Aspects of molecular medicine最新文献

{"title":"Polypharmacological assessment of Amoxicillin and its analogues against the bacterial DNA gyrase B using molecular docking, DFT and molecular dynamics simulation","authors":"Miah Roney ,&nbsp;Gagandeep Singh ,&nbsp;Amit Dubey ,&nbsp;Hemant Soni ,&nbsp;Smriti Tandon ,&nbsp;Cheemlapati Venkata Narasimhaji ,&nbsp;Aisha Tufail ,&nbsp;Moyeenul Huq Akm ,&nbsp;Mohd Fadhlizil Fasihi Mohd Aluwi","doi":"10.1016/j.amolm.2023.100024","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100024","url":null,"abstract":"<div><p>There has been an increase in the emergence and spread of drug-resistant pathogens, leading to a steep incline in the cases of antimicrobial resistance. Due to this, there is an imperative need for the development and identification of new antimicrobials to combat this menace of antimicrobial resistance. But this need is not being completely fulfilled by conventional drug discovery focused on a one molecule-one target approach. Polypharmacology, i.e., designing a drug in a way that acts on multiple cellular or molecular targets, a new approach for the identification of antimicrobial compounds, has been gaining attention. DNA gyrase B is one of the critical proteins involved in DNA replication and cell division in <em>E. coli</em>. In this study, the polypharmacological effect of amoxicillin and its analogues was studied on the DNA gyrase B and various other proteins of <em>E. coli</em>, using multiple in silico approaches like molecular docking, structural similarity, DFT, and molecular dynamics simulation. Both amoxicillin and its analogue, Cefaclor, tend to disrupt bacterial cell wall synthesis, but this study, based on in silico analysis, suggests a probable additional mode of action involving DNA gyrase B of <em>E. coli</em> which can be further explored to design novel dual-target inhibitors.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100024"},"PeriodicalIF":0.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49708081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers in acute myeloid leukemia: From state of the art in risk classification to future challenges of RNA editing as disease predictor and therapy target","authors":"Alberto Quattrocchi ,&nbsp;Luca Vincenzo Cappelli ,&nbsp;Giovanna De Simone ,&nbsp;Elisabetta De Marinis ,&nbsp;Martina Gentile ,&nbsp;Tecla Gasperi ,&nbsp;Alessandro Pulsoni ,&nbsp;Paolo Ascenzi ,&nbsp;Clara Nervi","doi":"10.1016/j.amolm.2023.100023","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100023","url":null,"abstract":"<div><p>Acute Myeloid Leukemia (AML) is currently diagnosed based on morphological assessment of myeloid cells’ features, immunophenotypic characterization of specific cell surface and intracellular markers, conventional cytogenetic testing and screening for genetic abnormalities in bone marrow and peripheral blood specimens. In recent years new technologies have shed light on the complexity and heterogeneity of this elusive leukemia and are providing useful biomarkers, predictive of prognosis in AML patients. Hence, technological efforts are being made in order to identify more accurate AML biomarkers also useful to track minimal residual disease at the various follow-up times. This remains an unmet need that, together with the intrinsic tumor features of AML, results in the highest death rate of all leukemias and a 5-year overall survival &lt;50%. This review provides insights into the state-of-the-art of AML-related biomarkers and their role in clinical practice as prognostic indicators, minimal residual disease detection or candidates for targeted therapy. In addition, we report modifications of RNA epitranscriptome during normal hematopoiesis that are de-regulated in AML, recently revealed by new and more sophisticated techniques. We focus on alterations of m⁶A modifications on mRNAs and of enzymes catalyzing them, which have been reported to affect normal hematopoiesis and leukemogenesis and are providing novel promising biomarkers for AML risk assessment and newly druggable targets for treatment.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100023"},"PeriodicalIF":0.0,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49708080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CaMKII: A link between metabolic disorders and cardiac arrhythmias","authors":"M. Federico ,&nbsp;C.A. Valverde ,&nbsp;L.A. Gonano ,&nbsp;J. Palomeque ,&nbsp;A. Mattiazzi","doi":"10.1016/j.amolm.2023.100022","DOIUrl":"10.1016/j.amolm.2023.100022","url":null,"abstract":"<div><p>The prevalence of metabolic diseases -such as obesity, prediabetes, metabolic syndrome or diabetes-has increased globally over the years. These diseases, mainly diabetes mellitus (DM), are among the leading causes of mortality and morbidity worldwide, with increased risk of diabetic cardiomyopathy (DC), cardiac arrhythmias, and heart failure (HF).</p><p>In metabolic diseases several steps and proteins involved in excitation-contraction coupling (ECC) are compromised, precluding an efficient and rhythmic cardiac contraction; moreover, calcium/calmodulin-dependent protein kinase II (CaMKII) a kinase involved in ECC, is upregulated in several metabolic maladies and significantly contributes to cardiac remodeling and arrhythmias, among which are calcium (Ca²⁺)-triggered arrhythmias. CaMKII activation is canonically produced by an increase and binding of Ca²⁺-calmodulin followed by auto-phosphorylation; furthermore, it may occur as a result of several post-translational modifications, including oxidation and O-GlcNAcylation that are usually present in metabolic illnesses and support chronic CaMKII upregulation and ECC impairment.</p><p>The aim of the present review is to summarize what is known about the different pathways modifying CaMKII activity and Ca²⁺ handling in metabolic disorders and may promote Ca²⁺-triggered arrhythmias even at the early stages of metabolic alterations. Future challenges in this field may encompass unraveling the precise mechanisms by which metabolic disturbances modulate CaMKII activity and its downstream effects on cardiac electrophysiology among different species. This would allow the development of robust and valid preclinical human models that can accurately recapitulate the pathophysiology of the human heart. Additionally, investigating the impact of targeted interventions, such as pharmacological inhibitors or gene therapies, could provide valuable insights into the feasibility and efficacy of manipulating CaMKII signaling to prevent or treat arrhythmias in metabolic disorders.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100022"},"PeriodicalIF":0.0,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48847691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin and butyrate induce fibroblast senescence without the emergence of fibrosis biomarkers","authors":"Siwei Chu ,&nbsp;Natali Joma ,&nbsp;Hui Wen Yong ,&nbsp;Dusica Maysinger ,&nbsp;Ashok Kakkar ,&nbsp;Ursula Stochaj","doi":"10.1016/j.amolm.2023.100021","DOIUrl":"10.1016/j.amolm.2023.100021","url":null,"abstract":"<div><h3>Background</h3><p>Small molecules have emerged as valuable tools to modulate cellular homeostasis and the changes associated with aging. In particular, the phytochemical curcumin elicits cytoprotective effects that promote human health and longevity. The short-chain fatty acid butyrate provides anti-fibrotic activities, but can also induce cellular senescence.</p></div><div><h3>Rationale</h3><p>The impact of curcumin and butyrate on living cells are not fully understood. To obtain this information, our work focuses on fibroblasts. We selected fibroblasts as cellular model, because they (i) are present in different tissues and organs, (ii) contribute essential functions that derail during organismal aging, and (iii) are prime targets for therapeutic interventions that ameliorate aging-related pathologies.</p></div><div><h3>Methods and results</h3><p>A panel of quantitative assessments determines how curcumin and its nanoformulation (nano-curcumin), either alone or in combination with butyrate, modulate fibroblast physiology. Several experimental approaches and biomarkers demonstrate that curcumin (i) diminishes fibroblast viability, and (ii) promotes cellular senescence in a concentration-dependent fashion. Specifically, curcumin and nano-curcumin increase the activity of senescence-associated β-galactosidase and reduce the abundance of lamin B. When combined with butyrate, both curcumin and nano-curcumin enhance cell death and senescence. Free curcumin decreases the levels of Nrf2, a transcription factor that is upregulated upon oxidative stress. Neither curcumin nor nano-curcumin changes the abundance of the transcription factor NFκB, which is critical for inflammatory responses. Free curcumin, butyrate and nano-curcumin/butyrate combinations significantly diminish the abundance of the lysine deacetylase SIRT1, which is a key regulator of cellular senescence. Notably, none of the compounds or their combinations elevates biomarkers of fibrosis.</p></div><div><h3>Conclusions</h3><p>This study defines the cellular and molecular changes produced in fibroblasts by curcumin, nano-curcumin, alone or together with butyrate. Collectively, our results set the stage to explore curcumin/butyrate-based treatments to control the cellular activities that are contributed by fibroblasts.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100021"},"PeriodicalIF":0.0,"publicationDate":"2023-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42153356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of serum Growth Differentiation Factor–15, SMAD7, miRNA-21 & miRNA-181b in pre-diabetics and type 2 diabetics without comorbidities-a case-control study","authors":"Dipayan Roy ,&nbsp;Manoj Khokhar ,&nbsp;Ravindra Kumar Shukla ,&nbsp;Praveen Sharma ,&nbsp;Purvi Purohit","doi":"10.1016/j.amolm.2023.100020","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100020","url":null,"abstract":"<div><h3>Background</h3><p>Growth Differentiation Factor-15 (GDF-15) is involved in insulin resistance and diabetes. But its association with mothers against decapentaplegic homolog 7 (Smad7), miR-21, and miR-181b in peripheral blood mononuclear cells (PBMCs) of prediabetes and type 2 diabetes (T2DM) patients without comorbidities is not established. The roles of miR-21 and miR-181b as diagnostic tools in these conditions also need exploration.</p></div><div><h3>Methods</h3><p>One hundred sixteen patients, including diabetics (n = 56), pre-diabetics (n = 30), and non-diabetic controls (n = 30), were recruited. Fasting venous blood samples were collected for biochemical analyses, total RNA isolation, and real-time PCR.</p></div><div><h3>Results</h3><p>Serum GDF-15 showed an increasing trend from healthy controls to pre-diabetic and T2DM patients. Our study also showed upregulated miR-21 and miR-181b and downregulated Smad7 expressions in prediabetes and T2DM groups. Serum GDF-15 was positively associated with miR-21 (ρ = 0.345, <em>p</em> &lt; 0.001) and miR-181b (ρ = 0.398, <em>p</em> &lt; 0.001), and negatively associated with Smad7 (ρ = −0.196, <em>p</em> = 0.035). Both miR-21 and miR-181b were positively associated with HbA1c, fasting blood sugar, and each other. In T2DM, miR-21 showed a significant discriminatory power (area under the curve 0.806, <em>p</em> &lt; 0.05) compared to healthy controls.</p></div><div><h3>Conclusion</h3><p>Our findings suggest that GDF-15 and miR-21 can be used as non-invasive and rapid tools for delineating prediabetes and T2DM states, which can be validated in larger prospective cohorts. The significant association of serum GDF-15 with miR-21, miR-181b, and Smad7 suggest possible regulatory roles of these molecules in prediabetes and T2DM. Further studies are necessary to explore these molecules as potential therapeutic targets.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49731881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morin hydrate promotes nephrin expression through modulation of Notch1-Snail signalling pathway in diabetic rats","authors":"Akeem Olalekan Lawal ,&nbsp;Ibukun Mary Folorunso ,&nbsp;Olufemi Adebisi ,&nbsp;Omowumi Funmilayo Koledoye ,&nbsp;Opeyemi Iwaloye","doi":"10.1016/j.amolm.2023.100019","DOIUrl":"10.1016/j.amolm.2023.100019","url":null,"abstract":"<div><p>Reduction in nephrin expression is usually observed in patients with diabetic nephropathy, and there is evidence that Notch1/Snail signalling pathway is essential for the expression of nephrin. This study investigated the role of morin hydrate (MH) on Notch1/Snail signalling pathway in the kidney of type-2 diabetic rats (T2D) exposed to diesel exhaust particles (DEP). The male wistar rats (n ​= ​40) were group into 8 groups: Group 1-Control; Group 2-DEP (0.5 ​mg/kg); Group 3-type-2 diabetic rat (T2D); Group 4-T2D ​+ ​DEP (0.5 ​mg/kg); Group 5-DEP (0.5 ​mg/kg) ​+ ​MH (30 ​mg/kg); Group 6-T2D ​+ ​MH (30 ​mg/kg); Group 7-T2D ​+ ​DEP 0.5 ​mg/kg ​+ ​MH 30 ​mg/kg; and Group 8-MH (30 ​mg/kg) only. Type-2 diabetes was induced in the rats through a one-time administration of STZ at 45 ​mg/kg after 14 days treatment with fructose solution at 20% w/v. The type-2 diabetic and non-diabetic rats were exposed to DEP at 0.5 ​mg/kg through nasal instillation every 48 ​h for 14 days. MH (30 ​mg/kg) was given orally every 24 ​h for 15 days. MH is a naturally occurring flavonoid chemical found in a variety of plants, and has been discovered to have a number of biological actions, including antioxidant, anti-inflammatory, and anticancer effects. The effect of MH on kidney function indices and electrolytes, and its modulatory role on Notch1/Snail signalling pathway were determined. <em>In silico</em> studies on binding affinity of MH with some proteins in this pathway was conducted and the electronic behavior of MH was predicted using DFT calculation<strong>.</strong> The results show that MH oral therapy ameliorates nephrotoxicity and protects the podocytes in T2D rats and T2D rats exposed to DEP. It decreased the serum levels of creatinine, urea and total protein, while also decreasing the levels of renal sodium and potassium ions and bicarbonate. MH increased mRNA expression of nephrin by modulating Notch1/Snail signalling pathway, and these results were supported by the molecular docking studies. This study suggests that MH promote glomerular filtration in T2D exposed to DEP.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100019"},"PeriodicalIF":0.0,"publicationDate":"2023-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43097407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of serum growth differentiation Factor–15, SMAD7, miR-21 & miR-181b in pre-diabetics and type 2 diabetics without comorbidities-a case control study","authors":"D. Roy, Manoj Khokhar, R. Shukla, P. Sharma, P. Purohit","doi":"10.1016/j.amolm.2023.100020","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100020","url":null,"abstract":"","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41729524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dielectrophoresis spectroscopy for nucleotide identification in DNA","authors":"Md Fahim Shahriar ,&nbsp;Janisa Kabir ,&nbsp;Ding Piaopiao","doi":"10.1016/j.amolm.2023.100009","DOIUrl":"10.1016/j.amolm.2023.100009","url":null,"abstract":"<div><p>DNA sequence with a known physical position on a chromosome is called a genetic marker, so the causal gene may identify with genetic markers in different kinds of hereditary diseases. DNA segments near one another on a chromosome often inherit the other concurrently; as a result, the inheritance of a neighboring gene that has not yet been discovered but whose general position is tracked by using genetic markers. So, Genetic markers can play a significant role in biological research because they can contribute to identifying many diseases. Single nucleotide polymorphism, or SNP (pronounced “snip”), is the variation of a single nucleotide in a DNA due to genetic disorders. For example, in a specific region of DNA, an SNP may displace the nucleotide cytosine (C) with the nucleotide thymine (T). SNPs, or single nucleotide polymorphisms, are one of the most common genetic variations that assist in detecting many human diseases such as Migraine, Cancer, Schizophrenia, Sickle Cell Anemia, Alzheimer's Disease, etc. Hyperchromicity, Short Oligonucleotide Analysis Program (SOAP), quantitative PCR techniques, Fluorescence Polarization Melting Curve Analysis, SNP Microarrays, Intercalating Dyes, and many other techniques are commonly used to identify SNPs nowadays. However, those methods are not much reliable, a bit costly, time-consuming, and difficult to use, whereas dielectrophoresis can be an excellent way to detect SNP easily. A non-uniform electric field generated by electrodes interacts with polarizable suspended particles to regulate and alter particle movement; this process is known as dielectrophoresis (DEP). Cell transfer, in vitro fertilization, and biological testing are a few uses for dielectrophoresis, particularly in the biomedical industry. Cell fusion using dielectrophoresis has also improved crossbreeding, cancer treatment, and scientific research. Most notably, dielectrophoresis is used to classify changes in the electrical characteristics of cells. In this phenomenon, when a dielectric particle is exposed to a non-uniform electric field, a force is produced on it, and this DEP force may be utilized to recognize the variations in a single location in a DNA sequence. DEP is less time-consuming, cheap, and reliable than other processes to detect SNPs easily.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"1 ","pages":"Article 100009"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41536137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"sgRNAs: A SARS-CoV-2 emerging issue","authors":"Antonio Mori ,&nbsp;Denise Lavezzari ,&nbsp;Elena Pomari,&nbsp;Michela Deiana,&nbsp;Chiara Piubelli,&nbsp;Maria Rosaria Capobianchi,&nbsp;Concetta Castilletti","doi":"10.1016/j.amolm.2023.100008","DOIUrl":"10.1016/j.amolm.2023.100008","url":null,"abstract":"<div><p>Like for other coronaviruses, SARS-CoV-2 gene expression strategy is based on the synthesis of a nested set of subgenomic mRNA species (sgRNAs). These sgRNA are synthesized using a “discontinuous transcription” mechanism that relies on template switching at Transcription Regulatory Sequences (TRS). Both canonical (c-sgRNA) and non-canonical (nc-sgRNA, less numerous) subgenomic RNA species can be produced. Currently, sgRNAs are investigated on the basis of sequence data obtained through next generation sequencing (NGS), and bioinformatic tools are crucial for their identification, characterization and quantification. To date, few software have been developed to this aim, whose reliability and applicability to all the available NGS platforms need to be established, to build confidence on the information resulting from such tools. In fact, these information may be crucial for the in depth elucidation of viral expression strategy, particularly in respect of the significance of nc-sgRNAs, and for the possible use of sgRNAs as potential markers of virus replicative activity in infected patients.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"1 ","pages":"Article 100008"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10105645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9909514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel linkage and association of the mineralocorticoid receptor gene (NR3C2) with familial type 2 diabetes and depression and their comorbidity","authors":"Mutaz Amin ,&nbsp;Shumail Syed ,&nbsp;Rongling Wu ,&nbsp;Teodor T. Postolache ,&nbsp;Claudia Gragnoli","doi":"10.1016/j.amolm.2023.100003","DOIUrl":"10.1016/j.amolm.2023.100003","url":null,"abstract":"<div><h3>Introduction</h3><p>The mineralocorticoid receptor gene (<em>NR3C2)</em> appears to modulate stress and cognitive performance in patients with major depressive disorder (MDD). In addition, abnormalities in <em>NR3C2</em> are associated in rodents with type 2 diabetes (T2D) and in humans with features of metabolic syndrome. Of note, NR3C2 antagonists are approved treatments in heart failure and chronic kidney disease with T2D. The <em>NR3C2</em> gene is therefore a candidate gene for studying T2D-MDD comorbidity. To our knowledge, no study has so far reported risk variants in the <em>NR3C2</em> gene with either MDD and/or T2D.</p></div><div><h3>Materials and methods</h3><p>In 212 multigenerational Italian families with enriched family history of T2D and with MDD, we analyzed 86 single nucleotide polymorphisms (SNPs) within the <em>NR3C2</em> gene for parametric linkage to and/or linkage disequilibrium (LD) with T2D and MDD.</p></div><div><h3>Results</h3><p>We identified a total of 7 independent SNPs significantly linked to/in LD with MDD only, 20 SNPs significantly linked to/in LD with T2D only, and 9 SNP significantly linked to/in LD with both T2D and MDD. The SNPs were statistically significant across different models. Two sets of LD blocks were MDD-specific, and one set was T2D-specific. <em>In silico</em> analysis of the risk variants predicted 3 variants with potential functional effects.</p></div><div><h3>Conclusions</h3><p>This is the first study to report <em>NR3C2</em> as a novel risk gene in T2D and MDD comorbidity. However, our results need to be replicated in other ethnicities.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"1 ","pages":"Article 100003"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49239824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}