Human Gene最新文献

{"title":"Distinguishing between founder and host population mtDNA lineages in the Ashkenazi population","authors":"Joseph Livni ,&nbsp;Karl Skorecki","doi":"10.1016/j.humgen.2025.201445","DOIUrl":"10.1016/j.humgen.2025.201445","url":null,"abstract":"<div><div>The size of the founding generation of founder populations is typically small. For example, studies estimate the Ashkenazi Jewish founder generation at around 150 families. Research has suggested that only a third of the original mitochondrial DNA (mtDNA) signatures survived. Unlike isolated populations, founder groups surrounded by larger populations tend to absorb mtDNA from the host population. A prior study reported that a significant portion of Ashkenazi Jews carry mtDNA of ancient European origin, leading to the hypothesis that the female founders were primarily European, while male founders were Near Eastern.</div><div>This study presents a method to distinguish between founder and absorbed mtDNA lineages in contemporary Ashkenazi Jews. Adjusting the sample size, absorbed lineages appear as singletons, while founder lineages show multiple occurrences. Our analysis found that less than 15 % of current Ashkenazi Jews carry absorbed mtDNA, consistent with patterns seen in many founder populations, where absorbed matrilineal lineages outnumber founder ones. However, this does not support a non-Jewish European origin for the founding generation.</div><div>Given that Y-chromosome analysis already confirms a Near Eastern origin for Ashkenazi paternal lineages, we propose that both maternal and paternal lineages share a common Near Eastern ancestry. This challenges the convoluted hypothesis of a mixed origin with Near Eastern paternal and predominantly European maternal founders. Our results reinforce the genetic evidence of a unified founding population and strongly favor a straightforward model consisting of a Near Eastern origin for both maternal and paternal founding lineages,</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201445"},"PeriodicalIF":0.5,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556693","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":"Influence of metformin on the expression of SESTRIN2, Nrf2, and TUG1 genes in the liver tissue of diabetic rats","authors":"Roya Zanganeh ,&nbsp;Hamed Fanaei ,&nbsp;Anis saadatmand ,&nbsp;Ali dashtkar ,&nbsp;Mohsen Saravani","doi":"10.1016/j.humgen.2025.201434","DOIUrl":"10.1016/j.humgen.2025.201434","url":null,"abstract":"<div><h3>Background</h3><div>This study, focusing on the role of metformin in reducing oxidative stress, examined the effects of this drug on the expression of stress-related genes SESTRIN2, Nrf2, and TUG1 in the liver of diabetic rats.</div></div><div><h3>Methods</h3><div>Animals (<em>n</em> = 30) were divided into four groups: a control group (C), a control group treated with metformin (400 mg/kg/day) (C + M), a diabetic group (D), and a diabetic group treated with metformin (D + M) (400 mg/kg/day). Streptozotocin (STZ) was injected to induce diabetes. Serum levels of fasting blood glucose (FBG), triglycerides (TG), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL<img>C), total cholesterol (TC), and insulin were measured. Gene expression was assessed using the RT-PCR technique.</div></div><div><h3>Results</h3><div>The expression levels of Nrf2 and SESTRIN2 were decreased in group D compared to groups C and C + M but were not statistically significant (<em>p</em> &gt; 0.05). However, the expression of Nrf2 and SESTRIN2 was increased in group D + M compared to group D, but only for Nrf2 was it significant (<em>p</em> = 0.0164). In addition, the expression of Nrf2 was significantly increased in group D + M compared to group C (<em>p</em> = 0.0299). The expression of TUG1 was increased in group D compared to group C, while the D + M group (1.36 ± 0.43) showed a decrease in TUG1 expression compared to group D (3 ± 1.64), which was not statistically significant. In addition, MET reduced the insulin resistance index, FBG, and lipid profile in the D + M group compared to the D group.</div></div><div><h3>Discussion</h3><div>Metformin suppresses oxidative stress by activating antioxidant pathways through increasing NRF2 gene expression, thereby improving diabetes and playing a protective role in the liver.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201434"},"PeriodicalIF":0.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556692","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":"miR-151 in health and disease: A comprehensive review of its implications in Cancer, diabetes, and more","authors":"Pourya Ahmadi ,&nbsp;Fatemeh Eizadifard ,&nbsp;Parsa Pahlavan ,&nbsp;Majid Tafrihi","doi":"10.1016/j.humgen.2025.201443","DOIUrl":"10.1016/j.humgen.2025.201443","url":null,"abstract":"<div><h3>Background</h3><div>MicroRNAs (miRNAs) are key post-transcriptional regulators involved in numerous physiological and pathological processes.</div></div><div><h3>Purpose</h3><div>This review focuses on miR-151, a functionally versatile miRNA, and synthesizes current evidence regarding its involvement across a spectrum of human diseases.</div></div><div><h3>Main findings</h3><div>miR-151 has been shown to play a dual role as both an oncogene and a tumor suppressor, depending on the cellular context and disease type. Its dysregulation has been implicated in the development and progression of various conditions, including multiple cancers, diabetes, osteoarthritis, cardiovascular disorders, intracranial aneurysms, and male infertility. Through modulation of target genes and signaling pathways, miR-151 influences cell proliferation, migration, apoptosis, and epithelial–mesenchymal transition. Importantly, its tissue-specific expression and regulatory dynamics underscore its potential as a diagnostic biomarker and therapeutic target.</div></div><div><h3>Conclusion</h3><div>By compiling and analyzing current research, this review aims to clarify the multifaceted roles of miR-151 in disease pathogenesis and to encourage further studies that may support its translational application in precision medicine.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201443"},"PeriodicalIF":0.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514197","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":"Potential of micro-RNAs 193a-3p, 378-3p, 210-3p, and 362-3p as serum biomarkers for clear cell renal cell carcinoma","authors":"Benedikt Ewig ,&nbsp;Thomas Büttner ,&nbsp;Glen Kristiansen ,&nbsp;Doris Schmidt ,&nbsp;Jörg Ellinger ,&nbsp;Stefan Hauser","doi":"10.1016/j.humgen.2025.201444","DOIUrl":"10.1016/j.humgen.2025.201444","url":null,"abstract":"<div><h3>Objective</h3><div>MicroRNAs (miRs) play a significant role in carcinogenesis and tumor progression, suggesting their potential as biomarkers. This study aimed to evaluate the diagnostic utility of four circulating miRs in patients with clear cell renal cell carcinoma (ccRCC).</div></div><div><h3>Methods</h3><div>Serum expression levels of miR-193a-3p, miR-378-3p, miR-210-3p, and miR-362-3p were quantified in 30 patients with clear cell renal cell carcinoma (ccRCC) and 15 non-tumor controls using real-time polymerase chain reaction. Mann–Whitney <em>U</em> tests and Receiver Operating Characteristics with Area under the curve (AUC) calculations were employed to evaluate the association between miR expression levels and patient group (ccRCC versus controls).</div></div><div><h3>Results</h3><div>Statistically significant differences in mean serum levels of miR-193a-3p and miR-378-3p were observed between ccRCC patients and controls. The median miR-193a-3p level was increased in ccRCC patients (median: 4.50 %, IQR: 1.38, 11.47) compared to controls (median: 2.57 %, IQR: 0.27, 3.87), <em>p</em> = 0.032; AUC for ccRCC detection was 0.70. Also, the median miR-378-3p level was higher in ccRCC patients (median: 2.01 %, IQR: 1.00, 3.33) compared to controls (median: 0.66 %, IQR: 0.44, 1.98), <em>p</em> = 0.049. AUC was 0.68. No significant differences were found for serum miR-362-3p and miR-210-3p expression in ccRCC patients and non-tumor controls (<em>p</em> = 0.547 for miR-362-3p and <em>p</em> = 0.791 for miR-210-3p).</div></div><div><h3>Conclusion</h3><div>These findings suggest that miR-193a-3p and miR-378-3p may have limited potential as diagnostic biomarkers for ccRCC. The data do not support further investigation of miR-362-3p and miR-210-3p for this purpose.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201444"},"PeriodicalIF":0.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490532","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":"Comparing DNA damage in fresh versus frozen blood from healthy individuals and patients with obesity in Egypt","authors":"Peter S.F. Erian ,&nbsp;Rania M.A. Abdel Kader ,&nbsp;Safinaz E. Eltoukhy","doi":"10.1016/j.humgen.2025.201441","DOIUrl":"10.1016/j.humgen.2025.201441","url":null,"abstract":"<div><div>The use of alkaline comet assay has increased in DNA damage assessment in various non-communicable diseases and epidemiological studies, which, in turn, requires a large sample size. Our objective is to compare the damage of DNA using comet assay in healthy individuals versus patients with obesity and to evaluate the feasibility of using frozen whole blood samples as a simple solution for the need for large sample size. Based on this study and previous literature, using frozen whole blood samples in the comet assay technique is a simple and feasible approach that can be readily applied in biomonitoring and epidemiological studies. Furthermore, this study compared comet tail length in healthy individuals and patients with obesity, revealing greater DNA damage in patients with obesity samples, which denotes a higher risk of mutations, chromosomal abnormalities, and cancer. Further enhancements and validation are recommended for technique improvement, and further studies of DNA damage in various non-communicable diseases, including obesity, are also recommended.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201441"},"PeriodicalIF":0.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471864","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":"βS haplotypes: Genetic profile and association with biochemical parameters in individuals with Sickle cell anemia in Western Bahia, Brazil","authors":"Ilana Luize Rocha Santana ,&nbsp;Raphael Magalhães ,&nbsp;Victoria Simões Bernardo ,&nbsp;Manoel Ferreira de Magalhães Filho ,&nbsp;Pâmela Lourdes Pereira da Silva ,&nbsp;Larissa Paola Rodrigues Venancio","doi":"10.1016/j.humgen.2025.201438","DOIUrl":"10.1016/j.humgen.2025.201438","url":null,"abstract":"<div><div>Sickle cell anemia (SCA) is a hemoglobinopathy with a heterogeneous clinical presentation that, in part, results from complex interactions between genetic factors, some of which are explained by haplotypes in the β-globin (β^S) gene cluster. This study identified the main haplotypic profiles of individuals with SCA in Western Bahia, Brazil, and evaluates the possible relationship between the genetic profile associated with haplotype inheritance and clinical follow-up parameters presented by the individuals participating in the study. The Bantu/Benin genotype was more frequent, although it did not show a statistically significant difference compared to the Bantu/Bantu genotype. As described in other locations in Brazil, the Bantu chromosome was the most frequent in this study (59 %), which supports the data on the formation and dynamics of the population concerning the geographical origin of the enslaved Africans trafficked to the capital of Western Bahia. Important hematological parameters, such as HbF, biochemical parameters associated with the hemolysis process, and phenotype severity, such as lactate dehydrogenase, aspartate aminostransferase, and direct bilirubin, were related to the Bantu/Bantu genotype. HbF levels were 4× lower, and biochemical parameters were up to 2.5× higher in Bantu/Bantu individuals who did not use hydroxycarbamide (HC) compared to carriers of the Bantu/Bantu genotype who used HC. The results indicate the importance of assessing the inheritance of β^S-haplotypes to help understand the phenotype and the relevance of HC use in the context of SCA.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201438"},"PeriodicalIF":0.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322953","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":"Genetic expression of NKX2-5 gene among first trimester pregnancy loss","authors":"Muraleedharan Santhamma Dhanya ,&nbsp;Selvaraj Karthick ,&nbsp;Reba Babu Alex ,&nbsp;Anandhi Dhanavel ,&nbsp;Shaiju Basheer ,&nbsp;Sreeja Sreenivasan ,&nbsp;Rajitha Puthiya Purayil ,&nbsp;Divakaran Dinesh Roy","doi":"10.1016/j.humgen.2025.201439","DOIUrl":"10.1016/j.humgen.2025.201439","url":null,"abstract":"<div><div>First-trimester pregnancy loss is a serious public health problem, affecting both physical and mental well-being. Occurring in 10–15 % of clinically recognized pregnancies, it remains a critical issue in reproductive health. Genetic factors impacting fetal development and maternal inflammatory responses are linked to early pregnancy loss. This case-control study included 120 participants: 60 cases (including maternal samples for evaluating inflammatory markers and their products of conception or terminated fetuses without normal cardiac activity or suspected congenital heart defects for the evaluation of NKX2–5 gene expression) and 60 healthy mothers having one or two live children without any congenital heart defects as controls. Inflammatory markers CRP and IL-6 were measured using ELISA kits. Gene expression of NKX2–5 was quantified by real-time PCR after RNA extraction from products of conception or terminated fetuses, cDNA synthesis, and amplification using specific primers. Relative expression was calculated using the 2^(-ΔΔCt) method. The findings revealed significantly higher CRP and IL-6 levels in cases than controls (<em>p</em> &lt; 0.001) and changes in NKX2–5 expression. The results indicate a significant increase in NKX2–5 expression in products of conception from women with early pregnancy loss compared to those with healthy pregnancies (<em>p</em> &lt; 0.05). Increased maternal levels of TSH were also revealed to be an independent predictor for early abortion (OR = 3.57, <em>p</em> = 0.004). Our findings suggest that NKX2–5 gene deregulation and inflammation in the maternal compartment can play a role in early pregnancy loss as future candidate targets for both diagnostic and treatment intervention.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201439"},"PeriodicalIF":0.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335986","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":"Autophagy protein 5 (ATG5) rs573775 protects Malaysian Malay women from systemic lupus erythematosus","authors":"Hwa Chia Chai,&nbsp;Kek Heng Chua","doi":"10.1016/j.humgen.2025.201435","DOIUrl":"10.1016/j.humgen.2025.201435","url":null,"abstract":"<div><h3>Objective</h3><div>Autophagy is one of the critical cellular processes implicated in the pathogenesis of SLE. Polymorphisms in the autophagy-related genes have been associated with increased susceptibility to SLE, particularly variations in the autophagy protein 5 (<em>ATG5</em>) gene which has been associated with SLE in several populations. This case-control study aimed to investigate the association between polymorphisms in <em>ATG5</em> and SLE in Malaysian population.</div></div><div><h3>Methods</h3><div>Tetra primer amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) was performed to genotype <em>ATG5</em> rs6937876, rs4945747, rs573775, rs2245214 and rs548234 in 233 SLE patients and 224 healthy controls, collected from 2000 to 2015.</div></div><div><h3>Results</h3><div>In the overall Malaysian population, AG genotype (adjusted <em>p</em> = 0.013, OR = 1.327, 95 % CI: 1.040 to 1.695) of rs6937876 were significantly associated with increased SLE susceptibility. The dominant model (AG + AA) (adjusted <em>p</em> = 0.006, OR = 0.671, 95 % CI: 0.464 to 0.972), additive model (adjusted <em>p</em> = 0.005, OR = 0.462, 95 % CI: 0.291 to 0.733), and minor A allele (adjusted <em>p</em> = 0.007, OR = 0.628, 95 % CI: 0.447 to 0.882) of rs573775 significantly associated with Malay population by providing protection against SLE.</div></div><div><h3>Conclusion</h3><div>The SNPs in <em>ATG5</em> seem to not only conferring SLE susceptibility to the Malaysian population but also protect them from SLE. Gene expression of these SNPs and their interactions with upstream or downstream genes and microenvironment in the Malaysian population, especially Malays, is worth further study.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201435"},"PeriodicalIF":0.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471863","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":"A study conducted in breast cancer cells found that (valproic acid) inhibits CIP2A/c-MYC/PI3K/Akt/mTOR signaling molecules and PD-L1","authors":"Elahe Zeinali ,&nbsp;Vahid Bagheri ,&nbsp;Esmaeil Rostami ,&nbsp;Gholamreza Anani Sarab","doi":"10.1016/j.humgen.2025.201437","DOIUrl":"10.1016/j.humgen.2025.201437","url":null,"abstract":"<div><div>Resistant cells significantly undermine the efficacy of breast cancer treatment. CIP2A and PD-L1 are among the major therapeutic challenges in breast cancer, as they are key drivers of drug resistance and immune evasion, respectively. Hence, identifying agents—particularly epigenetic drugs—that can suppress these factors by altering gene expression is of great interest. This study aimed to evaluate the molecular mechanisms and effects of valproic acid (VPA), a histone deacetylase inhibitor, on CIP2A and PD-L1 expression in the MCF-7 breast cancer cell line. VPA inhibited MCF-7 cell proliferation in a dose- and time-dependent manner. Treatment with VPA resulted in downregulation of CIP2A and its downstream signaling molecules c-MYC, PI3K, AKT, and mTOR. Moreover, VPA treatment reduced PD-L1 expression in MCF-7 cells. These findings suggest that VPA may offer a novel approach to addressing challenges associated with CIP2A and PD-L1. Therefore, either as a monotherapy or in combination with existing treatments, VPA could represent a promising strategy for enhancing the efficacy of breast cancer therapy.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201437"},"PeriodicalIF":0.5,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471865","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":"Systematic identification of molecular biomarkers and drug candidates targeting MAPK3 in multiple sclerosis","authors":"Bilal Khan,&nbsp;Ruqia Sartaj,&nbsp;Muhammad Rahiyab,&nbsp;Syed Shujait Ali,&nbsp;Zahid Hussain,&nbsp;Ishaq Khan,&nbsp;Arshad Iqbal","doi":"10.1016/j.humgen.2025.201436","DOIUrl":"10.1016/j.humgen.2025.201436","url":null,"abstract":"<div><div>Multiple sclerosis (MS) exists as a persistent autoimmune illness affecting the central nervous system because it produces demyelination and injures axons, besides causing CNS neuroinflammation. Research advances into MS pathophysiology have not solved the complexity of treating this condition. The research examined both vital MS-related molecular biomarkers as well as therapeutic possibilities through computational methods. GEO2R analyzed the gene expression dataset <span><span>GSE17393</span><svg><path></path></svg></span>, which reported that MS patients had differentially expressed genes than healthy controls. The biological processes involved in MS became clearer with the help of functional enrichment analyses, which contained both GO and KEGG pathway analysis. The STRING database enabled the construction of a PPI network, followed by hub gene identification through the CytoHubba application. The study revealed MAPK3 as the most influential hub gene essential for MS pathophysiological processes. Scientists used the Robetta server to forecast MAPK3's 3D structure, which they then optimized in Galaxy Refine before carrying out structural quality tests. Lab simulation using PyRx showed that potential medications such as Hypericin, Yibeissine, and Physalin F effectively bind with the MAPK3 protein. Among the compounds, Hypericin achieved the best binding affinity of −10.7 kcal/mol toward MAPK3, as Yibeissine and Physalin F reached −10.0 kcal/mol binding levels. MD simulations tested the stability of all MAPK3-ligand complex structures. The combination of ADME testing demonstrated that Yibeissine possessed ideal drug absorption features with strong blood-brain barrier penetration alongside good gastrointestinal absorption, yet Hypericin showed poor oral availability. The ProTox-II analysis revealed that the substance Hypericin presented major risks for mutation and cancer development, although Physalin F significantly damaged the human immune system. Current research indicates MAPK3 inhibition represents a promising treatment approach for MS, since Yibeissine stands out as the best drug candidate because it possesses an ideal ADME profile and low toxicity risks.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201436"},"PeriodicalIF":0.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299018","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}