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Primary aldosteronism: molecular medicine meets public health

Azizan EAB, Drake WM, Brown MJ

Nat Rev Nephrol, 2023 Dec;19(12):788-806.
PMID: 37612380 DOI: 10.1038/s41581-023-00753-6

Primary aldosteronism is the most common single cause of hypertension and is potentially curable when only one adrenal gland is the culprit. The importance of primary aldosteronism to public health derives from its high prevalence but huge under-diagnosis (estimated to be <1% of all affected individuals), despite the consequences of poor blood pressure control by conventional therapy and enhanced cardiovascular risk. This state of affairs is attributable to the fact that the tools used for diagnosis or treatment are still those that originated in the 1970-1990s. Conversely, molecular discoveries have transformed our understanding of adrenal physiology and pathology. Many molecules and processes associated with constant adrenocortical renewal and interzonal metamorphosis also feature in aldosterone-producing adenomas and aldosterone-producing micronodules. The adrenal gland has one of the most significant rates of non-silent somatic mutations, with frequent selection of those driving autonomous aldosterone production, and distinct clinical presentations and outcomes for most genotypes. The disappearance of aldosterone synthesis and cells from most of the adult human zona glomerulosa is the likely driver of the mutational success that causes aldosterone-producing adenomas, but insights into the pathways that lead to constitutive aldosterone production and cell survival may open up opportunities for novel therapies.

Matched MeSH terms: Molecular Medicine
Fulltext Molecular imaging: spawning a new melting-pot for biomedical imaging

Abdullah B

Biomed Imaging Interv J, 2006 Oct;2(4):e28.
PMID: 21614327 MyJurnal DOI: 10.2349/biij.2.4.e28

Predicting the future is a dangerous undertaking at best, and not meant for the faint-hearted. However, viewing the advances in molecular medicine, genomics and proteomics, it is easy to comprehend those who believe that molecular imaging methods will open up new vistas for medical imaging. The knock on effect will impact our capacity to diagnose and treat diseases. Anatomically detectable abnormalities, which have historically been the basis of the practice of radiology, will soon be replaced by molecular imaging methods that will reflect the under expression or over expression of certain genes which occur in almost every disease. Molecular imaging can then be resorted to so that early diagnosis and characterisation of disease can offer improved specificity. Given the growing importance of molecular medicine, imagers will find it profitable to educate themselves on molecular targeting, molecular therapeutics and the role of imaging in both areas.

Matched MeSH terms: Molecular Medicine
Fulltext Evaluation of the Diagnostic Performance of Recombinant Antigen B1 for Detection of Cystic Echinococcosis Using Lateral Flow Dipstick Test

Noordin R, Khanbabaie S, Hafiznur Yunus M, Marti H, Nickel B, Fasihi Harandi M, et al.

Iran J Parasitol, 2020 10 22;15(3):290-298.
PMID: 33082792 DOI: 10.18502/ijpa.v15i3.4191

Background: Human echinococcosis is a neglected zoonotic disease distributed worldwide. It comprises cystic and alveolar forms, the former being the more prevalent disease. Imaging techniques are the first choice for diagnosis of cystic echinococcosis and serology is used as an additional diagnostic technique in doubtful cases or as the sole test in low-resource settings. Rapid diagnostic tests are useful and convenient for immunodiagnosis of cystic echinococcosis in endemic areas, where medical facilities often struggle with limited resources.
Methods: Recently, we have developed Hyd Rapid™, an IgG4 lateral flow dipstick test using recombinant antigen B1 for detection of cystic echinococcosis. This study was performed between 2016 until 2018 at the Institute for Research in Molecular Medicine, Universiti Sains Malaysia. The diagnostic performance of Hyd Rapid™ was tested in-house and at two international laboratories in Switzerland and Iran.
Results: The overall diagnostic sensitivity for detection of cystic and alveolar echinococcosis was 95% (56/59). Meanwhile, the diagnostic specificity, with and without exclusion of cysticercosis and fascioliasis, was 100% (n=48) and 88% (63/72), respectively.
Conclusion: Hyd Rapid™ detected cystic echinococcosis as well as probable cases of alveolar echinococcosis. Therefore, Hyd Rapid™ showed good potential as a serological tool for echinococcosis, and merits further evaluation.

Matched MeSH terms: Molecular Medicine
Fulltext [Corrigendum] Antiproliferative effects of imatinib mesylate on ZR‑75‑1 and MDA‑MB‑231 cell lines via PDGFR‑β, PDGF‑BB, c‑Kit and SCF expression

Kadivar A, Noordin MI, Aditya A, Kamalidehghan B, Davoudi ET, Sedghi R, et al.

Int J Mol Med, 2019 05;43(5):2259.
PMID: 30864679 DOI: 10.3892/ijmm.2019.4119

An interested reader drew to our attention that the above study appeared to contain a high level of overlap with an article by the same authors published in the journal Drug Design, Development and Therapy [Kadivar A, Kamalidehghan B, Akbari Javar H, Karimi B, Sedghi R and Noordin MI: Antiproliferation effect of imatinib mesylate on MCF7, T‑47D tumorigenic and MCF 10A nontumorigenic breast cell lines via PDGFR‑β, PDGF‑BB, c‑Kit and SCF genes. Drug Des Devel Ther 11: 469‑481, 2017]. Following an internal investigation and also in liaison with the authors, it was established that, although the studies were conducted along broadly similar lines, the papers contained entirely different data involving two different subsets of cell lines; the submission to Drug Des Devel Ther aimed to explore the effects of imatinib mesylate on three different groups, with each group being represented by a cell line, whereas the submission to Int J Mol Med explored the effectiveness of imatinib mesylate in breast cancer cell lines. In spite of this, considering the relatedness of the articles and the fact that the paper to Drug Des Devel Ther was submitted first and published while the Int J Mol Med paper was passing through the peer‑review process, the authors concede that they should have properly referenced their paper submitted to Drug Des Devel Ther in the Int J Mol Med paper. Note that the publishers of Drug Des Devel Ther, with whom we were liaising, agreed with the decision to issue a Corrigendum for this paper that acknowledges the article published in Drug Des Devel Ther. The authors regret their failure to acknowledge the related paper in this instance, and apologize to the readership for this oversight. [the original article was published in International Journal of Molecular Medicine 14: 414‑424, 2018; DOI: 10.3892/ijmm.2018.3590].

Matched MeSH terms: Molecular Medicine
Therapeutic potential of combined viral transduction and CRISPR/Cas9 gene editing in treating neurodegenerative diseases

Kuruvilla J, Sasmita AO, Ling APK

Neurol Sci, 2018 Nov;39(11):1827-1835.
PMID: 30076486 DOI: 10.1007/s10072-018-3521-0

BACKGROUND AND PURPOSE: The central nervous system (CNS) faces unique difficulties in attaining permanent therapy for neurodegenerative disorder (ND). Genomic level forms of therapy have garnered interest in the recent decade, with the novel CRISPR/Cas9 gene editing tool continuing to be explored due to its efficiency, safety, and adaptability to varying conditions. With the aid of viral vectors as transport vectors, the gene editing tool has produced promising in vitro and in vivo findings in study models. Thus, this review focuses on the recent advancements and update of CRISPR/Cas9 to combat neurodegenerative diseases.
METHODS: Articles detailing potential applications of CRISPR/Cas9 in neurodegenerative settings were retrieved from PubMed and Google Scholar with the keywords "CRISPR," "gene editing," and "neurodegenerative diseases." Relevant information was collected and critically reviewed.
RESULTS: The utility of CRISPR/Cas9 coupled with viral transduction ranges from the disruption of amyloid precursor protein (APP) production at a genomic level in Alzheimer's disease (AD) to the deletion of varying exon portions of the Dmd gene in Duchenne muscular dystrophy (DMD) which would increase dystrophin expression. This usage of CRISPR/Cas9 also extends to experimentally ameliorate the neurodegenerative effects caused by viral infections.
CONCLUSION: The CRISPR/Cas9 gene editing tool is a powerful arsenal in the field of gene therapy and molecular medicine; hence, more research should be called to focus on the ample potential this tool has to offer in the field of neurodegenerative diseases.

Matched MeSH terms: Molecular Medicine