Aspects of molecular medicine最新文献

{"title":"Plants as a source of dietary bioactives: Flavonoids and basis for their health benefits","authors":"Andrea Galatro ,&nbsp;Agustin Lucini Mas ,&nbsp;Melisa Luquet ,&nbsp;Cesar G. Fraga ,&nbsp;Monica Galleano","doi":"10.1016/j.amolm.2024.100048","DOIUrl":"10.1016/j.amolm.2024.100048","url":null,"abstract":"<div><p>Flavonoids are a group of bioactive compounds widely distributed in edible plants. They have gained special attention given strong scientific evidence supporting their health promoting actions. This review summarizes current knowledge on the biosynthetic pathways of flavonoids in plants, the regulation of those pathways, and the conservation of flavonoids in plant road to becoming a food. Additionally, the main dietary sources of flavonoid, evidence from population and clinical studies, and possible mechanisms involved in the beneficial effects of flavonoids on human health are also discussed.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"4 ","pages":"Article 100048"},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000157/pdfft?md5=c64a4f91a9fc1c74480b36f391594b49&pid=1-s2.0-S2949688824000157-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141399001","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":"Genome-wide linkage and association of novel genes and pathways with type 2 diabetes in Italian families","authors":"Mutaz Amin ,&nbsp;Claudia Gragnoli","doi":"10.1016/j.amolm.2024.100046","DOIUrl":"10.1016/j.amolm.2024.100046","url":null,"abstract":"<div><h3>Background</h3><p>Type 2 diabetes mellitus (T2D) stands as one of the most prevalent chronic diseases globally, posing substantial health and economic burdens on society. Within the spectrum of T2D, familial cases emerge as a distinct entity characterized by a strong familial clustering of the disease. This phenomenon has long suggested that genetics contributes substantially to T2D susceptibility, motivating extensive research into the genetic determinants of familial T2D.</p></div><div><h3>Methods</h3><p>We recruited 212 multigenerational Italian families with multiple cases of T2D. The families were genotyped using genomic array (≥ 600k) derived from the UK Biobank Axiom Array platform. Informative markers were tested via Pseudomarker for linkage to and linkage disequilibrium (i.e., linkage joint to association) with T2D across the following models: dominant with complete penetrance (D1), dominant with incomplete penetrance (D2), recessive with complete penetrance (R1), and recessive with incomplete penetrance (R2).</p></div><div><h3>Results</h3><p>We identified a total of 566 variants reaching genome-wide significant (P &lt; 0.00005) linkage and/or association to/with the risk of T2D in Italian families. Of the 355 genes identified in our study, 341 (96%) are novel and have not been reported with T2D or any of its related phenotypes (i.e., obesity, metabolic syndrome, insulin resistance, polycystic ovary syndrome, and hyperglycemia).</p></div><div><h3>Conclusion</h3><p>Our study constitutes the first familial T2D-linkage and association study in the Italian population. However, the functional relevance of the novel variants and genes reported in our study remains to be explored.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"4 ","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000133/pdfft?md5=3aef99032194eb4bf3cd9f8b59833a30&pid=1-s2.0-S2949688824000133-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141275920","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":"Identification of biomarkers and molecular mechanisms implicated in genetic variations underlying Alzheimer's disease pathogenesis","authors":"Hai Duc Nguyen ,&nbsp;Giang Huong Vu ,&nbsp;Woong-Ki Kim","doi":"10.1016/j.amolm.2024.100045","DOIUrl":"10.1016/j.amolm.2024.100045","url":null,"abstract":"<div><p>We analyzed data from human genome-wide association studies (GWASs) to identify genetic variants and biological pathways linked to Alzheimer's disease (AD). Ten AD biomarkers (APOE, NECTIN2, APOC1, APOC1P1, TOMM40, RNU4-67P, KRAS, Y_RNA, THORLNC, LINC01956) were found across studies, including six central genetic variants (MAPT (rs242557-A), GRIN2B (rs74442473-G), APOE (rs438811-T), ANK3 (rs438811-T), BIN1 (rs744373-G), and BDNF (rs7481773-A)). ANK3 (rs438811-T) and GRIN2B (rs74442473-G) were essential hub biomarkers for amyloid plaques, while MAPT (rs242557-A) and BIN1 (rs744373-G) were crucial for neurofibrillary tangles (NFTs). Higher-risk AD biomarkers were associated with increased protein-lipid complex formation, while lower-risk AD biomarkers were correlated with improved synaptic function. Six essential miRNAs (hsa-miR-124–3p, 15a-5p, 16–5p, 204–5p, 520g-3p, 520h) and three transcription factors (ZMAT4, ZBED6, FOXG1) emerged as possible candidates to reveal the genetic differences that lead to amyloid plaques, NFTs, and ultimately AD. These findings serve as a basis for potential AD treatments and offer new avenues for therapeutic approaches to directly target the genetic variations and processes associated with the disease.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100045"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000121/pdfft?md5=162a70149a1664b1e8e571f8fab0e3a7&pid=1-s2.0-S2949688824000121-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141141702","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":"Hemostatic abnormalities for predicting and management of disease severity in COVID-19 affected patients: Review","authors":"Kovuri Umadevi ,&nbsp;Ruchira Clementina ,&nbsp;Dola Sundeep ,&nbsp;Mohd Imran Ali ,&nbsp;Rajarikam Nagarjuna Chary ,&nbsp;Arundhathi Shankaralingappa","doi":"10.1016/j.amolm.2024.100043","DOIUrl":"https://doi.org/10.1016/j.amolm.2024.100043","url":null,"abstract":"<div><p>The recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic has posed significant challenges to global healthcare, with a myriad of impacts on the human body, particularly noted in hemostatic abnormalities observed in COVID-19 patients. These abnormalities have been linked to an increased risk of serious thrombotic events like deep vein thrombosis, pulmonary embolism, and stroke. Unlike existing literature, this comprehensive review delves into the long-term implications of these abnormalities, providing invaluable guidance for ongoing patient care as we move into the post-pandemic era. We cover the entire spectrum of hemostatic abnormalities, including elevated levels of aPTT, D-dimer, PT, ferritin, INR, fibrinogen, fibrin, and FDP, all of which create a complex clinical scenario necessitating vigilant monitoring and targeted therapeutic interventions. With a focus on the heightened risk of thrombotic complications, we underscore the importance of timely anticoagulant therapy and other necessary interventions, tailored to the patient's unique clinical presentation. This review stands as a critical resource for clinicians, hematologists, and healthcare providers, equipping them to navigate the complexities of COVID-19 in both acute and long-term settings, ensuring optimal patient outcomes. As we collectively navigate the lasting impact of the pandemic, this targeted and in-depth analysis becomes an indispensable tool in advancing our understanding and management of COVID-19.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000108/pdfft?md5=2371a4894ef87a159df30cf582741213&pid=1-s2.0-S2949688824000108-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140893543","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":"The interaction between ultra-processed foods and genetic risk score on body adiposity index (BAI), appendicular skeletal muscle mass index (ASM), and lipid profile in overweight and obese women","authors":"Fatemeh Gholami ,&nbsp;Azadeh Lesani ,&nbsp;Neda Soveid ,&nbsp;Niloufar Rasaei ,&nbsp;Mahsa Samadi ,&nbsp;Niki Bahrampour ,&nbsp;Gholamali Javdan ,&nbsp;Khadijeh Mirzaei","doi":"10.1016/j.amolm.2024.100044","DOIUrl":"10.1016/j.amolm.2024.100044","url":null,"abstract":"<div><h3>Background &amp; aims</h3><p>Ultra-processed foods (UPF) are formulations of ingredients, resulting from a series of industrial processes. Excess intake of UPF is associated with an increased risk of obesity and chronic disease. The present study investigates the interaction between the consumption of UPF and genetic risk score with body composition, body adiposity index (BAI), and appendicular skeletal muscle mass (ASM) in overweight and obese women.</p></div><div><h3>Method</h3><p>The study is cross-sectional with 376 overweight and obese women aged 18–65 years. The food consumption was obtained with 147-item food frequency (FFQ), and food items were grouped according to the level of processing as per the NOVA classification. Three single nucleotide polymorphisms (SNPs), including <em>Caveolin_1 (Cav_1), Melanocortin4 receptor (MC4R),</em> and <em>cryptochrome circadian regulator 1 (CRY1)</em>, were used to calculate GRS. The individual risk allele for each SNP was calculated using the incremental genetic model. Each SNP was recoded as 0, 1, or 2 based on the number of risk alleles associated with a higher body mass index (BMI). Subsequently, the unweighted GRS was computed by summing the number of risk alleles across the three SNPs. The GRS scale spans from 0 to 6, with each point representing a risk allele.Anthropometric measurements and some blood parameters were measured by standard protocols.</p></div><div><h3>Results</h3><p>After controlling for confounders such as age, energy intake, and BMI a significant interaction was found for appendicular skeletal muscle mass (β = −1.65, P = 0.04) and appendicular skeletal muscle mass index (β = −0.38, P = 0.07) on the NOVA classification system and GRS.</p></div><div><h3>Conclusions</h3><p>The findings of this study showed a significant interaction between GRS and the NOVA classification system on some body composition, including appendicular skeletal muscle mass. A higher intake of ultra-processed foods may be associated with lower appendicular skeletal muscle mass in people with high obesity-GRS.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294968882400011X/pdfft?md5=b91b1fc46a2676788aea8ac2bae8948f&pid=1-s2.0-S294968882400011X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141044652","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":"Higher oxidative stress and inflammation in obese compared to lean patients with type 2 diabetes mellitus","authors":"Mohit Mehndiratta ,&nbsp;Edelbert Anthonio Almeida ,&nbsp;Diwesh Chawla ,&nbsp;S.V. Madhu ,&nbsp;Seema Garg ,&nbsp;Rajarshi Kar","doi":"10.1016/j.amolm.2024.100042","DOIUrl":"https://doi.org/10.1016/j.amolm.2024.100042","url":null,"abstract":"<div><h3>Aim</h3><p>To compare mRNA [messenger RNA] expression of <em>RELA, NFκB1</em>, <em>TNF-α, IL-6 and MCP-1</em> in whole blood &amp; serum Total Antioxidant status [TAS] in newly diagnosed lean and obese patients with T2DM.</p></div><div><h3>Methods</h3><p>Newly diagnosed treatment naïve patients of T2DM were enrolled in this study. The patients were divided into two groups of 30 patients each, lean (BMI&lt; 18.5 kg/m²) and obese (BMI &gt;25 kg/m²) groups. mRNA expression of <em>RELA, NFκB1, TNF-α, IL-6 and MCP-1</em> was measured by real time PCR. Serum TAS was measured using a commercially available kit.</p></div><div><h3>Results</h3><p>There was a 2.7-fold increase in mRNA expression of <em>RELA</em> in obese group compared to the lean group. There was a 1.3-fold increase in mRNA expression of <em>NFκB1</em>, a 3.24-fold increase in mRNA expression of <em>TNF-α,</em> a 4.7-fold increase in mRNA expression of <em>IL 6</em> and a 3.8-fold increase in mRNA expression of <em>MCP-1</em> in obese group compared to the lean group. Mean fasting serum insulin levels were 16.07 ± 8.39 μIU/mL in the lean group and 27.11 ± 4.91μIU/mL in the obese group (p = 0.001). Mean TAS level was 5.39 ± 2.28 μM Trolox Equivalents in the obese group and 3.85 ± 3.33 μM Trolox Equivalents in the lean group (p = 0.001).</p></div><div><h3>Conclusion</h3><p>Inflammation and OS is higher in obese patients of T2DM compared to lean patients of T2DM. This could be the result of excess adipokines production or resistance to the anti-inflammatory effects of insulin with multiple explanations. Our study suggests a difference in the pathogenic mechanism in lean patients when compared with obese T2DM patients.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100042"},"PeriodicalIF":0.0,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000091/pdfft?md5=2e3946877a417680f5fe6aa05f36b5b2&pid=1-s2.0-S2949688824000091-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140816625","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":"Corrigendum to “Advances in RNA cancer therapeutics: New insight into exosomes as miRNA delivery” [Aspect. Mol. Med. 1 (2023) 100005]","authors":"Luca Volpini ,&nbsp;Federica Monaco ,&nbsp;Lory Santarelli ,&nbsp;Jiri Neuzil ,&nbsp;Marco Tomasetti","doi":"10.1016/j.amolm.2024.100041","DOIUrl":"https://doi.org/10.1016/j.amolm.2024.100041","url":null,"abstract":"","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100041"},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294968882400008X/pdfft?md5=f88de81285365cf1afb22ce153b03c0d&pid=1-s2.0-S294968882400008X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140619463","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":"In silico drug discovery: Unveiling potential targets in Plasmodium falciparum","authors":"R. Murugesan,&nbsp;B. Kaleeswaran","doi":"10.1016/j.amolm.2024.100038","DOIUrl":"https://doi.org/10.1016/j.amolm.2024.100038","url":null,"abstract":"<div><h3>Objective</h3><p>Malaria, the plasmodium parasite, which causes and affects nearly half of the world's population, is the biggest human health issue. Malaria results in an annual death toll ranging from 1.2 to 2.7 million worldwide. Consequently, there is a pressing need for novel active ingredients with targeted effects to curb the worldwide spread of malaria.</p></div><div><h3>Methods</h3><p>This research is to explore innovative pharmacological molecules and employ bioinformatics methods (<em>in silico</em>) for the development of effective anti-malarial drugs. As part of the newest research into antimalarial chemicals, our study found seven drug combinations from different databases that showed drug-like properties and strong antimalarial activity <em>in silico</em>.</p></div><div><h3>Results</h3><p>The hexokinase-1 protein (PDB: <span>1CZA</span><svg><path></path></svg>) was docked with dioncophyllin-A, hugorosenone, marmesine, oxyprotostemonin, pachyrrhizin, plumbagin, and stemocurtisin. Among the pachyrrhizin compounds, the one with the highest docking score (−9.9 kcal/mol) was directed towards the 1CZA protein. Through superimposing the target and template structures, the active centres of the hexokinase I protein were identified, revealing structurally identical folds and undoubtedly conserved active sites. The SWISS-ADME tool was used to check how well the drug candidates were absorbed, distributed, broken down, and flushed out of the body (ADME).</p></div><div><h3>Conclusions</h3><p>In summary, our research identifies pachyrrhizin as a as a potential anti-malarial drug combination with strong <em>in silico</em> activity. We've elucidated their interaction with the hexokinase-1 protein and assessed their favourable pharmacokinetic properties. These findings represent a significant step toward developing effective treatments for malaria, emphasizing the importance of further experimental validation and clinical studies.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100038"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000054/pdfft?md5=50376b42a51241b43eebef812cef9138&pid=1-s2.0-S2949688824000054-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140344688","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":"Expression of hTERT and Lp-PLA(2) genes is increased in primary hypothyroidism.","authors":"Seema Garg ,&nbsp;Parul Gupta ,&nbsp;Satyam Wahi ,&nbsp;Mohit Mehndiratta ,&nbsp;S.V. Madhu ,&nbsp;Edelbert Almeida ,&nbsp;Rajarshi Kar","doi":"10.1016/j.amolm.2024.100040","DOIUrl":"https://doi.org/10.1016/j.amolm.2024.100040","url":null,"abstract":"<div><h3>Objective</h3><p>Sightly low serum free T4 levels are associated with longer life expectancy. However, hypothyroidism is associated with increased risk of inflammation and vascular complications. Therefore, relation of thyroid hormones (THs) with life expectancy seems to be complex. This study was carried out in an effort to understand the contribution of THs in inflammation and aging.</p></div><div><h3>Methodology</h3><p>15 cases of treatment naïve primary hypothyroidism and 15 age and sex matched euthyroid controls were recruited. mRNA expression of Telomerase (<em>hTERT</em>), leucocyte telomere length (LTL) and Lipoprotein associated phospholipase A2 (<em>Lp-PLA2</em>), a marker of vascular inflammation and risk predictor of cardiovascular events were measured by qPCR in whole blood.</p></div><div><h3>Result</h3><p>Expression of <em>hTERT</em> was found to be 6.95 times higher in the cases as compared to the controls. mRNA expression of <em>Lp-PLA(2)</em> was also 3.3 times higher in cases. LTL in euthyroid was approximately 81% of the length in hypothyroid patients.</p></div><div><h3>Conclusion</h3><p>A higher expression of <em>hTERT</em> indicates that hypothyroidism confers better cell survival in peripheral leucocytes inspite of the presence of vascular inflammation. However causal relationship cannot be ascertained with these results.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100040"},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000078/pdfft?md5=3fa9276642811680b0150755334a89ee&pid=1-s2.0-S2949688824000078-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140328049","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":"A canine mastocytoma with oncogenic c-kit activation by intra-exonic alternative splicing","authors":"Mengrui Li ,&nbsp;Stephanie Vanegas ,&nbsp;Mia R. Gonzalgo ,&nbsp;Joseph A. Lacret ,&nbsp;Wensi Tao ,&nbsp;Sapna Deo ,&nbsp;Sylvia Daunert ,&nbsp;Jean-Marc Zingg","doi":"10.1016/j.amolm.2024.100039","DOIUrl":"10.1016/j.amolm.2024.100039","url":null,"abstract":"<div><p>We report a subcutaneous mastocytoma in a mid-aged Italian greyhound dog with a small 41 bp genomic deletion of the c-kit gene leading to skipping of the authentic 3′-splice junction of intron 10. The shift to an alternative splice junction in exon 11 leads to a mis-spliced in-frame mRNA transcript with a 27 bp deletion of exon 11 coding for 9 amino acids in the juxtamembrane negative regulatory domain of c-kit tyrosine kinase. In the tumor, c-kit was activated as revealed by more pronounced c-kit-regulated signaling by the PI3K/Akt and G-coupled receptor pathways. The same 9 amino acids deletion was reported in several human gastrointestinal stromal tumors (GIST) pointing to a remarkable similarity of c-kit activation by small deletions and aberrant splicing in humans and dogs, independent of exact sequence context, tumor type and location. Interestingly, the alternative splice junction in exon 11 has been conserved in <em>Primates</em> but less in other <em>Orders</em> with increased body temperature such as ruminants. We hypothesize that elevated body temperature has acted as evolutionary pressure to eliminate the alternative splice site at this hotspot. At a molecular level, hyperthermia may increase the frequency of small deletions in the c-kit gene by facilitating base slipping or hindering repair. An RT-qPCR assay was developed to detect c-kit alternative splicing in tumors and cell lines exposed to hyperthermia. The molecular mechanisms of tumorigenesis are discussed.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100039"},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000066/pdfft?md5=157b42b40eb4a5bfe28ab4284d909c1f&pid=1-s2.0-S2949688824000066-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140403654","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}