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Background: The risk of cardiovascular disease is correlated with the frequency and control of associated risk factors in diabetes mellitus and may vary according to country. We evaluated risk factors for cardiovascular disease, cardiovascular events, and the use of preventive medications in patients with diabetes mellitus using the Prospective Urban and Rural Epidemiological Türkiye cohort. Methods: Patients with diabetes mellitus versus without diabetes mellitus were compared for risk factors, cardioprotective drugs (angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists, statins, and antiplatelets), and cardiovascular events. The primary outcome was major cardiovascular events (composite of cardiovas-cular death, myocardial infarction, stroke, or heart failure). Results: Among 4041 participants, 549 (13.6%) had diabetes mellitus. The mean age (54.8 +- 8.4 vs. 49.3 +- 9.0 years, P

The Global Capability Framework for Public Relations and Communication Management (Fawkes et at., 2018) is the first international proposal that applies the capability concept to the discipline in order to describe the scope and future potential of a global profession. A global framework with 11 capabilities is the result of an empirical research (Delphi, survey, interviews and focus groups) with more than 1.400 experts, scholars and practitioners, in nine countries of five continents (Argentina, Australia, Canada, Singapore, South Africa, Spain, Sweden, UK and USA). Also, each country has its own capability framework. In this paper it is presented for the first time the specific frameworks, and its comparison, from Argentina and Spain, the only participants' hispanic countries. As a general conclusion, the findings reveal a strong strategic and social orientation of the profession, but there are significant differences that may be explained by different regional contexts. [ABSTRACT FROM AUTHOR]

Phosphodiesterases (PDEs) mediate several physiological activities, and alterations in PDE expressions might cause conflicts between functional and clinical effects. This study clarifies the eventual relationship between the hepatic insulin resistance-associated signaling elements and PDEs together with inflammatory markers and investigates the role of kefir in the treatment.

Objective: Metabolic syndrome (MetS) includes several cardiovascular (CV) risk factors. This study aimed to assess CV risk of MetS, contribution of its components to the risk, and whether MetS provides additional risk beyond its components. Methods: The Prospective Urban Rural Epidemiology (PURE) Turkey cohort included 3933 individuals aged between 35 and 70 years, with a median follow-up of 8.9 years. MetS was diagnosed as the presence of any of the following criteria: high blood pressure, high fasting plasma glucose, abdominal obesity, low HDL-cholesterol, or high triglycerides. The primary outcome was the composite of fatal CV events, non-fatal myocardial infarction, stroke or heart failure, adjusted for age, sex, smoking, family history of CV diseases, and LDL-cholesterol. Results: The primary outcome was more common in the MetS group [178 (9.2%) vs. 70 (3.5%); corresponding incidence rate of 11.3 vs. 4.2 per 1000 person-years; log-rank p

Vitiligo is a multifactorial disorder commonly associated with hypo-/depigmentation in the skin and may influence both children and adults psychologically because of the notable leopard-skin-like appearance. This study was designed to investigate the thiol/disulfide homeostasis in patients with generalized vitiligo and to determine its relationship with some of the demographical characteristics. Seventy-six generalized vitiligo patients and 67 healthy individuals were included in the study. Blood serum native thiol, disulfide and total thiol concentrations, together with some hematological parameters, were determined. Results demonstrated that native and total thiol contents, and their ratios, were significantly lower in vitiligo patients. Disulfide/native thiol and disulfide/total thiol ratios were significantly higher in the patient group. Progressivity of the disease strongly regulated the thiol/disulfide homeostasis in such a way that active vitiligo patients had reduced native and total thiol levels but increased disulfide/native thiol and disulfide/total thiol ratios. Moreover, there was a statistically significant negative correlation between both duration of the vitiligo and native and total thiol contents. As these results clearly demonstrated that thiol/disulfide homeostasis was shifted toward disulfide formation in patients with generalized vitiligo, determining the dynamic nature of thiol/disulfide homeostasis can be used to monitor disease progression.

High dietary fructose intake causes a metabolic disorder and augments the risk of chronic kidney disease most likely due to oxidative stress. Probiotics could have antioxidant, antiinflammatory and immunoregulatory properties. The present study examined the influence of Lactobacillus helveticus and Lactobacillus plantarum supplementation on dietary fructose-induced metabolic changes and renal antioxidant/oxidant status of rats. Male Wistar rats were divided into four groups as follows: control; fructose; fructose plus L. helveticus; fructose plus L. plantarum. Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. The probiotic supplementation was applied by gastric gavage once a day for six weeks. Several metabolic parameters in the plasma, gene and protein expressions of the main antioxidant enzymes in renal tissues of rats were measured. Dietary fructose-induced elevations in plasma insulin, triglyceride, VLDL, creatinine as well as renal urea levels were alleviated after treatment with L. helveticus and L. plantarum. Moreover, L. helveticus and L. plantarum supplementation recovered the changes in renal protein expression level of SOD1, SOD2 and CAT. In conclusion, supplementation with L. helveticus and L. plantarum has an improving effect on specific metabolic parameters and renal antioxidative enzymes in a fructose-induced metabolic disorder.

Phase I-II detoxification and antioxidant enzymes are responsible for the detoxification and elimination of activated carcinogens, acting as important biomarkers for chemoprevention. Among them, cytochrome P450s plays a prominent role in the metabolic activation of xenobiotics. The herb Salicornia freitagii (SF) (Amaranthaceae) is known for its anticancer, antioxidant, antidiabetic and antiinflammatory activities. In this study, we determined the bioactive phenolics in the SF methanol extract and investigated its antiproliferative potential in HT-29 human colon cancer cells. We also investigated the modulation of some phase I and II enzyme (CYP 1A1, 1A2, 2E1, GSTP1 and GPx) mRNA expression and enzymatic activities by the SF extract and its major bioactive phenolic compounds. LC/MS-MS analysis showed that the main phenolic compounds of the methanolic SF extract are vanillic acid (48 μg/100g) and p-coumaric acid (10.8 μg/100g). SF extract, vanillic acid and p-coumaric acid exhibited high antiproliferative activities in HT-29 cells, with IC50 values of 81.79μg/mL, 98.8 μM and 221.6 μM, respectively. The mRNA expression levels of CYP1A2 and CYP2E1 were decreased, while those of GSTP1 and GPx in HT-29 cells were increased after application of either the SF extract or vanillic acid. The SF extract by itself also increased the activities of GPx and GSTP1 enzymes 1.68- and 1.49-fold, respectively. Our data indicate that the SF extract and its major bioactive compound, vanillic acid, could exert a modulatory effect on the expression of enzymes that are involved in xenobiotic activation and detoxification pathways in the gastrointestinal tract. For this reason, SF can be considered as a natural source of chemopreventive agents.

Summary: Background: Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status—wealth and education—differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management. Methods: In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorised as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family. Findings: Recruitment to the study began on Jan 12, 2001, with most participants enrolled between Jan 6, 2005, and Dec 4, 2014. 160 299 (87·9%) of 182 375 participants with baseline data had available follow-up event data and were eligible for inclusion. After exclusion of 6130 (3·8%) participants without complete baseline or follow-up data, 154 169 individuals remained for analysis, from five low-income, 11 middle-income, and four high-income countries. Participants were followed-up for a mean of 7·5 years. Major cardiovascular events were more common among those with low levels of education in all types of country studied, but much more so in low-income countries. After adjustment for wealth and other factors, the HR (low level of education vs high level of education) was 1·23 (95% CI 0·96–1·58) for high-income countries, 1·59 (1·42–1·78) in middle-income countries, and 2·23 (1·79–2·77) in low-income countries (pinteraction

Diabetes mellitus is a chronic inflammatory disease characterized by high blood glucose levels due to the absence of secretion of insulin or its inefficient use in the body. In this study, we investigated how resveratrol administration affects the renal functions and pro-inflammatory signaling pathway components in streptozotocin-induced diabetes in male Wistar rats. Rats were randomly divided into four groups: (1) control/vehicle; (2) control/20 mg/kg resveratrol; (3) diabetic/vehicle; and (4) diabetic/20 mg/kg resveratrol. In addition to renal glucose, lipid, angiopoietin-1 (ANG-1), asymmetric dimethylarginine (ADMA), erythropoietin (EPO), malondialdehyde (MDA) and neutrophil gelatinase-associated lipocalin (NGAL) content, the gene expressions of pro-inflammatory markers, including inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB), nuclear factor (erythroid-derived 2) like-2 (Nrf2), and the protein contents of interleukins-1β,6,8 (IL-1β,6,8) and tumor necrosis factor-α (TNF-α) were analyzed using qRT-PCR and ELISA, respectively. The rats in the diabetes group demonstrated significantly lower terminal body weight and renal ANG-1, but significantly higher renal glucose, cholesterol, triglyceride, ADMA and MDA concentrations. Diabetes triggered inflammation in kidney tissues, reflected as an increase in NGAL level. The renal inflammation observed in the diabetes group was associated with significant upregulation of components of the pro-inflammatory pathway, iNOS, NF-κB, Nrf2, IL-1β, IL-6, IL-8 and TNF-α. To some extent, resveratrol administration reversed the diabetes-induced changes in renal tissues, suggesting that resveratrol partially protected from diabetes-induced renal failure due to its restorative activities in tissue inflammation.

PURPOSEWe aimed to establish the first diagnostic reference levels (DRLs) for computed tomography (CT) examinations in adult and pediatric patients in Turkey and compare these with international DRLs.METHODSCT performance information and examination parameters (for head, chest, high-resolution CT of the chest [HRCT-chest], abdominal, and pelvic protocols) from 1607 hospitals were collected via a survey. Dose length products and effective doses for standard patient sizes were calculated from the reported volume CT dose index (CTDIvol).RESULTSThe median number of protocols reported from the 167 responding hospitals (10% response rate) was 102 across five different age groups. Third quartile CTDIvol values for adult pelvic and all pediatric body protocols were higher than the European Commission standards but were comparable to studies conducted in other countries.CONCLUSIONThe radiation dose indicators for adult patients were similar to those reported in the literature, except for those associated with head protocols. CT protocol optimization is necessary for adult head and pediatric chest, HRCT-chest, abdominal, and pelvic protocols. The findings from this study are recommended for use as national DRLs in Turkey.

OBJECTIVE: Acetylsalicylic acid (ASA) has a half-life of less than 30 minutes in the human body. This study aimed to test whether the effects of a single dose of ASA wane over a 24- hour period due to the daily release of new reactive blood platelets into the bloodstream. METHODS: The study included 30 patients (10 female and 20 male, mean age: 62.8+-9.0). Each took a single dose of 300 mg enteric coated ASA orally. Platelet aggregation was determined using VerifyNow® Aspirin kits immediately prior to intake, and at 12 and 24 hours following intake. Laboratory parameters such as serum CRP and CBC were also examined before ASA intake. Patients were included irrespective of routine ASA and/or clopidogrel use. RESULTS: Aspirin reaction unit (ARU) values were lower than 550 at 24 hours after drug intake in 26 (86.7%) patients. Values lower than 550 indicate therapeutic range of ASA on platelet function. Two (6.7%) patients were found to be responsive to ASA at 12 hours after intake, but unresponsive at 24 hours. Aspirin resistance was found in another 2 (6.7%) patients. CONCLUSION: Although ASA was found to be effective on platelet inhibition over a 24-hour period in most of the patients, there was a considerable number who were resistant to ASA, and who had developed unresponsiveness to ASA by the end of 24 hours. There is evidence in the literature regarding the clinical importance of ASA resistance, but the importance of loss ASA's effectiveness during a day warrants further studies.

Background and Objectives: Hyperglycemia is known to undermine the osteointegration process of implants. In this study, the effects of mangiferin (MF) on the post-implant osteointegration process in a type-II diabetes model were investigated molecularly and morphologically. Materials and Methods: Sprague Dawley male rats were divided into three groups: control, diabetes, and diabetes + MF. All animals were implanted in their tibia bones on day 0. At the end of the 3-month experimental period, the animals' blood and the implant area were isolated. Biochemical measurements were performed on blood samples and micro-CT, qRT-PCR, histological, and immunohistochemical measurements were performed on tibia samples. Results: MF significantly improved the increased glucose, triglyceride-VLDL levels, and liver enzymes due to diabetes. By administering MF to diabetic rats, the osteointegration percentage and bone volume increased while porosity decreased. DKK1 and BMP-2 mRNA expressions and OPN, OCN, and OSN mRNA-protein expressions increased by MF administration in diabetic rats. Additionally, while osteoblast and osteoid surface areas increased with MF, osteoclast and eroded surface areas decreased. Conclusions: The findings of our study indicate that MF will be beneficial to the bone-repairing process and osteointegration, which are impaired by type-II diabetes.

Background and Objectives : PIN1 is overexpressed in several human cancers, including prostate cancer, breast cancer, and oral squamous carcinomas. Juglone (J), derived from walnut, was reported to selectively inhibit PIN1 by modifying its sulfhydryl groups. In this study, the potential effects of juglone, also known as PIN1 inhibitor, on oral cancer and carcinogenesis were investigated at the molecular level. Materials and Methods : 4-Nitroquinoline N-oxide (4-NQO) was used to create an oral cancer model in animals. Wistar rats were divided into five groups: Control, NQO, Juglone, NQO+J, and NQO+J*. The control group received the basal diet and tap water throughout the experiment. The NQO group received 4-NQO for 8 weeks in drinking water only. The Juglone group was administered intraperitoneally in a juglone solution for 10 weeks (1 mg/kg/day). The NQO+J group received 4-NQO in drinking water for 8 weeks, starting 1 week after the cessation of 4-NQO treatment. They were then administered intraperitoneally in a juglone solution for 10 weeks. (1 mg/kg/day). NQO+J* group: received 4 NQO for 8 weeks in drinking water and administered intraperitoneally in a juglone solution for 10 weeks (1 mg/kg/day). They were sacrificed at the end of the 22-week experimental period. The tongue tissues of the rats were isolated after the experiment, morphological changes were investigated by histological examinations, and the molecular apoptotic process was investigated by rt-qPCR and western blot. Results : Histological results indicate that tumors are formed in the tongue tissue with 4-NQO, and juglone treatment largely corrects the epithelial changes that developed with 4-NQO. It has been determined that apoptotic factors p53, Bax, and caspases are induced by the effect of juglone, while antiapoptotic factors such as Bcl-2 are suppressed. However, it was observed that the positive effects were more pronounced in rats given juglone together with 4-NQO. Conclusions : The use of PIN1 inhibitors such as juglone in place of existing therapeutic approaches might be a promising and novel approach to the preservation and treatment of oral cancer and carcinogenesis. However, further research is required to investigate the practical application of such inhibitors.

Background and Objectives: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the autoantibody-mediated destruction of platelets. The treatment of ITP aims to maintain a sufficient platelet count to prevent bleeding. First-line treatment options include corticosteroids and intravenous immunoglobulin (IVIg), while second-line treatments include splenectomy, rituximab and other immunosuppressive agents, and thrombopoietin (TPO) receptor agonists. This study aims to discuss the treatment methods and results from 100 patients with ITP at the Muğla Training and Research Hospital through a pharmacological approach. Materials and Methods: Demographic characteristics, clinical findings, bone marrow aspiration and biopsy results, and treatments and treatment responses at the time of diagnosis of the 100 patients with ITP who were treated and followed up in the period 2015-2023 were evaluated retrospectively. Results: In the third month after treatment, the overall response percentage was 100% in patients who received steroids only and 88% in patients who received IVIg treatment alone or in combination with steroids ( p > 0.05). The most preferred second-line treatments were splenectomy (41%), eltrombopag (26%), and rituximab (10%). Bone marrow biopsy was performed in 54% of patients, where 35.1% showed increased megakaryocytes, 44.4% adequate megakaryocytes, and 14.8% decreased megakaryocytes. It is noted that eltrombopag and rituximab, in particular, yield higher complete remission rates than immunosuppressive drugs. Conclusions: Considering the side effects of immunosuppressive medications, IVIg, splenectomy, and steroid therapy, the use of new agents such as eltrombopag, which are easily tolerated and have a lower risk of side effects, is expected to increase.

The recognition of toxic Al 3+ in foods and biosystems has of great interest to researchers. Herein, a novel cyanobiphenyl-based chemosensor CATH (E)-N'-((4'-cyano-4-hydroxy-[1,1'-biphenyl]-3-yl)methylene)thiophene-2-carbohydrazide was fabricated and shown to recognize Al 3+ in HEPES buffer:EtOH (90:10, v:v, pH = 7.4) by ''lighting-up'' fluorescence sensing. The CATH evidenced high sensitivity (LOD = 13.1 nM) and excellent selectivity to Al 3+ over competing cations. The Job's plot, TOF-MS and theoretical computation studies were performed to probe the binding mechanism of Al 3+ to CATH. Additionally; CATH was successfully utilized to practical applications and employed to recover of Al 3+ from different food samples. More importantly, it was employed to intracellular Al 3+ detection in living cells including THLE2 and HepG2., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Penicillin allergy is a commonly listed medication allergy despite rare overall incidence. Many patients erroneously have this label, which has personal, health, and societal costs. Penicillin allergy delabelling requires an oral challenge, which can be a rate limiting step in the de-labeling process; this is even more relevant with the reduction of in-person visits during the COVID-19 pandemic., Objective: To identify the utility and broader applicability of using a virtually supported platform, initially adopted given COVID-19 restrictions, to expedite penicillin oral provocation challenge and penicillin de-labeling in patients at low to moderate risk of immediate hypersensitivity reaction and based on shared decision making., Methods: Patients in Vancouver catchment area were referred for penicillin allergy and virtually assessed by the consulting allergist between July 2020 and April 2021. Those deemed appropriate for oral challenge based on the allergist consultant were offered the option of a virtual oral provocation challenge to oral amoxicillin in a subsequent virtual visit. Patients who agreed and were consented underwent a virtually supervised oral amoxicillin challenge during the second virtual visit. Findings are summarized in this case series., Results: Twenty-three patients, both adult and pediatric, ranging from no to significant co-morbidities were consented and underwent the virtual challenge. One hundred percent of patients were successful with no reaction after an hour post virtual oral provocation challenge with amoxicillin., Conclusion: Virtual medicine is likely to remain in the allergist's practice. Virtually supported penicillin allergy delabelling, based on shared decision making and risk stratification, presents another pathway for penicillin allergy delabelling., (© 2023. The Author(s).)

Vitiligo is a disease characterized by acquired depigmentation, white macules, and patches on the skin due to the dysfunction of epidermal melanocytes. In this study, we attempt to profile the microRNA (miRNA) expression patterns and predict the potential targets, assessing the biological functions of differentially expressed miRNAs in the blood of generalized vitiligo patients. Peripheral blood samples were taken from all participants, and the expression levels of 89 identified miRNAs were analyzed with real-time quantitative polymerase chain reaction (PCR). The results indicated significant upregulation of six miRNAs and downregulation of 19 miRNAs in the plasma of vitiligo patients. The top three upregulated miRNAs were hsa-miR-451a, hsa-miR-25-3p, and hsa-miR-19a-3p, and the top three downregulated miRNAs were hsa-miR-146a-5p, hsa-miR-940, and hsa-miR-142-3p. Moreover, the miRNA expression profiles of patients with Type 3 and Type 4 phototypes were substantially different in such a way that the patients with Type 3 phototype would be more prone to the emergence of melanoma and cancer. While significant variations in the expression patterns of miRNAs in male and female vitiligo patients were demonstrated, miR-let-7i-5p, miR-19a-3p, miR-25-3p, and miR-451a were commonly upregulated, and miR-142-3p and miR-146a-5p were commonly repressed in both sexes. This study may shed light on the roles of differentially expressed miRNAs in vitiligo patients by examining the miRNA expression patterns and the combined effects of miRNA and their predicted targets., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Dermatology.)

In the present study, we investigated the influence of Lactobacillus plantarum and Lactobacillus helveticus supplementation on lipogenesis, insulin signalling and glucose transporters in liver of high-fructose-fed rats. Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Lactobacillus plantarum and L. helveticus supplementations were performed by gastric gavage once a day during final 6 weeks. Dietary high-fructose increased hepatic weight, lipid accumulation and FASN expression as well as caused a significant reduction in IRS-1 expression, pAKT/total AKT and peNOS/total eNOS ratios, but an elevation in GLUT2 and GLUT5 mRNAs in the liver. Lactobacillus plantarum supplementation decreased hepatic weight, triglyceride content and FASN expression as well as improved IRS-1/AKT/eNOS pathway and GLUT2 expression in the liver of high-fructose-fed rats. However, L. helveticus supplementation exerted a restoring effect on lipid accumulation by decreasing FASN expression, and regulating effect on IRS-1 and GLUT2 expressions.

Aims: Hypertension is one of the major causes of cardiac damage. In this study, the effects of resveratrol supplementation and regular exercise on hypertension-induced cellular stress responses of myocardium were compared., Main Methods: Hypertension was induced in male Wistar rats by deoxycorticosterone-acetate + salt administration for 12 weeks. Resveratrol and regular exercise were applied for the last six weeks. In addition to biochemical and molecular examinations, isoprenaline, phenylephrine and, acetylcholine-mediated contractions and sinus rate were recorded in the isolated cardiac tissues., Key Findings: Resveratrol and regular exercise reduced systolic blood pressure in hypertensive rats. The altered adrenergic and cholinergic responses of the right atrium and left papillary muscles in hypertension were separately improved by resveratrol and regular exercise. Resveratrol and regular exercise decreased plasma and cardiac total antioxidant capacity and, augmented the expression of antioxidant genes in hypertensive rats. While regular exercise restored the increase in p-PERK expression associated with endoplasmic reticulum stress and decrease in mitophagic marker PINK1 expression, resveratrol only ameliorated PINK1 expression in hypertensive rats. Resveratrol and exercise training suppressed hypertension-induced NLRP3 inflammasome activation by reversing the increase in NLRP3, p-NF-κB expression and the mature-IL-1β/pro-IL-1β and cleaved-caspase-1/pro-caspase-1 ratio. Resveratrol and exercise enhanced mRNA expression of caspase-3, bax, and bcl-2 involved in the apoptotic pathway, but attenuated phosphorylation of stress-related mitogenic proteins p38 and JNK induced by hypertension., Significance: Our study demonstrated the protective effect of resveratrol and exercise on hypertension-induced cardiac dysfunction by modulating cellular stress responses including oxidative stress, ER stress, mitophagy, NLRP3 inflammasome-mediated inflammation, and mitogenic activation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

There are limited data on the influence of fructose rich diet on the male reproductive system. Kefir may have health beneficial effects, but its mechanism of action remains mostly unclear. Herein, we investigated the impact of dietary high fructose on tight junction proteins and mitogenic pathways in rat testis as well as their modulation by kefir supplementation. Twenty-two male Wistar rats (4 weeks old) were divided into the following three groups: Control; Fructose; Fructose + Kefir. Fructose was added to drinking water at concentration of 20% and administered to the rats for 15 weeks and kefir was supplemented by gavage once a day during final 6 weeks. Dietary fructose-induced testicular degeneration was associated with the downregulation of the blood-testis barrier proteins, claudin-11 and N-cadherin as well as SIRT1 expression in testicular tissue of rats. However, p38MAPK, p-p38MAPK and p-ERK1/2 levels were increased in testis of fructose-fed rats. Interestingly, JNK1 and p-JNK1 protein levels were decreased following this dietary intervention. Raf1, ERK1/2, and caspase 3 and TUNEL staining of the testis reveal the activation of apoptosis due to fructose intake. Kefir supplementation markedly promoted the expression of claudin-11, SIRT1, JNK1 and p-JNK1 but suppressed testicular mitogenic and apoptotic factors in fructose-fed rats., (© 2021 Wiley-VCH GmbH.)

The aim of the study was to evaluate whether high-fructose corn syrup (HFCS) intake (20% beverages) impacts antioxidative structures and inflammation in the gingival tissue and masseter muscle of rats. Kefir was tested for its potential utility on changes induced by HFCS. Animals were randomly divided into four groups as control, kefir, HFCS, and HFCS plus kefir. HFCS was given as 20% solutions in drinking water while kefir supplementations were given by gastric gavage for 8 weeks. It has been clearly determined that the HFCS diet increased expressions of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α proinflammatory structures via lymphocyte infiltration by suppressing antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase in both tissues. Kefir improved these undesirable changes in rats fed with HFCS. The results of this current study, the first investigation to examine the effects of kefir on masseter muscle and gingival tissue, may provide new access to the restorative effects of kefir consumption on oral health disorders caused by high fructose in the diet. PRACTICAL APPLICATIONS: In this study, at an early age, the effects of kefir on improving inflammation via antioxidation in the masseter muscle and gingival tissue were investigated for the first time. We showed that kefir feeding ameliorates lymphocyte infiltration on the high-fructose corn syrup (HFCS)-induced masseter muscle and gingival tissue inflammation in rats. The mRNA expressions of inflammatory parameters measured in the study were supported by protein measurements via ELISA or immunohistochemistry. In the present study, kefir may play an important role in the antioxidation and inflammation process on the masseter muscle and gingival tissue against HFCS., (© 2021 Wiley Periodicals LLC.)

Herein, an easy assembled colorimetric and ''turn-on'' fluorescent sensor (probe P4SC) based on phenolphthalein was developed for carbonate ion (CO 3 2- ) sensing in a mixture of EtOH/H 2 O (v/v, 80/20, pH = 7, Britton-Robinson buffer) media. The probe P4SC demonstrated high sensitive and selective monitoring toward CO 3 2- over other competitive anions. Interaction of CO 3 2- with the probe P4SC resulted in a significant increment in emission intensity at λ em  = 498 nm (λ ex  = 384 nm) due to the strategy of blocking the photo induced electron transfer (PET) mechanism. 1 H NMR titration and Job's methods, as well as the theoretical study were carried out to support the probable stoichiometry of the reaction (1:2) between P4SC and CO 3 2- . The binding constant of the probe P4SC with CO 3 2- was calculated as 2.56 × 10 10  M -2 . The probe P4SC providing rapid response time (~0.5 min) with a satisfactorily low detection limit (14.7 nM) may be useful as a valuable realistic sensor. The imaging studies on the liver cancer cells (HepG2) shows the great potential of the probe P4SC for the sensation of intracellular CO 3 2- anions. Furthermore, the satisfactory recovery and RSD values obtained for water application confirming that the probe P4SC could be applied to sensing of CO 3 2- ion., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Excess intake of fructose may contribute to the high prevalence of metabolic disorder. In this study, we investigated the effects of kefir supplementation on the intestine-liver-adipose tissue axis in metabolic disorder induced by high-fructose diet in rats to describe mechanistic action and potential therapeutic value of kefir. Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Kefir was administrated by gastric gavage once a day during the final six weeks. Kefir supplementation improved metabolic parameters, including plasma triglyceride and insulin levels; hepatic weight, triglyceride content and fatty degeneration; omental fat mass in fructose-fed rats. Kefir supplementation decreased the ratio of Firmicutes/Bacteroidetes in feces, as well as necrotic degeneration, expression levels of nuclear factor-kappa B (NF-κB), and inducible nitric oxide synthase (iNOS), but increased expression of tight-junction proteins occludin and claudin-1, in the ileum of the fructose-fed rats. Kefir treatment also reduced the mRNA levels of key lipogenic genes sterol regulatory element-binding protein (SREBP-1c) and fatty acid synthase (FASN) together with a decline in expression of tumor necrosis factor-alpha (TNF-α), NF-κB, and glycosylated glycoprotein (CD68) in the liver. Moreover, kefir treatment improved insulin signaling at the level of insulin receptor substrate 1 (IRS-1) and phospho-endothelial nitric oxide synthase (peNOS) as well as fructose transporters (GLUT2 and GLUT5) in the liver, but not in the adipose tissue, of high-fructose-fed rats. Consequently, kefir supplementation suppresses hepatic lipogenesis and inflammatory status, but promotes insulin signaling, in association with a change of the fecal microbiota and attenuation of the intestinal permeability factors in high-fructose-fed rats. Thus, we propose that kefir has favorable effects on the hepatic and intestinal irregularities induced by fructose overconsumption., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We investigated the potential influence of kefir-induced juglone and resveratrol fractions (JRK) against Ehrlich Ascites Carcinoma (EAC) bearing BALB/c male mice. Kefir yeast was grown in the cell culture supplemented with juglone and resveratrol (1:2). After 48 h incubation, JRK solution was applied (0.1 mL/day i.p.) to the EAC-bearing mice throughout five days. Molecular regulatory mechanisms of apoptotic and anti-apoptotic pathway components were evaluated in the plasma of mice and isolated EAC cells with ELISA, qRT-PCR, and immunocytchemical experiments. EAC-induced upregulation in Bcl-2 and downregulation in Caspase-3 were normalized with JRK in the plasma of mice. Additionally, JRK upregulated the expression levels of apoptotic Bax, p53, Caspase-3,8,9, and APAF-1 proteins together with BAX, CASPASE-8, and CASPASE-9 genes in isolated EAC cells. These changes were also associated with decreased expression levels of anti-apoptotic Bcl-2 and Bcl-xl proteins. Immunocytochemical studies also confirmed the activation of apoptotic pathways and repression of anti-apoptotic proteins in EAC cells with JRK treatment. JRK activates apoptotic pathway and inhibits anti-apoptotic genes and proteins in Ehrlich ascites carcinoma- bearing BALB/c mice that could be beneficial in cancer treatment.

Synthesis of the 2-amino-4-phenyl-6- (isocoumarin-3-yl) -3-cyanopyridine (APICP) containing both isocoumarin and pyridine ring in its structure was carried out, and this compound was characterized by ATR-FTIR, 1 H NMR, and 13 C NMR spectral techniques. A fluorescence sensor determining Hg 2+ and Fe 3+ ions in DMSO/HEPES buffer solution (9/1 v/v, 5 μM, pH 7.0) was developed using the synthesized compound, and the detection limits of the sensor with exquisite selectivity were calculated as 8.12 nM and 5.51 nM for Hg 2+ and Fe 3+ ions, respectively. Jobs plot method was used to determine the stoichiometry of APICP-Hg 2+ /Fe 3+ complexes as 2:1 and FT-IR and ESI-MS methods confirmed the results. Besides, cell growth inhibitory potentials of the sensor over HepG2 cells and in vivo fluorescent cell imaging experiments were conducted. Findings revealed the relatively low cytotoxic effects of the synthesized sensor (IC 50 : 0.541 ± 0.039 mM), and it could be utilized as an intracellular imaging agent for the determination of Fe 3+ and Hg 2+ ions in biological systems., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Endoplasmic reticulum stress (ERS) has been shown to play a crucial role in the pathogenesis of hypertension. However, the role and mechanisms of ERS on hypertension-induced cardiac functional and morphological changes remain unclear. In this study, the effect of ERS inhibition with tauroursodeoxycholic acid (TUDCA) on hypertension-induced cardiac remodelling was examined., Methods: Hypertension was induced by deoxycorticosterone-acetate (DOCA) and salt administration in uni-nephrectomized rats for 12 weeks. TUDCA was administered for the last four weeks. Rhythmic activity and contractions of the right atrium and left papillary muscle (LPM) were recorded. In the left ventricle, the expression of various proteins was examined and histopathological evaluation was performed., Key Findings: Hypertension-induced increments in systolic blood pressure and ventricular contractions were reversed by TUDCA. In the hypertensive heart, while expressions of glucose-regulated protein-78 (GRP78), phospho-dsRNA-activated protein kinase-like ER kinase (p-PERK), sarcoplasmic reticulum Ca-ATPase-2 (SERCA2), matrix metalloproteinase-2 (MMP-2) and nuclear NF-κB p65 increased; Bcl-2 (B-cell lymphoma-2) expression decreased and the altered levels of all these markers were restored by TUDCA. In the microscopic examination, TUDCA treatment attenuated hypertension-stimulated cardiac inflammation and fibrosis., Conclusions: These results suggest that ERS inhibition may ameliorate cardiac contractility through improving ERS-associated calcium mishandling, apoptosis, inflammation and fibrosis, thereby offering therapeutic potential in hypertension-induced cardiac dysfunction., (© 2019 Royal Pharmaceutical Society.)

In this study, the effect of liver X receptor (LXR) activation on hypertension-induced cardiac structural and functional alterations was investigated. Hypertension was induced by deoxycorticosterone acetate (DOCA)-salt administration in uninephrectomized rats for 6 weeks. LXR agonist GW3965 (3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-amino]-propoxy}-phenyl)-acetic acid was given for the past week. Rhythmic activity and contractions of the isolated heart tissues were recorded. Biochemical parameters were assessed in ventricular tissue and plasma samples. Cardiac expressions of various proteins were examined, and histopathological evaluation was performed in the left ventricle and liver. GW3965 reduced systolic blood pressure and enhanced noradrenaline-stimulated papillary muscle contraction induced by DOCA-salt + uninephrectomy. Plasma and tissue total antioxidant capacity (TAC) increased and tissue 4-hydroxynonenal (4-HNE) levels decreased in the DOCA-salt group. GW3965 elevated plasma and tissue TAC levels in both of groups. Glucose-regulated protein-78 (GRP78), phospho-dsRNA-activated-protein kinase-like ER kinase (p-PERK), matrix metalloproteinase-2 (MMP-2), and nuclear factor-κB p65 (NF-κB p65) expression was augmented, and inhibitor-κB-α (IκB-α) expression was reduced in hypertensive hearts. The altered levels of all these markers were reversed by GW3965. Also, GW3965 ameliorated DOCA-salt + uninephrectomy-induced cardiac and hepatic inflammation and fibrosis. However, GW3965 unchanged the plasma lipid levels and hepatic balloon degeneration score. These results demonstrated that LXR activation may improve hypertension-induced cardiac changes without undesired effects.

Background and Objectives: The excess consumption of fructose in the diet may cause metabolic syndrome, which is associated with an increased risk of kidney disease. There is limited data on probiotic treatment in high-fructose-induced metabolic syndrome. The present study aims to investigate whether the supplementation of Lactobacillus plantarum (L. plantarum) and Lactobacillus helveticus ( L. helveticus) could provide an improving effect on the renal insulin signaling effectors, inflammatory parameters, and glucose transporters in fructose-fed rats. Materials and Methods: The model of metabolic syndrome in male Wistar rats was produced by fructose, which was given as 20% solution in drinking water for 15 weeks. L. plantarum and L. helveticus supplementations were given by gastric gavage from 10 to 15 weeks of age. Results: High-fructose consumption in rats reduced renal protein expressions of insulin receptor substrate (IRS)-1, protein kinase B (AKT), and endothelial nitric oxide synthase (eNOS), which were improved by L. plantarum and partially by L. helveticus supplementations. Dietary fructose-induced elevations in renal tissue levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, and IL-10, as well as expression of IL-6 mRNA, were attenuated, especially in L. plantarum treated rats. The increased renal expression of sodium-glucose cotransporter-2 (SGLT2), but not that of glucose transporter type-5 (GLUT5), was suppressed by the treatment with L. plantarum . Conclusion: Suppression in insulin signaling pathway together with the induction of inflammatory markers and upregulation of SGLT2 in fructose-fed rats were improved by L. plantarum supplementation. These findings may offer a new approach to the management of renal dysregulation induced by dietary high-fructose.

The increased consumption of high-fructose in diet may contribute to high prevalence of metabolic syndrome in the world. The influence of high-fructose diet on male reproductive system has been poorly documented. In this study, we investigated the effects of dietary high-fructose on the expression of inflammatory cytokines in association with certain testicular proteins and sex hormones in the testis of rats. Fructose was given to the rats as 20% solution (7.8 mg/kg) in drinking water for 15 weeks. Dietary high-fructose caused testicular degeneration, also decreased testicular concentration of testosterone and right testis absolute weight. This dietary intervention increased iNOS and TNF-α mRNAs as well as iNOS, NF-κB, and p-NF-κβ proteins, but decreased IL-10 and IL-6 mRNAs expressions, in testicular samples of rats. Moreover, testicular TNF-α, IL-1β, and iNOS and plasma IL-1β levels were significantly increased in rats fed with fructose. A marked increase in the expression level of IGF-1R protein was considered in testicular tissue of fructose-treated rats. The expression intensities of c-kit, claudin-1, and pan-cadherin were comparable in seminiferous tubules of control and fructose-treated rats. In conclusion, high-fructose intake of rats leads to activation of inflammatory cytokines, which is accompanied by testicular degeneration. These changes could be responsible for hormonal dysfunction with low intra-testicular testosterone level, which could be relevant to male infertility.

Phosphodiesterase enzymes (PDEs) are responsible for the adjustment of cyclic nucleotide levels. Alterations in PDE expressions in different tissues cause conflicts between functional and clinical effects of PDE inhibitors. Therefore, the aim of this study was to investigate the gene and protein expressions and the functional role of PDEs in atrium and ventricle of rat heart. The expressions of PDEs were examined in cardiac intact tissues and enzymatically isolated cells. The effects of PDE1-5 inhibitors (vinpocetine, EHNA, milrinone, rolipram, sildenafil, and IBMX) on basal and isoprenaline-stimulated contractions and sinus rate were recorded in the isolated spontaneously beating right atrium and electrically stimulated left papillary muscles. The mRNA and protein levels of PDEs were significantly different in atrial and ventricular intact tissues and isolated myocytes. Atrial contractions were increased with vinpocetine while suppressed by EHNA, milrinone, rolipram, sildenafil and IBMX. Milrinone, sildenafil and IBMX increased the heart rate whereas vinpocetine caused negative chronotropy. Papillary muscle contractions have been increased only with the vinpocetine and IBMX. Both the expression and the action of PDE-1-5 show atrial and ventricular differences. Therefore, these differences should be taken into account in the experimental or therapeutic approaches of the heart., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Hypertension has complex vascular pathogenesis and therefore the molecular etiology remains poorly elucidated. Endoplasmic reticulum stress (ERS), which is a condition of the unfolded/misfolded protein accumulation in the endoplasmic reticulum, has been defined as a potential target for cardiovascular disease. In the present study, the effects of ERS inhibition on hypertension-induced alterations in the vessels were investigated. In male Wistar albino rats, hypertension was induced through unilateral nephrectomy, deoxycorticosterone-acetate (DOCA) injection (20 mg/kg, twice a week) and 1% NaCl with 0.2% KCI added to drinking water for 12 weeks. An ERS inhibitor, tauroursodeoxycolic acid (TUDCA) (150 mg/kg/day, i.p.), was administered for the final four weeks. ERS inhibition in DOCA-salt induced hypertension was observed to have reduced systolic blood pressure, improved endothelial dysfunction, enhanced plasma nitric oxide (NO) level, reduced protein expressions of phosphorylated-double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (pPERK), 78 kDa glucose-regulated protein (GRP78), Inositol trisphosphate receptor1 (IP 3 R1) and Epidermal growth factor receptor (EGFR), increased expressions of endoplasmic reticulum Ca 2+ -ATPase2 (SERCA2) and B cell lymphoma2 (Bcl2) in vessels. These findings suggest that the beneficial effects of ERS inhibition on hypertension may be related to protection of vessel functions through restoration of endoplasmic reticulum calcium homeostasis, and apoptotic and mitotic pathways., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and objectives: Diabetes mellitus is a disease of insulin deficiency or its inability of usage by the target tissues leading to impairment of carbohydrate, lipid, and protein metabolisms. Resveratrol, having robust anti-inflammatory and anti-oxidant properties, has a high potential to treat or prevent the pathogenesis of diseases. This study was conducted to reveal the relationship between diabetes-induced oxidative stress and tissue inflammation with changes in main enzymatic antioxidants ( cat, sod, gpx, and gst ) and the components of the insulin signaling pathway ( insulin Rβ, irs -1, pi3k, akt , mtor ) in kidney tissues. Additionally, the effects of resveratrol on these parameters were evaluated. Materials and Methods: Male Wistar rats were randomly divided into four groups; (1) control/vehicle; (2) control/20 mg/kg resveratrol; (3) diabetic/vehicle; (4) diabetic/20 mg/kg resveratrol. Gene and protein expressions of antioxidant enzymes and insulin signaling elements were evaluated in renal tissues. Results: Downregulation of antioxidant enzymes' gene expression in the kidney tissues of diabetic rats was demonstrated and this situation was devoted partially to the reduced gene expression of nf κ b . Moreover, the components of renal insulin signaling elements were upregulated at both gene and protein expression levels in diabetic rats, and resveratrol treatment decreased this sensitization towards the control state. Conclusion: Resveratrol partially improved diabetes-induced renal oxidative stress and inflammation due to healing action on renal antioxidant enzymes and insulin signaling pathway components., Competing Interests: The authors declare that there is no conflict of interest associated with this work.

Aims: Liver X receptors (LXRs) play an important role in the regulation of cholesterol, fatty acid and glucose metabolisms together with inflammatory processes. In the present study, the effects of LXR agonist GW3965 on vascular reactivity and expression of functional proteins in DOCA-Salt induced hypertension were examined., Main Methods: Hypertension was induced through unilateral nephrectomy and deoxycorticosterone-acetate (DOCA) injection (20 mg/kg, twice a week) for 6 weeks in male Wistar albino rats (8 weeks old). An LXR agonist GW3965 (10 mg/kg/day, i.p.) was administered to animals for last seven days., Key Findings: GW3965 treatment reduced systolic blood pressures in hypertensive rats. Acetylcholine-induced endothelium-dependent and sodium nitroprusside-induced endothelium-independent vasorelaxations were decreased in hypertensive rats but not affected by GW3965. GW3965 treatment enhanced plasma nitrite levels in normotensive rats. KCl and phenylephrine (Phe)-induced vasocontractions were reduced in hypertensive groups and increased with GW3965 treatment. Decreased sarco/endoplasmic reticulum Ca 2+ -ATPase2 (SERCA2) expression in the hypertensive aorta was not changed by GW3965 treatment. Expression of inositoltrisphosphate receptor1 (IP3R1) was increased by GW3965 in normotensive animals. The nuclear factor kappaB (NF-κB) and tumor necrosis factor alpha (TNF-α) expressions were increased in hypertensive rats and reduced by GW3965 treatment., Significance: The results of study indicate that the LXR agonist, GW3965, exhibited a beneficial effect on increased blood pressure and improved hypertension-induced impairment in contractile activity of vessel and inflammatory markers in vascular tissue. Therefore, these effects of LXR agonists on vessel should be taken into account in experimental or therapeutic approaches to hypertension., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A new colorimetric and fluorescent chemosensor for visual determination of carbonate ions was developed by the microwave assisted solvent free synthesis of 7,8-dihydroxy-3-(4-methylphenyl) coumarin (DHMC). The structural characterization of DHMC was confirmed by microanalysis and spectroscopy methods (MALDI-TOF, FT-IR, 1 H NMR, 13 C NMR, and 2D HETCOR). The binding behaviors of DHMC were investigated towards various anions by UV-vis and fluorescence spectroscopy. DHMC showed a selective and sensitive fluorometric and colorimetric responses towards carbonate ion over other anions. The detection limit of CO 3 2- was found to be 1.03 µM. Moreover, the fluorescence imaging in living cells suggests that DHMC has a great potential in the biological imaging application. It has been demonstrated that DHMC can be used as a rapid and reliable sensor for the determination of carbonate anion in a variety of practical applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The purpose of this study was to determine the effects of resveratrol and regular aerobic exercise on vascular functions and biomarkers related to vessel responsiveness in an age and gender-dependent manner. The study used young (3 months) and old (12 months) male and female Wistar albino rats. Resveratrol was given in the drinking water (0.05 mg/ml; approximately 7.5 mg/kg) for 6 weeks. In the exercise group, all rats performed treadmill running at 20 m/min on a 0° incline, 40 min/day, 3 times a week, for 6 weeks. Acetylcholine-induced, endothelium-dependent and sodium nitroprusside-mediated, endothelium-independent relaxations of rat thoracic aorta and blood levels of biomarkers were separately changed by resveratrol intake and exercise-training in an age and gender-dependent manner. Antioxidant enzymes and eNOS expressions in vessels were elevated by resveratrol and exercise. Resveratrol and exercise enhanced gene expressions of non-selective PDE1, 2, 3 and cAMP selective PDE4 but not cGMP selective PDE5 in the aorta. In addition, the aortic mRNA expression of inflammation markers were altered by resveratrol and exercise-training. The results of the study demonstrated that vessel responsiveness and biomarkers related to vascular functions were altered by resveratrol consumption and exercise-training in an age and gender-dependent manner., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Transient elevations in blood glucose level may lead to changes in vascular function. Herein, we investigated the effects of high-glucose or high-fructose challenge, as well as potential influence of juglone or resveratrol on vascular reactivity, Akt/eNOS, and insulin signaling effectors in rat aorta. Aortic segments of rats were incubated with high glucose (30 mmol/L) or high fructose (2 mmol/L) in the absence and presence of juglone (5 μmol/L) or resveratrol (10 μmol/L). Acute high-glucose incubation markedly decreased acetylcholine-induced relaxation, which is further inhibited by juglone, but ameliorated by resveratrol. Incubation with high glucose caused significant reduction in pAkt/total Akt and peNOS/total eNOS ratios, as well as in the expression of some genes involved in insulin signaling. Juglone produced a further impairment, whereas resveratrol resulted in an improvement on the expression profiles of these proteins and genes. Acute exposure of aortic segments to high glucose causes a reduction in acetylcholine-induced relaxation in association with suppression of Akt/eNOS pathway, as well as several genes in insulin signaling pathway. Juglone and resveratrol have opposite actions on vascular relaxation and the above signaling targets. These findings could be relevant for the treatment of hyperglycemia-induced vascular complications.

Purpose: Relatively little is known about gender-dependent susceptibility to hepatic injury induced by nutritional factors. In the current study, we investigated dietary fructose-induced hepatic degeneration and roles of endothelial nitric oxide synthase (eNOS), insulin receptor (IRβ) and substrate-1 (IRS-1) expressions in association with inflammatory markers in male and female rats. Moreover, we examined potential effect of resveratrol on fructose-induced changes. Methods: Male and female rats were divided into 4 groups as control, resveratrol, fructose and resveratrol plus fructose. All rats were fed with a standard diet with or without resveratrol (500 mg/kg). Fructose was given as 10% in drinking waterfor 24 weeks. Results: Long-term dietary fructose caused parenchymal degeneration and hyperemia in association with impaired eNOS mRNA/protein expressions in liver of male and female rats. This dietary intervention also led to increases in hepatic triglyceride content, TNFα and IL-1β levels in both genders. Gender-related differences to consequence of fructose consumption were not obvious. Resveratrol supplementation markedly attenuated hepatic degeneration, hyperemia and triglyceride content in association with reduced TNFα and IL-1β levels, but enhanced IRβ mRNA and IRS-1 protein, in male and female rats upon fructose feeding. Conclusion: Long-term dietary fructose causes hepatic degeneration possibly via a decrease in eNOS, but increase in TNFα and IL-1β, in both genders. Resveratrol supplementation improved fructose-induced hepatic injury., (© Georg Thieme Verlag KG Stuttgart · New York.)

Context: Oxidative stress has been implicated in the progression of pathogenesis in diabetes mellitus and leads to a variety of deformations in the central nervous system. Recent studies have provided several insights on therapeutic uses of resveratrol in diabetic complications., Objective: The present study determines if resveratrol ameliorates oxidative stress and molecular changes in the brain frontal cortex of streptozotocin-induced diabetic rats., Materials and Methods: Rats were divided into four groups: control, diabetic, resveratrol-treated control, and resveratrol-treated diabetic. After diabetes induction, resveratrol (20 mg/kg) was given intraperitoneally once daily for 4 weeks. In addition to enzymatic activities, gene and protein expression of brain antioxidant enzymes were utilized by qRT-PCR and Western blot, respectively., Results: The results indicated a significant elevation in total oxidant species (1.22-fold) and malonedialdehyde (1.38-fold) contents in diabetic rat brain cortex tissues. In addition, significant augmentation in the activities of catalase (1.38-fold) and superoxide dismutase (3-fold) was witnessed with the gene and protein expression levels reflecting a transcriptional regulation. Resveratrol treatment significantly normalized diabetic malonedialdehyde and oxidized glutathione levels and strengthens the action of all antioxidant enzymes. Recovery of the diabetes-associated changes reflects the reduction of oxidative conditions by resveratrol and reveals the decrease in the requirement for the activation of antioxidant defense systems in the brain tissues of diabetic rats., Discussion and Conclusion: Potent antioxidant and neuroprotective properties of resveratrol against diabetes-induced oxidative damage were demonstrated and the results support the conduct of new studies searching for the molecular mechanism of diabetes-induced changes in brain tissues.

Background and Objective: Inflammatory bowel disease (IBD) encompasses 2 disorders of unknown etiology: Crohn disease (CD) and ulcerative colitis (UC). There has been a continuous search for markers for disease activity. Eosinophils are granulocytic leukocytes that are implicated in the pathogenesis of IBD. The aim of this study was to examine the prevalence and significance of peripheral eosinophilia (PE) at diagnosis in children with IBD., Methods: A comprehensive chart review of all children with diagnosed as having IBD between January 2006 and August 2014 was performed. Patients with PE at diagnosis were compared with those without in relation to disease clinical activity and disease course., Results: A total of 109 children (mean age 14.6 ± 2.77, range 4.5-17.9 years, 55 boys) with IBD (68 with CD and 41 with UC) who were studied for a mean duration of 2.82 ± 1.89 (range 0.1-9.2 years) were identified. At diagnosis, 44 (40.4%) children had PE, which was more prevalent in patients with UC compared with those with CD (61.3% vs 36.3%, P < 0.05). At diagnosis, PE was more common in patients with high eosinophilic count in colonic biopsy samples (P < 0.01) and was significantly associated with disease activity as indicated by Pediatric CD Activity Index for children with CD (P < 0.05), Pediatric UC Activity Index for children with UC (P < 0.01)., Conclusions: PE is a common finding at diagnosis in children with IBD especially in those with UC. Patients with PE at diagnosis are more likely to present with higher clinical activity indices. PE is associated with more eosinophils in colonic biopsy samples.