A phytotherapic blend immunity-6™ inhibits myeloid leukemic cells 2 activation involving purinergic signaling.

Leukemia is among the most common types of hematological cancers and the use of herbal medicines to prevent and treat leukemia are under quick development. Among several molecular pathways involved in leukemia pathogenesis and exacerbations, purinergic signaling is revealed as a key component. In the present study, the effects of two doses (5 ug/mL and 10 ug/mL) of Immunity-6™, a phytocomplex composed by beta-glucan, green tea (Camelia sinensis), chamomile (Matricaria chamomilla), and ascorbic acid (vitamin C) was tested in vitro, using chronic myelogenous leukemia cell line (K-562; 5 ×104/mL/well), which were challenged with lipopolysaccharide (LPS; 1 ug/mL) for 24 h. The results demonstrated that both doses of Immunity-6™ inhibited ATP release (p < 0.001) and P2×7 receptor at mRNA levels expression (p < 0.001). Purinergic inhibition by Immunity-6™ was followed by reduced release of proinflammatory cytokines IL-1beta (p < 0.001) and IL-6 (p < 0.001), while only 5 ug/mL of Immunity-6™ reduced the release of TNF-alpha (p < 0.001). Beyond to inhibit the release of pro-inflammatory cytokines, both doses of Immunity-6™ induced the release of anti-inflammatory cytokine IL-10 (p < 0.001), while only the higher dose (10 ug/mL) of Immunity-6™ induced the release of anti-inflammatory IL-1ra (p < 0.05) and klotho (p < 0.001). Thus, Immunity-6™ may be a promising adjuvant in the treatment of leukemia and further clinical trials are guaranteed.

Therapeutic use of intravenous selenium in respiratory and immunological diseases: evidence based on reviews focused on clinical trials.

The oxidative stress caused by systemic inflammatory response syndrome (SIRS), septic shock, and sepsis, is a risk factor triggering an increase in mortality in patients diagnosed with these pathologies. Selenium (Se) is an essential mineral that has antioxidant and cytoprotective functions, being strongly associated with the proper functioning of intracellular metabolic processes. In this context, the present study aims to investigate de therapeutic effects of intravenous selenium use considering pathologies such as SIRS, septic shock, sepsis, acute respiratory distress syndrome (ARDS), ventilator associated pneumonia (VAP), and coronavirus disease (COVID-19). This is an narrative literature review in which six main articles found in databases of SciELO, PubMed, and Google Scholar, were selected and analyzed. As a result, articles were found evidencing the benefit of Se in the inflammatory response, increasing the GPx-3 activity and decreasing the inflammatory cytokines, in addition to generating a lower risk of VAP, shortening the hospitalization time, and mortality. Thus, Se supplementation has beneficial evidence for acute respiratory diseases and should be considered as a viable option as adjuvant therapy.

l-Glutamine supplementation enhances glutathione peroxidase and paraoxonase-1 activities in HDL of exercising older individuals.

BACKGROUND: Oxidative stress is an important factor in the formation of atherosclerotic plaques. High-density lipoprotein (HDL) harbors paraoxonase-1 (PON-1) and glutathione peroxidase (GPx), key enzymes in the protection against the harmful effects of oxidative stress. Although exercise training can increase both HDL-c content and its antioxidant action, and glutamine (Gln) intake also promotes GPx-based defenses, the association between exercise training and Gln in the regulation of PON-1 activity was not explored. Therefore, the objective of this study was to investigate the effects of Gln supplementation on the redox balance and on the total HDL antioxidant capacity by evaluation of the activity of PON-1 and GPx enzymes in physically exercised elderly individuals compared to non-exercised ones. METHODS: Fifty-one practitioners of a combined exercise training program (CET, age: 71.9 ± 5.7 years) and 32 non-practitioners (NP, age: 73 ± 6.3 years) participated in the study. CET and NP groups were separated into 2 subgroups according to the supplementation: Gln, 0.3 g/kg/day + 10 g maltodextrin (CET-Gln, n = 26; and NP-Gln, n = 16) or placebo, 10 g maltodextrin (CET-PL, n = 25; and NP-PL, n = 16). Blood samples were drawn at baseline and after 30 days after commencement of the supplementation for biochemical and enzyme activity analyses. RESULTS: Increased HDL-c, total peroxidase (PRx), and GPx activities were found in both CET-Gln and NP-Gln after the supplementation period, compared to baseline, in opposition to CET-PL and NP-PL groups. PON-1 activity increased only in CET-Gln. In both CET-Gln and NP-Gln groups, there was a reduction of the total peroxides/PRx, iron/PRx, and total peroxides/GPX ratios after supplementation. In CET-Gln, thiobarbituric acid-reactive substances (TBARS)/PRx and TBARS/GPx ratios were also lower after supplementation. CET-Gln and CET-PL subgroups had lower glycemia than NP-Gln and NP-PL, either at baseline or after the supplementation periods. The other parameters were unchanged after supplementation [total cholesterol, LDL-c, triglycerides, non-HDL cholesterol, total peroxides, TBARS, iron serum, Trolox-equivalent antioxidant capacity (TEAC), and uric acid]. CONCLUSIONS: Gln supplementation can increase glutathione peroxidase activity regardless the individuals were physically active or sedentary, but the PON-1 activity only increased in physically active individuals. These results show the potential of Gln supplementation in the maintenance of the vascular redox balance, with potential implications for atherogenesis protection.

Elderly Subjects Supplemented with L-Glutamine Shows an Improvement of Mucosal Immunity in the Upper Airways in Response to Influenza Virus Vaccination.

BACKGROUND: Although glutamine is able to improve the immune response, its action in the upper airway immunity against the influenza virus vaccine remains unclear. Therefore, we aimed to evaluate the L-glutamine supplementation effect on the mucosal immune/inflammatory response of elderly subjects vaccinated against the influenza virus. METHODS: Saliva sampling from 83 physically active elderly volunteers were collected pre- and 30 days after influenza virus vaccination and supplementation with L-glutamine (Gln, n = 42) or placebo (PL, n = 41). RESULTS: Gln group showed higher salivary levels of interleukin (IL)-17, total secretory immunoglobulin A (SIgA), and specific-SIgA post-vaccination than values found pre-vaccination and in the PL group post-vaccination. Whereas higher salivary levels of IL-6 and IL-10 were observed post-vaccination in the Gln group, IL-37 levels were lower post-vaccination in both groups than the values pre-vaccination. Tumor necrosis factor (TNF)-α levels were unchanged. Positive correlations between IL-6 and IL-10 were found in all volunteer groups pre- and post-vaccination and also between IL-17 and IL-6 or IL-10 in the Gln group post-vaccination. A negative correlation between IL-37 and IL-10 was found pre- and post-vaccination in the PL group. CONCLUSION: Gln supplementation was able to modulate salivary cytokine profile and increase SIgA levels, both total and specific to the influenza virus vaccine, in physically active elderly subjects.

Combined Exercise Training and l-Glutamine Supplementation Enhances Both Humoral and Cellular Immune Responses after Influenza Virus Vaccination in Elderly Subjects.

BACKGROUND: Since aging affects the immune responses against vaccination, the present study evaluated the effects of L-glutamine (Gln) supplementation in the humoral and cellular immune responses in elderly subjects, practitioners or not, of physical exercise training. METHODS: Eighty-four elderly people (aged 72.6 ± 6.1), non-practitioners (NP, n = 31), and practitioners of combined-exercise training (CET, n = 53) were submitted to Influenza virus vaccination and supplemented with Gln (0.3 g/kg of weight + 10 g of maltodextrin, groups: NP-Gln (n = 14), and CET-Gln (n = 26)), or placebo (10 g of maltodextrin, groups: NP-PL (n = 17), and CET-PL (n = 27)). Blood samples were collected pre (baseline) and 30 days post-vaccination and supplementation. RESULTS: Comparing with the baseline values, whereas the NP-Gln and CET-PL groups showed higher specific-IgM levels, the CET-Gln group showed higher specific-IgM and IgA levels post-vaccination. The titer rate of hemagglutination inhibition was higher in the CET-Gln, NP-PL, and NP-Gln groups post-vaccination than baseline values. The absolute number of naive and effector CD4+ T cells was higher especially in the NP-Gln and CET-Gln groups, whilst activated CD4+ T cells were higher in CET subgroups post-vaccination. CONCLUSION: Our results showed that both l-glutamine supplementation and combined-exercise training can improve the immune responses to the Influenza virus vaccine in elderly subjects.

Creatine Supply Attenuates Ischemia-Reperfusion Injury in Lung Transplantation in Rats.

Ischemia-reperfusion injury (IRI) is one of the factors limiting the success of lung transplantation (LTx). IRI increases death risk after transplantation through innate immune system activation and inflammation induction. Some studies have shown that creatine (Cr) protects tissues from ischemic damage by its antioxidant action. We evaluated the effects of Cr supplementation on IRI after unilateral LTx in rats. Sixty-four rats were divided into four groups: water + 90 min of ischemia; Cr + 90 min of ischemia; water + 180 min of ischemia; and Cr + 180 min of ischemia. Donor animals received oral Cr supplementation (0.5 g/kg/day) or vehicle (water) for five days prior to LTx. The left lung was exposed to cold ischemia for 90 or 180 min, followed by reperfusion for 2 h. We evaluated the ventilatory mechanics and inflammatory responses of the graft. Cr-treated animals showed a significant decrease in exhaled nitric oxide levels and inflammatory cells in blood, bronchoalveolar lavage fluid and lung tissue. Moreover, edema, cell proliferation and apoptosis in lung parenchyma were reduced in Cr groups. Finally, TLR-4, IL-6 and CINC-1 levels were lower in Cr-treated animals. We concluded that Cr caused a significant decrease in the majority of inflammation parameters evaluated and had a protective effect on the IRI after LTx in rats.

L-Glutamine Supplementation Improves the Benefits of Combined-Exercise Training on Oral Redox Balance and Inflammatory Status in Elderly Individuals.

Although regular combined aerobic-resistance exercises can ameliorate the inflammatory status and redox balance in elderly population, it is unclear whether protein or specific amino acid supplementation could improve such benefits. Therefore, we aimed to evaluate the inflammatory status and redox indexes through of the saliva of 34 elderly subject nonpractitioners (NP group, 73.3 ± 6.6 years) and 49 elderly subject practitioners of a combined-exercise training in moderate intensity (CET group, 71.9 ± 5.8 years) before (pre) and after (post) 30 days of supplementation with L-glutamine (Gln) or placebo (PL). Our results showed that, both in pre- and postsupplementation, the salivary levels of nitric oxide (NO·) and TNF-α were lower, whereas the levels of uric acid and IL-10 (as well as IL-10/TNF-α ratio) were higher in the CET groups than in the NP groups. In postsupplementation, both groups supplemented with Gln (NP-Gln and CET-Gln) showed higher salivary uric acid levels compared to baseline. In addition, lower NO· levels were found in the CET-Gln group postsupplementation than presupplementation values. Whereas the CET-Gln group showed lower GSH levels postsupplementation, NP-Gln subjects showed lower GSSG levels at the same time point, both compared to baseline. Interestingly, salivary peroxidase activity was lower only in NP groups (NP-PL and NP-Gln) postsupplementation than baseline values. A positive significant correlation between salivary peroxidase activity and GSH levels, and also between salivary peroxidase activity and uric acid levels were observed in the CET-Gln group both pre- and postsupplementation. No differences were found in albumin, total antioxidant activity (TEAC), and reducing power analysis between groups, pre- or postsupplementation. In conclusion, the elderly subjects from the CET group showed a better inflammatory response and redox balance and, for the first time, it was shown that daily supplementation with Gln for 30 days can improve these benefits with putative association with a healthy aging.

A Mixture of Polyunsaturated Fatty Acids ω-3 and ω-6 Reduces Melanoma Growth by Inhibiting Inflammatory Mediators in the Murine Tumor Microenvironment.

BACKGROUND: Although it has been previously demonstrated that acute inflammation can promote the tumor growth of a sub-tumorigenic dose of melanoma cells through of 5-lipoxygenase inflammatory pathway and its product leukotriene B4, and also that the peritumoral treatment with eicosapentaenoic acid and its product, leukotriene B5, reduces the tumor development, the effect of the treatment by gavage with omega-3 and omega-6 in the tumor microenvironment favorable to melanoma growth associated with acute inflammation has never been studied. METHODS: C57BL/6 mice were coinjected with 1 × 106 apoptotic cells plus 1 × 103 viable melanoma cells into the subcutaneous tissue and treated by gavage with omega-3-rich fish oil or omega-6-rich soybean oil or a mixture of these oils (1:1 ratio) during five consecutive days. RESULTS: The treatment by gavage with a mixture of fish and soybean oils (1:1 ratio) both reduced the melanoma growth and the levels of leukotriene B4 (LTB4), prostaglandin E2 (PGE2), PGE2/prostaglandin E3 (PGE3) ratio, and CXC ligand 1 (CXCL1) and increased the levels of interleukin 10 (IL-10) to IL-10/CXCL1 ratio in the melanoma microenvironment. CONCLUSION: The oral administration of a 1:1 mixture of fish oil and soybean oil was able to alter the release of inflammatory mediators that are essential for a microenvironment favorable to the melanoma growth in mice, whereas fish oil or soybean oil alone was ineffective.

Acute Effects Using Light-Emitting Diode Therapy (LEDT) for Muscle Function during Isometric Exercise in Asthma Patients: A Pilot Study.

The aim of this study was to evaluate the effectiveness of acute application of LEDT in improving peripheral muscle performance during isometric exercise in patients with asthma. Eleven patients, with a mean age 38 ± 10, underwent a single LEDT and sham application in the femoral quadriceps' dominant member (cluster with 50 LED λ = 850 nm, 50 mW, 15 s; 37.5 J), 48 h apart in a randomized crossover design. Before and after LEDT and sham application, the patients were submitted an isometric endurance test (60% of the maximum isometric voluntary contraction), up to the limit of tolerance simultaneous recording of surface electromyography. There were no statistically significant differences between groups at the time of contraction (before 41±14 versus 44±16; after 46±12 versus 45±20 s) during the isometric contraction test and inflammatory markers before and after a single LEDT application. A single application of LEDT in the parameters and dose according to the equipment used in the study were not able to promote differences in the time of contraction and the fatigue response in asthmatic patients. However, the chronic effects of LEDT application for improving muscle performance in these patients are unknown and may present different responses during applications for a long time.

Low level laser therapy reduces acute lung inflammation in a model of pulmonary and extrapulmonary LPS-induced ARDS.

The present study aimed to investigate the effects low level laser therapy (LLLT) in a LPS-induced pulmonary and extrapulmonary acute respiratory distress syndrome (ARDS) in BALB/c mice. Laser (830nm laser, 9J/cm(2), 35mW, 80s per point, 3 points per application) was applied in direct contact with skin, 1h after LPS administration. Mice were distributed in control (n=6; PBS), ARDS IT (n=7; LPS orotracheally 10µg/mouse), ARDS IP (n=7; LPS intra-peritoneally 100µg/mouse), ARDS IT+Laser (n=9; LPS intra-tracheally 10µg/mouse), ARDS IP+Laser (n=9; LPS intra-peritoneally 100µg/mouse). Twenty-four hours after last LPS administration, mice were studied for pulmonary inflammation by total and differential cell count in bronchoalveolar lavage (BAL), cytokines (IL-1beta, IL-6, KC and TNF-alpha) levels in BAL fluid and also by quantitative analysis of neutrophils number in the lung parenchyma. LLLT significantly reduced pulmonary and extrapulmonary inflammation in LPS-induced ARDS, as demonstrated by reduced number of total cells (p<0.001) and neutrophils (p<0.001) in BAL, reduced levels of IL-1beta, IL-6, KC and TNF-alpha in BAL fluid and in serum (p<0.001), as well as the number of neutrophils in lung parenchyma (p<0.001). LLLT is effective to reduce pulmonary inflammation in both pulmonary and extrapulmonary model of LPS-induced ARDS.

Low-level laser therapy inhibits bronchoconstriction, Th2 inflammation and airway remodeling in allergic asthma.

Low-level laser therapy (LLLT) controls bronchial hyperresponsiveness (BHR) associated with increased RhoA expression as well as pro-inflammatory mediators associated with NF-kB in acute lung inflammation. Herein, we explore if LLLT can reduce both BHR and Th2 cytokines in allergic asthma. Mice were studied for bronchial reactivity and lung inflammation after antigen challenge. BHR was measured through dose-response curves to acetylcholine. Some animals were pretreated with a RhoA inhibitor before the antigen. LLLT (660 nm, 30 mW and 5.4 J) was applied on the skin over the right upper bronchus and two irradiation protocols were used. Reduction of BHR post LLLT coincided with lower RhoA expression in bronchial muscle as well as reduction in eosinophils and eotaxin. LLLT also diminished ICAM expression and Th2 cytokines as well as signal transducer and activator of transduction 6 (STAT6) levels in lungs from challenged mice. Our results demonstrated that LLLT reduced BHR via RhoA and lessened allergic lung inflammation via STAT6.

Wound-healing effects of low-level laser therapy in diabetic rats involve the modulation of MMP-2 and MMP-9 and the redistribution of collagen types I and III.

The present study aimed to determine if LLLT restores the balance between mRNA expression of matrix metalloproteinases (MMP-2 and MMP-9) and also the balance between collagen types I and III during the healing process of diabetic wounds. One hundred and twenty male Wistar rats were distributed in Control (untreated non-diabetic rats: UND); Laser (laser treated in non-diabetic rats: LTND); Diabetic (diabetic rats non-laser treated rats: UD); and Diabetic+ Laser (diabetic rats laser treated: DLT) groups. The diabetes model using streptozotocin efficiently induced diabetes, as demonstrated through increased levels of blood glucose. Diode laser (50 mW, 660 nm, 4 J/cm(2), 80 s) was applied a single time after scare induction. Twenty-four hours after LLLT application, rats were euthanized, the scarred areas were collected for MMP-2 and MMP-9 mRNA analysis and also for histological analysis (inflammation and types I and III collagen). The results demonstrated that scare in untreated diabetic rats significantly increased the MMP-2 and MMP-9 expression compared with that in non-diabetic rats (p < 0.05), while LLLT significantly reduced MMP-2 and MMP-9 expression compared with that in untreated diabetic rats (p < 0.05). To conclude, the results also showed that LLLT was able to alter the expression of MMP-9 as well as accelerate the production of collagen and increase the total percentage of collagen type III in diabetic animals.

Low-level laser therapy and sodium diclofenac in acute inflammatory response induced by skeletal muscle trauma: effects in muscle morphology and mRNA gene expression of inflammatory markers.

Pharmacological therapy is widely used in the treatment of muscle injuries. On the other hand, low-level laser therapy (LLLT) arises as a promising nonpharmacological treatment. The aim of this study was to analyze the effects of sodium diclofenac (topical application) and LLLT on morphological aspects and gene expression of biochemical inflammatory markers. We performed a single trauma in tibialis anterior muscle of rats. After 1 h, animals were treated with sodium diclofenac (11.6 mg g(-1) of solution) or LLLT (810 nm; continuous mode; 100 mW; 3.57 W cm(-2) ; 1, 3 or 9 J; 10, 30 or 90 s). Histological analysis and quantification of gene expression (real-time polymerase chain reaction-RT-PCR) of cyclooxygenase 1 and 2 (COX-1 and COX-2) and tumor necrosis factor-alpha (TNF-α) were performed at 6, 12 and 24 h after trauma. LLLT with all doses improved morphological aspects of muscle tissue, showing better results than injury and diclofenac groups. All LLLT doses also decreased (P < 0.05) COX-2 compared to injury group at all time points, and to diclofenac group at 24 h after trauma. In addition, LLLT decreased (P < 0.05) TNF-α compared both to injury and diclofenac groups at all time points. LLLT mainly with dose of 9 J is better than topical application of diclofenac in acute inflammation after muscle trauma.

Creatine supplementation exacerbates allergic lung inflammation and airway remodeling in mice.

Creatine supplement is the most popular nutritional supplement, and has various metabolic functions and sports medicine applications. Creatine supplementation increases muscle mass and can decrease muscular inflammation. Some studies have also suggested a beneficial role of creatine supplementation on chronic pulmonary diseases such as chronic obstructive pulmonary disease and cystic fibrosis. Among athletes, the prevalence of asthma is high, and many of these individuals may be taking creatine. However, the effects of creatine supplementation on chronic pulmonary diseases of allergic origin have not been investigated. In the present study, we analyzed the effects of creatine supplementation on a model of chronic allergic lung inflammation. Thirty-one Balb/c mice were divided into four groups: control, creatine (Cr), ovalbumin (OVA), and OVA+Cr. OVA and OVA+Cr groups were sensitized with intraperitoneal injections of OVA on Days 0, 14, 28, and 42. OVA challenge (OVA 1%) and Cr treatment (0.5 g/kg/d) were initiated on Day 21 and lasted until Day 53. We determined the index of hyperresponsiveness, the serum levels of OVA-specific immunoglobulin (Ig)E and IgG(1), and the total and differential cell counts in bronchoalveolar lavage fluid. We also quantified airway inflammation, and the airway density of IL-4+, IL-5+, IL-2+, IFN-gamma+, and insulin-like growth factor (IGF)-1+ cells, collagen and elastic fibers, and airway smooth muscle thickness. Our results showed that creatine in OVA-sensitized mice increased hyperresponsiveness; eosinophilic inflammation; airway density of IL-4+, IL-5+, and IGF-1 inflammatory cells; airway collagen and elastin content; and smooth muscle thickness. The results show that creatine supplementation exacerbates the lung allergic response to OVA through a T helper cell type 2 pathway and increased IGF-1 expression.