Denervation does not induce muscle atrophy through oxidative stress

Denervation leads to the activation of the catabolic pathways, such as the ubiquitin-proteasome and autophagy, resulting in skeletal muscle atrophy and weakness. Furthermore, denervation induces oxidative stress in skeletal muscle, which is thought to contribute to the induction of skeletal muscle atrophy. Several muscle diseases are characterized by denervation, but the molecular pathways contributing to muscle atrophy have been only partially described. Our study delineates the kinetics of activation of oxidative stress response in skeletal muscle following denervation. Despite the denervation-dependent induction of oxidative stress in skeletal muscle, treatments with anti-oxidant drugs do not prevent the reduction of muscle mass. Our results indicate that, although oxidative stress may contribute to the activation of the response to denervation, it is not responsible by itself of oxidative damage or neurogenic muscle atrophy

Peroxynitrite activates the NLRP3 inflammasome cascade in SOD1(G93A) mouse model of amyotrophic lateral sclerosis

Neuroinflammation, characterized by the appearance of reactive microglial and astroglial cells, is one of the several pathogenic mechanisms of amyotrophic lateral sclerosis (ALS), a fast-progressing and fatal neurodegenerative disease. Cerebrospinal fluid and spinal cord of ALS patients and SOD1 mutant mice show high concentrations of IL-1β. This interleukin, expressed as an inactive precursor, undergoes a proteolytic maturation by caspase1, whose activation, in turn, depends on inflammasomes. Whether and how inflammasome is activated in ALS models is still to be clarified. The mechanism of inflammasome activation was studied in murine microglial cells overexpressing hSOD1(G93A) and verified in the spinal cord of hSOD1(G93A) mice. Murine microglial hSOD1(G93A) cells express all the inflammasome components and LPS activates caspase1 leading to an increase in the secretion of IL-1β. By activating NF-κB, LPS increases ROS and NO levels that spontaneously react to form peroxynitrite, thus leading to protein nitration. Reduction in peroxynitrite levels results in a decrease in caspase1 activity. Protein nitration and caspase1 activity are concomitantly increased in the spinal cord of pre-symptomatic SOD1(G93A) mice. Oxidative/nitrosative stress induces peroxynitrite formation that may be a key trigger of caspase1/inflammasome activation. Peroxynitrite formation may play a critical role in inflammasome activation and might be exploited as potential therapeutic target for ALS

Oxidative stress-induced S100B accumulation in myoblasts converts myoblasts into brown preadipocytes via an NF-κB/YY1/MIR-133 axis and NF-κB/YY1/BMP7 axis

Muscles of sarcopenic people show hypotrophic myofibers and infiltration with adipose and, at later stages, fibrotic tissue. The origin of infiltrating adipocytes resides in fibro-adipogenic precursors, nonmyogenic mesenchymal progenitor cells, and satellite cells, the adult stem cells of skeletal muscles. Myoblasts and brown adipocytes share a common Myf5+ progenitor cell, and cell fate decision depends on levels of BMP7, a TGF-β family member; high BMP7 levels cause Myf5+ progenitor cells to differentiate in brown adipocytes. When expressed at relatively high levels as observed in myoblasts from sarcopenic humans, intracellular S100B, a Ca2+-binding protein of the EF-hand type (1), exerts anti-myogenic effects that are reversed by S100B knockdown (2,3). We show that ROS-activated NF-κB induces accumulation of S100B that causes myoblasts to convert into brown preadipocytes via 1) an NF-κB/YY1 axis that negatively regulates the promyogenic and anti-brown adipogenic miR-133 with consequent accumulation of the pro-brown adipogenic transcription factor, PRDM16, and 2) an NF-κB/YY1/BMP7 axis with resultant BMP7 autocrine activity. Also, culturing L6C8 (S100b-overexpressing) myoblasts (2) in adipocyte differentiation medium causes NF-κB-dependent upregulation of S100B expression, which precedes and is required for lipid droplet formation. Lastly, S100B knockdown in myoblast-derived brown adipocytes reconvert them into fusion competent myoblasts. Thus, S100B is a major molecular determinant of cell fate decision of proliferating myoblasts; while modulating myoblast differentiation (2,3), at high levels S100B promotes myoblast-brown adipocyte transition, which might have pathophysiological implications in sarcopenia.This work was supported by grants from MIUR FIRB RBFR12BUMH_003 and Fondazione CRP 2016.0136.021

Black Soldier Fly live larvae as environmental enrichment in medium-growing chicken diet

Introduction. Few studies on the effects of live larvae provision in poultry have been previously conducted [1,2,3]. However, trials on the long-term provision of live larvae in chicken reared for meat consumption have never been performed before. This study evaluated the impact of Black Soldier Fly (BSF) live larvae provision on growth performance and larvae consumption behavior of intermediate-growing strains. Material and methods. A total of 240 Label naked neck birds were reared from 21 to 82 days of age, and four experimental groups (10 birds/pen, 6 replicates/treatment) were considered according to the birds’ gender and larvae provision. Experimental groups were fed 10% supplementation of BSF live larvae based on the daily feed intake. The live weight (LW), feed conversion ratio (FCR), average daily feed intake (ADFI) and average daily gain (ADG) were evaluated considering two periods: 21-35d and 35-82d. The larvae were provided daily and consumption times were analyzed considering periods of 10 days (5 time frame-T1,T2,T3,T4,T5). Data were analyzed by means of a GLMM (SPSS software, P<0.05). Results. The larvae groups displayed a lower ADFI than the control groups regardless the birds’ gender at 21-35d (P=0.01). This could be explained by the larvae nutritional contribution that led to a lower feed consumption in the experimental groups. Moreover, treated birds revealed a lower FCR than control groups (21-35d; P<0.001). Otherwise, only treated males performed a better FCR than control groups during the second period (P<0.01). Overall, time of larvae consumption at T1 and T5was respectively higher and lower than the other considered periods in both sexes (P<0.05). Such differences could be related to a progressive birds’ adaptation to larvae consumption. Significant differences between sexes were recorded only at T5, when females employed much time than males in larvae consumption (P<0.05). Conclusion. Live larvae provision ameliorated both the ADFI and FCR. Furthermore, the time of larvae consumption shrinked as birds became older. References. [1] Star L. et al. (2020). Animals. 10,216. [2] Bellezza Oddon et al. (2021). J. Anim. Physiol. Anim. 00,1–9. [3] Veldkamp T. and T.G.C.M. Van Niekerk (2019). J. Insects as Food Feed. 5,301-31

Blood chemistry of medium-growing male and female chickens supplemented black soldier fly live larvae

Effects of live larvae provision on poultry chemical blood parameters have been poorly investigated. This study aims to evaluate the changes in blood chemistry parameters in medium-growing chickens supplemented black soldier fly (BSF) live larvae. Two hundred and forty 21d old sexed Label Naked Neck birds were divided into 4 experimental groups: females fed basal organic feed (BOF), males fed BOF, females fed BOF + 10% BSF live larvae supplementation based on the expected daily feed intake (DFI) and males fed BOF + 10% BSF live larvae supplementation based on the DFI (6 replicates/diet, 10 birds/replicate). Blood samples were collected at slaughter (82d old) from 2 birds/pen (12 birds/treatment). Serum samples were used for biochemical analysis. A compact liquid chemistry analyzer system (BT 1500 vet–Futurlab) was used to determine the concentrations of alanine aminotransferase (U/I), aspartate aminotransferase (U/I), creatinine total proteins (mg/dl), uric acid (mg/dl), cholesterol (mg/dl), triglycerides (mg/dl), gamma glutamyltransferase (GGT, U/I), phosphorus (mg/dl) and magnesium (mg/dl). Data were analyzed by GLMM (SPSS software, P<0.05). Overall, the blood parameters were not affected by the live larvae supplementation (P>0.05) in both sexes, thus being indicative of a good health status of the birds. Moreover, the GGT was detected in lower concentrations in the supplemented groups than in the control groups (P<0.05), suggesting a positive effect on the hepatic function. In conclusion, the live BSF larvae provision did not negatively affect the blood parameters of medium-growing chickens and could be beneficial for bird hepatic activity

Blood chemistry of medium-growing male and female chickens supplemented black soldier fly live larvae

Effects of live larvae provision on poultry chemical blood parameters have been poorly investigated. This study aims to evaluate the changes in blood chemistry parameters in medium-growing chickens supplemented black soldier fly (BSF) live larvae. Two hundred and forty 21d old sexed Label Naked Neck birds were divided into 4 experimental groups: females fed basal organic feed (BOF), males fed BOF, females fed BOF + 10% BSF live larvae supplementation based on the expected daily feed intake (DFI) and males fed BOF + 10% BSF live larvae supplementation based on the DFI (6 replicates/diet, 10 birds/replicate). Blood samples were collected at slaughter (82d old) from 2 birds/pen (12 birds/treatment). Serum samples were used for biochemical analysis. A compact liquid chemistry analyzer system (BT 1500 vet–Futurlab) was used to determine the concentrations of alanine aminotransferase (U/I), aspartate aminotransferase (U/I), creatinine total proteins (mg/dl), uric acid (mg/dl), cholesterol (mg/dl), triglycerides (mg/dl), gamma glutamyltransferase (GGT, U/I), phosphorus (mg/dl) and magnesium (mg/dl). Data were analyzed by GLMM (SPSS software, P<0.05). Overall, the blood parameters were not affected by the live larvae supplementation (P>0.05) in both sexes, thus being indicative of a good health status of the birds. Moreover, the GGT was detected in lower concentrations in the supplemented groups than in the control groups (P<0.05), suggesting a positive effect on the hepatic function. In conclusion, the live BSF larvae provision did not negatively affect the blood parameters of medium-growing chickens and could be beneficial for bird hepatic activity

Natriuretic Peptides: The Case of Prostate Cancer

Cardiac natriuretic peptides have long been known to act as main players in the homeostatic control of blood pressure, salt and water balance. However, in the last few decades, new properties have been ascribed to these hormones. A systematic review of English articles using MEDLINE Search terms included prostate cancer, inflammation, cardiac hormones, atrial natriuretic peptide, and brain natriuretic peptide. Most recent publications were selected. Natriuretic peptides are strongly connected to the immune system, whose two branches, innate and adaptive, are finely tuned and organized to kill invaders and repair injured tissues. These peptides control the immune response and act as anti-inflammatory and immune-modulatory agents. In addition, in cancers, natriuretic peptides have anti-proliferative effects by molecular mechanisms based on the inhibition/regulation of several pathways promoting cell proliferation and survival. Nowadays, it is accepted that chronic inflammation is a crucial player in prostate cancer development and progression. In this review, we summarize the current knowledge on the link between prostate cancer and inflammation and the potential use of natriuretic peptides as anti-inflammatory and anticancer agents