Impact of Serum Amyloid A Protein in the Human Breast: An In Vitro Study.

The mammary gland is an exocrine gland whose main function is to produce milk. Breast morphogenesis begins in the embryonic period; however, its greatest development takes place during the lactation period. Studies have found the expression of serum amyloid A protein (SAA) in both breast cells and breast milk, yet the function of this protein in these contexts remains unknown. Insufficient milk production is one of the most frequent reasons for early weaning, a problem that can be related to the mother, the newborn, or both. This study aims to investigate the relationship between lactogenesis II (the onset of milk secretion) and the role of SAA in the human breast. To this end, mammary epithelial cell cultures were evaluated for the expression of SAA and the influence of various cytokines. Additionally, we sought to assess the activation pathway through which SAA acts in the breast, its glucose uptake capacity, and the morphological changes induced by SAA treatment. SAA expression was observed in mammary epithelial cells; however, it was not possible to establish its activation pathway, as treatments with inhibitors of the ERK1/2, p38MAPK, and PI3K pathways did not alter its expression. This study demonstrated that SAA can stimulate IL-6 expression, inhibit glucose uptake, and cause morphological changes in the cells, indicative of cellular stress. These mechanisms could potentially contribute to early breastfeeding cessation due to reduced milk production and breast involution.

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

Ganoderma lucidum (a mushroom used in traditional Chinese medicine) compounds may attenuate ageing-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 2000 mg/d 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 polymerase chain reaction. We observed that in the Ganoderma lucidum group, concanavalin A stimulation increased lymphocyte proliferation. Further, we observed an increase in expression of Forkhead box P3, transforming growth factor-beta, IL-10, IL-6, retinoic acid receptor-related orphan receptor gamma, GATA-binding protein 3 and interferon gamma genes in the Ganoderma lucidum group. Furthermore, in the Ganoderma lucidum group, ionomycin and phorbol 12-myristate 13-acetate 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 signalling pathway.

Sleep impairment and altered pattern of circadian biomarkers during a long-term Antarctic summer camp.

Antarctic expeditions include isolation and exposure to cold and extreme photoperiods (with continuous natural light during summer) that may influence psychophysiological responses modulated by luminosity and sleep. We assessed changes in night sleep patterns by actigraphy, salivary biomarkers, and perceptual variables in seven participants in the following time points along a 50-day camping expedition in Antarctica (Nelson Island): Pre-Field (i.e., on the ship before camp), Field-1, Field-2, Field-3, Field-4 (from 1st to 10th, 11th to 20th, 21st to 35th and 36th to 50th days in camp, respectively), and Post-Field (on the ship after camp). We also characterized mood states, daytime sleepiness, and sleep quality by questionnaires. Staying in an Antarctic camp reduced sleep efficiency (5.2%) and increased the number of awakenings and wakefulness after sleep onset (51.8% and 67.1%, respectively). Furthermore, transient increases in time in bed (16.5%) and sleep onset latency (4.8 ± 4.0 min, from Pre- to Field-3) was observed. These changes were accompanied by an altered pattern of the emerging circadian marker ß-Arrestin-1 and a trend to reduce nocturnal melatonin [57.1%; P = 0.066, with large effect size (ES) from Pre-Field to Field-2 (ES = 1.2) and Field-3 (ES = 1.2)]. All changes returned to Pre-Field values during the Post-Field. The volunteers reported sleep-related physical complaints (feeling of cold and pain, discomfort to breathe, and cough or loud snoring), excessive daytime sleepiness, and reduced vigor during the camp. Thus, a 50-day camp alters neuroendocrine regulation and induces physical discomfort, which may explain the impaired sleep pattern and the consequent daytime sleepiness and mood changes.

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.

A 7-Week Summer Camp in Antarctica Induces Fluctuations on Human Oral Microbiome, Pro-Inflammatory Markers and Metabolic Hormones Profile.

Antarctic camps pose psychophysiological challenges related to isolated, confined, and extreme (ICE) conditions, including meals composed of sealed food. ICE conditions can influence the microbiome and inflammatory responses. Seven expeditioners took part in a 7-week Antarctic summer camp (Nelson Island) and were evaluated at Pre-Camp (i.e., at the beginning of the ship travel), Camp-Initial (i.e., 4th and 5th day in camp), Camp-Middle (i.e., 19th-20th, and 33rd-34th days), Camp-Final (i.e., 45th-46th day), and at the Post-Camp (on the ship). At the Pre-Camp, Camp-Initial, and Camp-Final, we assessed microbiome and inflammatory markers. Catecholamines were accessed Pre- and Post-Camp. Heart rate variability (HRV), leptin, thyroid stimulating hormone (TSH), and thyroxine (T4) were accessed at all time points. Students' t-tests or repeated-measures analysis of variance (one or two-way ANOVA) followed by Student-Newman-Keuls (post hoc) were used for parametric analysis. Kruskal-Wallis test was applied for non-parametric analysis. Microbiome analysis showed a predominance of Pseudomonadota (34.01%), Bacillota (29.82%), and Bacteroidota (18.54%), followed by Actinomycetota (5.85%), and Fusobacteria (5.74%). Staying in a long-term Antarctic camp resulted in microbiome fluctuations with a reduction in Pseudomonadota-a "microbial signature" of disease. However, the pro-inflammatory marker leptin and IL-8 tended to increase, and the angiogenic factor VEGF was reduced during camp. These results suggest that distinct Antarctic natural environments and behavioral factors modulate oral microbiome and inflammation.

A Single Bout of High Heels Dancing Causes an Increase in Circulating Markers of Muscle Tissue Degradation and MMP-3 in Young Healthy Women.

Prolonged wearing of high heels can cause chronic injury and inflammation. Herein, we investigated the presence of muscle injury, inflammation, and neutrophil function in young women after a single bout of stiletto dance class. Sixteen volunteers (23.4 ± 3.8 years; 61.7 ± 8.1 kg; 23.4 ± 2.3 kg/m2; and 27.2 ± 3.8% body fat) participated in the study. The plasma biomarkers matrix metalloproteinase 3 (MMP-3), muscle damage (myoglobin (Mb), total creatine kinase (CK), and lactate dehydrogenase (LDH)), and inflammation (interleukin 8 (IL-8), tumour necrosis factor-alpha (TNF-α), interleukin (IL]-1ß, and IL-6) were quantified before and immediately after a single stiletto class (60 min) of moderate intensity. After class, our data showed that the plasma concentration of MMP-3, Mb, and CK increased by 56% (p = 0.04; d = 0.8), 113% (p = 0.007; d = 1.1), and 21% (p < 0.001; d = 0.4), respectively. Reactive oxygen species produced by neutrophils and the plasma concentration of IL-8, TNF-α, IL-1ß, and IL-6 were not affected under the study conditions. We concluded that a single bout of stiletto dance class caused muscle damage but did not alter the plasma concentration of proinflammatory cytokines. These findings are crucial in preventing the progress of chronic injuries that are often noted in dancers with synovitis and arthritis.

Molecular and cellular mechanisms involved in tissue-specific metabolic modulation by SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is triggered by the SARS-CoV-2, which is able to infect and cause dysfunction not only in lungs, but also in multiple organs, including central nervous system, skeletal muscle, kidneys, heart, liver, and intestine. Several metabolic disturbances are associated with cell damage or tissue injury, but the mechanisms involved are not yet fully elucidated. Some potential mechanisms involved in the COVID-19-induced tissue dysfunction are proposed, such as: (a) High expression and levels of proinflammatory cytokines, including TNF-α IL-6, IL-1ß, INF-α and INF-ß, increasing the systemic and tissue inflammatory state; (b) Induction of oxidative stress due to redox imbalance, resulting in cell injury or death induced by elevated production of reactive oxygen species; and (c) Deregulation of the renin-angiotensin-aldosterone system, exacerbating the inflammatory and oxidative stress responses. In this review, we discuss the main metabolic disturbances observed in different target tissues of SARS-CoV-2 and the potential mechanisms involved in these changes associated with the tissue dysfunction.

Leukocyte metabolism in obese type 2 diabetic individuals associated with COVID-19 severity.

Recent studies show that the metabolic characteristics of different leukocytes, such as, lymphocytes, neutrophils, and macrophages, undergo changes both in the face of infection with SARS-CoV-2 and in obesity and type 2 diabetes mellitus (DM2) condition. Thus, the objective of this review is to establish a correlation between the metabolic changes caused in leukocytes in DM2 and obesity that may favor a worse prognosis during SARS-Cov-2 infection. Chronic inflammation and hyperglycemia, specific and usual characteristics of obesity and DM2, contributes for the SARS-CoV-2 replication and metabolic disturbances in different leukocytes, favoring the proinflammatory response of these cells. Thus, obesity and DM2 are important risk factors for pro-inflammatory response and metabolic dysregulation that can favor the occurrence of the cytokine storm, implicated in the severity and high mortality risk of the COVID-19 in these patients.

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.

Salivary Proteome, Inflammatory, and NETosis Biomarkers in Older Adult Practitioners and Nonpractitioners of Physical Exercise.

Since aging has been associated with increased production of inflammatory biomarkers, the ability to monitor older adults repeatedly is highly desirable, and saliva is an interesting biofluid for the search of biomarkers, as it is easily accessible in a noninvasive manner. However, given the incipient knowledge of salivary biomarkers in aging and its relationship to physical exercise, the present study is aimed at evaluating the protein expression and the levels of inflammatory and NETosis biomarkers in the saliva of practitioners (PE) and nonpractitioners (NPE) of physical exercise older adults. Six (6) practitioner and 4 nonpractitioner older adults were enrolled in this study. Unstimulated whole saliva was collected for analysis of the proteome by label-free mass spectrometry, as well as of the inflammatory status by evaluation of C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and cytokines (TNF-α, interleukin- (IL-) 1ß, and IL-8), while NETosis was assessed by myeloperoxidase (MPO) and neutrophil elastase. Regarding oral health, the decayed, missing, and filled teeth (DMF-T) index, bleeding on probing, suppuration, and probing depth measurement (mm) were evaluated. In addition, functional capacity was investigated using the General Physical Fitness Index (GPFI). In relation to the proteome analysis, 93 and 143 proteins were found exclusively in the PE and NPE groups, respectively; 224 proteins were common to both groups. Among these proteins, 10 proteins showed statistical difference (p < 0.05) between the groups: alpha-2-macroglobulin, component 3 of the complement, serotransferrin, and protein soluble in brain acid 1 were less expressed, while lactotransferrin, alpha-amylase 1, S100-A8, S100-A9, lactoperoxidase, and galectin-3 binding protein were more expressed in the PE group. No differences between groups were observed in the analysis of inflammatory and NETosis biomarkers. This study shows the potential utility of saliva for detecting protein biomarkers in a noninvasive biological sample of the elderly population.

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.

Hydrolyzed whey protein enriched with glutamine dipeptide attenuates skeletal muscle damage and improves physical exhaustion test performance in triathletes.

Purpose: To investigate the effects of hydrolyzed whey protein enriched with glutamine dipeptide on the percentage of oxygen consumption, second ventilatory threshold, duration and total distance covered, and skeletal muscle damage during an exhaustion test in elite triathletes. Methods: The study was a randomized, double-blinded, placebo-controlled, crossover trial. Nine male triathletes performed a progressive incremental test on a treadmill ergometer (1.4 km h-1·3 min-1) 30 min after ingesting either 50 g of maltodextrin plus four tablets of 700 mg hydrolyzed whey protein enriched with 175 mg of glutamine dipeptide diluted in 250 ml of water (MGln) or four tablets of 700 mg maltodextrin plus 50 g maltodextrin diluted in 250 ml of water (M). Each athlete was submitted to the two dietary treatments and two corresponding exhaustive physical tests with an interval of one week between the interventions. The effects of the two treatments were then compared within the same athlete. Maximal oxygen consumption, percentage of maximal oxygen consumption, second ventilatory threshold, and duration and total distance covered were measured during the exhaustion test. Blood was collected before and immediately after the test for the determination of plasma lactate dehydrogenase (LDH) and creatine kinase (CK) activities and lactate concentration (also measured 6, 10, and 15 min after the test). Plasma cytokines (IL-6, IL-1ß, TNF-α, IL-8, IL-10, and IL-1ra) and C-reactive protein levels were also measured. Results: A single dose of MGln increased the percentage of maximal oxygen consumption, second ventilatory threshold duration, and total distance covered during the exhaustion test and augmented plasma lactate levels 6 and 15 min after the test. MGln also decreased plasma LDH and CK activities indicating muscle damage protection. Plasma cytokine and C-reactive protein levels did not change across the study periods. Conclusion: Conditions including overnight fasting and a single dose of MGln supplementation resulted in exercising at a higher percentage of maximal oxygen consumption, a higher second ventilatory threshold, blood lactate levels, and reductions in plasma markers of muscle damage during an exhaustion test in elite triathletes. These findings support oral glutamine supplementation's efficacy in triathletes, but further studies require.

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.

A simple mathematical model for the evaluation of the long first wave of the COVID-19 pandemic in Brazil.

We propose herein a mathematical model to predict the COVID-19 evolution and evaluate the impact of governmental decisions on this evolution, attempting to explain the long duration of the pandemic in the 26 Brazilian states and their capitals well as in the Federative Unit. The prediction was performed based on the growth rate of new cases in a stable period, and the graphics plotted with the significant governmental decisions to evaluate the impact on the epidemic curve in each Brazilian state and city. Analysis of the predicted new cases was correlated with the total number of hospitalizations and deaths related to COVID-19. Because Brazil is a vast country, with high heterogeneity and complexity of the regional/local characteristics and governmental authorities among Brazilian states and cities, we individually predicted the epidemic curve based on a specific stable period with reduced or minimal interference on the growth rate of new cases. We found good accuracy, mainly in a short period (weeks). The most critical governmental decisions had a significant temporal impact on pandemic curve growth. A good relationship was found between the predicted number of new cases and the total number of inpatients and deaths related to COVID-19. In summary, we demonstrated that interventional and preventive measures directly and significantly impact the COVID-19 pandemic using a simple mathematical model. This model can easily be applied, helping, and directing health and governmental authorities to make further decisions to combat the pandemic.

Melatonin improves the antioxidant capacity in cardiac tissue of Wistar rats after exhaustive exercise.

We investigated the effects of melatonin on the onset and resolution of the oxidative stress in the cardiac muscle in melatonin-treated and nontreated rats subjected to an exhaustive exercise session. Forty male rats were divided into: melatonin-treated (20 mg/kg supplemented for 10 d) and control. On the 10th day, each group was subdivided according to euthanasia moments: control or melatonin-treated not exercised (C0h and M0h); immediately after the exercise (CIA and MIA); and 2 h after exercise (C2h and M2h). The heart of animals was removed and the levels of oxidative stress index (OSI) and the formation of thiobarbituric acid reactive substances (TBARS), protein carbonyl, and the activities of aconitase, catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were evaluated. Total antioxidant status (TAS), total oxidant status (TOS), and the protein expression of CAT, GPx, and SOD was also measured. Our data revealed significant differences on: (i) OSI (p=.029), CAT activity (p=.016), CAT content (p<.001), GPx content (p=.014), reduced glutathione levels (p<.001), and aconitase activity (p<.001) for interaction of melatonin; (ii) GPx activity (p=.005), reduced glutathione (p=.004), protein carbonyl (p=.035), and TBARS levels (p=.028) between groups, and (iii) TBARS levels (p=.016) for significance between moments. Although the exhaustive exercise protocol imposed mild oxidative stress on the cardiac tissue of rats, melatonin induced antioxidant responses that rebalanced the redox status of the cardiac tissue, especially after exhaustive exercise.

Grip and load force control and coordination in individuals with diabetes in different manipulation tasks.

The study aimed to investigate the control and coordination of grip force (normal component) and load force (tangential component) in three different manipulation tasks in individuals with diabetes with and with no diagnosis of diabetic peripheral neuropathy (DPN) and healthy controls. Twenty-four individuals with type 2 diabetes mellitus, 12 with no (nDPN) and 12 with DPN (wDPN), and 12 healthy controls performed three manipulation tasks (static holding, lifting and holding, and oscillation) with the dominant hand, using an instrumented handle. Relative safety margin (% of GF exerted above the minimum GF needed to hold the object) was measured in all tasks. Individuals with diabetes from the nDPN and wDPN groups set lower relative safety margin than controls only in the static holding task. No other group effect was revealed, except a lower coefficient of friction between skin and object surface in individuals with DPN. The coordination between grip and load force and grip force control was not affected by the diabetes during dynamic manipulation tasks (lifting and holding and oscillation). However, when individuals with diabetes without and with DPN performed a manipulation task in which the inflow of cutaneous information was small and stable (static holding), grip force control was affected by the disease. This finding indicates that individuals with type 2 diabetes mellitus not diagnosed with DPN, already show mild impairments in the nervous system that could affect grip force control and that could be one of the first signs of neuropathy caused by the diabetes.

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.

Melatonin, Zinc, and Vitamin C: Potential Adjuvant Treatment for COVID-19 Patients.

The use of nutraceutical approaches may regulate the immune system, performing a potential strategy to contain the worst outcomes of COVID-19. We reviewed the current evidence surrounding nutritional/nutraceutical approaches for the therapy in patients with COVID-19. We searched the PubMed database to report randomized controlled trials (RCTs) and observational research that used melatonin, zinc, or vitamin C supplementation as an intervention for COVID-19 treatment. To date, we found only three concluded studies that assessed zinc supplementation and melatonin therapy in patients with COVID-19, but with inconclusive data, relatively small sample size, and early termination of the trial. On the other hand, vitamin C therapy appears to reduce hyperinflammation and improve the oxygen support status of patients with COVID-19. However, a large part of this research involves pilot trials, and there are still conflicting data regarding mortality rate, mechanical ventilation, and duration of symptoms of patients with COVID-19. Melatonin, zinc, and vitamin C supplementation should be investigated further on the nutritional status-immune response, and data from ongoing trials are needed to understand these molecules as a therapy strategy in patients COVID-19.