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Antioxidants (Basel, Switzerland) Jun 2023Carnosine and anserine supplementation markedLy reduce diabetic nephropathy in rodents. The mode of nephroprotective action of both dipeptides in diabetes, via local...
Carnosine and anserine supplementation markedLy reduce diabetic nephropathy in rodents. The mode of nephroprotective action of both dipeptides in diabetes, via local protection or improved systemic glucose homeostasis, is uncertain. Global carnosinase-1 knockout mice (-KO) and wild-type littermates (WT) on a normal diet (ND) and high fat diet (HFD) ( = 10/group), with streptozocin (STZ)-induced type-1 diabetes ( = 21-23/group), were studied for 32 weeks. Independent of diet, -KO mice had 2- to 10-fold higher kidney anserine and carnosine concentrations than WT mice, but otherwise a similar kidney metabolome; heart, liver, muscle and serum anserine and carnosine concentrations were not different. Diabetic -KO mice did not differ from diabetic WT mice in energy intake, body weight gain, blood glucose, HbA1c, insulin and glucose tolerance with both diets, whereas the diabetes-related increase in kidney advanced glycation end-product and 4-hydroxynonenal concentrations was prevented in the KO mice. Tubular protein accumulation was lower in diabetic ND and HFD -KO mice, interstitial inflammation and fibrosis were lower in diabetic HFD -KO mice compared to diabetic WT mice. Fatalities occurred later in diabetic ND -KO mice versus WT littermates. Independent of systemic glucose homeostasis, increased kidney anserine and carnosine concentrations reduce local glycation and oxidative stress in type-1 diabetic mice, and mitigate interstitial nephropathy in type-1 diabetic mice on HFD.
PubMed: 37372000
DOI: 10.3390/antiox12061270 -
Journal of Cachexia, Sarcopenia and... Aug 2023Muscle wasting during cancer cachexia is mediated by protein degradation via autophagy and ubiquitin-linked proteolysis. These processes are sensitive to changes in...
BACKGROUND
Muscle wasting during cancer cachexia is mediated by protein degradation via autophagy and ubiquitin-linked proteolysis. These processes are sensitive to changes in intracellular pH ([pH] ) and reactive oxygen species, which in skeletal muscle are partly regulated by histidyl dipeptides, such as carnosine. These dipeptides, synthesized by the enzyme carnosine synthase (CARNS), remove lipid peroxidation-derived aldehydes, and buffer [pH] . Nevertheless, their role in muscle wasting has not been studied.
METHODS
Histidyl dipeptides in the rectus abdominis (RA) muscle and red blood cells (RBCs) of male and female controls (n = 37), weight stable (WS: n = 35), and weight losing (WL; n = 30) upper gastrointestinal cancer (UGIC) patients, were profiled by LC-MS/MS. Expression of enzymes and amino acid transporters, involved in carnosine homeostasis, was measured by Western blotting and RT-PCR. Skeletal muscle myotubes were treated with Lewis lung carcinoma conditioned medium (LLC CM), and β-alanine to study the effects of enhancing carnosine production on muscle wasting.
RESULTS
Carnosine was the predominant dipeptide present in the RA muscle. In controls, carnosine levels were higher in men (7.87 ± 1.98 nmol/mg tissue) compared with women (4.73 ± 1.26 nmol/mg tissue; P = 0.002). In men, carnosine was significantly reduced in both the WS (5.92 ± 2.04 nmol/mg tissue, P = 0.009) and WL (6.15 ± 1.90 nmol/mg tissue; P = 0.030) UGIC patients, compared with controls. In women, carnosine was decreased in the WL UGIC (3.42 ± 1.33 nmol/mg tissue; P = 0.050), compared with WS UGIC patients (4.58 ± 1.57 nmol/mg tissue), and controls (P = 0.025). Carnosine was significantly reduced in the combined WL UGIC patients (5.12 ± 2.15 nmol/mg tissue) compared with controls (6.21 ± 2.24 nmol/mg tissue; P = 0.045). Carnosine was also significantly reduced in the RBCs of WL UGIC patients (0.32 ± 0.24 pmol/mg protein), compared with controls (0.49 ± 0.31 pmol/mg protein, P = 0.037) and WS UGIC patients (0.51 ± 0.40 pmol/mg protein, P = 0.042). Depletion of carnosine diminished the aldehyde-removing ability in the muscle of WL UGIC patients. Carnosine levels were positively associated with decreases in skeletal muscle index in the WL UGIC patients. CARNS expression was decreased in the muscle of WL UGIC patients and myotubes treated with LLC-CM. Treatment with β-alanine, a carnosine precursor, enhanced endogenous carnosine production and decreased ubiquitin-linked protein degradation in LLC-CM treated myotubes.
CONCLUSIONS
Depletion of carnosine could contribute to muscle wasting in cancer patients by lowering the aldehyde quenching abilities. Synthesis of carnosine by CARNS in myotubes is particularly affected by tumour derived factors and could contribute to carnosine depletion in WL UGIC patients. Increasing carnosine in skeletal muscle may be an effective therapeutic intervention to prevent muscle wasting in cancer patients.
Topics: Female; Humans; Male; Aldehydes; beta-Alanine; Carcinoma, Lewis Lung; Carnosine; Chromatography, Liquid; Dipeptides; Muscle, Skeletal; Muscular Atrophy; Tandem Mass Spectrometry; Ubiquitins
PubMed: 37199284
DOI: 10.1002/jcsm.13258 -
Frontiers in Cellular and Infection... 2023The protozoan parasite is the primary cause of human babesiosis. This parasite invades and multiplies inside red blood cells (RBCs), and infections differ significantly...
INTRODUCTION
The protozoan parasite is the primary cause of human babesiosis. This parasite invades and multiplies inside red blood cells (RBCs), and infections differ significantly based on the age and immune competency of the host. The aim of this study was to investigate the use of serum metabolic profiling to identify systemic metabolic variations between -infected mice and noninfected controls.
METHODS
A serum metabolomics analysis of BALB/c mice that had been intraperitoneally injected with 10 -infected RBCs was performed. Serum samples from the early infected group (2 days postinfection), the acutely infected group (9 days postinfection), and the noninfected group were collected and evaluated using a liquid chromatography-mass spectrometry (LC-MS) platform. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) identified metabolomic profiles that differentiated the -infected and noninfected groups.
RESULTS
Our results confirm that the serum metabolome is significantly influenced by acute infection and show that infection results in dysregulation of metabolic pathways and perturbation of metabolites. Acutely infected mice displayed perturbations in metabolites associated with taurine and hypotaurine metabolism, histidine metabolism, and arachidonic acid metabolism. Taurocholic acid, anserine, and arachidonic acid may be potential candidates as serological biomarkers for diagnosing infection at the acute stage. These metabolites could be further examined for their role in disease complexity.
DISCUSSION
Our findings demonstrate that the acute stage of infection induces abnormalities in the metabolites present in mouse serum and provide new insight into the mechanisms involved in systemic metabolic changes that occur during infection.
Topics: Humans; Animals; Mice; Babesia microti; Babesiosis; Mice, Inbred BALB C; Arachidonic Acid; Metabolomics
PubMed: 37187473
DOI: 10.3389/fcimb.2023.1179967 -
Food Science & Nutrition May 2023This study aimed to characterize the metabolic composition of four types of commercially available chicken breeds [village chicken, colored broiler (Hubbard), broiler...
This study aimed to characterize the metabolic composition of four types of commercially available chicken breeds [village chicken, colored broiler (Hubbard), broiler (Cobb), and spent layers (Dekalb)] by H NMR coupling and discriminate them using multivariate analysis. Five chickens were collected for each chicken breed based on the marketing age from the respective commercial farms. The orthogonal partial least squares discriminant analysis (OPLS-DA) results showed an obvious separation of local village chickens from the other breeds based on the metabolites present in their serum and meat (pectoralis major). The cumulative values of , , and of the OPLS-DA model for chicken serum were 0.722, 0.877, and 0.841. For the pectoralis major muscle, the cumulative values of , , and of the OPLS-DA model were reported as 0.684, 0.781, and 0.786, respectively. The quality of both OPLS-DA models was accepted by the cumulative values of ≥ 0.5 and ≥ 0.65. The H NMR result with multivariate analysis has successfully distinguished local village chicken from the other three commercial chicken breeds based on serum and pectoralis major muscle. Nonetheless, colored broiler (Hubbard) was not distinguished from broiler (Cobb) and spent layers (Dekalb) in serum and pectoralis major, respectively. The OPLS-DA assessment in this study identified 19 and 15 potential metabolites for discriminating different chicken breeds in serum and pectoralis major muscle, respectively. Some of the prominent metabolites identified include amino acids (betaine, glycine, glutamine, guanidoacetate, phenylalanine, and valine), nucleotides (IMP and NAD+), organic acids (lactate, malate, and succinate), peptide (anserine), and sugar alcohol (myo-inositol).
PubMed: 37181311
DOI: 10.1002/fsn3.2968 -
Medical Journal of the Islamic Republic... 2023The success rate of extracorporeal shock wave therapy (ESWT) in treating epicondylitis, plantar fasciitis, rotator cuff tendonitis, Achilles tendonitis, and Jumper knee...
Comparison of the Effectiveness of Local Corticosteroid Injection and Extracorporeal Shockwave Therapy in Patients With Pes Anserine Bursitis: An Open-Label Randomized Clinical Trial.
The success rate of extracorporeal shock wave therapy (ESWT) in treating epicondylitis, plantar fasciitis, rotator cuff tendonitis, Achilles tendonitis, and Jumper knee has been reported to be 60% to 80%. Most published studies have compared focused ESWT at different intensities with local corticosteroid injection (LCI). We only identified a few studies that specifically compared ESWT with LCI in patients with pes anserine bursitis (PAB). This study aimed to compare the effectiveness of ESWT and LCI in patients with PAB. The present study was a randomized clinical trial. Patients diagnosed with PAB who were referred to the physical medicine and rehabilitation clinic underwent a complete physical examination. They (n = 60 patients) were randomly assigned to the ESWT and LCI groups if they met the study criteria. In the ESWT group, 1 ESWT session was performed weekly for 3 consecutive weeks. In the LCI group, 1 injection was performed under an ultrasonography guide. Pes anserine thickness, pain intensity, and treatment satisfaction were measured with visual analog scale (VAS) and quality of life (Short Form-12). A paired-samples t test was used to compare the results obtained in the pre-and posttests. Analysis of variance for repeated measures was used to detect differences over time. The null hypothesis would not be confirmed if the P value was less than the 0.05 level of significance. Pes anserine thickness and pain intensity decreased significantly during the study in both groups ( < 0.001). However, the mean difference of pes anserine thickness was more in the LCI group the ESWT group [(-0.6; 95% CI, -1.0 to -0.3) than (-0.1; 95% CI, -0.5, -0.2); = 0.008]. Also, the mean difference of pain intensity was lower in the ESWT group] than the LCI group [(-2.9; 95% CI, -3.7 to -2.1) (1.0; 95% CI, 0.1to 1.8); < 0.001]. Patients' quality of life in both groups increased significantly during the study period ( < 0.001), but the increase in quality of life in patients in the ESWT group (mean difference, 15.3 [95% CI, 10.6-19.9]) was considerably more than in the LCI group (mean difference, -5.3 (95% CI, -10.0 to -0.6). Overall, the results of this study showed that both local corticosteroid injections and extracorporeal shock wave therapy are safe and effective in PAB patients.
PubMed: 37123337
DOI: 10.47176/mjiri.37.10 -
Scientific Reports Apr 2023Balenine possesses some of carnosine's and anserine's functions, yet it appears more resistant to the hydrolysing CN1 enzyme. The aim of this study was to elucidate the...
Balenine possesses some of carnosine's and anserine's functions, yet it appears more resistant to the hydrolysing CN1 enzyme. The aim of this study was to elucidate the stability of balenine in the systemic circulation and its bioavailability in humans following acute supplementation. Two experiments were conducted in which (in vitro) carnosine, anserine and balenine were added to plasma to compare degradation profiles and (in vivo) three increasing doses (1-4-10 mg/kg) of balenine were acutely administered to 6 human volunteers. Half-life of balenine (34.9 ± 14.6 min) was respectively 29.1 and 16.3 times longer than that of carnosine (1.20 ± 0.36 min, p = 0.0044) and anserine (2.14 ± 0.58 min, p = 0.0044). In vivo, 10 mg/kg of balenine elicited a peak plasma concentration (Cmax) of 28 µM, which was 4 and 18 times higher than with 4 (p = 0.0034) and 1 mg/kg (p = 0.0017), respectively. CN1 activity showed strong negative correlations with half-life (ρ = - 0.829; p = 0.0583), Cmax (r = - 0.938; p = 0.0372) and incremental area under the curve (r = - 0.825; p = 0.0433). Overall, balenine seems more resistant to CN1 hydrolysis resulting in better in vivo bioavailability, yet its degradation remains dependent on enzyme activity. Although a similar functionality as carnosine and anserine remains to be demonstrated, opportunities arise for balenine as nutraceutical or ergogenic aid.
Topics: Humans; Carnosine; Anserine; Dietary Supplements
PubMed: 37081019
DOI: 10.1038/s41598-023-33300-1 -
Advanced Science (Weinheim,... Jun 2023Meat is among the most consumed foods worldwide and has a unique flavor and high nutrient density in the human diet. However, the genetic and biochemical bases of meat...
Meat is among the most consumed foods worldwide and has a unique flavor and high nutrient density in the human diet. However, the genetic and biochemical bases of meat nutrition and flavor are poorly understood. Here, 3431 metabolites and 702 volatiles in 423 skeletal muscle samples are profiled from a gradient consanguinity segregating population generated by Pekin duck × Liancheng duck crosses using metabolomic approaches. The authors identified 2862 metabolome-based genome-wide association studies (mGWAS) signals and 48 candidate genes potentially modulating metabolite and volatile levels, 79.2% of which are regulated by cis-regulatory elements. The level of plasmalogen is significantly associated with TMEM189 encoding plasmanylethanolamine desaturase 1. The levels of 2-pyrrolidone and glycerophospholipids are regulated by the gene expression of AOX1 and ACBD5, which further affects the levels of volatiles, 2-pyrrolidone and decanal, respectively. Genetic variations in GADL1 and CARNMT2 determine the levels of 49 metabolites including L-carnosine and anserine. This study provides novel insights into the genetic and biochemical basis of skeletal muscle metabolism and constitutes a valuable resource for the precise improvement of meat nutrition and flavor.
Topics: Animals; Humans; Genome-Wide Association Study; Ducks; Meat; Metabolome; Muscle, Skeletal; Carboxy-Lyases
PubMed: 37013465
DOI: 10.1002/advs.202300148 -
Scientific Reports Mar 2023This integrative study of transcriptomics and metabolomics aimed to improve our understanding of Wooden Breast myopathy (WB). Breast muscle samples from 8 WB affected...
This integrative study of transcriptomics and metabolomics aimed to improve our understanding of Wooden Breast myopathy (WB). Breast muscle samples from 8 WB affected and 8 unaffected male broiler chickens of 47 days of age were harvested for metabolite profiling. Among these 16 samples, 5 affected and 6 unaffected also underwent gene expression profiling. The Joint Pathway Analysis was applied on 119 metabolites and 3444 genes exhibiting differential abundance or expression between WB affected and unaffected chickens. Mitochondrial dysfunctions in WB was suggested by higher levels of monoacylglycerols and down-regulated genes involved in lipid production, fatty acid beta oxidation, and oxidative phosphorylation. Lower levels of carnosine and anserine, along with down-regulated carnosine synthase 1 suggested decreased carnosine synthesis and hence impaired antioxidant capacity in WB. Additionally, Weighted Gene Co-expression Network Analysis results indicated that abundance of inosine monophosphate, significantly lower in WB muscle, was correlated with mRNA expression levels of numerous genes related to focal adhesion, extracellular matrix and intercellular signaling, implying its function in connecting and possibly regulating multiple key biological pathways. Overall, this study showed not only the consistency between transcript and metabolite profiles, but also the potential in gaining further insights from analyzing multi-omics data.
Topics: Animals; Male; Transcriptome; Chickens; Pectoralis Muscles; Carnosine; Gene Expression Profiling; Muscular Diseases; Energy Metabolism; Poultry Diseases
PubMed: 36959331
DOI: 10.1038/s41598-023-31429-7 -
Journal of Pain Research 2023Knee osteoarthritis (KOA) is a chronic inflammatory disease highly associated with intra-articular hypertension, hypoxia and angiogenesis of synovial tissue. Our...
PURPOSE
Knee osteoarthritis (KOA) is a chronic inflammatory disease highly associated with intra-articular hypertension, hypoxia and angiogenesis of synovial tissue. Our previous studies showed that acupotomy could treat KOA in a variety of ways, including reducing cartilage deterioration and enhancing biomechanical qualities. However, the mechanism of hypoxia and angiogenesis induced by acupotomy in KOA synovium remains unclear. This study looked for the benign intervention of acupotomy in synovial pathology.
METHODS
The rabbits were divided into 3 groups, Normal group, KOA group, and KOA + Acupotomy (Apo) group, with 11 rabbits in each group. The KOA rabbit model was established by the modified Videman method with six weeks. The KOA + Apo group performed the intervention. The tendon insertion of vastus medialis, vastus lateralis, rectus femoris, biceps femoris, and anserine bursa were selected as treatment points in rabbits. Rabbits were treated once every 7 days for 3 weeks. We observed the intra-articular pressure and oxygen partial pressure (BOLD MRI). The synovial morphology was monitored by Hematoxylin-Eosin Staining (HE Staining). The expression of hypoxia-inducible transcription factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) was detected using Immunohistochemical (IHC), Western Blot and Enzyme-Linked Immunosorbent Assay (ELISA).
RESULTS
Acupotomy reduced intra-articular hypertension and improved the synovial oxygen situation, synovial inflammatory and angiogenesis. HIF-1α, VEGF, IL-1β and TNF-α expression were downregulated by acupotomy.
CONCLUSION
Acupotomy may reduce inflammation and angiogenesis in KOA rabbit by reducing abnormally elevated intra-articular pressure and improving synovial oxygen environment. The above may provide a new theoretical foundation for acupotomy treatment of KOA.
PubMed: 36919160
DOI: 10.2147/JPR.S396955