Molecular Biotechnology最新文献

{"title":"Exploring Natural Compounds as Potential CDK4 Inhibitors for Therapeutic Intervention in Neurodegenerative Diseases through Computational Analysis.","authors":"Neetu Rani, Pravir Kumar","doi":"10.1007/s12033-024-01258-8","DOIUrl":"10.1007/s12033-024-01258-8","url":null,"abstract":"<p><p>CDK4 is a member of the serine-threonine kinase family, which has been found to be overexpressed in a plethora of studies related to neurodegenerative diseases. CDK4 is one of the most validated therapeutic targets for neurodegenerative diseases. Hence, the discovery of potent inhibitors of CDK4 is a promising candidate in the drug discovery field. Firstly, the reference drug Palbociclib was identified from the available literature as a potential candidate against target CDK4. In the present study, the Collection of Open Natural Products (COCONUT) database was accessed for determining potential CDK4 inhibitors using computational approaches based on the Tanimoto algorithm for similarity with the target drug, i.e., Palbociclib. The potential candidates were analyzed using SWISSADME, and the best candidates were filtered based on Lipinski's Rule of 5, Brenk, blood-brain barrier permeability, and Pains parameter. Further, the molecular docking protocol was accessed for the filtered compounds to anticipate the CDK4-ligand binding score, which was validated by the fastDRH web-based server. Based on the best docking score so obtained, the best four natural compounds were chosen for further molecular dynamic simulation to assess their stability with CDK4. In this study, two natural products, with COCONUT Database compound ID-CNP0396493 and CNP0070947, have been identified as the most suitable candidates for neuroprotection.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3310-3329"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109624","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":"Recent Review on the Extraction and Qualitative Assay of Cysteine and Other Amino Acids from Vellore Feather Waste and Molecular Docking Studies of Cysteine for Pharmacological Applications.","authors":"Sathvika Kamaraj, Suneetha Vuppu","doi":"10.1007/s12033-023-00862-4","DOIUrl":"10.1007/s12033-023-00862-4","url":null,"abstract":"<p><p>Products produced from waste are a relatively recent innovation. Feather substrates are abundant in keratin content and improper disposal can cause ecosystem contamination. However, these pollutants can be transformed into value-added products for industrial application. Physical, chemical and cutting-edge microbiological methods were utilized for decomposing keratin and aid in the identification and estimation of amino acids from poultry feather wastes. These beneficial approaches are receiving more attention due to their retrieval of harmless and value added byproducts. These keratin-based compounds are used widely in pharmaceutical, livestock feed, fertilizer, and a variety of other industrial sectors. Since keratin is primarily consisting of amino acids, it can be utilized to affirm and estimate the amino acids in these feather substrates. This study primarily highlights the various methodologies employed for the qualitative estimation of amino acids in feather waste samples and the inhibitory activity of keratinase enzyme by EDTA and pepstatin in order to accumulate amino acids for drug delivery purpose and their importance in various pharmaceutical industries. In addition to that, molecular docking studies of cysteine with many standard pharmaceutical drugs like acetaminophen, pethidine, methylphenidate, carbamazepine, cillin and amlodipine were performed using autodock to demonstrate how cysteine greatly reduces conventional drug toxicity and its side effects.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2902-2930"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10321855","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":"Study of the Immune Infiltration and Sonic Hedgehog Expression Mechanism in Synovial Tissue of Rheumatoid Arthritis-Related Interstitial Lung Disease under Machine Learning CIBERSORT Algorithm.","authors":"Qunqun Lu, Yizhen Jiang, Xiaofeng Cang, Jiaojiao Pan, Xiaowen Shen, Ruoyu Tang, Zhe Zhou, Yiwen Zhu","doi":"10.1007/s12033-024-01245-z","DOIUrl":"10.1007/s12033-024-01245-z","url":null,"abstract":"<p><p>Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is one of the common complications in patients with RA, which affects their quality of life. The CIBERSORT algorithm is widely employed to determine the proportion of immune cells (ICs) in diseased tissues, while the Sonic Hedgehog (Shh) signaling pathway, as an imperative regulatory factor, has also attracted attention in the pathology of RA-ILD. This work was to explore the mechanisms of RA-ILD immune infiltration and synovial tissue (ST) Shh expression based on the CIBERSORT algorithm. The differential genes of RA-ILD were subjected to pathway enrichment analysis using R language. The content and proportion of 22 types of ICs in RA-ILD lung tissues were analyzed using machine learning-based CIBERSORT algorithm. Meanwhile, immunoblotting was employed to detect and analyze the expression of Shh, Smoothened (Smo), and bone morphogenetic proteins (BMPs) proteins in ST samples from RA-ILD and Ctrl groups (RA patients without ILD). The hub target genes in the protein network associated with RA-ILD include BSG, CCL2, CTLA4, FGFBP1, GLI1, HHIP, HLA-DRB1, IFNAR1, IL17A, IL23A, IL-6, INPP4A, LILRB1, MUC5B, PADI4, PPM1A, PTCH1, PTPN22, RSPO4, Shh, SMO, STAT4, SUFU, TAOK2, TIMP2, and TWSG1, which are involved in multiple pathways, such as B cell regulation, transcription factors of the Shh pathway, and ST immune tolerance-related pathways. In the immunological analysis of RA-ILD using the CIBERSORT algorithm, HLA (r = - 0.26), PTPN22 (r = - 0.36), STAT4 (r = - 0.18), IL-6 (r = - 0.17), CTLA4 (r = - 0.27), and PADI4 (r = - 0.21) were all found to exhibit negative correlations with CD4+T cells (P < 0.05). Monocytes were found to be more abundant in RA-ILD patients' serum versus the Ctrl group. Shh, Smo, and BMP expressions were drastically lower in the RA-ILD group versus Ctrl group (P < 0.05). Significant immune cell infiltration was observed in the lung tissues of RA-ILD patients. Further analysis utilizing the CIBERSORT algorithm revealed alterations in the proportions of different IC subtypes, indicating their association with disease severity and prognosis. Moreover, there was a significant decrease in the expression levels of Shh, Smo, and BMP. These findings underscore the importance of immune cells in the pathophysiology of RA-ILD and suggest a potential involvement of the Shh signaling pathway in the pathogenesis of RA-ILD.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3217-3233"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897790","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":"A Simple and Rapid Method of Probiotic Bacterial Ghost Cell Preparation to Deliver Mycobacterium tuberculosis Antigen.","authors":"Yesupatham Aarthi, Aravindha Anjana, Glaudia Tejal, Meenakshi Shanmugaraja, S Ramadevi, R Princess","doi":"10.1007/s12033-024-01260-0","DOIUrl":"10.1007/s12033-024-01260-0","url":null,"abstract":"<p><p>A bacterial ghost cell is an empty cell envelope of bacteria lacking cytoplasmic content. Bacterial ghost cells (BGs) can be used for various applications such as vaccines, adjuvants, and drug delivery systems. Since BGs offer many advantages over classically prepared vaccines, developing novel methods for the preparation of high-quality BGs remains to be an interesting field of study by various research groups. Several novel methodologies have been reported that involve the biological (gene E mediated) and combination of various chemicals such as NaOH, SDS, H₂O₂, CaCO₃, and ethanol, non-detergent method using Tween80, limulus antimicrobial peptide, and high hydrostatic pressure method, the porcine myeloid antimicrobial peptide (PMPA) 36-lysozyme fusion method, NaOH-Penicillin/Streptolysin combination method. In this study, we have reported a novel methodology that combines the action of chemical and physical factors to produce ghost cells from gram-negative bacteria, the probiotic E.coli Nissle 1917. The mild detergent Triton X-100 and NaCl alter the permeability of the cell membrane which is further amplified by heat shock induction. This enables the cell to expel its cytoplasmic components without affecting the external morphology. The efficiency of this method was analyzed based on viability assay, cell leakage assay, live-dead cell assay, and scanning electron microscopic analysis. Moreover, the protein loading capacity was optimized for Mycobacterium tuberculosis antigen namely, ESAT-6.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3243-3254"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004850","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":"Enhanced SELEX Platforms for Aptamer Selection with Improved Characteristics: A Review.","authors":"Reza Didarian, Hatice K Ozbek, Veli C Ozalp, Ozcan Erel, Nimet Yildirim-Tirgil","doi":"10.1007/s12033-024-01256-w","DOIUrl":"10.1007/s12033-024-01256-w","url":null,"abstract":"<p><p>This review delves into the advancements in molecular recognition through enhanced SELEX (Systematic Evolution of Ligands by Exponential Enrichment) platforms and post-aptamer modifications. Aptamers, with their superior specificity and affinity compared to antibodies, are central to this discussion. Despite the advantages of the SELEX process-encompassing stages like ssDNA library preparation, incubation, separation, and PCR amplification-it faces challenges, such as nuclease susceptibility. To address these issues and propel aptamer technology forward, we examine next-generation SELEX platforms, including microfluidic-based SELEX, capillary electrophoresis SELEX, cell-based aptamer selection, counter-SELEX, in vivo SELEX, and high-throughput sequencing SELEX, highlighting their respective merits and innovations. Furthermore, this article underscores the significance of post-aptamer modifications, particularly chemical strategies that enhance aptamer stability, reduce renal filtration, and expand their target range, thereby broadening their utility in diagnostics, therapeutics, and nanotechnology. By synthesizing these advanced SELEX platforms and modifications, this review illuminates the dynamic progress in aptamer research and outlines the ongoing efforts to surmount existing challenges and enhance their clinical applicability, charting a path for future breakthroughs in this evolving field.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2962-2977"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996149","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":"Unraveling the Interaction Mechanism of the Compounds From Cladophora sp to Recognize Prospective Larvicidal and Bactericidal Activities: In vitro and In Silico Approaches.","authors":"K T Nachammai, S Amaradeepa, S Raageshwari, A V Swathilakshmi, M Poonkothai, K Langeswaran","doi":"10.1007/s12033-023-00902-z","DOIUrl":"10.1007/s12033-023-00902-z","url":null,"abstract":"<p><p>The present investigation aims to validate the larvicidal and antibacterial potential of Cladophora sp through in vitro and in silico approaches. The presence of phytoconstituents, functional groups and the compounds responsible for antibacterial and larvicidal activity were assessed through FT-IR and GC-MS analyses which unveiled the existence of active secondary metabolites, hydroxyl, alkane and carbonyl groups. The larvicidal and antibacterial activity of algal extract were examined and revealed complete mortality and substantial zone of inhibition was observed against Culex quinquefasciatus and E. coli. To support the in vitro investigation in silico studies were performed. Molecular docking investigations of the selected compounds from GC-MS which exhibited favorable agreement with drug likeness and ADMET properties indicated robust interactions with the larvicidal and bacterial proteins showcasing considerable binding affinities. Notably, 1,2,4-Oxadiazole, 3-(1,3-benzodioxol-5-yl)-5-[(4-iodo-1H-pyrazol-1-yl) methyl]- exhibited strong interactions with the target proteins. Density Functional Theory revealed that the energy gap of the lead compound was reduced and substantiates the occurrence of intermolecular charge transfer. Molecular Dynamic simulations confirms the stability and flexibility of the lead compound. Hence, this investigation offers computational perspectives on the molecular interactions of Cladophora sp, suggesting its suitability as a promising biocontrol agent.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3154-3174"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41236910","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":"Cellulose Degradation Enzymes in Filamentous Fungi, A Bioprocessing Approach Towards Biorefinery.","authors":"Abdulmoseen Segun Giwa, Nasir Ali, Mohammed Salim Akhter","doi":"10.1007/s12033-023-00900-1","DOIUrl":"10.1007/s12033-023-00900-1","url":null,"abstract":"<p><p>The economic exploration of renewable energy resources has hot fundamentals among the countries besides dwindling energy resources and increasing public pressure. Cellulose accumulation is a major bio-natural resource from agricultural waste. Cellulases are the most potential enzymes that systematically degrade cellulosic biomass into monomers which could be further processed into several efficient value-added products via chemical and biological reactions including useful biomaterial for human benefits. This could lower the environmental risks problems followed by an energy crisis. Cellulases are mainly synthesized by special fungal genotypes. The strain Trichoderma orientalis could highly express cellulases and was regarded as an ideal strain for further research, as the genetic tools have found compatibility for cellulose breakdown by producing effective cellulose-degrading enzymes. This strain has found a cellulase production of about 35 g/L that needs further studies for advancement. The enzyme activity of strain Trichoderma orientalis needed to be further improved from a molecular level which is one of the important methods. Considering synthetic biological approaches to unveil the genetic tools will boost the knowledge about commercial cellulases bioproduction. Several genetic transformation methods were significantly cited in this study. The transformation approaches that are currently researchers are exploring is transcription regulatory factors that are deeply explained in this study, that are considered essential regulators of gene expression.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2931-2945"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41236830","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":"Fermentative Biohydrogen and Biomethane Production from High-Strength Industrial Food Waste Hydrolysate Using Suspended Cell Techniques.","authors":"Onjira Kongthong, Pannipha Dokmaingam, Chen-Yeon Chu","doi":"10.1007/s12033-023-00939-0","DOIUrl":"10.1007/s12033-023-00939-0","url":null,"abstract":"<p><p>The food waste was very difficult to treat in a proper way since its high-organic matter. The novel biohythane (H₂ + CH₄) production from high-strength industry food waste hydrolysate in two steps anaerobic well mixed batch bioreactor was carried out in this study using cultivated microflora. The temperature was controlled at 37 °C and initial substrate concentration of industrial food waste hydrolysate varied from 60, 80, 100, and 120 g COD/L, respectively. The pH, TS, VS, and SCOD were analyzed from the influent and effluent samples. These analytical parameters showed the correlations between the biogas production rates and yields in the batch fermentation system. This study was the first time to use the industry food waste hydrolysate which was collected from the subcritical water hydrolysis process. In this study, the optimal biohydrogen and biomethane yield production by using suspended cells were 0.65 mL H₂/g COD and 203.72 mL CH₄/g COD where the initial substrate concentrations of total COD and SCOD were 60 g/L and 39.80 g/L, respectively. The optimal of the biohydrogen and biomethane yields production by using suspended cells were 0.65 mL H₂/g COD and 203.72 mL CH₄/g COD where the initial substrate concentrations of total COD and SCOD were 60 g/L and 39.80 g/L, respectively. The results of this study supported that the cultivation of inoculum in a suspended cell type can have a higher tolerance for the biohydrogen and biomethane production in a high-strength initial substrate concentration of 60 g COD/L.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3186-3193"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483789","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 Pyroptosis-Related Molecular Subtypes and Diagnostic Model development in Major Depressive Disorder.","authors":"Lin Feng, Jiabo Yuan, Li Li, Junze Tang","doi":"10.1007/s12033-024-01252-0","DOIUrl":"10.1007/s12033-024-01252-0","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is a prevalent psychological disorder associated with inflammation, with complex pathological mechanisms. Pyroptosis has been suggested to contribute to inflammation in central nervous system diseases. Little research, however, has examined what role pyroptosis played in MDD. In the present study, the differential expression pyroptosis-related genes (DE-PRGs) in MDD were identified from the GEO database (GSE98793 and GSE19738). Then, consensus clustering analysis was used to evaluate differences in MDD molecular subtypes characteristics based on PRGs. The characteristic diagnostic biomarkers for MDD were identified by Weighted Correlation Network Analysis (WGCNA) and multiple machine learning algorithms. Three intersection genes (GZMA, AKR1C3, and CD52) were obtained, which are expected to become potential biomarkers for MDD with excellent reliability and accuracy. Subsequently, the immune infiltration characteristics result indicated that the development of MDD is mediated by immune-related function, where three DE-PRGs were strongly related to the immune infiltration landscape of MDD. The biological experiments in vitro further proved that three unique PRGs are emerging as important players in MDD diagnosis. Our research aimed to provide novel ideas and biomarkers targeting MDD.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3281-3295"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036429","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":"Antioxidant, In Vitro Cytotoxicity, and Anti-diabetic Attributes of a Drug-Free Guar Gum Nanoformulation as a Novel Candidate for Diabetic Wound Healing.","authors":"Debojyoti Mandal, Jayanta K Sarmah, Vancha Harish, Jeena Gupta","doi":"10.1007/s12033-024-01261-z","DOIUrl":"10.1007/s12033-024-01261-z","url":null,"abstract":"<p><p>The escalating intersection of diabetes and impaired wound healing poses a substantial societal burden, marked by an increasing prevalence of chronic wounds. Diabetic individuals struggle with hindered recovery, attributed to compromised blood circulation and diminished immune function, resulting in prolonged healing periods and elevated healthcare expenditures. To address this challenge, we report here a drug-free novel guar gum (GG)-based nano-formulation which is effective against diabetic wound healing. Nanoparticles with an average particle size of 32.4 nm display stability with negative zeta potential. Differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) analysis reveal alterations in thermal properties and molecular structures induced by the nano-particulation process. In vitro studies highlight the antioxidant potential of GGNP through concentration-dependent free radical scavenging activity in DPPH and ABTS assays. The nanoformulation also exhibits inhibitory effects on α-glucosidase and α-amylase enzymes. Cell viability studies have indicated moderate cytotoxicity in L929 cells and significant proliferation and migration in HaCaT cells, suggesting a positive impact on skin cells. In vitro enzymatic activity assessments under hyperglycaemic conditions reveal the potential of GGNP to modulate glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase activities as well as decreasing lipid peroxidation (LPO) levels, showcasing an antioxidant response. These results suggest GGNP as a promising candidate in diabetic wound healing.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"3330-3344"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109623","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}