{"title":"Electric-field induced sleep promotion and lifespan extension in Gaucher's disease model flies","authors":"Takaki Nedachi , Haruhisa Kawasaki , Eiji Inoue , Takahiro Suzuki , Yuzo Nakagawa-Yagi , Norio Ishida","doi":"10.1016/j.bbrep.2025.101915","DOIUrl":"10.1016/j.bbrep.2025.101915","url":null,"abstract":"<div><div>Gaucher's disease (GD) is a genetic disease characterized by a mutation in the metabolic enzyme glucocerebrosidase (GBA1), leading to the accumulation of glucosylceramide in tissues. We previously discovered that a <em>minos</em>-inserted mutation in the <em>GBA1</em> gene of fruit flies, <em>Drosophila melanogaster</em>, mimics human neuronopathic GD (nGD) characteristics, providing a promising model for studying the molecular mechanisms of the disease. We also reported that extremely low-frequency electric fields (ELF-EFs) promote sleep and extend the lifespan of wild-type flies.</div><div>In this study, we show that ELF-EFs have health-promoting effects on nGD model flies.</div><div>Firstly, the total sleep time and sleep episode duration of EF-exposed nGD model flies increased. EFs also extended the lifespans of nGD model flies. Additionally, the expression of the endoplasmic reticulum stress-related gene <em>PERK</em> and autophagy-related gene <em>p62</em> were elevated after EF exposure. The effects of EF exposure on nGD flies are associated with the change of these genes expression. Our findings suggest that EF exposure may be effective as an additional therapy for nGD.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101915"},"PeriodicalIF":2.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063516","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}
{"title":"Identification of novel microRNAs: Biomarkers for pathogenesis of hepatocellular carcinoma in mice model","authors":"Shivani Priya , Lakhon Kma","doi":"10.1016/j.bbrep.2024.101896","DOIUrl":"10.1016/j.bbrep.2024.101896","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is the most fatal cancer that has affected both male and female populations globally. With poor diagnosis and patient survival rates, it has become a global need for scientists to come to the aid. The main objective of the study was to profile the miRNAs in the serum of Control and DEN-treated mice at different time intervals (4 Weeks, 8 Weeks, 12 Weeks, and 16 Weeks) and identify HCC-associated miRNA as putative early biomarkers along with the miRNA regulated candidate gene which may be involved in HCC. Our study group involves 4,8,12, & 16 weeks 16-week-old treated male mice. Each group was sacrificed and analyzed for the stages of HCC. We employed <em>in silico</em> techniques for the small RNA-Seq and bioinformatics pipeline for further analysis. Our analysis revealed over 400 differentially expressed miRNAs in each treated sample and 10 novel miRNAs. The downstream analysis of these differentially expressed miRNAs, and their target genes opened an arena of different biological processes and pathways that these miRNAs affect during the development of HCC. The work has a promising role as the miRNAs predicted through this study can be used as biomarkers for early detection of HCC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101896"},"PeriodicalIF":2.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063518","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}
{"title":"A comprehensive outline of the role of non-coding RNAs in vitiligo","authors":"Fateme Sadat Feghahati, Soudeh Ghafouri-Fard","doi":"10.1016/j.bbrep.2025.101916","DOIUrl":"10.1016/j.bbrep.2025.101916","url":null,"abstract":"<div><div>Vitiligo is a common skin depigmentation condition caused by selective destruction of melanocytes. It is regarded as a polygenic disorder. In addition to protein-coding loci, non-coding regions of the genome contribute to the pathogenesis of vitiligo. A bulk of evidence highlights contribution of different classes of non-coding RNAs in this condition. Expression profile of different non-coding RNAs has been evaluated in the plasma, serum, blood cells and skin samples of patients with vitiligo. Notably, these transcripts not only partake the pathogenesis of vitiligo, but also are regarded as putative targets for prospective treatment strategies for this disorder. The current review focuses on depicting the role of miRNAs, long non-coding RNAs and circular RNAs in the etiology of vitiligo. Moreover, we discuss the shared functions of these transcripts in the pathogenesis of vitiligo and melanoma.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101916"},"PeriodicalIF":2.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063515","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}
{"title":"Methylmalonic acid at the serum level in the elderly contributes to cell growth via mitochondrial dysfunction in colorectal cancer cell spheroids","authors":"Arowu R. Tanaka, Chiho Murakami, Hideya Yamamoto","doi":"10.1016/j.bbrep.2024.101909","DOIUrl":"10.1016/j.bbrep.2024.101909","url":null,"abstract":"<div><div>Methylmalonic acid (MMA) is a small molecule produced during the metabolism of propionate and branched-chain amino acids. Recently, it has been reported that the blood concentration of MMA increases with age and promotes lung cancer metastasis. However, little is known regarding its effects on cancers other than lung cancer. In the present study, we examined the effects of MMA on colorectal cancer cell spheroids. We found that MMA promoted the proliferation of colorectal cancer spheroids at physiological concentrations that can be exhibited by the elderly and induced mitochondrial reactive oxygen species generation, which in turn affected the promotion of cell growth. MMA treatment also induces a metabolic shift in the glycolytic system. These results suggest that MMA may promote cancer cell proliferation by decreasing mitochondrial function, inducing a metabolic shift, and provide new insights into the effects of aging on cancer.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101909"},"PeriodicalIF":2.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063519","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}
Noah Shackelford, Zach Zavodny, Samantha Schindler, Nathan Fancher, Allen A. Thomas, Michael A. Moxley
{"title":"Human citrate synthase kinetic simulation to fit rapid, direct, and thiol probe coupled kinetic data","authors":"Noah Shackelford, Zach Zavodny, Samantha Schindler, Nathan Fancher, Allen A. Thomas, Michael A. Moxley","doi":"10.1016/j.bbrep.2025.101914","DOIUrl":"10.1016/j.bbrep.2025.101914","url":null,"abstract":"<div><div>Human citrate synthase (hCS) was kinetically characterized through full progress curve kinetic modelling using kinetic simulation, global fitting of the direct AcCoA to CoA transition, and a coupled thiol probe reaction to better determine the kinetics with low substrate concentration. Our analysis provides one of the most rigorous kinetic analyses of any citrate synthase ruling out the need to invoke complex cooperative mechanisms to explain progress curve data. Furthermore, we collected and modeled stopped-flow pH-dependent kinetic data with CoA and popular thiol probes such as Ellman's reagent (DTNB) and 4,4′-Dithiodipyridine (DPS), providing the opportunity for detailed kinetic simulations using these thiol probes with CoA producing enzymes. Global fitting suggests that the DPS/CoA bimolecular rate constant increased 100-fold via protonation of the pyridine ring (pKa = 5.2), quantifying its kinetic advantage relative to DTNB. To explore the kinetic effects of polar substituents on the pyridine ring, we synthesized three different DPS analogs by adding either an alcohol, amine, or carboxylic acid moiety to the pyridine ring. Of these, the alcohol group provided the most similar kinetic characteristics to DPS but greatly increases thiol probe polarity offering an alternative to DPS.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101914"},"PeriodicalIF":2.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063517","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}
{"title":"Computational identification of novel natural inhibitors against triple mutant DNA gyrase A in fluoroquinolone-resistant Salmonella Typhimurium","authors":"Sree Haryini, George Priya Doss C","doi":"10.1016/j.bbrep.2024.101901","DOIUrl":"10.1016/j.bbrep.2024.101901","url":null,"abstract":"<div><div>The rising resistance to fluoroquinolones in <em>Salmonella</em> Typhimurium poses a significant global health challenge. This computational research addresses the pressing need for new therapeutic drugs by utilizing various computational tools to identify potential natural compounds that can inhibit the triple mutant DNA gyrase subunit A enzyme, which is crucial in fluoroquinolone resistance. Initially, the three-dimensional structure of the wild-type DNA gyrase A protein was modeled using homology modeling, and followed by <em>in silico</em> mutagenesis to create the clinically relevant triple mutant (SER83PHE, ASP87GLY, ALA119SER) DNA gyrase A protein structure. The structural stability and integrity of the modeled protein were ensured through rigorous validation. Subsequently, a high-throughput virtual screening of a curated library of natural compounds was conducted to identify potential inhibitors against wild-type and triple-mutant proteins. The selected potent lead molecules comprehensively evaluated their physicochemical properties, ADME/T properties, and binding affinities via ADME/T assessment and molecular docking studies. The safest and most promising ligands were chosen for dynamics studies to analyze their dynamic behavior and protein stability before and after the binding of ligands. Our results showed that the natural compounds from the ChemDiv database, CID: 0407–0108, N039-0003, 1080–0568, and 0099–0261 have binding energies ranging from −4.32 to −5.69 kcal/mol and exhibit excellent physio-chemical properties, affinities, and are stable in their dynamic environments over 100 ns for both wild-type and triple mutant DNA gyrase A complexes. These compounds provide a promising alternative treatment for fluoroquinolone-resistant <em>Salmonella</em> Typhimurium infections.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101901"},"PeriodicalIF":2.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045532","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}
ZhongLi Liao , XueFeng Tang , Bin Yang , Jian Yang
{"title":"Dopamine receptors and organ fibrosis","authors":"ZhongLi Liao , XueFeng Tang , Bin Yang , Jian Yang","doi":"10.1016/j.bbrep.2024.101910","DOIUrl":"10.1016/j.bbrep.2024.101910","url":null,"abstract":"<div><div>Organ fibrosis, considered as a major global health concern, is a pathological condition often occurring after tissue injury in various organs. The pathogenesis of fibrosis involves multiple phases and multiple cell types. Dopamine is involved in various life activities by activating five receptors (D1, D2, D3, D4, D5). Activation or loss of function of dopamine receptors has been reported to be associated with the fibrosis of several organs, such as ocular, lung, liver, heart, and kidney. In this paper, we review dopamine receptors’ potential roles in organ fibrosis and mechanisms by which organ fibrosis develops or decreases when dopamine receptors function is activated or perturbed.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101910"},"PeriodicalIF":2.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045534","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}
{"title":"Elucidating the therapeutic potential of indazole derivative bindarit against K-ras receptor: An in-silico analysis using molecular dynamics exploration","authors":"Parmar Keshri Nandan, Jayanthi Sivaraman","doi":"10.1016/j.bbrep.2024.101913","DOIUrl":"10.1016/j.bbrep.2024.101913","url":null,"abstract":"<div><div>Ras gene is frequently mutated in cancer. Among different subtypes of Ras gene, K-Ras mutation occurs in nearly 30 % of human cancers. K-Ras mutation, specifically K-Ras (G12D) mutation is prevalent in cancers like lung, colon and pancreatic cancer. During cancer occurrence, mutant Ras remain in activated form (GTP bound state) for cancer cell proliferation. In the quest for a potential K-Ras inhibitor, nitrogen-containing indazole derivatives can show promise as inhibitors, as they have numerous therapeutic properties like anti-inflammatory, anti-viral and anti-tumor. Furthermore, among various indazole derivatives, “Bindarit” is an important therapeutic compound which could have potential inhibitory action against K-Ras due to its structural resemblance with reference compound “Benzimidazole”. So, the current study is an attempt to find out the inhibitory effect of Bindarit against K-Ras activation by binding to a pocket which is adjacent to the switch I/II regions of the K-Ras receptor. AutoDock tool was used to investigate the binding affinity of protein ligand interaction and GROMACS package was utilised to assess their interactions in a dynamic setting. Bindarit shows better binding affinity than reference with binding energy of −7.3 kcal/mol. Upon ligand binding conformational changes take place, which could lead to the loss of GTPase activity. Consequently, further downstream signalling of the K-Ras pathway would be blocked and this could lead to the inhibition of K-Ras dependent cancer cell proliferation. However, further validation of present study can be done through experimental assay such as cytotoxic and protein expression analysis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101913"},"PeriodicalIF":2.3,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045537","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}
Lichao Cao , Ying Ba , Fang Chen , Dandan Li , Shenrui Zhang , Hezi Zhang
{"title":"The prognostic significance of epoxide hydrolases in colorectal cancer","authors":"Lichao Cao , Ying Ba , Fang Chen , Dandan Li , Shenrui Zhang , Hezi Zhang","doi":"10.1016/j.bbrep.2024.101912","DOIUrl":"10.1016/j.bbrep.2024.101912","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a common malignant cancer. Epoxide hydrolases (EHs) are involved in the development of cancer by regulating epoxides, but their relationship with CRC is unclear. We used multiple datasets to confirm the expression of different EPHX family members in CRC tissues, and to explore their association with different clinicopathologic characteristics. The Kaplan–Meier method, correlation analysis and random forest algorithm were used to evaluate the prognostic value of EPHX family members for CRC. Finally, the cell experiment verified function of EPHX4 in CRC. The expressions of EPHX1 and EPHX2 were significantly decreased, while those of EPHX3 and EPHX4 were significantly increased in CRC. The expressions of EPHX family members were correlated with some clinicopathologic features and overall survival. The expressions of the EPHX family were positively associated with CD274, CTLA4, HAVCR2, and TIGIT. EPHX2 and EPHX4 were diagnostic and predictive biomarkers for CRC. EPHX4 promoted the malignant phenotype of CRC cells. Our study firstly elucidated the prognostic significance of EPHX family members in CRC and identified novel diagnostic and prognostic biomarkers for CRC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101912"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027582","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}
{"title":"Exploring miRNA profile associated with cisplatin resistance in ovarian cancer cells","authors":"Yaman Alghamian , Chadi Soukkarieh , Abdulmunim Aljapawe , Hossam Murad","doi":"10.1016/j.bbrep.2024.101906","DOIUrl":"10.1016/j.bbrep.2024.101906","url":null,"abstract":"<div><div>Ovarian cancer is a common and lethal malignancy among women, whereas chemoresistance is one of the major challenges to its treatment and prognosis. Chemoresistance is a multifactorial phenomenon, involving various mechanisms that collectively modify the cell's response to treatment. Among the changes that arise in cells after acquiring chemoresistance is miRNA dysregulation. Here, this study aimed to identify miRNAs expression changes related to cisplatin resistance in ovarian cancer cells. The miRNA expression profiles of a cisplatin-sensitive A2780 cell line and two cisplatin-resistant cell lines, A2780cis and SK-OV-3, were analyzed using PCR array and qPCR. Accordingly, the miRNAs that were differentially expressed were further investigated to identify their biological functions and the target pathways using Gene Ontology (GO) annotation and KEGG pathway analyses. In order to evaluate the clinical significance of the differentially expressed miRNAs, survival analysis was carried out using expression data for ovarian cancer patients available in the Kaplan-Meier (KM) plotter database. The current work demonstrates that Nine miRNAs were found to be upregulated in cells resistant to cisplatin. Clearly, these miRNAs have functions in cell death/survival related processes and treatment response. They may also target pathways involved in treatment response like PI3K-Akt, pathway in cancer and MAPK. Interestingly, High expression of hsa-miR-133b, hsa-miR-512-are, hsa-miR-200b-3p, and hsa-miR-451a is related to poor overall survival in patients diagnosed with ovarian cancer. Our findings suggest that hsa-miR-133b, hsa-miR-512-5p, hsa-miR-200b-3p, and hsa-miR-451a are good candidates for future studies aimed to establishing functional links and exploring therapeutic interventions to overcome cisplatin resistance.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101906"},"PeriodicalIF":2.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999293","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}