Molecular Biotechnology最新文献

{"title":"PerR: A Peroxide Sensor Eliciting Metal Ion-dependent Regulation in Various Bacteria","authors":"Divya Kandari, Hemant Joshi","doi":"10.1007/s12033-024-01266-8","DOIUrl":"https://doi.org/10.1007/s12033-024-01266-8","url":null,"abstract":"<p>Bacteria have to thrive in difficult conditions wherein their competitors generate partially reduced forms of oxygen, like hydrogen peroxide and superoxides. These oxidative stress molecules can also arise from within via the autoxidation of redox enzymes. To adapt to such conditions, bacteria express detox enzymes as well as repair proteins. Transcription factors regulate these defenses, and PerR is one of them. PerR is a Fur family transcriptional regulator that senses peroxide stress. Metal-bound PerR (either Mn²⁺ or Fe²⁺) can repress transcription of its regulon, but only the Fe²⁺-bound form of PerR can sense H₂O₂. This review describes different aspects of PerR and its varied roles, specifically in bacterial pathogens. Despite having roles beyond sensing peroxides, it is an underrated regulator that needs to be explored more deeply in pathogens.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254001","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":"Identification of the Potential Role of the E4orf4 Protein in Adenovirus A, B, C, and D Groups in Cancer Therapy: Computational Approaches","authors":"Niloofar Khakpour, Amin Zahmatkesh, Seyed Younes Hosseini, Hassan Ghamar, Navid Nezafat","doi":"10.1007/s12033-024-01278-4","DOIUrl":"https://doi.org/10.1007/s12033-024-01278-4","url":null,"abstract":"<p>The human adenovirus (HADV) early region 4 open reading frame 4 (E4orf4) protein plays a regulatory role in promoting viral infection by interacting with various cellular proteins. E4orf4 can induce death in cancer cells. One of the death pathways that is induced by this protein is related to the formation of membrane blebbing following the phosphorylation of tyrosine amino acids. The activation of this pathway requires the interaction of E4orf4 with Src family kinases (SFKs). The modulation mechanism of Src-dependent signaling via E4orf4 is not yet fully understood. However, evidence suggests that a physical association between the Src kinase domain and the arginine-rich motif of E4orf4 is crucial. Physically connecting E4orf4 to Src kinase leads to the deregulation of the Src-related signaling pathway, thereby inducing cytoplasmic death. In this study, we mapped the E4orf4 interaction site in Src to investigate the interaction between E4orf4 and Src in detail. We also compared the binding strength of E4orf4 proteins from different HADV groups. To this end, we performed bioinformatics structural analysis of the Src kinase domain and E4orf4 to identify E4orf4 interaction sites. The group with the lowest binding energy was predicted to be the most likely candidate for the highest cytoplasmic death in tumor cells based on the energy of the E4orf4–Src complex in various HADV groups. These results show that HADV-A and HADV-C have minimal binding energies to the E4orf4–Src complex, while the dissociation constant (Kd) of HADV-A was less than that of HADV-C. According to the obtained results, E4orf4 of the HADV-A group is more effective at triggering cytoplasmic death based on its most robust interaction with the Src kinase domain.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217361","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":"The First Introduction of an Exogenous 5ʹ Untranslated Region for Control of Plastid Transgene Expression in Chlamydomonas reinhardtii","authors":"Mohammad Ali Abbasi-Vineh, Masoumeh Emadpour","doi":"10.1007/s12033-024-01279-3","DOIUrl":"https://doi.org/10.1007/s12033-024-01279-3","url":null,"abstract":"<p>The utilization of heterologous 5' untranslated regions (5′UTRs) for expressing foreign proteins in the chloroplast of <i>Chlamydomonas reinhardtii</i> (<i>C. reinhardtii</i>) has posed a persistent challenge over the years. This challenge stems from the lack of a defined and comprehensive set of translational <i>cis</i>-elements responsible for stability, ribosome binding, and translation initiation, which are mediated by <i>trans</i>-acting factors native to <i>C. reinhardtii</i>. In the current study, we aimed to address this bottleneck by employing the 5′UTR from gene 10 of the T7 bacteriophage (T7g10 5'UTR), fused to the promoter of <i>C. reinhardtii</i> small subunit ribosomal RNA (<i>rrn</i>S), to facilitate the translation of a reporter gene, <i>YFP</i>. Using a chimeric construct, the YFP mRNA was efficiently translated utilizing the heterologous T7g10 5′UTR. Furthermore, the accumulation of YFP protein under the control of the T7g10 5′UTR was approximately one third of that observed under the control of the endogenous <i>psaA</i> promoter/5′UTR in the <i>C. reinhardtii</i> chloroplast. The results of computational analyses demonstrated that the T7g10 5ʹUTR sequence shares common elements with the endogenous 5ʹUTRs of the chloroplast genes. Moreover, the findings of the current study highlighted the potential of employing bacteriophage 5′UTRs for the foreign protein accumulation from the chloroplast genome of <i>C. reinhardtii</i>.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253867","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":"Angiotensin-Converting Enzyme-2 (ACE2) Downregulation During Coronavirus Infection","authors":"Nurshamimi Nor Rashid, Lina Amrani, Abdullah Alwan, Zulqarnain Mohamed, Rohana Yusof, Hussin Rothan","doi":"10.1007/s12033-024-01277-5","DOIUrl":"https://doi.org/10.1007/s12033-024-01277-5","url":null,"abstract":"<p>Angiotensin-converting enzyme-2 (ACE2) downregulation represents a detrimental factor in people with a baseline ACE2 deficiency associated with older age, hypertension, diabetes, and cardiovascular diseases. Human coronaviruses, including HCoV-NL63, SARS-CoV-1, and SARS CoV-2 infect target cells via binding of viral spike (S) glycoprotein to the ACE2, resulting in ACE2 downregulation through yet unidentified mechanisms. This downregulation disrupts the enzymatic activity of ACE2, essential in protecting against organ injury by cleaving and disposing of Angiotensin-II (Ang II), leading to the formation of Ang 1–7, thereby exacerbating the accumulation of Ang II. This accumulation activates the Angiotensin II type 1 receptor (AT1R) receptor, leading to leukocyte recruitment and increased proinflammatory cytokines, contributing to organ injury. The biological impacts and underlying mechanisms of ACE2 downregulation during SARS-CoV-2 infection have not been well defined. Therefore, there is an urgent need to establish a solid theoretical and experimental understanding of the mechanisms of ACE2 downregulation during SARS-CoV-2 entry and replication in the host cells. This review aims to discuss the physiological impact of ACE2 downregulation during coronavirus infection, the relationship between ACE2 decline and virus pathogenicity, and the possible mechanisms of ACE2 degradation, along with the therapeutic approaches.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217267","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":"Potential of Exosomes as Multifunctional Nanocarriers for Targeted Drug Delivery","authors":"Safa Ali Al-Ani, Qiao Ying Lee, Danesha Maheswaran, Yuh Miin Sin, Jian Sheng Loh, Jhi Biau Foo, Sharina Hamzah, Jeck Fei Ng, Li Kar Stella Tan","doi":"10.1007/s12033-024-01268-6","DOIUrl":"https://doi.org/10.1007/s12033-024-01268-6","url":null,"abstract":"<p>Exosomes are small vesicles that form when multivesicular bodies fuse with the plasma membrane and are released into body fluids. They play a vital role in facilitating communication between cells by transferring different biomolecules, including DNA, RNA, proteins, and lipids, over both short and long distances. They also function as vital mediators in both states of health and disease, exerting an impact on several physiological processes. Exosomes have been modified to overcome the limitations of natural exosomes to enhance their potential as carriers for drug delivery systems, and these modifications aim to improve the drug delivery efficiency, enhance tissue and organ targeting, and prolong the circulating half-life of exosomes. This review discussed recent advancements in exosome nanotechnology, as well as the progression and use of exosomes for drug delivery. The potential commercialisation and challenges associated with the use of exosome-based drug delivery systems were also discussed, aiming to motivate the development of exosome-based theranostic nanoplatforms and nanotechnology for improved healthcare treatments.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217303","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":"Phytochemicals of Different Medicinal Herbs as Potential Inhibitors Against Dengue Serotype 2 Virus: A Computational Approach","authors":"Diya Roy, M. Manumol, Kalichamy Alagarasu, Deepti Parashar, Sarah Cherian","doi":"10.1007/s12033-024-01282-8","DOIUrl":"https://doi.org/10.1007/s12033-024-01282-8","url":null,"abstract":"<p>Dengue is one of the major mosquito-borne infectious diseases of the present century, reported to affect about 100–400 million people globally. The lack of effective therapeutic options has inspired several in vitro and in silico studies for the search of antivirals. Our previous study revealed the anti-dengue activity of different plant extracts from <i>Plumeria alba, Bacopa monnieri, Vitex negundo,</i> and <i>Ancistrocladus heyneanus</i>. Therefore, the current in silico study was designed to identify the phytochemicals present in the aforementioned plants, which are possibly responsible for the anti-dengue activity. Different plant databases as well as relevant literature were explored to find out the major compounds present in the above-stated plants followed by screening of the retrieved phytochemicals for the assessment of their binding affinity against different dengue viral proteins via molecular docking. The best poses of protein–ligand complexes obtained after molecular docking were selected for the calculation of binding free energy via MM-GBSA method. Based on the highest docking score and binding energy, six complexes were considered for further analysis. To analyze the stability of the complex, 100 ns molecular dynamics (MD) simulations were carried out using Desmond module in the Schrodinger suite. The MD simulation analysis showed that four compounds viz<i>.</i> liriodendrin, bacopaside VII, isoorientin, and cynaroside exhibited stability with viral targets including the RdRp, NS3 helicase, and E protein indicating their potential as novel anti-dengue antivirals.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227122","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":"Nonsense-Mediated mRNA Decay in Human Health and Diseases: Current Understanding, Regulatory Mechanisms and Future Perspectives","authors":"Amrita Behera, Gagan Kumar Panigrahi, Annapurna Sahoo","doi":"10.1007/s12033-024-01267-7","DOIUrl":"https://doi.org/10.1007/s12033-024-01267-7","url":null,"abstract":"<p>Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that is conserved across all eukaryotes ensuring the quality of transcripts by targeting messenger RNA (mRNA) harbouring premature stop codons. It regulates the gene expression by targeting aberrant mRNA carrying pre-termination codons (PTCs) and eliminates C-terminal truncated proteins. NMD distinguishes aberrant and non-aberrant transcript by looking after long 3′ UTRs and exon-junction complex (EJC) downstream of stop codon that indicate the presence of PTC. Therefore, NMD modulates cellular surveillance and eliminates the truncated proteins but if the PTC escapes the surveillance pathway it can lead to potential negative phenotype resulting in genetic diseases. The alternative splicing also contributes in formation of NMD-sensitive isoforms by introducing PTC. NMD plays a complex role in cancer, it can either aggravate or downregulates the tumour. Some tumours agitate NMD to deteriorate mRNAs encoding tumour suppressor proteins, stress response proteins and neoantigens. In other case, tumours suppress the NMD to encourage the expression of oncoproteins for tumour growth and survival. This mechanism augmented in the development of new therapeutics by PTC read-through mechanism and personalized medicine. Detailed studies on NMD surveillance will possibly lead towards development of strategies for improving human health aligning with United Nations sustainable development goals (SDG 3: Good health and well-being). The potential therapeutic applications of NMD pose a challenge in terms of safe and effective modulation. Understanding the complexities of NMD regulation and its interaction with other cellular processes can lead to the development of new interventions for various diseases.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217363","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":"Marine Compound-Carpatamide D as a Potential Inhibitor Against TOP2A and Its Mutant D1021Y in Colorectal Cancer: Insights from DFT, MEP and Molecular Dynamics Simulation","authors":"P. Priyamvada, Gayathri Ashok, Shalini Mathpal, Anand Anbarasu, Sudha Ramaiah","doi":"10.1007/s12033-024-01265-9","DOIUrl":"https://doi.org/10.1007/s12033-024-01265-9","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Colorectal cancer (CRC) ranks as the third most prevalent cancer globally, hence there is an urgent need for new and effective therapeutic options. DNA topoisomerase 2A (TOP2A) plays a crucial role in the cell cycle and is involved in CRC progression, making it essential to identify structural and functional relevant alterations. Among the 24 mutations, our findings indicated that mutation D1021Y has the most deleterious effect on the TOP2A protein. Based on virtual screening of 31,561 compounds, we identified three lead candidates: 17683 (nigrospoxydon C), 28461 (carpatamide D), and 28853 (6′-<i>O</i>-acetyl-isohomaarbutin), which showed promising inhibitory effect against TOP2A and its mutant form. These compounds were assessed for their stability using density functional theory (DFT) analysis, where carpatamide D possessed the least energy gap of 4.398 eV showing its high reactivity among all. Further, molecular docking also shows the carpatamide D as the top candidate, which exhibited favourable docking energy against the TOP2A wild type (− 7.47 kcal/mol) and with D1021Y mutant (− 7.62 kcal/mol) as compared to reference compound PK1, which showed − 6.11 kcal/mol TOP2A wild type and − 6.24 kcal/mol against mutant type. The molecular dynamics simulation was performed to analyse the dynamics and stability of complex, which revealed TOP2A_28641 and D1021Y_28641 complexes to be stable with least root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF). Molecular mechanics/Poisson–Boltzmann surface area calculations indicated that TOP2A_28641 and D1021Y_28641 complexes exhibited the lowest binding energy of − 23.55 kcal/mol and − 25.03 kcal/mol, respectively. Our findings suggest carpatamide D as a promising lead compound for the TOP2A_D1021Y targeted cancer therapies, which needs further experimental validation.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227123","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":"Multi-omics and Single Cell Sequencing Analyses Reveal Associations of Mitophagy-Related Genes Predicting Clinical Prognosis and Immune Infiltration Characteristics in Osteosarcoma","authors":"Shengquan Ren, Rongfang Pan, Zhengdan Wang","doi":"10.1007/s12033-024-01280-w","DOIUrl":"https://doi.org/10.1007/s12033-024-01280-w","url":null,"abstract":"<p>Despite recent advances in clinical treatments, identifying high-risk osteosarcoma (OS) patients remains an unresolved clinical challenge. Mitophagy, a specialized form of cellular autophagy, selectively reduces the number of mitochondria or repairs their abnormal functions in response to external stress, thereby ensuring mitochondrial quality and maintaining mitochondrial function. Mitophagy plays a crucial role in cancer development, including processes such as mitochondrial repair, homeostasis maintenance, and tumor metabolism. However, its impact on OS has not yet been reported. In this study, we collected 58 mitophagy-related genes (MPRGs) from the TARGET and GEO databases and bioinformatically screened for those associated with OS prognosis. By LASSO-multivariable Cox regression algorithm, we subsequently developed a novel scoring system, the MPRG score, and validated its significance in predicting OS prognosis. Immune landscape analysis showed patients in the low MPRG group had a higher immune infiltration level than those in the high MPRG group. Drug sensitivity differences highlighted the potential need for alternative therapeutic strategies based on MPRG scoring system. The distribution characteristics of the MPRG signature in different cell subtypes of OS were explored by single-cell sequencing analyses. In vitro experiments further confirmed the abnormal expression of screened targets in OS. Our findings highlight the role of mitophagy in OS and its potential as a therapeutic target.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217362","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":"Milk Lipid Regulation in Dairy Goats: A Comprehensive Review","authors":"Bingzhi Li, Yu Li, Wanqiang Tian, Belete Kuraz Abebe, Sayed Haidar Abbas Raza, Hengwei Yu","doi":"10.1007/s12033-024-01283-7","DOIUrl":"https://doi.org/10.1007/s12033-024-01283-7","url":null,"abstract":"<p>The growth, development, and milk production traits of dairy goats, which are important sources of high-quality animal protein, are significantly influenced by a combination of genetic and environmental factors. It is imperative to identify key genetic loci that govern economically valuable traits in order to enhance breeding programs. Despite advancements in genomic technologies, there are still gaps in knowledge regarding the interplay between genetic factors and environmental influences, particularly in relation to the regulation of milk production and quality. Therefore, the aim of this paper was to synthesize advancements in the genetic and environmental factors affecting milk production and quality in dairy goats and identify key regulatory mechanisms. This review summarizes the recent progress on the identification of genes associated with milk production traits using whole-genome resequencing, the use of transcriptomic profiling to identify genes linked to milk production, the exploration of regulatory mechanisms of lipid metabolism in goat mammary epithelial cells, and the evaluation of the influence of nutritional factors on milk quality. A comprehensive understanding of these interactions is essential for enhancing breeding strategies and ensuring the sustainability of dairy goat farming. Future research should incorporate multi-omics approaches to unravel the intricate regulatory processes governing milk production and adapt practices to meet global demand while upholding economic and environmental sustainability.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217364","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}