Current molecular pharmacology最新文献

{"title":"Preface","authors":"Michael Kahn","doi":"10.2174/187446721601221110105607","DOIUrl":"https://doi.org/10.2174/187446721601221110105607","url":null,"abstract":"It is currently estimated that 57 million people (1 in 4 adults) in the Unites States have prediabetes, many of whom will develop diabetes in ensuing years unless significant modifications in lifestyle occur, including diet, weight loss, and exercise. Furthermore, a small but significant number may already be at risk for developing vascular disease. Hence, prediabetes constitutes a major international public health concern that threatens to increase dramatically given the growing prevalence of worldwide obesity. Prediabetes is also associatedwith considerable financial expenditure with higher rates of medical visits for hypertension, metabolic and renal complications, and general medical conditions. The national annual medical cost of prediabetes has been estimated to exceed $25 billion. Since it therefore impacts considerably an already burdened healthcare system, the recently passed Affordable Care Act is opportune, as it addresses the critical need for preventive approaches to this epidemic. A major factor contributing to the difficulty in ascertaining who has prediabetes pertains to the way it, as diabetes per se, has been defined. As discussed in greater detail in this issue, the diagnosis of prediabetes hasbeenpredicated on absolute criteria defined by blood glucose measurements, which is one of the reasons the American Diabetes Association adopted a range of HbA1c values as a basis for identifying those at risk for developing diabetes. However, as neither glucose nor HbA1c determinations may be sufficiently sensitive to diagnose early metabolic abnormalities precisely, the practitioner requires considerable judgment in assessing these subtle conditions. Thus, defining prediabetes categorically by relatively arbitrary threshold criteria may inadvertently lead to the failure to diagnose individuals with lower glucose levels who may still be at risk for progression to diabetes or cardiovascular disease. Rather than viewing the evolving disease process as a continuum, the traditional dichotomous approach to definingmetabolic entitiesmost likely addresses only a small segment of a much larger problem and hence underestimates the considerable prevalence of this condition. One potential approach for overcoming the uncertainty associated with absolute diagnostic criteria is the use of a “personalized profile,” which would","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2022-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44915217","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":"Molecular Insights into Agonist/Antagonist Effects on Macromolecules Involved in Human Disease Mechanisms.","authors":"C. Selvaraj, S. Sakkiah, Dhurvas Chandrasekaran Dinesh","doi":"10.2174/1874467215999220317164522","DOIUrl":"https://doi.org/10.2174/1874467215999220317164522","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41494541","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":"Withdrawn: Variations in Altered Global Gene Expression caused by Topoisomerase II Poisons Assessed with Reference to Differences in DNA Binding","authors":"Malek Zihlif, Daniel R Catchpoole, Bernard W Stewart, Laurence P G Wakelin","doi":"10.2174/1874467215666220301115946","DOIUrl":"10.2174/1874467215666220301115946","url":null,"abstract":"<p><p>The article has been withdrawn at the request of the authors of the journal Current Molecular Pharmacology.</p><p><p>Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.</p><p><p>The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php.</p><p><strong>Bentham science disclaimer: </strong>It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously\u0000submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere\u0000must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting\u0000the article for publication the authors agree that the publishers have the legal right to take appropriate action against the\u0000authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright\u0000of their article is transferred to the publishers if and when the article is accepted for publication.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43724729","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":"Inactivation of Parathyroid Hormone: Perspectives of Drug Discovery to Combating Hyperparathyroidism.","authors":"Amit Kumar,&nbsp;Jochen Balbach","doi":"10.2174/1874467214666210126112839","DOIUrl":"https://doi.org/10.2174/1874467214666210126112839","url":null,"abstract":"<p><p>Hormonal coordination is tightly regulated within the human body and thus regulates human physiology. The parathyroid hormone (PTH), a member of the endocrine system, regulates the calcium and phosphate level within the human body. Under non-physiological conditions, PTH levels get upregulated (hyperparathyroidism) or downregulated (hypoparathyroidism) due to external or internal factors. In case of hyperparathyroidism, elevated PTH stimulates cellular receptors present in the bones, kidneys, and intestines to increase the blood calcium level, leading to calcium deposition. This eventually causes various symptoms, including kidney stones. Currently, there is no known medication that directly targets PTH in order to suppress its function. Therefore, it is of great interest to find novel small molecules or any other means that can modulate PTH function. The molecular signaling of PTH starts by binding its N-terminus to the G-protein coupled PTH1/2 receptor. Therefore, any intervention that affects the N-terminus of PTH could be a lead candidate for treating hyperparathyroidism. As a proof-of-concept, there are various possibilities to inhibit molecular PTH function by (i) a small molecule, (ii) N-terminal PTH phosphorylation, (iii) fibril formation and (iv) residue-specific mutations. These modifications put PTH into an inactive state, which will be discussed in detail in this review article. We anticipate that exploring small molecules or other means that affect the N-terminus of PTH could be lead candidates in combating hyperparathyroidism.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25358490","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":"Advances in Research on microRNAs Related to the Invasion and Metastasis of Nasopharyngeal Carcinoma.","authors":"ShanShan Zhang,&nbsp;BaiQi Wang,&nbsp;LuLu Zheng,&nbsp;ZhuQiong Fu,&nbsp;YiTing Fu,&nbsp;WeiGuo Huang,&nbsp;AiLan Cheng","doi":"10.2174/1874467214666210614150720","DOIUrl":"https://doi.org/10.2174/1874467214666210614150720","url":null,"abstract":"<p><p>Nasopharyngeal Carcinoma (NPC), which is associated with latent Epstein-Barr virus infection in most cases, is a unique epithelial malignancy arising from the nasopharyngeal mucosal lining. Accumulating evidence is providing insights into the genetic and molecular aberrations that likely drive nasopharyngeal tumor development and progression. We review recent analyses of microRNAs (miRNAs), including Epstein-Barr virus-encoded miRNAs (EBV-encoded miRNAs) and dysregulated cellular miRNAs, that may be related to the metastasis of nasopharyngeal carcinoma. The studies summarized herein have greatly expanded our knowledge of the molecular biology of NPC involving miRNAs, and they may provide new biological targets for clinical diagnosis and reveal the potential of microRNA therapeutics. However, much remains to be uncovered.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39231225","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":"Disruption of Wnt/β-catenin Pathway Elevates the Sensitivity of Gastric Cancer Cells to PD-1 Antibody.","authors":"Jian Li,&nbsp;Hui Zhang,&nbsp;Songhua Bei,&nbsp;Xiaohong Zhang,&nbsp;Huanqing Li,&nbsp;Li Ye,&nbsp;Li Feng","doi":"10.2174/1874467214666210617163821","DOIUrl":"https://doi.org/10.2174/1874467214666210617163821","url":null,"abstract":"<p><strong>Background: </strong>Gastric Cancer (GC) is the fifth most common malignancy tumor and the third cause of cancer-related death around the world. Immune checkpoint inhibitors (ICIs) such as programmed cell death-1 (PD-1) antibodies play an active role in tumor therapy. A recent study reveals that Wnt/β-catenin signaling pathway is negatively correlated with T-cell infiltration in tumor microenvironment (TME), thereby influencing the therapeutic efficacy of PD-1 antibody.</p><p><strong>Objective: </strong>In this study, we aimed to uncover the relationship of Wnt/β-catenin pathway to CD8+ T cell activity as well as its effect on anti-PD-1 therapeutic efficacy in GC.</p><p><strong>Methods and results: </strong>We first collected clinical samples and went through an immunohistochemical analysis and found that a high β-catenin expression in GC tissues was often associated with a significant absence of CD8+ T-cell infiltration. In addition, our data further indicated that disruption of the Wnt/β-catenin pathway in GC cells inhibited their migratory and invasive ability. Meanwhile, enhanced sensitivity of GC cells to PD-1 blockade therapy was evident by decreased Jurkat cell apoptosis rate and increased GC cell apoptosis rate in a tumor and Jurkat cells co-culture system with the presence of Wnt/β-catenin pathway inhibition.</p><p><strong>Conclusion: </strong>Collectively, these findings indicated Wnt/β-catenin pathway may play a significant role in modulating the activity of Jurkat cells and downregulation of Wnt/β-catenin may enhance the sensitivity of GC cells to PD-1 antibody in vitro. This result further indicated that β-catenin and PD-1 targeted inhibition might become a potential and effective therapy for GC patients.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39241862","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":"Reviewing Antiviral Research against Viruses Causing Human Diseases - a Structure-Guided Approach.","authors":"Arunima Sikdar,&nbsp;Rupali Gupta,&nbsp;Evzen Boura","doi":"10.2174/1874467214666210804152836","DOIUrl":"https://doi.org/10.2174/1874467214666210804152836","url":null,"abstract":"<p><p>The smallest of all the pathogens, viruses, have continuously been the foremost strange microorganisms. Viral infections can cause extreme sicknesses as evidenced by the HIV/AIDS widespread or the later Ebola or Zika episodes. Apprehensive framework distortions are also regularly observed as consequences of numerous viral infections. Besides, numerous viral infections are of oncoviruses, which can trigger different types of cancer. Nearly every year, a modern infectious species emerges, debilitating the world population with an annihilating episode. Subsequently, there is a need to create antivirals to combat such rising infections. From the discovery of the antiviral drug Idoxuridine in 1962 to the revelation of Baloxavir marboxil (Xofluza) that was approved by the FDA in 2018, the whole process and criteria of creating antivirals have changed significantly. In this article, different auxiliary science strategies are described that can serve as a referral for therapeutic innovation.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39275644","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":"Key miRNAs in Modulating Aging and Longevity: A Focus on Signaling Pathways and Cellular Targets.","authors":"Aliabbas Zia,&nbsp;Tahereh Farkhondeh,&nbsp;Faezeh Sahebdel,&nbsp;Ali Mohammad Pourbagher-Shahri,&nbsp;Saeed Samarghandian","doi":"10.2174/1874467214666210917141541","DOIUrl":"https://doi.org/10.2174/1874467214666210917141541","url":null,"abstract":"<p><p>Aging is a multifactorial process accompanied by gradual deterioration of most biological procedures of cells. MicroRNAs (miRNAs) are a class of short non-coding RNAs that post-transcriptionally regulate the expression of mRNAs through sequence-specific binding, contributing to many crucial aspects of cell biology. Several miRNAs are expressed differently in various organisms through aging. The function of miRNAs in modulating aging procedures has been disclosed recently with the detection of miRNAs that modulate longevity in the invertebrate model organisms through the IIS pathway. In these model organisms, several miRNAs have been detected to both negatively and positively regulate lifespan via commonly aging pathways. miRNAs modulate age-related procedures and disorders in different mammalian tissues by measuring their tissue- specific expression in older and younger counterparts, including heart, skin, bone, brain, and muscle tissues. Moreover, several miRNAs have contributed to modulating senescence in different human cells, and the roles of these miRNAs in modulating cellular senescence have allowed illustrating some mechanisms of aging. The review discusses the available data on the role of miRNAs in the aging process, and the roles of miRNAs as aging biomarkers and regulators of longevity in cellular senescence, tissue aging, and organism lifespan have been highlighted.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39427591","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":"siRNAs and Viruses: The good, the Bad and the Way Forward.","authors":"Cassandra Soobramoney,&nbsp;Raveen Parboosing","doi":"10.2174/1874467214666210420113427","DOIUrl":"https://doi.org/10.2174/1874467214666210420113427","url":null,"abstract":"<p><p>There are no available antivirals for many viruses or strains, while current antivirals are limited by toxicity and drug resistance. Therefore, alternative strategies, such as RNA interference (RNAi) are required. RNAi suppresses gene expression of any mRNA, making it an attractive candidate for antiviral therapeutics. Studies have evaluated siRNAs in a range of viruses, with some showing promising results. However, issues with stability and delivery of siRNAs remain. These issues may be minimized by modifying the siRNA structure, using an efficient delivery vector and targeting multiple regions of a virus's genome in a single dose. Finding these solutions could accelerate the progress of RNAi-based antivirals. This review highlights selected examples of antiviral siRNAs, limitations of RNAi and strategies to overcome these limitations.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38828697","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":"Pretreatment with Gallic Acid Mitigates Cyclophosphamide Induced Inflammation and Oxidative Stress in Mice.","authors":"Saeed Baharmi,&nbsp;Heibatullah Kalantari,&nbsp;Mojtaba Kalantar,&nbsp;Mehdi Goudarzi,&nbsp;Esrafil Mansouri,&nbsp;Hadi Kalantar","doi":"10.2174/1874467214666210531162741","DOIUrl":"https://doi.org/10.2174/1874467214666210531162741","url":null,"abstract":"<p><strong>Background: </strong>Cyclophosphamide (CP) as an alkylating compound has been widely applied to treat cancer and autoimmune diseases. CP is observed to be nephrotoxic in humans and animals because it produces reactive oxygen species. Gallic Acid (GA), a polyhydroxy phenolic compound, is reported to exhibit antioxidant and anti-inflammatory effects.</p><p><strong>Objective: </strong>The current research aimed at evaluating the GA effect on CP-related renal toxicity.</p><p><strong>Methods: </strong>In total, 35 male mice were assigned to 5 groups. Group1: receiving normal saline, group 2: CP group, receiving one CP injection (200 mg/kg; i.p.) on day 6. Groups 3 and 4: GA+CP, GA (10 and 30 mg/kg; p.o.; respectively) received through six consecutive days plus CP on the 6th day 2 hr after the last dose of GA, group 5: received GA (30 mg/kg; p.o.) for six consecutive days. Then on day 7, blood samples were collected for determining Creatinine (Cr), serum kidney injury molecule-1 (KIM-1), Blood Urea Nitrogen (BUN), and Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentrations. Malondialdehyde (MDA), Nitric Oxide (NO) concentration, Catalase (CAT), Superoxide Dismutase (SOD), Glutathione (GSH), Glutathione Peroxidase (GPx) activities, and IL-1β, TNF-α levels were assessed in renal tissue.</p><p><strong>Results: </strong>CP administration significantly increases KIM-1, NGAL, Cr, BUN, MDA, NO, IL-1β, and TNF-α level. It also decreases GSH concentration, SOD, GPx, and CAT function. Pretreatment with GA prevented these changes. Histopathological assessments approved the GA protective effect.</p><p><strong>Conclusion: </strong>Our results showed that GA is possibly effective as a protective agent in cyclophosphamide- associated toxicities.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39037082","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}