Hypertonic Solution in Severe COVID-19 Patient: A Potential Adjuvant Therapy.

Coronavirus disease 2019 (COVID-19) features hyper-inflammation, cytokine storm, neutrophil function changes, and sodium chloride (NaCl) homeostasis disruption, while the treatment with NaCl hypertonic solutions (HS) controls electrolytic body homeostasis and cell functions. HS treatment is a simple, popular, economic, and feasible therapy to regulate leukocyte function with a robust anti-inflammatory effect in many inflammatory diseases. The purpose of this narrative review is to highlight the knowledge on the use of HS approaches against viral infection over the past years and to describe the mechanisms involved in the release of neutrophil extracellular traps (NETs) and production of cytokine in severe lung diseases, such as COVID-19. We reported the consequences of hyponatremia in COVID-19 patients, and the immunomodulatory effects of HS, either in vitro or in vivo. We also described the relationship between electrolyte disturbances and COVID-19 infection. Although there is still a lack of clinical trials, hypertonic NaCl solutions have marked effects on neutrophil function and NETs formation, emerging as a promising adjuvant therapy in COVID-19.

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.

Technical bioanalytical considerations for detection and quantification of cytokines in ELISA assays.

Enzyme-linked Immunosorbent Assays (ELISAs) techniques are widely known for the robust signal amplification with high sensitivity and specificity for the quantitation of antibodies and antigens in complex biological fluids. However, strict caution in the pre-analytical, analytical, and post-analytical phases is crucial to warrant an immunoassay quality. Since analytical errors are commonly seen in papers, this study aimed to discuss the main principles and guidelines to guarantee the specificity and sensitivity in the post-analytical phase of the ELISA method. Briefly, we highlighted the relevance of the analytical noise, as well as the limit of detection and quantitation, in the sensitivity of an immunoassay. Moreover, strategies involving the use of reverse pipetting and the spike-and-recovery test can decrease the inter-assay variance, while the linearity-of-dilution assay may protect against the prozone (or hook) effect. Addressed to researchers from different fields, we offer recommendations to limit variability and increase the usefulness of the ELISA assay in a practical way that will assist scientists to prevent future analytical errors.

Hypertonic solution in severe COVID-19 patient: a potential adjuvant therapy

Coronavirus disease 2019 (COVID-19) features hyper-inflammation, cytokine storm, neutrophil function changes, and sodium chloride (NaCl) homeostasis disruption, while the treatment with NaCl hypertonic solutions (HS) controls electrolytic body homeostasis and cell functions. HS treatment is a simple, popular, economic, and feasible therapy to regulate leukocyte function with a robust anti-inflammatory effect in many inflammatory diseases. The purpose of this narrative review is to highlight the knowledge on the use of HS approaches against viral infection over the past years and to describe the mechanisms involved in the release of neutrophil extracellular traps (NETs) and production of cytokine in severe lung diseases, such as COVID-19. We reported the consequences of hyponatremia in COVID-19 patients, and the immunomodulatory effects of HS, either in vitro or in vivo. We also described the relationship between electrolyte disturbances and COVID-19 infection. Although there is still a lack of clinical trials, hypertonic NaCl solutions have marked effects on neutrophil function and NETs formation, emerging as a promising adjuvant therapy in COVID-19.

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.

Recovery of Diabetic Rats After Physical Exhaustion: Kinetic Alterations in Muscle Inflammation and Muscle-Signaling Proteins to Atrophy and Hypertrophy.

The complexity of the adaptive response of diabetics to intense exercise is still poorly understood. To optimize exercise interventions in diabetics, the chronology of inflammatory mediators in muscle and the signaling involved in muscle hypertrophy/atrophy must be understood. Herein, we studied the kinetic inflammatory profile and cellular signaling pathways modulated by physical exhaustion after the induction of type 1 diabetes by streptozotocin in rats. Soleus muscle samples were obtained from diabetic and control groups at the following moments: baseline (no exercise); immediately after exhaustive exercise; and at 2 h, 24 h, 48 h, and 72 h after a treadmill exhaustive exercise. Kinetic production of cytokines and kinetic activation of proteins related to muscle synthesis (p70S6K and Akt) and degradation (GSK3, MuRF1, and MAFbx) were measured in the soleus muscle. We observed that the muscle TNF-α (0.9-fold; p = 0.0007), IL-1ß (0.8-fold; p = 0.01), IL-6 (0.8-fold; p = 0.0013), L-selectin (1.0-fold; p = 0.0019), and CINC-2α/ß (0.9-fold; p = 0.04) levels were higher in almost all stages of the study in the diabetic animals compared with the control group. Our data showed that exhaustive exercise decreased MAFbx expression in diabetic animals compared to the control group in a time-dependent manner. The decreased activation ratios of MAFbx were followed by a decrease in TNF-α, IL-1ß, and IL-6 levels. p70S6k phosphorylation was also decreased in the diabetic group compared to the control group after physical exhaustion. Regarding the activation of proteins related to muscle synthesis and degradation, we found that the alterations induced by exhaustive exercise in the diabetic rats might involve pathways related to synthesis and muscle breakdown. Moreover, after an exhaustive exercise session, the recovery of the inflammatory response in the diabetic animals was slower than that in the control rats while the return of inflammatory cytokines to baseline levels was more effective in the diabetic animals.

Topical anti-inflammatory activity of palmitoleic acid improves wound healing.

This study investigated the effects of palmitoleic acid on different phases of the healing process. Macroscopic analyses were performed on wounds in rats with or without palmitoleic acid treatment, and the results showed that palmitoleic acid directly hastened wound closure. The topical treatment of wounds with palmitoleic acid resulted in smaller wounds than those observed in the control group. The anti-inflammatory activity of palmitoleic acid may be responsible for healing, especially in the stages of granulation tissue formation and remodelling. Palmitoleic acid modified TNF-α, IL-1ß, IL-6, CINC-2α/ß, MIP-3α and VEGF-α profiles at the wound site 24, 48, 120, 216 and 288 hours post-wounding. Assays assessing neutrophil migration and exudate formation in sterile inflammatory air pouches revealed that palmitoleic acid had potent anti-inflammatory activity, inhibiting the LPS-induced release of TNF-α (73.14%, p≤0.05), IL-1ß (66.19%, p≤0.001), IL-6 (75.19%, p≤0.001), MIP-3α (70.38%, p≤0.05), and l-selectin (16%, p≤0.05). Palmitoleic acid also inhibited LPS-stimulated neutrophil migration. We concluded that palmitoleic acid accelerates wound healing via an anti-inflammatory effect.

Neutrophil Migration and Adhesion Molecule Expression after Acute High-Intensity Street Dance Exercise.

The physical demands of street dancing may result in inflammation and changes in leukocyte numbers/function, impairing the health of dancers. Herein, we investigated the effect of street dancing on inflammation, adhesion molecules, and neutrophil function. Fifteen amateur dancers (mean ± SE: age 22.4 ± 1.08 years, BMI 24.8 ± 0.69 kg/m2, and body fat 12.3 ± 1.52%) participated in a single high-intensity street dance class. Blood samples were taken before and after the class. The dance class had no effect on the plasma concentration of CRP, TNF-α, IL-6, IL-10, and IL-8; however, we noted an increase in levels of IL-1ß (4.06%) and sL-selectin (17.67%). The dance class resulted in a 12.36% increase in neutrophil counts, while neutrophil CD62L expression and migration were reduced (25.27% and 78.92%, resp.). After the dance class, neutrophil production of IL-8 and TNF-α increased, respectively, by 59.75% and 49.23%, in the control condition, and 43.55% and 32.22%, after LPS stimulation. A single bout of street dancing induced inflammation and reduced neutrophil migration and adhesion molecule expression. These findings may contribute to a better understanding of the susceptibility to infection after acute dance exercise.

The Effect of a Competitive Futsal Match on T Lymphocyte Surface Receptor Signaling and Functions.

In this study, the lymphocyte activation status (surface expression of CD95, CD28, CD25, and CTLA-4), lymphocyte number, lymphocyte subpopulations, lymphocyte necrosis and/or apoptosis, and lymphocyte release of reactive oxygen species (ROS) were investigated in blood samples from 16 futsal athletes before and immediately following a competitive match. Lymphocytes were isolated from the blood samples, and the cellular parameters were assessed by flow cytometry. The futsal match induced lymphocytosis and lymphocyte apoptosis, as indicated by phosphatidylserine externalization, CD95 expression, and DNA fragmentation. Additionally, the competitive match induced the necrotic death of lymphocytes. No differences in the percentage of CD4+ and CD8+ T cells or in the T-helper/suppressor profile between before and immediately after the match were observed. Additionally, after the futsal match, the CD95 and CD28 expression levels were decreased, and the lymphocytes spontaneously released higher levels of ROS. Regardless of the origin, the situation-specific knowledge of lymphocyte behavior obtained herein may facilitate the design of strategies to control the processes that result in infection and tissue injury and that subsequently decrease athletic performance.

Correction to: Effects of exergaming on cardiovascular risk factors and adipokine levels in women.

The original article was corrected.

Effects of exergaming on cardiovascular risk factors and adipokine levels in women.

The aim of this study was to examine the effects of exergaming on the cardiovascular risk factors and adipokine levels of women engaged in the music video game Just Dance using the Xbox 360 Kinect console. Triglycerides, total cholesterol, HDL, LDL, FFA, CRP, TNF-α, Il-1ß, IL-6, leptin, and resistin were measured in sedentary women before and 1 month after the practice of exergaming. We also evaluated anthropometric parameters. Our results indicate that total serum cholesterol, triglycerides, and LDL were reduced by 64, 29, and 12%, respectively. HDL levels were not altered in the conditions of this study. A significant decrease was also found in the concentrations of TNF-α (57%), CRP (84.7%), resistin (68.4%), leptin (35%), FFA (90%), body mass index (10.5%), fat percentage (10.9%), weight (5.6%), abdominal circumference (2.3%), hip circumference (2.5%), and waist circumference (1.9%) after the training period. We concluded that exergaming was successful in reducing body fat, serum adipokine levels, and lipid profiles, thus reducing cardiovascular risks for women.

Melatonin decreases muscular oxidative stress and inflammation induced by strenuous exercise and stimulates growth factor synthesis.

Strenuous exercise is detrimental to athletes because of the overproduction of reactive oxygen species. Melatonin, a classic antioxidant, has been shown to exhibit beneficial effects regarding intense exercise and tissue repair. In this study, we evaluated the onset and resolution of inflammation in melatonin-treated and nontreated rats subjected to a strenuous exercise session. We also analyzed the formation of thiobarbituric acid reactive substances (TBARS) and the activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Control and treated rats were subjected to exhaustive exercise after a period of 10 days of melatonin treatment (20 mg/dL). Plasma and muscle levels of tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), cytokine-induced neutrophil chemoattractant-2-alpha/beta (CINC-2α/ß), l-selectin, macrophage inflammatory protein-3-alpha (MIP-3α), and vascular endothelial growth factor (VEGF) were measured prior to, immediately after, and 2 hr after exercise. Our data revealed decreases in the muscle concentrations of IL-1ß (35%), TNF-α (13%), IL-6 (48%), and TBARS (40%) in the melatonin-treated group compared with the control group. We also observed decreases in the plasma concentrations of IL-1ß (17%) in the melatonin-treated group. VEGF-α concentrations and SOD activity increased by 179% and 22%, respectively, in the melatonin-treated group compared with the control group. We concluded that muscle inflammation and oxidative stress resulting from exhaustive exercise were less severe in the muscles of melatonin-treated animals than in the muscles of control animals. Thus, melatonin treatment may reverse exercise-induced skeletal muscle inflammation and stimulate growth factor synthesis.

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.

Oleic, linoleic and linolenic acids increase ros production by fibroblasts via NADPH oxidase activation.

The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of ß-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47 (phox) phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47 (phox) mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts.

Fibroblast growth factor 2 restrains Ras-driven proliferation of malignant cells by triggering RhoA-mediated senescence.

Fibroblast growth factor 2 (FGF2) is considered to be a bona fide oncogenic factor, although results from our group and others call this into question. Here, we report that exogenous recombinant FGF2 irreversibly inhibits proliferation by inducing senescence in Ras-dependent malignant mouse cells, but not in immortalized nontumorigenic cell lines. We report the following findings in K-Ras-dependent malignant Y1 adrenocortical cells and H-Ras V12-transformed BALB-3T3 fibroblasts: (a) FGF2 inhibits clonal growth and tumor onset in nude and immunocompetent BALB/c mice, (b) FGF2 irreversibly blocks the cell cycle, and (c) FGF2 induces the senescence-associated beta-galactosidase with no accompanying signs of apoptosis or necrosis. The tyrosine kinase inhibitor PD173074 completely protected malignant cells from FGF2. In Y1 adrenal cells, reducing the constitutively high levels of K-Ras-GTP using the dominant-negative RasN17 mutant made cells resistant to FGF2 cytotoxicity. In addition, transfection of the dominant-negative RhoA-N19 into either Y1 or 3T3-B61 malignant cell lines yielded stable clonal transfectants that were unable to activate RhoA and were resistant to the FGF2 stress response. We conclude that in Ras-dependent malignant cells, FGF2 interacts with its cognate receptors to trigger a senescence-like process involving RhoA-GTP. Surprisingly, attempts to select FGF2-resistant cells from the Y1 and 3T3-B61 cell lines yielded only rare clones that (a) had lost the overexpressed ras oncogene, (b) were dependent on FGF2 for proliferation, and (c) were poorly tumorigenic. Thus, FGF2 exerted a strong negative selection that Ras-dependent malignant cells could rarely overcome.

GenFlow: Generic flow for integration, management and analysis of molecular biology data

A large number of DNA sequencing projects all over the world have yielded a fantastic amount of data, whose analysis is, currently, a big challenge for computational biology. The limiting step in this task in the integration of large volumes of data stored in highly heterogeneous repositories of genomic and cDNA sequences, as well as gene expression results. Solving this problem requires automated analytical tools to optimize operations and efficiently generate knowledge. This paper presents an generic flow model, called GenFlow, that can tackle this analytical task.