Host defense peptides combined with MTA extract increase the repair in dental pulp cells: in vitro and ex vivo study.

Host Defense Peptides (HDPs) have, in previous studies, been demonstrating antimicrobial, anti-inflammatory, and immunomodulatory capacity, important factors in the repair process. Knowing these characteristics, this article aims to evaluate the potential of HDPs IDR1018 and DJK-6 associated with MTA extract in the repair process of human pulp cells. Antibacterial activity of HDPs, MTA and HDPs combined with MTA in Streptococcus mutans planktonic bacteria and antibiofilm activity was evaluated. Cell toxicity was assayed with MTT and cell morphology was observed by scanning electron microscopy (SEM). Proliferation and migration of pulp cells were evaluated by trypan blue and wound healing assay. Inflammatory and mineralization related genes were evaluated by qPCR (IL-6, TNFRSF, DSPP, TGF-ß). Alkaline phosphatase, phosphate quantification and alizarin red staining were also verified. The assays were performed in technical and biological triplicate (n = 9). Results were submitted for the calculation of the mean and standard deviation. Then, normality verification by Kolmogorov Smirnov test, analyzing one-way ANOVA. Analyses were considered at a 95% significance level, with a p-value < 0.05. Our study demonstrated that HDPs combined with MTA were able to reduce biofilms performed in 24 h and biofilm performed over 7 days S. mutans biofilm (p < 0.05). IDR1018 and MTA, as well as their combination, down-regulated IL-6 expression (p < 0.05). Tested materials were not cytotoxic to pulp cells. IDR1018 induced high cell proliferation and combined with MTA induced high cellular migration rates in 48 h (p < 0.05). Furthermore, the combination of IDR1018 and MTA also induced high expression levels of DSPP, ALP activity, and the production of calcification nodules. So, IDR-1018 and its combination with MTA could assist in pulp-dentine complex repair process in vitro.

Paternal Resistance Training Modulates Calcaneal Tendon Proteome in the Offspring Exposed to High-Fat Diet.

The increase in high-energy dietary intakes is a well-known risk factor for many diseases, and can also negatively impact the tendon. Ancestral lifestyle can mitigate the metabolic harmful effects of offspring exposed to high-fat diet (HF). However, the influence of paternal exercise on molecular pathways associated to offspring tendon remodeling remains to be determined. We investigated the effects of 8 weeks of paternal resistance training (RT) on offspring tendon proteome exposed to standard diet or HF diet. Wistar rats were randomly divided into two groups: sedentary fathers and trained fathers (8 weeks, three times per week, with 8-12 dynamic movements per climb in a stair climbing apparatus). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into four groups (five animals per group): offspring from sedentary fathers were exposed either to control diet (SFO-C), or to high-fat diet (SFO-HF); offspring from trained fathers were exposed to control diet (TFO-C) or to a high-fat diet (TFO-HF). The Nano-LC-MS/MS analysis revealed 383 regulated proteins among offspring groups. HF diet induced a decrease of abundance in tendon proteins related to extracellular matrix organization, transport, immune response and translation. On the other hand, the changes in the offspring tendon proteome in response to paternal RT were more pronounced when the offspring were exposed to HF diet, resulting in positive regulation of proteins essential for the maintenance of tendon integrity. Most of the modulated proteins are associated to biological pathways related to tendon protection and damage recovery, such as extracellular matrix organization and transport. The present study demonstrated that the father's lifestyle could be crucial for tendon homeostasis in the first generation. Our results provide important insights into the molecular mechanisms involved in paternal intergenerational effects and potential protective outcomes of paternal RT.

Extreme Conditioning Program Induced Acute Hypotensive Effects are Independent of the Exercise Session Intensity.

The aim of the study was to determine the acute systolic (SBP) and diastolic (DBP) blood pressure, rating of perceived exertion (RPE) and heart rate (HR) responses following two intense training sessions (24 hours apart). Nine male extreme conditioning program (ECP) practitioners with more than 6 months of experience (age 26.7 ± 6.6 years; body mass 78.8 ± 13.2 kg; body fat 13.5 ± 6.2 %) completed two experimental ECP sessions. Cardiovascular variables were measured before, immediately after and every 15 min during a 45 min recovery following each experimental session. Compared with pre-exercise data, our results showed a SBP decrease at 30 min post exercise session 1 (P≤0.05) and at 45 min following exercise session 2. DBP decreased (P≤0.05) at 15 min and 30 min following exercise session 1 and at 30 min after the exercise session 2, respectively. HR remained significantly higher (P≤0.05) 45 min following the first and second exercise session compared with pre-exercise values. Exercise session 1 induced a higher increase in HR (86 ± 11% of HRmax versus 82 ± 12% of HRmax, p = 0.01) and RPE (8.8 ± 1.2 versus 8.0 ± 1.2, p = 0.02) when compared to exercise session 2. In conclusion, post-exercise hypotension occurs following strenuous exercise sessions, regardless of the session design, which may have an important role in the prevention of cardiovascular diseases.

Endothelial nitric oxide synthase Glu298Asp gene polymorphism influences body composition and biochemical parameters but not the nitric oxide response to eccentric resistance exercise in elderly obese women.

Both endothelial nitric oxide synthase (eNOS) gene polymorphism and nitric oxide (NO) are involved in important cardiovascular, muscular and inflammatory physiological mechanisms during ageing and response to exercise. The aim of this study was to investigate the NO kinetic response following an acute eccentric resistance exercise (ERE) session and the possible effect of the Glu298Asp eNOS gene polymorphism in elderly obese women. Eighty-seven women (age 69·4 ± 6·1 years, body weight 74·9 ± 12·7 kg, height 151·9 ± 6·0 cm and BMI 32·5 ± 5·7 kg m-2 ) completed seven sets of ten eccentric repetitions at 110% of the ten repetitions maximum (10RM). NO concentrations remained elevated up to 48 h following the acute ERE session as compared with baseline, for GG and GT/TT groups (P<0·05), with no differences between genotypes. The GG genotype group had higher body weight, prevalence of obesity (BMI classification - 81% versus 56%), BMI and higher relative muscle strength, while they had significantly lower triglycerides, VLDL and urea concentrations as compared with TT/TG group. In conclusion, NO remains elevated for up to 48 h after an acute ERE session, without genotype interaction. The TT/TG genotype had a negative impact on triglycerides, VLDL and urea concentrations. Thus, T carriers should increase their attention to cardiovascular risk factor and metabolic disorders.

Understanding the responsiveness of nitric oxide to acute eccentric resistance exercise in elderly obese women.

BACKGROUND AND AIM: The aim of the present study was to examine nitrite concentration responses following eccentric resistance exercise (ERE) in elderly obese women. We also investigated the existence of high (HR) and low responders (LR) for nitrite and the possible differences with respect to creatine kinase (CK) response, metabolic and body composition variables. METHODS: Forty-nine elderly obese women completed an ERE session utilizing knee extensor exercise. LR for serum nitrite were defined as a ∆nitrite ≤ 20th percentile or 24.1 µmol/L and HR as a ∆nitrite > 20th percentile. RESULTS: Ten subjects were classified as LR and the remaining as HR (n = 39). The HR group displayed greater nitrite concentration at 0 h, 3 h, 24 h and 48 h following the ERE as compared with the LR (p < 0.05), and CK increased after 24 h and 48 h only for the HR group following the ERE (p < 0.05). Peak nitrite concentration was higher in the HR group versus the LR group (p < 0.05), while there was no difference between groups for pre-exercise nitrite values. The LR group displayed higher (p < 0.05) body fat, cholesterol, LDL and lower upper limb fat-free mass as compared with the HR group. The LR had lower (p < 0.05) upper limb fat-free mass than the HR group. CONCLUSIONS: Elderly obese women classified as HR displayed higher nitrite responses to ERE. Thus, researchers should be aware of the presence of different responsiveness of nitrite to acute exercise to avoid misinterpretation of data and to identify the higher cardiovascular risk factor of those classified as LR. RELEVANCE FOR PATIENTS: The elevated NO up to 48 h following an ERE session may suggest an important protective cardiovascular effect. The higher body fat, cholesterol, LDL and lower upper limb fat-free mass in the LR group might represent a deleterious effect of lower serum levels of nitrite.

Role of exercise intensity on GLUT4 content, aerobic fitness and fasting plasma glucose in type 2 diabetic mice.

Type 2 diabetes mellitus (T2D) results in several metabolic and cardiovascular dysfunctions, clinically characterized by hyperglycaemia due to lower glucose uptake and oxidation. Physical exercise is an effective intervention for glycaemic control. However, the effects of exercising at different intensities have not yet been addressed. The present study analysed the effects of 8 weeks of training performed at different exercise intensities on type 4 glucose transporters (GLUT4) content and glycaemic control of T2D (ob/ob) and non-diabetic mice (ob/OB). The animals were divided into six groups, with four groups being subjected either to low-intensity (ob/obL and ob/OBL: 3% body weight, three times/week/40 min) or high-intensity (ob/obH and ob/OBH: 6% body weight, three times per week per 20 min) swimming training. An incremental swimming test was performed to measure aerobic fitness. After the training intervention period, glycaemia and the content of GLUT4 were quantified. Although both training intensities were beneficial, the high-intensity regimen induced a more significant improvement in GLUT4 levels and glycaemic profile compared with sedentary controls (p < 0.05). Only animals in the high-intensity exercise group improved aerobic fitness. Thus, our study shows that high-intensity training was more effective for increasing GLUT4 content and glycaemia reduction in insulin-resistant mice, perhaps because of a higher metabolic demand imposed by this form of exercise.

Immune Response Profile against Persistent Endodontic Pathogens Candida albicans and Enterococcus faecalis In Vitro.

INTRODUCTION: Persistent microorganisms such as Candida albicans and Enterococcus faecalis might be directly related to endodontic treatment failure. The host response to these microorganisms impairs the reestablishment of intraradicular and periradicular health. METHODS: The present investigation evaluated the expression of inflammatory mediators produced by RAW 264.7 cells in the presence of heat-killed antigens (HK) C. albicans and E. faecalis. Cultures of RAW cells were stimulated with both antigens in the presence or absence of recombinant interferon (rIFN)-γ. Parameters of cell viability, production of nitric oxide (NO), as well as the synthesis of interleukin (IL)-1α, IL-6, IL-10, IL-12, monocyte chemotactic protein-1, and tumor necrosis factor (TNF)-α were analyzed. RESULTS: Results demonstrated that cell viability was especially reduced in antigens and rIFN-γ-stimulated groups. Groups stimulated with HK C. albicans upregulated IL-10 production. Otherwise, the addition of rIFN-γ to HK C. albicans upregulated TNF-α and NO production. Groups stimulated with HK E. faecalis upregulated TNF-α production. HK E. faecalis and rIFN-γ upregulated TNF-α and NO synthesis. The production of other cytokines remained unchanged by all stimuli. CONCLUSIONS: Knowledge regarding the host mechanism of response to microorganisms that perpetuate endodontic infection and the periradicular lesions can contribute to optimization of endodontic therapy. The mentioned inflammatory mediators and virulence factors involved in endodontic failure might guide lesion progression and also be targets in the development of disinfectant and immunomodulatory agents.

Classification of pro-inflammatory status for interleukin-6 affects relative muscle strength in obese elderly women.

BACKGROUND: Obesity, defined by an excess amount of body fat or a percent body fat higher than 30 % for women is a complex chronic disorder with multifactorial etiology and is accompanied by chronic low-grade inflammation, which results in elevated pro-inflammatory cytokines. AIMS: The aim of this study was to compare muscle strength between high and low pro-inflammatory status in obese elderly women and to verify the relationship of IL-6 with muscle strength and fat-free mass. METHODS: Eighty-nine elderly women (age 69.47 ± 6.07 years; body mass 64.70 ± 12.04 kg; height 1.52 ± 0.06 m; body mass index 27.78 ± 4.75 kg/m(2)) were divided into two groups: high and low inflammatory status for IL-6. Lower limb muscle strength was tested using bilateral leg extension with the ten repetitions maximum test, IL-6 was measured by ELISA and body composition by dual-energy X-ray absorptiometry. RESULTS: Women classified from the high pro-inflammatory status presented lower relative muscle strength (P = 0.056) when compared with the low inflammatory status group, with no differences for absolute muscle strength (P = 0.18). There was a significant negative correlation of IL-6 with relative muscle strength (P = 0.03, R = -0.22) and a considerable trend toward significance (P = 0.06, R = -0.19) and negative association with fat-free mass (P = 0.84, R = -0.02). CONCLUSIONS: This study provides insights that a high pro-inflammatory status in sedentary obese elderly women might impair muscle strength and negatively affect fat-free mass. Thus, elderly women classified with high pro-inflammatory status for IL-6 should receive further health care attention to prevent this deleterious condition.

Enhancing of women functional status with metabolic syndrome by cardioprotective and anti-inflammatory effects of combined aerobic and resistance training.

These data describe the effects of combined aerobic plus resistance training (CT) with regards to risk factors of metabolic syndrome (MetS), quality of life, functional capacity, and pro- and anti-inflammatory cytokines in women with MetS. In this context, thirteen women (35.4 ± 6.2 yr) completed 10 weeks of CT consisting of three weekly sessions of ~60 min aerobic training (treadmill at 65-70% of reserve heart rate, 30 min) and resistance training (3 sets of 8-12 repetitions maximum for main muscle groups). Dependent variables were maximum chest press strength; isometric hand-grip strength; 30 s chair stand test; six minute walk test; body mass; body mass index; body adiposity index; waist circumference; systolic (SBP), diastolic and mean blood pressure (MBP); blood glucose; HDL-C; triglycerides; interleukins (IL) 6, 10 and 12, osteoprotegerin (OPG) and serum nitric oxide metabolite (NOx); quality of life (SF-36) and Z-Score of MetS. There was an improvement in muscle strength on chest press (p = 0.009), isometric hand-grip strength (p = 0.03) and 30 s chair stand (p = 0.007). There was a decrease in SBP (p = 0.049), MBP (p = 0.041), Z-Score of MetS (p = 0.046), OPG (0.42 ± 0.26 to 0.38 ± 0.19 ng/mL, p<0.05) and NOx (13.3 ± 2.3 µmol/L to 9.1 ± 2.3 µmol/L; p<0.0005). IL-10 displayed an increase (13.6 ± 7.5 to 17.2 ± 12.3 pg/mL, p < 0.05) after 10 weeks of training. Combined training also increased the perception of physical capacity (p = 0.011). This study endorses CT as an efficient tool to improve blood pressure, functional capacity, quality of life and reduce blood markers of inflammation, which has a clinical relevance in the prevention and treatment of MetS.

Pharmacological potential of exercise and RAS vasoactive peptides for prevention of diseases.

The Renin-Angiotensin-System (RAS) molecular network has been widely studied, especially with attention to angiotensin II, the main effector peptide among RAS. The relation of Ang II to hypertension pathogenesis has led to research being extended to other molecules from the RAS, such as angiotensin III and IV, angiotensin (1-5), and angiotensin (1-9). Moreover, great pharmacologic advances have been made in hypertension treatment by inhibiting renin and angiotensin converting enzymes and blocking the bonding of angiotensin II to its receptor AT1. Thus, RAS molecular signaling and its effect on blood pressure as well as its relationship to renal function and cardiovascular disease are still being investigated. It is a great challenge to fully cover and understand all molecules from the RAS, especially those that interfere with or have vasoactive properties. Some of these targets respond to exercise, stimulating nitric oxide synthesis and endothelial vasodilation. The activation of these specific molecules via exercise is a systematic way of controlling high blood pressure without pharmacological treatment. Angiotensin (1-7) has been focused due to its vasodilation properties and its responses to exercise, improving vascular function. Thus, stimulation of the ACE2/Ang (1-7)/Mas axis has been gaining ground as a prospective clinical means to attenuate cardiovascular diseases such as hypertension by modulating RAS activity. This review focuses on the vasoactive peptides from the RAS, their responses to exercise and possible trends for pharmacological development. In several cases where exercise training is not achievable, cardiovascular drug therapy with vasodilator peptides may possibly be an option.

Acute and chronic effects of resistance exercise on blood pressure in elderly women and the possible influence of ACE I/D polymorphism.

This study investigated the chronic effect of blood pressure (BP) and post-exercise hypotension (PEH) during resistance training (RT) and its relation with the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in hypertensive elderly women. Participants were divided into two groups: an experimental group (EG) with exercise and a control group (CG) without exercise. The EG performed one adaptation month and one repetition maximum load (1RM) test at the end of this period. After the first month, the EG conducted a three-month program of RT at 60%, 70%, and 80% of 1RM, respectively, for each month. The CG was evaluated at the end of each month. Systolic (SBP) and diastolic (DBP) blood pressure (Microlife BP 3AC1-1) were measured, with the subject in a seated position, during an acute session for both GE and CG as follows: every 5 minutes for 20 minutes at pre-exercise rest, immediately after the resistance exercise and control, and every 15 minutes during 1 hour of recovery after exercise and CG. Analysis of covariance showed reduction in SBP and DBP (P ≤ 0.05) rest values after the RT program. PEH was observed only for the EG in acute sessions, for SBP after the second and third months (P ≤ 0.05), and for DBP after the second and fourth months (P ≤ 0.05). No significant differences in main effects and interaction effects between blood pressure and ACE I/D were observed. The occurrence of chronic reduction of blood pressure and PEH through EG may have a protective effect on the cardiovascular system with no ACE I/D polymorphism influence for this population.