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International Journal of Molecular... Jun 2024The composition of skeletal muscle fiber types affects the quality of livestock meat and human athletic performance and health. L-arginine (Arg), a semi-essential amino...
The composition of skeletal muscle fiber types affects the quality of livestock meat and human athletic performance and health. L-arginine (Arg), a semi-essential amino acid, has been observed to promote the formation of slow-twitch muscle fibers in animal models. However, the precise molecular mechanisms are still unclear. This study investigates the role of Arg in skeletal muscle fiber composition and mitochondrial function through the mTOR signaling pathway. In vivo, 4-week C56BL/6J male mice were divided into three treatment groups and fed a basal diet supplemented with different concentrations of Arg in their drinking water. The trial lasted 7 weeks. The results show that Arg supplementation significantly improved endurance exercise performance, along with increased SDH enzyme activity and upregulated expression of the MyHC I, MyHC IIA, PGC-1α, and NRF1 genes in the gastrocnemius (GAS) and quadriceps (QUA) muscles compared to the control group. In addition, Arg activated the mTOR signaling pathway in the skeletal muscle of mice. In vitro experiments using cultured C2C12 myotubes demonstrated that Arg elevated the expression of slow-fiber genes (MyHC I and Tnnt1) as well as mitochondrial genes (PGC-1α, TFAM, MEF2C, and NRF1), whereas the effects of Arg were inhibited by the mTOR inhibitor rapamycin. In conclusion, these findings suggest that Arg modulates skeletal muscle fiber type towards slow-twitch fibers and enhances mitochondrial functions by upregulating gene expression through the mTOR signaling pathway.
Topics: Animals; TOR Serine-Threonine Kinases; Signal Transduction; Mice; Arginine; Male; Muscle Fibers, Skeletal; Mice, Inbred C57BL; Muscle Fibers, Slow-Twitch; Muscle, Skeletal; Cell Line
PubMed: 38892371
DOI: 10.3390/ijms25116184 -
International Journal of Molecular... Jun 2024Both tissue and blood lead levels are elevated in renal cell carcinoma (RCC) patients. These studies assessed the impact of the subchronic lead challenge on the...
Both tissue and blood lead levels are elevated in renal cell carcinoma (RCC) patients. These studies assessed the impact of the subchronic lead challenge on the progression of RCC in vitro and in vivo. Lead challenge of Renca cells with 0.5 μM lead acetate for 10 consecutive passages decreased E-cadherin expression and cell aggregation. Proliferation, colony formation, and wound healing were increased. When lead-challenged cells were injected into mice, tumor size at day 21 was increased; interestingly, this increase was seen in male but not female mice. When mice were challenged with 32 ppm lead in drinking water for 20 weeks prior to tumor cell injection, there was an increase in tumor size in male, but not female, mice at day 21. To investigate the mechanism underlying the sex differences, the expression of sex hormone receptors in Renca cells was examined. Control Renca cells expressed estrogen receptor (ER) alpha but not ER beta or androgen receptor (AR), as assessed by qPCR, and the expression of ERα was increased in tumors in both sexes. In tumor samples harvested from lead-challenged cells, both ERα and AR were detected by qPCR, yet there was a significant decrease in AR seen in lead-challenged tumor cells from male mice only. This was paralleled by a plate-based array demonstrating the same sex difference in BMP-7 gene expression, which was also significantly decreased in tumors harvested from male but not female mice; this finding was validated by immunohistochemistry. A similar expression pattern was seen in tumors harvested from the mice challenged with lead in the drinking water. These data suggest that lead promotes RCC progression in a sex-dependent via a mechanism that may involve sex-divergent changes in BMP-7 expression.
Topics: Animals; Female; Carcinoma, Renal Cell; Male; Bone Morphogenetic Protein 7; Mice; Kidney Neoplasms; Cell Line, Tumor; Cell Proliferation; Lead; Receptors, Androgen; Gene Expression Regulation, Neoplastic; Humans; Estrogen Receptor alpha; Sex Factors
PubMed: 38892327
DOI: 10.3390/ijms25116139 -
International Journal of Molecular... May 2024Skeletal muscle atrophy (SMA) is caused by a rise in muscle breakdown and a decline in protein synthesis, with a consequent loss of mass and function. This study...
Skeletal muscle atrophy (SMA) is caused by a rise in muscle breakdown and a decline in protein synthesis, with a consequent loss of mass and function. This study characterized the effect of an amino acid mixture (AA) in models of SMA, focusing on mitochondria. C57/Bl6 mice underwent immobilization of one hindlimb (I) or cardiotoxin-induced muscle injury (C) and were compared with controls (CTRL). Mice were then administered AA in drinking water for 10 days and compared to a placebo group. With respect to CTRL, I and C reduced running time and distance, along with grip strength; however, the reduction was prevented by AA. Tibialis anterior (TA) muscles were used for histology and mitochondria isolation. I and C resulted in TA atrophy, characterized by a reduction in both wet weight and TA/body weight ratio and smaller myofibers than those of CTRL. Interestingly, these alterations were lightly observed in mice treated with AA. The mitochondrial yield from the TA of I and C mice was lower than that of CTRL but not in AA-treated mice. AA also preserved mitochondrial bioenergetics in TA muscle from I and C mice. To conclude, this study demonstrates that AA prevents loss of muscle mass and function in SMA by protecting mitochondria.
Topics: Animals; Mice; Energy Metabolism; Muscle, Skeletal; Mice, Inbred C57BL; Amino Acids; Muscular Atrophy; Male; Disease Models, Animal; Mitochondria, Muscle; Mitochondria
PubMed: 38892242
DOI: 10.3390/ijms25116056 -
International Journal of Molecular... May 2024Binge alcohol consumption during adolescence can produce lasting deficits in learning and memory while also increasing the susceptibility to substance use disorders. The...
Binge alcohol consumption during adolescence can produce lasting deficits in learning and memory while also increasing the susceptibility to substance use disorders. The adolescent intermittent ethanol (AIE) rodent model mimics human adolescent binge drinking and has identified the nucleus basalis magnocellularis (NbM) as a key site of pathology. The NbM is a critical regulator of prefrontal cortical (PFC) cholinergic function and attention. The cholinergic phenotype is controlled pro/mature neurotrophin receptor activation. We sought to determine if p75NTR activity contributes to the loss of cholinergic phenotype in AIE by using a p75NTR modulator (LM11A-31) to inhibit prodegenerative signaling during ethanol exposure. Male and female rats underwent 5 g/kg ethanol (AIE) or water (CON) exposure following 2-day-on 2-day-off cycles from postnatal day 25-57. A subset of these groups also received a protective dose of LM11A-31 (50 mg/kg) during adolescence. Rats were trained on a sustained attention task (SAT) and behaviorally relevant acetylcholine (ACh) activity was recorded in the PFC with a fluorescent indicator (AChGRAB 3.0). AIE produced learning deficits on the SAT, which were spared with LM11A-31. In addition, PFC ACh activity was blunted by AIE, which LM11A-31 corrected. Investigation of NbM ChAT+ and TrkA+ neuronal expression found that AIE led to a reduction of ChAT+TrkA+ neurons, which again LM11A-31 protected. Taken together, these findings demonstrate the p75NTR activity during AIE treatment is a key regulator of cholinergic degeneration.
Topics: Animals; Cholinergic Neurons; Rats; Male; Acetylcholine; Female; Ethanol; Prefrontal Cortex; Atrophy; Behavior, Animal; Receptors, Nerve Growth Factor; Rats, Sprague-Dawley; Disease Models, Animal; Nerve Tissue Proteins; Receptors, Growth Factor
PubMed: 38891978
DOI: 10.3390/ijms25115792 -
International Journal of Molecular... May 2024The consequences of stroke include cognitive deficits and sensorimotor disturbances, which are largely related to mitochondrial impairments in the brain. In this work,...
The consequences of stroke include cognitive deficits and sensorimotor disturbances, which are largely related to mitochondrial impairments in the brain. In this work, we have shown that the mimetic of the ketogenic diet beta-hydroxybutyrate (βHB) can improve neurological brain function in stroke. At 3 weeks after photothrombotic stroke, mice receiving βHB with drinking water before and after surgery recovered faster in terms of sensorimotor functions assessed by the string test and static rods and cognitive functions assessed by the Morris water maze. At the same time, the βHB-treated mice had lower expression of some markers of astrocyte activation and inflammation (, , ). We hypothesize that long-term administration of βHB promotes the activation of the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway, which leads to increased expression of antioxidant genes targeting mitochondria and genes involved in signaling pathways necessary for the maintenance of synaptic plasticity. βHB partially maintained mitochondrial DNA (mtDNA) integrity during the first days after photothrombosis. However, in the following three weeks, the number of mtDNA damages increased in all experimental groups, which coincided with a decrease in expression, which plays an important role in mtDNA repair. Thus, we can assume that βHB is not only an important metabolite that provides additional energy to brain tissue during recovery from stroke under conditions of mitochondrial damage but also an important signaling molecule that supports neuronal plasticity and reduces neuroinflammation.
Topics: Animals; Mice; 3-Hydroxybutyric Acid; Cognitive Dysfunction; Ischemic Stroke; Male; Disease Models, Animal; NF-E2-Related Factor 2; DNA, Mitochondrial; Mitochondria; Thrombosis; Brain; Mice, Inbred C57BL
PubMed: 38891898
DOI: 10.3390/ijms25115710 -
Animals : An Open Access Journal From... May 2024The aim of the study was to investigate in vitro the antibacterial activity of 8 commercial drinking water additives against major zoonotic poultry pathogens ( spp., ,...
The aim of the study was to investigate in vitro the antibacterial activity of 8 commercial drinking water additives against major zoonotic poultry pathogens ( spp., , Typhimurium, and spp.). We tested two essential oil-based phytogenics (Phyto CSC Liquide B, AEN 350 B Liquid), two acid-based eubiotics (Salgard liquid, Intesti-Flora), and four blends of essential oils and organic acids (ProPhorce SA Exclusive, Herbal acid, Rigosol-N and Eubisan 3000). The antibacterial activity was determined by estimating the minimum inhibitory concentration (MIC) using a microdilution method. The MICs of the products against spp. ranged from 0.071% to 0.568% /, in which Herbal acid, a blend rich in lactic and phosphoric acids, also containing thyme and oregano oils, exhibited the highest efficacy (MIC: 0.071% /) against all the tested strains. The MICs of the tested products against ranged between 0.071% and 1.894% /. Specifically, the MIC of Rigosol-N, a blend of high concentrations of lactic and acetic acid, was 0.142% / for both tested strains, whereas the MICs of Intesti-Flora, a mixture rich in lactic and propionic acid, ranged from 0.284% to 0.568% /. The MICs of the products against Typhimurium were between 0.095% and 1.894% /. Specifically, the MIC of Eubisan 3000, a blend rich in oregano oil, was 0.284% /. The MICs against were between 0.142% and 9.090% /. The MICs of Phyto CSC Liquide B, which is rich in -cinnamaldehyde, were between 3.030% and 9.090% /, showing the highest MIC values of all tested products. Finally, the MIC values of the tested commercial products against spp. were 0.095% to 3.030% /. The MICs of ProPhorce SA Exclusive, a highly concentrated blend of formic acid and its salts, were 0.095-0.142% / against spp., while the MICs of AEN 350 B Liquid were between 0.284% and 1.894% exhibiting high spp. strain variability. In conclusion, all the selected commercial products exhibited more or less antibacterial activity against pathogenic bacteria and, thus, can be promising alternatives to antibiotics for the control of zoonotic poultry pathogens and the restriction of antimicrobial-resistant bacteria.
PubMed: 38891658
DOI: 10.3390/ani14111611 -
Animals : An Open Access Journal From... May 2024Different resources, such as environmental enrichment, are being evaluated in order to minimize animal stress and promote better conditions during the life cycle of...
Different resources, such as environmental enrichment, are being evaluated in order to minimize animal stress and promote better conditions during the life cycle of animals, as consumers are increasingly concerned about animal welfare issues. Lairage represents an important stage in the swine production chain and is directly related to animal welfare. The aim of this study was to evaluate the effect of lairage time in the slaughterhouse and environmental enrichment on the level of skin lesions and behavioral responses in pigs. A total of 648 finishing pigs of both sexes were assessed before and after lairage at the slaughterhouse with a five-point scale (0 = none, to 4 = ≥16 superficial lesions or >10 deep lesions). After lairage (after slaughter), lesions were also classified according to their source (mounting, fighting, and handling). Pigs were distributed into two treatments groups during lairage: with environmental enrichment (EE) on the pen, with hanging metal chains, and with no enrichment (NE). Behavior was monitored during the first four hours of lairage. Proportional odds, mixed linear model for longitudinal data, and non-parametric Wilcoxon signed rank tests were used to analyze the relation between treatments, skin lesions, and behavior. The simple metal chains did not affect skin lesion score or pigs' behavior ( > 0.05), whereas lairage duration influenced standing (SA), sitting (S), lying (L), idleness (I), and drinking water (D) ( < 0.001). The main source of skin lesions was handling, which did not differ between treatments (EE and NE) ( > 0.05). It was observed that the severity of the lesions (highest scores of 3, 4, and 5) increased in the different anatomical regions of the pigs when compared before and after slaughter, with the exception of the frontal area, which was the same ( = 0.7547). Lairage time has a proportional relation with skin lesions, and hanging chains at the slaughterhouse pens was not enough to reduce the number of lesions and to change pig behavior.
PubMed: 38891638
DOI: 10.3390/ani14111591 -
Animals : An Open Access Journal From... May 2024This experiment was conducted to evaluate the effects of drinking water salinity levels on water intake and loss, feed intake and digestion, body weight (BW),...
Effects of Salinity Levels of Drinking Water on Water Intake and Loss, Feed Utilization, Body Weight, Thermoregulatory Traits, and Blood Constituents in Growing and Mature Blackhead Ogaden Sheep and Somali Goats.
This experiment was conducted to evaluate the effects of drinking water salinity levels on water intake and loss, feed intake and digestion, body weight (BW), thermoregulation, and blood characteristics on growing and mature (18.8 ± 0.39 and 21.8 ± 0.40 kg BW, and 0.6-1 and 1.5-2 years of age, respectively) Blackhead Ogaden sheep and Somali goats. The animals were assigned to a 4 (water salinity) × 2 (sheep and goat species) × 2 (growing and mature animals) factorial arrangement for the 60-day experimental period and 10-day digestibility determination. Water treatments were fresh water (FRW) and low (SW-L), moderate (SW-M), and high (SW-H) levels of salinity (i.e., the addition of NaCl to obtain 10, 13.5, and 17 g of total dissolved salts (TDSs)/L, respectively). The salinity of drinking water did not affect feed intake, BW, thermoregulatory traits (respiration rate, rectal temperature, and heart rate), or blood parameters ( > 0.05); however, drinking water, total water intake, urine excretion, and total water loss increased ( < 0.01) while apparent dry matter digestibility decreased quadratically ( < 0.01) with increasing water salinity. Analysis of the interaction between water treatment and species showed that PCV ( = 0.059) and hemoglobin ( = 0.070) levels tended to be higher in sheep than in goats drinking FRW, and AST activities were greater ( = 0.036) in goats consuming SW-M than in sheep consuming water with the same salinity level. In conclusion, increasing the salinity level of drinking water by adding NaCl to up to 17 g/L of TDSs had no adverse effect on the water intake, feed intake, BW, and health status of growing and mature Blackhead Ogaden sheep and Somali goats.
PubMed: 38891612
DOI: 10.3390/ani14111565 -
Foods (Basel, Switzerland) May 2024Veterinary medications are necessary for both contemporary animal husbandry and food production, but their residues can linger in foods obtained from animals and pose a... (Review)
Review
Veterinary medications are necessary for both contemporary animal husbandry and food production, but their residues can linger in foods obtained from animals and pose a dangerous human risk. In this review, we aim to highlight the sources, occurrence, human exposure pathways, and human health effects of drug residues in food-animal products. Following the usage of veterinary medications, pharmacologically active compounds known as drug residues can be found in food, the environment, or animals. They can cause major health concerns to people, including antibiotic resistance development, the development of cancer, teratogenic effects, hypersensitivity, and disruption of normal intestinal flora. Drug residues in animal products can originate from variety of sources, including water or food contamination, extra-label drug use, and ignoring drug withdrawal periods. This review also examines how humans can be exposed to drug residues through drinking water, food, air, and dust, and discusses various analytical techniques for identifying these residues in food. Furthermore, we suggest some potential solutions to prevent or reduce drug residues in animal products and human exposure pathways, such as implementing withdrawal periods, monitoring programs, education campaigns, and new technologies that are crucial for safeguarding public health. This review underscores the urgency of addressing veterinary drug residues as a significant and emerging public health threat, calling for collaborative efforts from researchers, policymakers, and industry stakeholders to develop sustainable solutions that ensure the safety of the global food supply chain.
PubMed: 38890858
DOI: 10.3390/foods13111629 -
Biology of Sex Differences Jun 2024Prenatal alcohol exposure (PAE) can result in lifelong disabilities known as foetal alcohol spectrum disorder (FASD) and is associated with childhood growth deficiencies...
BACKGROUND
Prenatal alcohol exposure (PAE) can result in lifelong disabilities known as foetal alcohol spectrum disorder (FASD) and is associated with childhood growth deficiencies and increased bone fracture risk. However, the effects of PAE on the adult skeleton remain unclear and any potential sexual dimorphism is undetermined. Therefore, we utilised a murine model to examine sex differences with PAE on in vitro bone formation, and in the juvenile and adult skeleton.
METHODS
Pregnant C57BL/6J female mice received 5% ethanol in their drinking water during gestation. Primary calvarial osteoblasts were isolated from neonatal offspring and mineralised bone nodule formation and gene expression assessed. Skeletal phenotyping of 4- and 12-week-old male and female offspring was conducted by micro-computed tomography (µCT), 3-point bending, growth plate analyses, and histology.
RESULTS
Osteoblasts from male and female PAE mice displayed reduced bone formation, compared to control (≤ 30%). Vegfa, Vegfb, Bmp6, Tgfbr1, Flt1 and Ahsg were downregulated in PAE male osteoblasts only, whilst Ahsg was upregulated in PAE females. In 12-week-old mice, µCT analysis revealed a sex and exposure interaction across several trabecular bone parameters. PAE was detrimental to the trabecular compartment in male mice compared to control, yet PAE females were unaffected. Both male and female mice had significant reductions in cortical parameters with PAE. Whilst male mice were negatively affected along the tibial length, females were only distally affected. Posterior cortical porosity was increased in PAE females only. Mechanical testing revealed PAE males had significantly reduced bone stiffness compared to controls; maximum load and yield were reduced in both sexes. PAE had no effect on total body weight or tibial bone length in either sex. However, total growth plate width in male PAE mice compared to control was reduced, whilst female PAE mice were unaffected. 4-week-old mice did not display the altered skeletal phenotype with PAE observed in 12-week-old animals.
CONCLUSIONS
Evidence herein suggests, for the first time, that PAE exerts divergent sex effects on the skeleton, possibly influenced by underlying sex-specific transcriptional mechanisms of osteoblasts. Establishing these sex differences will support future policies and clinical management of FASD.
Topics: Animals; Female; Male; Sex Characteristics; Pregnancy; Mice, Inbred C57BL; Prenatal Exposure Delayed Effects; Ethanol; Osteoblasts; Osteogenesis; Mice; Bone and Bones; X-Ray Microtomography
PubMed: 38890762
DOI: 10.1186/s13293-024-00626-y