Current Research in Pharmacology and Drug Discovery最新文献

{"title":"WITHDRAWN: Myoinositol supplementation for the prevention of gestational diabetes in at-risk patients. Systematic review and meta-analysis","authors":"Anthéa Bertrand ,&nbsp;Denis Gallot ,&nbsp;Bruno Pereira ,&nbsp;Amélie Delabaere","doi":"10.1016/j.crphar.2022.100140","DOIUrl":"https://doi.org/10.1016/j.crphar.2022.100140","url":null,"abstract":"<div><p>This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (<span>http://www.elsevier.com/locate/withdrawalpolicy)</span><svg><path></path></svg>.</p><p>This article has been withdrawn at the request of Author.</p><p>The publisher apologizes to the readers for this unfortunate error.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100140"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49769293","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":"Sex differences in drug effects and/or toxicity in oncology","authors":"H.T. Rakshith ,&nbsp;S. Lohita ,&nbsp;Anvil Preem Rebello ,&nbsp;Prakash S. Goudanavar ,&nbsp;N. Raghavendra Naveen","doi":"10.1016/j.crphar.2022.100152","DOIUrl":"10.1016/j.crphar.2022.100152","url":null,"abstract":"<div><p>The prevalence, incidence, and severity of a wide variety of diseases and ailments are significantly influenced by the significant disparities that occur between the sexes. The way that men and women react to pharmacological treatment also varies. Therefore, it is crucial to comprehend these reactions in order to conduct risk assessment correctly and to develop safe and efficient therapies. Even from that limited vantage point, the manner and timing of our drug usage might have unintended and unanticipated consequences. There are sex-specific differences in the incidence and mortality of certain malignancies. One of the most important discoveries in cancer epidemiology is the gender inequalities. Cancer incidence differences between the sexes are thought to be regulated at the genetic and molecular levels and by sex hormones like oestrogen. Differences based on sex and gender are among the least investigated factors impacting cancer susceptibility, progression, survival, and therapy response despite their established importance in clinical care. The molecular mechanisms underlying sex differences in particular are poorly known, hence the majority of precision medicine approaches employ mutational or other genetic data to assign therapy without taking into account how the patient's sex may affect therapeutic efficacy. In patients receiving chemotherapy, there are definite gender-dependent disparities in response rates and the likelihood of side effects. This review explores the influence of sex as a biological variable in drug effects or toxicity in oncology.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100152"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/75/72/main.PMC9881040.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10586700","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":"Mechanistic update of Trisenox in blood cancer","authors":"Ananta ,&nbsp;Swati Benerjee ,&nbsp;Paul B. Tchounwou ,&nbsp;Sanjay Kumar","doi":"10.1016/j.crphar.2023.100166","DOIUrl":"https://doi.org/10.1016/j.crphar.2023.100166","url":null,"abstract":"<div><p>Acute promyelocytic leukemia (APL)/blood cancer is M3 type of acute myeloid leukemia (AML) formed inside bone marrow through chromosomal translocation mutation usually between chromosome 15 &amp; 17. It accounts around 10% cases of AML worldwide. Trisenox (TX/ATO) is used in chemotherapy for treatment of all age group of APL patients with highest efficacy and survival rate for longer period. High concentration of TX inhibits growth of APL cells by diverse mechanism however, it cures only PML-RARα fusion gene/oncogene containing APL patients. TX resistant APL patients (different oncogenic make up) have been reported from worldwide. This review summarizes updated mechanism of TX action via PML nuclear bodies formation, proteasomal degradation, autophagy, p53 activation, telomerase activity, heteromerization of pRb &amp; E2F, and regulation of signaling mechanism in APL cells. We have also provided important information of combination therapy of TX with other molecules mechanism of action in acute leukemia cells. It provides updated information of TX action for researcher which may help finding new target for further research in APL pathophysiology or new TX resistant APL patients drug designing.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"5 ","pages":"Article 100166"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257123000147/pdfft?md5=e35d9be6096f3a275318fe96a9be2041&pid=1-s2.0-S2590257123000147-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138430849","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":"OCE-205 in rats and non-human primates: Pharmacokinetic and pharmacodynamic analysis","authors":"Stan Bukofzer ,&nbsp;Geoff Harris ,&nbsp;Edward E. Cable","doi":"10.1016/j.crphar.2023.100163","DOIUrl":"10.1016/j.crphar.2023.100163","url":null,"abstract":"<div><p>Treatment for complications associated with the hemodynamic consequences of decompensated cirrhosis remains suboptimal. Terlipressin, the latest pharmacological management of hepatorenal syndrome–acute kidney injury (HRS-AKI), targets the vasopressin system but has serious side effects. OCE-205 is a novel peptide designed to target the vasopressin receptor system as a mixed V1a agonist/antagonist, resulting in effective partial agonism without V2 agonism. We examined the <em>in vivo</em> pharmacokinetic/pharmacodynamic properties of OCE-205 in healthy rats and cynomolgus monkeys. OCE-205 was administered by IV or SC bolus injection; arginine vasopressin (AVP) or terlipressin were comparators. After IV OCE-205 administration in rats, mean plasma concentration decreased in a mostly linear manner to 2 mg/mL after 120 min, and for SC administration, slowly decreased to ∼50 ng/mL after 300 min. Compared with pre-test values, arterial blood pressure values significantly increased after all OCE-205 doses tested. For monkeys, the concentration after IV OCE-205 administration was mostly linear to 5 ng/mL after 180 min, and for SC administration, ∼3 ng/mL after 480 min. Subcutaneous OCE-205 administration increased mean arterial pressure (MAP) versus baseline, with ΔMAP in OCE-205–treated animals marked and long-lasting while terlipressin induced an increase from baseline in MAP, with negligible ΔMAP, on average, by 150 min after administration in all groups. AVP, but not OCE-205, significantly increased blood lactate concentrations. OCE-205 was well tolerated in adult male rats and cynomolgus monkeys following single-dose bolus administration. The preclinical results of OCE-205, with its demonstrated V1a selective partial agonist activity and potentially tolerable safety profile, suggest its potential utility for treatment of the cardiovascular complications of cirrhosis.</p></div><div><h3>Institutional protocol number</h3><p>Procedures were approved by the Ferring Research Institute (FRI) Institutional Animal Care and Use Committee (IACUC) on November 27, 2006 under protocol FRI 06-011, and by the Sinclair Research Center IACUC under protocol S11177.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"5 ","pages":"Article 100163"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ca/d8/main.PMC10440361.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10055261","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":"Exploring genetic and immune underpinnings of the sexual dimorphism in tumor response to immune checkpoints inhibitors: A narrative review","authors":"Giulia Mazzaschi ,&nbsp;Federico Quaini ,&nbsp;Sebastiano Buti","doi":"10.1016/j.crphar.2022.100146","DOIUrl":"10.1016/j.crphar.2022.100146","url":null,"abstract":"<div><h3>Introduction</h3><p>In spite of the undisputed relevance of sex as critical biologic variable of the immune landscape, still limited is our understanding of the basic mechanisms implicated in sex-biased immune response thereby conditioning the therapeutic outcome in cancer patients. This hindrance delays the actual attempts to decipher the heterogeneity of cancer and its immune surveillance, further digressing the achievement of predictive biomarkers in the current immunotherapy-driven scenario. <em>Body</em>: The present review concisely reports on genetic, chromosomal, hormonal, and immune features underlying sex-differences in the response to immune checkpoint inhibitors (ICIs). In addition to outline the need of robust data on ICI pharmaco-kinetics/dynamics, our survey might provide new insights on sex determinants of ICI efficacy and suggests uncovered pathways that warrant prospective investigations.</p></div><div><h3>Conclusion</h3><p>According to a sharable view, we propose to widely include sex among the co-variates when assessing the clinical response to ICI in cancer patients.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100146"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/32/c7/main.PMC9772791.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10438228","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":"Recent advancements of miRNAs in the treatment of bone diseases and their delivery potential","authors":"Ashish Ranjan Sharma,&nbsp;Yeon-Hee Lee,&nbsp;Sang-Soo Lee","doi":"10.1016/j.crphar.2022.100150","DOIUrl":"10.1016/j.crphar.2022.100150","url":null,"abstract":"<div><p>Advances in understanding miRNAs as endogenous posttranscriptional regulatory units have projected them as novel therapeutics for several untreatable diseases. miRNAs are endogenous non-coding small single-stranded RNA molecules (20–24 nucleotides) with specific gene regulatory functions like repression of mRNA translation by degrading mRNAs. Emerging evidence suggests the role of miRNAs in various stages of bone growth and development. Undoubtedly, due to their critical role in bone remodeling, miRNAs might be projected as a novel approach to treating bone-related diseases. However, the instability associated with miRNAs in their complex environment, such as degradation by nucleases, is a concern. Thus, recent attention is being paid to maintaining the miRNAs' safety and efficacy in the cells. Various efficient delivery systems and chemical modifications of miRNAs are being developed to make them a potential therapeutic option for bone diseases. Here, we have tried to recapitulate the recent advances in the role of miRNAs in bone disease, along with the potential delivery systems for their efficient delivery to the cells.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100150"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c0/79/main.PMC9860349.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9183230","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":"Kinetic conversion of BIOGF1K enriched in compound K from in vitro 3-D human tissue model","authors":"Woo-Hyun Kim ,&nbsp;Won-Jo Choi ,&nbsp;Jeong-Eun Kim ,&nbsp;Joonho Choi ,&nbsp;Yong-Deok Hong ,&nbsp;Jin Nam ,&nbsp;Won-Seok Park ,&nbsp;Soon-Mi Shim","doi":"10.1016/j.crphar.2023.100165","DOIUrl":"https://doi.org/10.1016/j.crphar.2023.100165","url":null,"abstract":"<div><p>The purposes of current study were to investigate the effect of ginsenosides from BIOGF1K enriched in compound K (CK) and compound Y (CY) on the skin barrier function, the deposition in <em>in vitro</em> 3-D human tissue model (EpiDermFT™ Full Thickness 400), and to identify and quantify kinetic bioconversion of the ginsenosides in artificial skin by utilizing the Fourier transform infrared spectroscopy (FT-IR) and liquid chromatography mass spectrometry (LC-MS), respectively. Epidermal barrier integrity evaluated using transepithelial electrical resistance (TEER) was significantly higher in the BIOGF1K treatment than the CY or CK individual treatment throughout incubation (p &lt; 0.05). Skin deposition (%) of CY and CK from BIOGF1K treatment was approximately 4 and 2 times higher than the CY and CK single component treatment, respectively. Total amount of CK found in human skin by deposition and bioconversion was approximately 1087.3, 528.82, and 867.76 μM after topical treatment of BIOGF1K, CK, and CY. Results from the current study reveal that topical treatment of BIOGF1K more effectively induced CK deposition as well as bioconversion of CY to CK than that of a single treatment of CY or CK, suggesting that BIOGF1K could be a useful cosmetic preparation for enhancing skin function.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"5 ","pages":"Article 100165"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49854422","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":"Retraction notice to “Myoinositol supplementation for the prevention of gestational diabetes in at-risk patients. Systemativ review and meta-analysis” [Curr. Res. Pharmacol. Drug Discov. 4C (2023) 100140]","authors":"Anthéa Bertrand ,&nbsp;Denis Gallot ,&nbsp;Bruno Pereira ,&nbsp;Amélie Delabaere","doi":"10.1016/j.crphar.2023.100154","DOIUrl":"10.1016/j.crphar.2023.100154","url":null,"abstract":"","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100154"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10369383/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9927214","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":"Regulation of biofilm formation by non-coding RNA in prokaryotes","authors":"Arindam Mitra ,&nbsp;Suman Mukhopadhyay","doi":"10.1016/j.crphar.2022.100151","DOIUrl":"10.1016/j.crphar.2022.100151","url":null,"abstract":"<div><p>Biofilm refers to microbes that associate with each other or to a surface via self-synthesized exopolysaccharides and other surface-related structures. The presence of biofilms consisting of pathogenic microbes in the food and clinical environment can pose a threat to human health as microbes in biofilms are highly robust and are difficult to remove. Understanding the process of biofilm formation is crucial for the development of novel strategies to control or harness biofilm. The complex network of proteins, small RNA, and diverse molecules regulate biofilm formation at different steps in biofilm development, including triggering the switch from planktonic to sessile cells, maturation of biofilms, and eventual dispersion of microbes from the biofilms. Small non-coding RNAs are relatively small RNAs that are not translated into proteins and play diverse roles in metabolism, physiology, pathogenesis, and biofilm formation. In this review, we primarily focused on non-coding regulatory RNA that regulates biofilm formation in clinically relevant pathogens or threatens human health. Even though many ncRNA have recently been identified in Archaea, much characterization work remains. The mechanisms and regulatory processes controlled by ncRNA in prokaryotes are covered in this review.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100151"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/1f/main.PMC9829692.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9091811","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":"Heme-heme oxygenase-2 reduces the atherosclerosis by preventing inflammation","authors":"Zhenzhen Wang ,&nbsp;Xiaoqiang Zhan ,&nbsp;Shuai Yang ,&nbsp;Yang Chen ,&nbsp;Yingchao Bi ,&nbsp;Xuemei Xian ,&nbsp;Quangang Chen ,&nbsp;Xufeng Han ,&nbsp;Zhangping Yang ,&nbsp;Renjin Chen","doi":"10.1016/j.crphar.2022.100141","DOIUrl":"10.1016/j.crphar.2022.100141","url":null,"abstract":"<div><h3>Objective</h3><p>Heme oxygenase (HO) has been shown to have important antioxidant and anti-inflammatory properties, resulting in a vascular antitherogenic effect. This study was undertaken to evaluate the role of HO-2 in atherosclerosis.</p></div><div><h3>Method and results</h3><p>The expression levels of HO-2 were evaluated in M1 and M2 bone marrow macrophage induced by LPS and IL4. The expression of HO-2 was significantly higher in M2 macrophage than in M1 macrophage. Western diet (WD) caused a significant increase in HO-2 expression in ApoE^−/− mice. The adeno-associated viral (AAV) vectors expressing HO-2 was constructed, and the mice were received saline (ApoE^−/−), AAV (ApoE^−/−), AAV–HO–2 (ApoE^−/−) on WD at 12 weeks and their plasma lipids, inflammatory cytokines, atherosclerosis were evaluated for 16 weeks. The results showed AAV–HO–2 was robust, with a significant decrease in the en face aortas, lipids levels, inflammatory cytokines and M1 macrophage content in AAV–HO–2 ApoE^−/− compared to control AAV-ApoE^−/−.</p></div><div><h3>Conclusion</h3><p>HO-2 expression in macrophages plays an important role of the antiatherogenic effect, decreasing the inflammatory component of atherosclerotic lesions. These results suggest that HO-2 may be a novel therapeutic target for cardiovascular diseases.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100141"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9804009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10477047","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}