Role of metabolic stress for enhancing muscle adaptations: Practical applications

Metabolic stress is a physiological process that occurs during exercise in response to low energy that leads to metabolite accumulation [lactate, phosphate inorganic(Pi) and ions of hydrogen(H^+)] in muscle cells.Traditional exercise protocol(i.e., Resistance training) has an important impact on the increase of metabolite accumulation, which influences hormonal release, hypoxia, reactive oxygen species(ROS) production and cell swelling.Changes in acute exercise routines, such as intensity, volume and rest between sets, are determinants for the magnitude of metabolic stress, furthermore, different types of training, such as lowintensity resistance training plus blood flow restriction and high intensity interval training, could be used to maximize metabolic stress during exercise.Thus, the objective of this review is to describe practical applications that induce metabolic stress and the potential effects of metabolic stress to increase systemic hormonal release, hypoxia, ROS production, cell swelling and muscle adaptations.

Cell senescence,loss of splicing,and lipid metabolism in TDP-43-related neurodegenerative processes

In recent work,we have shown that cell senescence of mouse fibroblasts in vitro associates with a build-up of cryptic exons in selected mRNAs,whose level is usually controlled by the activity of TAR DNA binding protein of 43 kDa(Tdp-43)(Torres et al.,2022).In vivo,we also found traits of cell senescence in the motor neuron disease model achieved by overexpressing SOD-G93A,the SOD1 gene(harboring a single amino acid substitution of glycine to alanine at codon 93).

Necrotizing enterocolitis: A multifactorial disease with no cure

Necrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature o the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Developmen of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.

Statin, testosterone and phosphodiesterase 5-inhibitor treatments and age related mortality in diabetes

AIM To determine how statins, testosterone(T) replacement therapy(TRT) and phosphodiesterase 5-inhibitors(PDE5I) influence age related mortality in diabetic men.METHODS We studied 857 diabetic men screened for the BLAST study, stratifying them(mean follow-up = 3.8 years) into:(1) Normal T levels/untreated(total T > 12 nmol/L and free T > 0.25 nmol/L), Low T/untreated and Low T/treated;(2) PDE5I/untreated and PDE5I/treated; and(3) statin/untreated and statin/treated groups. The relationship between age and mortality, alone and with T/TRT, statin and PDE5 I treatment was studied using logistic regression. Mortality probability and 95%CI were calculated from the above models for each individual. RESULTS Age was associated with mortality(logistic regression, OR = 1.10, 95%CI: 1.08-1.13, P < 0.001). With all factors included, age(OR = 1.08, 95%CI: 1.06-1.11, P < 0.001), Low T/treated(OR = 0.38, 95%CI: 0.15-0.92, P = 0.033), PDE5I/treated(OR = 0.17, 95%CI: 0.053-0.56, P = 0.004) and statin/treated(OR = 0.59, 95%CI: 0.36-0.97, P = 0.038) were associated with lower mortality. Age related mortality was as described by Gompertz, r2 = 0.881 when Ln(mortality) was plotted against age. The probability of mortality and 95%CI(from logistic regression) of individuals, treated/untreated with the drugs, alone and in combination was plotted against age. Overlap of 95%CI lines was evident with statins and TRT. No overlap was evident with PDE5 I alone and with statins and TRT, this suggesting a change in the relationship between age and mortality. CONCLUSION We show that statins, PDE5 I and TRT reduce mortality in diabetes. PDE5 I, alone and with the other treatments significantly alter age related mortality in diabetic men.

Effect of microencapsulated watermelon(Citrullus lanatus)intake on plasma amino acids and glycemic response in healthy adults

Watermelon is an L-citrulline-rich fruit that has been used as a supplement to increase L-arginine in plasma,which in turn plays a critical role in the synthesis of nitric oxide,a molecule that regulates vascular tone.Watermelon rind,similar to its pulp,presents a high L-citrulline content,yet a lower concentration of sugar,which would be more convenient for individuals who need to refrain from excessive sugar ingestion(i.e.,diabetics and obese individuals).Further,ingestion of watermelon rind can be a sustainable alternative to increase plasma L-arginine,given that rind of fruits is commonly discarded.Therefore,we evaluated the effect of ingestion of a product derived from watermelon rind and pulp(microencapsulation in spray drier)on plasma amino acids(L-citrulline,L-arginine and L-ornithine),glucose,and insulin.Eleven participants(28.36±5.70 years)were enrolled in a single blind,cross-over and randomized study.They ingested microencapsulated watermelon rind and pulp(containing 4 g of L-citrulline)plasma amino acids,glucose,and insulin were evaluated before and 30,60,90 and 120 min after ingestion.It was observed that both microencapsulated watermelon rind and pulp increased L-citrulline through 120 min and microencapsulated watermelon rind significantly increased L-arginine at 30 min.In addition,microencapsulated watermelon rind and pulp similarly increased plasma glucose and insulin levels.In conclusion,these findings suggest that both microencapsulated watermelon rind and pulp are effective to increase plasma L-citrulline and microencapsulated watermelon rind effectively increases plasma L-arginine.In addition,rind and pulp promote similar changes on plasma glucose and insulin.