Human Gene最新文献

{"title":"Assessment of the PCR inhibitory effect of the hair dye constituents and its role in forensic DNA analysis","authors":"Hirak Ranjan Dash ,&nbsp;Vaishnavi Gupta ,&nbsp;Dnyaneshwar Tanpure ,&nbsp;Braja Kishore Mohapatra","doi":"10.1016/j.humgen.2025.201471","DOIUrl":"10.1016/j.humgen.2025.201471","url":null,"abstract":"<div><div>Hair is among the most frequent types of biological evidence recovered at crime scenes, playing a crucial role in identifying culprits. Often, the recovered hair samples are dyed with various routinely used hair dyes. A survey of 182 individuals showed that the majority (82 %) of individuals dye their hair frequently, at least once a month. Cetearyl alcohol, propylene glycol, and disodium EDTA are the most common ingredients of the commercially available hair dyes. <em>In-silico</em> analysis predicted that the citric acid component of hair dye has the strongest affinity with Taq Polymerase (−6.1 Kcal/mol), followed by ascorbic acid (−5.5 Kcal/mol), resorcinol (−5.0 Kcal/mol), trisodium EDTA (−4.8 Kcal/mol), phosphoric acid (−4.0 Kcal/mol), glycerin and cetyl alcohol (−3.7 Kcal/mol), propylene glycol (−3.5 Kcal/mol), ethanolamine (−3.0 Kcal/mol) and hydrogen peroxide (−2.9 Kcal/mol). Molecular docking studies further revealed that the residues of arginine, threonine, glutamine, lysine, threonine, asparagine, serine, aspartic acid, phenylalanine, leucine, methionine, and tryptophan are the responsible motifs of Taq Polymerase which bind with different hair dye chemical constituents. In a singleplex PCR, the <em>CYCLO</em> gene was amplified only in the presence of cetyl alcohol, glycerin, and ethanolamine. All 23 STR markers were amplified using the Fusion 6C kit in the presence of hair dyes. However, the dye constituents adversely affected the Locus Balance of the STR profiles. Thus, most of the hair dye components act as potential PCR inhibitors by interacting with Taq Polymerase and suitable mitigation strategies should be employed for such forensic biological samples.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201471"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917761","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":"Altered expression patterns of lncRNA MEG3 and LINC01611 in patients with colorectal cancer","authors":"Niloofar Faraji ,&nbsp;Mohammad Almasi ,&nbsp;Majid Mirmazloumi ,&nbsp;Nasim Padasht ,&nbsp;Sahand Sadat Mansouri ,&nbsp;Fatemeh Ghaderibarmi ,&nbsp;Haniyeh Royatpour ,&nbsp;Fatemeh Modaresi ,&nbsp;Kourosh Kazempour Samak ,&nbsp;Fahimeh Abedini Bajgiran ,&nbsp;Tahereh Zeinali ,&nbsp;Narges Eslami ,&nbsp;Dariush Shanehbandi ,&nbsp;Ali Salehzadeh","doi":"10.1016/j.humgen.2025.201470","DOIUrl":"10.1016/j.humgen.2025.201470","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a major global health challenge, with long non-coding RNAs (lncRNAs) gaining attention as potential diagnostic biomarkers. This study aimed to experimentally validate bioinformatics findings on the expression patterns of maternally expressed gene 3 (MEG3) and LINC01611 in CRC patients from a specific ethnic population while considering associated risk factors. This in vitro study initially recruited 50 patients from a single ethnic group, with 48 completing the analysis after the exclusion of two samples. Two lncRNAs, MEG3 and LINC01611, were selected using Gene Expression Omnibus (GEO) microarray data and identified via R/BioConductor. Paired tissue samples (tumor and adjacent margins) were collected during surgery, and RNAs were extracted. Demographic and clinical data of patients were recorded, and gene expression was analyzed using quantitative real-time PCR (qPCR), with GAPDH as the internal control. Data analysis was performed using GraphPad Prism and SPSS software, with the significance level set at <em>P</em> &lt; 0.05. The mean age of the patients was 59.5 ± 3.53 years, with 58.3 % (<em>n</em> = 28) being male, and 37.5 % of the patients had a history of smoking. The majority of patients had poorly differentiated (41.7 %) and stage II tumor (43.8 %), with lymph node metastasis commonly observed (60.4 %). The Wilcoxon signed-rank test revealed significant downregulation of MEG3 (32.396 fold change)and LINC01611(38.923 fold change) in tumor tissues compared to adjacent margins. A family history of CRC was associated with higher expression levels of MEG3 (1.48-fold, <em>P</em> = 0.038) and LINC01611 (1.03-fold, <em>P</em> = 0.007) in both tumor and margin tissues. Multivariable regression analysis demonstrated that lncRNAs had a significant association with tumor differentiation (<em>P</em> &lt; 0.05), while other variables showed no statistically significant association (<em>P</em> &gt; 0.05). Also, positive correlations were observed between MEG3 and LINC01611 expression levels in tumor (<em>r</em> = 0.649, <em>P</em> &lt; 0.001) and margin (<em>r</em> = 0.424, <em>P</em> = 0.003) tissues. The significant downregulation of MEG3 and LINC01611 in tumor tissues compared to adjacent margin tissues highlights their potential role as tumor suppressors in CRC. These findings support further investigation into these lncRNAs as diagnostic biomarkers.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201470"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931728","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":"The interplay between IL-18 rs1946518 polymorphism, TSH dysregulation, and vitamin D3 deficiency in Hashimoto's thyroiditis","authors":"Noor Al-Huda Saber Sadiq,&nbsp;Dhifaf Zeki Aziz","doi":"10.1016/j.humgen.2025.201465","DOIUrl":"10.1016/j.humgen.2025.201465","url":null,"abstract":"<div><h3>Background</h3><div>Hashimoto's thyroiditis (HT) is an autoimmune thyroid disorder shaped by both genetic predisposition and environmental influences. One gene of growing interest is interleukin-18 (IL-18), particularly its rs1946518 (T/G) promoter polymorphism, which may affect inflammatory responses. Meanwhile, vitamin D3 has emerged as a key immunomodulatory factor, yet its interaction with genetic markers in HT remains unclear.</div></div><div><h3>Objective</h3><div>The primary objective of this study was to examine the potential role of the IL-18 gene promoter polymorphism (rs1946518, T/G) in the development of Hashimoto's thyroiditis (HT) among Iraqi patients. The investigation focused on whether this genetic variation affects serum IL-18 levels and contributes to immune and endocrine disturbances commonly observed in HT, including altered levels of thyroid-stimulating hormone (TSH), vitamin D3, and thyroid-specific autoantibodies (anti-TPO and anti-Tg). To further explore the functional implications of IL-18 in the disease process, molecular docking analysis was conducted to evaluate the potential interaction between IL-18 and active vitamin D3 [1,25(OH)₂D₃], aiming to examine the potential molecular interaction how vitamin D may modulate inflammatory responses in HT.</div></div><div><h3>Methods</h3><div>A total of 100 participants were included in a case-control design: 60 patients with HT and 40 matched health controls. Genotyping for rs1946518 was performed using Tetra-ARMS PCR. Serum levels of IL-18, 25(OH)D₃, TSH, anti-TPO, and anti-Tg were measured. Statistical comparisons and molecular docking analyses were conducted to understand both genetic and biochemical patterns.</div></div><div><h3>Results</h3><div>Carriers of the G allele showed significantly higher IL-18 levels, elevated TSH and autoantibodies, and lower vitamin D3 compared to TT/TG genotypes. Newly diagnosed patients had the highest IL-18 and lowest vitamin D3 concentrations. Molecular docking indicated a stable interaction between IL-18 and 1,25(OH)₂D₃, suggesting vitamin D might directly influence IL-18 function.</div></div><div><h3>Conclusion</h3><div>The <em>IL-18</em> rs1946518 G allele may predispose individuals to stronger inflammatory activity in HT, while concurrent vitamin D3 deficiency could amplify this response.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201465"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867063","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":"Estimating drivers of breast tissue transitions from normal to tumor state","authors":"Swapnil Kumar,&nbsp;Vaibhav Vindal","doi":"10.1016/j.humgen.2025.201506","DOIUrl":"10.1016/j.humgen.2025.201506","url":null,"abstract":"<div><div>Tumor tissues are characterized by dysregulated gene expression patterns leading to altered cellular pathways and molecular functions as a result of their transition from normal to tumor state. Further, tumor-adjacent normal tissues (TANTs), utilized as a control in cancer research, are not molecularly normal and differ from healthy normal tissues. These TANTs represent a distinctive transitional state between normal and tumor states. However, the mechanism underlying this state transition, expression dysregulation, and perturbed regulation remain largely unexplored and elusive. Herein, the transitions of breast tissues from normal and TANT to tumor states were modeled using gene expression and regulation data to estimate key drivers underlying these transitions. As a result, we identified 645 shared driver genes underlying the transitions of breast tissues from the healthy normal state to the adjacent normal and tumor states. Besides, we identified 635 shared driver genes underlying the transitions of TANTs to different subtypes. When we intersected both lists of shared driver genes, 615 commonly shared driver genes across the state transitions were observed. Subsequently, functional annotations of these driver genes revealed their involvement in cell growth and maintenance-related activity. Additionally, key pathways associated with cancer pathogenesis, such as Wnt signaling, Notch signaling, NF-kappa B signaling, and PD-L1 expression and PD-1 checkpoint pathway in cancer, were found significantly enriched with these shared driver genes. Thus, the shared driver genes identified across tissue transitions provide ways forward to devise more efficient diagnostic and therapeutic strategies for early and effective disease management.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201506"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465897","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":"Transcription Factor driven gene regulation in Autism Spectrum Disorder","authors":"Nimisha Ghosh ,&nbsp;Walter Arancio ,&nbsp;Tariq Al Jabry ,&nbsp;Raya Al Maskari ,&nbsp;Daniele Santoni","doi":"10.1016/j.humgen.2025.201489","DOIUrl":"10.1016/j.humgen.2025.201489","url":null,"abstract":"<div><div>Autism Spectrum Disorders (ASD) encompass a group of neurodevelopmental disorders in which an affected individual faces challenges in social interaction and communication, along with restricted and repetitive stereotypic behavioral patterns and interests. In this work, we have studied the differential gene regulation between patients and controls, mediated by Transcription Factors (TFs), of key genes involved in ASD. Nine and seven TFs have been identified as potential regulators of the set of syndromic and non-syndromic key high confident genes retrieved by the Simons Foundation Autism Research Initiative (SFARI) database. We have also identified significant couples of Transcription Factor - Target Gene potentially associated with an altered regulation in ASD patients. Consistently, many identified couples are involved in processes associated with brain morphogenesis and development. In this regard, this biased regulation could be the target of some experimental design in order to (1) test this hypothesis and (2) try to target this altered regulation pattern in ASD samples. In conclusion, we would like to emphasize that the present work proposes an effective and reliable computational approach that could be applied to any disease with known key genes and available gene expression data.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201489"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319598","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":"Exploring genetic associations in Parkinson's disease: The role of IL-10; −1087G>a and mir146a; rs2910164 C>G polymorphisms","authors":"Javid Ashtari Mahini ,&nbsp;Zahra Shahbazi ,&nbsp;Maryam Rahimi ,&nbsp;Maryam Seyedolmohadesin","doi":"10.1016/j.humgen.2025.201493","DOIUrl":"10.1016/j.humgen.2025.201493","url":null,"abstract":"<div><h3>Introduction</h3><div>Defining the etiology of multifactorial diseases, such as Parkinson's disease (PD), poses significant challenges in diagnosis, management, and treatment strategies. PD is characterized by progressive neurological degeneration. Current scientific evidence indicates that this condition arises from an intricate interplay of genetic and environmental factors. Notably, single nucleotide polymorphisms (SNPs) identified in various genes have been implicated in enhancing susceptibility to this disease. This study aims to investigate the association of two specific polymorphisms, <em>IL-10</em> gene; −1087 G &gt; A and <em>mir146a</em> gene<em>;</em> rs2910164 C &gt; G, with the prevalence of PD.</div></div><div><h3>Methods</h3><div>This investigation employed a case-control design that included 96 participants in both the case and control groups. The identification of alleles was executed using the Tetra-primer Amplification Refractory Mutation System-Polymerase Chain Reaction (T-ARMS-PCR) method. Subsequent genetic and statistical analyses of the findings were performed utilizing POPGENE and SPSS software.</div></div><div><h3>Result</h3><div>The results indicated that the distribution of <em>mir146a</em> gene SNPs within the control and patient populations did not adhere to Hardy-Weinberg equilibrium. Specifically, the frequency of the G allele in patients diagnosed with PD was significantly lower than that observed in the control cohort. Furthermore, individuals carrying the GC genotype exhibited an elevated risk of developing PD, with <em>p</em>-values &lt;0.05. Conversely, the distribution of <em>IL-10</em> gene SNPs conformed to Hardy-Weinberg equilibrium within both groups, and no statistically significant association was found between <em>IL-10</em> gene SNPs and the risk of PD.</div></div><div><h3>Conclusion</h3><div>The findings from this study suggest that the <em>IL-10</em> gene −1087 G &gt; A polymorphism does not contribute to increased susceptibility to PD within the studied population. Conversely, the <em>mir146a</em> gene rs2910164 C &gt; G polymorphism appears to be associated with PD risk. Notably, the G allele of this SNP correlates with a decreased risk of the disease, while the GC genotype is linked to an increased likelihood of developing Parkinson's disease.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201493"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465900","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":"Structural and functional analysis of SOX9 mutations in disorders of sex development (DSD): Integration of clinical data and in silico modeling","authors":"Fatou Diop Gueye ,&nbsp;Mama Sy Diallo ,&nbsp;Arame Ndiaye ,&nbsp;Mame Venus Gueye ,&nbsp;Ndiaga Diop ,&nbsp;Adji Dieynaba Diallo ,&nbsp;Rokhaya Ndiaye ,&nbsp;Oumar Faye","doi":"10.1016/j.humgen.2025.201461","DOIUrl":"10.1016/j.humgen.2025.201461","url":null,"abstract":"<div><div>The <em>SOX9</em> gene, located on chromosome 17q24, belongs to the <em>SOX</em> family of transcription factors and shares over 70 % homology with <em>SRY</em>. It plays a central role in testis differentiation and cartilage formation, notably by regulating key genes such as <em>AMH</em>. Mutations in <em>SOX9</em> are known to cause Disorders of Sex Development (DSD) and skeletal malformations such as campomelic dysplasia.</div></div><div><h3>Objective</h3><div>This study aimed to analyze the structural and functional impact of <em>SOX9</em> mutations identified in DSD patients, using in silico predictive tools including IntFOLD, to evaluate changes in protein conformation and correlate them with observed phenotypes.</div></div><div><h3>Methods</h3><div>Twenty-eight patients with DSD (46,XX or 46,XY karyotypes) were enrolled. The <em>SRY</em> and <em>SOX9</em> genes were amplified by PCR and sequenced. Four 46,XX patients were found to be <em>SRY</em>-positive, and two 46,XY patients were <em>SRY</em>-negative. Ten <em>SOX9</em> variants were identified in 12 patients, including two novel intronic variants, two in the 3′UTR region, three synonymous, and three non-synonymous coding variants. All variants were found in the heterozygous state, and the presence of a normal allele was used to assess its functional implications.</div></div><div><h3>Results</h3><div>Non-synonymous mutations located within the <em>HMG</em> and <em>dimerization domains</em> were predicted to be deleterious. 3D modeling using IntFOLD revealed conformational changes, altered protein stability, and disrupted ligand-binding residues. These structural alterations correlated with the DSD phenotypes observed. The overall <em>SOX9</em> structure showed a largely disordered organization, with ordered segments within key functional domains.</div></div><div><h3>Conclusion</h3><div>Our findings confirm the role of <em>SOX9</em> in the etiology of DSD and highlight the relevance of structural modeling for interpreting rare variants. The integration of clinical, genetic, and in silico data contributes to a better understanding of sex differentiation mechanisms and may support improved molecular diagnosis of DSD.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201461"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831345","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":"Evaluation of the frequency of Dectin-1 rs3901533 A > C and rs7309123 G > C gene variants in patients with acute myeloid leukemia (AML): A case-control study","authors":"Davood Alinezhad Dezfuli ,&nbsp;Ehsan Sarbazjoda ,&nbsp;Nasrin Amirrajab ,&nbsp;Tina Vosoughi ,&nbsp;Alireza Momeni ,&nbsp;Mohammad Ali Jalali Far","doi":"10.1016/j.humgen.2025.201482","DOIUrl":"10.1016/j.humgen.2025.201482","url":null,"abstract":"<div><h3>Background</h3><div>Acute myeloid leukemia (AML) is a serious blood cancer mainly affecting adults, and its predisposing genetic factors remain unclear. While recent studies have linked dectin-1 polymorphisms to fungal infection risk in AML, their relationship with AML susceptibility has not been studied. This study evaluates the association between two dectin-1 single-nucleotide polymorphisms (SNPs) of rs3901533 A &gt; C and rs7309123 G &gt; C and AML risk.</div></div><div><h3>Methods &amp; materials</h3><div>A total of 103 participants (53 AML patients and 50 age- and sex-matched healthy controls) from the Iranian population were included in this study. Both of the polymorphisms were genotyped using the tetra-ARMS-PCR method.</div></div><div><h3>Results</h3><div>The genotype distributions of rs3901533 A &gt; C and rs7309123 G &gt; C polymorphisms did not differ significantly between AML patients and controls under additive, dominant, or recessive genetic models (<em>p-value</em> &gt; 0.05). Furthermore, allele frequencies for both SNPs showed no significant association with AML risk (<em>p-value</em> &gt; 0.05). None of the genotypes or alleles increased the risk of AML (<em>p-value</em> &gt; 0.05).</div></div><div><h3>Conclusions</h3><div>Neither the rs3901533 A &gt; C nor the rs7309123 G &gt; C polymorphisms are contributors to increased susceptibility to AML. However, further investigations are needed.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201482"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265696","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":"Annexin A1 as a potential anti-inflammatory marker in diabetic foot ulcer: A cross-sectional study","authors":"Shwetha Shetty Kalladka ,&nbsp;Raushan Kumar Chaudhary ,&nbsp;Prakash Patil ,&nbsp;Praveenkumar Shetty ,&nbsp;Suchetha Kumari Nalilu ,&nbsp;Abhijith Shetty","doi":"10.1016/j.humgen.2025.201505","DOIUrl":"10.1016/j.humgen.2025.201505","url":null,"abstract":"<div><h3>Background</h3><div>Annexin A1 (AnxA1) is known to suppress inflammation by inhibiting the synthesis of pro-inflammatory molecules and promoting the release of immune-suppressive molecules. This suggests AnxA1 may be a vital marker for modulating inflammation and cell proliferation in Diabetic Foot Ulcer (DFU) patients. The current study aimed to investigate the expression and role of AnxA1 in relation to other key inflammatory molecules in DFU.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted among 40 participants (20 DFU patients and 20 healthy subjects) to evaluate the expression of AnxA1, IL-10, IL-1β, IL-6, and TNF-α from both the blood and tissue samples.</div></div><div><h3>Results</h3><div>The mean relative expression of anti-inflammatory molecules such as AnxA1 (0.507, 0.442) and IL-10 (2.273, 0.602) were found to be downregulated in tissue and blood, respectively among DFU patients compared to healthy controls. Conversely, the pro-inflammatory molecules like IL-1β (2.393, 0.988), IL-6 (0.830, 0.748), and TNF-α (1.81, 1.099) were upregulated among DFU patients compared to healthy controls. The mean relative expression of AnxA1 and IL-1β was significantly higher in tissue and blood samples respectively of gangrenous DFU compared to non-gangrenous DFU (<em>P</em> &lt; 0.05). Furthermore, AnxA1 expression showed a significant negative correlation with HbA1c and triglyceride levels (in blood and tissue) as well as wound grade and cholesterol levels (in tissue).</div></div><div><h3>Conclusion</h3><div>The relative down-expression of AnxA1 in DFU patients and its negative correlation with HbA1c, total cholesterol, and triglycerides indicate that AnxA1 has the potential to decrease inflammatory harm in DFU. These findings highlight AnxA1 as a promising target for novel therapeutic strategies against diabetic foot ulceration.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201505"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465898","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":"Genomic, transcriptomics, and epigenomic alterations in AREG gene in LUSC and HNSCC","authors":"K. Akshaya Krishnan ,&nbsp;P. Anitha ,&nbsp;J. Vijayashree Priyadharsini ,&nbsp;A. Paramasivam","doi":"10.1016/j.humgen.2025.201477","DOIUrl":"10.1016/j.humgen.2025.201477","url":null,"abstract":"<div><h3>Objectives</h3><div>Cancers of the head and neck region and lungs share similar risk factors. The increased prevalence of these two cancer types underscores the need to identify diagnostic, therapeutic, and prognostic biomarkers for their management. In this context, the present study aims to identify genetic alterations in the <em>AREG</em> gene and their possible association with HNSCC and LUSC.</div></div><div><h3>Methods</h3><div>The study employed a computational design, utilizing the following databases and tools to identify the association between disease phenotypes and genes. The cBioPortal database was used to analyze genetic alterations in the <em>AREG</em> gene across TCGA datasets for HNSCC and LUSC. The survival probability and gene expression profile were analyzed using UALCAN. Welch's test demonstrated the statistical significance between the normal and tumor tissues. The microRNA targets of <em>AREG</em> were assessed using the miRDB.</div></div><div><h3>Results</h3><div>The <em>AREG</em> gene presented with less than 1 % alteration in HNSCC and 4 % in LUSC. Interestingly, a significant upregulation of <em>the AREG</em> gene was observed in HNSCC patients, whereas downregulation was noted in LUSC. The increased gene expression profile correlated well with a poor prognosis in HNSCC patients, while low expression was associated with a good prognosis in LUSC patients. Experimental validation of OSCC samples revealed a decrease in gene expression compared to normal samples. Furthermore, the microRNAs <em>hsa-miR-1185-1</em> and <em>hsa-miR-487b</em> were identified as potential targets of <em>AREG</em>, influencing the survival of patients with HNSCC.</div></div><div><h3>Conclusions</h3><div>The overexpression of <em>AREG</em> in HNSCC, along with its poor prognosis, highlights the oncogenic role played by this gene. Interestingly, the epigenetic component, specifically microRNAs <em>hsa-miR-1185-1</em> and <em>hsa-miR-487b</em>, was found to be downregulated, suggesting their influence on AREG expression. These findings require further validation through functional studies to elucidate the association between AREG and the cancer phenotype.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201477"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109374","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}