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Perspectives About Ascorbic Acid to Treat Inflammatory Bowel Diseases. 关于抗坏血酸治疗炎症性肠病的观点。
IF 2.2 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-01 Epub Date: 2024-03-11 DOI: 10.1055/a-2263-1388
Ian Richard Lucena Andriolo, Larissa Venzon, Luisa Mota da Silva

It is known that reactive oxygen species cause abnormal immune responses in the gut during inflammatory bowel diseases (IBD). Therefore, oxidative stress has been theorized as an agent of IBD development and antioxidant compounds such as vitamin C (L-ascorbic acid) have been studied as a new tool to treat IBD. Therefore, the potential of vitamin C to treat IBD was reviewed here as a critical discussion about this field and guide future research. Indeed, some preclinical studies have shown the beneficial effects of vitamin C in models of ulcerative colitis in mice and clinical and experimental findings have shown that deficiency in this vitamin is associated with the development of IBD and its worsening. The main mechanisms that may be involved in the activity of ascorbic acid in IBD include its well-established role as an antioxidant, but also others diversified actions. However, some experimental studies employed high doses of vitamin C and most of them did not perform dose-response curves and neither determined the minimum effective dose nor the ED50. Allometric extrapolations were also not made. Also, clinical studies on the subject are still in their infancy. Therefore, it is suggested that the research agenda in this matter covers experimental studies that assess the effective, safe, and translational doses, as well as the appropriate administration route and its action mechanism. After that, robust clinical trials to increase knowledge about the role of ascorbic acid deficiency in IBD patients and the effects of their supplementation in these patients can be encouraged.

众所周知,活性氧会在炎症性肠病(IBD)期间引起肠道异常免疫反应。因此,氧化应激被认为是 IBD 发病的诱因之一,而维生素 C(左旋抗坏血酸)等抗氧化化合物已被研究为治疗 IBD 的新工具。因此,本文对维生素 C 治疗 IBD 的潜力进行了综述,以对这一领域进行批判性讨论并指导未来的研究。事实上,一些临床前研究显示,维生素 C 对小鼠溃疡性结肠炎模型有益处,临床和实验研究结果表明,缺乏维生素 C 与 IBD 的发生和恶化有关。抗坏血酸在 IBD 中的活性可能涉及的主要机制包括其作为抗氧化剂的公认作用,以及其他多样化的作用。然而,一些实验研究采用了高剂量的维生素 C,其中大多数研究没有绘制剂量反应曲线,也没有确定最小有效剂量或 ED50。也没有进行异速推断。此外,有关该主题的临床研究仍处于起步阶段。因此,建议在这一问题上的研究议程包括评估有效、安全和转化剂量的实验研究,以及适当的给药途径和作用机制。在此之后,可以鼓励开展强有力的临床试验,以增加对抗坏血酸缺乏在 IBD 患者中的作用以及补充抗坏血酸对这些患者的影响的了解。
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引用次数: 0
Preclinical Targeting of the PGRMC1-CK2 Axis with Silmitasertib: A Potential Strategy for Lung Adenocarcinoma Therapy. 临床前使用 Silmitasertib 靶向 PGRMC1-CK2 轴:肺腺癌治疗的潜在策略。
IF 2.2 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-01 Epub Date: 2024-03-20 DOI: 10.1055/a-2273-2389
S Solaipriya, M Anbalagan, V Sivaramakrishnan

Progesterone receptor membrane component 1 (PGRMC1) is a pleiotropic protein over-expressed in lung adenocarcinoma (LUAD). The precise molecular mechanisms underlying the signature motif of Casein kinase (CK2) presence in PGRMC1 and their role in LUAD remain unclear. X-ray crystallographic structure for CK2 and PGRMC1 from the PubChem database was obtained and subjected to protein-protein interaction (PPI) analysis to identify their interactions. In addition, the CK2 inhibitor - Silmitasertib was also utilised to understand the interaction between PGRMC1-CK2. The PPI complex (PGRMC1-CK2) and the PPI-ligand interaction analysis and their Molecular Dynamics (MD) studies revealed the stability of their interactions and critical amino acid contacts within the 5Ǻ vicinity of the CK2 signature motif "T/S-x-x-E/D". Moreover, in-vitro colony formation assay, migration assay, and gene expression analysis using quantitative Real-time PCR revealed that Silmitasertib (IC50-2.5 μM) was highly influential in suppressing the PGRMC1-CK2 expression axis. In conclusion, our study infers that PGRMC1-CK-2 axis inhibition could be a potential therapeutic option to limit the promotion and progression of lung cancer.

孕酮受体膜组件 1(PGRMC1)是一种在肺腺癌(LUAD)中过度表达的多向蛋白。酪蛋白激酶(CK2)在 PGRMC1 中的标志性基团及其在 LUAD 中作用的确切分子机制仍不清楚。我们从 PubChem 数据库中获得了 CK2 和 PGRMC1 的 X 射线晶体结构,并对其进行了蛋白质-蛋白质相互作用(PPI)分析,以确定它们之间的相互作用。此外,还利用 CK2 抑制剂 Silmitasertib 来了解 PGRMC1-CK2 之间的相互作用。PPI 复合物(PGRMC1-CK2)和 PPI 配体相互作用分析及其分子动力学(MD)研究揭示了它们之间相互作用的稳定性以及 CK2 标志性图案 "T/S-x-x-E/D "5Ǻ附近的关键氨基酸接触。此外,体外集落形成试验、迁移试验和基因表达定量实时荧光定量 PCR 分析表明,Silmitasertib(IC50-2.5 μM)对抑制 PGRMC1-CK2 表达轴的影响很大。总之,我们的研究推断,PGRMC1-CK-2轴抑制可能是一种潜在的治疗方法,可限制肺癌的发生和发展。
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引用次数: 0
Characterization of Diclofenac-induced Renal Damage in Normotensive and Hypertensive Rats: A Comparative Analysis. 双氯芬酸诱导的正常血压大鼠和高血压大鼠肾损伤的特征:比较分析
IF 2.2 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-01 Epub Date: 2024-03-19 DOI: 10.1055/a-2277-8458
Thaise Boeing, Alana Bittencourt F Lima, Maria Eduarda Busana, Luísa Nathália Bolda Mariano, Luisa Mota da Silva, Rita de Cássia Vilhena da Silva, Priscila de Souza

Background: Diclofenac is the non-steroidal anti-inflammatory drug (NSAID) mostly prescribed worldwide, but it is highly associated with hypertension and acute kidney injury. Despite that, little information is available about the renal effects of diclofenac in hypertensive individuals, which led us to carry out this comparative study between the renal effects of this NSAID in normotensive (NTR) and spontaneously hypertensive rats (SHR).

Methods: Male Wistar NTR and SHR were orally treated with vehicle (V: 10 mL/kg) or diclofenac sodium (D: 100 mg/kg) once a day for 3 days. Urine volume, electrolytes excretion (Na+, K+, Cl-, and Ca2+), urea, creatinine, pH, and osmolarity were evaluated. Furthermore, blood samples and renal tissue were collected to perform biochemical and histological analysis.

Results: Diclofenac increased the renal corpuscle and bowman's space in the SHR, while no microscopic changes were observed in the renal tissue of NTR. Regarding the urinary parameters, diclofenac reduced urine volume, pH, osmolarity, and all electrolytes excretion, followed by decreased urea and creatinine levels in both lineages. Moreover, it also induced hyponatremia, hypokalemia, and hypocalcemia in SHR, while reduced glutathione-S-transferase activity, lipid hydroperoxides, and nitrite levels in renal tissue.

Conclusions: The data presented herein demonstrated that diclofenac induces renal damage and impaired renal function in both NTR and SHR, but those effects are exacerbated in SHR, as seen by the histological changes and electrolytes balance disturbance, therefore, reinforcing that diclofenac may increase the risks of cardiovascular events in hypertensive patients.

背景:双氯芬酸是全球处方最多的非甾体抗炎药(NSAID),但它与高血压和急性肾损伤高度相关。尽管如此,有关双氯芬酸对高血压患者肾脏影响的信息却很少,因此我们对这种非甾体抗炎药对正常血压大鼠(NTR)和自发性高血压大鼠(SHR)的肾脏影响进行了比较研究:雄性 Wistar NTR 和自发性高血压大鼠口服载体(V:10 mL/kg)或双氯芬酸钠(D:100 mg/kg),每天一次,连续 3 天。对尿量、电解质排泄量(Na+、K+、Cl- 和 Ca2+)、尿素、肌酐、pH 值和渗透压进行了评估。此外,还采集了血液样本和肾组织,以进行生化和组织学分析:结果:双氯芬酸增加了SHR的肾小球和鲍曼间隙,而在NTR的肾组织中未观察到显微变化。在尿液参数方面,双氯芬酸降低了两种血型的尿量、pH值、渗透压和所有电解质的排泄,继而降低了尿素和肌酐水平。此外,双氯芬酸还会诱发 SHR 低钠血症、低钾血症和低钙血症,同时降低肾组织中谷胱甘肽-S-转移酶活性、脂质氢过氧化物和亚硝酸盐水平:本文提供的数据表明,双氯芬酸会诱发NTR和SHR的肾损伤和肾功能受损,但从组织学变化和电解质平衡紊乱可以看出,这些影响在SHR中会加剧,因此,双氯芬酸可能会增加高血压患者发生心血管事件的风险。
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引用次数: 0
Therapeutic Potential of Diosgenin in Amelioration of Carbon Tetrachloride-Induced Murine Liver Injury. 薯蓣皂苷在改善四氯化碳诱发的小鼠肝损伤中的治疗潜力
IF 2.2 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-01 Epub Date: 2024-03-08 DOI: 10.1055/a-2263-1329
Mohamad-Hasan Ghosian-Moghaddam, Parvaneh Mohseni-Moghaddam, Mehrdad Roghani

Diosgenin is a sapogenin with antidiabetic, antioxidant, and anti-inflammatory properties. The current study investigated whether diosgenin could ameliorate carbon tetrachloride (CCL4)-induced liver injury. To cause liver injury, CCL4 was injected intraperitoneally twice a week for 8 weeks. Daily oral administration of diosgenin at doses of 20, 40, and 80 mg/kg was started one day before CCL4 injection and continued for 8 weeks. Finally, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and also albumin were assessed. Catalase and superoxide dismutase (SOD) activities in addition to glutathione (GSH) and malondialdehyde (MDA) levels were also quantified in the liver homogenate and routine histological evaluation was also conducted. Elevated serum levels of liver enzymes and decreased serum level of albumin caused by CCL4 were significantly restored following diosgenin administration at doses of 40 and 80 mg/kg. Long-term administration of CCL4 increased inflammatory and apoptotic factors such as IL-1β, caspase 3, TNF-α, and IL-6 and decreased SOD and catalase activities as well as GSH level in liver homogenates; while MDA level was increased. Treatment with diosgenin increased SOD and catalase activities and GSH levels in the liver of injured animals. In addition, liver MDA, IL-1β, caspase 3, TNF-α, and IL-6 level or activity decreased by diosgenin treatment. Additionally, diosgenin aptly prevented aberrant liver histological changes. According to obtained results, diosgenin can dose-dependently diminish CCl4-induced liver functional deficits and histological changes in a dose-dependent manner, possibly due to its antioxidant and anti-inflammation properties, and its beneficial effect is comparable to known hepatoprotective agent silymarin.

薯蓣皂苷是一种具有抗糖尿病、抗氧化和抗炎特性的苷元。本研究探讨了薯蓣皂苷能不能改善四氯化碳(CCL4)诱导的肝损伤。为了造成肝损伤,每周两次腹腔注射 CCL4,连续注射 8 周。在注射 CCL4 前一天开始每天口服剂量为 20、40 和 80 毫克/千克的薯蓣皂苷,并持续 8 周。最后,对血清中的天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)和白蛋白水平进行了评估。此外,还对肝脏匀浆中的过氧化氢酶和超氧化物歧化酶(SOD)活性、谷胱甘肽(GSH)和丙二醛(MDA)水平进行了量化,并进行了常规组织学评估。在服用剂量为 40 和 80 毫克/千克的 diosgenin 后,CCL4 导致的肝酶血清水平升高和白蛋白血清水平降低得到了显著恢复。长期服用 CCL4 会增加炎症和凋亡因子,如 IL-1β、caspase 3、TNF-α 和 IL-6,降低 SOD 和过氧化氢酶活性以及肝匀浆中的 GSH 水平,同时增加 MDA 水平。使用薯蓣皂苷治疗可提高损伤动物肝脏中的 SOD 和过氧化氢酶活性以及 GSH 水平。此外,肝脏中的 MDA、IL-1β、caspase 3、TNF-α 和 IL-6 的水平或活性也在 diosgenin 处理后下降。此外,薯蓣皂苷能有效防止肝脏组织学的异常变化。研究结果表明,薯蓣皂苷能以剂量依赖的方式减轻CCl4诱导的肝功能缺陷和组织学变化,这可能是由于薯蓣皂苷的抗氧化和抗炎特性,其有益效果与已知的保肝药物水飞蓟素相当。
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引用次数: 0
An Observational Study on Cosmetics Use-related Adverse Effects: Cosmetovigilance Need of the Day. 化妆品使用相关不良反应的观察研究:当今化妆品警戒的需要。
IF 2.2 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-01 Epub Date: 2024-03-11 DOI: 10.1055/a-2251-6655
Geetika Mehta, Daksh Raj Tyagi, Monika Sachdeva, Rashmi Tripathi, Himanshu Tyagi

Introduction: The pursuit of aesthetic attractiveness and increased awareness have contributed significantly to the growth of the cosmetic industry. However, it is crucial to recognize that even the minimal use of cosmetics may have harmful consequences for both the overall well-being and the broader community, an issue that has yet to be adequately recognized or addressed.

Objective: This study is aimed at providing insights into the usage pattern of consumer behavior regarding skin care products and to assess the prevalence and determinants of cosmetic-related adverse events among the general populace.

Materials and methods: A community-based cross-sectional study was carried out for four months in a satellite city of the National Capital Region (NCR) of India. The data from 435 respondents was collected using a self-administered questionnaire and analyzed using frequencies and percentages.

Results: Among 435 participants, 32.9% experienced one or more adverse effects owing to the use of skincare products; the prevalence was higher in females (36.3%). Hair loss, allergies, and dry skin were the most frequently reported adverse effects. The majority of the adverse reactions were reported with soap (21%), followed by shampoo (17%). The gender-wise difference between adverse effects of skin care products was found to be statistically significant.

Conclusion: To improve the system's efficiency, a comprehensive review of the current regulatory protocols for cosmetics is crucial. Additionally, it is essential to widely disseminate information on Cosmetovigilance and promote the reporting of any adverse effects of cosmetics within the community; this is the demand of the present time.

导 言对美感的追求和意识的提高极大地促进了化妆品行业的发展。然而,我们必须认识到,即使是极少量使用化妆品,也可能对整体健康和更广泛的社会造成有害影响,而这一问题尚未得到充分认识或解决:本研究旨在深入了解消费者使用护肤品的行为模式,并评估与化妆品有关的不良事件在普通人群中的发生率和决定因素:在印度国家首都地区(NCR)的一个卫星城市开展了一项为期四个月的社区横断面研究。研究采用自填问卷的方式收集了 435 名受访者的数据,并使用频率和百分比对数据进行了分析:结果:在 435 名受访者中,32.9% 的人因使用护肤品而出现过一种或多种不良反应;女性的发生率更高(36.3%)。脱发、过敏和皮肤干燥是最常见的不良反应。大多数不良反应都与肥皂有关(21%),其次是洗发水(17%)。护肤品不良反应的性别差异具有统计学意义:为了提高系统的效率,全面审查当前的化妆品监管规程至关重要。此外,必须广泛传播化妆品警戒信息,促进社区内对化妆品不良反应的报告;这是当前的要求。
{"title":"An Observational Study on Cosmetics Use-related Adverse Effects: Cosmetovigilance Need of the Day.","authors":"Geetika Mehta, Daksh Raj Tyagi, Monika Sachdeva, Rashmi Tripathi, Himanshu Tyagi","doi":"10.1055/a-2251-6655","DOIUrl":"10.1055/a-2251-6655","url":null,"abstract":"<p><strong>Introduction: </strong>The pursuit of aesthetic attractiveness and increased awareness have contributed significantly to the growth of the cosmetic industry. However, it is crucial to recognize that even the minimal use of cosmetics may have harmful consequences for both the overall well-being and the broader community, an issue that has yet to be adequately recognized or addressed.</p><p><strong>Objective: </strong>This study is aimed at providing insights into the usage pattern of consumer behavior regarding skin care products and to assess the prevalence and determinants of cosmetic-related adverse events among the general populace.</p><p><strong>Materials and methods: </strong>A community-based cross-sectional study was carried out for four months in a satellite city of the National Capital Region (NCR) of India. The data from 435 respondents was collected using a self-administered questionnaire and analyzed using frequencies and percentages.</p><p><strong>Results: </strong>Among 435 participants, 32.9% experienced one or more adverse effects owing to the use of skincare products; the prevalence was higher in females (36.3%). Hair loss, allergies, and dry skin were the most frequently reported adverse effects. The majority of the adverse reactions were reported with soap (21%), followed by shampoo (17%). The gender-wise difference between adverse effects of skin care products was found to be statistically significant.</p><p><strong>Conclusion: </strong>To improve the system's efficiency, a comprehensive review of the current regulatory protocols for cosmetics is crucial. Additionally, it is essential to widely disseminate information on Cosmetovigilance and promote the reporting of any adverse effects of cosmetics within the community; this is the demand of the present time.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":" ","pages":"164-170"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101265","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
Understanding the Potential of mRNA as Biomarker to Revolutionize Diagnosis of Colorectal Cancer. 了解 mRNA 作为生物标记物的潜力,彻底改变结直肠癌诊断。
IF 2.2 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-01 Epub Date: 2024-02-13 DOI: 10.1055/a-2244-6572
Rina Das, Dinesh Kumar Mehta, Nidhi Gupta

MicroRNA as potential biomarker for early diagnosis, differentiating various stages, interpreting the success of postoperative curative surgery and predicting early relapse of Colorectal cancer.In the realm of medical research, the quest to find effective biomarkers for various diseases has always been a top priority. Colorectal cancer (CRC), one of the leading causes of cancer-related deaths worldwide, is no exception. The emergence of microRNA (mRNA) as a potential biomarker for CRC has sparked immense interest among scientists and clinicians alike. mRNA, a molecule responsible for translating genetic information into functional proteins, presents a promising avenue for early detection and personalized treatment of this deadly disease. By analyzing the specific patterns and levels of mRNA expression in CRC cells, researchers have the ability to identify signatures that can aid in accurate diagnosis, predict patient prognosis, and even guide targeted therapies. This breakthrough in molecular biology not only enhances our understanding of CRC but also holds the potential to revolutionize the field of cancer diagnostics and treatment. In this article, we will delve deeper into the potential of mRNA as a biomarker for CRC, exploring its benefits and challenges in the field of cancer research.

微RNA作为潜在的生物标志物,可用于结直肠癌的早期诊断、区分不同阶段、解读术后根治手术的成功率以及预测早期复发。在医学研究领域,寻找各种疾病的有效生物标志物一直是重中之重。在医学研究领域,寻找各种疾病的有效生物标记物一直是重中之重,结直肠癌(CRC)作为全球癌症相关死亡的主要原因之一也不例外。mRNA是一种负责将遗传信息转化为功能性蛋白质的分子,它为这种致命疾病的早期检测和个性化治疗提供了一条很有前景的途径。通过分析 CRC 细胞中 mRNA 表达的特定模式和水平,研究人员有能力找出有助于准确诊断、预测患者预后甚至指导靶向治疗的特征。分子生物学领域的这一突破不仅增进了我们对 CRC 的了解,还有可能彻底改变癌症诊断和治疗领域。在本文中,我们将深入探讨 mRNA 作为 CRC 生物标记物的潜力,探讨它在癌症研究领域的优势和挑战。
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引用次数: 0
Encyclopaedic Review of Glipizide Pre-clinical and Clinical Status. 格列吡嗪临床前和临床现状百科全书。
IF 2.2 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-01 Epub Date: 2024-02-26 DOI: 10.1055/a-2237-8566
Saad Mohammed, Tarique Mahmood, Arshiya Shamim, Farogh Ahsan, Mohammad Shariq, Saba Parveen, Rufaida Waseem, Aditya Singh

Glipizide is an oral glucose-lowering medication that is beneficial for the treatment of type 2 diabetes. This study compiles exhaustively all accessible information on glipizide, from preclinical to clinical studies. Glipizide may be used in concert with TRAIL to treat cancer cells; in vitro studies have shown that it suppresses angiogenesis and vasculogenesis while shielding cells from glycation-induced damage. Anticonvulsant effects and modifications in the pharmacokinetics of other medications, such as Divalproex Sodium, were seen in glipizide in vivo experiments. Propranolol amplifies glipizide's hypoglycemic effect briefly in normal animals but consistently enhances it in diabetic ones. In the treatment of cancer and neurodegenerative poly(Q) illnesses, glipizide has demonstrated to offer potential therapeutic advantages. It is ineffective in preventing DENA-induced liver cancer and may cause DNA damage over time. The way glipizide interacts with genetic variants may increase the risk of hypoglycemia. Combining Syzygium cumini and ARBE to glipizide may enhance glycemic and lipid control in type 2 diabetes. Individuals with coronary artery disease who take glipizide or glyburide have an increased risk of death. The risk of muscular responses and acute pancreatitis is minimal when glipizide and dulaglutide are combined. In conclusion, glipizide has shown promising therapeutic efficacy across a variety of disorders.

格列吡嗪是一种有益于治疗 2 型糖尿病的口服降糖药物。本研究详尽汇编了格列吡嗪从临床前研究到临床研究的所有可用信息。格列吡嗪可与 TRAIL 协同用于治疗癌细胞;体外研究表明,格列吡嗪可抑制血管生成和脉管生成,同时保护细胞免受糖化引起的损伤。格列吡嗪的体内实验显示,它具有抗惊厥作用,并能改变其他药物(如双丙戊酸钠)的药代动力学。普萘洛尔能短暂增强格列吡嗪对正常动物的降血糖作用,但持续增强对糖尿病动物的降血糖作用。在治疗癌症和多发性神经退行性疾病方面,格列吡嗪具有潜在的治疗优势。格列吡嗪对预防 DENA 诱导的肝癌无效,长期服用可能会造成 DNA 损伤。格列吡嗪与基因变异的相互作用方式可能会增加低血糖的风险。将茜草和 ARBE 与格列吡嗪合用,可加强 2 型糖尿病患者的血糖和血脂控制。冠心病患者服用格列吡嗪或格列本脲会增加死亡风险。格列吡嗪和度拉鲁肽合用时,发生肌肉反应和急性胰腺炎的风险很小。总之,格列吡嗪对各种疾病都有良好的疗效。
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引用次数: 0
From Hypertension to Beyond: Unraveling the Diverse Mechanisms of Olmesartan in Disease Modulation. 从高血压到其他疾病:揭示奥美沙坦在疾病调节中的多种机制。
IF 2.2 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-01 Epub Date: 2024-02-13 DOI: 10.1055/a-2244-3136
Laiba Rind, Tarique Mahmood, Mohammed Haris Siddiqui, Farogh Ahsan, Arshiya Shamim, Aamir Anwar, Rajnish Kumar Yadav

Olmesartan, originally known for its antihypertensive properties, exhibits promising potential in addressing inflammation-mediated diseases. As an angiotensin II receptor blocker (ARB), Olmesartan influences pivotal pathways, including reactive oxygen species, cytokines, NF-κB, TNF-α, and MAPK. This suggests a viable opportunity for repurposing the drug in conditions such as ulcerative colitis, neuropathy, nephropathy, and cancer, as supported by multiple preclinical studies. Ongoing clinical trials, particularly in cardiomyopathy and nephropathy, suggest a broader therapeutic scope for Olmesartan. Repurposing efforts would entail comprehensive investigations using disease-specific preclinical models and dedicated clinical studies. The drug's established safety profile, wide availability, and well-understood ARB mechanism of action offer distinct advantages that could facilitate a streamlined repurposing process. In summary, Olmesartan's versatile impact on inflammation-related pathways positions it as a promising candidate for repurposing across various diseases. Ongoing clinical trials and the drug's favorable attributes enhance its appeal for further exploration and potential application in diverse medical contexts.

奥美沙坦最初因其抗高血压特性而闻名,在治疗炎症介导的疾病方面展现出巨大潜力。作为一种血管紧张素 II 受体阻断剂(ARB),奥美沙坦能影响关键通路,包括活性氧、细胞因子、NF-κB、TNF-α 和 MAPK。这表明,在溃疡性结肠炎、神经病变、肾病和癌症等病症中重新使用这种药物是可行的,多项临床前研究也证明了这一点。正在进行的临床试验,尤其是心肌病和肾病的临床试验,表明奥美沙坦的治疗范围更广。奥美沙坦酯的再利用工作需要利用针对特定疾病的临床前模型和专门的临床研究进行全面调查。该药物已确立的安全性、广泛的可获得性和广为人知的 ARB 作用机制具有明显的优势,可促进再利用过程的简化。总之,奥美沙坦对炎症相关通路的多方面影响使其有望成为各种疾病的再利用候选药物。正在进行的临床试验和该药物的良好特性增强了其进一步探索的吸引力,并有可能应用于不同的医疗领域。
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引用次数: 0
Protective Effects of Xanthine Derivatives Against Arsenic Trioxide-Induced Oxidative Stress in Mouse Hepatic and Renal Tissues. 黄嘌呤衍生物对三氧化二砷诱导的小鼠肝脏和肾脏组织氧化应激的保护作用
IF 2.2 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-01 Epub Date: 2024-02-13 DOI: 10.1055/a-2247-5232
Navid Omidifar, Ahmad Gholami, Mansoureh Shokripour, Mohammad Ali Nourani, Milad Mohkam, Seyyed Mojtaba Mousavi, Seyyed Alireza Hashemi, Bagher Khorram, Amir Nili Ahmadabadi, Mahintaj Dara

In this study, the protective efficacy of pentoxifylline (PTX) as a xanthine derivative against arsenic trioxide (ATO)-induced kidney and liver damage in mice was investigated. Thirty-six mice were divided into six groups, receiving intraperitoneal injections of saline, ATO, PTX, or a combination for four weeks. Blood samples were analyzed for serum biochemistry, while hepatic tissue underwent examination for histopathological changes and assessment of oxidative stress markers and antioxidant gene expression through Real-Time PCR. ATO exposure significantly increased serum markers (creatinine, ALT, BUN, ALP, AST) and induced histopathological changes in the liver. Moreover, it elevated renal and hepatic nitric oxide (NO) and lipid peroxidation (LPO) levels, and reduced antioxidant enzyme expression (CAT, GSR, GPx, MPO, SOD), total thiol groups (TTGs), and total antioxidant capacity (TAC). Conversely, PTX treatment effectively lowered serum hepatic and renal markers, improved antioxidant markers, and induced histopathological alterations. Notably, PTX did not significantly affect renal and hepatic NO levels. These findings suggest that PTX offers therapeutic potential in mitigating liver and acute kidney injuries induced by various insults, including exposure to ATO.

本研究探讨了作为黄嘌呤衍生物的喷托塞林(PTX)对三氧化二砷(ATO)诱导的小鼠肝肾损伤的保护作用。研究人员将 36 只小鼠分为 6 组,分别腹腔注射生理盐水、ATO、PTX 或其组合,为期四周。对血样进行血清生化分析,同时对肝组织进行组织病理学变化检查,并通过实时 PCR 评估氧化应激标记物和抗氧化基因的表达。暴露于 ATO 会明显增加血清指标(肌酐、谷丙转氨酶、尿素氮、谷草转氨酶、谷草转氨酶),并诱发肝脏组织病理学变化。此外,它还会升高肾脏和肝脏的一氧化氮(NO)和脂质过氧化(LPO)水平,降低抗氧化酶(CAT、GSR、GPx、MPO、SOD)、总硫醇基团(TTGs)和总抗氧化能力(TAC)的表达。相反,PTX 治疗可有效降低血清肝脏和肾脏指标,改善抗氧化指标,并诱导组织病理学改变。值得注意的是,PTX 对肾脏和肝脏的 NO 水平没有明显影响。这些研究结果表明,PTX 在减轻各种损伤(包括暴露于 ATO)引起的肝脏和急性肾脏损伤方面具有治疗潜力。
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引用次数: 0
The Perspective of Using Flow Cytometry for Unpuzzling Hypoxia-Inducible Factors Signalling. 使用流式细胞仪揭示缺氧诱导因子信号的视角。
IF 2.2 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-01 Epub Date: 2024-02-13 DOI: 10.1055/a-2248-9180
Vishal J Patel, Amit Joharapurkar, Mukul R Jain

Hypoxia-inducible factors (HIFs) are transcription factors that are responsible for adapting to the changes in oxygen levels in the cellular environment. HIF activity determines the expression of cellular proteins that control the development and physiology of the cells and pathophysiology of a disease. Understanding the role of specific HIF (HIF-1-3) in cellular function is essential for development of the HIF-targeted therapies. In this review, we have discussed the use of flow cytometry in analysing HIF function in cells. Proper understanding of HIF-signalling will help to design pharmacological interventions HIF-mediated therapy. We have discussed the role of HIF-signalling in various diseases such as cancer, renal and liver diseases, ulcerative colitis, arthritis, diabetes and diabetic complications, psoriasis, and wound healing. We have also discussed protocols that help to decipher the role of HIFs in these diseases that would eventually help to design promising therapies.

缺氧诱导因子(HIF)是一种转录因子,负责适应细胞环境中氧含量的变化。HIF 的活性决定着细胞蛋白质的表达,而细胞蛋白质的表达控制着细胞的发育和生理以及疾病的病理生理学。了解特定 HIF(HIF-1-3)在细胞功能中的作用对于开发 HIF 靶向疗法至关重要。在这篇综述中,我们讨论了流式细胞术在分析细胞中 HIF 功能中的应用。正确理解 HIF 信号有助于设计 HIF 介导的药物干预疗法。我们讨论了 HIF 信号在癌症、肾病和肝病、溃疡性结肠炎、关节炎、糖尿病和糖尿病并发症、银屑病和伤口愈合等各种疾病中的作用。我们还讨论了有助于破译 HIF 在这些疾病中的作用的方案,这些方案最终将有助于设计有前途的疗法。
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