AMB Express最新文献_第4页

Identification of novel natural compounds against CFTR p.Gly628Arg pathogenic variant. 针对 CFTR p.Gly628Arg 致病变体的新型天然化合物的鉴定。

IF 3.5 3区生物学

AMB Express Pub Date : 2024-09-09 DOI: 10.1186/s13568-024-01762-9

Muhammad Umer Khan, Azra Sakhawat, Raima Rehman, Abbas Haider Wali, Muhammad Usman Ghani, Areeba Akram, Muhammad Arshad Javed, Qurban Ali, Zhou Yu-Ming, Daoud Ali, Zhou Yu-Ming

{"title":"Identification of novel natural compounds against CFTR p.Gly628Arg pathogenic variant.","authors":"Muhammad Umer Khan, Azra Sakhawat, Raima Rehman, Abbas Haider Wali, Muhammad Usman Ghani, Areeba Akram, Muhammad Arshad Javed, Qurban Ali, Zhou Yu-Ming, Daoud Ali, Zhou Yu-Ming","doi":"10.1186/s13568-024-01762-9","DOIUrl":"10.1186/s13568-024-01762-9","url":null,"abstract":"Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an ion channel found in numerous epithelia and controls the flow of water and salt across the epithelium. The aim of our study to find natural compounds that can improve lung function for people with cystic fibrosis (CF) caused by the p.Gly628Arg (rs397508316) mutation of CFTR protein. The sequence of CFTR protein as a target structure was retrieved from UniProt and PDB database. The ligands that included Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and one Trikafta (R*) reference drug were screened out from PubChem database. Autodock vina software carried out docking, and binding energies between the drug and the target were included using docking-score. The following tools examined binding energy, interaction, stability, toxicity, and visualize protein-ligand complexes. The compounds having binding energies of -6.4, -5.1, -6.6, -5.1, and - 6.5 kcal/mol for Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and R*-drug, respectively with mutated CFTR (Gly628Arg) structure were chosen as the most promising ligands. The ligands bind to the mutated CFTR protein structure active sites in hydrophobic bonds, hydrogen bonds, and electrostatic interactions. According to ADMET analyses, the ligands Armepavine and Quercetin also displayed good pharmacokinetic and toxicity characteristics. An MD simulation for 200 ns was also established to ensure that Armepavine and Quercetin ligands attached to the target protein favorably and dynamically, and that protein-ligand complex stability was maintained. It is concluded that Armepavine and Quercetin have stronger capacity to inhibit the effect of mutated CFTR protein through improved trafficking and restoration of original function.","PeriodicalId":7537,"journal":{"name":"AMB Express","volume":"14 1","pages":"99"},"PeriodicalIF":3.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11383896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heterologous expression of lasso peptides with apparent participation in the morphological development in Streptomyces. 在链霉菌中异源表达明显参与形态发育的拉索肽。

IF 3.5 3区生物学

AMB Express Pub Date : 2024-09-03 DOI: 10.1186/s13568-024-01761-w

Alma Ofelia Reyna-Campos, Beatriz Ruiz-Villafan, Martha Lydia Macías-Rubalcava, Elizabeth Langley, Romina Rodríguez-Sanoja, Sergio Sánchez

{"title":"Heterologous expression of lasso peptides with apparent participation in the morphological development in Streptomyces.","authors":"Alma Ofelia Reyna-Campos, Beatriz Ruiz-Villafan, Martha Lydia Macías-Rubalcava, Elizabeth Langley, Romina Rodríguez-Sanoja, Sergio Sánchez","doi":"10.1186/s13568-024-01761-w","DOIUrl":"10.1186/s13568-024-01761-w","url":null,"abstract":"Lasso peptides, ribosomally synthesized and post-translationally modified peptides, are primarily produced by bacteria and some archaea. Streptomyces lasso peptides have been known for their antimicrobial, anticancer, and antiviral properties. However, understanding their role in the morphology and production of secondary metabolites remains limited. We identified a previously unknown lasso peptide gene cluster in the genome of Streptomyces sp. L06. This gene cluster (LASS) produces two distinct lasso peptides, morphosin-1 and - 2. Notably, morphosin-2 is a member of a new subfamily of lasso peptides, with BGCs exhibiting a similar structure. When LASS was expressed in different Streptomyces hosts, it led to exciting phenotypic changes, including the absence of spores and damage in aerial mycelium development. In one of the hosts, LASS even triggered antibiotic formation. These findings open up a world of possibilities, suggesting the potential role of morphosins in shaping Streptomyces' morphological and biochemical development.","PeriodicalId":7537,"journal":{"name":"AMB Express","volume":"14 1","pages":"97"},"PeriodicalIF":3.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of a GDS(L)-like hydrolase from Pleurotus sapidus with an unusual SGNH motif. 具有不寻常 SGNH 基序的鞘氨醇 GDS(L)-like 水解酶的特征。

IF 3.5 3区生物学

AMB Express Pub Date : 2024-09-03 DOI: 10.1186/s13568-024-01752-x

Miriam A Fingerhut, Lea Henrich, Christiane Lauber, Niklas Broel, Parviz Ghezellou, Dominik Karrer, Bernhard Spengler, Kim Langfelder, Timo Stressler, Holger Zorn, Martin Gand

{"title":"Characterization of a GDS(L)-like hydrolase from Pleurotus sapidus with an unusual SGNH motif.","authors":"Miriam A Fingerhut, Lea Henrich, Christiane Lauber, Niklas Broel, Parviz Ghezellou, Dominik Karrer, Bernhard Spengler, Kim Langfelder, Timo Stressler, Holger Zorn, Martin Gand","doi":"10.1186/s13568-024-01752-x","DOIUrl":"10.1186/s13568-024-01752-x","url":null,"abstract":"The GDS(L)-like lipase from the Basidiomycota Pleurotus sapidus (PSA_Lip) was heterologously expressed using Trichoderma reesei with an activity of 350 U L-1. The isoelectric point of 5.0 was determined by isoelectric focusing. The novel PSA_Lip showed only 23.8-25.1%, 25.5%, 26.6% and 28.4% identity to the previously characterized GDSL-like enzymes phospholipase, plant lipase, acetylcholinesterase and acetylxylan esterase, from the carbohydrate esterase family 16, respectively. Therefore, the enzyme was purified from the culture supernatant and the catalytic properties and the substrate specificity of the enzyme were investigated using different assays to reveal its potential function. While no phospholipase, acetylcholinesterase and acetylxylan esterase activities were detected, studies on the hydrolysis of ferulic acid methyl ester (~ 8.3%) and feruloylated carbohydrate 5-O-transferuloyl-arabino-furanose (~ 0.8%) showed low conversions of these substrates. By investigating the hydrolytic activity towards p-nitrophenyl-(pNP)-esters with various chain-lengths, the highest activity was determined for medium chain-length pNP-octanoate at 65 °C and a pH value of 8, while almost no activity was detected for pNP-hexanoate. The enzyme is highly stable when stored at pH 10 and 4 °C for at least 7 days. Moreover, using consensus sequence analysis and homology modeling, we could demonstrate that the PSA_Lip does not contain the usual SGNH residues in the actives site, which are usually present in GDS(L)-like enzymes.","PeriodicalId":7537,"journal":{"name":"AMB Express","volume":"14 1","pages":"98"},"PeriodicalIF":3.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An efficient gene targeting system using Δku80 and functional analysis of Cyp51A in Trichophyton rubrum. 使用 Δku80 的高效基因打靶系统和红毛癣菌中 Cyp51A 的功能分析。

IF 3.5 3区生物学

AMB Express Pub Date : 2024-08-31 DOI: 10.1186/s13568-024-01755-8

Masaki Ishii, Tsuyoshi Yamada, Shinya Ohata

{"title":"An efficient gene targeting system using Δku80 and functional analysis of Cyp51A in Trichophyton rubrum.","authors":"Masaki Ishii, Tsuyoshi Yamada, Shinya Ohata","doi":"10.1186/s13568-024-01755-8","DOIUrl":"10.1186/s13568-024-01755-8","url":null,"abstract":"Trichophyton rubrum is one of the most frequently isolated fungi in patients with dermatophytosis. Despite its clinical significance, the molecular mechanisms of drug resistance and pathogenicity of T. rubrum remain to be elucidated because of the lack of genetic tools, such as efficient gene targeting systems. In this study, we generated a T. rubrum strain that lacks the nonhomologous end-joining-related gene ku80 (Δku80) and then developed a highly efficient genetic recombination system with gene targeting efficiency that was 46 times higher than that using the wild-type strain. Cyp51A and Cyp51B are 14-α-lanosterol demethylase isozymes in T. rubrum that promote ergosterol biosynthesis and are the targets of azole antifungal drugs. The expression of cyp51A mRNA was induced by the addition of the azole antifungal drug efinaconazole, whereas no such induction was detected for cyp51B, suggesting that Cyp51A functions as an azole-responsive Cyp51 isozyme. To explore the contribution of Cyp51A to susceptibility to azole drugs, the neomycin phosphotransferase (nptII) gene cassette was inserted into the cyp51A 3'-untranslated region of Δku80 to destabilize the mRNA of cyp51A. In this mutant, the induction of cyp51A mRNA expression by efinaconazole was diminished. The minimum inhibitory concentration for several azole drugs of this strain was reduced, suggesting that dermatophyte Cyp51A contributes to the tolerance for azole drugs. These findings suggest that an efficient gene targeting system using Δku80 in T. rubrum is applicable for analyzing genes encoding drug targets.","PeriodicalId":7537,"journal":{"name":"AMB Express","volume":"14 1","pages":"96"},"PeriodicalIF":3.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-epitope vaccine design of African swine fever virus considering T cell and B cell immunogenicity. 考虑到 T 细胞和 B 细胞免疫原性的非洲猪瘟病毒多表位疫苗设计。

IF 3.5 3区生物学

AMB Express Pub Date : 2024-08-31 DOI: 10.1186/s13568-024-01749-6

Ting-Yu Chen, Yann-Jen Ho, Fang-Yu Ko, Pei-Yin Wu, Chia-Jung Chang, Shinn-Ying Ho

{"title":"Multi-epitope vaccine design of African swine fever virus considering T cell and B cell immunogenicity.","authors":"Ting-Yu Chen, Yann-Jen Ho, Fang-Yu Ko, Pei-Yin Wu, Chia-Jung Chang, Shinn-Ying Ho","doi":"10.1186/s13568-024-01749-6","DOIUrl":"10.1186/s13568-024-01749-6","url":null,"abstract":"T and B cell activation are equally important in triggering and orchestrating adaptive host responses to design multi-epitope African swine fever virus (ASFV) vaccines. However, few design methods have considered the trade-off between T and B cell immunogenicity when identifying promising ASFV epitopes. This work proposed a novel Pareto front-based ASFV screening method PFAS to identify promising epitopes for designing multi-epitope vaccines utilizing five ASFV Georgia 2007/1 sequences. To accurately predict T cell immunogenicity, four scoring methods were used to estimate the T cell activation in the four stages, including proteasomal cleavage probability, transporter associated with antigen processing transport efficiency, class I binding affinity of the major histocompatibility complex, and CD8 + cytotoxic T cell immunogenicity. PFAS ranked promising epitopes using a Pareto front method considering T and B cell immunogenicity. The coefficient of determination between the Pareto ranks of multi-epitope vaccines and survival days of swine vaccinations was R2 = 0.95. Consequently, PFAS scored complete epitope profiles and identified 72 promising top-ranked epitopes, including 46 CD2v epitopes, two p30 epitopes, 10 p72 epitopes, and 14 pp220 epitopes. PFAS is the first method of using the Pareto front approach to identify promising epitopes that considers the objectives of maximizing both T and B cell immunogenicity. The top-ranked promising epitopes can be cost-effectively validated in vitro. The Pareto front approach can be adaptively applied to various epitope predictors for bacterial, viral and cancer vaccine developments. The MATLAB code of the Pareto front method was available at https://github.com/NYCU-ICLAB/PFAS .","PeriodicalId":7537,"journal":{"name":"AMB Express","volume":"14 1","pages":"95"},"PeriodicalIF":3.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular docking and antimicrobial activities of photoexcited inhibitors in antimicrobial photodynamic therapy against Enterococcus faecalis biofilms in endodontic infections. 抗菌光动力疗法中光激发抑制剂对牙髓感染中粪肠球菌生物膜的分子对接和抗菌活性。

IF 3.5 3区生物学

AMB Express Pub Date : 2024-08-31 DOI: 10.1186/s13568-024-01751-y

Maryam Pourhajibagher, Zahra Javanmard, Abbas Bahador

{"title":"Molecular docking and antimicrobial activities of photoexcited inhibitors in antimicrobial photodynamic therapy against Enterococcus faecalis biofilms in endodontic infections.","authors":"Maryam Pourhajibagher, Zahra Javanmard, Abbas Bahador","doi":"10.1186/s13568-024-01751-y","DOIUrl":"10.1186/s13568-024-01751-y","url":null,"abstract":"Antimicrobial photodynamic therapy (aPDT) is a promising approach to combat antibiotic resistance in endodontic infections. It eliminates residual bacteria from the root canal space and reduces the need for antibiotics. To enhance its effectiveness, an in silico and in vitro study was performed to investigate the potential of targeted aPDT using natural photosensitizers, Kojic acid and Parietin. This approach aims to inhibit the biofilm formation of Enterococcus faecalis, a frequent cause of endodontic infections, by targeting the Ace and Esp proteins. After determining the physicochemical characteristics of Ace and Esp proteins and model quality assessment, the molecular dynamic simulation was performed to recognize the structural variations. The stability and physical movement of the protein-ligand complexes were evaluated. In silico molecular docking was conducted, followed by ADME/Tox profiling, pharmacokinetics characteristics, and assessment of drug-likeness properties of the natural photosensitizers. The study also investigated the changes in the expression of genes (esp and ace) involved in E. faecalis biofilm formation. The results showed that both Kojic acid and Parietin complied with Lipinski's rule of five and exhibited drug-like properties. In silico analysis indicated stable complexes between Ace and Esp proteins and the natural photosensitizers. The molecular docking studies demonstrated good binding affinity. Additionally, the expression of the ace and esp genes was significantly downregulated in aPDT using Kojic acid and Parietin with blue light compared to the control group. This investigation concluded that Kojic acid and Parietin with drug-likeness could efficiently interact with Ace and Esp proteins with a strong binding affinity. Hence, natural photosensitizers-mediated aPDT can be considered a promising adjunctive treatment against endodontic infections.","PeriodicalId":7537,"journal":{"name":"AMB Express","volume":"14 1","pages":"94"},"PeriodicalIF":3.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Candida boidinii isolates from olive curation water: a promising platform for methanol-based biomanufacturing. 从橄榄腌制水中分离出的布氏念珠菌：甲醇基生物制造的理想平台。

IF 3.5 3区生物学

AMB Express Pub Date : 2024-08-28 DOI: 10.1186/s13568-024-01754-9

Marta N Mota, Margarida Palma, Isabel Sá-Correia

{"title":"Candida boidinii isolates from olive curation water: a promising platform for methanol-based biomanufacturing.","authors":"Marta N Mota, Margarida Palma, Isabel Sá-Correia","doi":"10.1186/s13568-024-01754-9","DOIUrl":"10.1186/s13568-024-01754-9","url":null,"abstract":"Methanol is a promising feedstock for biomanufacturing, but the efficiency of methanol-based bioprocesses is limited by the low rate of methanol utilization pathways and methanol toxicity. Yeast diversity is an attractive biological resource to develop efficient bioprocesses since any effort with strain improvement is more deserving if applied to innate robust strains with relevant catabolic and biosynthetic potential. The present study is in line with such rational and describes the isolation and molecular identification of seven isolates of the methylotrophic species Candida boidinii from waters derived from the traditional curation of olives, in different years, and from contaminated superficial soil near fuel stations. The yeast microbiota from those habitats was also characterized. The four C. boidinii isolates obtained from the curation of olives' water exhibited significantly higher maximum specific growth rates (range 0.15-0.19 h-1), compared with the three isolates obtained from the fuel contaminated soils (range 0.05-0.06 h-1) when grown on methanol as the sole C-source (1% (v/v), in shake flasks, at 30°C). The isolates exhibit significant robustness towards methanol toxicity that increases as the cultivation temperature decreases from 30°C to 25°C. The better methanol-based growth performance exhibited by C. boidinii isolates from olives´ soaking waters could not be essentially attributed to higher methanol tolerance. These methanol-efficient catabolizing isolates are proposed as a promising platform to develop methanol-based bioprocesses.","PeriodicalId":7537,"journal":{"name":"AMB Express","volume":"14 1","pages":"93"},"PeriodicalIF":3.5,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biosynthesis of iron oxide nanoparticles using plant extracts and evaluation of their antibacterial activity. 利用植物提取物生物合成氧化铁纳米颗粒并评估其抗菌活性。

IF 3.5 3区生物学

AMB Express Pub Date : 2024-08-16 DOI: 10.1186/s13568-024-01746-9

Omima Elkhateeb, Mohamed B Atta, Esawy Mahmoud

{"title":"Biosynthesis of iron oxide nanoparticles using plant extracts and evaluation of their antibacterial activity.","authors":"Omima Elkhateeb, Mohamed B Atta, Esawy Mahmoud","doi":"10.1186/s13568-024-01746-9","DOIUrl":"10.1186/s13568-024-01746-9","url":null,"abstract":"The biosynthesis of iron oxide nanoparticles has received increasing attention in the field of food nanotechnology because of their non-toxicity, high efficiency, high antibacterial power, and decontamination features. Therefore, biosynthesis of iron oxide nanoparticles (nFe) was prepared from the leaves of some vegetables, such as cabbage (C) and turnips (T), as well as moringa leaves (M). Alcoholic extracts of these nanoparticles were also tested on Staphylococcus aureus and Escherichia coli to evaluate their antibacterial activity. The results revealed that the particle sizes of the biosynthesis nanomaterials studied ranged from 12.99 to 22.72 nm, and the particles were spherical, irregular, and surrounded by black color. It also contains many functional groups and minerals. Iron nanoparticles modified with Moringa oleifera extract at a concentration of 200 ppm had the highest phenol content compared to other biosynthesis nanoparticles studied. TnFe and MnFe at 200 ppm had a maximum zone of inhibition of 25 mm and 24 mm against Staphylococcus aureus and Escherichia coli, respectively. While the minimum inhibition zone of 8.0 mm was observed at 25 ppm for nFe against Escherichia coli. Therefore, it is recommended to use these extracts of biosynthesis iron oxide nanoparticles as antibacterial agents for stored foods.","PeriodicalId":7537,"journal":{"name":"AMB Express","volume":"14 1","pages":"92"},"PeriodicalIF":3.5,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational modeling study of IL-15-NGR peptide fusion protein: a targeted therapeutics for hepatocellular carcinoma. IL-15-NGR多肽融合蛋白的计算模型研究：肝细胞癌的靶向治疗药物

IF 3.5 3区生物学

AMB Express Pub Date : 2024-08-07 DOI: 10.1186/s13568-024-01747-8

Tehreem Fatima, Mian Muhammad Mubasher, Hafiz Muhammad Rehman, Sakina Niyazi, Abdullah R Alanzi, Maria Kalsoom, Sania Khalid, Hamid Bashir

{"title":"Computational modeling study of IL-15-NGR peptide fusion protein: a targeted therapeutics for hepatocellular carcinoma.","authors":"Tehreem Fatima, Mian Muhammad Mubasher, Hafiz Muhammad Rehman, Sakina Niyazi, Abdullah R Alanzi, Maria Kalsoom, Sania Khalid, Hamid Bashir","doi":"10.1186/s13568-024-01747-8","DOIUrl":"10.1186/s13568-024-01747-8","url":null,"abstract":"The primary challenge to improving existing cancer treatment is to develop drugs that specifically target tumor cell. NGR peptide is tumor homing peptide that selectively target cancer cells while interleukin 15 is a pleiotropic cytokine with anticancer properties. This study computationally engineered a IL15-NGR fusion peptide by linking the homing peptide NGR with the targeting peptide IL-15. After evaluating and validating the chimeric peptide, we docked it to the IL-15Rα/IL-15Rβ/γc heterodimer receptor, examining the interactions and binding energy and lastly, molecular dynamics simulations were performed. The secondary and tertiary structures, along with physicochemical properties of the designed IL-15-NGR chimeric protein, were predicted using GOR IV, trRosetta and ProtParam online servers respectively. The quality and 3D structure validation were confirmed via ProSA-web and SAVES 6.0 analysis which predicted an ERRAT score of 96.72%, with 97.6% of residues in the Ramachandran plot, validating its structure. Finally, Docking, MD simulations and interaction analysis were performed using ClusPro 2.0 and GROMACS and PDBsum, which exhibited significant hydrogen bonding and salt bridges, confirming the formation of a stable docked complex. These results were further corroborated by simulation analysis, which demonstrated a stable and dynamic behavior of the docked complex in a biological environment. The predicted high expression value of fusion protein was 0.844 in E.coli using SOLUPROT tool. These findings suggest efficient expression of the IL15-NGR fusion protein if its gene is inserted into E. coli and indicates its potential as a safe and effective anticancer treatment, paving the way for targeted therapeutic interventions.","PeriodicalId":7537,"journal":{"name":"AMB Express","volume":"14 1","pages":"91"},"PeriodicalIF":3.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lactocaseibacillus-deglycosylated isoflavones prevent Aβ 40-induced Alzheimer's disease in a rat model. 乳酸杆菌脱糖异黄酮在大鼠模型中预防 Aβ 40 诱发的阿尔茨海默病

IF 3.5 3区生物学

AMB Express Pub Date : 2024-08-06 DOI: 10.1186/s13568-024-01735-y

Chin-Feng Liu, Zong-Yang Young, Tsung-Wei Shih, Tzu-Ming Pan, Chun-Lin Lee

{"title":"Lactocaseibacillus-deglycosylated isoflavones prevent Aβ 40-induced Alzheimer's disease in a rat model.","authors":"Chin-Feng Liu, Zong-Yang Young, Tsung-Wei Shih, Tzu-Ming Pan, Chun-Lin Lee","doi":"10.1186/s13568-024-01735-y","DOIUrl":"10.1186/s13568-024-01735-y","url":null,"abstract":"Alzheimer's disease (AD) is the most common neurodegenerative disease, with symptoms appearing in the cerebral cortex and hippocampus. amyloid β peptide (Aβ) has been shown to deposit in the brain, causing oxidative stress and inflammation, leading to impaired memory and learning. Lactocaseibacillus fermentation can produce deglycosylated isoflavones with high physiological activity, which can scavenge free radicals, enhance total antioxidant capacity and inhibit oxidative inflammatory responses. Therefore, in this study, Lactocaseibacillus paracasei subsp. paracasei NTU101 (NTU101) fermented soybean milk and its extracts were used as test substances, and AD model rats were established by infusion of Aβ40 in the brain for 28 days, and the preventive and ameliorating effects of NTU 101 fermented soymilk were discussed. Effects of soymilk and unfermented soymilk on AD, and explore its effects on AD. Main functional ingredients. The results showed that deglycosylated isoflavones in NTU101 fermented soybean milk improved AD symptoms. Mechanisms of actions include the inhibition of oxidative inflammation; reduction in the expression of risk factors for tau protein and apo E protein production, the deposition of Aβ40 around the hippocampus, and the expression of TLR-2 and RAGE proteins in astrocytes and microglia; and improvement in the memory and learning ability.","PeriodicalId":7537,"journal":{"name":"AMB Express","volume":"14 1","pages":"90"},"PeriodicalIF":3.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0