Differential Responses to Blood Pressure and Oxidative Stress in Streptozotocin-Induced Diabetic Wistar-Kyoto Rats and Spontaneously Hypertensive Rats: Effects of Antioxidant (Honey) Treatment

Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress

A panel of three microRNA signatures as a potential biomarker for CRC screening based on stages and functional prediction using bioinformatic analysis

Background: MicroRNA (miRNA) has been linked to colorectal cancer (CRC) tumorigenesis due to its post-transcriptional mechanism in targeting cancer-associated genes. Although miRNAs appear to be promising screening biomarkers, functional prediction analysis is required to shed light on their role in CRC tumorigenesis. Therefore, this study aims to identify the significantly deregulated miRNAs in CRC tumorigenesis. (2) Methods: Three upregulated miRNAs (hsa-miR-20a-5p, hsa-miR-21-5p, and hsa-miR210-3p) from 14 significant differentially expressed miRNAs (DEMs) were chosen from microarray profiling to be validated in plasma. Bioinformatics analyses showed that these miRNAs generally contributed to tumorigenesis, but only hsa-miR-20a-5p and hsa-miR-21-5p were specifically linked to CRC. Only two miRNAs showed a positive correlation when compared to their expression in plasma. However, further analysis showed that all three miRNAs in plasma were significantly difference between the early and advanced stages of CRC. ROC curve analysis was used to evaluate miRNAs’ diagnostic performance in the early and advanced stages. (3) Results: Collectively, hsa-miR-20a-5p showed the highest discriminative value (AUC= 0.82, sensitivity = 86%, and specificity= 88%) in discriminating early CRC, while both hsa-miR-21-5p and hsa-miR-210-3p give a perfect performance for advance CRC. In addition, the performance of all miRNAs’ combinations also gives a perfect performance for diagnosis in both early and advanced CRC, except the combination of hsa-miR-20a-5p and hsa-miR-210-3p. (4) Conclusions: A few potential miRNA panels as CRC biomarker is needed for better prediction of disease. The reflective circulating miRNAs can be contributed to by minimal invasive screening tools

Antioxidant Protective Effect of Glibenclamide and Metformin in Combination with Honey in Pancreas of Streptozotocin-Induced Diabetic Rats

Hyperglycemia exerts toxic effects on the pancreatic β-cells. This study investigated the hypothesis that the common antidiabetic drugs glibenclamide and metformin, in combination with tualang honey, offer additional protection for the pancreas of streptozotocin (STZ)-induced diabetic rats against oxidative stress and damage. Diabetes was induced in male Sprague Dawley rats by a single dose of STZ (60 mg/kg; ip). Diabetic rats had significantly elevated levels of lipid peroxidation (TBARS), up-regulated activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) while catalase (CAT) activity was significantly reduced. Glibenclamide and metformin produced no significant effects on TBARS and antioxidant enzymes except GPx in diabetic rats. In contrast, the combination of glibenclamide, metformin and honey significantly up-regulated CAT activity and down-regulated GPx activity while TBARS levels were significantly reduced. These findings suggest that tualang honey potentiates the effect of glibenclamide and metformin to protect diabetic rat pancreas against oxidative stress and damage

Obesity: A Prerequisite for Major Chronic Illnesses

Obesity is rampantly soaring at an alarming rate globally and simultaneously causing an increased incidence, and predisposition to various comorbidities. obesity is body mass index of >30kg/m2, while <18kg/m2 is underweight. The world at large fails to recognize obesity as an inevitable disease that requires strict measures to control this modifiable risk factor. W.H.O news release reported that over one billion people globally are obese among which 650 million were adults, 340 million were adolescents, and 39 million were children. The lowest obesity prevalence was reported in Timor Leste at 3.80%, Bangladesh at 3.60%, and Vietnam at 2.10% while the highest were noted in Nauru at 61%, cook island at 55.9%, and Palau at 55.3%. obesity is the most prevailing health problem (15% globally) associated with an increased propensity for development of several medical illnesses, obesity-associated adverse outcomes causing fatal complications that are difficult to manage, and premature mortality. The obese often feel they are not socially cared for by society and are accorded limited time by physicians who don’t view their health concerns from their own perspectives. Thus, making them pessimistic from low self-esteem and discrimination, body shaming, and stigmatization. They eventually develop depressive-anxiety disorder because of distrust insight

Comparison of Antioxidant Effects of Honey, Glibenclamide, Metformin, and Their Combinations in the Kidneys of Streptozotocin-Induced Diabetic Rats

Hyperglycemia-induced increase in oxidative stress is implicated in diabetic complications. This study investigated the effect of metformin and/or glibenclamide in combination with honey on antioxidant enzymes and oxidative stress markers in the kidneys of streptozotocin (60 mg/kg; intraperitoneal)-induced diabetic rats. Diabetic rats were randomized into eight groups of five to seven rats and received distilled water (0.5 mL); honey (1.0 g/kg); metformin (100 mg/kg); metformin (100 mg/kg) and honey (1.0 g/kg); glibenclamide (0.6 mg/kg); glibenclamide (0.6 mg/kg) and honey (1.0 g/kg); metformin (100 mg/kg) and glibenclamide (0.6 mg/kg); or metformin (100 mg/kg), glibenclamide (0.6 mg/kg) and honey (1.0 g/kg) orally once daily for four weeks. Malondialdehyde (MDA) levels, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were significantly elevated while catalase (CAT) activity, total antioxidant status (TAS), reduced glutathione (GSH), and GSH:oxidized glutathione (GSSG) ratio was significantly reduced in the diabetic kidneys. CAT, glutathione reductase (GR), TAS, and GSH remained significantly reduced in the diabetic rats treated with metformin and/or glibenclamide. In contrast, metformin or glibenclamide combined with honey significantly increased CAT, GR, TAS, and GSH. These results suggest that combination of honey with metformin or glibenclamide might offer additional antioxidant effect to these drugs. This might reduce oxidative stress-mediated damage in diabetic kidneys

Clinicopathological and Prognostic Characteristics of Malaysian Triple Negative Breast Cancer Patients Undergoing TAC Chemotherapy Regimen

Triple negative breast cancer (TNBC) is associated with aggressive tumour phenotype and early tumour relapse following diagnosis. Generally, clinicopathological features such as tumour size, patient’s age at diagnosis, tumour histology subtypes, grade and stage, involvement of lymph nodes, and menopausal status are commonly used for predicting disease progression, prospects of recurrence, and treatment response. Prognostic value of clinicopathological features on Malaysian TNBC patients is limited. Thus, this study is aimed at investigating the association of clinicopathological features on disease-free survival (DFS) and overall survival (OS) of Malaysian TNBC patients undergoing TAC chemotherapy. Seventy-six (76) immunohistochemistry-confirmed TNBC patients were recruited. The clinicopathological features of TNBC patients were collected and recorded. Kaplan-Meier and log-rank followed by a Cox proportional hazard regression model were performed to evaluate the TNBC patients’ survival. Out of 76 TNBC patients, 25 were chemoresistant and 51 were chemoresponders to the TAC chemotherapy regimen. The overall 5-year cumulative DFS and OS of TNBC patients were 63.5% and 76.3%, respectively. Multivariate Cox analysis demonstrated that medullary and metaplastic histology subtypes and positive axillary lymph node metastasis were significant prognostic factors associated with relapse with adjusted HR: 5.76, 95% CI: 2.35, 14.08 and adjusted HR: 3.55, 95% CI: 1.44, 8.74, respectively. Moreover, TNBC patients with medullary and metaplastic histology subtypes and positive axillary lymph node metastases had a higher risk to death than patients who had infiltrating ductal carcinoma and negative axillary lymph node metastasis (adjusted HR: 8.30, 95% CI: 2.38, 28.96 and adjusted HR: 6.12, 95% CI: 1.32, 28.42, respectively). Our results demonstrate the potential use of medullary and metaplastic histology subtype and positive axillary lymph node metastasis as a potential biomarker in predicting relapse and survival of the TNBC patients. This warrants further studies on intensification of chemotherapy and also identification and development of targeted therapy to reduce relapses and improve survival of TNBC patients