Exploration of drug science最新文献

{"title":"Histological diagnosis of primary biliary cholangitis in one patient without cholestasis alterations: a case report that escaped guidelines","authors":"Matteo Biagi, Elisa Bernasconi, C. Cursaro, Enrico Ronconi, Filippo Zanni, Pamela Sighinolfi, Pietro Andreone","doi":"10.37349/eds.2024.00033","DOIUrl":"https://doi.org/10.37349/eds.2024.00033","url":null,"abstract":"Primary biliary cholangitis (PBC) is an autoimmune cholangiopathy that affects mainly women and, if untreated, can evolve into biliary cirrhosis. Its prevalence varies worldwide, depending on race, and accounts for 22.27 cases/100,000 habitants in Europe. To establish the diagnosis of PBC according to the European Association for the Study of the Liver (EASL) guidelines, two criteria must be satisfied among alkaline phosphatase (ALP) alterations, autoantibody positivity, and histologic abnormalities. Early treatment is effective in prolonging survival. Current guidelines do not suggest hepatic biopsy in patients with autoantibody positivity without cholestasis alterations. However, many patients with these characteristics have been diagnosed with PBC disease only histologically, mainly patients with normal ALP and elevated gamma-glutamyl transferase (GGT), whose normalization has been used as a marker for the follow-up. In contrast, this is the case of a patient with autoantibody positivity and both ALP and GGT within the range, diagnosed for PBC by histology. The manuscript wants to propose the re-evaluation of the role of liver biopsy in PBC diagnosis and the need for a serological or histological biomarker in the follow-up of patients without cholestatic alterations.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"70 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139606878","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}

{"title":"Mechanism of the blood-brain barrier modulation by cadherin peptides.","authors":"Elinaz Farokhi, Ahmed L Alaofi, Vivitri D Prasasty, Filia Stephanie, Marlyn D Laksitorini, Krzysztof Kuczera, Teruna J Siahaan","doi":"10.37349/eds.2024.00049","DOIUrl":"10.37349/eds.2024.00049","url":null,"abstract":"<p><strong>Aim: </strong>This study was aimed at finding the binding site on the human E-cadherin for Ala-Asp-Thr Cyclic 5 (ADTC5), ADTC7, and ADTC9 peptides as blood-brain barrier modulator (BBBM) for determining their mechanism of action in modulating the blood-brain barrier (BBB).</p><p><strong>Methods: </strong>ADTC7 and ADTC9 were derivatives of ADTC5 where the Val6 residue in ADTC5 was replaced by Glu6 and Tyr6 residues, respectively. The binding properties of ADTC5, ADTC7, and ADTC9 to the extracellular-1 (EC1) domain of E-cadherin were evaluated using chemical shift perturbation (CSP) method in the two dimensional (2D) ¹H-¹⁵N-heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) spectroscopy. Molecular docking experiments were used to determine the binding sites of these peptides to the EC1 domain of E-cadherin.</p><p><strong>Results: </strong>This study indicates that ADTC5 has the highest binding affinity to the EC1 domain of E-cadherin compared to ADTC7 and ADTC9, suggesting the importance of the Val6 residue as shown in our previous in vitro study. All three peptides have a similar binding site at the hydrophobic binding pocket where the domain swapping occurs. ADTC5 has a higher overlapping binding site with ADTC7 than that of ADTC9. Binding of ADTC5 on the EC1 domain influences the conformation of the EC1 C-terminal tail.</p><p><strong>Conclusions: </strong>These peptides bind the domain swapping region of the EC1 domain to inhibit the <i>trans</i>-cadherin interaction that creates intercellular junction modulation to increase the BBB paracellular porosity.</p>","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"2 3","pages":"322-338"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing the power of seaweed: unveiling the potential of marine algae in drug discovery","authors":"Leonel Pereira, A. Valado","doi":"10.37349/eds.2023.00032","DOIUrl":"https://doi.org/10.37349/eds.2023.00032","url":null,"abstract":"Seaweeds, also known as marine algae, have gained attention as a promising source of bioactive compounds with potential applications in drug discovery. This review explores the emerging field of seaweed-based drug discovery and highlights the diverse range of bioactive compounds found in seaweeds, including polysaccharides, phlorotannins, pigments, and peptides. These compounds exhibit various pharmacological activities such as antioxidant, anti-inflammatory, antimicrobial, antiviral, and anticancer effects. Seaweeds have demonstrated particular promise in the areas of cancer research, with certain species showing potent antitumor properties. Additionally, their anti-inflammatory, antimicrobial, and neuroprotective potential has captured scientific interest in the treatment of chronic diseases and neurodegenerative disorders. However, challenges related to compound identification, extraction methods, scalability of seaweed cultivation, and understanding the mechanisms of action still need to be addressed. As researchers employ advanced technologies and dive deeper into the chemical composition of seaweeds, the untapped potential of these marine organisms in drug discovery awaits further exploration and holds significant promise for future therapeutic advancements.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"26 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139150549","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}

{"title":"Hybrid azole-based conjugates as upcoming anticancer and antimicrobial agents","authors":"Luís M. T. Frija, Bruno Guerreiro, Inês C. C. Costa, V. Isca, L. Saraíva, B. G. Neves, Mariana Magalhães, Célia Cabral, M. L. Cristiano, P. Rijo","doi":"10.37349/eds.2023.00028","DOIUrl":"https://doi.org/10.37349/eds.2023.00028","url":null,"abstract":"Aim: This study discloses the synthesis and the antimicrobial and anticancer activities of four molecules of structural basis saccharin-thiadiazolyl (4), saccharin-pyridyl (6, 8), and tetrazole-thiadiazolyl (11). Methods: Antimicrobial properties of the molecules were evaluated by the well-diffusion method, against Gram-positive bacteria [Staphylococcus aureus American Type Culture Collection (ATCC) 25923, Staphylococcus epidermidis ATCC 12228, Mycobacterium smegmatis ATCC 607], Gram-negative bacteria (Pseudomonas aeruginosa ATCC 27853) and yeast (Saccharomyces cerevisiae ATCC 2601 and Candida albicans ATCC 10231) strains. The anticancer activity of the compounds was assessed through i) proliferation assays for HCT116, MCF-7, and A375 human cell lines [cells were treated with serial dilutions of compounds and the effect on cell propagation was evaluated by sulforhodamine B (SRB) assay]; ii) antiproliferative and cytotoxic assays for glioma-type cell lines A172 (glioblastoma), U87 (brain-likely glioblastoma), and H4 (neuroglioma; cells were treated with diverse concentrations and the cell viability was assessed using a modified Alamar blue® assay). Results: Compound 11 exhibited significant inhibitory activity against S. aureus and S. epidermidis, with the further molecules demonstrating some inhibitory potential against all the tested Gram-positive, Gram-negative, and yeast strains. Similarly, derivative 11 showed an interesting antiproliferative activity against human colon adenocarcinoma (HCT116), human breast adenocarcinoma (MCF-7), and melanoma (A375) cells, with 50% growth inhibition (GI50) values varying from 3.55 µmol/L to 11.5 µmol/L, in the same order of magnitude of those shown by etoposide. Treatment of brain-like glioblastoma cells (U87) with 11, at the concentration of 100 µg/mL, induced a decrease in cell viability by 50% after 48 h and 72 h. Besides, results attained for A172 cells have shown that compound 11 only induces a significant decrease in cell viability upon treatment at 100 µg/mL for 72 h. A divergent observation was recorded for H4 cells, where the treatment with derivative 11 had promoted a significant decrease in cell viability (< 40–60%), even at concentrations as low as 0.39 µg/mL, after 24 h. Conclusions: This investigation reveals the potential of distinct azole-based conjugates, in particular the tetrazole-thiadiazolyl (11) derivative, as scaffolds worth further investigations, in the frame of antimicrobial and antineoplastic chemotherapy.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"41 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139246172","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}

{"title":"Could flavonoid aglycones prevent the absorption of flavonoid glycosides by inhibiting sodium-dependent glucose transporter-1 in the small intestine?","authors":"K. Sak","doi":"10.37349/eds.2023.00019","DOIUrl":"https://doi.org/10.37349/eds.2023.00019","url":null,"abstract":"Flavonoids present a large group of natural polyphenols with numerous important health benefits for preventing and treating a diverse variety of pathological conditions. However, the actual therapeutic use of these phytochemicals is impeded by their low oral bioavailability. In this commentary article, an interesting paradox is presented: while the ingested flavonoid glycosides can be absorbed by means of sodium-dependent glucose transporters (SGLTs; SGLT1) located in the brush border membrane facing the lumen of the small intestine, certain flavonoid aglycones are able to inhibit these shuttle proteins. It is expected that avoiding the co-intake of such SGLT1 inhibitors concomitantly with flavonoid-rich foods might provide a new option for enhancing the oral bioavailability of flavonoids, thereby preventing the transport of unabsorbed compounds to the large intestine and conversion into catabolites by the colonic microbiota. Altogether, the administration of flavonoids in appropriate combinations is highlighted for getting the maximal health benefits from consuming these bioactive compounds.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91020712","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}

{"title":"Single or multiple treatments with lusutrombopag in subjects with thrombocytopenia and chronic liver disease needing an invasive procedure","authors":"Davide Scalabrini, Paolo Sciuto, C. Felicani, A. Rudilosso, P. Andreone","doi":"10.37349/eds.2023.00020","DOIUrl":"https://doi.org/10.37349/eds.2023.00020","url":null,"abstract":"Thrombocytopenia is one of the most frequent implications of liver cirrhosis. This condition, when present in the severe form [platelet count (PLT) less than 50 × 109/L] correlates, with an increased risk of bleeding during the main diagnostic-therapeutic procedures which cirrhotic patients usually undergone. In these cases, generally, an infusion of platelets is performed, albeit in recent years has been replaced by a cycle of second generation thrombopoietin receptor (TpoR) agonists. This article reports two different cases concerning respectively an 83-year-old female patient suffering from arterial hypertension, aneurysm of the sub-renal aorta, hepatitis C virus (HCV)-positive liver cirrhosis responsive to treatment with antiviral drugs, and a 2.0 cm diameter hepatocellular carcinoma (HCC) nodule localized in the hepatic segment III and a 53-year-old female patient with HCV-positive liver cirrhosis complicated by portal hypertension with splenomegaly, thrombocytopenia, and F3 esophageal varices at high risk of bleeding. Both of them, eligible for invasive procedures such as HCC transarterial chemoembolization (TACE) and for esophageal variceal band ligation, were prescribed prophylaxis with TpoR agonists due to their severe and persistent thrombocytopenia. These two cases show how a short course of lusutrombopag allows to safely perform one or more invasive procedures and how the administration of the drug can be repeated without losing efficacy. Furthermore, this drug shows an excellent safety profile and avoids the risks of platelet transfusion. In conclusion, second generation TpoR agonists can be considered the prophylactic treatment of choice to reduce the risk of bleeding in patients with liver cirrhosis and severe thrombocytopenia.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86463391","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}

{"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}

{"title":"Natural compounds from medicinal plants against COVID-19","authors":"A. Kolodnitsky, N. Ionov, I. Gravel, V. Poroikov","doi":"10.37349/eds.2023.00017","DOIUrl":"https://doi.org/10.37349/eds.2023.00017","url":null,"abstract":"The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), known to cause the coronavirus disease 2019 (COVID-19), was declared a pandemic in early 2020. During the past time, several infections control methods have been developed. Nevertheless, all of them have certain limitations: uncertainty in duration, limited efficacy of vaccines, and lack of effective drugs for COVID-19 treatment. So, the issue of creating drugs for symptomatic and etiotropic therapy is still relevant. This review summarizes the current knowledge of using natural compounds as anti-SARS-CoV-2 agents by analysing the results of in vitro studies and completed clinical trials (CTs). Also, this work highlighted the most active molecules and discussed the possibility of using some compounds in clinical practice.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88624414","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}

{"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}

{"title":"Approved antibacterial drugs in the last 10 years: from the bench to the clinic","authors":"M. García-Castro, F. Sarabia, Amelia Díaz-Morilla, J. López-Romero","doi":"10.37349/eds.2023.00013","DOIUrl":"https://doi.org/10.37349/eds.2023.00013","url":null,"abstract":"Bacterial infections constitute one of the major cases of primary medical incidences worldwide. Historically, the fight against bacterial infections in humans has been an ongoing battle, due to the ability of bacteria to adapt and to survive. Indeed, bacteria have developed various mechanisms of resistance against several therapeutic agents. Consequently, the scientific community is always interested in search of new therapeutic agents, which are able to efficiently kill resistant-bacterial strains. This article covers the most recent antibacterial molecules approved by the Food and Drugs Administration (FDA) and European Medicines Agency (EMA) from 2012 to 2022 and intends to focus on synthetic derivatives to give a pedagogical view, with the goal of highlighting the importance of organic synthesis to obtain greater efficacy. A focus will be made on studies describing the structure and activity of the organic molecules and their interactions with their respective biological targets.","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":"81838944","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}