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Uracil walking primer PCR: An accurate and efficient genome-walking tool
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2025-03-13 DOI: 10.1016/j.jgeb.2025.100478
Hong Chen , Bingkun Tian , Rongrong Wang , Zhenkang Pan , Dandan Gao , Haixing Li
{"title":"Uracil walking primer PCR: An accurate and efficient genome-walking tool","authors":"Hong Chen ,&nbsp;Bingkun Tian ,&nbsp;Rongrong Wang ,&nbsp;Zhenkang Pan ,&nbsp;Dandan Gao ,&nbsp;Haixing Li","doi":"10.1016/j.jgeb.2025.100478","DOIUrl":"10.1016/j.jgeb.2025.100478","url":null,"abstract":"<div><div>Genome walking PCR has been extensively used to acquire unknown genomic regions bordering known DNAs. However, non-target amplification challenges the efficacy of existing genome-walking PCRs. Herein, we conceived a new genome-walking method termed Uracil walking Primer PCR (UP-PCR). The UP-PCR features introducing an uracil base at the penultimate position of arbitrary walking primer (AWP) 3′ end. A UP-PCR set comprises three nested amplification steps, which are performed by an AWP sequentially coupling a set of three nested site-specific primers, respectively. Prior to secondary UP-PCR, primary UP-PCR product is processed with uracil DNA glycosylase to destroy the carried AWP. As a result, only target primary product is exponentially amplified in the next UP-PCR(s), as it is the only product with binding sites for the both primers. The performance of UP-PCR has been validated by walking three selected genes. The walking experiments showed that each secondary or tertiary UP-PCR generated one to two amplicon ranging in size from 0.2 to 5.0 kb, while with a negligible non-target background; and the amplicons of the secondary UP-PCRs were all correct, indicating that tertiary UP-PCR is generally unnecessary. These findings suggested that UP-PCR has a satisfactory walking ability, specificity, and speed. Collectively, the proposed UP-PCR is a potential candidate method for genome walking.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 2","pages":"Article 100478"},"PeriodicalIF":3.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Computational and molecular insights on non-synonymous SNPs associated with human RAAS genes: Consequences for Hypertension vulnerability
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2025-03-01 DOI: 10.1016/j.jgeb.2025.100476
Jeyanthi Sankar , Beena Briget Kuriakose , Amani Hamad Alhazmi , Ling Shing Wong , Karthikeyan Muthusamy
{"title":"Computational and molecular insights on non-synonymous SNPs associated with human RAAS genes: Consequences for Hypertension vulnerability","authors":"Jeyanthi Sankar ,&nbsp;Beena Briget Kuriakose ,&nbsp;Amani Hamad Alhazmi ,&nbsp;Ling Shing Wong ,&nbsp;Karthikeyan Muthusamy","doi":"10.1016/j.jgeb.2025.100476","DOIUrl":"10.1016/j.jgeb.2025.100476","url":null,"abstract":"<div><div>Hypertension is the foremost modifiable risk factor for cardiovascular and renal diseases, and overall mortality on a global scale. Genetic variants have the potential to alter an individual’s drug responses. In the present study, we employed a comprehensive computational analysis to evaluate the structural and functional implications of deleterious missense variants to examine the influence of RAAS genes such as AT1R, AT2R, and MasR on susceptibility to hypertension. The objective of this research was to identify potentially deleterious missense variants within these target genes. A total of 13 <em>in silico</em> tools were used to identify deleterious missense SNPs. Protein stability, evolutionary conservation, and 3D structural modeling were assessed using tools like I-Mutant 3.0, MUpro, DynaMut2, ConSurf, and Project HOPE, while protein–protein interactions were analyzed via STRING. Our findings revealed three deleterious missense variants (rs397514687, rs886058071, rs368951368) in AT1R; two deleterious missense variants (rs3729979 and rs372930194) in AT2R; and three deleterious missense variants (rs768037685, rs149100513, and rs377679974) in MasR, all of which exhibited significant damaging effects as determined by the 13 Computational tools employed. All these deleterious missense variants adversely affected protein stability and were found to be highly conserved. Notably, these variants altered the charge, size, and hydrophobicity of the amino acids, with a predominant occurrence in alpha helix regions, with the exception of rs377679974 in MasR. The computational analysis and structural comparisons conducted in this study indicate that these deleterious missense variants have a discernible impact on the structure and function of the target proteins. However, it is essential to conduct experimental validation to verify the detrimental effects of the missense variants identified through this computational analysis. Therefore, we may conduct future experimental analyses to validate these findings. This research will aid in the identification of candidate deleterious markers that may serve as potential targets for therapeutic strategies and disease diagnosis.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100476"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NanoFlora: Unveiling the therapeutic potential of Ipomoea aquatica nanoparticles 纳米植物:揭示水生苕纳米颗粒的治疗潜力
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2025-03-01 DOI: 10.1016/j.jgeb.2025.100470
Manickavasagam Sasikala , Sellappan Mohan , Arjunan Karuppaiah , Vedi Karthick , Palanigoundar Atheyannan Ragul , Arumugam Nagarajan
{"title":"NanoFlora: Unveiling the therapeutic potential of Ipomoea aquatica nanoparticles","authors":"Manickavasagam Sasikala ,&nbsp;Sellappan Mohan ,&nbsp;Arjunan Karuppaiah ,&nbsp;Vedi Karthick ,&nbsp;Palanigoundar Atheyannan Ragul ,&nbsp;Arumugam Nagarajan","doi":"10.1016/j.jgeb.2025.100470","DOIUrl":"10.1016/j.jgeb.2025.100470","url":null,"abstract":"<div><h3>Introduction</h3><div>Improving the pharmacokinetics of drugs is achieved through nano formulations and the role of natural product in the synthesis of nanomaterials is gaining prominence due to its eco-friendly nature, cost-effectiveness, and demonstrated efficacy. Metal nanoparticles (NPs) derived from <em>Ipomoea aquatica</em> Forsskal have been synthesized and evaluated for their antioxidant and antidiabetic properties towards enhancing the anticancer activity of the plant extracts.</div></div><div><h3>Methodology</h3><div>Hydroalcoholic extract was obtained from the entire Ipomoea aquatica plant and utilized as a key ingredient in the green synthesis of metal NPs. The characterization of the synthesized NPs involved UV/visible and FT-IR spectroscopic analyses, along with particle size determination using Zetasizer technology. Antioxidant activity was assessed through DPPH radical scavenging assays, while antidiabetic potential was evaluated via alpha-amylase inhibitory activity using HPTLC bioautography.</div></div><div><h3>Results</h3><div>The formation of silver nanoparticles (AgNPs) was confirmed by a color change from light brown to dark brown. UV–VIS spectrum analysis showed strong absorbance between 380 and 400 nm, with a peak at 428 nm, indicating successful synthesis via bioreduction by <em>Ipomoea aquatica</em> extract. FT-IR spectra revealed phytochemicals like flavonoids and proteins, with shifts in peak positions confirming AgNP formation. DLS showed an average particle size of 36.27 nm, and TEM images confirmed spherical morphology. The AgNPs exhibited significant antioxidant and antidiabetic activities, outperforming standards such as ascorbic acid and Glibenclamide. Toxicity prediction identified the extract as slightly toxic, guiding safe dose administration.</div></div><div><h3>Conclusion</h3><div>The study underscores the potential of plant-based nanoparticles in scavenging free radicals and supporting cytotoxicity, thus hinting at their potential role in cancer therapy. Moreover, the nanoparticles derived from Ipomoea aquatica exhibit promising antioxidant and antidiabetic activities compared to the crude plant extract. This research paves the way for further exploration of <em>Ipomoea aquatica</em> nanoparticles as a novel therapeutic intervention for various diseases.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100470"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MEFV gene variations in COVID-19 pneumonia patients (Pilot study)
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2025-03-01 DOI: 10.1016/j.jgeb.2025.100473
Noha A. Radwan , Heba El Gohary , Dalia Hamed , Noha M. Khalil , Dalia Abdelfatah , Amal Abdel Wahab , Marwa Mahmoud Elsharkawy
{"title":"MEFV gene variations in COVID-19 pneumonia patients (Pilot study)","authors":"Noha A. Radwan ,&nbsp;Heba El Gohary ,&nbsp;Dalia Hamed ,&nbsp;Noha M. Khalil ,&nbsp;Dalia Abdelfatah ,&nbsp;Amal Abdel Wahab ,&nbsp;Marwa Mahmoud Elsharkawy","doi":"10.1016/j.jgeb.2025.100473","DOIUrl":"10.1016/j.jgeb.2025.100473","url":null,"abstract":"<div><h3>Background</h3><div>The emergence of worldwide pandemic caused by coronavirus 2 (SARS-CoV-2) has caused a radical change in everyday life. Patients diseased with FMF show manifestations and labs highly similar to COVID infected patients. In the current study, we evaluate the presence of variants in exon 10 of <em>MEFV</em> gene and the relation with severity of symptoms in patients with COVID-19 pneumonia.</div></div><div><h3>Method</h3><div>Thirty-nine COVID-19 infected patients admitted to Kasr Alainy medical school were divided into two groups moderate and severe. Sanger sequencing of exon 10 in <em>MEVF</em> gene was scanned in the 39 subjects.</div></div><div><h3>Results</h3><div>We identified variants in 10 out of 39 patients (26 %) with heterozygous variants in 9 patients (23 %) and homozygous in one patient (2.5 %). The most frequent variant found was the silent variant p.(P706 = ) (12.9 %) followed by missense variants p.(A744S) (7.7 %) and p.(V726A) (5.1 %). Striking result was that 90 % of patients with <em>MEFV</em> variants had moderate symptoms and without progression into the severe form of COVID-19 pneumonia.</div></div><div><h3>Conclusion</h3><div>Our results indicated that the presence of variants in <em>MEFV</em> gene (either benign or of uncertain significance) could have a role in determination of COVID-19 severity.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100473"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identifying promising peptide targets for leprosy serological tests: From prediction to ELISA
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2025-03-01 DOI: 10.1016/j.jgeb.2025.100475
Augusto César Parreiras de Jesus , Vanêssa Gomes Fraga , Samuel Alexandre Pimenta-Carvalho , Tania Mara Pinto Dabés Guimarães , Marcio Sobreira Silva Araújo , Jairo Campos de Carvalho , Marcio Bezerra Santos , Marcelo Grossi Araújo , Marcelo Antonio Pascoal-Xavier , Sandra Lyon , Sebastião Rodrigo Ferreira , Rocio Arreguin-Campos , Kasper Eersels , Bart van Grinsven , Thomas Cleij , Lilian Lacerda Bueno , Daniella Castanheira Bartholomeu , Cristiane Alves da Silva Menezes , Ana Laura Grossi de Oliveira , Ricardo Toshio Fujiwara
{"title":"Identifying promising peptide targets for leprosy serological tests: From prediction to ELISA","authors":"Augusto César Parreiras de Jesus ,&nbsp;Vanêssa Gomes Fraga ,&nbsp;Samuel Alexandre Pimenta-Carvalho ,&nbsp;Tania Mara Pinto Dabés Guimarães ,&nbsp;Marcio Sobreira Silva Araújo ,&nbsp;Jairo Campos de Carvalho ,&nbsp;Marcio Bezerra Santos ,&nbsp;Marcelo Grossi Araújo ,&nbsp;Marcelo Antonio Pascoal-Xavier ,&nbsp;Sandra Lyon ,&nbsp;Sebastião Rodrigo Ferreira ,&nbsp;Rocio Arreguin-Campos ,&nbsp;Kasper Eersels ,&nbsp;Bart van Grinsven ,&nbsp;Thomas Cleij ,&nbsp;Lilian Lacerda Bueno ,&nbsp;Daniella Castanheira Bartholomeu ,&nbsp;Cristiane Alves da Silva Menezes ,&nbsp;Ana Laura Grossi de Oliveira ,&nbsp;Ricardo Toshio Fujiwara","doi":"10.1016/j.jgeb.2025.100475","DOIUrl":"10.1016/j.jgeb.2025.100475","url":null,"abstract":"<div><div>Leprosy remains a significant health concern, particularly in India, Brazil, and Indonesia. Early diagnosis is essential to prevent complications, highlighting the need for improved diagnostic tools. This study aimed to identify novel <em>Mycobacterium leprae</em> antigens and assess their effectiveness against human sera through immunotools for antibody response evaluation. Using bioinformatics, we predicted B-cell epitopes in <em>M. leprae</em>, which were chemically synthesized and tested via dot blotting with sera from leprosy patients, tuberculosis patients, and healthy controls. Promising peptides underwent further analysis through ELISA using 465 serum samples from leprosy patients, household contacts, and healthy controls across Brazil. The samples were also tested against known antigens HSA-NDO, LID-1, and NDO-LID. A total of 102 epitope sequences were generated, of which eight (PEP1 to PEP8) demonstrated the ability to differentiate between individuals with and without exposure to <em>M. leprae</em>. The results of the ELISA test exhibited statistically significant differences in absorbance responses between the experimental groups for the novel synthetic peptides (p &lt; 0.05). PEP3, PEP4, and PEP5 demonstrated the most favorable outcomes, with values of the area under the receiver operating characteristic curve (AUC) of 0.9759, 0.9796 and 0.9551 respectively in the comparison of healthy controls with household contacts, and 0.8257, 0.7945, and 0.7961 comparing the same controls with patients. Furthermore, the synthetic peptides demonstrated superior sensitivity, specificity, and AUC compared to HSA-NDO, LID-1, and NDO-LID. The identified peptides showed significant responses in samples from patients and household contacts (HHC), indicating their potential for tracing exposure to <em>M. leprae</em> bacilli. These novel synthetic peptides could enhance the sensitivity of rapid diagnostic tests for leprosy, facilitating early detection of the infection. This could help prevent disease progression and interrupt transmission.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100475"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Designing of multi-valent epitope vaccine displaying interactions with diverse HLA alleles against Candida auris using immuno-informatics
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2025-03-01 DOI: 10.1016/j.jgeb.2025.100474
Vaishali Ahlawat, Kiran Sura, Mehak Dangi, Anil Kumar Chhillar
{"title":"Designing of multi-valent epitope vaccine displaying interactions with diverse HLA alleles against Candida auris using immuno-informatics","authors":"Vaishali Ahlawat,&nbsp;Kiran Sura,&nbsp;Mehak Dangi,&nbsp;Anil Kumar Chhillar","doi":"10.1016/j.jgeb.2025.100474","DOIUrl":"10.1016/j.jgeb.2025.100474","url":null,"abstract":"<div><div>The emergence of multidrug resistance<!--> <!-->against several antifungal drugs and the absence of alternate therapy limits the treatment choices leading to the spread of Candida auris infections, especially in<!--> <!-->immunocompromised patients. This work aims to construct the multi-epitope vaccine using an immuno-informatics approach<!--> <!-->due to the lack of efficient treatments for <em>C. auris</em>. Very few <em>in-silico</em> studies have been conducted to design a vaccine against <em>C. auris</em> majorly targeting the specific proteins regardless of the importance of non-structural proteins. The whole proteome was targeted to identify the antigenic proteins because components other than non-structural proteins can also potentially act as immunogens. The antigenic determinants were mapped in the target proteins and screened via IEDB analysis and prediction tools. Distinctive HLA types manifested at varied genotypic frequencies in diverse ethnicities. Therefore, to design an effectual vaccine construct, the candidate T-cell antigenic determinants were employed for population coverage. Various bioinformatics tools and servers were used for the 3D analysis of vaccine structure, including prediction, refinement, and validation. The computational validation of the molecular interaction of the proposed vaccine with TLR4, TLR5, HLA-A*11:01, and HLA-A*02:01 was done using docking studies. The docked complexes were subjected to molecular dynamics (MD) simulations to confirm their stability, compactness, and flexibility. Simulation studies demonstrated that the vaccine complexed with immune and MHC receptors was stable during the simulation time. The outcome of the current study suggests the designed vaccine can be a potential vaccine candidate and elicit the immune response against <em>C. auris</em>. However, experimental verification (<em>in-vitro/in-vivo</em>) is required to confirm the effectiveness and safety of the designed vaccine construct.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100474"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cardioprotective, anti-inflammatory, and antioxidative outcome of costus against bleomycin-induced cardiotoxicity in rat model
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2025-02-21 DOI: 10.1016/j.jgeb.2025.100466
Barakat M. Alrashdi , Hussam Askar , Mousa O. Germoush , Maged Fouda , Diaa Massoud , Sarah Alzwain , Naser Abdelsater , Laila M.S. Salim , Mohamed H.A. Gadelmawla , Mahmoud Ashry
{"title":"Cardioprotective, anti-inflammatory, and antioxidative outcome of costus against bleomycin-induced cardiotoxicity in rat model","authors":"Barakat M. Alrashdi ,&nbsp;Hussam Askar ,&nbsp;Mousa O. Germoush ,&nbsp;Maged Fouda ,&nbsp;Diaa Massoud ,&nbsp;Sarah Alzwain ,&nbsp;Naser Abdelsater ,&nbsp;Laila M.S. Salim ,&nbsp;Mohamed H.A. Gadelmawla ,&nbsp;Mahmoud Ashry","doi":"10.1016/j.jgeb.2025.100466","DOIUrl":"10.1016/j.jgeb.2025.100466","url":null,"abstract":"<div><div>Due to bleomycin’s cytotoxic characteristics, which include cardiotoxicity, this investigation looked at the effectiveness of costus ethanolic extract in reducing cardiotoxicity in male rats receiving bleomycin therapy. Forty adult male rats (160–200 g) were evenly allocated into four groups: group (1) included normal rats serving as the control; group (2) included normal rats administered 200 mg/kg of costus ethanolic extract (CEE) orally for 6 weeks; group (3) consisted of rats receiving bleomycin (15 mg/kg twice weekly, ip) for 6 weeks; and group (4) involved rats treated orally with CEE (200 mg/kg/day) for 6 weeks following bleomycin intoxication. The results indicated that the CEE significantly reversed the cardiological deteriorations brought on by bleomycin; this was demonstrated by a considerable increase in cardiac SOD, GPx, GSH, and CAT, along with a substantial decrease in cardiac MDA, NO, and DNA fragmentation. Also, serum, LDH, CK-MB, CK- total, TNF-α, IL-4, IL-6 IL-10, IL-1β, triglycerides, cholesterol, and LDL were significantly reduced, while CD4 levels increased, and HDL declined significantly. The results of the histological and immunohistochemical analyses revealed a notable regeneration. In conclusion, CEE’s anti-cardiotoxic, anti-inflammatory, and antioxidant properties prove its ability to be a cardio-protective supplement. This may be mediated by its active constituents’ radical scavenging and antioxidant properties, particularly high phenolic content.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100466"},"PeriodicalIF":3.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive system biology analysis of microRNA-101-3p regulatory network identifies crucial genes and pathways in hepatocellular carcinoma
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2025-02-18 DOI: 10.1016/j.jgeb.2025.100471
Nasim Rahimi-Farsi , Abozar Ghorbani , Negar Mottaghi-Dastjerdi , Taha Shahbazi , Fatemeh Bostanian , Parvin Mohseni , Fateme Yazdani
{"title":"Comprehensive system biology analysis of microRNA-101-3p regulatory network identifies crucial genes and pathways in hepatocellular carcinoma","authors":"Nasim Rahimi-Farsi ,&nbsp;Abozar Ghorbani ,&nbsp;Negar Mottaghi-Dastjerdi ,&nbsp;Taha Shahbazi ,&nbsp;Fatemeh Bostanian ,&nbsp;Parvin Mohseni ,&nbsp;Fateme Yazdani","doi":"10.1016/j.jgeb.2025.100471","DOIUrl":"10.1016/j.jgeb.2025.100471","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. This study aimed to explore the role of hsa-miR-101-3p in HCC pathogenesis by identifying key genes and pathways. A comprehensive bioinformatics analysis revealed twelve hub genes (ETNK1, BICRA, IL1R1, KDM3A, ARID2, GSK3β, EZH2, NOTCH1, SMARCA4, FOS, CREB1, and CASP3) and highlighted their involvement in crucial oncogenic pathways, including PI3K/Akt, mTOR, MAPK, and TGF-β. Gene expression analysis showed significant overexpression of ETNK1, KDM3A, EZH2, SMARCA4, and CASP3 in HCC tissues, correlating with poorer survival outcomes. Drug screening identified therapeutic candidates, including Tazemetostat for EZH2 and lithium compounds for GSK3β, underscoring their potential for targeted treatment. These findings provide novel insights into the complexity of HCC pathogenesis, suggesting that the identified hub genes could serve as diagnostic or prognostic biomarkers and therapeutic targets. While bioinformatics-driven, this study offers a strong basis for future clinical validation to advance precision medicine in HCC.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100471"},"PeriodicalIF":3.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unraveling the mechanisms of benzimidazole resistance in hookworms: A molecular docking and dynamics study
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2025-02-17 DOI: 10.1016/j.jgeb.2025.100472
Jan Clyden B. Tenorio , Muhammad Fikri Heikal , Alok Kafle , Mark Andrian B. Macalalad , Fredmoore L. Orosco , Prasert Saichua , Sutas Suttiprapa
{"title":"Unraveling the mechanisms of benzimidazole resistance in hookworms: A molecular docking and dynamics study","authors":"Jan Clyden B. Tenorio ,&nbsp;Muhammad Fikri Heikal ,&nbsp;Alok Kafle ,&nbsp;Mark Andrian B. Macalalad ,&nbsp;Fredmoore L. Orosco ,&nbsp;Prasert Saichua ,&nbsp;Sutas Suttiprapa","doi":"10.1016/j.jgeb.2025.100472","DOIUrl":"10.1016/j.jgeb.2025.100472","url":null,"abstract":"<div><h3>Background</h3><div>Benzimidazole resistance is an emerging challenge among parasitic helminths. It is caused by single nucleotide polymorphisms (SNPs) in specific loci in helminths’ β-tubulin genes. Field studies and laboratory investigations reported resistance-associated SNPs in 4 codon locations with 7 allelic variations among hookworms. This study aimed to determine the effects of these mutations on the binding efficiency and behavior of the β-tubulin protein in four hookworm species against four benzimidazole drugs.</div></div><div><h3>Methods</h3><div>β-tubulin gene coding sequences of <em>Ancylostoma caninum, A. duodenale, A. ceylanicum,</em> and <em>Necator americanus</em> were retrieved, assessed phylogenetically, and used to construct the 3D structure models of the proteins. The modeled protein structures were verified and edited to contain the reported SNPs: Q134H, F167Y, E198A, E198K, E198V, F200L, and F200Y. Benzimidazole drugs such as albendazole (ABZ), fenbendazole (FBZ), mebendazole (MBZ) and oxfendazole (OBZ) were used as ligands. Molecular docking experiments were performed with the wild-type and mutated proteins. Molecular dynamics simulation assessed the dynamic behavior of the β-tubulin-benzimidazole complex.</div></div><div><h3>Results</h3><div><em>In silico</em> docking assessments showed that various amino acid substitutions due to resistance-associated SNPs cause alterations in binding affinities and positions. E198K and Q134H in hookworm β-tubulins substantially weakened the binding affinities and altered the binding positions of benzimidazole drugs. Molecular dynamics analysis revealed that these mutations also caused marked reductions in the binding free energies owing to diminished hydrogen bond contacts with the benzimidazole ligands.</div></div><div><h3>Conclusion</h3><div>The evidence shown herein indicates that mutations at positions 198 and 134 are detrimental to conferring benzimidazole resistance among hookworms. The presence of these mutations may alter the efficacy of pharmacological interventions. Hence, further studies should be conducted to assess their emergence among hookworms in endemic areas with histories of chemotherapy.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 1","pages":"Article 100472"},"PeriodicalIF":3.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Personalized medicine in pancreatic cancer: Harnessing the potential of mRNA vaccines
IF 3.5
Journal of Genetic Engineering and Biotechnology Pub Date : 2025-02-17 DOI: 10.1016/j.jgeb.2025.100469
Aariz Hussain, Areeba Fareed
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