Muscle strength deficits are associated with low bone mineral density in young pediatric cancer survivors:The iBoneFIT project

Background Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density(aBMD).However,the prevalence of muscle strength deficits is not well documented,and the associations of muscle strength with aBMD are unknown in this population.Therefore,this study aimed to investigate the prevalence of upper-and lower-body muscle strength deficits and to examine the associations of upper-and lower-body muscle strength with age-,sex,and race-specific aBMD Z-scores at the total body,total hip,femoral neck,and lumbar spine.Methods This cross-sectional study included 116 pediatric cancer survivors(12.1±3.3 years old,mean±SD;42.2%female).Upper-and lower-body muscle strength were assessed by handgrip and standing long jump test,respectively.Dual‑energy X‑ray absorptiometry was used to measure aBMD(g/cm2).Associations between muscle strength and aBMD were evaluated in multivariable linear regression models.Logistic regression was used to evaluate the contribution of muscle strength(1-decile lower)to the odds of having low aBMD(Z-score≤1.0).All analyses were adjusted for time from treatment completion,radiotherapy exposure,and body mass index.Results More than one-half of survivors were within the 2 lowest deciles for upper-(56.9%)and lower-body muscle strength(60.0%)in comparison to age-and sex-specific reference values.Muscle strength deficits were associated with lower aBMD Z-scores at all sites(B=0.133–0.258,p=0.001–0.032).Each 1-decile lower in upper-body muscle strength was associated with 30%–95%higher odds of having low aBMD Z-scores at all sites.Each 1-decile lower in lower-body muscle strength was associated with 35%–70%higher odds of having low aBMD Z-scores at total body,total hip,and femoral neck.Conclusion Muscle strength deficits are prevalent in young pediatric cancer survivors,and such deficits are associated with lower aBMD Z-scores at all sites.These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added benefit of improving aBMD.

Physical activity and amyloid beta in middle-aged and older adults:A systematic review and meta-analysis

Background:One of the pathological hallmarks distinguishing Alzheimer’s disease from other dementias is the accumulation of amyloid beta(Aβ).Higher physical activity is associated with decreased dementia risk,and one potential path could be through Aβlevels modulation.We aimed to explore the relationship between physical activity and Aβin middle-aged and older adults.Methods:A systematic search of PubMed,Web of Science,PsycINFO,Cochrane Central Register of Controlled Trials,and SPORTDiscus was performed from inception to April 28,2022.Studies were eligible if they included physical activity and Aβdata in adults aged 45 years or older.Multi-level metaanalyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβlevels.Results:In total,37 articles were included(8 randomized controlled trials,3 non-randomized controlled trials,4 prospective longitudinal studies,and 22 cross-sectional studies).The overall effect size of physical activity interventions on changes in blood Aβwas medium(pooled standardized mean difference=-0.69,95%confidence interval(95%CI):-1.41 to 0.03;I^(2)=74.6%).However,these results were not statistically significant,and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid(CSF)and brain Aβ.Data from observational studies were examined based on measurements of Aβin the brain using positron emission tomography scans,CSF,and blood.Higher physical activity was positively associated with Aβonly in the CSF(Estimate r=0.12;95%CI:0.05-0.18;I^(2)=38.00%).Conclusion:Physical activity might moderately reduce blood Aβin middle-aged and older adults.However,results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies.In observational studies,higher levels of physical activity were positively associated with Aβonly in CSF.Therefore,further research is needed to understand the modulating role of physical activity in the brain,CSF,and blood Aβ,as well as its implication for cognitive health.

Expression of miR‑138 in cryopreserved bovine sperm is related to their fertility potential

Background MicroRNAs(miRNAs)are small,single-stranded,non-coding RNA molecules of 22–24 nucleotides that regulate gene expression.In the last decade,miRNAs have been described in sperm of several mammals,including cattle.It is known that miRNAs can act as key gene regulators of early embryogenesis in mice and humans;however,little is known about the content,expression,and function of sperm-borne miRNAs in early bovine embryo.In this study,total sperm RNA was isolated from 29 cryopreserved sperm samples(each coming from a separate bull)using a RNeasy kit and treatment with DNase I.RNA concentration and purity were determined through an Epoch spectrophotometer and an Agilent Bioanalyzer.The expression of 10 candidate miRNAs in bovine sperm(bta-miR-10a,bta-miR-10b,bta-miR-138,bta-miR-146b,bta-miR-19b,bta-miR-26a,bta-miR-34a,bta-miR-449a,bta-miR-495 and btamiR-7),previously identified in testis and/or epididymis,was evaluated with RT-qPCR.The cel-miR-39-3p was used as a spike-in exogenous control.Nonparametric Mann–Whitney tests were run to evaluate which miRNAs were differentially expressed between bulls with high fertility[HF;non-return rates(NRR)ranging from 39.5 to 43.5]and those with subfertility(SF;NRR ranging from 33.3 to 39.3).Several sperm functionality parameters(e.g.,viability,membrane stability or oxygen consumption,among others)were measured by multiplexing flow cytometry and oxygen sensing technologies.Results RNA concentration and purity(260/280 nm ratio)(mean±SD)from the 29 samples were 99.3±84.6 ng/μL and 1.97±0.72,respectively.Bioanalyzer results confirmed the lack of RNA from somatic cells.In terms of the presence or absence of miRNAs,and after applying the Livak method,8 out of 10 miRNAs(bta-miR-10b,-138,-146b,-19b,-26a,-449a,-495,-7)were consistently detected in bovine sperm,whereas the other two(bta-miR-10a,and-34a)were absent.Interestingly,the relative expression of one miRNA(bta-miR-138)in sperm was significantly lower in the SF than in the HF group(P=0.038).In addition to being associated to fertility potential,the presence of this miRNA was found to be negatively correlated with sperm oxygen consumption.The expression of three other miRNAs(bta-miR-19b,bta-miR-26a and bta-miR-7)was also correlated with sperm function variables.Conclusions In conclusion,although functional validation studies are required to confirm these results,this study suggests that sperm bta-miR-138 is involved in fertilization events and beyond,and supports its use as a fertility biomarker in cattle.

Laparoscopic sleeve gastrectomy:More than a restrictive bariatric surgery procedure?

Sleeve gastrectomy(SG) is a restrictive bariatric surgery technique that was first used as part of restrictive horizontal gastrectomy in the original Scopinaro type biliopancreatic diversion. Its good results as a single technique have led to a rise in its use, and it is currently the second most performed technique worldwide. SG achieves clearly better results than other restrictive techniques and is comparable in some aspects to the Roux-en-Y gastric bypass, the current gold standard in bariatric surgery. These benefits have been associated with different pathophysiologic mechanisms unrelated to weight loss such as increased gastric emptying and intestinal transit, and activation of hormonal mechanisms such as increased GLP-1 hormone and decreased ghrelin. The aim of this review was to highlight the salient aspects of SG regarding its historical evolution, pathophysiologic mechanisms, main results, clinical applications and perioperative complications.

Effects of resveratrol and other polyphenols in hepatic steatosis

Non-alcoholic fatty liver disease covers a wide spectrum of liver pathologies which range from simple steatosis to non-alcoholic steatohepatitis.Polyphenols are members of a very large family of plant-derived compounds that can have beneficial effects on human health,and thus their study has become an increasingly important area of human nutrition research.The aim of the present review is to compile published data concerning the effects of both isolated polyphenols as well as polyphenol extracts,on hepatocyte and liver fat accumulation under different steatosis-inducing conditions.The results reported clearly show that this group of biomolecules is able to reduce fat accumulation,but further studies are needed to establish the optimal dose and treatment period length.With regard to the potential mechanisms of action,there is a good consensus.The anti-lipidogenic effect of polyphenols is mainly due to reduced fatty acid and triacylglycerol synthesis,increased in fatty acid oxidation,and reduced of oxidative stress and inflammation.As a general conclusion,it can be stated that polyphenols are biomolecules which produce hepatoprotective effects.To date,these beneficial effects have been demonstrated in cultured cells and animal models.Thus,studies performed in humans are needed before these molecules can be considered as truly useful tools in the prevention of liver steatosis.

Inflammation, lipid metabolism and cardiovascular risk in rheumatoid arthritis: A qualitative relationship?

Life expectancy in patients with rheumatoid arthritis(RA)is reduced compared to the general population owing to an increase in cardiovascular diseases(CVD)not fully explained by traditional cardiovascular risk factors.In recent years,interest has been focused on the alterations in lipid metabolism in relation to chronic inflammation as one of the possible mechanisms involvedin the pathogenesis of atherosclerosis of RA patients.Research regarding this issue has revealed quantitative alterations in lipoproteins during the acute-phase reaction,and has also demonstrated structural alterations in these lipoproteins which affect their functional abilities.Although many alterations in lipid metabolism have been described in this regard,these structural changes associated with inflammation are particularly important in high-density lipoproteins as they affect their cardioprotective functions.In this respect,excessive oxidation in low-density lipoprotein(LDL)and increased lipoprotein(a)with a predominance of smaller apolipoprotein(a)isoforms has also been reported.This article will discuss proinflammatory high-density lipoproteins(pi HDL),oxidized LDL and lipoprotein(a).Elevated concentrations of these lipoproteins with marked pro-atherogenic properties have been observed in RA patients,which could help to explain the increased cardiovascular risk of these patients.

Opposite fates of fructose in the development of metabolic syndrome

This short review comments on the recently published work of Ishimoto et al regarding the opposing effects of fructokinase C and A isoforms on fructoseinduced metabolic syndrome in mice. The framework for the commentary is the preexisting background of epidemiological and experimental data regarding the association between ingestion of fructose, as present in sweetened beverages, and the development of metabolic syndrome. The work of Ishimoto et al clearly confirms the negative effect of fructose on lipid and glucose metabolism, independently from the amount of energy provided by the ingested sugar. It also confirms the absolute requirement of liver fructose metabolism, driven by fructokinase activity, in order to develop the full spectrum of metabolic syndrome alterations.

Commercial Bakery, Fast-Food, and Soft Drink Consumption and Quality of Life in the SUN Project

Objective: Few studies have related nutritional factors with quality of life in healthy populations. Our aim was to analyze the relationship between commercial bakery, fast food or soft drinks consumption and mental and physical quality of life. Study Design: This analysis included 8335 participants from the 'Seguimiento Universidad de Navarra' (SUN) Project (a multipurpose, dynamic cohort). Methods: The consumption of commercial bakery, fast food and soft drinks was assessed through a validated food-frequency questionnaire at baseline. Quality of life was measured after 4 years of follow-up with the Short-Form 36 (SF-36) Health Survey. Generalized Linear Models were fit to assess the regression coefficients (b) and their 95% confidence intervals (95% CI) for the association between commercial bakery, fast food and soft drinks consumption and each domain and the two standardized measures of the SF-36. Results: As compared to the participants in the lowest quintile of consumption, those participants in the highest quintile of consumption of commercial bakery, fast food and soft drinks showed a score significantly lower (>2 points) for vitality (b = -2.14, 95% CI = -3.31 to -0.96), role emotional (b = -2.23, 95% CI = -4.33 to -0.13), and role physical (b = -2.31, 95% IC = -4.26 to -0.36) domains with statistically significant dose-response relationships (p for trend < 0.05). When the food groups were analysed separately, significant inverse associations were found only for commercial bakery and fast-food consumption. Conclusions: The results suggest that high consumption of commercial bakery, fast-food and soft drinks at baseline was associated with worse scores on self-perceived quality of life. This association was stronger for the mental domains of the SF-36.

Serum levels of the novel adipokine isthmin-1 are associated with obesity in pubertal boys

Objectives To evaluate whether there is an association between the serum levels of the novel insulin-like adipokine isthmin-1(ISM1)and obesity-related phenotypes in a population of Spanish children and to investigate the plausible molecular alterations behind the alteration of the serum levels of this protein in children with obesity.Methods The study population is a sub-cohort of the PUBMEP research project,consisting of a cross-sectional population of 119 pubertal children with overweight(17 boys,19 girls),obesity(20 boys,25 girls),and normal weight(17 boys,21 girls).All subjects were classified into experimental groups according to their sex,obesity,and insulin resistance(IR)status.They were counted anthropometry,glucose and lipid metabolism,inflammation and cardiovascular biomarkers as well as isthmin-1(ISM1)serum levels.This population was intended as a discovery population to elucidate the relationship between obesity and ISM1 levels in children.Furthermore,the study population had blood whole-genome DNA methylation examined,allowing deepening into the obesity–ISM1 molecular relationship.Results Higher serum ISM1 levels were observed in boys with obesity than in normal weight(P=0.004)and overweight(P=0.007)boys.ISM1 serum levels were positively associated with body mass index(BMI)Z-score(P=0.005)and fat mass(P=0.058)and negatively associated with myeloperoxidase(MPO)(P=0.043)in boys.Although we did not find associations between ISM1 serum levels and metabolic outcomes in girls,which may indicate a putative sexual dimorphism,fat mass was positively associated in all children,including boys and girls(P=0.011).DNA methylation levels in two-enhancer-related CpG sites of ISM1(cg03304641 and cg14269097)were associated with serum levels of ISM1 in children.Conclusions ISM1 is associated with obesity in boys at the pubertal stage,elucidating how this protein might be of special relevance as a new biomarker of obesity in children.Further studies including a longitudinal design during puberty are needed.

以食物为基础的膳食模式与慢性疾病预防

Matthias B Schulze及其同事讨论了目前已知的膳食模式与癌症、冠心病、卒中及2型糖尿病的关联,重点在仍不确定的领域和未来的研究方向。

NLRP3 inflammasome blockade reduces adipose tissue inflammation and extracellular matrix remodeling

The NLRP3-IL-1β pathway plays an important role in adipose tissue(AT)-induced inflammation and the development of obesityassociated comorbidities.We aimed to determine the impact of NLRP3 on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and extracellular matrix(ECM)remodeling.Samples obtained from 98 subjects were used in a case-control study.The expression of different components of the inflammasome as well as their main effectors and inflammation-and ECM remodeling-related genes were analyzed.The impact of blocking NLRP3 using siRNA in lipopolysaccharide(LPS)-mediated inflammation and ECM remodeling signaling pathways was evaluated.We demonstrated that obesity(P<0.01),obesity-associated T2D(P<0.01)and NAFLD(P<0.05)increased the expression of different com ponents of the inflammasome as well as the expression and release of IL-1β and IL-18 in AT.We also found that obese patients with T2D exhibited increased(P<0.05)hepatic gene expression levels of NLRP3,IL1B and IL18.We showed that NLRP3,but not NLRP1,is regulated by inflammation and hypoxia in visceral adipocytes.We revealed that the inhibition of NLRP3 in human visceral adipocytes significantly blocked(P<0.01)LPS-induced inflammation by downregulating the mRNA levels of CCL2,IL1B,IL6,IL8,S100A8,S100A9,TLR4 and TNF as well as inhibiting(P<0.01)the secretion of IL1-β into the culture medium.Furthermore,blocking NLRP3 attenuated(P<0.01)the LPS-induced expression of important molecules involved in AT fibrosis(COL1A1,COL4A3,COL6A3 and MMP2).These novel findings provide evidence that blocking the expression of NLRP3 reduces AT inflammation with significant fibrosis attenuation.

Diagnostic performance of serum interleukin-6 in pediatric acute appendicitis:a systematic review

Background Despite the radiological and analytical advances of the last decades,there is still a significant rate of diagnostic error in pediatric acute appendicitis.In recent years,multiple biomarkers have emerged as potential diagnostic tools.This study aimed to examine the diagnostic performance of serum interleukin-6 in pediatric acute appendicitis.Methods We conducted a systematic review of the literature that involved an extensive search in the main databases of medical bibliography(Medline,PubMed,Web of Science and SciELO).Two independent reviewers selected the relevant articles based on the previously defined inclusion and exclusion criteria.Methodological quality of the selected article was rated using the QUADAS2 index.Data extraction was performed by two independent reviewers.Results The research in the medical bibliography databases resulted in 68 articles.We removed 26 duplicates.Among the remaining 42 articles,we excluded 33 following the inclusion and exclusion criteria.Of the final 9 studies included in this review,8 provided measured serum interleukin-6 values,and all of them reported significant differences between groups,but inconsistent results regarding sensitivity and specificity.Conclusions The diagnostic performance of interleukine-6 alone for the diagnosis of acute appendicitis in children is limited.The sensitivity and specificity of interleukine-6 for the diagnosis of non-complicated acute appendicitis in the pediatric population are moderate but increased in complicated appendicitis.There seems to be a direct relationship between serum level of interleukin-6 and the hours of evolution of abdominal pain in children with acute appendicitis.The increasingly widespread use of non-operative management of acute appendicitis warrants further exploration of the classificatory potential of this marker between complicated and uncomplicated appendicitis.We consider that this may be an avenue of research to explore in the future.

Prevalence of and risk factors for erectile dysfunction in young nondiabetic obese men:results from a regional study

Erectile dysfunction(ED),a condition closely related to cardiovascular morbidity and mortality,is frequently associated with obesity.In this study,we aimed to determine the prevalence of ED and evaluate the associated risk factors in a cohort of 254 young(18–49 years)nondiabetic obese(body mass index[BMI]≥30 kg m−2)men from primary care.Erectile function(International Index of Erectile Function[IIEF-5]questionnaire),quality of life(Aging Males'Symptoms[AMS scale]),and body composition analysis(Tanita MC-180MA)were determined.Total testosterone was determined using high-performance liquid chromatography–mass spectrometry.Multivariate logistic regression analysis was used to study the factors associated with ED.ED prevalence was 42.1%.Subjects with ED presented higher BMI,waist circumference,number of components of the metabolic syndrome,AMS score,insulin resistance,and a more unfavorable body composition than those without ED.Multivariate logistic regression analysis showed that a pathological AMS score(odds ratio[OR]:4.238,P<0.001),degree of obesity(BMI≥40 kg m−2,OR:2.602,P=0.005,compared with BMI 30–34.9 kg m−2),high-density lipoprotein(HDL)-cholesterol levels(OR:0.956,P=0.004),and age(OR:1.047,P=0.016)were factors independently associated with ED.In conclusion,we demonstrate that,in a primary care-based cohort of nondiabetic young obese men,ED affected>40%of subjects.A pathological AMS score,the degree of obesity,and age were positively associated with ED,while elevated HDL-cholesterol levels were inversely associated with the odds of presenting ED.Further prospective studies are needed to evaluate the long-term consequences of ED in this population.

Mediterranean diet as the ideal model for preventing non-alcoholic fatty liver disease (NAFLD)

The prevalence of nonalcoholic fatty liver disease(NAFLD)has dramatically increased in the 2–3 last decades and it represents the most frequent global cause of liver disease,affecting 25%to 45%of adults in most studies(1).

Antioxidant response of the brown algae Dictyota dichotoma epiphytized by the invasive red macroalgae Lophocladia lallemandii

Objective:To evaluate the response of the brown alga Dictyota dichotoma(D.dichotoma)epiphytized by the red alga Lophocladia lallemandii in Mallorca coastal waters(Balearic Islands)by means of biomarker measures.Methods:Samples of epiphytized and non-epiphytized D.dichotoma were collected in Cala Morlanda(East Mallorca,Balearic Islands).Markers of lipid peroxidation and activities of antioxidant enzymes were measured in D.dichotoma.Results:Lipid peroxidation measured as malondialdehyde and all the antioxidant activities measured were significantly higher in the epiphytized brown algae when compared with the control algae.Conclusions:In conclusion,the invasive algae Lophocladia lallemandii seems to produce a more oxidized status in the epiphytized D.dichotoma and cellular damage that could induce increased mortality.

Parental perception of child's weight,their attitudes towards child's dietary habits and the risk of obesity

Background The association between parental perception of child's weight and their attitudes towards his/her dietary habits has not been reported yet.This study aimed to assess the association between parental underestimation of child's weight and parental attitudes towards child's dietary habits.Methods We conducted a cross-sectional analysis of SENDO cohort participants recruited between January 2015 and June 2020.All information was collected through online questionnaires completed by parents.We calculated crude and multivariable-adjusted odds ratio(OR)and 95%confidence intervals(CI)for unhealthy attitudes towards child's dietary habits associated with parental underestimation of child's weight.Results Sixteen percent of children in the SENDO project had parents who underestimated their weight.Parents who under-estimated their child's weight status were more likely to have unhealthy attitudes toward his/her dietary habits[OR 3.35;95%CI(1.71-6.53)].Conclusions Parental underestimation of child's weight was associated with unhealthy attitudes towards child's dietary hab-its.Pediatricians and public health practitioners should pay attention to the parental perception of child's weight to identify parents who underestimate it as an at-risk group in which to inquire about lifestyle and dietary habits.

Discriminatory capacity of serum interleukin-6 between complicated and uncomplicated acute appendicitis in children:a prospective validation study

Background Serum interleukin-6(IL-6)has a moderate diagnostic performance in pediatric acute appendicitis(PAA).The evidence regarding its capacity to discern between complicated and uncomplicated PAA is scarce.Methods We designed a prospective observational study to validate serum IL-6 as a marker for diagnostic classification between complicated and uncomplicated PAA.This study included 205 patients divided into three groups:(1)patients who underwent major outpatient surgery(n=57);(2)patients with non-surgical abdominal pain(NSAP)in whom the diagnosis of PAA was excluded(n=53),and(3)patients with a confirmed diagnosis of PAA(n=95).The PAA patients were further classified as uncomplicated or complicated PAA.IL-6 concentration was determined in all patients at diagnosis.Comparative statistical analysis was performed using the Mann-Whitney U test,the Fisher exact test and the Kruskall Wallis test.The area under the receiver operating characteristic curves(AUC)were calculated.Results Median(interquartile range,IQR)serum IL-6 values were 2 pg/mL(2.0–3.4)in group 1,3.9 pg/mL(2.4–11.9)in group 2,and 23.9 pg/mL(11.1–61.0)in group 3(P<0.001).Among the participants in group 3,those with uncomplicated PAA had median(IQR)serum IL-6 values of 17.2 pg/mL(8.5–36.8),and those with complicated PAA had 60.25 pg/mL(27.1–169)serum IL-6(P<0.001).At the cut-off point of 19.55 pg/mL,the AUC for the discrimination between patients in group 2 vs.3 was 0.83[95%confidence interval(CI)0.76–0.90],with a sensitivity of 61.3%and a specificity of 86.8.The AUC for the discrimination between patients with uncomplicated and complicated PAA was 0.77(95%CI 0.68–0.86)and the cut-off point was 25.90 pg/mL,with a sensitivity and specificity of 84.6%and 65.6%,respectively.Conclusions Serum IL-6 has a good performance in discerning between complicated and uncomplicated PAA.A score including clinical and radiological variables may increase the diagnostic performance of this molecule.

FNDC4 and FNDC5 reduce SARS-CoV-2 entry points and spike glycoprotein S1-induced pyroptosis, apoptosis, and necroptosis in human adipocytes

A sedentary lifestyle and obesity are important risk factors for severe COVID-19 complications and death[1,2].Excessive adipose tissue(AT)might contribute to more extensive viral spread with increased shedding,immune activation,and cytokine amplification[3].Several factors secreted by contracting muscle,termed myokines,mediate the beneficial effects of exercise in a wide range of diseases,including obesity[4].Thus,we conducted a study to explore the potential role of myokines of the fibronectin type III domain-containing family,FNDC4 and FNDC5,in mechanisms underlying the increased susceptibility to COVID-19 complications in obesity.

SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation

Sirtuin 3(SIRT3)is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress.Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances.In this study,we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells.SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1.Consistent with this,SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α.Notably,these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1.Finally,we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter.These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway.Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy,heart failure,and diabetic cardiomyopathy,our results point to SIRT3 as a potential target for treating these diseases.

Natural products,PGC-1α,and Duchenne muscular dystrophy

Peroxisome proliferator-activated receptorγ(PPARγ)is a transcriptional coactivator that binds to a diverse range of transcription factors.PPARγcoactivator 1(PGC-1)coactivators possess an extensive range of biological effects in different tissues,and play a key part in the regulation of the oxidative metabolism,consequently modulating the production of reactive oxygen species,autophagy,and mitochondrial biogenesis.Owing to these findings,a large body of studies,aiming to establish the role of PGC-1 in the neuromuscular system,has shown that PGC-1 could be a promising target for therapies targeting neuromuscular diseases.Among these,some evidence has shown that various signaling pathways linked to PGC-1αare deregulated in muscular dystrophy,leading to a reduced capacity for mitochondrial oxidative phosphorylation and increased reactive oxygen species(ROS)production.In the light of these results,any intervention aimed at activating PGC-1 could contribute towards ameliorating the progression of muscular dystrophies.PGC-1αis influenced by different patho-physiological/pharmacological stimuli.Natural products have been reported to display modulatory effects on PPARγactivation with fewer side effects in comparison to synthetic drugs.Taken together,this review summarizes the current knowledge on Duchenne muscular dystrophy,focusing on the potential effects of natural compounds,acting as regulators of PGC-1α.