Exploration of drug science最新文献_第3页

In silico study about β-amyloid’s role in Alzheimer’s disease and glaucoma and prediction of its interactions with glaucoma related proteins β-淀粉样蛋白在阿尔茨海默病和青光眼中的作用及其与青光眼相关蛋白相互作用的预测

Exploration of drug science Pub Date : 2023-08-29 DOI: 10.37349/eds.2023.00018

N. Maurya

{"title":"In silico study about β-amyloid’s role in Alzheimer’s disease and glaucoma and prediction of its interactions with glaucoma related proteins","authors":"N. Maurya","doi":"10.37349/eds.2023.00018","DOIUrl":"https://doi.org/10.37349/eds.2023.00018","url":null,"abstract":"Aim: The significance of β-amyloid protein as a key player in neuro-degenerative disorders viz. Alzheimer’s disease (AD), Parkinson’s disease (PD) has been extensively researched and reported. Glaucoma being another prominent form of neuro-degeneration involving the loss of retinal ganglion cells (RGCs) and human trabecular meshwork (HTM) cells, is also found to be similar to AD in many aspects, but its relation with β-amyloid has not been studied too far up to understanding its causation and pathogenesis where β-amyloid is expected to play important role. This study is an attempt to evaluate the chances of β-amyloid’s role in pathogenesis of retinal neurodegenerative disorder called glaucoma, in silico.\u0000Methods: The study involved determination of feasibility of interaction between β-amyloid and well known glaucoma related proteins namely, myocilin and optineurin. The computational tool called Hex 8.0.0 has been used in this work.\u0000Results: The docking score for β-amyloid and myocilin was found to be –724.1 kJ mol–1 while that for β-amyloid and wild-type optineurin pair was found to be –296.9 kJ mol–1 and that for β-amyloid and mutated optineurin was –607.1 kJ mol–1.\u0000Conclusions: Interaction of β-amyloid with myocilin and optineurin in both forms (wild-type and mutated) is quite energetically favorable. The binding between β-amyloid and mutated optineurin is higher in comparison to that between β-amyloid and wild-type optineurin. Thus, functional significance of β-amyloid in glaucoma pathogenesis is fairly possible which should be studied and proved through in vitro and in vivo studies.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83927595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Natural compounds from medicinal plants against COVID-19 抗COVID-19的药用植物天然化合物

Exploration of drug science Pub Date : 2023-08-28 DOI: 10.37349/eds.2023.00017

A. Kolodnitsky, N. Ionov, I. Gravel, V. Poroikov

引用次数: 0

Iron depletion in “metabolic fatty liver syndromes”: a strong biological rationale with disappointing liver outcomes “代谢性脂肪肝综合征”中的铁缺乏:一个令人失望的肝脏结局的强有力的生物学原理

Exploration of drug science Pub Date : 2023-08-28 DOI: 10.37349/eds.2023.00016

A. Lonardo

{"title":"Iron depletion in “metabolic fatty liver syndromes”: a strong biological rationale with disappointing liver outcomes","authors":"A. Lonardo","doi":"10.37349/eds.2023.00016","DOIUrl":"https://doi.org/10.37349/eds.2023.00016","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD), its more rapidly progressive steatohepatitic variant [nonalcoholic steatohepatitis, (NASH)], and the recently defined metabolic dysfunction-associated fatty liver disease (MAFLD) may be collectively alluded to as “metabolic fatty liver syndromes” (MFLS). MFLS is a common clinical complaint for which no licensed drug treatment is available and a public health issue posing a heaven burden on healthcare systems. Iron plays a key role in many of the key pathogenic steps concurring in the development and progression of MFLS, notably including genetics, intestinal dysbiosis, adipositis, insulin resistance (IR), metaflammation, oxidative stress and ferroptosis, endoplasmic reticulum (ER) stress, and hepatic fibrosis (FIB). This notion raises the logical expectation that iron depletion, which can easily be implemented with venesection, might improve several aspects of MFLS. However, few published studies have globally failed to support these expectations. In conclusion, venesection in MFLS exhibits a strong biological rationale and possible metabolic benefits. However, confronted with failures in hepato-histological outcomes, data call for additional studies aimed to reconcile these inconsistencies.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76209156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Approved antibacterial drugs in the last 10 years: from the bench to the clinic 过去10年被批准的抗菌药物:从实验室到临床

Exploration of drug science Pub Date : 2023-06-30 DOI: 10.37349/eds.2023.00013

M. García-Castro, F. Sarabia, Amelia Díaz-Morilla, J. López-Romero

引用次数: 0

A dextrorotatory residues-incorporated bioactive dodecapeptide against enterohemorrhagic Escherichia coli 抗肠出血性大肠杆菌的右旋残渣结合生物活性十二肽

Exploration of drug science Pub Date : 2023-06-30 DOI: 10.37349/eds.2023.00014

Ping Zeng, Xuemei Yang, K. Wong, Sheng Chen, Kin-Fai Chan, S. Leung, Lanhua Yi

{"title":"A dextrorotatory residues-incorporated bioactive dodecapeptide against enterohemorrhagic Escherichia coli","authors":"Ping Zeng, Xuemei Yang, K. Wong, Sheng Chen, Kin-Fai Chan, S. Leung, Lanhua Yi","doi":"10.37349/eds.2023.00014","DOIUrl":"https://doi.org/10.37349/eds.2023.00014","url":null,"abstract":"Aim: This study aims to report an engineered peptide zp39 with favorable bioactivity against enterohemorrhagic Escherichia coli (E. coli, EHEC). Its antibacterial mechanisms and application in a real food system are assessed.\u0000Methods: Spatial conformation of synthetic peptide zp39 (GIIAGIIiKIKk-NH2, lowercase letters indicate dextrorotatory amino acids) was predicted by PEPstrMOD and its secondary structure was further determined by circular dichroism (CD) spectroscopy. Then, standard E. coli O157:H7 strain ATCC 43888 was used to evaluate the bioactivity of zp39. A double dilution method was applied to investigate its efficacy in normal broth medium, serum, and highly saline conditions. Its effects on cell membrane permeability and potential were measured by fluorescent assays. Thereafter, morphological changes of E. coli O157:H7 cells were monitored by electron microscopy technologies. Finally, the potential application of zp39 in controlling EHEC in food was tested with spinach juice and the Galleria mellonella larvae model was employed to assess the in vivo efficacy.\u0000Results: Peptide zp39 presented an amphiphilic helical structure. It effectively inhibited the growth of E. coli O157:H7 at a concentration of 4 μmol/L in a bactericidal mode. Mechanistic studies revealed that it affected membrane permeability and potential in a dose-dependent manner. Moreover, zp39 maintained satisfactory bioactivity against E. coli O157:H7 even in the presence of 70% serum or 1,000 μmol/L chloride salts. In spinach juice application, > 90% E. coli O157:H7 cells were killed within 2 h after exposure to 64 μmol/L zp39. In vivo study proved that treatment with 64 μmol/L zp39 could effectively boost the survival ratio of infected larvae by 50%.\u0000Conclusions: This study depicts a synthetic dodecapeptide that shows the potential application in controlling EHEC. This molecule may be developed into a highly effective antimicrobial agent applied to prevent food contamination and associated infections.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83172877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of an inter-cysteine loop potentially involved in the activity of Opisthorchis viverrini-granulin-1 半胱氨酸间环的鉴定可能参与了蛇胸菌颗粒蛋白-1的活性

Exploration of drug science Pub Date : 2023-06-30 DOI: 10.37349/eds.2023.00012

R. Takjoo, David T. Wilson, P. Bansal, A. Loukas, M. Smout, N. Daly

{"title":"Identification of an inter-cysteine loop potentially involved in the activity of Opisthorchis viverrini-granulin-1","authors":"R. Takjoo, David T. Wilson, P. Bansal, A. Loukas, M. Smout, N. Daly","doi":"10.37349/eds.2023.00012","DOIUrl":"https://doi.org/10.37349/eds.2023.00012","url":null,"abstract":"Aim: Identification of small bioactive regions in proteins and peptides can be useful information in drug design studies. The current study has shown that an inter-cysteine loop of the N-terminal domain of Opisthorchis viverrini granulin-1 (Ov-GRN-1), a granulin protein from the flatworm liver fluke Opisthorchis viverrini which has potent wound healing properties, maintains the bioactivity of the full-length protein.\u0000Methods: Peptides corresponding to the three inter-cysteine loops of the N-terminal domain were produced using synthetic chemistry, and their structures and bioactivities were analyzed using nuclear magnetic resonance (NMR) spectroscopy and cell proliferation assays, respectively.\u0000Results: As expected for such small peptides, NMR analysis indicated that the peptides were poorly structured in solution. However, a seven-residue peptide corresponding to loop 2 (GRN-L2) promoted cell proliferation, in contrast to the other fragments.\u0000Conclusions: The results from the current study suggest that GRN-L2 might be responsible, in part, for the bioactivity of Ov-GRN-1, and might be a useful lead molecule for subsequent wound healing studies.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80991920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nature-inspired and medicinally relevant short peptides 自然启发和医学相关的短肽

Exploration of drug science Pub Date : 2023-06-27 DOI: 10.37349/eds.2023.00011

M. G. Ciulla, M. Civera, S. Sattin, Kamal Kumar

{"title":"Nature-inspired and medicinally relevant short peptides","authors":"M. G. Ciulla, M. Civera, S. Sattin, Kamal Kumar","doi":"10.37349/eds.2023.00011","DOIUrl":"https://doi.org/10.37349/eds.2023.00011","url":null,"abstract":"Peptides constitute an important component of Nature’s pharmacy and they play a significant role in several signaling pathways acting as natural biological messengers. While nature has mastered the cycle of creation, application, and destruction of large and short peptides to the benefit of the host organism, organic and medicinal chemists have in their capacity and small steps, made big developments in the field of peptide synthesis as well as in developing them as therapeutics. In comparison to their big counterparts, i.e. proteins, short peptides encompass several advantages, from the ease of synthesis to their physico-chemical properties. However, the real challenge for in vivo application of therapeutic peptides is to overcome their low plasma availability and their fast enzymatic degradation. This review briefly covers the relevant areas of medicinally important short peptides and the recent developments made to turn these peptides into therapeutics. Also presented in this article are important efforts and strategies used to overcome some of the inherent limitations of peptidic molecules and thereby facilitate their progression in the clinical phases towards approved drugs.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"220 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88025246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Heterogeneous graph convolutional neural network for protein-ligand scoring 蛋白质配体评分的异构图卷积神经网络

Exploration of drug science Pub Date : 2023-04-30 DOI: 10.37349/eds.2023.00010

Kevin Crampon, Alexis Giorkallos, X. Vigouroux, S. Baud, L. Steffenel

{"title":"Heterogeneous graph convolutional neural network for protein-ligand scoring","authors":"Kevin Crampon, Alexis Giorkallos, X. Vigouroux, S. Baud, L. Steffenel","doi":"10.37349/eds.2023.00010","DOIUrl":"https://doi.org/10.37349/eds.2023.00010","url":null,"abstract":"Aim: Drug discovery is a long process, often taking decades of research endeavors. It is still an active area of research in both academic and industrial sectors with efforts on reducing time and cost. Computational simulations like molecular docking enable fast exploration of large databases of compounds and extract the most promising molecule candidates for further in vitro and in vivo tests. Structure-based molecular docking is a complex process mixing both surface exploration and energy estimation to find the minimal free energy of binding corresponding to the best interaction location.\u0000Methods: Hereafter, heterogeneous graph score (HGScore), a new scoring function is proposed and is developed in the context of a protein-small compound-complex. Each complex is represented by a heterogeneous graph allowing to separate edges according to their class (inter- or intra-molecular). Then a heterogeneous graph convolutional network (HGCN) is used allowing the discrimination of the information according to the edge crossed. In the end, the model produces the affinity score of the complex.\u0000Results: HGScore has been tested on the comparative assessment of scoring functions (CASF) 2013 and 2016 benchmarks for scoring, ranking, and docking powers. It has achieved good performances by outperforming classical methods and being among the best artificial intelligence (AI) methods.\u0000Conclusions: Thus, HGScore brings a new way to represent protein-ligand interactions. Using a representation that involves classical graph neural networks (GNNs) and splitting the learning process regarding the edge type makes the proposed model to be the best adapted for future transfer learning on other (protein-DNA, protein-sugar, protein-protein, etc.) biological complexes.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85736473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nano theranostics involved in bladder cancer treatment 纳米疗法在膀胱癌治疗中的应用

Exploration of drug science Pub Date : 2023-04-28 DOI: 10.37349/eds.2023.00008

Kun Liu, Qixin Mo, Z. Ding, Shicong Lai, Jian Ren, Qingsong Yu

引用次数: 0

Machine learning for drug science 药物科学的机器学习

Exploration of drug science Pub Date : 2023-04-16 DOI: 10.37349/eds.2023.00007

de Azevedo Jr. Walter F.

引用次数: 0