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《Saudi Pharmaceutical Journal》2022,30(6):669-678
BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction. 相似文献
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A molecular perspective for the use of type IV tyrosine kinase inhibitors as anticancer therapeutics
《Drug discovery today》2022,27(3):808-821
Tyrosine kinases are enzymes that can transfer a phosphate group from ATP to a specific protein tyrosine, serine or threonine residue within a cell, operating as a switch that can turn ‘on’ and ‘off’ causing different physiological alterations in the body. Mutated kinases have been shown to display an equilibrium shift toward the activated state. Types I–III have been studied intensively leading to drugs like imatinib (type II), cobimetinib (type III), among others. It is the same scenario for types V–VII; however, there is a lacuna in information regarding type IV inhibitors, although recently some advances have surfaced. This review aims to accumulate the knowledge gained so far about type IV inhibitors. 相似文献
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Nanotherapy: New Approach for Impeding Hepatic Cancer Microenvironment via Targeting Multiple Molecular Pathways 下载免费PDF全文
Ahmed A Abd-Rabou Hanaa H Ahmed Safaa H MohamedSoheir E KotobMohamed S Kishta 《Asian Pacific journal of cancer prevention》2022,23(12):4261-4273
Objective: Hepatocellular carcinoma (HCC) microenvironment has been recognized as a key contributor for cancer progression, metastasis, and drug resistance. The crosstalk between tumor cells, the vascular endothelial growth factor (VEGF), and the chemokine (C-C motif) ligand 2 (CCL2) signaling networks mediates immunoinhibitory impact and facilitates tumor angiogenesis. The current investigation aimed at exploring the potent anti-cancer activity of the newly designed nano-based anti-cancer therapy comprising anti-VEGF drug, avastin (AV), and CCR2 antagonist (CR) to counteract HCC and tracking its mode of action in vivo. Methods: The prepared AV, CR, and AVCR nanoprototypes were characterized by nanoscale characterization techniques in our previous work. Here, they are applied for unearthing their anti-cancer properties / mechanisms in hepatic cancer-induced rats via analyzing protein levels and genetic expression of the elements incorporated in the angiogenesis, apoptosis, and metastasis signalling pathways. Results: The present results revealed a significant down-regulation in the angiogenesis, survival and metastasis indices along with up-regulation in the pro-apoptotic mediators upon treatment of hepatic cancer-bearing rats with the novel synthesized nanomaterials when compared with the untreated counterparts. We showed across HCC model that anti-VEGF in combination with CCR2 antagonism therapy leads to sensitization and enhanced tumor response over anti-VEGF or CCR2 antagonism monotherapy, particularly in its nanoscale formulation. Conclusion: The present approach provides new mechanistic insights into the powerful anti-hepatic cancer advantage of the novel nanoprototypes which is correlated with modulating critical signal transduction pathways implicated in tumor microenviroment such as angiogenesis, apoptosis and metastasis. This research work presents a substantial foundation for future studies focused on prohibiting cancer progression and recovery by targeting tumor microenviroment. 相似文献
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《Nutrition, metabolism, and cardiovascular diseases : NMCD》2022,32(1):151-159
Background & aimsTo determine the trends of self-reported non-adherence rates among adults taking Type 2 medicines (T2D) medicines between 2017 and 2019 and to identify the patterns for the frequently reported reasons for non-adherence in the United States.Methods & resultsData from the National Health and Wellness Survey, a self-administered, internet-based cross-sectional survey of US adults from 2017 to 2019 was used. Non-adherence was measured using the self-reported Medication Adherence Reasons Scale (MAR-Scale). Frequencies were used to identify the reasons for non-adherence for insulin and non-insulin therapies for T2D.Data were obtained from 2983 respondents in 2017, 5416 in 2018, and 5268 in 2019. Based on the MAR-Scale, the self-reported medication non-adherence rate was 25% in 2017, 21% in 2018, and 27% in 2019. The most common reason for non-adherence across all the three years was simple forgetfulness, yet patients reported the lowest mean number of days missing medication for that reason. Though less frequently reported, non-adherence lasted longer when patient did not know how to take their medicines, cost was a reason, or had concerns about the long term effects of the medicines.ConclusionsWith no significant improvement in adherence with T2D medicines over time, regardless of better awareness and extensive diabetes education, focus should be on individualized non-adherence reasons-based interventions. 相似文献
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《Nutrition, metabolism, and cardiovascular diseases : NMCD》2022,32(7):1742-1752
Background and aimTo evaluate the effectiveness of structured exercise appropriate the circadian rhythm in terms of blood sample test (BST), functionality and quality of life (QoL) in individuals with type 2 diabetes.Methods and resultsThis was a parallel-group, single-blind, crossover study. Thirty individuals with type 2 diabetes aged 35–65 years were enrolled in the study and allocated into 2 groups as the Morning Chronotype (MC) Group (n = 15) and the Evening Chronotype (EC) Group (n = 15) using Morningness-Eveningness Questionnaire which was used to determine the chronotypes. Participants were evaluated in terms of BST, functionality and QoL at the beginning of the study (T0), at 6 (T1), 12 (T2), and 18 (T3) weeks after the study started. A structured exercise program for 3 days a week over 6 weeks was applied in accordance with the chronotypes (T1-T2) and cross-controlled for the chronotypes (T2-T3). Significant differences were found in favor of the exercise given at the appropriate time for the chronotype in all parameters in both groups within groups (T0-T1-T2-T3) (p < 0.05). In the time1group interactions, exercise in accordance with the appropriate chronotype in both groups provided the highest statistical improvement in all parameters (p < 0.05).ConclusionIt was concluded that structured exercise performed at the appropriate time for chronotype improves HbA1c, fasting blood glucose, HDL-LDL cholesterol, triglyceride, total cholesterol, functionality and quality of life in type 2 diabetes. This variation in blood values was observed to reflect the quantitative effects of exercise administered according to the circadian rhythm in individuals with type 2 diabetes.Trial registrationClinicalTrials.gov (NCT04427488). The protocol of the study was registered at ClinicalTrials.gov (NCT04427488). 相似文献