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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 -
Cardiovascular and Interventional... Nov 2023Transarterial embolization for the treatment of chronic musculoskeletal diseases is gaining increasing interest in the field of interventional radiology. Overuse sports... (Review)
Review
Transarterial embolization for the treatment of chronic musculoskeletal diseases is gaining increasing interest in the field of interventional radiology. Overuse sports injury is defined as an injury occurring in the absence of a single, identifiable traumatic cause. In the treatment of this condition, there is a need for reliable results and a quick return to activity. Minimally invasive treatments with short periods of missed practice are required. Intra-arterial embolization has the potential to meet this need. In this article, we describe cases of embolization for refractory overuse sports injuries including patellar tendinopathy, pes anserine, plantar fasciitis, triangular fibrocartilage complex injury, hamstring injury, infrapatellar fat pad inflammation, Achilles tendinopathy, delayed union metatarsal bone fracture, lumbar spondylolysis, and repetitive hamstrings strain.
Topics: Humans; Athletic Injuries; Achilles Tendon; Tendinopathy; Cumulative Trauma Disorders; Embolization, Therapeutic
PubMed: 37433909
DOI: 10.1007/s00270-023-03496-w -
Research Square Nov 2023Muscle wasting is a serious complication in heart failure patients, and oxidative stress is involved in the pathogenesis of muscle wasting. Oxidative stress leads to the...
BACKGROUND
Muscle wasting is a serious complication in heart failure patients, and oxidative stress is involved in the pathogenesis of muscle wasting. Oxidative stress leads to the formation of toxic lipid peroxidation products, such as 4-hydroxy-2-nonenal (HNE) and acrolein, which causemuscle wasting. In tissues, these toxic aldehydes are metabolically removed by enzymes such asaldo keto reductases and endogenous nucleophiles, such as glutathione and carnosine. Whether these metabolic pathways could be affected in skeletal muscle during heart failure has never been studied.
METHODS
Male wild-type C57BL/6J mice were subjected to a pressure overload model of hypertrophy by transaortic constriction (TAC) surgery, and echocardiography was performed after 14 weeks. Different skeletal muscle beds were weighed and analyzed for atrophic and inflammatory markers, and and , respectively, by RT-PCR. Levels of acrolein and HNE-protein adducts, aldehyde-removing enzymes, aldose reductase (AKR1B1) and aldehyde dehydrogenase 2 (ALDH2) were measured by Western blotting, and histidyl dipeptides and histidyl dipeptide aldehyde conjugates were analyzed by LC/MS-MS in the gastrocnemius and soleus muscles of sham- and TAC-operated mice. Furthermore, histidyl dipeptide synthesizing enzyme carnosine synthase (CARNS) and amino acid transporters (PEPT2 and TAUT)wasmeasured in the gastrocnemius muscles of the sham and TAC-operated mice.
RESULTS
TAC-induced heart failure decreases body weight and gastrocnemius and soleus muscle weights. The expression of the atrophic and inflammatory markers and TNF-α, respectively, wasincreased (~1.5-2-fold), and the formation of HNE and acrolein-protein adducts was increased in the gastrocnemius muscle of TAC-operated mice. The expression of AKR1B1 remained unchanged, whereas ALDH2 was decreased, in the gastrocnemius muscle of TAC mice. Similarly, in the atrophic gastrocnemius muscle, levels of total histidyl dipeptides (carnosine and anserine) and, in particular,carnosine were decreased. Depletion of histidyl dipeptides diminished the aldehyde removal capacity of the atrophic gastrocnemius muscle. Furthermore, the expression of CARNS and TAUT wasdecreased in the atrophic gastrocnemius muscle.
CONCLUSIONS
Collectively, these results show that metabolic pathways involved in the removal of lipid peroxidation products and synthesis of histidyl dipeptides are diminished in atrophic skeletal muscle during heart failure, which could contribute to muscle atrophy.
PubMed: 38045249
DOI: 10.21203/rs.3.rs-3621159/v1 -
European Journal of Orthopaedic Surgery... Aug 2023During the posteromedial approach to the tibial plateau fracture (TPF), pes anserine is generally retracted. However, pes anserine detachment could provide a better...
PURPOSE
During the posteromedial approach to the tibial plateau fracture (TPF), pes anserine is generally retracted. However, pes anserine detachment could provide a better fracture site exposure. Even so, the general conception is that the latter could negatively affect flexor muscle strength. We aimed to evaluate the effect of pes anserine detachment on the flexion force and functional outcomes of TPF with posteromedial involvement.
METHODS
In this retrospective-prospective cohort study, 22 TPF patients with Schatzker type IV who were managed with posteromedial approach and pes anserine detachment were included. The knee flexion force was measured 12 months after the surgery at several angles of flexion (30°, 60°, and 90°) and rotations (internal and external). The International Knee Documentation Committee (IKDC) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were used to assess knee function. A visual analog scale (VAS) was used to measure knee pain.
RESULTS
The mean strength of the knee flexor muscle was not statistically different between the involved and non-involved sides at 30°, 60°, and 90° knee flexion, and also at the internal and external rotation. The mean IKDC score of the patients was 81.6 ± 7.8. The mean KOOS score of the patients was 82.2 ± 9.1. The mean VAS for pain was 2.4 ± 1.8. The mean knee range of motion was 124 ± 10.5°.
CONCLUSION
Pes anserine release and re-attachment in the posteromedial approach to the TPF has no detrimental effect on the flexion muscle strength and knee function.
LEVEL OF EVIDENCE
Therapeutic Level IV.
Topics: Humans; Anserine; Retrospective Studies; Prospective Studies; Tibial Plateau Fractures; Tibial Fractures; Knee Joint; Fracture Fixation, Internal; Treatment Outcome
PubMed: 36446957
DOI: 10.1007/s00590-022-03447-0 -
Pharmacological Research Oct 2023Solute carrier (SLC) transport proteins are fundamental for the translocation of endogenous compounds and drugs across membranes, thus playing a critical role in disease...
Solute carrier (SLC) transport proteins are fundamental for the translocation of endogenous compounds and drugs across membranes, thus playing a critical role in disease susceptibility and drug response. Because only a limited number of transporter substrates are currently known, the function of a large number of SLC transporters is elusive. Here, we describe the proof-of-concept of a novel strategy to identify SLC transporter substrates exemplarily for the proton-coupled peptide transporter (PEPT) 2 (SLC15A2) and multidrug and toxin extrusion (MATE) 1 transporter (SLC47A1), which are important renal transporters of drug reabsorption and excretion, respectively. By combining metabolomic profiling of mice with genetically-disrupted transporters, in silico ligand screening and in vitro transport studies for experimental validation, we identified nucleobases and nucleoside-derived anticancer and antiviral agents (flucytosine, cytarabine, gemcitabine, capecitabine) as novel drug substrates of the MATE1 transporter. Our data confirms the successful applicability of this new approach for the identification of transporter substrates in general, which may prove particularly relevant in drug research.
Topics: Animals; Mice; Ligands; Membrane Transport Proteins; Solute Carrier Proteins; Biological Transport
PubMed: 37775020
DOI: 10.1016/j.phrs.2023.106941 -
Advances in Orthopedics 2023Pes anserine bursitis (PAB) is one of the most common causes of painful knee syndromes. This study aimed at examining the efficacy of local corticosteroid injection,...
Comparing the Efficacy of Local Corticosteroid Injection, Platelet-Rich Plasma, and Extracorporeal Shockwave Therapy in the Treatment of Pes Anserine Bursitis: A Prospective, Randomized, Comparative Study.
BACKGROUND
Pes anserine bursitis (PAB) is one of the most common causes of painful knee syndromes. This study aimed at examining the efficacy of local corticosteroid injection, platelet-rich plasma (PRP) injection, and extracorporeal shock wave therapy (ESWT) as different modalities to alleviate pain and enhance function in patients with pes anserine bursitis (PAB).
METHODS
A prospective, randomized, comparative study was conducted on 180 patients diagnosed with chronic PAB. They were equally divided into three groups as follows: Group I received a local corticosteroid injection of 40 mg of methylprednisolone acetate/1 ml; Group II received a PRP injection; and in Group III, ESWT was used. Outcome measures included the visual analog scale (VAS), Western Ontario and McMaster Universities (WOMAC) pain score, WOMAC physical function score, and Ritchie articular index (RAI) for tenderness, which were recorded at the baseline, after 1 week, and after 8 weeks.
RESULTS
Before the application of procedures, there was a statistically significant increase in the WOMAC pain score in the local corticosteroid group compared to the PRP group and the ESWT group ( < 0.001). After the application of procedures, there was a statistically significant improvement in the 1-week and 8-week WOMAC pain score, WOMAC physical function score, and VAS in the local corticosteroid group in comparison to the PRP group and the ESWT group. ( < 0.001). Moreover, RAI for tenderness shows statistically significant improvement at 8 weeks in the local corticosteroid groups compared to the PRP groups ( < 0.001) and ESWT groups ( < 0.001). Similarly, a statistically significant difference was found between the PRP and ESWT groups (=0.023).
CONCLUSION
Our data suggest that in patients with PAB, local corticosteroid injection is more efficient than PRP injection and ESWT for reducing pain and enhancing function.
PubMed: 37810418
DOI: 10.1155/2023/5545520 -
Animal Bioscience Apr 2024Carnosine and anserine affect the meat flavor. The contents of carnosine and anserine in meat are affected by genetic and environmental factors. This study aimed to...
OBJECTIVE
Carnosine and anserine affect the meat flavor. The contents of carnosine and anserine in meat are affected by genetic and environmental factors. This study aimed to discover the single-nucleotide polymorphisms (SNPs) in the HNMT and HNMT-like genes and to associate them with the content of carnosine and anserine in Korean native chicken-red brown line (KNC-R ).
METHODS
This study used a total of 384 birds (males, n=192; females, n=192) aged 10 weeks old, for genotyping HNMT and HNMT-like genes. One synonymous SNP (rs29009298C/T) of the HNMT gene was genotyped by PCR-RFLP methods whereas four missense SNPs (rs734406537G/A; rs736514667A/G; rs15881680G/A and rs316765035T/C) of the HNMT gene, and one missense SNP rs737657949A/C of the HNMT-like gene were genotyped by PACE genotyping technology. Two-way ANOVA of the R program was used to associate HNMT genotypes with the contents of carnosine and anserine in KNC- R chickens.
RESULTS
There were significant associations (p<0.05) between the genotypes of the synonymous SNP:rs29009298C/T, missense SNP rs736514667A/G of the HNMT gene and the content of carnosine in KNC-Rs. This study also reported the sex effect on the carnosine content, where females had more content of carnosine compared to that of male KNC-R.
CONCLUSION
Two SNPs (synonymous: rs735769522C/T) and missense: rs736514667A/G) in the HNMT gene might be used as genetic markers in the selection and breeding of chickens with better taste and high-flavored meat.
PubMed: 38665079
DOI: 10.5713/ab.23.0552 -
Frontiers in Pharmacology 2024This study aimed to explore the regulatory effect of anserine on HUVEC cell injury and thrombosis in deep venous thrombosis (DVT) rats, and to elucidate the underlying...
BACKGROUND
This study aimed to explore the regulatory effect of anserine on HUVEC cell injury and thrombosis in deep venous thrombosis (DVT) rats, and to elucidate the underlying molecular mechanisms.
METHODS
Non-targeted metabolomics data analyses were conducted using an ultra-performance liquid chromatography system Vanquish UHPLC and mass spectrometer to detect plasma metabolism profiles. The transcriptome sequencing and gene intervention experiments were performed to verify the regulatory effect. Further and experiments were performed. Enzyme-linked immunosorbent assay was used to detect the levels of P-selectin, E-selectin, and vWF, hematoxylin-eosin (HE) staining was performed to observe thrombotic and inflammatory cell infiltration, flow cytometry and TUNEL assays were performed to detect apoptosis, and qPCR and WB assays were conducted to determine the gene and protein expression.
RESULTS
Anserine alleviated HUVECs injury, reduced adhesion molecule expression, and inflammation. It decreased P-selectin, E-selectin, vWF, THBD, TFPI levels, and apoptosis while promoting NOS3, ET-1, and NO release in HUVECs. In DVT rats, anserine reduced P-selectin, E-selectin, vWF, thrombosis, cell infiltration, apoptosis, and promoted NO release. Transcriptome sequencing and gene intervention confirmed anserine's regulation of the PI3K-Akt pathway and coagulation via MYB. CARNMT1, a regulatory enzyme for anserine metabolism, increased anserine content, inhibiting coagulation, thrombosis, cell infiltration, and promoting NO release in rats.
CONCLUSION
This study confirmed anserine could alleviate DVT by improving the inflammatory response, inhibiting blood agglutination, and promoting vasodilation, providing new potential therapeutic targets, important scientific evidence for the development of DVT management, and new clues for an in-depth understanding of its molecular mechanisms.
PubMed: 38846090
DOI: 10.3389/fphar.2024.1402758 -
Molecular Nutrition & Food Research Mar 2024To investigate the efficacy of anserine on antiobesity, C57BL/6 mice are orally administered with a high-fat diet (HFD) and different doses of anserine (60, 120, and...
To investigate the efficacy of anserine on antiobesity, C57BL/6 mice are orally administered with a high-fat diet (HFD) and different doses of anserine (60, 120, and 240 mg/kg/day) for 16 weeks. Body weight, lipid, and epididymal fat content in mice are measured, and their liver damage is observed. The results display that the body weight, epididymal fat content, and low-density lipoprotein cholesterol (LDL-C) content in anserine groups are decreased by 4.36-18.71%, 7.57-35.12%, and 24.32-44.40%, respectively. To further investigate the antiobesity mechanism of anserine, the expression of SREBP-1, NLRP3, NF-κB p65 (p65), and p-NF-κB p65 (p-p65) proteins in the liver and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1-α) and UCP-1 proteins in brown adipose tissue (BAT) is analyzed by Western blot. Results show that anserine can significantly decrease the expression of the NLRP3, p65, p-p65, and the SREBP-1 proteins and increase the expression of the PGC1-α and UCP-1 proteins. This study demonstrates that anserine lowered blood lipids and prevented obesity; its antiobesity mechanism may be related to the activation of brown fat by inflammation.
Topics: Mice; Animals; Diet, High-Fat; Anserine; Sterol Regulatory Element Binding Protein 1; NLR Family, Pyrin Domain-Containing 3 Protein; NF-kappa B; Mice, Inbred C57BL; Obesity; Body Weight; Anti-Obesity Agents
PubMed: 38400696
DOI: 10.1002/mnfr.202300471 -
Animals : An Open Access Journal From... Nov 2023The physical properties, free amino acids, and metabolites of Beijing-You chicken (BYC) breast meat aged 90, 120, and 150 days were analyzed to investigate the flavor...
The physical properties, free amino acids, and metabolites of Beijing-You chicken (BYC) breast meat aged 90, 120, and 150 days were analyzed to investigate the flavor changes with age. The shear force and intramuscular fat increased from 90 to 120 days significantly. The contents of total free amino acids and essential amino acids decreased from 90 to 120 days significantly. No significant differences were detected between 120 and 150 days. The contents of sweet amino acids, bitter amino acids, and umami amino acids showed no significant differences between different ages. In addition, GC-MS and LC-MS were integrated for metabolite detection in breast meat. A total of 128, 142, and 88 differential metabolites were identified in the comparison groups of 120 d vs. 90 d, 150 d vs. 90 d, and 150 d vs. 120 d. Amino acids and lipids were the main differential metabolites. The pathway analysis showed that arginine biosynthesis, histidine metabolism, purine metabolism, and cysteine and methionine metabolism were the main pathways involved in flavor formation during BYC development. It was also found that the metabolites associated with flavor, such as methionine, cysteine, glucose, anserine, arachidonic acid, and glycerol 1-phosphate, were significantly affected by age.
PubMed: 37958174
DOI: 10.3390/ani13213419