Sesamin Mitigates Inflammation and Oxidative Stress in Endothelial Cells Exposed to Oxidized Low-Density Lipoprotein

[[abstract]]Sesamin, a lignan from sesame oil, has been shown to have anti hypertensive and antioxidative properties. This study examined the effects of sesamin on oxidized low-density lipoprotein (oxLDL)-induced endothelial dysfunction. Oxidative stress was determined by measuring the generation of intracellular reactive oxygen species (ROS) and by measuring the expression levels of superoxide dismutase (SOD) and endothelial nitric oxide synthase (eNOS). To assess the pro-inflammatory effects of oxLDL, ELISA was used to detect IL-8 expressions endothelin-1 (ET-1) secretion, and nuclear factor-kappa B (NF-kappa B) activation. The expression of adhesion molecules (ICAM-1, VCAM-1, and E-selectin) was examined by flow cytometry. In addition, several apoptotic signaling pathways were also investigated. The data showed that sesamin significantly ameliorated oxLDL-induced ROS generation and SOD-1 inactivation. Sesamin also attenuated the oxLDL-induced activation of NF-kappa B, suggesting that the inhibitory effects of sesamin on IL-8 and ET-1 release, adhesion molecule expression, and the adherence of THP-1 cells were at least partially through the blockade of NF-kappa B activation, Furthermore, sesamin attenuated oxLDL-induced apoptotic features, such as intracellular calcium accumulation and the subsequent collapse of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-3. Results from this study may provide insight into possible molecular mechanisms underlying sesamin's beneficial effects against oxLDL-mediated vascular endothelial dysfunction

Aqueous Extract from Hibiscus sabdariffa Linnaeus Ameliorate Diabetic Nephropathy via Regulating Oxidative Status and Akt/Bad/14-3-3γ in an Experimental Animal Model

Several studies point out that oxidative stress maybe a major culprit in diabetic nephropathy. Aqueous extract of Hibiscus sabdariffa L. (HSE) has been demonstrated as having beneficial effects on anti-oxidation and lipid-lowering in experimental studies. This study aimed at investigating the effects of Hibiscus sabdariffa L. on diabetic nephropathy in streptozotocin induced type 1 diabetic rats. Our results show that HSE is capable of reducing lipid peroxidation, increasing catalase and glutathione activities significantly in diabetic kidney, and decreasing the plasma levels of triglyceride, low-density lipoprotein (LDL) and increasing high-density lipoprotein (HDL) value. In histological examination, HSE improves hyperglycemia-caused osmotic diuresis in renal proximal convoluted tubules (defined as hydropic change) in diabetic rats. The study also reveals that up-regulation of Akt/Bad/14-3-3γ and NF-κB-mediated transcription might be involved. In conclusion, our results show that HSE possesses the potential effects to ameliorate diabetic nephropathy via improving oxidative status and regulating Akt/Bad/14-3-3γ signaling

Dysregulated Apoptosis Through the Intrinsic Pathway in the Internal Spermatic Vein of Patients With Varicocele

Background/PurposeApoptosis plays a critical role in various physiological processes. Varicocele is the most common cause of male infertility in adults. The dilated and thickened wall of the internal spermatic vein (ISV) in varicocele is considered similar to that in varicose veins. We investigated apoptotic protein expression in the ISV of varicocele, including Bcl-2, Fas, caspase-8 and caspase-9, to determine the intrinsic or extrinsic pathway.MethodsThe study group consisted of 10 patients with grade 3 left varicocele. The control group consisted of 10 patients with left indirect inguinal hernia. A 1-cm section of ISV was resected, using left inguinal incision, from each patient in both groups. The ISV sections were used to detect the mediators that regulate the intrinsic (Bcl-2 and caspase-9) and extrinsic (Fas and caspase-8) apoptotic pathways, by immunoblotting and immunohistochemical staining. Results were analyzed using Student's t tests.ResultsBcl-2, Fas, caspase-8 and caspase-9 immunoblots from both groups revealed a single band. The relative intensities of the Bcl-2 and caspase-9 protein bands differed significantly between the varicocele and control groups. Thickening of the smooth muscle layer of the ISV was found in patients with varicocele compared with the control group. Bcl-2 overexpression and downregulation of caspase-9 expression were noted in the varicocele group. There was no significant difference in Fas or caspase-8 expression in either group.ConclusionWe showed overexpression of Bcl-2 and downregulation of caspase-9 expression in the ISV under hypoxic stress. This indicated dysregulated apoptosis through the intrinsic pathway in the ISV of patients with varicocele. To the best of our knowledge, this is the first study of the apoptotic pathway in the human ISV. Additional studies are needed to establish whether adjunctive hyperbaric oxygen therapy reduces the recurrence rate after varicocelectomy

Efficacy of Mammographic Evaluation of Breast Cancer in Women Less Than 40 Years of Age: Experience from a Single Medical Center in Taiwan

Background/PurposeMammography is the standard imaging modality for breast cancer diagnosis. However, the value of mammographic diagnosis in breast cancer patients aged less than 40 years old has not been well assessed. The goal of our study was to determine the diagnostic efficacy of mammography for the detection of breast cancer in women under 40 years of age in a single medical center in Taiwan.MethodsOf 1766 women diagnosed with breast cancer in one medical center between 1999 and 2005, 227 (12.9%) who were younger than 40 years of age were enrolled, and 105 of these 227 patients had pre-biopsy mammograms available for analysis. The sensitivities for mammography at first (prospective) and second (retrospective) readings and for corresponding ultrasound were calculated. The distribution of different breast composition between the mammographic true-positive (TP) and false-negative (FN) lesions at the first and second readings was analyzed.ResultsOf the 105 patients, 104 presented with a palpable mass and the other one was asymptomatic. There were 109 pathologically proven breast cancers from the 105 patients; 92 of 109 cancerous lesions were detected at the first mammographic reading (sensitivity 84.4%), and the most common mammographic sign was microcalcifications (40.2%). The second reading detected seven additional cancers (99 of 109 lesions; sensitivity 90.8%). There was no significant difference between mammographic TP and FN lesions for the different breast composition on first and second readings. Ninety patients also had ultrasound available for correlation with 94 cancers diagnosed from them. The diagnostic sensitivity of ultrasound was 94.7% (89 of 94 lesions).ConclusionMammography has an acceptable sensitivity for the detection of breast cancer in women aged less than 40 years, regardless of different breast composition. Breast ultrasound can offer a higher sensitivity for such a population

Aspirin prevents resistin-induced endothelial dysfunction by modulating AMPK, ROS, and Akt/eNOS signaling

BackgroundResistin, an adipocytokine, plays a potential role in cardiovascular disease and may contribute to increased atherosclerotic risk by modulating the activity of endothelial cells. A growing body of evidence suggests that aspirin is a potent antioxidant. We investigated whether aspirin mitigates resistin-induced endothelial dysfunction via modulation of reactive oxygen species (ROS) generation and explored the role that AMP-activated protein kinase (AMPK), a negative regulator of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, plays in the suppressive effects of aspirin on resistin-induced endothelial dysfunction.MethodsHuman umbilical vein endothelial cells (HUVECs) were pretreated with various doses of aspirin (10-500 μg/mL) for 2 hours and then incubated with resistin (100 ng/mL) for an additional 48 hours. Fluorescence produced by the oxidation of dihydroethidium (DHE) was used to quantify the production of superoxide in situ; superoxide dismutase (SOD) and catalase activities were determined by an enzymatic assay; and protein levels of AMPK-mediated downstream signaling were investigated by Western blot.ResultsTreatment of HUVECs with resistin for 48 hours resulted in a 2.9-fold increase in superoxide production; however, pretreatment with aspirin resulted in a dose-dependent decrease in production of superoxide (10-500 μg/mL; n = 3 experiments; all P < .05). Resistin also suppressed the activity of superoxide dismutase and catalase by nearly 50%; that result, however, was not observed in HUVECs that had been pretreated with aspirin at a concentration of 500 μg/mL. The membrane translocation assay showed that the levels of NADPH oxidase subunits p47phoxand Rac-1 in membrane fractions of HUVECs were threefold to fourfold higher in cells that had been treated with resistin for 1 hour than in untreated cells; however, pretreatment with aspirin markedly inhibited resistin-induced membrane assembly of NADPH oxidase via modulating AMPK-suppressed PKC-α activation. Application of AMPKα1-specific siRNA resulted in increased activation of PKC-α and p47phox. In addition, resistin significantly decreased AMPK-mediated downstream Akt/endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling and induced the phosphorylation of p38 mitogen-activated protein kinases, which in turn activated NF-κB-mediated inflammatory responses such as the release of interleukin (IL)-6 and IL-8, the overexpression of adhesion molecules, and stimulation of monocytic THP-1 cell attachment to HUVECs (2.5-fold vs control; n = 3 experiments). Furthermore, resistin downregulated eNOS and upregulated inducible NO synthase (iNOS) expression, thereby augmenting the formation of NO and protein nitrosylation. Pretreatment with aspirin, however, exerted significant cytoprotective effects in a dose-dependent manner (P < .05).ConclusionsOur findings suggest a direct connection between adipocytokines and endothelial dysfunction and provide further insight into the protective effects of aspirin in obese individuals with endothelial dysfunction.Clinical RelevanceResistin has been reported to involve in the inflammatory process, which is a common feature in metabolic syndrome, insulin resistance status, and vascular diseases. This study underscores the potential clinical benefits and application of aspirin in prevention of obese-associated vascular dysfunction

On the Infra-Red Spectra of Solutions of O-Chlorophenol and Phenol

<p><b>a–d Immunoblotting of different proteins in control and study groups of gastric adenocarcinoma.</b> (a) Representative immunoblots of different target proteins in gastric epithelium of the control and study groups (from patients 1 to 4) with GAPDH as a loading control. M, marker. Relative protein abundance of NKA α1 (b), NKA β1 (c), and E-cadherin (d) in gastric epithelium of the control and study groups. The asterisks indicate a significant difference between the control and study groups. Values were expressed as the means ± SEM. A.u., arbitrary unit. ***, P < 0.001; ****, P < 0.0001.</p

Shorter GT repeats in the heme oxygenase-1 gene promoter are associated with a lower severity score in coronary artery disease

Abstract Background: The glutathione thymidine repeats [(GT) n ] of the heme oxygenase (HO)-1 gene promoter have been shown to be correlated with the incidence of coronary artery disease (CAD), patients with shorter repeats being less likely to have CAD. In this study, we investigated whether (GT) n repeats in the HO-1 promoter were related to a quantitative angiographic severity of CAD. Methods: The allele frequency of the HO-1 gene promoter (GT) n repeats was examined in CAD patients with de novo lesions (n ¼ 328). Patients&apos; baseline coronary severity was quantified using the Jeopardy scoring system. Results: The allele frequency of GT repeats in the HO-1 gene promoter had bimodal peaks at (GT) 23 and (GT) 30. Therefore, we defined allele classes as follows: S allele (&lt;23 repeats), M allele (23e29 repeats), and L allele (!30 repeats). The group with severe CAD (Jeopardy score !8) had a significantly lower frequency of the S allele (3.7% vs. 8.9%; p ¼ 0.042) than the group with moderate CAD (Jeopardy score &lt;8). None of the patient with the highest score of 12 (n ¼ 17) carried the class S allele. In a multivariate binary logistic analysis, being a carrier of shorter GT repeats was a significant negative predictor (odds ratio 0.393; p ¼ 0.024) of a higher Jeopardy score grade of CAD. Conclusion: Our study showed that shorter (GT) n repeat in the HO-1 gene promoter were associated with a lower Jeopardy severity score in patients with significant CAD

Systematic realist synthesis of health-related and lifestyle interventions designed to decrease overweight, obesity and unemployment in adults.

BACKGROUND: Obesity and unemployment are complex social and health issues with underlying causes that are interconnected. While a clear link has been established, there is lack of evidence on the underlying causal pathways and how health-related interventions could reduce obesity and unemployment using a holistic approach. OBJECTIVES: The aim of this realist synthesis was to identify the common strategies used by health-related interventions to reduce obesity, overweight and unemployment and to determine for whom and under what circumstances these interventions were successful or unsuccessful and why. METHODS: A realist synthesis approach was used. Systematic literature searches were conducted in Cochrane library, Medline, SocIndex, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and PsychInfo. The evidence from included studies were synthesised into Context-Mechanism-Outcome configurations (CMOcs) to better understand when and how programmes work, for which participants and to refine the final programme theory. RESULTS: A total of 83 articles met the inclusion criteria. 8 CMOcs elucidating the contexts of the health-related interventions, underlying mechanisms and outcomes were identified. Interventions that were tailored to the target population using multiple strategies, addressing different aspects of individual and external environments led to positive outcomes for reemployment and reduction of obesity. CONCLUSION: This realist synthesis presents a broad array of contexts, mechanisms underlying the success of health-related interventions to reduce obesity and unemployment. It provides novel insights and key factors that influence the success of such interventions and highlights a need for participatory and holistic approaches to maximise the effectiveness of programmes designed to reduce obesity and unemployment. TRIAL REGISTRATION: PROSPERO 2020 CRD42020219897

The Chromosome 9p21 Variant Not Predicting Long-Term Cardiovascular Mortality in Chinese with Established Coronary Artery Disease: An Eleven-Year Follow-Up Study

Introduction. We examined whether the variant at chromosome 9p21, rs4977574, was associated with long-term cardiovascular mortality in Han Chinese patients with coronary artery disease (CAD). Methodology. Subjects who underwent coronary angiography for chest pain were consecutively enrolled. Fasting blood samples were collected for laboratory and genotype assessments. The information was correlated with data collected from the national death database. Results. There were 925 cases with CAD and 634 without CAD enrolled in the present study. The G allele conferred a significant increase in risk of CAD (odds ratio = 1.47, P=0.003 in the dominant model; odds ratio = 1.36, P=0.018 in the recessive model). During a median of 11 years (inter-quartile range between 5.2 and 12.5 years) of follow-up, neither the total nor the cardiovascular mortality was different among CAD subjects with different genotypes. Using Cox regression analysis, genotypes of rs4977574 still failed to predict cardiovascular mortality (hazard ratio = 1.25, P=0.138 in the dominant model; hazard ratio = 1.05, P=0.729 in the recessive model). Conclusions. The rs4977574 at chromosome 9p21 is associated with presence of CAD in Han Chinese. However, rs4977574 could not predict cardiovascular mortality in these CAD subjects during the eleven-year period of the study