Yerba Mate (Ilex paraguariensis) modulates NF-kappaB pathway and AKT expression in the liver of rats fed on a high-fat diet

To investigate the effect of Yerba Mate (YM) aqueous extract intake on the NF-kB pathway and AKT expression in the liver, muscle, and adipose tissue of rats submitted to a high-fat diet (HFD). Male Wistar rats were fed a control (CON) (n?=?24) or a HFD (n?=?24) for 12 weeks. Afterwards, rats received YM daily (1?g/kg body weight) for 4 weeks. Intake of YM aqueous extract reduced body weight gain (p?p?相似文献   

Increased cavernosal relaxation by Phoneutria nigriventer toxin, PnTx2-6, via activation at NO/cGMP signaling

Erectile dysfunction (ED) mechanisms in diabetic patients are multifactorial and often lead to resistance to current therapy. Animal toxins have been used as pharmacological tools to study penile erection. Human accidents involving the venom of Phoneutria nigriventer spider are characterized by priapism. We hypothesize that PnTx2-6 potentiates cavernosal relaxation in diabetic mice by increasing cyclic guanosine monophosphate (cGMP). This effect is neuronal nitric oxide synthase (nNOS) dependent. Cavernosal strips were contracted with phenylephrine (10(-5)?M) and relaxed by electrical field stimulation (20?V, 1-32?Hz) in the presence or absence of PnTx2-6 (10(-8)?M). Cavernosal strips from nNOS- and endothelial nitric oxide synthase (eNOS)-knockout (KO) mice, besides nNOS inhibitor (10(-5)?M), were used to evaluate the role of this enzyme in the potentiation effect evoked by PnTx2-6. Tissue cGMP levels were determined after stimulation with PnTx2-6 in presence or absence of N-nitro-L-arginine methyl ester (L-NAME) (10(-4)?M) and ω-conotoxin GVIA (10(-6)?M), an N-type calcium channel inhibitor. Results showed that PnTx2-6 enhanced cavernosal relaxation in diabetic mice (65%) and eNOS KO mice, but not in nNOS KO mice. The toxin effect in the cavernosal relaxation was abolished by nNOS inhibitor. cGMP levels are increased by PnTx2-6, however, L-NAME abolished this enhancement as well as ω-conotoxin GVIA. We conclude that PnTx2-6 facilitates penile relaxation in diabetic mice through a mechanism dependent on nNOS, probably via increasing nitric oxide/cGMP production.     

The Synergy of ‐260T T CD14 and ‐308GG TNF‐α Genotypes in Survival of Critically Ill Patients

Literature suggests that the analysis of several polymorphic genetic markers is more informative than the analysis of a single polymorphism. In this study, we tested whether the shared inheritance of TLR2 and TLR4 and TNF‐α allelic variants may act in synergy with ‐260C>T CD14 SNP on the outcome from critical conditions. We monitored 524 critically ill patients from South Brazilian, daily from the ICU admission to their discharge from hospital, or death. Our results revealed that TLR2, TLR4 or TNF‐α SNPs alone did not show a significant role in the outcome from critical illness. However, when we performed a combined analysis with the CD14 inheritance, we detected a significant higher survivor rate in ‐260TT CD14/‐308GG TNF‐α individuals (P = 0.037). In the adjusted analysis including the main clinical predictors to mortality, we observed that ‐260TT/‐308GG double‐genotype was a significant protective factor towards survival (P = 0.046). An increased probability for survival of ‐260TT/‐308GG was also observed by ‘pathway genetic load’ analysis (unweighted: P = 0.041; weighted: P = 0.036). When we applied a hazard function analysis with the ‐260TT/‐308GG variable as a discriminating factor, ‐260TT/‐308GG patients group had, in fact, a higher survivor rate (P = 0.024). Connected to the beneficial effect of ‐260TT CD14, the ‐308GG TNF‐α genotype was protective against the reported over expression of TNF‐α caused by ‐308A rare allele. Results support the hypothesis that the interaction between ‐260C>T CD14 and ‐308G>A TNF‐α functional SNPs may be synergistically influencing the outcome of critically ill patients.     

Prevalence of 12-month mental and substance use disorders in sexual minority college students in Mexico

Purpose

Mental health disparities have been documented among sexual minority college students, but there is a dearth of evidence from developing countries. The aim is to estimate the prevalence of 12-month mental and substance use disorders across a range of sexual identities among first-year college students in Mexican universities, and test whether there is an association between sexual identity and disorders and whether the association is moderated by gender.

Method

The University Project for Healthy Students, a web-based survey conducted as part of the World Health Organization’s World Mental Health International College Student initiative, recruited 7874 students from nine Mexican universities in 2016 and 2017. Logistic regressions estimated the association of sexual identity with 12-month major depressive episode, generalized anxiety disorder, panic disorder, alcohol abuse/dependence, and drug abuse/dependence, with interaction terms for gender.

Results

Compared to heterosexual students reporting no same-sex attraction (SSA), heterosexual students with SSA (AORs range 1.77–3.67) and lesbian/gay and bisexual students (AORs range 2.22–5.32) were at a higher risk for several disorders. Asexual students were at higher risk for drug abuse/dependence (AOR = 3.64). Students unsure of their sexual identity were at a higher risk for major depressive episode, panic disorder, and drug abuse/dependence (AORs range 2.25–3.82). Gender differences varied across sexual identity and disorder.

Conclusion

These findings are the first empirical report of sexual minority psychiatric disparities among a college student population from a developing nation and underscore the importance of clinical interventions that address mental health needs among sexual minority college students.

     

Expression of peroxiredoxins I and IV in multiple myeloma: association with immunoglobulin accumulation

B cell malignancies are classified according to the postulated differentiation stage of the originating cell. During differentiation, structural and molecular changes occur to support massive processing of immunoglobulin in the endoplasmic reticulum (ER) of plasma cells at the final stage. When overloaded, the ER generates unfolded proteins and hydrogen peroxide (H₂O₂), which may cause cell death. Peroxiredoxins (Prxs) I and IV belong to a family of proteins able to catalyze peroxide detoxification. Here, we investigated a potential association of these enzymes with immunoglobulin production in B cell neoplasms. Our results demonstrated that the expression of Prx IV was induced as cells became competent to synthesize immunoglobulin light chains, as observed by immunohistochemistry in tissue sections of B cell neoplasms and also by qPCR and Western blotting analyses in malignant B cell lines. Prx I was frequently highly expressed, indicating additional regulatory processes besides ER activity. Results obtained exclusively with myeloma cells have shown that expression of Prxs I and IV, both at mRNA and protein levels, was associated with light chain secretion quantified by ELISA. We suggest that Prxs I and IV may provide survival advantages for terminally differentiated neoplastic B cells by the elimination of H₂O₂ and, in the case of Prx IV, by the conversion of this toxic in a functional agent driving oxidative protein folding in the ER. In this sense, multiple myeloma and lymphomas demonstrated to synthesize immunoglobulin chains may benefit from strategic therapies targeting the adaptive pathway to ER stress, including inhibition of Prxs I and IV activity.     

Different parasite inocula determine the modulation of the immune response and outcome of experimental Trypanosoma cruzi infection

During infection, the host response develops effector mechanisms to combat the parasite. However, this response can become uncontrolled or regulated by mechanisms that modulate the inflammatory reaction. The number of parasites that infects the host, such as trypomastigotes in Chagas disease, may also influence immune activation and disease pathology. We evaluated the inflammation and immune regulation that follows Trypanosoma cruzi infection with low (300), intermediate (3000) or high (30 000) parasite loads. Our results showed that the load of parasite inoculum influenced disease outcome: the higher the number of parasites in the inoculum, the lower were the survival rates. There was a strong association between parasitism and inflammatory infiltrate in the heart and the parasite inoculum determined cytokine interplay in this tissue, as shown by increased interferon‐γ, tumour necrosis factor‐α, interleukin‐17 (IL‐17) and IL‐23 in the 300 and 30 000 inoculum groups, higher IL‐4 and IL‐10 in the intermediate‐inoculum mice, and elevated IL‐6 production in the heart of mice in the 3000 and 30 000 groups. The number of T cells and antigen‐presenting cells was augmented in the infected groups, especially for the splenic CD4⁺ CD25⁺ regulatory T cells expressing CD45RB^low, GITR, PD‐1 and FoxP3 in the group with the highest inoculum. Interestingly, these mice also presented an apparent decrease in CD4⁺ CD25⁺ FoxP3⁺ cells in the cardiac infiltrate, in contrast to the intermediate inoculum group, which showed elevated numbers of these regulatory leucocytes in the heart. Finally, our results demonstrated that parasite load during T. cruzi infection is linked to the response pattern that will result in parasite/inflammation control or tissue damage.     

Incidence and profile of benign epithelial tumors of salivary glands from a single center in Northeast of Brazil

Background Benign tumors of the salivary glands are a group of lesions with varied histopathological and clinical spectrum. The aim was to determine the incidence and clinicopathological characteristics of benign salivary gland neoplasms diagnosed between 2007 and 2016 in a single center located in northeastern Brazil. Material and Methods Records regarding sex, age, anatomical location, histopathological subtype and treatment were retrieved, and data were analyzed using the Stata/IC software (version 12.0). Results There were above 7,100 cases of neoplasms in the head and neck region, of which 403 corresponded to salivary gland neoplasms. Of these, 238 (59%) were benign, being pleomorphic adenoma (PA) the most frequent neoplasm (n=178; 74.8%), followed by Warthin''s tumor (WT) (n=23; 9.7%). Overall, most cases occurred in females (n=136; 57.1%) and age ranged from 11 to 83 years. The parotid gland (n=188; 79%) was the most common anatomical site, and all patients were treated by surgical excision. Of the cases diagnosed as PA, malignant transformation to carcinoma ex-pleomorphic adenoma (CAEXPA) occurred in 7 (3.9%) cases. Conclusions The present study confirmed the clinical and demographic profile of benign salivary gland neoplasms, which contributes to the continuous knowledge of current data about these lesions. Key words:Salivary gland, benign neoplasms, epidemiology.     

The combined use of systemic analgesic/anti-inflammatory drugs and a bioactive topical desensitizer for reduced in-office bleaching sensitivity without jeopardizing the hydrogen peroxide efficacy: a randomized,triple blinded,split-mouth clinical trial

Clinical Oral Investigations - To evaluate the effect of combined systemic administration of paracetamol 500 mg/codeine phosphate 30 mg (PACO) and postoperative topical...