Pharmaceutical Science Advances最新文献_第7页

Ab initio modeling and ligand docking of quercetin and the MC-LR transporter protein Oatp1b2/OATP1B3 槲皮素与MC-LR转运蛋白Oatp1b2/OATP1B3的从头算建模及配体对接

Pharmaceutical Science Advances Pub Date : 2023-09-09 DOI: 10.1016/j.pscia.2023.100011

Kriti Shrinet , Ritika K. Singh , Riden Saxena , Avinash K. Chaurasia , Arvind Kumar

{"title":"Ab initio modeling and ligand docking of quercetin and the MC-LR transporter protein Oatp1b2/OATP1B3","authors":"Kriti Shrinet , Ritika K. Singh , Riden Saxena , Avinash K. Chaurasia , Arvind Kumar","doi":"10.1016/j.pscia.2023.100011","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100011","url":null,"abstract":"<div><p>Trans-membrane proteins (TMPs) play a crucial role in the translocation of organic and inorganic molecules. Unlike other proteins, TMPs are difficult to model structurally because of their location within the amphipathic plasma membrane. In this study, we focused on examining the transport of the cyanotoxin microcystin-LR (MC-LR) through organic ion transporting polypeptides (OATPs) and whether the bioactive phytoconstituent quercetin can function as a barrier to the transportation of MC-LR. To test this hypothesis, we first modeled the transporters OATP1B3 and Oatp1b2 localized in the human and mouse liver, respectively, by <em>ab initio</em> modeling with the Iterative Threading ASSEmbly Refinement server and refined the generated model using the refinement tool of the ModLoop server. Using different tools and servers, the structural quality of the transmembrane helices was validated and found to be an accurate structure of a TMP. Docking analysis was performed with the ligands MC-LR and quercetin with both OATPs using the PatchDock and FireDock online servers. The results, in the form of the global energy of both docked structures, were based on predictions made earlier. The Oatp1b2 global energy for quercetin was −36.4 kcal/mol, compared with the corresponding value at the MC-LR location which was only −5.59 kcal/mol. Similarly, in the case of OATP1B3 with quercetin, the global energy was found to be −39.0 kcal/mol, whereas with MC-LR it was −15.6 kcal/mol. These results clearly show that quercetin competitively inhibits the binding of MC-LR to its respective targets.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"1 2","pages":"Article 100011"},"PeriodicalIF":0.0,"publicationDate":"2023-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50190384","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

Blockage of HSP90 and IDO1 pathway by α-MSH modified nanoelicitor to dual-facilitate mild photothermal therapy α-MSH修饰的纳米激发子阻断HSP90和IDO1通路双重促进温和光热治疗

Pharmaceutical Science Advances Pub Date : 2023-07-22 DOI: 10.1016/j.pscia.2023.100009

Shunli Fu, Qingping Ma, Jiangnan Li, Yifan Wang, Chunyan Yang, Panpan Gu, Weihan Zhang, Yongjun Liu, Na Zhang

{"title":"Blockage of HSP90 and IDO1 pathway by α-MSH modified nanoelicitor to dual-facilitate mild photothermal therapy","authors":"Shunli Fu, Qingping Ma, Jiangnan Li, Yifan Wang, Chunyan Yang, Panpan Gu, Weihan Zhang, Yongjun Liu, Na Zhang","doi":"10.1016/j.pscia.2023.100009","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100009","url":null,"abstract":"<div><p>Mild photothermal therapy (PTT) kills tumors at low temperatures (<45 °C) with less non-specific thermal diffusion through adjacent normal tissues, making it a promising antitumor strategy. Although mild PTT can directly convert light energy into heat to kill tumors and indirectly induce immune cell death to prime the immune response, it simultaneously induces negative regulatory factors in the body to resist antitumor functions. In particular, the direct killing effects were reversed by the upregulation of heat shock protein 90 (HSP90) induced by mild PTT. The antitumor effects of T-cell-based immunotherapy counter indoleamine 2,3-dioxygenase1 (IDO1)-catalyzed kynurenine accumulation. Current studies have mainly focused on promoting direct killing effects or utilizing the priming immune response to strengthen the immunotherapy of mild PTT. Therefore, it is necessary to investigate whether the simultaneous promotion of direct killing and indirect immune activation would synergistically maximize mild PTT efficacy. This study reports on the development of a tumor-targeting nanoelicitor, α-<strong>M</strong>SH-<strong>G</strong>A/<strong>I</strong>R780/1-<strong>M</strong>T-<strong>Lip</strong>osome (M-GIM-Lip), by co-loading the photothermal agent IR780, HSP90 inhibitor geldanamycin, and IDO1 inhibitor 1-MT into liposomes with a melanoma-specific target ligand α-MSH modification. After accumulating in the tumor, the M-GIM-Lip could significantly inhibit tumor progress by combinate blockage of HSP90 and IDO1 pathways at 41 °C treatment of mild PTT. The study offers an innovative co-regulation strategy for enhancing the antitumor effects of mild PTT.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"1 2","pages":"Article 100009"},"PeriodicalIF":0.0,"publicationDate":"2023-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50190382","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

Controlled release of bilayer tablet comprising vitamin B6 rapid-release layer and melatonin sustained-release layer 含有维生素B6快速释放层和褪黑素缓释层的双层片剂的控释

Pharmaceutical Science Advances Pub Date : 2023-05-15 DOI: 10.1016/j.pscia.2023.100008

Yan Wang , Jiaqi Xu , Nan Gao , Hongqian Lv , Minge Sun , Peng Zhang

{"title":"Controlled release of bilayer tablet comprising vitamin B6 rapid-release layer and melatonin sustained-release layer","authors":"Yan Wang , Jiaqi Xu , Nan Gao , Hongqian Lv , Minge Sun , Peng Zhang","doi":"10.1016/j.pscia.2023.100008","DOIUrl":"https://doi.org/10.1016/j.pscia.2023.100008","url":null,"abstract":"<div><p>Here, the formulation of a novel bilayer tablet comprising a vitamin B<sub>6</sub> rapid-release layer and a melatonin sustained-release layer is described. The effects of viscosity and concentration of the sustained-release matrix material, amount of diluent, and melatonin particle size on the release characteristics of melatonin were examined. In addition, the drug-release behavior of the prepared bilayer tablets was examined in different dissolution media. Further, drug-release kinetics and melatonin behavior in the sustained-release layer were evaluated based on dissolution profiles and changes in tablet weight during dissolution. Furthermore, the stability of the bilayer tablet was established. The <em>in vitro</em> release test revealed that vitamin B<sub>6</sub> was completely released within 10–15 min, with melatonin demonstrating ∼90% cumulative release within 8 h. Based on kinetic model fitting results, melatonin release was well fitted to the Ritger-Peppas model; the release mechanism was non-Fick diffusion with both diffusion and erosion. The drug-release study confirmed that the melatonin sustained-release layer predominantly underwent polymer swelling rather than polymer erosion. The stability test results showed that the bilayer tablets had good stability under high temperature, high humidity, and light conditions. The bilayer tablets offer an alternative for the controlled-release oral administration of melatonin, although their <em>in vivo</em> effects need to be investigated in human studies.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"1 2","pages":"Article 100008"},"PeriodicalIF":0.0,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50190387","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

The inaugural editorial of pharmaceutical science advances 《药物科学进展》创刊社论

Pharmaceutical Science Advances Pub Date : 2023-03-01 DOI: 10.1016/j.pscia.2023.100003

引用次数: 0

Covalent coating strategy for enhancing the biocompatibility and hemocompatibility of blood-contacting medical materials 共价涂层策略提高血液接触医用材料的生物相容性和血液相容性

Pharmaceutical Science Advances Pub Date : 2023-03-01 DOI: 10.1016/j.pscia.2022.100001

Kangjia Sheng , Yan Gao , Tao Bao , Sicen Wang

{"title":"Covalent coating strategy for enhancing the biocompatibility and hemocompatibility of blood-contacting medical materials","authors":"Kangjia Sheng , Yan Gao , Tao Bao , Sicen Wang","doi":"10.1016/j.pscia.2022.100001","DOIUrl":"https://doi.org/10.1016/j.pscia.2022.100001","url":null,"abstract":"<div><p>Blood-contacting medical devices/materials are widely used in the diagnosis and treatment of a variety of diseases. Functional coatings of medical devices are considered one of the core functions in the future, overcoming the limitations of medical devices/materials without modification, including plasma proteins adhesion, platelet activation and coagulation cascade normally result in clotting and thrombosis in clinical use, posing a serious threat to the health and life of patients. In order to improve the anticoagulant properties of material/device surfaces, several surface modified techniques have been developed. Among them, covalent graft method has attracted much attention due to its high stability and excellent hemocompatibility. This review encompasses various covalent modification methods on the surface of blood-contacting medical materials, such as chemical polymers, metallic biomaterials, nylon net membrane, glass slide and etc. Firstly, an overview of the covalent immobilization method for coating is summarized. Secondly, surface coating methods including physical adsorption, electrostatic attachment and layer-by-layer deposition are presented. Finally, the advantages and disadvantages of covalent immobilization method and other methods are compared. Collectively, the information complied should serve as a comprehensively repository in covalent coating strategy for blood-contacting surface, expecting to provide a general retrospect and prospect on the research progress of anticoagulant surface construction and its application in medical devices.</p></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"1 1","pages":"Article 100001"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50189489","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: 2

Magic bullets, magic shields, and antimicrobials in between 魔法子弹、魔法盾牌和介于两者之间的抗菌药物

Pharmaceutical Science Advances Pub Date : 2023-03-01 DOI: 10.1016/j.pscia.2022.100002

Praveen Prathapan

引用次数: 0