Pub Date : 2025-12-01DOI: 10.1016/j.jgeb.2025.100620
Bharati Pandey , Manbir Singh
C2H2 zinc finger (ZF) transcription factors (TFs) are among the most abundant and versatile regulatory proteins, playing critical roles in development, differentiation, apoptosis, stress response, and immune regulation. In livestock, especially within the Bovidae family, these TFs regulate gene expression linked to economically important traits such as growth, reproduction, milk production, and disease resistance. However, genome-wide identification of C2H2-ZF TFs in Bovidae remains limited due to the lack of specialized computational tools. To address this, we developed DeepBovC2H2-ZF, a deep learning-based framework for predicting C2H2-ZF TFs using only protein sequence information. The model was trained on a curated dataset of validated C2H2-ZF and non-C2H2-ZF TFs, utilizing sequence-derived features that capture the unique domain signatures. DeepBovC2H2-ZF achieved high prediction accuracy, sensitivity, and specificity, outperforming traditional machine learning models. A correctly predicted C2H2-ZF protein, Krüppel-like factor 4 (KLF4), was further validated through molecular docking and three independent molecular dynamics (MD) simulations of both the protein and its DNA-bound complex. The simulations confirmed structural stability and strong DNA-binding affinity, supporting the reliability of DeepBovC2H2-ZF for functional genomics studies in Bovidae.
{"title":"DeepBovC2H2-ZF: deep learning-guided prediction and molecular dynamics validation of C2H2 zinc finger transcription factors in Bovidae","authors":"Bharati Pandey , Manbir Singh","doi":"10.1016/j.jgeb.2025.100620","DOIUrl":"10.1016/j.jgeb.2025.100620","url":null,"abstract":"<div><div>C2H2 zinc finger (ZF) transcription factors (TFs) are among the most abundant and versatile regulatory proteins, playing critical roles in development, differentiation, apoptosis, stress response, and immune regulation. In livestock, especially within the Bovidae family, these TFs regulate gene expression linked to economically important traits such as growth, reproduction, milk production, and disease resistance. However, genome-wide identification of C2H2-ZF TFs in Bovidae remains limited due to the lack of specialized computational tools. To address this, we developed DeepBovC2H2-ZF, a deep learning-based framework for predicting C2H2-ZF TFs using only protein sequence information. The model was trained on a curated dataset of validated C2H2-ZF and non-C2H2-ZF TFs, utilizing sequence-derived features that capture the unique domain signatures. DeepBovC2H2-ZF achieved high prediction accuracy, sensitivity, and specificity, outperforming traditional machine learning models. A correctly predicted C2H2-ZF protein, Krüppel-like factor 4 (KLF4), was further validated through molecular docking and three independent molecular dynamics (MD) simulations of both the protein and its DNA-bound complex. The simulations confirmed structural stability and strong DNA-binding affinity, supporting the reliability of DeepBovC2H2-ZF for functional genomics studies in Bovidae.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100620"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622935","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 : 2025-12-01DOI: 10.1016/j.jgeb.2025.100625
Fatma F. El-Gneady , Ahmed M. Ashour , Fahad S. Ashehri , Ali Khames , Alzahraa A. Elhemiely , Marwa Ahmed Mahmoud , Nievin Ahmed Mahran , Khaled M. Alam-ElDein , Mohamed H.A. Gadelmawla
Background
Hyperthyroidism frequently impairs liver function through oxidative stress, inflammation, and apoptosis. Effective hepatoprotective therapies remain limited, targeting the effects of natural agents such as Diceratella Elliptica. The current study assessed the hepatoprotective efficacy of Diceratella Elliptica (DE) in an experimental model of L-thyroxin–induced hyperthyroidism.
Methods
This study performed on 40 male albino rats randomly allocated equally into five groups, control group (HT), L-thyroxin alone (orally, 600 mg/kg daily for 12 days) or in combination with propyl Thiourcil (PU) (intraperitoneally, 10 mg/kg daily for 15 days), and Diceratella Elliptica extract in 200 mg/kg and 400 mg/kg (orally, with a daily dose for 15 days). Hepatic function (ALT, AST, total protein), oxidative stress markers (SIRT1, Nrf2, MDA, NO, GSH, SOD and CAT), inflammatory markers (HMGB1, TLR4, NFκ-B, IL-6 and TNF-α), and apoptotic marker (Caspase-3) were measured, alongside histopathological evaluation.
Results
Hyperthyroid rats exhibited marked hepatic injury, with significant elevations in ALT (+85 %), AST (+72 %), MDA (+90 %), NO (+65 %), TNF-α (+70 %), IL-6 (+68 %), and Caspase-3 (+60 %) (P < 0.05), accompanied by substantial reductions in SIRT1 (−45 %), Nrf2 (−40 %), GSH (−50 %), SOD (−42 %), and CAT (−38 %) compared to control. Treatment with D. Elliptica (especially 400 mg/kg) significantly restored liver function, normalizing ALT and AST by nearly 50 %, enhancing antioxidant enzyme activities by 35–55 %, and down-regulating inflammatory and apoptotic markers (p < 0.05). Histological examination revealed restoration of hepatic cords, reduced inflammatory infiltration, and preserved hepatocyte morphology.
Conclusion
Diceratella Elliptica exerts potent hepatoprotective activity against hyperthyroidism-induced hepatic injury. Its concurrent activation of SIRT1 and Nrf2, along with suppression of NF-κB–mediated inflammation and Caspase-3–dependent apoptosis, suggests modulation of the oxidative stress–inflammation–apoptosis axis. These findings support Diceratella Elliptica as a promising natural therapeutic candidate for thyroid-related liver dysfunction.
{"title":"Decoding the effect of Diceratella elliptica on the oxidative stress–Inflammation axis in hyperthyroid-induced hepatotoxicity","authors":"Fatma F. El-Gneady , Ahmed M. Ashour , Fahad S. Ashehri , Ali Khames , Alzahraa A. Elhemiely , Marwa Ahmed Mahmoud , Nievin Ahmed Mahran , Khaled M. Alam-ElDein , Mohamed H.A. Gadelmawla","doi":"10.1016/j.jgeb.2025.100625","DOIUrl":"10.1016/j.jgeb.2025.100625","url":null,"abstract":"<div><h3>Background</h3><div>Hyperthyroidism frequently impairs liver function through oxidative stress, inflammation, and apoptosis. Effective hepatoprotective therapies remain limited, targeting the effects of natural agents such as <em>Diceratella Elliptica</em>. The current study assessed the hepatoprotective efficacy of <em>Diceratella Elliptica</em> (DE) in an experimental model of L-thyroxin–induced hyperthyroidism.</div></div><div><h3>Methods</h3><div>This study performed on 40 male albino rats randomly allocated equally into five groups, control group (HT), L-thyroxin alone (orally, 600 mg/kg daily for 12 days) or in combination with propyl Thiourcil (PU) (intraperitoneally, 10 mg/kg daily for 15 days), and <em>Diceratella Elliptica</em> extract in 200 mg/kg and 400 mg/kg (orally, with a daily dose for 15 days). Hepatic function (ALT, AST, total protein), oxidative stress markers (SIRT1, Nrf2, MDA, NO, GSH, SOD and CAT), inflammatory markers (HMGB1, TLR4, NFκ-B, IL-6 and TNF-α), and apoptotic marker (Caspase-3) were measured, alongside histopathological evaluation.</div></div><div><h3>Results</h3><div>Hyperthyroid rats exhibited marked hepatic injury, with significant elevations in ALT (+85 %), AST (+72 %), MDA (+90 %), NO (+65 %), TNF-α (+70 %), IL-6 (+68 %), and Caspase-3 (+60 %) (P < 0.05), accompanied by substantial reductions in SIRT1 (−45 %), Nrf2 (−40 %), GSH (−50 %), SOD (−42 %), and CAT (−38 %) compared to control. Treatment with D. Elliptica (especially 400 mg/kg) significantly restored liver function, normalizing ALT and AST by nearly 50 %, enhancing antioxidant enzyme activities by 35–55 %, and down-regulating inflammatory and apoptotic markers (p < 0.05). Histological examination revealed restoration of hepatic cords, reduced inflammatory infiltration, and preserved hepatocyte morphology.</div></div><div><h3>Conclusion</h3><div>Diceratella Elliptica exerts potent hepatoprotective activity against hyperthyroidism-induced hepatic injury. Its concurrent activation of SIRT1 and Nrf2, along with suppression of NF-κB–mediated inflammation and Caspase-3–dependent apoptosis, suggests modulation of the oxidative stress–inflammation–apoptosis axis. These findings support Diceratella Elliptica as a promising natural therapeutic candidate for thyroid-related liver dysfunction.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100625"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623553","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 : 2025-12-01DOI: 10.1016/j.jgeb.2025.100617
Fatma El Zahraa A. Elkady , Walaa A. Moselhy , Fatma I. Abo El-Ela , Abeer M. Abd El-Hameed , Mohamed I. Zanaty
The prevalence of hepatotoxicity has sharply increased worldwide in recent decades. Our study aimed to enhance quercetin’s effectiveness against paracetamol (PCM)-induced hepatotoxicity using a quercetin liposome nano formulation. The quercetin liposome (QL) nano formula was fabricated by applying the thin-film hydration method. It was examined via dynamic light scattering, confirmed with a transmission electron microscope (TEM), and followed by assessments of drug-loading capacity, encapsulation efficiency (EE%), and Fourier transform infrared (FTIR) spectroscopy. The release features and cell cytotoxicity were also assessed. The in vivo parameters were completed. We effectively synthesized and characterized the quercetin liposome nanoformula with a 501.9 nm particle size and a –22.8 mV zeta potential. TEM imaging showed that quercetin liposomes were spherical. The EE% for the optimized formulation was 77.1 %. FTIR test confirmed the quercetin liposome spectra. Sustained release behavior of about 67.45 % of quercetin was released from liposomes by 24 h. The IC50 value was reduced from 71.32 µg/ml to 51.28 µg/ml for quercetin and quercetin-loaded liposomes. For the in vivo study, quercetin liposome improved all the altered biochemical markers, alleviating the levels of Malondialdehyde (MDA), Nitric oxide (NO), Superoxide dismutase (SOD), and Glutathione peroxidase (GPx), and upregulating Nuclear factor erythroid 2-related factor 2 (Nrf2) with a downregulation of Kelch-like ECH-associated protein 1 (Keap1), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and p38 Mitogen-activated protein kinase (P38 MAPK) gene expression that paralleled the histopathological amelioration. Our results suggested that the quercetin liposome nano formulation had potent hepatoprotective activity through ameliorating biochemical indicators, oxidative stress markers, upregulation of anti-apoptotic genes, and improvement in the histopathological index.
{"title":"Quercetin-liposomes effectively regulated the Nrf2/Keap1 and NF-κB/P38 MAPK signaling pathways and protected the liver against paracetamol-induced damage","authors":"Fatma El Zahraa A. Elkady , Walaa A. Moselhy , Fatma I. Abo El-Ela , Abeer M. Abd El-Hameed , Mohamed I. Zanaty","doi":"10.1016/j.jgeb.2025.100617","DOIUrl":"10.1016/j.jgeb.2025.100617","url":null,"abstract":"<div><div>The prevalence of hepatotoxicity has sharply increased worldwide in recent decades. Our study aimed to enhance quercetin’s effectiveness against paracetamol (PCM)-induced hepatotoxicity using a quercetin liposome nano formulation. The quercetin liposome (QL) nano formula was fabricated by applying the thin-film hydration method. It was examined via dynamic light scattering, confirmed with a transmission electron microscope (TEM), and followed by assessments of drug-loading capacity, encapsulation efficiency (EE%), and Fourier transform infrared (FTIR) spectroscopy. The release features and cell cytotoxicity were also assessed. The in vivo parameters were completed. We effectively synthesized and characterized the quercetin liposome nanoformula with a 501.9 nm particle size and a –22.8 mV zeta potential. TEM imaging showed that quercetin liposomes were spherical. The EE% for the optimized formulation was 77.1 %. FTIR test confirmed the quercetin liposome spectra. Sustained release behavior of about 67.45 % of quercetin was released from liposomes by 24 h. The IC50 value was reduced from 71.32 µg/ml to 51.28 µg/ml for quercetin and quercetin-loaded liposomes. For the in vivo study, quercetin liposome improved all the altered biochemical markers, alleviating the levels of Malondialdehyde (MDA), Nitric oxide (NO), Superoxide dismutase (SOD), and Glutathione peroxidase (GPx), and upregulating Nuclear factor erythroid 2-related factor 2 (<em>Nrf2</em>) with a downregulation of Kelch-like ECH-associated protein 1 (<em>Keap1</em>), Nuclear factor kappa-light-chain-enhancer of activated B cells (<em>NF-κB</em>), and p38 Mitogen-activated protein kinase (<em>P38 MAPK</em>) gene expression that paralleled the histopathological amelioration. Our results suggested that the quercetin liposome nano formulation had potent hepatoprotective activity through ameliorating biochemical indicators, oxidative stress markers, upregulation of anti-apoptotic genes, and improvement in the histopathological index.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100617"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623558","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 : 2025-12-01DOI: 10.1016/j.jgeb.2025.100619
Chatchai Kunyawut, Idtisak Paopo, Chakkrit Umpuch
Carotenoids are potent antioxidants and high-value bioactive compounds that green microalgae can efficiently synthesize. This study aimed to enhance carotenoid production in Chlorococcum humicola TISTR 8551 using a two-stage cultivation strategy in a 10-L air-lift photobioreactor (ALPBR), separating biomass accumulation and stress induction phases. During the “green stage” (9 days), cells were grown in modified BG-11 medium (N:P ratio 31:1) under 3,500 Lux white LED light with varying CO2 concentrations (1–3 % v/v) to maximize biomass yield. In the subsequent “red stage” (15 days), environmental stressors, including elevated salinity and intensified light exposure, were applied to stimulate carotenoid biosynthesis. The highest total carotenoid content (38.72 ± 1.04 mg/L, 0.313 ± 0.018 mg/g biomass) was observed under 3 % CO2 supplementation, likely due to enhanced photosynthetic carbon fixation and improved precursor availability via glucose metabolism. An optimal white light intensity of 25,000 Lux produced 32.03 ± 1.52 mg/L carotenoids. Additionally, the combination of 100,000 Lux white light with 1,600 Lux blue light significantly increased β-carotene content (6.98 ± 0.28 % of total carotenoids), while 2,400 Lux blue light yielded the highest astaxanthin level (5.01 ± 0.18 % of total carotenoids). These results highlight the synergistic effects of CO2 enrichment, spectral light modulation, and stage-specific stress application in promoting targeted carotenoid biosynthesis. This study offers practical insights for optimizing large-scale microalgal pigment production in controlled photobioreactor systems.
{"title":"Enhanced carotenoid accumulation in Chloroccocum humicola under controlled CO2 and light conditions","authors":"Chatchai Kunyawut, Idtisak Paopo, Chakkrit Umpuch","doi":"10.1016/j.jgeb.2025.100619","DOIUrl":"10.1016/j.jgeb.2025.100619","url":null,"abstract":"<div><div>Carotenoids are potent antioxidants and high-value bioactive compounds that green microalgae can efficiently synthesize. This study aimed to enhance carotenoid production in <em>Chlorococcum humicola</em> TISTR 8551 using a two-stage cultivation strategy in a 10-L air-lift photobioreactor (ALPBR), separating biomass accumulation and stress induction phases. During the “green stage” (9 days), cells were grown in modified BG-11 medium (N:P ratio 31:1) under 3,500 Lux white LED light with varying CO<sub>2</sub> concentrations (1–3 % v/v) to maximize biomass yield. In the subsequent “red stage” (15 days), environmental stressors, including elevated salinity and intensified light exposure, were applied to stimulate carotenoid biosynthesis. The highest total carotenoid content (38.72 ± 1.04 mg/L, 0.313 ± 0.018 mg/g biomass) was observed under 3 % CO<sub>2</sub> supplementation, likely due to enhanced photosynthetic carbon fixation and improved precursor availability via glucose metabolism. An optimal white light intensity of 25,000 Lux produced 32.03 ± 1.52 mg/L carotenoids. Additionally, the combination of 100,000 Lux white light with 1,600 Lux blue light significantly increased β-carotene content (6.98 ± 0.28 % of total carotenoids), while 2,400 Lux blue light yielded the highest astaxanthin level (5.01 ± 0.18 % of total carotenoids). These results highlight the synergistic effects of CO<sub>2</sub> enrichment<strong>,</strong> spectral light modulation<strong>,</strong> and stage-specific stress application in promoting targeted carotenoid biosynthesis. This study offers practical insights for optimizing large-scale microalgal pigment production in controlled photobioreactor systems.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100619"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622934","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 : 2025-12-01DOI: 10.1016/j.jgeb.2025.100616
K.M. Tanjida Islam , Roksana Khanam , Aninda Roy , Ramisa Binti Mohiuddin , Jannati Akter , Samia Haque , Sheikh Abdullah Al Ashik , Saborni Sarker , A.K.M. Mohiuddin , Shahin Mahmud
Renal cell carcinoma (RCC) is often associated with metabolic disorders such as type 2 diabetes mellitus (T2DM) and hypertension. While existing research has established connections between these metabolic conditions and RCC, the underlying mechanisms driving RCC followed by pancreatic metastasis remain incompletely understood. Therefore, our study aimed to investigate the complex interplay between metabolic disorders (type 2 diabetes and hypertension) and malignancies (renal cell carcinoma and pancreatic cancer). To investigate the hidden link, we performed an integrative transcriptomic analysis. The analysis focuses only on T2DM and hypertension to identify a connection with the RCC pathway. Our analysis revealed that 190 significantly upregulated genes, of which MET emerged as a master regulator in RCC, while KRAS was the key regulator in pancreatic cancer. Furthermore, we identified key microRNAs (has-mir-1-3p, has-mir-16-5p, and has-mir-455-3p) and transcription factors (MBD1, TFDP1, and KLF9) regulate these targets. Additionally, we identified and validated CDC42, PTPN11, TGFB3, and MET as potential prognostic or theragnostic biomarkers. MET, KRAS, and PIK3CD emerged as the most promising therapeutic targets against a panel of 28 repurposable inhibitory drugs. The genetic and immune association suggested that CD8 + T cells are the key immune infiltrate significantly associated with poor survival outcomes in RCC and pancreatic cancer patients. Mutational analysis further highlighted the significance of KRAS G12C, G12V, and G12D mutations, which were common between RCC and pancreatic metastasis. Our study provides critical insights into the statistically significant associations between metabolic disorders and malignancies, emphasizing the potential of tailored therapies alongside shared therapies in managing RCC and its progression to pancreatic metastasis.
{"title":"Transcriptomics analysis unveils the complex interplay between diabetes and hypertension in regulating renal cell carcinoma pathway followed by pancreatic metastasis","authors":"K.M. Tanjida Islam , Roksana Khanam , Aninda Roy , Ramisa Binti Mohiuddin , Jannati Akter , Samia Haque , Sheikh Abdullah Al Ashik , Saborni Sarker , A.K.M. Mohiuddin , Shahin Mahmud","doi":"10.1016/j.jgeb.2025.100616","DOIUrl":"10.1016/j.jgeb.2025.100616","url":null,"abstract":"<div><div>Renal cell carcinoma (RCC) is often associated with metabolic disorders such as type 2 diabetes mellitus (T2DM) and hypertension. While existing research has established connections between these metabolic conditions and RCC, the underlying mechanisms driving RCC followed by pancreatic metastasis remain incompletely understood. Therefore, our study aimed to investigate the complex interplay between metabolic disorders (type 2 diabetes and hypertension) and malignancies (renal cell carcinoma and pancreatic cancer). To investigate the hidden link, we performed an integrative transcriptomic analysis. The analysis focuses only on T2DM and hypertension to identify a connection with the RCC pathway. Our analysis revealed that 190 significantly upregulated genes, of which MET emerged as a master regulator in RCC, while KRAS was the key regulator in pancreatic cancer. Furthermore, we identified key microRNAs (has-mir-1-3p, has-mir-16-5p, and has-mir-455-3p) and transcription factors (MBD1, TFDP1, and KLF9) regulate these targets. Additionally, we identified and validated CDC42, PTPN11, TGFB3, and MET as potential prognostic or theragnostic biomarkers. MET, KRAS, and PIK3CD emerged as the most promising therapeutic targets against a panel of 28 repurposable inhibitory drugs. The genetic and immune association suggested that CD8 + T cells are the key immune infiltrate significantly associated with poor survival outcomes in RCC and pancreatic cancer patients. Mutational analysis further highlighted the significance of KRAS G12C, G12V, and G12D mutations, which were common between RCC and pancreatic metastasis. Our study provides critical insights into the statistically significant associations between metabolic disorders and malignancies, emphasizing the potential of tailored therapies alongside shared therapies in managing RCC and its progression to pancreatic metastasis.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100616"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623021","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}
SRC is a proto-oncogene that regulates cell proliferation and survival, and its dysregulation is commonly observed in diverse cancers. While SRC kinase dysregulation is well-established as a cancer driver, the functional consequences of its genetic variants, particularly non-synonymous single-nucleotide polymorphisms (nsSNPs) are not fully understood. Therefore, we employed an integrative computational approach to identify nsSNPs in SRC and analyze their impact on protein function and structure. Out of the 512 missense nsSNPs analyzed, 42 were predicted to be deleterious, with 12 likely to destabilize protein structure. Among these, three mutations, namely W151C (rs746439256), Y419N (rs2147125119), and P465S (rs1251532695), were particularly significant, causing substantial physicochemical changes. Molecular dynamics simulations revealed that these variations reduce protein stability and flexibility, resulting in conformational alterations. Docking study demonstrated that these mutations disrupt the binding interface residues of the SRC-FAK complex and affect dasatinib binding affinity. Additionally, gene expression analysis linked mutated SRC to dysregulation of cancer-related genes, especially in multiple myeloma and uterine cancer, and suggested reciprocal regulation by other mutated genes across malignancies. These findings highlight the oncogenic potential of SRC mutations and pave the way for future population-based studies exploring their role as diagnostic biomarkers, therapeutic targets, and modulators of drug response in personalized cancer treatment.
{"title":"Bioinformatics-driven identification of pathogenic missense nsSNPs in the human proto-oncogene SRC and cancer susceptibility","authors":"Md. Shakil Ahamed, Roksana Khanam, K.M. Tanjida Islam, Fahmida Tabassum, Md. Al Amin, Jannatul Fardous, Nadira Hoque Tashpie, A.K.M. Mohiuddin, Shahin Mahmud","doi":"10.1016/j.jgeb.2025.100618","DOIUrl":"10.1016/j.jgeb.2025.100618","url":null,"abstract":"<div><div>SRC is a proto-oncogene that regulates cell proliferation and survival, and its dysregulation is commonly observed in diverse cancers. While SRC kinase dysregulation is well-established as a cancer driver, the functional consequences of its genetic variants, particularly non-synonymous single-nucleotide polymorphisms (nsSNPs) are not fully understood. Therefore, we employed an integrative computational approach to identify nsSNPs in SRC and analyze their impact on protein function and structure. Out of the 512 missense nsSNPs analyzed, 42 were predicted to be deleterious, with 12 likely to destabilize protein structure. Among these, three mutations, namely W151C (rs746439256), Y419N (rs2147125119), and P465S (rs1251532695), were particularly significant, causing substantial physicochemical changes. Molecular dynamics simulations revealed that these variations reduce protein stability and flexibility, resulting in conformational alterations. Docking study demonstrated that these mutations disrupt the binding interface residues of the SRC-FAK complex and affect dasatinib binding affinity. Additionally, gene expression analysis linked mutated SRC to dysregulation of cancer-related genes, especially in multiple myeloma and uterine cancer, and suggested reciprocal regulation by other mutated genes across malignancies. These findings highlight the oncogenic potential of SRC mutations and pave the way for future population-based studies exploring their role as diagnostic biomarkers, therapeutic targets, and modulators of drug response in personalized cancer treatment.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100618"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623022","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}
Bitter gourd is recognized for its anticancer and antidiabetic properties, largely attributed to charantin, and is also a rich source of carotenoids, including β-carotene. In this study, considerable variation was observed in both the accumulation and gene expression patterns associated with charantin and β-carotene biosynthesis across diverse genotypes. PVGy-201 exhibited the strongest gene expression profile, with the highest transcript levels for five key genes, including McIDI (∼16,493-fold), McPMK (∼694-fold), and McSE (∼466-fold), which corresponded with the maximum charantin content (38.53 µg/g FW). Similarly, DBGS-2 showed elevated expression of McHMGR1 (∼271-fold) and McMK (∼13-fold), supporting its high charantin accumulation (35.27 µg/g FW). The wild species Momordica balsamina demonstrated strong expression of McHMGR2 and McSE, consistent with charantin content of 29.36 µg/g FW. For β-carotene, DBGS-21-06 recorded peak expression of McPSY (∼17.2-fold), McZDS (∼4.9-fold), and McCHXB (∼2.8-fold), aligning with high carotenoid levels at both edible (18.46 µg/g FW) and ripening (52.31 µg/g FW) stages. Pusa Rasdar showed elevated expression of McZEP (∼6.9-fold) and McPDS (∼10.8-fold), correlating with maximum carotenoid content (19.49 µg/g FW at edible stage and 55.66 µg/g FW at ripening). DBGS-100-0 expressed McLCYE1 (∼2.9-fold) and McLCYE2 (∼3.1-fold), with high carotenoids (15.91 µg/g FW) at the edible stage. Collectively, PVGy-201 and DBGS-2 were identified as promising candidates for charantin enrichment, while DBGS-21-06 and Pusa Rasdar emerged as superior for β-carotene accumulation. These genotype-specific insights provide a molecular framework to support marker-assisted selection, transcriptome-based screening, and metabolic engineering for the development of nutritionally enhanced bitter gourd cultivars with stable metabolite profiles.
{"title":"Molecular insights into charantin and β-carotene biosynthesis in bitter gourd (Momordica charantia L.): Gene expression dynamics and metabolite profiling","authors":"Banoth Tharun , Gograj Singh Jat , Manisha Mangal , Vishal Sunartiya , Sachin Kumar , Rakesh Bhardwaj , Naveen Singh , Jeetendra Kumar Ranjan , Avinash Tomer , Deepak Singh , Tusar Kanti Behera","doi":"10.1016/j.jgeb.2025.100626","DOIUrl":"10.1016/j.jgeb.2025.100626","url":null,"abstract":"<div><div>Bitter gourd is recognized for its anticancer and antidiabetic properties, largely attributed to charantin, and is also a rich source of carotenoids, including β-carotene. In this study, considerable variation was observed in both the accumulation and gene expression patterns associated with charantin and β-carotene biosynthesis across diverse genotypes. PVGy-201 exhibited the strongest gene expression profile, with the highest transcript levels for five key genes, including <em>McIDI</em> (∼16,493-fold), <em>McPMK</em> (∼694-fold), and <em>McSE</em> (∼466-fold), which corresponded with the maximum charantin content (38.53 µg/g FW). Similarly, DBGS-2 showed elevated expression of <em>McHMGR1</em> (∼271-fold) and <em>McMK</em> (∼13-fold), supporting its high charantin accumulation (35.27 µg/g FW). The wild species <em>Momordica balsamina</em> demonstrated strong expression of <em>McHMGR2</em> and <em>McSE</em>, consistent with charantin content of 29.36 µg/g FW. For β-carotene, DBGS-21-06 recorded peak expression of <em>McPSY</em> (∼17.2-fold), <em>McZDS</em> (∼4.9-fold), and <em>McCHXB</em> (∼2.8-fold), aligning with high carotenoid levels at both edible (18.46 µg/g FW) and ripening (52.31 µg/g FW) stages. Pusa Rasdar showed elevated expression of <em>McZEP</em> (∼6.9-fold) and <em>McPDS</em> (∼10.8-fold), correlating with maximum carotenoid content (19.49 µg/g FW at edible stage and 55.66 µg/g FW at ripening). DBGS-100-0 expressed <em>McLCYE1</em> (∼2.9-fold) and <em>McLCYE2</em> (∼3.1-fold), with high carotenoids (15.91 µg/g FW) at the edible stage. Collectively, PVGy-201 and DBGS-2 were identified as promising candidates for charantin enrichment, while DBGS-21-06 and Pusa Rasdar emerged as superior for β-carotene accumulation. These genotype-specific insights provide a molecular framework to support marker-assisted selection, transcriptome-based screening, and metabolic engineering for the development of nutritionally enhanced bitter gourd cultivars with stable metabolite profiles.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100626"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693136","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 : 2025-12-01DOI: 10.1016/j.jgeb.2025.100615
Deboral Eshak, Mohanapriya Arumugam
Amyotrophic lateral sclerosis (ALS) is a prevalent and debilitating neurodegenerative disorder characterized by the selective degeneration of motor neurons. This study aims to unravel the molecular mechanisms underlying ALS through an integrated analysis of drug-target networks and gene expression data. Gene expression datasets related to ALS, including GSE115130 and GSE76220, were retrieved from the GEO database and systematically analyzed. Differential gene expression (DEG) analysis identified key upregulated and downregulated genes, while weighted gene co-expression network analysis (WGCNA) uncovered gene modules associated with ALS pathology. DEG analysis revealed genetic insights into ALS by pinpointing genes potentially involved in disease development and progression. WGCNA provided a systems-level understanding of ALS mechanisms, identifying highly correlated gene clusters and their relationship with clinical ALS characteristics. In the GSE115130 dataset, 6,105 genes were upregulated and 6,069 were downregulated. Conversely, the GSE76220 dataset showed 4,850 upregulated genes and 7,691 downregulated genes. Using the STRING database, a protein–protein interaction (PPI) network was constructed to investigate the functional relationships among ALS-associated genes. The findings highlighted the significant role of the survival motor neuron 1 (SMN1) gene in ALS, particularly in sporadic cases. Additionally, drug-target network mapping identified potential therapeutic targets and candidate drugs, offering valuable insights into the molecular mechanisms of ALS and possible interventions. This integrative approach underscored SMN1 as a novel diagnostic biomarker and potential therapeutic target for ALS, emphasizing its critical role in disease pathogenesis. These findings pave the way for further mechanistic studies and clinical validation, aiming to enhance therapeutic strategies for ALS.
{"title":"Integrative analysis of transcriptomics and drug-target networks identifies SMN1 as a novel biomarker and therapeutic target for amyotrophic lateral sclerosis","authors":"Deboral Eshak, Mohanapriya Arumugam","doi":"10.1016/j.jgeb.2025.100615","DOIUrl":"10.1016/j.jgeb.2025.100615","url":null,"abstract":"<div><div>Amyotrophic lateral sclerosis (ALS) is a prevalent and debilitating neurodegenerative disorder characterized by the selective degeneration of motor neurons. This study aims to unravel the molecular mechanisms underlying ALS through an integrated analysis of drug-target networks and gene expression data. Gene expression datasets related to ALS, including GSE115130 and GSE76220, were retrieved from the GEO database and systematically analyzed. Differential gene expression (DEG) analysis identified key upregulated and downregulated genes, while weighted gene co-expression network analysis (WGCNA) uncovered gene modules associated with ALS pathology. DEG analysis revealed genetic insights into ALS by pinpointing genes potentially involved in disease development and progression. WGCNA provided a systems-level understanding of ALS mechanisms, identifying highly correlated gene clusters and their relationship with clinical ALS characteristics. In the GSE115130 dataset, 6,105 genes were upregulated and 6,069 were downregulated. Conversely, the GSE76220 dataset showed 4,850 upregulated genes and 7,691 downregulated genes. Using the STRING database, a protein–protein interaction (PPI) network was constructed to investigate the functional relationships among ALS-associated genes. The findings highlighted the significant role of the survival motor neuron 1 (SMN1) gene in ALS, particularly in sporadic cases. Additionally, drug-target network mapping identified potential therapeutic targets and candidate drugs, offering valuable insights into the molecular mechanisms of ALS and possible interventions. This integrative approach underscored SMN1 as a novel diagnostic biomarker and potential therapeutic target for ALS, emphasizing its critical role in disease pathogenesis. These findings pave the way for further mechanistic studies and clinical validation, aiming to enhance therapeutic strategies for ALS.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100615"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693135","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 : 2025-12-01DOI: 10.1016/j.jgeb.2025.100621
Katsuyoshi Kumagai , Ayumi Chiba , Hiroaki Yajima
Recent advances in design biology, including artificial cells, DNA nanostructures, artificial intelligence (AI)-driven molecular design, biofoundries, and next-generation genome editing, are transforming the health sciences of mind and body (HS-MB). Moving beyond traditional observational paradigms, these technologies enable predictive and design-oriented strategies for regulating stress, emotional health, achieving immune homeostasis, and managing lifestyle-related disorders. Psychological and social factors profoundly influence core physiological systems, including neuroendocrine (hypothalamic–pituitary–adrenal [HPA]) axis and cortisol rhythm, autonomic (vagal tone and heart rate variability), immune (cytokine balance and inflammatory control), metabolic (glucose–insulin regulation), and sleep–circadian systems. Artificial cells serve as controllable models for neurotransmitter signaling, immune interactions, and gut–brain communication, while DNA origami provides programmable nanocarriers that complement lipid nanoparticles (LNPs). Genome-editing innovations—such as prime, base, and epigenome editing—facilitate precise and reversible modulation of psychiatric risk genes, particularly when combined with induced pluripotent stem cell (iPSC) and brain-organoid models. Biofoundries integrate AI into Design–Build–Test–Learn (DBTL) cycles, automating molecular discovery and optimization. Ethical and regulatory considerations, including AI transparency, biocontainment, and dual-use governance, must be incorporated from the outset. Collectively, design biology, when strategically aligned with HS-MB, establishes a foundational framework for twenty-first-century medicine that bridges molecular engineering and holistic well-being.
{"title":"Design biology and mind–body health","authors":"Katsuyoshi Kumagai , Ayumi Chiba , Hiroaki Yajima","doi":"10.1016/j.jgeb.2025.100621","DOIUrl":"10.1016/j.jgeb.2025.100621","url":null,"abstract":"<div><div>Recent advances in design biology, including artificial cells, DNA nanostructures, artificial intelligence (AI)-driven molecular design, biofoundries, and next-generation genome editing, are transforming the health sciences of mind and body (HS-MB). Moving beyond traditional observational paradigms, these technologies enable predictive and design-oriented strategies for regulating stress, emotional health, achieving immune homeostasis, and managing lifestyle-related disorders. Psychological and social factors profoundly influence core physiological systems, including neuroendocrine (hypothalamic–pituitary–adrenal [HPA]) axis and cortisol rhythm, autonomic (vagal tone and heart rate variability), immune (cytokine balance and inflammatory control), metabolic (glucose–insulin regulation), and sleep–circadian systems. Artificial cells serve as controllable models for neurotransmitter signaling, immune interactions, and gut–brain communication, while DNA origami provides programmable nanocarriers that complement lipid nanoparticles (LNPs). Genome-editing innovations—such as prime, base, and epigenome editing—facilitate precise and reversible modulation of psychiatric risk genes, particularly when combined with induced pluripotent stem cell (iPSC) and brain-organoid models. Biofoundries integrate AI into Design–Build–Test–Learn (DBTL) cycles, automating molecular discovery and optimization. Ethical and regulatory considerations, including AI transparency, biocontainment, and dual-use governance, must be incorporated from the outset. Collectively, design biology, when strategically aligned with HS-MB, establishes a foundational framework for twenty-first-century medicine that bridges molecular engineering and holistic well-being.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100621"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623554","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 : 2025-11-21DOI: 10.1016/j.jgeb.2025.100612
Amany I. Almars , Shahad W. Kattan
Leukemogenesis fundamentally depends on the interaction between Menin and MLL1 fusion proteins, especially in the context of aggressive mixed-lineage leukemia (MLL)-rearranged subtypes. This interaction can be disrupted to facilitate a focused therapeutic strategy. This study aimed to employ a comprehensive in silico drug repurposing strategy to identify new inhibitors of the Menin-MLL1 interaction. A comprehensive library of FDA-approved pharmaceuticals was subjected to a rigorous screening process utilizing virtual methodologies, clustering techniques, and a machine learning-based model (PSICHIC) to forecast binding affinity, subsequently complemented by molecular docking and an assessment of drug-likeness. Compounds that surpassed the antagonist value of the control (0.97076 kcal/mol) were selected for subsequent molecular docking investigations. The leading candidate, compound 52920501, exhibited a remarkable binding energy of − 8.89 kcal/mol in contrast to the control (DS-1594b), alongside advantageous pharmacokinetic characteristics and electronic stability, as validated by Density Functional Theory (DFT). Consistent docking interactions with critical residues (Asn282, Asp285, Asn244) facilitated by 52920501. Molecular dynamics simulations (300 ns) demonstrated that 52,920,501 sustained a stable interaction with Menin, promoted protein compaction, and reduced structural fluctuations. The MM/GBSA analysis conducted over the final 50 ns of the MD simulation revealed that compound 52,920,501 established a stable protein–ligand complex, exhibiting a final ΔTOTAL energy of − 12.83 kcal/mol. This value is comparable to the control, which recorded − 13.41 kcal/mol, yet demonstrates stronger individual interaction components. The inclusion of entropic contributions indicated a binding free energy (ΔG Binding) of − 4.75 kcal/mol for 52920501, in contrast to + 7.05 kcal/mol for the control, highlighting its enhanced binding thermodynamics. The steered molecular dynamics (SMD) simulations provided additional validation of 52920501′s robust binding affinity, exhibiting a greater resistance (600 kJ/mol/nm) to external pulling forces in comparison to the control. In summary, compound 52,920,501 presents itself as a promising therapeutic candidate, bolstered by persuasive computational data that underscores its potential as a Menin-MLL1 inhibitor. It warrants further exploration through subsequent in vitro and in vivo studies.
{"title":"Identification of novel Menin-MLL interaction inhibitors targeting leukemia using in-silico virtual screening and structure-based drug design approaches","authors":"Amany I. Almars , Shahad W. Kattan","doi":"10.1016/j.jgeb.2025.100612","DOIUrl":"10.1016/j.jgeb.2025.100612","url":null,"abstract":"<div><div>Leukemogenesis fundamentally depends on the interaction between Menin and MLL1 fusion proteins, especially in the context of aggressive mixed-lineage leukemia (MLL)-rearranged subtypes. This interaction can be disrupted to facilitate a focused therapeutic strategy. This study aimed to employ a comprehensive in silico drug repurposing strategy to identify new inhibitors of the Menin-MLL1 interaction. A comprehensive library of FDA-approved pharmaceuticals was subjected to a rigorous screening process utilizing virtual methodologies, clustering techniques, and a machine learning-based model (PSICHIC) to forecast binding affinity, subsequently complemented by molecular docking and an assessment of drug-likeness. Compounds that surpassed the antagonist value of the control (0.97076 kcal/mol) were selected for subsequent molecular docking investigations. The leading candidate, compound <strong>52920501</strong>, exhibited a remarkable binding energy of − 8.89 kcal/mol in contrast to the control (DS-1594b), alongside advantageous pharmacokinetic characteristics and electronic stability, as validated by Density Functional Theory (DFT). Consistent docking interactions with critical residues (Asn282, Asp285, Asn244) facilitated by <strong>52920501</strong>. Molecular dynamics simulations (300 ns) demonstrated that <strong>52,920,501</strong> sustained a stable interaction with Menin, promoted protein compaction, and reduced structural fluctuations. The MM/GBSA analysis conducted over the final 50 ns of the MD simulation revealed that compound <strong>52,920,501</strong> established a stable protein–ligand complex, exhibiting a final ΔTOTAL energy of − 12.83 kcal/mol. This value is comparable to the control, which recorded − 13.41 kcal/mol, yet demonstrates stronger individual interaction components. The inclusion of entropic contributions indicated a binding free energy (ΔG Binding) of − 4.75 kcal/mol for <strong>52920501</strong>, in contrast to + 7.05 kcal/mol for the control, highlighting its enhanced binding thermodynamics. The steered molecular dynamics (SMD) simulations provided additional validation of <strong>52920501</strong>′s robust binding affinity, exhibiting a greater resistance (600 kJ/mol/nm) to external pulling forces in comparison to the control. In summary, compound <strong>52,920,501</strong> presents itself as a promising therapeutic candidate, bolstered by persuasive computational data that underscores its potential as a Menin-MLL1 inhibitor. It warrants further exploration through subsequent in vitro and in vivo studies.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100612"},"PeriodicalIF":2.8,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578752","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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