Aspects of molecular medicine最新文献

{"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}

{"title":"Advances in RNA cancer therapeutics: New insight into exosomes as miRNA delivery","authors":"Luca Volpini ,&nbsp;Federica Monaco ,&nbsp;Lory Santarelli ,&nbsp;Jiri Neuzil ,&nbsp;Marco Tomasetti","doi":"10.1016/j.amolm.2023.100005","DOIUrl":"10.1016/j.amolm.2023.100005","url":null,"abstract":"<div><p>We are now entering a new era of RNA therapies, such that mRNA-based vaccines and RNA interference approaches such as siRNA have already been launched on the pharmaceutical market. However, there are no FDA-approved RNA-based therapeutics for cancer treatment. Among RNA molecules, miRNAs represent a promising solution against cancer. Despite the ability to target multiple pathways, miRNA-based therapeutics struggle to reach phase 3 clinical trial. A reason of this delay is linked to complications of selective administration of miRNAs to their target, the tumor cell. Because of this, an efficient delivery system is necessary. In this sense, exosomes are considered the most promising miRNA-based therapeutic carriers in terms of safety and efficient cargo delivery. Furthermore, researchers have developed a new strategy to overcome the tumor capacity by using exosomes to release unnecessary miRNAs, shedding light on a new generation therapy of cancer treatment. The review describes recent advances in the application of miRNAs in the treatment of cancer, the use of exosomes for miRNA delivery, focusing on new approaches to overcome the limits of miRNA-loaded exosomes in clinical applications.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"1 ","pages":"Article 100005"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47624218","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":"Unusual Monkeypox virus outbreak in 2022: Phenotypic and molecular characteristics","authors":"Alberta Azzi","doi":"10.1016/j.amolm.2023.100001","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100001","url":null,"abstract":"<div><p>Monkeypox virus, first identified in 1958 in Asian monkeys employed for experiments in a laboratory in Denmark and then in 1970 in humans in Africa, in the Democratic Republic of Congo (DRC), has continued to circulate for about 50 years in some regions of Africa, indicated as Congo Basin (CB) and West Africa (WA) where it has become endemic. Rare outbreaks have occurred outside endemic countries, linked to importation of the virus from endemic areas. Suddenly, since early May 2022, cases of MPX developed outside the endemic areas and their number increased rapidly. Important differences in the epidemiology of 2022 MPX compared to previous MPX spread have begun to be observed soon. First, the 2022 cases could not be traced to contacts with infected cases or animals from endemic countries. The 2022 cases are due to human-to-human transmission and not to contact with infected animals; among the transmission routes the sexual route seems to predominate, particularly among men who have sex with men (MSM). Affected countries are located on several continents, mainly in America and Europe, but also in Asia and Australia. As of mid-November 2022, 110 countries have reported MPX cases, for a total of more than 79,000 confirmed cases and 50 deaths. What is behind this new MPXV behavior and what consequences might it have? This review aims to clarify the possible underpinnings of this 2022 MPX outbreak, with a focus on the molecular mechanisms, through an analysis of the literature. Most of the studies undertaken for this purpose are concerned with the molecular genetics of MPXVs and have been based on analysis and sequence comparison of the different species of the OPXV genus, of isolates of the two different MPXV Clades, of MPXVs in circulation before and during 2022, as well as of MPXVs identified from May 2022 onwards. These studies, reveal some variations mainly in the sequences of the Inverted Terminal Repeats (ITRs), known, on the other hand, as more variable regions of the viral genome. These are variations mainly in the genes involved in the virus-host relationship, virulence and immune evasion. However, further studies are needed to confirm the real significance of these variations in virus evolution. Of particular interest is the observation, shared by many authors, of the frequency of mutations in the MPXVs 2022 genome associated with APOBEC activity. These mutations may in fact represent a marker of human-to-human transmission that characterizes the new MPXV isolates. Overall, the variability of the MPXVs 2022, grouped in the B.1 lineage of Clade IIb, is not particularly high compared, for example, to many RNA viruses. However, it is still much higher than that of the previously circulated MPXV. Even if the epidemiological curve has changed trend in the past 3 months, it remains important to shed full light on the causes the multinational MPX outbreak of 2022.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"1 ","pages":"Article 100001"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49773632","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}