Molecular Biotechnology最新文献

{"title":"Targeting Monkeypox Virus Methyltransferase: Virtual Screening of Natural Compounds from Middle-Eastern Medicinal Plants.","authors":"Hayder O Hashim, Jafar M B Al-Shuhaib, Mudher K Mohammed, Mohammed Baqur S Al-Shuhaib","doi":"10.1007/s12033-024-01246-y","DOIUrl":"https://doi.org/10.1007/s12033-024-01246-y","url":null,"abstract":"<p><p>Monkeypox is an infectious disease resulting from the monkeypox virus, and its fatality rate varies depending on the virus clade and the location of the outbreak. In monkeypox virus, methyltransferase (MTase) plays a crucial role in modifying the cap structure of viral mRNA. This alteration assists the virus in evading the host's immune system, enhances viral protein synthesis, and ultimately enables successful infection and replication within host cells. Given the significance of MTase in viral infection and spread within the host, our study aimed to identify a natural inhibitor for this enzyme using docking and molecular dynamic (MD) simulations. We collected a total of 12,971 natural compounds from 200 medicinal plants in the Middle East. After eliminating duplicate compounds, we had 5,749 unique ligand conformers, which we then subjected to high-throughput virtual screening against MTase. The most promising hits were further evaluated using the extra-precision (XP) tool. The affinity of these hits was also assessed by Prime-Molecular Mechanics/Generalized Born Surface Area (MMGBSA) tool. The analysis revealed that two standard controls (sinefungin and TO1119) and two Middle-Eastern compounds (folic acid and 1,2,4,6-tetragalloylglucose) exhibited the best XP docking scores. According to Prime MMGBSA calculations, the Middle-Eastern compounds showed higher affinities, with values of - 60.61 kcal/mol for 1,2,4,6-tetragalloylglucose and - 51.87 kcal/mol for folic acid, surpassing the controls (TO1119 at - 35.71 kcal/mol and sinefungin at - 31.51 kcal/mol). In the majority of Molecular dynamic (MD) simulations, folic acid exhibited demonstrated greater stability than sinefungin. Further investigation revealed that folic acid occupied a critical position in the active site of MTase, which reduced its interaction with the mRNA substrate. Based on these findings, it can be concluded that folic acid is a highly promising natural compound for potential use in the cost-effective treatment of monkeypox virus. The identification of folic acid as a potential antiviral agent highlights the importance of nature in providing new therapeutic uses that have significant implications for global health, particularly in regions where monkeypox viral outbreaks are prevalent. However, it is essential to note that further wet-lab validations are necessary to confirm its efficacy for treatment in a medical context.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bibliometric Analysis of Global Research on Circular RNA: Current Status and Future Directions.","authors":"Lv Yehui, Li Zhihong, Tong Fang, Zeng Zixuan, Zhang Mengyuan, Yang Zhifang, Zhao Jiuhong","doi":"10.1007/s12033-023-00830-y","DOIUrl":"10.1007/s12033-023-00830-y","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) have gained significant attention in recent years. This bibliometric analysis aimed to provide insights into the current state and future trends of global circRNA research. The scientific output on circRNAs from 2010 to 2022 was retrieved from the Web of Science Core Collection with circRNA-related terms as the subjects. Key bibliometric indicators were calculated and evaluated using CiteSpace. A total of 7385 studies on circRNAs were identified. The output and citation number have increased rapidly after 2015. China, the USA, and Germany were top three publishing countries. Currently, circCDR1as, circHIPK3, circPVT1, circSHPRH, and circZNF609 are the most studied circRNAs; and all are related to cancer. The theme of research have shifted from transcript, exon circularization and miRNA sponge topics to the transcriptome, tumor suppressor, and biomarkers, indicating that research interests have evolved from basic to applied research. CircRNAs will continue to be a highly active research area in the near future. From the current understanding of circRNA characterization and regulatory mechanisms as miRNA sponges in cancer, future directions may examine potential diagnostic and therapeutic roles of circRNAs in cancers or the function and mechanism of circRNAs in other diseases.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10013806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription Factor FOXA1 Facilitates Glycolysis and Proliferation of Lung Adenocarcinoma via Activation of TEX19.","authors":"Yanfei Zhang, Huichao Sheng, Yuan Fu, Lin Chen","doi":"10.1007/s12033-023-00848-2","DOIUrl":"10.1007/s12033-023-00848-2","url":null,"abstract":"<p><p>Glycolysis is a shared feature in various cancers including lung adenocarcinoma (LUAD). Testis Expressed 19 (TEX19) is correlated with cancer progression. But its effect on LUAD remains an unanswered question. The focus of our study was primarily to investigate how TEX19 works exactly in LUAD. We first downloaded mRNA data from TCGA-LUAD and performed differential expression analysis. Then, we performed a Kaplan-Meier analysis to analyze the relationship between mRNA expression and patients' prognoses. hTFtarget database was utilized for the prediction of upstream transcription factors of mRNA. Next, qRT-PCR was employed for detecting TEX19 and Forkhead box A1 (FOXA1) expression. Western blot was adopted to detect the expression of glycolysis-related proteins. We also used CCK-8, colony formation, and flow cytometry assays to detect cell viability, proliferation, and apoptosis. Seahorse XF Extracellular Flux Analyzers were introduced to analyze extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Detection kits were used to detect pyruvate, lactate, citric acid, and malic acid. TEX19 was highly expressed in LUAD tissues. Real-time quantitative PCR (qRT-PCR) assay showed that TEX19 was significantly overexpressed in LUAD cell lines compared with normal bronchial epithelial cells BEAS-2B. Knockdown of TEX19 remarkably inhibited cell activity and proliferation, and promoted cell apoptosis, TEX19 was enriched in the glycolytic pathway. Meanwhile, the knockdown of TEX19 significantly hampered the contents of pyruvate, lactate, citric acid, and malic acid. The bioinformatics analysis, dual luciferase reporter experiment, and chromatin immunoprecipitation (ChIP) assay showed that FOXA1 was bound with TEX19. FOXA1 had a high expression level in LUAD. The rescue assay demonstrated that FOXA1, by activating TEX19 expression, enhanced glycolysis and proliferation and inhibited apoptosis of LUAD cells. In summary, FOXA1 promoted glycolysis and proliferation of LUAD cells by activating TEX19. This result can provide a theoretical basis for future research on LUAD.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10037776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple Functions of Compatible Solute Ectoine and Strategies for Constructing Overproducers for Biobased Production.","authors":"Wei Zhang, Kun Liu, Fang Kong, Tao Ye, Tianwen Wang","doi":"10.1007/s12033-023-00827-7","DOIUrl":"10.1007/s12033-023-00827-7","url":null,"abstract":"<p><p>Ectoine and its derivative 5-hydroxyectoine are compatible solutes initially found in the hyperhalophilic bacterium Ectothiorhodospira halochloris, which inhabits the desert in Egypt. The habitat of ectoine producers implies the primary function of ectoine as a cytoprotectant against harsh conditions such as high salinity, drought, and high radiation. More extensive and in-depth studies have revealed the multiple functions of ectoine in its native producer bacterial cells and other types of cells and its biomolecular components (such as proteins and DNA) as a general protective agent. Its chemical properties as a bio-based amino acid derivative make it attractive for basic scientific research and related industries, such as the food/agricultural industry, cosmetic manufacturing, biologics, and therapeutic agent preparation. This article first discusses the functions and applications of ectoine and 5-hydroxyectoine. Subsequently, more emphasis was placed on advances in bio-based ectoine and/or 5-hydroxyectoine production. Strategies for developing more robust cell factories for highly efficient ectoine and/or 5-hydroxyectoine production are further discussed. We hope this review will provide a valuable reference for studies on the bio-based production of ectoine and 5-hydroxyectoine.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10242594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of Potential Inhibitors Targeting the Main Protease Structure of SARS-CoV-2 via Molecular Docking, and Approach with Molecular Dynamics, RMSD, RMSF, H-Bond, SASA and MMGBSA.","authors":"Aluísio Marques da Fonseca, Bernardino Joaquim Caluaco, Junilson Martinho Canjanja Madureira, Sadrack Queque Cabongo, Eduardo Menezes Gaieta, Faustino Djata, Regilany Paulo Colares, Moises Maia Neto, Carla Freire Celedonio Fernandes, Gabrielle Silva Marinho, Hélcio Silva Dos Santos, Emmanuel Silva Marinho","doi":"10.1007/s12033-023-00831-x","DOIUrl":"10.1007/s12033-023-00831-x","url":null,"abstract":"<p><p>Severe Acute Respiratory Syndrome caused by a coronavirus is a recent viral infection. There is no scientific evidence or clinical trials to indicate that possible therapies have demonstrated results in suspected or confirmed patients. This work aims to perform a virtual screening of 1430 ligands through molecular docking and to evaluate the possible inhibitory capacity of these drugs about the M^pro protease of Covid-19. The selected drugs were registered with the FDA and available in the virtual drug library, widely used by the population. The simulation was performed using the MolAiCalD algorithm, with a Lamarckian genetic model (GA) combined with energy estimation based on rigid and flexible conformation grids. In addition, molecular dynamics studies were also performed to verify the stability of the receptor-ligand complexes formed through analyses of RMSD, RMSF, H-Bond, SASA, and MMGBSA. Compared to the binding energy of the synthetic redocking coupling (-6.8 kcal/mol/RMSD of 1.34 Å), which was considerably higher, it was then decided to analyze the parameters of only three ligands: ergotamine (-9.9 kcal/mol/RMSD of 2.0 Å), dihydroergotamine (-9.8 kcal/mol/RMSD of 1.46 Å) and olysio (-9.5 kcal/mol/RMSD of 1.5 Å). It can be stated that ergotamine showed the best interactions with the M^pro protease of Covid-19 in the in silico study, showing itself as a promising candidate for treating Covid-19.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9866682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of SDC-1 Gene Alleviates the Metabolic Pathway for the Development of MODS.","authors":"Jiangang Xie, Yuexiang Ma, Yang Huang, Qianmei Wang, Yunyun Xu, Qi Zhang, Jing Yang, Wen Yin","doi":"10.1007/s12033-023-00809-9","DOIUrl":"10.1007/s12033-023-00809-9","url":null,"abstract":"<p><p>This study aims to reveal the metabolic differences between SDC-1 knockout mice and wild-type mice and the metabolic differences caused by shock in SDC-1 knockout mice by integrating transcriptomics and metabolomics. A total of 1009 differential metabolites were differentially expressed based on untargeted metabolomics and high-resolution mass spectrometry detection techniques. According to Kyoto Encyclopedia of Genes and Genomes enrichment, SDC-1 knockout significantly altered fat digestion and absorption, GnRH signaling pathway, fructose and mannose metabolism, and some other amino-related metabolic pathways and significantly modulated positively regulated longevity regulatory pathways, longevity regulatory pathways-worm, nicotinamide and niacinamide metabolism, and vitamin digestion and absorption pathways after its shock. Our findings indicate that SDC-1 knockout may have potential therapeutic effects in hemorrhagic shock by increasing nicotinamide metabolism.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9879678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement in Bacterial Cellulolytic Enzyme Production Using Acid-Pretreated Banana Peel Waste: A Comparative Evaluation.","authors":"Pathan Ahemad Khan, Basant Lal, Preeti Singh, Rajeev Singh, Asad Syed, Abdallah M Elgorban, Meenakshi Verma, P K Mishra, Bhawna Verma, Neha Srivastava, Anthonia O'Donovan","doi":"10.1007/s12033-023-00816-w","DOIUrl":"10.1007/s12033-023-00816-w","url":null,"abstract":"<p><p>Banana peel waste is one of the major contributors in the issue raised from solid waste, however, it can be valorized effectively due to high content of cellulose and hemicellulose. Significant conversion of banana waste includes cellulolytic enzymes and bioenergy production. In the present study, bacterial cellulase was produced using raw banana peel and ripe banana peel under SSF. Additionally, impact of acid pretreatment was investigated as one of strategy to improve cellulolytic enzyme production. A comparative evaluation of raw and ripe banana peels showed that ripe banana peels showed better enzyme production after pretreatment with 0.5% dilute HCl acid. In the series of enhancement of the enzyme production, temperature and pH of the SSF medium were also investigated, and found temperature 35 °C and pH 6.0 were optimum to produce maximum 3.5-U/ml FPA, 39-U/ml BGL, and 54-U/ml EG in 18-h SSF incubation. The study presented eco-friendly waste management to produce industrial enzyme for its promising application in waste valorization and biorefinery area.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9967417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Quantum Computing in the Next-Generation Computational Biology Landscape: from Protein Folding to Molecular Dynamics.","authors":"Soumen Pal, Manojit Bhattacharya, Sang-Soo Lee, Chiranjib Chakraborty","doi":"10.1007/s12033-023-00881-1","DOIUrl":"10.1007/s12033-023-00881-1","url":null,"abstract":"","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"O-GlcNAcylation of NLRP3 Contributes to Lipopolysaccharide-Induced Pyroptosis of Human Gingival Fibroblasts.","authors":"Hao Yang, Li Xiao, Dongxue Wu, Tingting Zhang, Ping Ge","doi":"10.1007/s12033-023-00846-4","DOIUrl":"10.1007/s12033-023-00846-4","url":null,"abstract":"<p><p>Periodontitis is a leading chronic oral disorder and poses a serious burden on public health. O-GlcNAc glycosylation (O-GlcNAcylation) is regulated only by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) and participates in the regulation of human gingival fibroblasts (HGFs) function. Hence, the purpose of this study is to investigate whether HGFs cell function and periodontitis pathogenesis are regulated by O-GlcNAcylation. Herein, we first established cell model of periodontitis induced by lipopolysaccharide (LPS). The cell viability was measured with CCK-8 assay. Pyroptosis was measured by flow cytometry and western blot. The inflammatory factors levels were detected with ELISA kits. Afterward, our findings indicated that LPS elevated the O-GlcNAcylation level of HGFs and inhibition of O-GlcNAcylation improved LPS-induced pyroptosis of HGFs. Mechanistically, LPS heightened the expression of OGT to induce the O-GlcNAcylation of NLRP3. Subsequently, we certified that Thr542 was the O-GlcNAcylation site of NLRP3. More importantly, upregulation of NLRP3 reversed the effects of OGT knockdown on LPS-induced pyroptosis. In general, the current research demonstrated that LPS contributed to the pyroptosis of HGFs by enhancing the OGT expression to promote O-GlcNAcylation of NLRP3, which suggested that O-GlcNAcylation of NLRP3 was a driving factor for periodontitis and offered a novel insight into the treatment of this disease.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9975217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laggera alata Attenuates Inflammatory Response by Regulating Macrophage Polarization in Rheumatoid Arthritis Mice.","authors":"Jiangcun Wei, Yunli Tang, Suhong Qin, Xiumei Ma, Wen Zhong, Peng Yang, Qingmei Deng, Jiabao Ma","doi":"10.1007/s12033-023-00808-w","DOIUrl":"10.1007/s12033-023-00808-w","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a type of joint injury, which can induce the activation of inflammatory factors and polarization of tissue macrophages. Total phenolics from Laggera alata (TPLA) has been reported to exhibit anti-inflammatory effect in various diseases. However, its specific function in RA is still unknown. Here, the protective properties of TPLA were studied in collagen-induced arthritis (CIA)-induced RA mice. RA mouse model was established through the CIA induction. Arthritis score, hind paw thickness, and the body weight of the RA mice were evaluated in each group. H&E staining was conducted in hind paw and joint tissues for histopathological staining. The distal femur was analyzed by microCT, and bone loss-related indicators were assessed. The expression of macrophage polarization markers was detected by immunofluorescence staining in RA mice. The serum levels of inflammatory markers were determined by enzyme-linked immunosorbent assay (ELISA). TPLA reduced the CIA-induced arthritis score and hind paw thickness in mice. The body weight of the CIA mouse was significantly increased by TPLA treatment. TPLA improved the CIA-induced histopathological changes in the hind paw and joint tissues from the mice. TPLA inhibited the bone loss and alleviated bone destruction in CIA mouse model. TPLA altered the macrophage phenotype from M1 macrophages into M2 in CIA mice. TPLA suppressed the levels of inflammatory markers both in the serum and joint tissues of the CIA mice. TPLA mitigated RA development by suppressing inflammatory reaction through the inhibition of M1 microphage polarization.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9868641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}