Pharmacological Reports最新文献

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Melatonin and oral diseases: possible therapeutic roles based on cellular mechanisms 褪黑激素与口腔疾病:基于细胞机制的可能治疗作用
IF 4.4 3区 医学
Pharmacological Reports Pub Date : 2024-04-12 DOI: 10.1007/s43440-024-00593-6
Azam Hosseinzadeh, Ali Jamshidi Naeini, Mohammad Sheibani, Babak Gholamine, Russel J. Reiter, Saeed Mehrzadi
{"title":"Melatonin and oral diseases: possible therapeutic roles based on cellular mechanisms","authors":"Azam Hosseinzadeh, Ali Jamshidi Naeini, Mohammad Sheibani, Babak Gholamine, Russel J. Reiter, Saeed Mehrzadi","doi":"10.1007/s43440-024-00593-6","DOIUrl":"https://doi.org/10.1007/s43440-024-00593-6","url":null,"abstract":"<p>Oral diseases, including periodontal disorders, oral cancer, periodontitis, and mucositis are the major challenges for both patients and healthcare providers. These conditions often involve inflammation, oxidative stress, and impaired cellular processes, leading to symptoms ranging from discomfort to severe debilitation. Conventional treatments for such oral diseases exhibit constraints, prompting the investigation of innovative therapeutic approaches. Considering the anti-inflammatory, anti-oxidant, and anti-cancer effects of melatonin, this study was carried out to investigate the potential protective effects of melatonin in mitigating the severity of oral diseases. Studies indicate that melatonin influences the differentiation of periodontal stem cells, inhibits oral cancer progression, reduces inflammation associated with periodontitis, and alleviates the severity of oral mucositis. Melatonin has demonstrated potential efficacy in both preclinical and clinical investigations; however, findings are frequently heterogeneous and contingent upon contextual factors. This review provides a comprehensiveoverview of current state of knowledge in this domain, elucidating the multifaceted role that melatonin may assume in combatingoral diseases. Further research should be directed toward determining the most effective dosing, timing, and administration methods for melatonin-based therapies for oral diseases.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":"81 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mediator kinase module proteins, genetic alterations and expression of super-enhancer regulated genes in colorectal cancer 大肠癌中的介导激酶模块蛋白、基因改变和超级增强子调控基因的表达
IF 4.4 3区 医学
Pharmacological Reports Pub Date : 2024-04-11 DOI: 10.1007/s43440-024-00589-2
Ioannis A. Voutsadakis
{"title":"Mediator kinase module proteins, genetic alterations and expression of super-enhancer regulated genes in colorectal cancer","authors":"Ioannis A. Voutsadakis","doi":"10.1007/s43440-024-00589-2","DOIUrl":"https://doi.org/10.1007/s43440-024-00589-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Genetic alterations are well characterized as contributors to the pathogenesis of cancers. Epigenetic abnormalities can lead to perturbations of the expression of genes in cancer cells without structural defects. Deregulation of proteins of the transcription machinery may result in perturbations of target genes. Mediator, a multiprotein component of the transcription machinery facilitates the function of RNA polymerase II, which transcribes most human genes. A part of the mediator with kinase activity, called the Mediator kinase module shows genetic alterations in a sub-set of colorectal cancers.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Data from publicly available genomic series of colorectal cancer patients were examined to determine alterations of Mediator kinase module component genes, including <i>MED12</i>, <i>MED12L</i>, <i>MED13</i>, <i>MED13L</i>, <i>CDK8</i>, <i>CDK19,</i> and <i>CCNC</i>. The prevalence of alterations in genomically defined colorectal cancer sub-sets was also interrogated. The effect of Mediator kinase module member gene expression on colorectal cancer relapse-free survival was investigated.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Mutations in genes of the Mediator kinase module were present in a small percentage of colorectal cancers, ranging between 2 to 10% for <i>MED12</i> and <i>MED13</i> and alternative units <i>MED12L</i> and <i>MED13L</i> and below 2% for kinases CDK8 and CDK19 and cyclin C. Amplifications of the <i>CDK8</i> gene were observed in 3% to 5% of colorectal cancers. The highest prevalence of mutations was observed in MSI cancers and the equivalent CMS1 group, with other genomic groups showing much lower frequency. An association of higher expression of MED12 with inferior relapse-free survival was observed. In contrast, higher expression of cyclin C was associated with improved survival. Colorectal cancer cell lines with <i>CDK8</i> amplifications displayed sensitivity to several small molecule inhibitors of the KRAS/PI3K pathway but not to BET inhibitors.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The Mediator kinase module is deregulated in a sub-set of colorectal cancers with differences observed in genomically defined groups. These variations may result in differences in sensitivity to targeted therapies and may have to be taken into consideration as such therapies are developed.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":"29 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Redox homeostasis in human renal cells that had been treated with amphotericin B in combination with selected 1,3,4-thiadiazole derivatives 经两性霉素 B 与特定 1,3,4-噻二唑衍生物联合处理的人类肾脏细胞的氧化还原稳态
IF 4.4 3区 医学
Pharmacological Reports Pub Date : 2024-04-08 DOI: 10.1007/s43440-024-00592-7
Magdalena Kimsa-Dudek, Celina Kruszniewska-Rajs, Jolanta Adamska, Barbara Strzałka-Mrozik, Arkadiusz Matwijczuk, Dariusz Karcz, Mariusz Gagoś, Joanna Magdalena Gola
{"title":"Redox homeostasis in human renal cells that had been treated with amphotericin B in combination with selected 1,3,4-thiadiazole derivatives","authors":"Magdalena Kimsa-Dudek, Celina Kruszniewska-Rajs, Jolanta Adamska, Barbara Strzałka-Mrozik, Arkadiusz Matwijczuk, Dariusz Karcz, Mariusz Gagoś, Joanna Magdalena Gola","doi":"10.1007/s43440-024-00592-7","DOIUrl":"https://doi.org/10.1007/s43440-024-00592-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The use of amphotericin B (AmB) in the therapy of systemic mycosis is associated with strong side effects, including nephrotoxicity, and hepatotoxicity. Therefore, agents that can reduce the toxic effects of AmB while acting synergistically as antifungal agents are currently being sought. 1,3,4-thiadiazole derivatives are promising compounds that have an antifungal activity and act synergically with AmB. Such combinations might allow the dose of AmB, which is essential for preventing patients from having serious side effects, to be decreased. This might result from the antioxidant properties of 1,3,4-thiadiazoles. Thus, the aim of the study was to investigate redox homeostasis in human renal proximal tubule epithelial cells (RPTEC) after they had been treated with AmB in combination with 1,3,4-thiadiazole derivatives.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Cellular redox homeostasis was assessed by investigating the total antioxidant capacity (TAC) of cells, the malondialdehyde (MDA) concentration, and the activity of antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT). TAC was measured using an ABTS method. The MDA concentration, and the activity of SOD, GPX, and CAT were determined spectrophotometrically using commercially available assays. Additionally, the antioxidant defense system-related gene expression profile was determined using oligonucleotide microarrays (HG-U133A 2.0). Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to confirm the microarray results.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Amphotericin B and selected 1,3,4-thiadiazole derivatives had a significant effect on the total antioxidant capacity of the RPTEC cells, and the activity of the antioxidant enzymes. We also revealed that the effect of thiadiazoles on the SOD and CAT activities is dependent on the treatment of RPTEC cells with AmB. At the transcriptional level, the expression of several genes was affected by the studied compounds and their combinations.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The results confirmed that thiadiazoles can stimulate the RPTEC cells to defend against the oxidative stress that is generated by AmB. In addition, together with the previously demonstrated synergistic antifungal activity, and low nephrotoxicity, these compounds have the potential to be used in new therapeutic strategies in the treatment of fungal infections.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":"80 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: Protective effect of hygrolansamycin C against corticosterone-induced toxicity and oxidative stress-mediated via autophagy and the MAPK signaling pathway 更正:土霉素 C 通过自噬和 MAPK 信号通路对皮质酮诱导的毒性和氧化应激具有保护作用
IF 4.4 3区 医学
Pharmacological Reports Pub Date : 2024-04-04 DOI: 10.1007/s43440-024-00591-8
Jongtae Roh, Jun-Pil Jang, Taehoon Oh, Jihong Kim, Byeongsan Lee, Young-Soo Hong, Jae-Hyuk Jang, Sung-Kyun Ko
{"title":"Correction: Protective effect of hygrolansamycin C against corticosterone-induced toxicity and oxidative stress-mediated via autophagy and the MAPK signaling pathway","authors":"Jongtae Roh, Jun-Pil Jang, Taehoon Oh, Jihong Kim, Byeongsan Lee, Young-Soo Hong, Jae-Hyuk Jang, Sung-Kyun Ko","doi":"10.1007/s43440-024-00591-8","DOIUrl":"https://doi.org/10.1007/s43440-024-00591-8","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":"34 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neuroprotective effect of apelin-13 and other apelin forms—a review 凋亡磷脂素-13和其他凋亡磷脂素形式的神经保护作用--综述
IF 4.4 3区 医学
Pharmacological Reports Pub Date : 2024-04-03 DOI: 10.1007/s43440-024-00587-4
{"title":"Neuroprotective effect of apelin-13 and other apelin forms—a review","authors":"","doi":"10.1007/s43440-024-00587-4","DOIUrl":"https://doi.org/10.1007/s43440-024-00587-4","url":null,"abstract":"<h3>Abstract</h3> <p>Neurodegenerative diseases, which occur when neurons begin to deteriorate, affect millions of people worldwide. These age-related disorders are becoming more common partly because the elderly population has increased in recent years. While no treatments are accessible, every year an increasing number of therapeutic and supportive options become available. Various substances that may have neuroprotective effects are currently being researched. One of them is apelin. This review aims to illustrate the results of research on the neuroprotective effect of apelin amino acid oligopeptide which binds to the apelin receptor and exhibits neuroprotective effects in the central nervous system. The collected data indicate that apelin can protect the central nervous system against injury by several mechanisms. More studies are needed to thoroughly investigate the potential neuroprotective effects of this peptide in neurodegenerative diseases and various other types of brain damage.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":"14 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association between gene polymorphisms and initial warfarin therapy in patients after heart valve surgery. 心脏瓣膜手术后患者的基因多态性与初始华法林治疗之间的关系。
IF 4.4 3区 医学
Pharmacological Reports Pub Date : 2024-04-01 Epub Date: 2024-03-08 DOI: 10.1007/s43440-024-00575-8
Zhaohui Liu, Fengming Luo, Juan Zhao, Weinan Chen, Wei Gao, Zhou Zhou
{"title":"Association between gene polymorphisms and initial warfarin therapy in patients after heart valve surgery.","authors":"Zhaohui Liu, Fengming Luo, Juan Zhao, Weinan Chen, Wei Gao, Zhou Zhou","doi":"10.1007/s43440-024-00575-8","DOIUrl":"10.1007/s43440-024-00575-8","url":null,"abstract":"<p><strong>Background: </strong>Warfarin is widely used for the prevention and treatment of thrombotic events. This study aimed to examine the influence of gene polymorphisms on the early stage of warfarin therapy in patients following heart valve surgery.</p><p><strong>Methods: </strong>Nine single nucleotide polymorphisms were genotyped using microarray chips, categorizing patients into three groups: normal responders (Group I), sensitive responders (Group II), and highly sensitive responders (Group III). The primary clinical outcomes examined were time in therapeutic range (TTR) and international normalized ratio (INR) variability. To investigate potential influencing factors, a generalized linear regression model was employed.</p><p><strong>Results: </strong>Among 734 patients, the prevalence of CYP2C9*3-1075A > C, CYP2C19*3-636G > A, and CYP2C19*17-806C > T variants were 11.2%, 9.9%, and 1.9% of patients, respectively. VKORC1-1639G > A or the linked -1173C > T variant was observed in 99.0% of the patients. Generalized linear model analysis revealed an impact of sensitivity grouping on INR variability. Compared to Group I, Group II showed higher TTR values (p = 0.023), while INR variability was poorer in Group II (p < 0.001) and Group III (p < 0.001). Individual gene analysis identified significant associations between CYP2C9*3-1075A > C (p < 0.001), VKORC1-1639G > A or the linked -1173 C > T (p = 0.009) and GGCX-3261G > A (p = 0.019) with INR variability.</p><p><strong>Conclusion: </strong>The genotypes of CYP2C9, VKORC1, and GGCX were found to have a significant impact on INR variability during the initial phase of warfarin therapy. However, no significant association was observed between TTR and gene polymorphisms. These findings suggest that focusing on INR variability is crucial in clinical practice, and preoperative detection of gene polymorphisms should be considered to assist in the initiation of warfarin therapy.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"390-399"},"PeriodicalIF":4.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Are there sex differences in oxytocin and vasopressin V1a receptors ligand binding affinities? 催产素和血管加压素 V1a 受体配体结合亲和力是否存在性别差异?
IF 4.4 3区 医学
Pharmacological Reports Pub Date : 2024-04-01 Epub Date: 2024-03-13 DOI: 10.1007/s43440-024-00577-6
Jack H Taylor, H Elliott Albers
{"title":"Are there sex differences in oxytocin and vasopressin V1a receptors ligand binding affinities?","authors":"Jack H Taylor, H Elliott Albers","doi":"10.1007/s43440-024-00577-6","DOIUrl":"10.1007/s43440-024-00577-6","url":null,"abstract":"<p><strong>Background: </strong>There is substantial evidence for sex differences in the functioning of one of the most common receptor systems; G protein-coupled receptors (GPCRs). There are many points along the GPCR-mediated molecular signaling pathway at which males and females may differ, one of the first of which, chronologically, is in the stability of the interaction between the ligand and the receptor, or its binding affinity. Here we investigate the binding affinities of oxytocin (OT) and vasopressin (AVP) at the oxytocin receptor (OTR) and the vasopressin V1a receptor (V1aR), both of which are present in numerous in brain regions associated with social behavior.</p><p><strong>Method: </strong>In order to investigate sex- and estrous cycle-dependent differences in ligand-receptor binding affinity, male (n = 6) Syrian hamsters (Mesocricetus auratus), females on the day of estrus (E females, n = 6), and females on the second day of diestrus (D2 females n = 6) were chosen for study. Brains from hamsters were mounted on slides and competition and saturation binding assays were conducted.</p><p><strong>Results: </strong>We report a remarkable similarity in the binding affinities of OT and AVP in males and females. Small differences were detected, however, in receptor and ligand specificity in females depending on whether they were in the estrous or diestrous stage of their ovulatory cycle.</p><p><strong>Conclusion: </strong>These data suggest that sex differences in binding affinity are not a likely source of the many sex differences that have been observed in the effects of OT and AVP in hamsters and other species.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"416-423"},"PeriodicalIF":4.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effect of valproate on the amino acids, monoamines, and kynurenic acid concentrations in brain structures involved in epileptogenesis in the pentylenetetrazol-kindled rats. 丙戊酸钠对戊四唑诱发的大鼠大脑结构中涉及癫痫发生的氨基酸、单胺和犬尿氨酸浓度的影响。
IF 4.4 3区 医学
Pharmacological Reports Pub Date : 2024-04-01 Epub Date: 2024-03-22 DOI: 10.1007/s43440-024-00573-w
Aleksandra Wisłowska-Stanek, Danuta Turzyńska, Alicja Sobolewska, Karolina Kołosowska, Janusz Szyndler, Anna Skórzewska, Piotr Maciejak
{"title":"The effect of valproate on the amino acids, monoamines, and kynurenic acid concentrations in brain structures involved in epileptogenesis in the pentylenetetrazol-kindled rats.","authors":"Aleksandra Wisłowska-Stanek, Danuta Turzyńska, Alicja Sobolewska, Karolina Kołosowska, Janusz Szyndler, Anna Skórzewska, Piotr Maciejak","doi":"10.1007/s43440-024-00573-w","DOIUrl":"10.1007/s43440-024-00573-w","url":null,"abstract":"<p><strong>Background: </strong>The study aimed to assess the influence of a single valproate (VPA) administration on inhibitory and excitatory neurotransmitter concentrations in the brain structures involved in epileptogenesis in pentylenetetrazol (PTZ)-kindled rats.</p><p><strong>Methods: </strong>Adult, male Wistar rats were kindled by repeated intraperitoneal (ip) injections of PTZ at a subconvulsive dose (30 mg/kg, three times a week). Due to the different times required to kindle the rats (18-22 injections of PTZ), a booster dose of PTZ was administrated 7 days after the last rats were kindled. Then rats were divided into two groups: acute administration of VPA (400 mg/kg) or saline given ip. The concentration of amino acids, kynurenic acid (KYNA), monoamines, and their metabolites in the prefrontal cortex, hippocampus, amygdala, and striatum was assessed by high-pressure liquid chromatography (HPLC).</p><p><strong>Results: </strong>It was found that a single administration of VPA increased the gamma-aminobutyric acid (GABA), tryptophan (TRP), 5-hydroxyindoleacetic acid (5-HIAA), and KYNA concentrations and decreased aspartate (ASP) levels in PTZ-kindled rats in the prefrontal cortex, hippocampus, amygdala and striatum.</p><p><strong>Conclusions: </strong>Our results indicate that a single administration of VPA in the PTZ-kindled rats restored proper balance between excitatory (decreasing the level of ASP) and inhibitory neurotransmission (increased concentration GABA, KYNA) and affecting serotoninergic neurotransmission in the prefrontal cortex, hippocampus, amygdala, and striatum.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"348-367"},"PeriodicalIF":4.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats. 大麻二酚可防止大鼠因肺动脉高压导致右心室肥大而继发充血性肝病。
IF 4.4 3区 医学
Pharmacological Reports Pub Date : 2024-04-01 Epub Date: 2024-03-22 DOI: 10.1007/s43440-024-00579-4
Anna Krzyżewska, Marta Baranowska-Kuczko, Anna Galicka, Irena Kasacka, Krzysztof Mińczuk, Hanna Kozłowska
{"title":"Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats.","authors":"Anna Krzyżewska, Marta Baranowska-Kuczko, Anna Galicka, Irena Kasacka, Krzysztof Mińczuk, Hanna Kozłowska","doi":"10.1007/s43440-024-00579-4","DOIUrl":"10.1007/s43440-024-00579-4","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) can cause right ventricular (RV) failure and subsequent cardiohepatic syndrome referred to as congestive hepatopathy (CH). Passive blood stasis in the liver can affect inflammation, fibrosis, and ultimately cirrhosis. Cannabidiol (CBD) has many beneficial properties including anti-inflammatory and reduces RV systolic pressure and RV hypertrophy in monocrotaline (MCT)-induced PH in rats. Thus, it suggests that CBD may have the potential to limit CH development secondary to RV failure. The present study aimed to determine whether chronic administration of CBD can inhibit the CH secondary to RV hypertrophy associated with MCT-induced PH.</p><p><strong>Methods: </strong>The experiments involved rats with and without MCT-induced PH. CBD (10 mg/kg) or its vehicle was administered once daily for 3 weeks after MCT injection (60 mg/kg).</p><p><strong>Results: </strong>Monocrotaline administration increased the liver/body weight ratio. In histology examinations, we observed necrosis and vacuolar degeneration of hepatocytes as well as sinusoidal congestion. In biochemical studies, we observed increased levels of nuclear factor-κappa B (NF-κB), tumour necrosis factor-alpha (TNA-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CBD administration to PH rats reduced the liver/body weight ratio, improved the architecture of the liver, and inhibited the formation of necrosis. Cannabidiol also decreased the level of NF-κB, TNF-α, IL-1β and IL-6.</p><p><strong>Conclusions: </strong>The studies show that CBD can protect the liver from CH probably through attenuating PH, protective effects on the RV, and possibly direct anti-inflammatory effects on liver tissue through regulation of the NF-κB pathway.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"424-434"},"PeriodicalIF":4.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transcriptome analysis of an AKT inhibitor-resistant endometrial cancer cell line. AKT 抑制剂耐药子宫内膜癌细胞系的转录组分析。
IF 4.4 3区 医学
Pharmacological Reports Pub Date : 2024-04-01 Epub Date: 2024-03-13 DOI: 10.1007/s43440-024-00581-w
Takafumi Onishi, Tsuyoshi Takashima, Kazuki Shibahara, Shoji Takagi, Shinichi Tanaka, Michihiro Mori, Hirokazu Odashima, Yukihiko Osawa, Manabu Hattori
{"title":"Transcriptome analysis of an AKT inhibitor-resistant endometrial cancer cell line.","authors":"Takafumi Onishi, Tsuyoshi Takashima, Kazuki Shibahara, Shoji Takagi, Shinichi Tanaka, Michihiro Mori, Hirokazu Odashima, Yukihiko Osawa, Manabu Hattori","doi":"10.1007/s43440-024-00581-w","DOIUrl":"10.1007/s43440-024-00581-w","url":null,"abstract":"<p><strong>Background: </strong>Drug resistance in endometrial cancer (EC) is a serious problem and a barrier to improving prognosis. The PI3K/AKT/mTOR pathway is highly activated in EC and can serve as a potential therapeutic target. Inhibitors against AKT have been developed, but resistance to these inhibitors is a concern. This study aimed to establish AKT inhibitor resistant cell lines and identify differentially expressed genes (DEGs) between parental and AKT inhibitor resistant cell lines to understand the mechanism of drug resistance to AKT inhibitors in EC.</p><p><strong>Methods: </strong>The sensitivity of eight EC cell lines to AKT inhibitor was analyzed. One of them was used to establish a drug-resistant cell line. DEGs were examined using RNA sequencing (RNA-seq). Furthermore, DEGs were comprehensively analyzed to identify hub genes. Hub genes were evaluated using quantitative real-time polymerase chain reaction.</p><p><strong>Results: </strong>RNA-seq identified 617 DEGs. Hub genes were selected using bioinformatics analysis. The top 10 hub genes were TNF, CDH1, CCND1, COL1A1, CDH2, ICAM1, CAV1, THBS1, NCAM1, and CDKN2A. Relative mRNA expression was significantly upregulated for TNF, CDH1, CCND1, THBS1, p16<sup>INK4a</sup>, and p14<sup>ARF</sup> and significantly downregulated for CDH2, ICAM1, and NCAM1 in borussertib-resistant EC cell line.</p><p><strong>Conclusions: </strong>Drug resistance to AKT inhibitors may depend on genes related to cell adhesion-mediated resistance and transforming growth factor β signaling.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"379-389"},"PeriodicalIF":4.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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