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Network pharmacology, single gene survival analysis and molecular docking to study the mechanism of Sotetsuflavone in the treatment of pancreatic cancer 通过网络药理学、单基因生存分析和分子对接研究苏铁黄酮治疗胰腺癌的机制
Pharmacological Research - Reports Pub Date : 2024-03-01 DOI: 10.1016/j.prerep.2024.100010
Zi-Yong Chu , Xue-Jiao Zi
{"title":"Network pharmacology, single gene survival analysis and molecular docking to study the mechanism of Sotetsuflavone in the treatment of pancreatic cancer","authors":"Zi-Yong Chu ,&nbsp;Xue-Jiao Zi","doi":"10.1016/j.prerep.2024.100010","DOIUrl":"https://doi.org/10.1016/j.prerep.2024.100010","url":null,"abstract":"<div><p>Pancreatic cancer is a highly lethal cancer with limited treatment options. The number of pancreatic cancer patients is increasing rapidly worldwide. Many natural products have been shown to have anticancer activity in a range of studies. Sotetsuflavone is derived from <em>Cycas revoluta</em> Thunb. and exhibits anticancer activity. The present study incorporates network pharmacology, single gene survival analysis, gene expression analysis and molecular docking to reveal the mechanism of Sotetsuflavone in the treatment of pancreatic cancer. We have acquired 31 hub targets for the treatment of pancreatic cancer by Sotetsuflavone, namely ABCB1, AURKA, CDK1, and so on. Kaplan-Meier survival analyses demonstrated that ABCB1, AURKA, CDK1, HDAC6, MET, and MMP3 are promising hub targets that can be used as biomarkers for pancreatic cancer diagnosis and prognosis. These hub targets are highly expressed in pancreatic cancer tissues compared to normal tissues. The molecular docking results showed a strong binding capacity of Sotetsuflavone to these hub targets. In summary, it is proposed that Sotetsuflavone is a new anticancer drug, which can regulate pancreatic cancer-related signalling pathways by inhibiting the activities of ABCB1, AURKA, CDK1, HDAC6, MET, and MMP3, which are hub targets with up-regulated expression in pancreatic cancer tissues, in order to treat pancreatic cancer. However, it also requires a series of in vivo and in vitro studies to ensure its safety and efficacy.</p></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100010"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950200424000107/pdfft?md5=ec0f71c0bf1559690366d7ef6e9c5241&pid=1-s2.0-S2950200424000107-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141084724","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}
引用次数: 0
Refinement by gentle handling of mice affects oral-dosing pharmacokinetic end points and response to stress under drug administration and sampling 轻柔处理小鼠会影响口服药物的药代动力学终点以及给药和取样时的应激反应
Pharmacological Research - Reports Pub Date : 2024-03-01 DOI: 10.1016/j.prerep.2024.100020
Julia Swan , Elina Kallio , Johanna Magga , Janne Mannila , Elin Weber , Elin Törnqvist
{"title":"Refinement by gentle handling of mice affects oral-dosing pharmacokinetic end points and response to stress under drug administration and sampling","authors":"Julia Swan ,&nbsp;Elina Kallio ,&nbsp;Johanna Magga ,&nbsp;Janne Mannila ,&nbsp;Elin Weber ,&nbsp;Elin Törnqvist","doi":"10.1016/j.prerep.2024.100020","DOIUrl":"10.1016/j.prerep.2024.100020","url":null,"abstract":"<div><div>Lifting mice by their tails is a common handling method used for laboratory mice, yet it causes substantial stress. Alternative handling methods have a positive impact on animal welfare, but, there are limited studies on the effects of handling and habituation on scientific endpoints; hindering implementation and refinement in academia and industry. The purpose of this study was to investigate the effects of handling method (tail lifting vs. tube lifting) and habituation to handling (habituation) on drug uptake, exposure, and welfare parameters in a basic pharmacokinetic study. CD1 mice were either tail lifted without habituation, tube lifted without habituation, or tube lifted and habituated using a 10-day habituation protocol. A compound (mexiletine) was then administered by oral gavage and a 24 h pharmacokinetics study was performed in an industrial setting. The habituated group had a higher maximum serum concentration (C<sub>max</sub>), lower time to C<sub>max</sub> (T<sub>max</sub>) and a 30 % higher drug exposure than the tail and tube-lifted groups. These effects correlated well with reduced stress levels, as indicated by lower facial grimace scores in the tube-lifted groups than in the tail-lifted group. Handler interaction, after repeated blood sampling, was highest in the habituated group, and only the habituated group voluntarily climbed on the handler after blood sampling. Our results indicate that stress caused by tail lifting, oral gavage, and blood sampling results in reduced drug uptake and exposure. This stress can be reduced by gentle handling and habituation, which may result in more relevant pharmacokinetic data, increased scientific quality, and improved animal welfare.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S295020042400020X/pdfft?md5=049134362260496908e5ecb62d2013a4&pid=1-s2.0-S295020042400020X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142311186","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}
引用次数: 0
Antihyperlipidemic and antioxidant effects of biogenic copper oxide nanoparticles in diabetic rats 生物纳米氧化铜对糖尿病大鼠的降血脂和抗氧化作用
Pharmacological Research - Reports Pub Date : 2024-03-01 DOI: 10.1016/j.prerep.2024.100008
Manisha Nitin Chalse , Urmila Manoj Aswar , Aniroodha Vasant Pethkar
{"title":"Antihyperlipidemic and antioxidant effects of biogenic copper oxide nanoparticles in diabetic rats","authors":"Manisha Nitin Chalse ,&nbsp;Urmila Manoj Aswar ,&nbsp;Aniroodha Vasant Pethkar","doi":"10.1016/j.prerep.2024.100008","DOIUrl":"10.1016/j.prerep.2024.100008","url":null,"abstract":"<div><p>Diabetes mellitus is often associated with metabolic disorders like hyperglycemia, hyperlipidemia, oxidative stress and obesity. Health problems related to these disorders are on a rise globally. Although nanotechnology based approaches have been explored for diabetes treatment, specific information on alleviation of the associated health problem is scanty. Here we report the beneficial effects of copper oxide nanoparticles (CuOnpls) for the control of hyperlipidemia and oxidative stress caused due to diabetes. Wistar rats were fasted overnight and type 2 diabetes was induced by intraperitoneal (i.p.) injection of freshly prepared nicotinamide followed by streptozotocin. Induction of diabetes was confirmed by estimation of blood glucose levels of the animals. Estimation of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein-cholesterol (HDL-c) from the serum was carried out for ascertaining hyperlipidemia. Biogenic CuOnpls (spherical, 88.25 nm diameter) capped with bud extract of <em>Syzygium aromaticum</em> and α-tocopherol were administered in the animals per-oral route. Superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels were determined to evaluate antioxidant activity of CuOnpls. The nanoparticles were characterized for surface chemical groups by FTIR and HRLC-MS. The nanoparticles revealed novel surface groups responsible for site-specific delivery and beneficial effects. Diabetic rats showed enhanced serum BG, TC, TG and LDL levels and reduction in levels of HDL-c, SOD, CAT and GSH. Administration of CuOnpls caused significant reversal of the effects of diabetes on lipid profile and oxidative stress enzymes. The results pointed to the beneficial effects of CuOnpls for management of post-diabetes complications.</p></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100008"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950200424000089/pdfft?md5=807c3783fbb2dfdffaf9d693aa35d217&pid=1-s2.0-S2950200424000089-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141048841","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}
引用次数: 0
Potential mechanisms underlying Taohong Siwu Decoction ameliorates vascular calcification in chronic kidney disease based on network pharmacology and molecular docking 基于网络药理学和分子对接的桃红四物汤改善慢性肾病血管钙化的潜在机制
Pharmacological Research - Reports Pub Date : 2024-03-01 DOI: 10.1016/j.prerep.2024.100003
Yurou Chen, Dongping Chen, Zhaodong Liu, Lin Xu, Yuan Zhou, Shengchun Liao, Yufeng Xing, Yijing Zhou, Chaoyang Ye
{"title":"Potential mechanisms underlying Taohong Siwu Decoction ameliorates vascular calcification in chronic kidney disease based on network pharmacology and molecular docking","authors":"Yurou Chen, Dongping Chen, Zhaodong Liu, Lin Xu, Yuan Zhou, Shengchun Liao, Yufeng Xing, Yijing Zhou, Chaoyang Ye","doi":"10.1016/j.prerep.2024.100003","DOIUrl":"https://doi.org/10.1016/j.prerep.2024.100003","url":null,"abstract":"","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140277608","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
Hepatic and osteogenic effects of dulaglutide and semaglutide in an acute model of hepatotoxicity in mice 杜拉鲁肽和塞马鲁肽在小鼠急性肝毒性模型中的肝脏和成骨效应
Pharmacological Research - Reports Pub Date : 2024-03-01 DOI: 10.1016/j.prerep.2024.100019
Bruna Christ Faria , Kauê Marcel de Oliveira , Débora Rasec Radulski , Maria Carolina Stipp , Claudia Martins Galindo , Gabriela Saidel Pereira , Olair Carlos Beltrame , Rafaela Ceron , Fernando Augusto de Oliveira Ganzella , Rosangela Locatelli Dittrich , Edneia Amancio de Souza Ramos , Carolina Aguiar Moreira , Alexandra Acco
{"title":"Hepatic and osteogenic effects of dulaglutide and semaglutide in an acute model of hepatotoxicity in mice","authors":"Bruna Christ Faria ,&nbsp;Kauê Marcel de Oliveira ,&nbsp;Débora Rasec Radulski ,&nbsp;Maria Carolina Stipp ,&nbsp;Claudia Martins Galindo ,&nbsp;Gabriela Saidel Pereira ,&nbsp;Olair Carlos Beltrame ,&nbsp;Rafaela Ceron ,&nbsp;Fernando Augusto de Oliveira Ganzella ,&nbsp;Rosangela Locatelli Dittrich ,&nbsp;Edneia Amancio de Souza Ramos ,&nbsp;Carolina Aguiar Moreira ,&nbsp;Alexandra Acco","doi":"10.1016/j.prerep.2024.100019","DOIUrl":"10.1016/j.prerep.2024.100019","url":null,"abstract":"<div><p>Hepatic liver diseases are among the most common chronic diseases worldwide, with few available treatments. Bone diseases, such as osteoporosis, are associated with liver disease and other conditions and represent another challenge to treatment. The present study investigated effects of the antidiabetic glucagon-like peptide 1 (GLP-1) analogs semaglutide and dulaglutide on hepatic and osteogenic parameters in an acute CCl<sub>4</sub>-induced hepatotoxicity model. Two protocols were used in male Swiss mice: treatment and pretreatment with one or two administrations of semaglutide (0.021 mg/kg, i.p.), dulaglutide (0.014 mg/kg, i.p.), silymarin (100 mg/kg, p.o., positive control), or vehicle (10 ml/kg, i.p.). The mice were euthanized 48 h after the challenge with 1.5 % CCl<sub>4</sub> (0.25 ml, i.p.). The results indicated that dulaglutide exerted greater hepatoprotective effects than semaglutide, reducing liver necrosis, hepatic glutathione-<em>S</em>-transferase activity, and plasma alanine aminotransferase levels. Semaglutide improved the biliary excretion of cholesterol, benefiting more the biliary system than the hepatic parenchyma. Both drugs induced the gene expression of <em>Cyclin D1</em>, improving the proliferative phase of liver regeneration. With regard to bone remodeling, semaglutide increased the osteoblast surface (O.b/S) and its function by increasing the osteoid surface (OS/BS), suggesting an increase in bone formation. These data indicate that dulaglutide has potential as an alternative treatment for hepatotoxicity that is mainly induced by drugs, and semaglutide can improve bone development, demonstrating the potential of this GLP-1 analog for the prevention of bone fragility that is related to liver diseases.</p></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"2 ","pages":"Article 100019"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2950200424000193/pdfft?md5=96df7a5794cb382c384a47ed26396214&pid=1-s2.0-S2950200424000193-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241552","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}
引用次数: 0
Cashew nut-supplemented diet on testicular injury in rats exposed to sub-acute alcohol 腰果辅食对亚急性酒精暴露大鼠睾丸损伤的影响
Pharmacological Research - Reports Pub Date : 2023-12-01 DOI: 10.1016/j.prerep.2024.100001
Adewale Segun James , Beno Okechukwu Onunkwor , Victor O. Akinseye , Emmanuel Ifeanyichukwu Ugwor , Okere Uchenna Daniel , Eigele Emmanuel Eigbe , Uche David Ariguzo , Christiana Oluwakunmisola Igbin , Charity Chiamaka Amaogu , Somtochukwu Ezeonye , Gabriella Akagu , Regina Ngozi Ugbaja
{"title":"Cashew nut-supplemented diet on testicular injury in rats exposed to sub-acute alcohol","authors":"Adewale Segun James ,&nbsp;Beno Okechukwu Onunkwor ,&nbsp;Victor O. Akinseye ,&nbsp;Emmanuel Ifeanyichukwu Ugwor ,&nbsp;Okere Uchenna Daniel ,&nbsp;Eigele Emmanuel Eigbe ,&nbsp;Uche David Ariguzo ,&nbsp;Christiana Oluwakunmisola Igbin ,&nbsp;Charity Chiamaka Amaogu ,&nbsp;Somtochukwu Ezeonye ,&nbsp;Gabriella Akagu ,&nbsp;Regina Ngozi Ugbaja","doi":"10.1016/j.prerep.2024.100001","DOIUrl":"10.1016/j.prerep.2024.100001","url":null,"abstract":"<div><div><span><span><span>Binge drinking is a major global health issue, causing over 3.3 million mortalities yearly and might induce male infertility<span>. Cashew nut contains many constituents with health benefits. This study investigated the effect of a cashew nut-supplemented diet (CND) against ethanol-invoked </span></span>testicular injury in male </span>Wistar rats<span>. Thirty male rats were randomly assigned to five groups (n = 6). The groups are as follows: Group 1: (fed with standard diet only), Group 2: ethanol (received 30% v/v; 4 mL /kg body weight, orally) and regular diet, Group 3: (received ethanol and fed with 5% CND), Group 4: (received ethanol and provided with CND 10%), and Group 5: (10% CND) only. After fourteen days of ethanol administration and diet regimen, animals were fasted overnight and euthanized. Testis and blood were collected for biochemical and histological analyses. Testis was investigated for </span></span>oxidative stress<span><span><span> indices, glycogen level, antioxidant biomarkers, </span>alcohol metabolism </span>enzymes<span><span>, and histopathology. Serum cholesterol<span>, testosterone, and follicle-stimulating hormone (FSH) levels were also determined. Ethanol caused significant inhibition/reduction of antioxidant enzymes, cholesterol, testosterone, and FSH levels. Furthermore, there were increased levels of oxidative stress markers and histological impairment of the testis. However, the treatment with CND dose-dependently decreased the oxidative stress and aberrant histological features while augmenting the lowered antioxidant systems, normalizing the alcohol metabolizing enzymes and the hormones levels. This study shows that CND might protect against testicular injury by attenuating oxidative stress and boosting antioxidant and </span></span>steroidogenesis in male rats.</span></span></div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"1 ","pages":"Article 100001"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139687629","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
Next -generation probiotics as potential therapeutic supplement for gastrointestinal infections 新一代益生菌作为潜在的胃肠道感染治疗补充剂
Pharmacological Research - Reports Pub Date : 2023-12-01 DOI: 10.1016/j.prerep.2024.100002
Nidhi Gupta , Kajal Kachhawaha , Deepak Kumar Behera , Vijay Kumar Verma
{"title":"Next -generation probiotics as potential therapeutic supplement for gastrointestinal infections","authors":"Nidhi Gupta ,&nbsp;Kajal Kachhawaha ,&nbsp;Deepak Kumar Behera ,&nbsp;Vijay Kumar Verma","doi":"10.1016/j.prerep.2024.100002","DOIUrl":"10.1016/j.prerep.2024.100002","url":null,"abstract":"<div><h3>Introduction</h3><div>The experimental evolution of gut microbiota<span><span> and human wellness<span><span> has witnessed increased recognition in the past decade. In the human gastrointestinal tract<span>, about 100 million bacteria, viruses, and fungi exist that play a symbiotic relationship with human immunity. Simultaneously, the rising concerns and consequences of antimicrobial and </span></span>antibiotic resistance are shrinking new antibiotic discoveries and demanding alternative approaches for eradicating infectious diseases. The next-generation </span></span>probiotics (NGPs) could be a potential answer to this global challenge.</span></div></div><div><h3>Methods</h3><div><span><span>Recognizing the limitations of traditional probiotics in terms of diversity and scope, the study explored the broader applications of NGPs and their potential to address various gut health issues, </span>dysbiosis<span><span>, and gastrointestinal disorders. Here, we have strengthened the connections between the </span>gut microbiome and overall health, specifically focusing on </span></span><span><em>Helicobacter pylori</em></span> (<em>H. pylori</em><span><span>) infection and inflammatory bowel disease<span> (IBD). Using a narrative approach, the strengths and weaknesses of currently available therapies and </span></span>fecal microbiota transplantation (FMT) have been described.</span></div></div><div><h3>Results and discussion</h3><div>The outcome of this study reveals the promising potential of NGPs in offering targeted interventions that overcome the limitations of existing approaches. We highlight the perspective of NGPs by addressing the benefits, with their anti-inflammatory properties and ability to enhance gut health. However, we also acknowledge crucial gaps in current knowledge in the field of NGPs’ treatment, particularly the limited clinical evidence for their efficacy etc.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"1 ","pages":"Article 100002"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140464066","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
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