Obesity-dependent molecular alterations in fatal COVID-19: A retrospective postmortem study of metabolomic profile of adipose tissue.

We investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI], 26.5 ± 2.3 kg m-2) or obese (OB BMI 34.2 ± 5.1 kg m-2). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OB group showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6 and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.

Physical Exercise-Induced Activation of NRF2 and BDNF as a Promising Strategy for Ferroptosis Regulation in Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. Ferroptosis, an iron-dependent form of regulated cell death, may contribute to the progression of PD owing to an unbalanced brain redox status. Physical exercise is a complementary therapy that can modulate ferroptosis in PD by regulating the redox system through the activation of nuclear factor (erythroid-derived 2)-like 2 (NRF2) and brain-derived neurotrophic factor (BDNF) signaling. However, the precise effects of physical exercise on ferroptosis in PD remain unclear. In this review, we explored how physical exercise influences NRF2 and BDNF signaling and affects ferroptosis in PD. We further investigated relevant publications over the past two decades by searching the PubMed, Web of Science, and Google Scholar databases using keywords related to physical exercise, PD, ferroptosis, and neurotrophic factor antioxidant signaling. This review provides insights into current research gaps and demonstrates the necessity for future research to elucidate the specific mechanisms by which exercise regulates ferroptosis in PD, including the assessment of different exercise protocols and their long-term effects. Ultimately, exploring these aspects may lead to the development of improved exercise interventions for the better management of patients with PD.

Bone-marrow mononuclear cells and acellular human amniotic membrane improve global cardiac function without inhibition of the NLRP3 Inflammasome in a rat model of heart failure.

Recent studies have suggested that therapies with stem cells and amniotic membrane can modulate the inflammation following an ischemic injury in the heart. This study evaluated the effects of bone-marrow mononuclear cells (BMMC) and acellular human amniotic membrane (AHAM) on cardiac function and NLRP3 complex in a rat model of heart failure.On the 30th day,the echocardiographic showed improvements on ejection fraction and decreased pathological ventricular remodeling on BMMC and AHAM groups.Oxidative stress analysis was similar between the three groups,and the NLRP3 inflammasome activity were not decreased with the therapeutic use of both BMMC and AHAM,in comparison to the control group.

Physical Training Protects Against Brain Toxicity in Mice Exposed to an Experimental Model of Glioblastoma.

Glioma 261 (Gl261) cell-mediated neurotoxicity has been reported in previous studies examining glioblastoma (GBM), and the effects of physical exercise (PE) on this neurotoxicity have been poorly investigated. This study aimed to evaluate the effects of a PE program in animals with experimental GBM. Male C57BL/6J mice were randomized into sham or GBM groups and subjected to a PE program for four weeks. Gl261 cells were administered into the intraventricular region at 48 h after the last exercise session. Body weight, water and feed consumption, and behavior were all evaluated for 21 days followed by euthanasia. The right parietal lobe was removed for the analysis of glial fibrillary acidic protein (GFAP), epidermal growth factor receptor (EGFR), vimentin, C-myc, nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), hydrogen peroxide, the glutathione system, and oxidative damage to proteins. The results revealed changes in the behavioral patterns of the trained animals, and no anatomopathological changes were observed in response to PE training. In contrast, animals with GBM subjected to PE exhibited lower immunoexpression of c-MYC, vimentin, and GFAP. Although experimental GBM altered the redox profile and inflammatory mediators, no significant alterations were observed after PE. In conclusion, our data provide consistent evidence of the relationship between PE and the improvement of tumorigenic parameters against the neurotoxicity of GL261 cells.

Lung Inflammasome Activation in SARS-CoV-2 Post-Mortem Biopsies.

The inflammasome complex is a key part of chronic diseases and acute infections, being responsible for cytokine release and cell death mechanism regulation. The SARS-CoV-2 infection is characterized by a dysregulated cytokine release. In this context, the inflammasome complex analysis within SARS-CoV-2 infection may prove beneficial to understand the disease's mechanisms. Post-mortem minimally invasive autopsies were performed in patients who died from COVID-19 (n = 24), and lung samples were compared to a patient control group (n = 11) and an Influenza A virus H1N1 subtype group from the 2009 pandemics (n = 10). Histological analysis was performed using hematoxylin-eosin staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: ACE2, TLR4, NF-κB, NLRP-3 (or NALP), IL-1ß, IL-18, ASC, CASP1, CASP9, GSDMD, NOX4, TNF-α. Data obtained from digital analysis underwent appropriate statistical tests. IHC analysis showed biomarkers that indicate inflammasome activation (ACE2; NF-κB; NOX4; ASC) were significantly increased in the COVID-19 group (p < 0.05 for all) and biomarkers that indicate cell pyroptosis and inflammasome derived cytokines such as IL-18 (p < 0.005) and CASP1 were greatly increased (p < 0.0001) even when compared to the H1N1 group. We propose that the SARS-CoV-2 pathogenesis is connected to the inflammasome complex activation. Further studies are still warranted to elucidate the pathophysiology of the disease.

Effect of taurine associated gold nanoparticles on oxidative stress in muscle of mice exposed to overuse model.

Muscle overuse and its consequent muscle damage has no cure. Therefore, the present study aimed to investigate the regulatory role of tau-AuNPs on muscle recovery of muscle overuse model. The animals (Male Swiss mice) were randomly divided into four groups: Control (Ctr; n=6); tau-AuNPs (n=6); overuse (n=6); and overuse plus tau-AuNPs (n=6). Exercise sessions were performed for 21 consecutive days, and one exercise model was applied daily in the following sequence: low intensity, moderate intensity, and high intensity. The mice were then sacrificed. The quadriceps muscles were surgically removed for subsequent biochemical analysis (oxidative stress parameters, DNA damage markers and muscle differentiation protein). The overuse group significantly increased the oxidative stress parameters and DNA damage markers, whereas tau-AuNPs significantly decreased the oxidative stress parameters in the overuse animal model. However, there were no significant differences observed between overuse group and overuse plus tau-AuNPs administrated group in relation to DNA damage markers including DNA damage frequency and index levels when compared to control and tau-AuNPs groups. Muscle differentiation protein Myf-5 was increased in the overuse plus tau-AuNPs administration group when compared to control group. In conclusion, tau-AuNPs had significant effect on reducing oxidative stress parameters and increasing myogenic regulatory protein Myf-5 in the overuse group. However, it did not have significant effect on reducing DNA damage.

Yerba mate (Ilex paraguariensis St. Hil.) extract inhibits hand-rolled cornhusk cigarette smoke-induced oxidative pulmonary damage.

The aim of this study was to investigate the effects of yerba mate (Ilex paraguariensis St. Hil.) extract (YME) on oxidative stress parameters and pathological changes in the lungs of mice chronically exposed to hand-rolled cornhusk cigarette (HRC) smoke. Twenty-four male Swiss mice were divided into four groups exposed to the following treatments: control (ambient air), HRC, YME, and HRC plus YME. The animals were exposed to four HRCs per session, with 3 sessions/day, every day for 30 days. Twenty-four hours after the last inhalation, the mice were killed, and the left lungs were removed. The results showed that HRC contains elevated levels of tin and carbon oxide, but less arsenic, cobalt, manganese, and selenium than commercial cigarettes. YME administration reversed fibrosis, alveolar enlargement, and hemorrhage induced by HRC smoke. In addition, the YME and HRC significantly reduced the production of oxidants, oxidative damage and promoted a significant increase in total thiol. In conclusion, exposure to HRC smoke compromised pulmonary histoarchitecture by promoting structural changes and increasing oxidative stress in tissues. However, concomitant treatment with YME regulated the redox state and reduced the harmful effects of HRC smoke exposure in the lungs.

The role of continuous versus fractionated physical training on muscle oxidative stress parameters and calcium-handling proteins in aged rats.

Age-associated decline in skeletal muscle mass and strength is associated with oxidative stress and Ca(2+) homeostasis disturbance. Exercise should be considered a viable modality to combat aging of skeletal muscle. This study aimed to investigate whether continuous and fractionated training could be useful tools to attenuate oxidative damage and retain calcium-handling proteins. We conducted the study using 24-month-old male Wistar rats, divided into control, continuous, and fractionated groups. Animals ran at 13 m min(-1) for five consecutive days (except weekends) for 6 weeks, for a total period of 42 days. Each session comprised 45 min of exercise, either continuous or divided into three daily sessions of 15 min each. Metabolic and oxidative stress markers, protein levels of mitochondrial transcription factors, and calcium-handling proteins were analyzed. Continuous exercise resulted in reduced ROS production as well as showed a decrease in TBARS levels and carbonyl content. On the other hand, fractionated training increased the antioxidant enzyme activities. The ryanodine receptor and phospholamban protein were regulated by continuous training while sodium calcium exchange protein was increased by the fractionated training. These data suggest that intracellular Ca(2+) can be modulated by various training stimuli. In addition, the modulation of oxidative stress by continuous and fractionated training may play an important regulatory role in the muscular contraction mechanism of aged rats, due to changes in calcium metabolism.

Treadmill training increases SIRT-1 and PGC-1 α protein levels and AMPK phosphorylation in quadriceps of middle-aged rats in an intensity-dependent manner.

The present study investigated the effects of running at 0.8 or 1.2 km/h on inflammatory proteins (i.e., protein levels of TNF- α , IL-1 ß , and NF- κ B) and metabolic proteins (i.e., protein levels of SIRT-1 and PGC-1 α , and AMPK phosphorylation) in quadriceps of rats. Male Wistar rats at 3 (young) and 18 months (middle-aged rats) of age were divided into nonexercised (NE) and exercised at 0.8 or 1.2 km/h. The rats were trained on treadmill, 50 min per day, 5 days per week, during 8 weeks. Forty-eight hours after the last training session, muscles were removed, homogenized, and analyzed using biochemical and western blot techniques. Our results showed that: (a) running at 0.8 km/h decreased the inflammatory proteins and increased the metabolic proteins compared with NE rats; (b) these responses were lower for the inflammatory proteins and higher for the metabolic proteins in young rats compared with middle-aged rats; (c) running at 1.2 km/h decreased the inflammatory proteins and increased the metabolic proteins compared with 0.8 km/h; (d) these responses were similar between young and middle-aged rats when trained at 1.2 km. In summary, the age-related increases in inflammatory proteins, and the age-related declines in metabolic proteins can be reversed and largely improved by treadmill training.

The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice.

Extensive research has confirmed numerous advantages of exercise for promoting brain health. More recent studies have proposed the potential benefits of lactate, the by-product of exercise, in various aspects of brain function and disorders. However, there remains a gap in understanding the effects of lactate dosage and its impact on aged rodents. The present study first examined the long-term effects of three different doses of lactate intervention (2000 mg/kg, 1000 mg/kg, and 500 mg/kg) and high-intensity interval training (HIIT) on aging mice (20-22 months) as the 1st experiment. Subsequently, in the 2nd experiment, we investigated the long-term effects of 500 mg/kg lactate intervention and HIIT on brain neuroplasticity in aged mice (25-27 months). The results of the 1st experiment demonstrated that both HIIT and different doses of lactate intervention (500 mg/kg and 2000 mg/kg) positively impacted the neuroplasticity biomarker VEGF in the hippocampus of aging mice. Subsequently, the 2nd experiment revealed that long-term HIIT significantly improved the performance of mice in open-field, novel object recognition, and passive avoidance tests. However, lactate intervention did not significantly affect these behavioral tests. Moreover, compared to the control group, both HIIT and lactate intervention positively influenced the angiogenesis signaling pathway (p/t-AKT/ENOS/VEGF), mitochondrial biomarker (SDHA), and metabolic protein (p/t-CREB, p/t-HSL, and LDH) in the hippocampus of aged mice. Notably, only lactate intervention significantly elevated the BDNF (PGC-1α, SIRT1, and BDNF) signaling pathway and metabolic content (lactate and pyruvate). In the end, long-term HIIT and lactate intervention failed to change the protein expression of p/t-MTOR, iNOS, nNOS, HIF-1α, SYNAPSIN, SIRT3, NAMPT, CS, FNDC5 and Pan Lactic aid-Lysine in the hippocampus of aged mice. In summary, the present study proved that long-term HIIT and lactate treatment have positive effects on the brain functions of aged mice, suggesting the potential usage of lactate as a therapeutic strategy in neurodegenerative diseases in the elderly population.

Resveratrol and fish oil reduce catecholamine-induced mortality in obese rats: role of oxidative stress in the myocardium and aorta.

The exact mechanisms of the relationship between obesity and cardiovascular events are not yet fully understood; however, oxidative stress may be involved. Thus, the aim of the present study was to evaluate the effects of resveratrol and fish oil on catecholamine-induced mortality in obese rats. To begin with, rats were divided into five groups: (1) lean, (2) obese, (3) obese supplemented with resveratrol, (4) obese supplemented with fish oil and (5) obese supplemented with resveratrol and fish oil (n 18 rats per group), for 2 months. After supplementation, the groups were subdivided as with (n 10) and without (n 8) cardiovascular catecholaminergic stress after isoproterenol (60 mg/kg) injection. At 24 h later, the survival rate was analysed. The obese group showed lower survival rates (10 %) when compared with the lean group (70 %). On the other hand, resveratrol (50 %) and fish oil (40 %) increased the survival rate of obese rats (χ(2) test, P= 0·019). Biochemical analyses of the myocardium and aorta revealed that obese rats had higher levels of superoxide and oxidative damage to lipids and protein. This was associated with reduced superoxide dismutase and glutathione peroxidase activity in both the myocardium and aorta. The supplementation increased antioxidant enzyme activities and reduced oxidative damage. We also evaluated the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 antioxidant pathway. Nrf2 protein levels that were reduced in obese rats were increased by the antioxidant treatment. Taken together, these results showed that resveratrol and fish oil reduce catecholamine-induced mortality in obese rats, partly through the reduction of oxidative stress.

Creatine supplementation does not decrease oxidative stress and inflammation in skeletal muscle after eccentric exercise.

Thirty-six male rats were used; divided into 6 groups (n = 6): saline; creatine (Cr); eccentric exercise (EE) plus saline 24 h (saline + 24 h); eccentric exercise plus Cr 24 h (Cr + 24 h); eccentric exercise plus saline 48 h (saline + 48 h); and eccentric exercise plus Cr 48 h (Cr + 48 h). Cr supplementation was administered as a solution of 300 mg · kg body weight(-1) · day(-1) in 1 mL water, for two weeks, before the eccentric exercise. The animals were submitted to one downhill run session at 1.0 km · h(-1) until exhaustion. Twenty-four and forty-eight hours after the exercise, the animals were killed, and the quadriceps were removed. Creatine kinase levels, superoxide production, thiobarbituric acid reactive substances (TBARS) level, carbonyl content, total thiol content, superoxide dismutase, catalase, glutathione peroxidase, interleukin-1b (IL-1ß), nuclear factor kappa B (NF-kb), and tumour necrosis factor (TNF) were analysed. Cr supplementation neither decreases Cr kinase, superoxide production, lipoperoxidation, carbonylation, total thiol, IL-1ß, NF-kb, or TNF nor alters the enzyme activity of superoxide dismutase, catalase, and glutathione peroxides in relation to the saline group, respectively (P < 0.05). There are positive correlations between Cr kinase and TBARS and TNF-α 48 hours after eccentric exercise. The present study suggests that Cr supplementation does not decrease oxidative stress and inflammation after eccentric contraction.

A remote, fully oriented personalized program of physical exercise for women in follow-up after breast cancer treatment improves body composition and physical fitness.

This study aimed to evaluate the efficacy of an individualized remote exercise program on the improvement of body composition and physical fitness of a heterogeneous group of patients who completed breast cancer treatment. This prospective study included 107 women aged 18 to 60, shortly after curative treatment for localized breast cancer, at the Erasto Gaertner Cancer Hospital (HEG) in Curitiba, PR, Brazil. Body composition, maximal oxygen consumption, and muscle resistance were evaluated after nine months of intervention while considering adherence to the program, level of physical activity, presence of binge eating disorder, tumor classification, and treatment type. Seventy-eight women (72.8%) adhered to the training program. Adherent participants showed significant changes in body mass ([-4.3 â€‹± â€‹3.6] kg; p â€‹< â€‹0.000 1), body mass index ([-1.6 â€‹± â€‹1.5] kg·m-2; p â€‹< â€‹0.000 1), body fat (-3.4% â€‹± â€‹3.1%; p â€‹< â€‹0.000 1), maximal oxygen consumption ([7.5 â€‹± â€‹2.0] ml·kg-1·min-1); p â€‹< â€‹0.000 1), and abdominal resistance ([11.2 â€‹± â€‹2.8] reps; p â€‹< â€‹0.000 1). In contrast, these variables did not change significantly in the non-adherent group. Among the adherent participants, those subclassified in the severe binge group showed a more noticeable reduction in body mass, body mass index, and body fat (p â€‹< â€‹0.05) than those in the non-binge group. Individualized remotely-guided physical exercise programs can improve the body composition and physical fitness of women undergoing post-breast cancer surveillance, regardless of pathological history or treatment.

Voluntary exercise does not increase gastrointestinal motility but increases spatial memory, intestinal eNOS, Akt levels, and Bifidobacteria abundance in the microbiome.

The interaction between the gut and brain is a great puzzle since it is mediated by very complex mechanisms. Therefore, the possible interactions of the brain-exercise-intestine-microbiome axis were investigated in a control (C, N = 6) and voluntarily exercised (VE, N = 8) middle-aged rats. The endurance capacity was assessed by VO2max on the treadmill, spatial memory by the Morris maze test, gastrointestinal motility by EMG, the microbiome by 16S RNA gene amplicon sequencing, caveolae by electron microscopy, and biochemical assays were used to measure protein levels and production of reactive oxygen species (ROS). Eight weeks of voluntary running increased VO2max, and spatial memory was assessed by the Morris maze test but did not significantly change the motility of the gastrointestinal tract or production of ROS in the intestine. The protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) protein levels significantly increased in the intestine, while peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM), nuclear respiratory factor 1 (NFR1), SIRT1, SIRT3, nicotinamide phosphoribosyl transferase (NAMPT), and nuclear factor κB (NF-κB) did not change. On the other hand, voluntary exercise increased the number of caveolae in the smooth muscles of the intestine and relative abundance of Bifidobacteria in the microbiome, which correlated with the Akt levels in the intestine. Voluntary exercise has systemic effects and the relationship between intestinal Akt and the microbiome of the gastrointestinal tract could be an important adaptive response.

Regulation of Redox Profile and Genomic Instability by Physical Exercise Contributes to Neuroprotection in Mice with Experimental Glioblastoma.

Glioblastoma (GBM) is an aggressive, common brain cancer known to disrupt redox biology, affecting behavior and DNA integrity. Past research remains inconclusive. To further understand this, an investigation was conducted on physical training's effects on behavior, redox balance, and genomic stability in GBMA models. Forty-seven male C57BL/6J mice, 60 days old, were divided into GBM and sham groups (n = 15, n = 10, respectively), which were further subdivided into trained (Str, Gtr; n = 10, n = 12) and untrained (Sut, Gut; n = 10, n = 15) subsets. The trained mice performed moderate aerobic exercises on a treadmill five to six times a week for a month while untrained mice remained in their enclosures. Behavior was evaluated using open-field and rotarod tests. Post training, the mice were euthanized and brain, liver, bone marrow, and blood samples were analyzed for redox and genomic instability markers. The results indicated increased latency values in the trained GBM (Gtr) group, suggesting a beneficial impact of exercise. Elevated reactive oxygen species in the parietal tissue of untrained GBM mice (Gut) were reduced post training. Moreover, Gtr mice exhibited lower tail intensity, indicating less genomic instability. Thus, exercise could serve as a promising supplemental GBM treatment, modulating redox parameters and reducing genomic instability.

Pulsed ultrasound associated with gold nanoparticle gel reduces oxidative stress parameters and expression of pro-inflammatory molecules in an animal model of muscle injury.

BACKGROUND: Nanogold has been investigated in a wide variety of biomedical applications because of the anti-inflammatory properties. The purpose of this study was to evaluate the effects of TPU (Therapeutic Pulsed Ultrasound) with gold nanoparticles (GNP) on oxidative stress parameters and the expression of pro-inflammatory molecules after traumatic muscle injury. MATERIALS AND METHODS: Animals were divided in nine groups: sham (uninjured muscle); muscle injury without treatment; muscle injury + DMSO; muscle injury + GNP; muscle injury + DMSO + GNP; muscle injury + TPU; muscle injury + TPU + DMSO; muscle injury + TPU + GNP; muscle injury + TPU + DMSO + GNP. The ROS production was determined by concentration of superoxide anion, modulation of antioxidant defenses was determined by the activity of superoxide dismutase, catalase and glutathione peroxidase enzymes, oxidative damage determined by formation of thiobarbituric acid-reactive substance and protein carbonyls. The levels of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were measured as inflammatory parameters. RESULTS: Compared to muscle injury without treatment group, the muscle injury + TPU + DMSO + GNP gel group promoted a significant decrease in superoxide anion production and lipid peroxidation levels (p < 0.050). It also showed a significant decrease in TNF-α and IL-1ß levels (p < 0.050) when compared to muscle injury without treatment group. CONCLUSIONS: Our results suggest that TPU + DMSO + GNP gel presents beneficial effects on the muscular healing process, inducing a reduction in the production of ROS and also the expression of pro-inflammatory molecules.

Alterations in muscular oxidative metabolism parameters in incremental treadmill exercise test in untrained rats.

The present study investigates the effects of incremental exercise test on muscular oxidative metabolism. Thirty-six 2-month-old male Wistar rats were distributed in seven groups that performed exercise at different levels: first level (control), second level (0.6 km/h), third level (0.6 and 0.8 km/h), fourth level (0.6, 0.8 and 1.0 km/h), fifth level (0.6, 0.8, 1.0 and 1.2 km/h), sixth level (0.6, 0.8, 1.0, 1.2 and 1.4 km/h), and seventh level (0.6, 0.8, 1.0, 1.2, 1.4 and 1.6 km/h). At the end of the exercise challenge, level of blood lactate (BL), glycogen content (MG), creatine kinase (CK), complexes (CI, CII, CIII, CIV), oxidative damage, succinate dehydrogenase (SDH), cytochrome c oxidase as well as antioxidant enzymes (SOD and CAT) expression were measured. The speed of 1.0 km/h increased BL level, while 1.2 km/h decreased MG and increased serum CK. Increased SDH expression was observed after intensity levels 6 and 7, and cytochrome c oxidase expression increased after levels 5, 6 and 7, in comparison with lower intensity levels, ETC enzyme activities increased when exercise was applied at intensities of 0.8 km/h (CI), 1.0 km/h (CII and CIII), and 1.2 km/h (CIV). The increase in SOD expression did not occur as observed for superoxide production, except for rats that underwent exercise at level 7, but CAT expression increased significantly in all levels, starting from level 3. Our results show interesting alterations in the muscular metabolism parameters, and suggest a differential response of muscle oxidative metabolism when intense exercise is applied at different speeds.

Redox Status Is the Mainstay of SARS-CoV-2 and Host for Producing Therapeutic Opportunities.

Over hundreds of years, humans have faced multiple pandemics and have overcome many of them with scientific advancements. However, the recent coronavirus disease (COVID-19) has challenged the physical, mental, and socioeconomic aspects of human life, which has introduced a general sense of uncertainty among everyone. Although several risk profiles, such as the severity of the disease, infection rate, and treatment strategy, have been investigated, new variants from different parts of the world put humans at risk and require multiple strategies simultaneously to control the spread. Understanding the entire system with respect to the commonly involved or essential mechanisms may be an effective strategy for successful treatment, particularly for COVID-19. Any treatment for COVID-19 may alter the redox profile, which can be an effective complementary method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and further replication. Indeed, redox profiles are one of the main barriers that suddenly shift the immune response in favor of COVID-19. Fortunately, several redox components exhibit antiviral and anti-inflammatory activities. However, access to these components as support elements against COVID-19 is limited. Therefore, understanding redox-derived species and their nodes as a common interactome in the system will facilitate the treatment of COVID-19. This review discusses the redox-based perspectives of the entire system during COVID-19 infection, including how redox-based molecules impact the accessibility of SARS-CoV-2 to the host and further replication. Additionally, to demonstrate its feasibility as a viable approach, we discuss the current challenges in redox-based treatment options for COVID-19.

Gold Nanoparticle-Based Therapy for Muscle Inflammation and Oxidative Stress.

Proinflammatory cytokines and reactive oxygen species are released after muscle damage, and although they are necessary for the muscle regeneration process, an excess of these substances leads to the destruction of biomolecules and impairment of the repair system. Several drugs have emerged in recent years to control the muscle inflammatory response, and studies have shown that gold nanoparticles (AuNPs) have anti-inflammatory and antioxidant properties. This review reveals the effects of AuNPs on the inflammatory and redox mechanisms of muscles. We assessed the results of several studies published in different journals over the last 20 years, with a focus on the effects of AuNPs on possible aspects of muscle regeneration or recovery, namely, inflammatory processes and redox system mechanisms. A systematic database search was conducted using PubMed, Medline, Bireme, Web of Science, and Google Scholar to identify peer-reviewed studies from the 2000s. Combinations of keywords related to muscle damage, regeneration or repair, AuNPs, oxidative stress, and antioxidants were used in the search. This review did not address other variables, such as specific diseases or other biological effects; however, these variables should be considered for a complete understanding of the effects of AuNPs on skeletal muscles.

Resistance Exercise Training Improves Metabolic and Inflammatory Control in Adipose and Muscle Tissues in Mice Fed a High-Fat Diet.

This study investigates whether ladder climbing (LC), as a model of resistance exercise, can reverse whole-body and skeletal muscle deleterious metabolic and inflammatory effects of high-fat (HF) diet-induced obesity in mice. To accomplish this, Swiss mice were fed for 17 weeks either standard chow (SC) or an HF diet and then randomly assigned to remain sedentary or to undergo 8 weeks of LC training with progressive increases in resistance weight. Prior to beginning the exercise intervention, HF-fed animals displayed a 47% increase in body weight (BW) and impaired ability to clear blood glucose during an insulin tolerance test (ITT) when compared to SC animals. However, 8 weeks of LC significantly reduced BW, adipocyte size, as well as glycemia under fasting and during the ITT in HF-fed rats. LC also increased the phosphorylation of AktSer473 and AMPKThr172 and reduced tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL1-ß) contents in the quadriceps muscles of HF-fed mice. Additionally, LC reduced the gene expression of inflammatory markers and attenuated HF-diet-induced NADPH oxidase subunit gp91phox in skeletal muscles. LC training was effective in reducing adiposity and the content of inflammatory mediators in skeletal muscle and improved whole-body glycemic control in mice fed an HF diet.