Pub Date : 2025-11-05DOI: 10.1016/j.humgen.2025.201509
{"title":"Editorial: Application and integration of Omics data in disease biology","authors":"","doi":"10.1016/j.humgen.2025.201509","DOIUrl":"10.1016/j.humgen.2025.201509","url":null,"abstract":"","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201509"},"PeriodicalIF":0.7,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568394","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}
Pub Date : 2025-11-02DOI: 10.1016/j.humgen.2025.201508
Shubhrajit Barman , Senthil Kumar Ganesan
Background
Insulin-like growth factor II (IGF2) is an imprinted growth-regulatory polypeptide essential for embryonic development, tissue growth, and metabolic regulation. Variants in IGF2 have been implicated in cancer and metabolic disorders, yet the structural and functional impact of most nonsynonymous single-nucleotide polymorphisms (nsSNPs) remains uncharacterized.
Methods
We screened IGF2 coding variants from dbSNP using multiple pathogenicity predictors (SIFT, PolyPhen-2, PANTHER, SNPs&GO, Meta-SNP, PredictSNP, PMut) and structural assessment tools. Secondary structure alterations were analysed using Project HOPE, while protein–protein docking with HDOCK was performed to investigate interactions between IGF2 and IGF2R.
Results
Seven nsSNPs (C33R, R48L, R48C, G65D, C71R, R125H, and R125S) were consistently predicted to be deleterious. These substitutions were associated with a reduction in α-helical content and distortion of the overall secondary structure. Docking analysis further revealed that, with the exception of R48C, all variants exhibited decreased binding affinity compared to the wild-type IGF2 protein.
Conclusions
These seven nsSNPs represent high-priority candidates for functional validation, as computational evidence suggests potential destabilization of IGF2 structure and altered interaction with IGF2R. Our findings demonstrate the utility of in-silico pipelines for prioritizing gene variants for downstream experimental and clinical studies.
{"title":"Computational identification and structural characterization of deleterious non-synonymous SNPs in human IGF2","authors":"Shubhrajit Barman , Senthil Kumar Ganesan","doi":"10.1016/j.humgen.2025.201508","DOIUrl":"10.1016/j.humgen.2025.201508","url":null,"abstract":"<div><h3>Background</h3><div>Insulin-like growth factor II (IGF2) is an imprinted growth-regulatory polypeptide essential for embryonic development, tissue growth, and metabolic regulation. Variants in IGF2 have been implicated in cancer and metabolic disorders, yet the structural and functional impact of most nonsynonymous single-nucleotide polymorphisms (nsSNPs) remains uncharacterized.</div></div><div><h3>Methods</h3><div>We screened IGF2 coding variants from dbSNP using multiple pathogenicity predictors (SIFT, PolyPhen-2, PANTHER, SNPs&GO, Meta-SNP, PredictSNP, PMut) and structural assessment tools. Secondary structure alterations were analysed using Project HOPE, while protein–protein docking with HDOCK was performed to investigate interactions between IGF2 and IGF2R.</div></div><div><h3>Results</h3><div>Seven nsSNPs (C33R, R48L, R48C, G65D, C71R, R125H, and R125S) were consistently predicted to be deleterious. These substitutions were associated with a reduction in α-helical content and distortion of the overall secondary structure. Docking analysis further revealed that, with the exception of R48C, all variants exhibited decreased binding affinity compared to the wild-type IGF2 protein.</div></div><div><h3>Conclusions</h3><div>These seven nsSNPs represent high-priority candidates for functional validation, as computational evidence suggests potential destabilization of IGF2 structure and altered interaction with IGF2R. Our findings demonstrate the utility of in-silico pipelines for prioritizing gene variants for downstream experimental and clinical studies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201508"},"PeriodicalIF":0.7,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465870","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}
Glioblastoma (GBM) remains one of the most aggressive and therapy-refractory primary brain tumors, with patient survival exhibiting only marginal gains despite decades of intensive research and therapeutic advancement. Standard-of-care interventions, including maximal surgical resection, radiotherapy, and the alkylating agent temozolomide, confer only modest clinical benefit. The limited therapeutic efficacy is primarily attributed to pronounced intra- and intertumoral heterogeneity, the persistence of therapy-resistant glioblastoma stem-like cells, and the restrictive nature of the blood–brain barrier (BBB), which collectively impede durable treatment responses. These therapeutic challenges have intensified efforts to develop novel treatment strategies for glioblastoma. Recent advances in preclinical research increasingly leverage patient-derived stem cell and organoid models, which more faithfully recapitulate the molecular and phenotypic heterogeneity of human tumors and enable the identification of broadly effective therapeutic vulnerabilities. Emerging approaches include the exploration of histone deacetylase (HDAC) inhibitors, cyclin-dependent kinase (CDK) inhibitors, and other rationally designed small-molecule agents. In parallel, innovative drug delivery platforms such as nanoparticle-based formulations, convection-enhanced delivery, and focused ultrasound are being actively investigated to enhance blood–brain barrier permeability and improve intra-tumoral drug distribution.
Emerging therapeutic modalities, including immunotherapies such as immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapies, and cancer vaccines, together with oncolytic virotherapy and gene-editing technologies, are broadening the therapeutic landscape of glioblastoma. This review synthesizes current advances in preclinical and translational research, emphasizing how the convergence of personalized medicine, multi-targeted pathway inhibition, and next-generation delivery platforms may collectively enhance therapeutic efficacy and ultimately improve patient survival.
{"title":"Frontiers in glioblastoma therapy: Novel therapeutics, molecular pathways, and future clinical perspectives","authors":"Sandeep Pandey , Akanksha Dwivedi , Ranjana Singh , Nimra Habib , Dharmendra Kashyap , Vaishali Saini , Arjit Singh , Ankit Sharma , Hem Chandra Jha","doi":"10.1016/j.humgen.2025.201507","DOIUrl":"10.1016/j.humgen.2025.201507","url":null,"abstract":"<div><div>Glioblastoma (GBM) remains one of the most aggressive and therapy-refractory primary brain tumors, with patient survival exhibiting only marginal gains despite decades of intensive research and therapeutic advancement. Standard-of-care interventions, including maximal surgical resection, radiotherapy, and the alkylating agent temozolomide, confer only modest clinical benefit. The limited therapeutic efficacy is primarily attributed to pronounced intra- and intertumoral heterogeneity, the persistence of therapy-resistant glioblastoma stem-like cells, and the restrictive nature of the blood–brain barrier (BBB), which collectively impede durable treatment responses. These therapeutic challenges have intensified efforts to develop novel treatment strategies for glioblastoma. Recent advances in preclinical research increasingly leverage patient-derived stem cell and organoid models, which more faithfully recapitulate the molecular and phenotypic heterogeneity of human tumors and enable the identification of broadly effective therapeutic vulnerabilities. Emerging approaches include the exploration of histone deacetylase (HDAC) inhibitors, cyclin-dependent kinase (CDK) inhibitors, and other rationally designed small-molecule agents. In parallel, innovative drug delivery platforms such as nanoparticle-based formulations, convection-enhanced delivery, and focused ultrasound are being actively investigated to enhance blood–brain barrier permeability and improve intra-tumoral drug distribution.</div><div>Emerging therapeutic modalities, including immunotherapies such as immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapies, and cancer vaccines, together with oncolytic virotherapy and gene-editing technologies, are broadening the therapeutic landscape of glioblastoma. This review synthesizes current advances in preclinical and translational research, emphasizing how the convergence of personalized medicine, multi-targeted pathway inhibition, and next-generation delivery platforms may collectively enhance therapeutic efficacy and ultimately improve patient survival.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201507"},"PeriodicalIF":0.7,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616457","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}
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.
Methods
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.
Results
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 (P < 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).
Conclusion
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.
{"title":"Annexin A1 as a potential anti-inflammatory marker in diabetic foot ulcer: A cross-sectional study","authors":"Shwetha Shetty Kalladka , Raushan Kumar Chaudhary , Prakash Patil , Praveenkumar Shetty , Suchetha Kumari Nalilu , 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> < 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":"2025-10-31","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}
Pub Date : 2025-10-30DOI: 10.1016/j.humgen.2025.201502
Md Kamal Hossain Ripon , A.K. Azad Chowdhury , Mamun Al-Mahtab , Zobaer Al Mahmud , Nahid Sharmin , Sheikh Zahir Raihan
Polymorphism of the transmembrane 6 superfamily member 2 (TM6SF2) gene influences the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). It is unclear how TM6SF2 is related to the consequence of MASLD in the Bangladeshi people. This case-control study aims to determine whether the polymorphism in the TM6SF2 gene is linked with MASLD subjects in Bangladesh. Genomic DNA was isolated from peripheral blood samples. Sanger sequencing was completed for the genotype of single nucleotide polymorphisms (SNPs). SPSS was used to analyze the data for statistics. A total of 138 Bangladeshi people participated in the study. Binary logistic regression assisted in determining the link between MASLD and genetic variants. The MASLD group had a significantly higher minor allele frequency in the rs 58542926 (T), rs 72999063 (T) and rs 72999068 (G) of TM6SF2 compared to the healthy controls (P = 0.018, <0.001, 0.001, respectively). After adjusting for age and gender, the dominant model of rs 58542926 moderately elevated the risk of MASLD (OR: 3.29, 95 % CI: 1.00–10.89; P = 0.051). In our study group, rs 72999063, rs 72999068 and rs 2074299 were not found to have any significant effect on the risk of developing MASLD after adjusting for age, gender and rs 58542926. However, polymorphism rs 58542926 was found to be moderately LD (linkage disequilibrium) with both rs 72999063 and rs 72999068 (D′ = 0.804, r = 0.597, P < 0.05 and D′ = 0.746, r = 0.611, P < 0.05, respectively). Whereas rs 72999063 and rs 72999068 are strongly LD together with D′ = 0.999 and r = 0.904, P < 0.05. This study will help identify rs 58542926, rs 72999063, and rs 72999068 polymorphisms of TM6SF2 in various global populations. Further analyses are needed to better understand the effects of the TM6SF2 polymorphism on MASLD susceptibility, including a larger sample size and more physiological details.
跨膜6超家族成员2 （TM6SF2）基因多态性影响代谢功能障碍相关脂肪变性肝病（MASLD）的风险。目前尚不清楚TM6SF2与孟加拉国人患MASLD的后果有何关系。本病例对照研究旨在确定TM6SF2基因多态性是否与孟加拉国MASLD受试者有关。从外周血样本中分离基因组DNA。完成单核苷酸多态性（snp）基因型的Sanger测序。采用SPSS软件对数据进行分析统计。共有138名孟加拉国人参与了这项研究。二元逻辑回归有助于确定MASLD和遗传变异之间的联系。与健康对照组相比，MASLD组TM6SF2小等位基因rs 58542926 (T)、rs 72999063 (T)和rs 72999068 (G)的频率显著升高（P = 0.018, <0.001, 0.001）。在调整了年龄和性别后，rs 58542926的优势模型中度升高了MASLD的风险（OR: 3.29, 95% CI: 1.00-10.89; P = 0.051）。在我们的研究组中，在调整了年龄、性别和58542926后，没有发现72999063、72999068和2074299对发生MASLD的风险有任何显著影响。多态性rs 58542926与rs 72999063和rs 72999068均存在中度不平衡（D′= 0.804,r = 0.597, P < 0.05）， D′= 0.746,r = 0.611, P < 0.05)。而rs 72999063和rs 72999068是强LD，且D ' = 0.999, r = 0.904, P < 0.05。该研究将有助于确定TM6SF2在全球不同人群中的rs 58542926、rs 72999063和rs 72999068多态性。为了更好地了解TM6SF2多态性对MASLD易感性的影响，需要进一步的分析，包括更大的样本量和更多的生理细节。
{"title":"Association of transmembrane 6 superfamily member 2 rs 58542926, rs 187429064, rs 142056540, rs 72999063, rs 72999068 and rs 2074299 with susceptibility of metabolic dysfunction-associated steatotic liver disease in Bangladeshi population","authors":"Md Kamal Hossain Ripon , A.K. Azad Chowdhury , Mamun Al-Mahtab , Zobaer Al Mahmud , Nahid Sharmin , Sheikh Zahir Raihan","doi":"10.1016/j.humgen.2025.201502","DOIUrl":"10.1016/j.humgen.2025.201502","url":null,"abstract":"<div><div>Polymorphism of the transmembrane 6 superfamily member 2 (<em>TM6SF2</em>) gene influences the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). It is unclear how <em>TM6SF2</em> is related to the consequence of MASLD in the Bangladeshi people. This case-control study aims to determine whether the polymorphism in the <em>TM6SF2</em> gene is linked with MASLD subjects in Bangladesh. Genomic DNA was isolated from peripheral blood samples. Sanger sequencing was completed for the genotype of single nucleotide polymorphisms (SNPs). SPSS was used to analyze the data for statistics. A total of 138 Bangladeshi people participated in the study. Binary logistic regression assisted in determining the link between MASLD and genetic variants. The MASLD group had a significantly higher minor allele frequency in the rs 58542926 (T), rs 72999063 (T) and rs 72999068 (G) of <em>TM6SF2</em> compared to the healthy controls (<em>P</em> = 0.018, <0.001, 0.001, respectively). After adjusting for age and gender, the dominant model of rs 58542926 moderately elevated the risk of MASLD (OR: 3.29, 95 % CI: 1.00–10.89; <em>P</em> = 0.051). In our study group, rs 72999063, rs 72999068 and rs 2074299 were not found to have any significant effect on the risk of developing MASLD after adjusting for age, gender and rs 58542926. However, polymorphism rs 58542926 was found to be moderately LD (linkage disequilibrium) with both rs 72999063 and rs 72999068 (D′ = 0.804, <em>r</em> = 0.597, <em>P</em> < 0.05 and D′ = 0.746, <em>r</em> = 0.611, <em>P</em> < 0.05, respectively). Whereas rs 72999063 and rs 72999068 are strongly LD together with D′ = 0.999 and <em>r</em> = 0.904, <em>P</em> < 0.05. This study will help identify rs 58542926, rs 72999063, and rs 72999068 polymorphisms of <em>TM6SF2</em> in various global populations. Further analyses are needed to better understand the effects of the <em>TM6SF2</em> polymorphism on MASLD susceptibility, including a larger sample size and more physiological details.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201502"},"PeriodicalIF":0.7,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465872","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}
Pub Date : 2025-10-30DOI: 10.1016/j.humgen.2025.201506
Swapnil Kumar, Vaibhav Vindal
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.
{"title":"Estimating drivers of breast tissue transitions from normal to tumor state","authors":"Swapnil Kumar, 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":"2025-10-30","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}
Pub Date : 2025-10-29DOI: 10.1016/j.humgen.2025.201504
Chenxi Liu , Wen Wen , Zheng Zhang
This study reports a familial hypertrophic cardiomyopathy (HCM) case caused by the MYH6 c.5467G > T (p. Glu1823Ter) nonsense variant. The proband, a 44-year-old male, presented with sudden-onset chest pain and dyspnea. Echocardiography revealed left atrial enlargement, asymmetric septal hypertrophy, and left ventricular outflow tract obstruction, while cardiac magnetic resonance imaging demonstrated mid-septal delayed enhancement, confirming HCM diagnosis. Genetic analyses via next-generation sequencing (NGS) and Sanger sequencing identified a heterozygous nonsense variant (c.5467G > T) in the MYH6 gene, predicted to induce nonsense-mediated mRNA decay (NMD). Three-generation pedigree analysis showed complete co-segregation of this variant with HCM phenotype. Mutation carriers exhibited varying degrees of HCM, whereas non-carriers had normal cardiac structures. These findings suggest the MYH6 c.5467G > T variant as a contributor to HCM development.
{"title":"Novel nonsense mutation in MYH6 gene identified as the cause of familial hypertrophic cardiomyopathy – A case report and literature review","authors":"Chenxi Liu , Wen Wen , Zheng Zhang","doi":"10.1016/j.humgen.2025.201504","DOIUrl":"10.1016/j.humgen.2025.201504","url":null,"abstract":"<div><div>This study reports a familial hypertrophic cardiomyopathy (HCM) case caused by the MYH6 c.5467G > T (p. Glu1823Ter) nonsense variant. The proband, a 44-year-old male, presented with sudden-onset chest pain and dyspnea. Echocardiography revealed left atrial enlargement, asymmetric septal hypertrophy, and left ventricular outflow tract obstruction, while cardiac magnetic resonance imaging demonstrated mid-septal delayed enhancement, confirming HCM diagnosis. Genetic analyses via next-generation sequencing (NGS) and Sanger sequencing identified a heterozygous nonsense variant (c.5467G > T) in the MYH6 gene, predicted to induce nonsense-mediated mRNA decay (NMD). Three-generation pedigree analysis showed complete co-segregation of this variant with HCM phenotype. Mutation carriers exhibited varying degrees of HCM, whereas non-carriers had normal cardiac structures. These findings suggest the MYH6 c.5467G > T variant as a contributor to HCM development.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201504"},"PeriodicalIF":0.7,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465899","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}
Green synthesis is a preferred method for producing silver nanoparticles (Ag-NPs). In addition to its advantages for industrial and biomedical applications, it also represents a promising research field. This study aimed to evaluate the effects of chlorpyrifos (CPF) on thyroid hormone levels and the expression of inflammatory factors while highlighting the therapeutic potential of curcumin-synthesized silver nanoparticles (CUR-Ag-NPs) in mitigating CPF-induced thyroid damage.
Materials and methods
Six groups of rats were studied: control, CPF (5 mg/kg), CUR-AgNPs 40 μg/kg, CUR-AgNPs 80 μg/kg, CPF+ CUR-AgNPs 40, μg/kg, and CPF+ CUR-AgNPs 80 μg/kg. Treatments were administered daily for 30 days. At the end of the study, the rats were anesthetized with ketamine (50 mg/kg), and xylazine, (10 mg/kg). Blood was collected for serum analysis of thyroid hormone levels and thyroid gland tissue was preserved in RNAlater to the evaluation of inflammation markers.
Results
CPF exposure increased the expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nitric oxide synthase 2 (NOS2). Co-administration of CUR-AgNPs significantly reduced the expression of these genes. CPF also disrupted thyroid hormone secretion, while CUR-AgNPs treatment in CPF-exposed rats nearly restored thyroid function.
Conclusion
These findings suggest that CUR-AgNPs can attenuate CPF-induced thyroid toxicity, offering potential therapeutic value.
{"title":"Curcumin-synthesized silver nanoparticles modulate inflammatory and thyroid-related gene expression in pubertal rats exposed to chlorpyrifos","authors":"Mohammad Hossein Gorji Dizabadi , Maryam Rezaei , Tahereh Farkhondeh , Saeed Samargahndian , Zahra Khademi , Atena Mansouri","doi":"10.1016/j.humgen.2025.201503","DOIUrl":"10.1016/j.humgen.2025.201503","url":null,"abstract":"<div><h3>Introduction</h3><div>Green synthesis is a preferred method for producing silver nanoparticles (Ag-NPs). In addition to its advantages for industrial and biomedical applications, it also represents a promising research field. This study aimed to evaluate the effects of chlorpyrifos (CPF) on thyroid hormone levels and the expression of inflammatory factors while highlighting the therapeutic potential of curcumin-synthesized silver nanoparticles (CUR-Ag-NPs) in mitigating CPF-induced thyroid damage.</div></div><div><h3>Materials and methods</h3><div>Six groups of rats were studied: control, CPF (5 mg/kg), CUR-AgNPs 40 μg/kg, CUR-AgNPs 80 μg/kg, CPF+ CUR-AgNPs 40, μg/kg, and CPF+ CUR-AgNPs 80 μg/kg. Treatments were administered daily for 30 days. At the end of the study, the rats were anesthetized with ketamine (50 mg/kg), and xylazine, (10 mg/kg). Blood was collected for serum analysis of thyroid hormone levels and thyroid gland tissue was preserved in RNAlater to the evaluation of inflammation markers.</div></div><div><h3>Results</h3><div>CPF exposure increased the expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nitric oxide synthase 2 (NOS2). Co-administration of CUR-AgNPs significantly reduced the expression of these genes. CPF also disrupted thyroid hormone secretion, while CUR-AgNPs treatment in CPF-exposed rats nearly restored thyroid function.</div></div><div><h3>Conclusion</h3><div>These findings suggest that CUR-AgNPs can attenuate CPF-induced thyroid toxicity, offering potential therapeutic value.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201503"},"PeriodicalIF":0.7,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415608","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}
Diabetic foot ulcers (DFUs) are a prominent and serious outcome of diabetes that can have a major impact on quality of life. Diabetic foot ulcers (DFUs) exhibit a delayed recovery owing to the physiological healing cascade. The typical wound healing process, which encompasses angiogenesis, inflammation, and extracellular matrix (ECM) remodeling, is disrupted and inhibited in diabetic foot ulcers (DFUs). Upon injury to the tissue, neutrophils and monocytes migrate to the site of injury and secrete reactive oxygen species (ROS), matrix metalloproteinase (MMP)-8. In addition to that, the other biomarkers like procalcitonin, pentraxin-3, C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor-α (TNF-α), are secreted as an inflammatory response. These inflammatory mediators play a significant role as novel biomarkers reflecting the impact of therapeutic interventions. Numerous studies state that, single nucleotide variants (SNVs) in multiple genes may contribute to abnormal inflammatory response leading to the delayed healing of diabetic foot ulcers (DFUs). This article summarizes current information on the generation of diabetic foot ulcers (DFUs) concerning single-nucleotide variants (SNVs). This review unveils a comprehensive summary of emerging biomarkers and single-nucleotide variants (SNVs) that facilitate accurate diagnosis and risk assessment of diabetic foot ulcers (DFUs).
{"title":"Genetic and molecular insights into diabetic foot ulcers: Unveiling biomarkers for precision medicine","authors":"Ratanjeet Singh Sudan, Priyanka Garg, Palakurthi Yanadaiah","doi":"10.1016/j.humgen.2025.201500","DOIUrl":"10.1016/j.humgen.2025.201500","url":null,"abstract":"<div><div>Diabetic foot ulcers (DFUs) are a prominent and serious outcome of diabetes that can have a major impact on quality of life. Diabetic foot ulcers (DFUs) exhibit a delayed recovery owing to the physiological healing cascade. The typical wound healing process, which encompasses angiogenesis, inflammation, and extracellular matrix (ECM) remodeling, is disrupted and inhibited in diabetic foot ulcers (DFUs). Upon injury to the tissue, neutrophils and monocytes migrate to the site of injury and secrete reactive oxygen species (ROS), matrix metalloproteinase (MMP)-8. In addition to that, the other biomarkers like procalcitonin, pentraxin-3, C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor-α (TNF-α), are secreted as an inflammatory response. These inflammatory mediators play a significant role as novel biomarkers reflecting the impact of therapeutic interventions. Numerous studies state that, single nucleotide variants (SNVs) in multiple genes may contribute to abnormal inflammatory response leading to the delayed healing of diabetic foot ulcers (DFUs). This article summarizes current information on the generation of diabetic foot ulcers (DFUs) concerning single-nucleotide variants (SNVs). This review unveils a comprehensive summary of emerging biomarkers and single-nucleotide variants (SNVs) that facilitate accurate diagnosis and risk assessment of diabetic foot ulcers (DFUs).</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201500"},"PeriodicalIF":0.7,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415619","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}
Pub Date : 2025-10-24DOI: 10.1016/j.humgen.2025.201499
Mina Kazemzadeh , Reza Safaralizadeh , Amir Ali Mokhtarzadeh , Mohammad Ali Hosseinpour Feizi
Background
The significance of long non-coding RNAs, a new class of regulatory RNAs, is progressively emerging in the initiation, progression, and invasion of cancers, including thyroid cancer. PURPL (LINC01021) is one of the novel lincRNAs that has just been identified in a few human cancers. Considering the inadequate comprehension of PURPL expression and its alteration in thyroid cancer, the primary objective of this study was to quantitatively assess PURPL expression in thyroid tissue and to explore its dysregulation in patients with thyroid cancer for the first time.
Materials and methods
The Cancer Genome Atlas database was utilized to evaluate the relative expression of PURPL across various cancer types. Subsequently, quantitative real-time PCR was employed to assess PURPL expression in paired tumor and adjacent tumor-free tissue samples obtained from 30 individuals with thyroid cancer. Bioinformatics analysis was then performed to identify co-expressed genes and associated pathways with PURPL. One of the identified co-expressed genes, MDM2, was further investigated for its correlation with PURPL expression through real-time PCR. Additionally, efforts were made to correlate PURPL expression with clinicopathological features of thyroid cancer.
Results
Real-time PCR analysis revealed the upregulation of PURPL during tumorigenesis in thyroid cancer. However, dysregulation of PURPL did not show a significant correlation with clinical characteristics. Bioinformatics analysis identified approximately 1000 genes correlated with PURPL expression, with MDM2 exhibiting the highest positive correlation. Experimental validation through real-time PCR confirmed a positive correlation between MDM2 and PURPL expression in thyroid cancer cells. Additionally, the oncogenic CASC19 and tumor suppressor TLE5 demonstrated strong positive and negative correlations with PURPL, respectively, suggesting a complex regulatory role in thyroid cancer progression.
Conclusion
The significant upregulation of PURPL in thyroid cancer, along with its positive correlation with oncogenes such as MDM2, underscores the potential role of PURPL in cancer-associated pathways.
{"title":"Understanding the dysregulation of PURPL, a novel long intergenic noncoding RNA, in thyroid cancer progression","authors":"Mina Kazemzadeh , Reza Safaralizadeh , Amir Ali Mokhtarzadeh , Mohammad Ali Hosseinpour Feizi","doi":"10.1016/j.humgen.2025.201499","DOIUrl":"10.1016/j.humgen.2025.201499","url":null,"abstract":"<div><h3>Background</h3><div>The significance of long non-coding RNAs, a new class of regulatory RNAs, is progressively emerging in the initiation, progression, and invasion of cancers, including thyroid cancer. PURPL (LINC01021) is one of the novel lincRNAs that has just been identified in a few human cancers. Considering the inadequate comprehension of PURPL expression and its alteration in thyroid cancer, the primary objective of this study was to quantitatively assess PURPL expression in thyroid tissue and to explore its dysregulation in patients with thyroid cancer for the first time.</div></div><div><h3>Materials and methods</h3><div>The Cancer Genome Atlas database was utilized to evaluate the relative expression of PURPL across various cancer types. Subsequently, quantitative real-time PCR was employed to assess PURPL expression in paired tumor and adjacent tumor-free tissue samples obtained from 30 individuals with thyroid cancer. Bioinformatics analysis was then performed to identify co-expressed genes and associated pathways with PURPL. One of the identified co-expressed genes, MDM2, was further investigated for its correlation with PURPL expression through real-time PCR. Additionally, efforts were made to correlate PURPL expression with clinicopathological features of thyroid cancer.</div></div><div><h3>Results</h3><div>Real-time PCR analysis revealed the upregulation of PURPL during tumorigenesis in thyroid cancer. However, dysregulation of PURPL did not show a significant correlation with clinical characteristics. Bioinformatics analysis identified approximately 1000 genes correlated with PURPL expression, with MDM2 exhibiting the highest positive correlation. Experimental validation through real-time PCR confirmed a positive correlation between MDM2 and PURPL expression in thyroid cancer cells. Additionally, the oncogenic CASC19 and tumor suppressor TLE5 demonstrated strong positive and negative correlations with PURPL, respectively, suggesting a complex regulatory role in thyroid cancer progression.</div></div><div><h3>Conclusion</h3><div>The significant upregulation of PURPL in thyroid cancer, along with its positive correlation with oncogenes such as MDM2, underscores the potential role of PURPL in cancer-associated pathways.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201499"},"PeriodicalIF":0.7,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415609","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}
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