C. Clifford
Keyword(s):  
Gene Expression ◽  
Tumor Suppressor Genes ◽  
Molecular Basis ◽  
Gene Disruption ◽  
Functional Role ◽  
Promoter Hypermethylation ◽  
Therapeutic Approaches ◽  
Primary Tumors ◽  
Molecular Events ◽  
Epigenetic Events

Over the last decade, the analysis of genetic defects in primary tumors has been central to the identification of molecular events and biological pathways involved in the pathogenesis of medulloblastoma, the most common malignant brain tumor of childhood. Despite this, understanding of the molecular basis of the majority of cases remains poor. In recent years, the emerging field of epigenetics, which describes heritable alterations in gene expression that occur in the absence of DNA sequence changes, has forced a revision of the understanding of the mechanisms of gene disruption in cancer. Accumulating evidence indicates a significant involvement for epigenetic events in medulloblastoma development. Recent studies have identified a series of candidate tumor suppressor genes (for example, RASSF1A, CASP8, and HIC1) that are each specifically epigenetically inactivated in a large proportion (> 30%) of medulloblastomas by promoter hypermethylation, leading to the silencing of their gene expression. These findings shed new light on medulloblastoma and offer great potential for an improved understanding of its molecular pathology. The authors review the current understanding of epigenetic events in cancer and their contribution to medulloblastoma development. Their nature, origins, and functional role(s) in tumorigenesis are considered, and the authors assess the potential utility of these events as a basis for novel diagnostic and therapeutic approaches.

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