Ganoderma lucidum dry extract supplementation modulates T lymphocyte function in older women.

Ganoderma lucidum (a mushroom used in traditional Chinese medicine) compounds may attenuate aging-related physiological changes and restore normal immunity. However, studies on the physiological effects of Ganoderma lucidum dry extract food supplements are few. Therefore, here, we aimed to investigate the effects of Ganoderma lucidum dry extract food supplement on the lymphocyte function of older women. This was a double-blind clinical trial (n = 60) with a final 39 older volunteers, divided into two groups, Ganoderma lucidum (n = 23) and placebo (n = 16). The Ganoderma lucidum group received 2,000 mg/day of Ganoderma lucidum dry extract for 8 weeks. We used flow cytometry to determine the lymphocyte profile. CD4+ lymphocyte gene expression was evaluated by real-time PCR. We observed that in the Ganoderma lucidum group, concanavalin A (ConA) stimulation increased lymphocyte proliferation. Further, we observed an increase in expression of FOXP3, TGF-ß, IL-10, IL-6, RORγ, GATA-3, and IFN-γ genes in the Ganoderma lucidum group. Furthermore, in the Ganoderma lucidum group, ionomycin and PMA stimulation led to decrease in Th17+ cells and increase in Th2+ cells. Thus, in older women, Ganoderma lucidum regulates T lymphocyte function leading to a predominant anti-inflammatory action but does not induce T lymphocyte proliferation through CD28 signaling pathway.

Essential metabolism required for T and B lymphocyte functions: an update.

Lymphocytes act as regulatory and effector cells in inflammation and infection situations. A metabolic switch towards glycolytic metabolism predominance occurs during T lymphocyte differentiation to inflammatory phenotypes (Th1 and Th17 cells). Maturation of T regulatory cells, however, may require activation of oxidative pathways. Metabolic transitions also occur in different maturation stages and activation of B lymphocytes. Under activation, B lymphocytes undergo cell growth and proliferation, associated with increased macromolecule synthesis. The B lymphocyte response to an antigen challenge requires an increased adenosine triphosphate (ATP) supply derived mainly through glycolytic metabolism. After stimulation, B lymphocytes increase glucose uptake, but they do not accumulate glycolytic intermediates, probably due to an increase in various metabolic pathway 'end product' formation. Activated B lymphocytes are associated with increased utilization of pyrimidines and purines for RNA synthesis and fatty acid oxidation. The generation of plasmablasts and plasma cells from B lymphocytes is crucial for antibody production. Antibody production and secretion require increased glucose consumption since 90% of consumed glucose is needed for antibody glycosylation. This review describes critical aspects of lymphocyte metabolism and functional interplay during activation. We discuss the primary fuels for the metabolism of lymphocytes and the particularities of T and B cell metabolism, including the differentiation of lymphocytes, stages of development of B cells, and the production of antibodies.

Green tea beneficial effects involve changes in the profile of immune cells in the adipose tissue of obese mice.

PURPOSE: During obesity, the adipose tissue is usually infiltrated by immune cells which are related to hallmarks of obesity such as systemic inflammation and insulin resistance (IR). Green tea (GT) has been widely studied for its anti-inflammatory actions, including the modulation in the proliferation and activity of immune cells, in addition to preventing cardiovascular and metabolic diseases. METHODS: The aim of the present study was to analyze the population of immune cells present in the subcutaneous and epididymal white adipose tissue (WAT) of mice kept at thermoneutrality (TN) and fed with a high-fat diet (HFD) for 16 weeks, supplemented or not with GT extract (500 mg/kg/12 weeks). RESULTS: The HFD in association with TN has induced chronic inflammation, and IR in parallel with changes in the profile of immune cells in the subcutaneous and epidydimal WAT, increasing pro-inflammatory cytokines release, inflammatory cells infiltration, and fibrotic aspects in WAT. On the other hand, GT prevented body weight gain, in addition to avoiding IR and inflammation, and the consequent tissue fibrosis, maintaining a lower concentration of cytokines and a profile of immune cells similar to the control mice, preventing the harmful modulations induced by both HFD and TN. CONCLUSIONS: GT beneficial effects in WAT abrogated the deleterious effects triggered by HFD and TN, maintaining all immune cells and fibrotic markers at the same level as in lean mice. These results place WAT immune cells population as a potential target of GT action, also highlighting the positive effects of GT in obese mice housed at TN.

Early Signs of Inflammation With Mild Oxidative Stress in Mixed Martial Arts Athletes After Simulated Combat.

ABSTRACT: Gomes-Santos, JAF, Lambertucci, RH, Vardaris, CV, Passos, MEP, Silva-Junior, EP, Hatanaka, E, Gorjão, R, McAnulty, SR, Souza-Junior, TP, and Barros, MP. Early signs of inflammation with mild oxidative stress in Mixed Martial Arts athletes after simulated combat. J Strength Cond Res 36(1): 180-186, 2022-Combat sports involve a combination of strenuous physical activity, usually at the anaerobic threshold, followed by intermittent low-intensity recovery periods for energy re-establishment. Oxidative stress and inflammation are inevitable exercise-related processes that could drastically affect athletic performance and practitioners' health, unless efficiently controlled during and after physical activities. This study aims to measure oxidative stress and inflammation biomarkers in the plasma of 12 top ranked professional Mixed Martial Arts (MMAs) athletes before and after simulated combats under official rules (pre-post study). Our results show that the athletes exhibited mild oxidative imbalances in plasma, evidenced by significant (p < 0.01) higher contents of both reduced (+7.3%) and oxidized glutathione (+28%), uric acid (+21%), and "free" iron (+21%) after combat, whereas variation tendencies (0.05 < p < 0.01) were observed in the antioxidant capacity in plasma (-40%), and SOD (-27%) or GPX (+20%) antioxidant activities in erythrocytes. However, a clear pro-inflammatory state was detected by increases in circulating cytokines IL-6 (+6,020%), IL-1ß (+4,357%), and tumor necrosis factor alpha (+63%), and by an abrupt drop of the anti-inflammatory cytokine IL-10 (-98%). A significant correlation was observed between pre-post variations of IL-6 and GSH/GSSG ratio in plasma (p < 0.0001), which reinforces the integration between oxidative stress and inflammation during MMA combats. Considering metabolic and mechanical stresses (imposed by combat techniques, e.g., punches and joint locks), this study indicates pre-existing inflammation, although minor oxidative stress, in MMA professionals after combat.

Updating futsal physiology, immune system, and performance.

Futsal promotes stress by handling the ball, physical contact, and exhaustive muscle contractions, elevating the risks for injury, oxidative stress, and inflammation after a training session or a match. In this review, we critically evaluate the more recent advances in the performance and health of futsal players. We searched the effects of futsal on performance, physiological parameters, muscle injury, inflammation, and oxidative stress. Although the stressful factors apply to all futsal players, goalkeepers require special attention during the competition and the recovery phase. We also show that the FIFA injury prevention programme, called The 11+, is effective in improving athletic performance and avoiding injury in futsal players. Research with different training durations and intensities and a wider range of studies involving oxidative stress, inflammation, and physiological mechanisms are of interest to design a more precise map of the biochemical regulation of training load and competition season in futsal.

Host cell glutamine metabolism as a potential antiviral target.

A virus minimally contains a nucleic acid genome packaged by a protein coat. The genome and capsid together are known as the nucleocapsid, which has an envelope containing a lipid bilayer (mainly phospholipids) originating from host cell membranes. The viral envelope has transmembrane proteins that are usually glycoproteins. The proteins in the envelope bind to host cell receptors, promoting membrane fusion and viral entry into the cell. Virus-infected host cells exhibit marked increases in glutamine utilization and metabolism. Glutamine metabolism generates ATP and precursors for the synthesis of macromolecules to assemble progeny viruses. Some compounds derived from glutamine are used in the synthesis of purines and pyrimidines. These latter compounds are precursors for the synthesis of nucleotides. Inhibitors of glutamine transport and metabolism are potential candidate antiviral drugs. Glutamine is also an essential nutrient for the functions of leukocytes (lymphocyte, macrophage, and neutrophil), including those in virus-infected patients. The increased glutamine requirement for immune cell functions occurs concomitantly with the high glutamine utilization by host cells in virus-infected patients. The development of antiviral drugs that target glutamine metabolism must then be specifically directed at virus-infected host cells to avoid negative effects on immune functions. Therefore, the aim of this review was to describe the landscape of cellular glutamine metabolism to search for potential candidates to inhibit glutamine transport or glutamine metabolism.

Physical exercise increases global and gene-specific (interleukin-17 and interferon-γ) DNA methylation in lymphocytes from aged women.

NEW FINDINGS: What is the central question of this study? Is lymphocyte DNA methylation differentially modulated by resistance training and aerobic exercise in older women? What is the main finding and its importance? The practice of resistance training led to an increased global DNA methylation in lymphocytes. The exercise-induced increase of inflammatory genes methylation may be associated with immune function impairment during ageing. ABSTRACT: Ageing-induced increase in inflammatory gene expression through a reduction in DNA methylation might contribute to chronic diseases. Regular physical exercise practices, in turn, are associated with a decrease in the incidence of inflammatory diseases. We herein evaluated the effects of three exercise modalities on lymphocyte global and gene-specific (interferon γ (IFN-γ) and interleukin 17A (IL-17A) DNA methylation in aged women (68 ± 7.5 years). This cross-sectional study included 86 women, divided into four groups according to the physical exercise practice: 20 were practicing resistance training (RT); 24 were practicing water aerobics exercise (W); 22 were practicing water aerobics and resistance exercise (RWT), and 20 did not practice any physical exercise (CON). We evaluated volunteer functional capability using the Timed Up and Go (TUG) test, global lymphocyte DNA methylation by enzyme-linked immunosorbent assay, IFN-γ and IL-17A methylation by qPCR and CD4+ IFN-γ+ and CD4+ IL-17+ cell percentage by flow cytometry. The three physically exercised groups performed functional capability tests in a shorter period and showed a higher global lymphocyte DNA methylation and methylated CpGs of IL-17A and IFN-γ promoter regions than the control group. The practice of resistance training (RT and RWT groups) lead to high global DNA methylation. The combination of resistance training and aerobic exercise led to the increase of lymphocyte IL-17A and IFN-γ gene methylation induced by each separately. However, the percentage of IFN-γ+ and IL-17+ cells was lower only in the RT group. The exercise-induced increase of inflammatory-gene methylation may be associated with gene expression changes and immune function impairment during ageing.

COVID-19 Pandemic in Brazil: History, Characteristics, and Evolution.

This chapter describes the eruption and spread of the SARS-COV-2 virus throughout Brazil. We also describe the governmental measures used to combat the virus, the regional influences impacting viral spreading, and the prevalence of the disease in different Brazilian subpopulations. It is hoped that such information will contribute to the control of the virus and help to prepare the region for future pandemics.

Recreational Dance Practice Modulates Lymphocyte Profile and Function in Diabetic Women.

This study aimed to investigate the impact of a 16-week dance-based aerobic exercise program on lymphocyte function in healthy and type 2 diabetes mellitus (T2DM) women. We enrolled 23 women: 11 with T2DM and 12 non-diabetic controls. Initially, we performed anthropometry and body composition measurements, afterwards, plasma levels of C-reactive protein, lipids, and glucose were determined. We used flow cytometry to measure the CD25 and CD28 expression in circulating lymphocytes, T-regulatory (Treg) cell percentage, lymphocyte proliferation, and cytokines released by cultured lymphocytes. The T2DM group had a lower proportion of CD28+ cells and a higher percentage of Treg lymphocytes and proliferative capacity at the baseline compared with the control group. After 16 weeks of the program, differences in lymphocytes between the T2DM and the control groups disappeared. The dance program promoted IL-10 increase in both groups. We found decreased IL-4, IL-2, and IL-6 secretion in lymphocytes from the control group and increased IL-17 secretion and IL-10/IL-17 ratio in the T2DM group after the program. The program promoted marked changes in lymphocytes in diabetic women, leading to a balance between the different profiles.

The Critical Role of Cell Metabolism for Essential Neutrophil Functions.

Neutrophils were traditionally considered as short-lived cells with abundant secretory and protein synthetic activity. Recent studies, however, indicate neutrophils are in reality a heterogeneous population of cells. Neutrophils differentiate from pluripotent stem cells in the bone marrow, and can further mature in the blood stream and can have different phenotypes in health and disease conditions. Neutrophils undergo primary functions such as phagocytosis, production of reactive oxygen species (ROS), release of lipid mediators and inflammatory proteins (mainly cytokines), and apoptosis. Neutrophils stimulate other neutrophils and trigger a cascade of immune and inflammatory responses. The underpinning intracellular metabolisms that support these neutrophil functions are herein reported. It has been known for many decades that neutrophils utilize glucose as a primary fuel and produce lactate as an end product of glycolysis. Neutrophils metabolize glucose through glycolysis and the pentose- phosphate pathway (PPP). Mitochondrial glucose oxidation is very low. The PPP provides the reduced nicotinamide adenine dinucleotide phosphate (NADPH) for the NADPH-oxidase (NOX) complex activity to produce superoxide from oxygen. These cells also utilize glutamine and fatty acids to produce the required adenosine triphosphate (ATP) and precursors for the synthesis of molecules that trigger functional outcomes. Neutrophils obtained from rat intraperitoneal cavity and incubate for 1 hour at 37°C metabolize glutamine at higher rate than that of glucose. Glutamine delays neutrophil apoptosis and maintains optimal NOX activity for superoxide production. Under limited glucose provision, neutrophils move to fatty acid oxidation (FAO) to obtain the required energy for the cell function. FAO is mainly associated with neutrophil differentiation and maturation. Hypoxia, hormonal dysfunction, and physical exercise markedly change neutrophil metabolism. It is now become clear that neutrophil metabolism underlies the heterogeneity of neutrophil phenotypes and should be intense focus of investigation.

Dance Training Improves Cytokine Secretion and Viability of Neutrophils in Diabetic Patients.

BACKGROUND: Evidence suggests that exercise improves neutrophil function. The decreased functional longevity of neutrophils and their increased clearance from infectious sites contribute to the increased susceptibility to infection and severity of infection observed in patients with diabetes. OBJECTIVE: Herein, we investigated the effects of a dance program on neutrophil number, function, and death in type 2 diabetes mellitus (T2DM) patients and healthy volunteers. METHODS: Ten patients with T2DM and twelve healthy individuals participated in a moderate-intensity dance training program for 4 months. The plasma levels of leptin, free fatty acids (FFAs), tumour necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-1ß (IL-1ß), and interleukin-1 receptor antagonist (IL-1ra); neutrophil counts; extent of DNA fragmentation; cell membrane integrity; and production of TNF-α, interleukin-8 (IL-8), interleukin-6 (IL-6), and IL-1ß in neutrophils were measured before and after training. RESULTS: Training reduced plasma levels of TNF-α (1.9-fold in controls and 2.2-fold in patients with T2DM) and CRP (1.4-fold in controls and 3.4-fold in patients with T2DM). IL-1ra levels were higher in the control group (2.2-fold) after training. After training, neutrophil DNA fragmentation was decreased in patients with T2DM (90%), while the number of neutrophils increased (70% in controls and 1.1-fold in patients with T2DM). CONCLUSION: Dance training is a nonpharmacological strategy to reduce inflammation and improve neutrophil clearance in patients with T2DM.

Overweight/obese children are associated with lower caries experience than normal-weight children/adolescents.

AIM: To compare (a) enamel carious (EC) and dentin carious (DC) lesions and (b) caries risk, between normal-weight (NW) and overweight/obese (OW) children/adolescents. DESIGN: In this cross-sectional study, 91 participants aged 6-12 years were classified according to the body mass index (BMI): NW (n = 50) and OW (n = 41). Caries experience was evaluated using the International Caries Detection and Assessment System (ICDAS) with two thresholds: "EC/DC" (ICDAS 1-3/4-6) and "DC" (ICDAS 4-6). Caries risk was determined by the Caries Management by Risk Assessment (CAMBRA) system. A logistic regression analysis was performed to determine the association among OW, caries thresholds, and caries risk. RESULTS: Caries experience was similar for both groups at the "EC/DC" threshold (P = .477) and higher for the NW group at the "DC" threshold (P = .009). For CAMBRA, caries risk classification was similar for both groups (P = .082). The logistic regression showed the OW group was less likely to exhibit radiographically visible proximal carious lesions (odds ratio [OR] of 0.330, P = .019), thick biofilm visible on the tooth surface (OR = 0.360, P = .019), high caries risk (OR = 0.367, P = .039), and moderate-to-high caries levels (OR = 0.190, P = .022). CONCLUSION: OW children/adolescents had lower caries experience, at both ICDAS thresholds, and lower caries risk, compared to NW children/adolescents.

Atopy in Elite Endurance Athletes.

OBJECTIVE: To assess the frequency of atopy (specific IgE levels), to evaluate the allergic symptoms using the Allergy Questionnaire for Athletes (AQUA), and to determine whether atopy is associated with allergic symptoms in elite endurance athletes. DESIGN: Cross-sectional study. SETTING: Assessments were performed at Hospital das Clinicas-São Paulo University Medical School. PARTICIPANTS: Fifty-nine elite endurance athletes (triathletes and runners). MAIN OUTCOME MEASURES: Allergic symptoms were assessed by a validated self-report AQUA questionnaire and atopy by specific IgE level. RESULTS: The frequency of atopy (specific IgE to at least one inhalant allergen) and allergic symptoms was 57.6% and 54.2%, respectively. In addition, no association was observed between atopy and allergic symptoms. CONCLUSIONS: A possible implication from our results is that atopy screening in elite athletes should be performed using AQUA questionnaire and measuring specific IgE simultaneously.

Immune and Inflammatory Response in Atopic Elite Endurance Athletes.

The present study aimed to compare the immune and inflammatory responses between atopic (n=20) and non-atopic (n=39) elite endurance athletes. Fifty-nine elite runners and triathletes were assessed for the following measurements: Th1, Th2 and lymphocyte phenotyping and plasma levels of cortisol, chemokines, inflammatory cytokines and specific immunoglobulin E (IgE). Levels of salivary IgA, allergic symptoms and training data were also evaluated. No difference was observed in baseline lymphocyte levels. However, the Th1 lymphocytes of atopic athletes presented a lower response after activation. In contrast to this result, levels of salivary IgA and CXCL9 chemokine were higher in the atopic athletes. It was observed that the volume of training per week was linearly associated with Th1 levels, allergic symptoms and IgE levels. In addition, linear multiple regression analysis demonstrated that the volume of training was the only factor associated with allergic symptoms in atopic athletes (r=0.53; p=0.04). These results suggest that compared to non-atopic athletes, atopic athletes present a reduced Th1 response and higher levels of salivary IgA. Training volume is associated with the immune response and allergic symptoms, which suggests that they may play a role in the atopy in elite endurance athletes.

Inflammatory markers in saliva as indicators of gingival inflammation in cerebral palsy children with and without cervical motor control.

AIM: To evaluate the relation among gingival inflammation, salivary osmolality, levels of IL-1ß, IL-6, IL-8, TNF-α, and s-IgA concentrations in children with spastic CP with or without cervical motor control in a cross-sectional study. DESIGN: Unstimulated whole saliva and the gingival index were collected in 37 and 34 CP children with and without cervical motor control, respectively. The data were dichotomized as follows: (=0) absence of gingival inflammation and (≥0.1) presence of gingival inflammation. RESULTS: The group without cervical control presented statistically higher mean values of salivary osmolality, s-IgA, and cytokines. In addition, statistically positive correlation between the gingival index and salivary cytokines was observed in the group with cervical control. Salivary osmolality, salivary cytokines, and s-IgA from both groups presented a significant positive correlation. Significant differences (P = 0.00336) in the values of salivary osmolality were observed between the CP individuals with (93.9 ± 32.7) and without gingival inflammation (74.4 ± 16.6). ROC analysis was performed, and values of salivary osmolality >80 indicated a sensitivity of 0.54 and a specificity of 0.79. CONCLUSIONS: Children without cervical motor control presented a more pronounced oral inflammatory status that was characterized by higher levels of cytokines.

Regulation of Gene Expression by Exercise-Related Micrornas.

Gene expression control by microRNAs (miRs) is an important mechanism for maintenance of cellular homeostasis in physiological and pathological conditions as well as in response to different stimuli including nutritional factors and exercise. MiRs are involved in regulation of several processes such as growth and development, fuel metabolism, insulin secretion, immune function, miocardium remodeling, cell proliferation, differenciation, survival, and death. These molecules have also been proposed to be potential biomarkers and/or therapeutical targets in obesity, type 2 diabetes mellitus, cardiovascular diseases, metabolic syndrome, and cancer. MiRs are released by most cells and potentially act on intercellular communication to borderer or distant cells. Various studies have been performed to elucidate the involvement of miRs in exercise-induced effects. The aims of this review are: 1) to bring up the main advances for the comprehension of the mechanisms of action of miRs; 2) to present the main results on miR involvement in physical exercise; 3) to discuss the physiological effects of miRs modified by exercise. The state of the art and the perspectives on miRs associated with physical exercise will be presented. Thus, this review is important for updating recent advances and driving further strategies and studies on the exercise-related miR research.

Chronic inflammation and neutrophil activation as possible causes of joint diseases in ballet dancers.

UNLABELLED: Herein, we investigated the effects of a ballet class on the kinetic profiles of creatine kinase (CK) and lactate dehydrogenase (LDH) activities, cytokines, complement component 3 (C3), and the concentrations of immunoglobulin (Ig), IgA and IgM, in ballerinas. We also verified neutrophil death and ROS release. Blood samples were taken from 13 dancers before, immediately after, and 18 hours after a ballet class. The ballet class increased the plasma activities of CK-total (2.0-fold) immediately after class, while the activities of CK-cardiac muscle (1.0-fold) and LDH (3.0-fold) were observed to increase 18 hours after the class. Levels of the TNF-α , IL-1ß, IgG, and IgA were not affected under the study conditions. The exercise was found to induce neutrophil apoptosis (6.0-fold) 18 hours after the ballet class. Additionally, immediately after the ballet class, the neutrophils from the ballerinas were found to be less responsive to PMA stimulus. CONCLUSION: Ballet class was found to result in inflammation in dancers. The inflammation caused by the ballet class remained for 18 hours after the exercise. These findings are important in preventing the development of chronic lesions that are commonly observed in dancers, such as those with arthritis and synovitis.

Changes in Skeletal Muscle Protein Metabolism Signaling Induced by Glutamine Supplementation and Exercise.

AIM: To evaluate the effects of resistance exercise training (RET) and/or glutamine supplementation (GS) on signaling protein synthesis in adult rat skeletal muscles. METHODS: The following groups were studied: (1) control, no exercise (C); (2) exercise, hypertrophy resistance exercise training protocol (T); (3) no exercise, supplemented with glutamine (G); and (4) exercise and supplemented with glutamine (GT). The rats performed hypertrophic training, climbing a vertical ladder with a height of 1.1 m at an 80° incline relative to the horizontal with extra weights tied to their tails. The RET was performed three days a week for five weeks. Each training session consisted of six ladder climbs. The extra weight load was progressively increased for each animal during each training session. The G groups received daily L-glutamine by gavage (one g per kilogram of body weight per day) for five weeks. The C group received the same volume of water during the same period. The rats were euthanized, and the extensor digitorum longus (EDL) muscles from both hind limbs were removed and immediately weighed. Glutamine and glutamate concentrations were measured, and histological, signaling protein contents, and mRNA expression analyses were performed. RESULTS: Supplementation with free L-glutamine increased the glutamine concentration in the EDL muscle in the C group. The glutamate concentration was augmented in the EDL muscles from T rats. The EDL muscle mass did not change, but a significant rise was reported in the cross-sectional area (CSA) of the fibers in the three experimental groups. The levels of the phosphorylated proteins (pAkt/Akt, pp70S6K/p70S6K, p4E-BP1/4E-BP1, and pS6/S6 ratios) were significantly increased in EDL muscles of G rats, and the activation of p4E-BP1 was present in T rats. The fiber CSAs of the EDL muscles in T, G, and GT rats were increased compared to the C group. These changes were accompanied by a reduction in the 26 proteasome activity of EDL muscles from T rats. CONCLUSION: Five weeks of GS and/or RET induced muscle hypertrophy, as indicated by the increased CSAs of the EDL muscle fibers. The increase in CSA was mediated via the upregulated phosphorylation of Akt, 4E-BP1, p70S6k, and S6 in G animals and 4E-BP1 in T animals. In the EDL muscles from T animals, a decrease in proteasome activity, favoring a further increase in the CSA of the muscle fibers, was reported.

LDLR missense variants disturb structural conformation and LDLR activity in T-lymphocytes of Familial hypercholesterolemia patients.

Familial hypercholesterolemia (FH) is caused by deleterious mutations in the LDLR that increase markedly low-density lipoprotein (LDL) cholesterol and cause premature atherosclerotic cardiovascular disease. Functional effects of pathogenic LDLR variants identified in Brazilian FH patients were assessed using in vitro and in silico studies. Variants in LDLR and other FH-related genes were detected by exon-target gene sequencing. T-lymphocytes were isolated from 26 FH patients, and 3 healthy controls and LDLR expression and activity were assessed by flow cytometry and confocal microscopy. The impact of LDLR missense variants on protein structure was assessed by molecular modeling analysis. Ten pathogenic or likely pathogenic LDLR variants (six missense, two stop-gain, one frameshift, and one in splicing region) and six non-pathogenic variants were identified. Carriers of pathogenic and non-pathogenic variants had lower LDL binding and uptake in activated T-lymphocytes compared to controls (p < 0.05), but these variants did not influence LDLR expression on cell surface. Reduced LDL binding and uptake was also observed in carriers of LDLR null and defective variants. Modeling analysis showed that p.(Ala431Thr), p.(Gly549Asp) and p.(Gly592Glu) disturb intramolecular interactions of LDLR, and p.(Gly373Asp) and p.(Ile488Thr) reduce the stability of the LDLR protein. Docking and molecular interactions analyses showed that p.(Cys184Tyr) and p.(Gly373Asp) alter interaction of LDLR with Apolipoprotein B (ApoB). In conclusion, LDLR null and defective variants reduce LDL binding capacity and uptake in activated T-lymphocytes of FH patients and LDLR missense variants affect LDLR conformational stability and dissociation of the LDLR-ApoB complex, having a potential role in FH pathogenesis.

Fish Oil Supplementation Improves the Repeated-Bout Effect and Redox Balance in 20-30-Year-Old Men Submitted to Strength Training.

Herein, we investigated the effect of fish oil supplementation combined with a strength-training protocol, for 6 weeks, on muscle damage induced by a single bout of strength exercise in untrained young men. Sixteen men were divided into two groups, supplemented or not with fish oil, and they were evaluated at the pre-training period and post-training period. We investigated changes before and 0, 24, and 48 h after a single hypertrophic exercise session. Creatine kinase (CK) and lactate dehydrogenase (LDH) activities, plasma interleukin-6 (IL-6) and C-reactive protein (CRP) levels, and the redox imbalance were increased in response to the single-bout session of hypertrophic exercises at baseline (pre-training period) and decreased during the post-training period in the control group due to the repeated-bout effect (RBE). The fish oil supplementation exacerbated this reduction and improved the redox state. In summary, our findings demonstrate that, in untrained young men submitted to a strength-training protocol, fish oil supplementation is ideal for alleviating the muscle injury, inflammation, and redox imbalance induced by a single session of intense strength exercises, highlighting this supplementation as a beneficial strategy for young men that intend to engage in strength-training programs.