Protein Breakdown Research Articles

Rapid stimulation of protein synthesis in digesting snakes: Unveiling a novel gut-pancreas-muscle axis.

Snakes exhibit remarkable physiological shifts when their large meals induce robust postprandial growth after prolonged fasting. To understand the regulatory mechanisms underlying this rapid metabolic transition, we examined the regulation of protein synthesis in pythons, focusing on processes driving early postprandial tissue remodeling and growth. Using the SUnSET method with puromycin labeling, we measured invivo protein synthesis in fasting and digesting snakes at multiple post-feeding intervals. Pyloric ligation, pancreatectomy, and plasma transfusions were performed to explore the roles of gastrointestinal luminal signaling and pancreatic function across key tissues. We observed profound and early stimulation of protein synthesis in gastrointestinal tissues and skeletal muscle already 3 h after ingestion, before any measurable rise in plasma amino acids from the meal. The gastrointestinal stimulation appears to be driven by luminal factors, while the stimulation of skeletal muscle protein synthesis is humoral with pancreatic insulin release as an integral mediator. The pre-absorptive anabolic activity is supported by the release of amino acids from the breakdown of endogenous proteins. Our findings suggest that snakes initiate protein synthesis via distinct, tissue-specific pathways preceding nutrient absorption. This "pay before pumping" model shows how early protein synthesis prepares the digestive and muscular systems for later nutrient assimilation and growth. This intricate humoral regulation, involving a gut-pancreas-muscle axis, governs postprandial protein synthesis in snakes and provides insights into fundamental mechanisms driving metabolic adaptations and broader hyperplastic and hypertrophic responses.

The effect of molecular chaperone mediated autophagy on ApoE expression in retinal pigment epithelial cells: Molecular structure and protein action mechanism.

Chaperone mediated autophagy (CMA) represents a specialized mechanism of lysosomal protein breakdown, playing a crucial role as a metabolic pathway that helps to regulate and sustain cellular and systemic physiological equilibrium. Within the CMA process, proteins that contain sequences similar to KFERQ are specifically identified by the heat shock cognate protein 70. These proteins are then chaperoned to the lysosomes for subsequent degradation, a process facilitated by the lysosome associated membrane protein 2A. This particular research employed bioinformatics techniques to systematically screen for potential substrates of CMA. ApoE has a KFERQ like motif, which may be a substrate for CMA. Under conditions of starvation, hypoxia, H2O2, PA, and NaIO3, the expression of the rate limiting factor LAMP2A in CMA and ApoE increased significantly (P<0.05). Under conditions of NaIO3, the expression of CMA related gene mRNA increased significantly (P<0.05). When we use lysosomal blocker CQ to inhibit CMA activity, the expression level of ApoE in retinal pigment epithelial cells increased, and the difference was statistically significant (P<0.05). When we inhibit CMA, the accumulation of ApoE in retinal pigment epithelial cells increases and cell viability decreases. When we activate CMA, the accumulation of ApoE decreases and cell viability increases. In retinal pigment epithelial cells, the drusen associated protein ApoE can be degraded through the CMA pathway.

Microplastics and Dechlorane Plus co-exposure amplifies their impacts on soybean plant.

The co-existence of microplastics (MPs) and organic pollutants on agricultural ecosystems pose potential implications for both food safety and environmental integrity. The combined effects of MPs with Dechlorane Plus (DP), a newly listed banned flame retardant, remain unknown. This study explores the biological responses of soybean plants to exposure from polyethylene (PE) and polyvinyl chloride (PVC) MPs and DP. Results showed that combined exposure altered the activity of antioxidant enzymes and inhibited the growth of soybean plants, compared with DP or MPs exposure alone. DP markedly reduced both the root length and root weight of soybean plants in a dose-dependent manner. Proteomics profiling suggests that PE interacts with protein translation and modification pathways, particularly via the regulation of heat shock protein binding. High concentration DP (HDP) treatment group enhances the plant's stress resistance by regulating relevant proteins through the modulation of hydrogen peroxide catabolic protein expression and the formation of water channel proteins. In the combined treatments, low concentration DP with PVC triggered increased protein expression related to photosynthesis response, further demonstrating the enhanced inhibitory effects. This study for the first time maps the changes in the physiological and the molecular mechanisms of the impacts on higher plant caused by MPs and DP co-exposure.

Role of major cardiovascular surgery-induced metabolic reprogramming in acute kidney injury in critical care.

Major cardiovascular surgery imposes high physiologic stress, often causing severe organ dysfunction and poor outcomes. The underlying mechanisms remain unclear. This study investigated metabolic changes induced by major cardiovascular surgery and the potential role of identified metabolic signatures in postoperative acute kidney injury (AKI). A prospective observational study included 53 patients undergoing major cardiovascular surgery in 3 groups: cardiac surgery with cardiopulmonary bypass (CPB n = 33), without CPB (n = 10), and major vascular surgery (n = 10). For each patient, peripheral blood samples were collected pre-surgery, and at 6h and 24h post-surgery. Untargeted metabolomics using mass spectrometry quantified 8668 metabolic features in serum samples. Linear mixed-effect models (adjusted for age, sex, and body mass index) and pathway analyses were performed. In the cardiac surgery with CPB group, 772 features were significantly altered (P < 2.8E - 05) across the 3 time points. These features were enriched in five classes, all related to protein metabolism, with glycine and serine metabolism being the most represented. Cardiac surgery with CPB showed a distinct metabolic signature compared to other groups. Patients who developed postoperative AKI exhibited increased protein catabolism (including valine, leucine, and isoleucine degradation), disruptions in the citric acid cycle, and plasmatic accumulation of acylcarnitines. Major cardiovascular surgery, particularly with CPB, induces significant changes in protein metabolism. Patients developing postoperative AKI exhibited specific metabolic signatures. These findings may be critical for designing interventions to minimize organ dysfunction, including AKI, and improve outcomes in major cardiovascular surgery.

Effects of Physical Exercise on MuRF-1/TRIM63 mRNA Expression in Humans: A Systematic Review

Background/Objectives: Muscle-specific RING finger protein 1 (MuRF-1) is a pivotal regulator of muscle protein breakdown, an essential process for post-exercise muscle adaptation. This systematic review aimed to evaluate the effects of physical exercise on MuRF-1 mRNA expression in humans. Methods: A literature search was conducted in PubMed, Scopus, Cochrane Library, Google Scholar, and Web of Science following the PRISMA guidelines. The search was limited to studies published from 1 January 2001 to 1 December 2024. The inclusion and exclusion criteria were defined using the PICOS strategy. Two investigators independently performed the study selection, data extraction, and assessment of methodological quality, with any disagreements resolved by a third investigator. The PEDro scale was used to evaluate the risk of bias. Results: Forty-six studies met the eligibility criteria and were included. The findings evidenced that physical exercise significantly modulates MuRF-1 mRNA expression in humans. Resistance exercise induces transient increases, typically peaking between 1 and 4 h, whereas endurance exercise elicits similar responses within 40 min to 4 h post-exercise. Combined exercise protocols that include resistance and endurance exercises significantly increased MuRF-1 mRNA expression at 3 h post-exercise. The effects of physical exercise on MuRF-1 mRNA expression are influenced by factors such as exercise order, intensity, contraction mode, age, sex, and fitness level. Conclusions: This systematic review shows that MuRF-1 mRNA expression is significantly modulated by physical exercise in humans and is sensitive to different exercise modalities. These findings suggest that this key protein involved in muscle protein breakdown and turnover is essential for exercise-induced adaptations, contributing to skeletal muscle recovery and remodeling after exercise.

Upregulation of FAM129B protects against glucocorticoid-induced skeletal muscle atrophy via regulating long non-coding RNA NEAT1.

Skeletal muscle atrophy, manifested by a reduction in muscle size and quantity, is primarily attributed to excessive protein catabolism. FAM129B, an antioxidant protein, has been previously implicated in muscle growth and development in cattle. Aim of this study is to elucidate the role of FAM129B in muscle atrophy. FAM129B was consistently down-regulation in muscle atrophy models in vitro and in vivo and in human steroid-treated gluteus muscles. FAM129B depletion resulted in myotubes atrophy with reduced diameter, increased MuRF-1 and Atrogin-1. Conversely, FAM129B overexpression ameliorated muscle atrophy by increasing myotube diameter and reducing Atrogin-1 and MuRF-1. Mice overexpressing FAM129B exhibited resistance to muscle atrophy, evidenced by increased grip strength, increased tibial anterior weight, increased myofiber cross-sectional area and decreased MuRF-1 and Atrogin-1. RNA sequencing revealed NEAT1 as a downstream gene of FAM129B. Mechanistically, FAM129B was found to influence the stability of NEAT1 by directly binding to it. The enhanced stability of NEAT1 subsequently led to increased FoxO1 expression and subsequent protein degradation. Our study has provided evidence that the upregulation of FAM129B rescues the Dex-induced skeletal muscle atrophy, suggesting that FAM129B may be a potential target for alleviating skeletal muscle atrophy.

The Role of E3 Ubiquitin Ligase Gene FBK in Ubiquitination Modification of Protein and Its Potential Function in Plant Growth, Development, Secondary Metabolism, and Stress Response.

As a crucial post-translational modification (PTM), protein ubiquitination mediates the breakdown of particular proteins, which plays a pivotal role in a large number of biological processes including plant growth, development, and stress response. The ubiquitin-proteasome system (UPS) consists of ubiquitin (Ub), ubiquitinase, deubiquitinating enzyme (DUB), and 26S proteasome mediates more than 80% of protein degradation for protein turnover in plants. For the ubiquitinases, including ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3), the FBK (F-box Kelch repeat protein) is an essential component of multi-subunit E3 ligase SCF (Skp1-Cullin 1-F-box) involved in the specific recognition of target proteins in the UPS. Many FBK genes have been identified in different plant species, which regulates plant growth and development through affecting endogenous phytohormones as well as plant tolerance to various biotic and abiotic stresses associated with changes in secondary metabolites such as phenylpropanoid, phenolic acid, flavonoid, lignin, wax, etc. The review summarizes the significance of the ubiquitination modification of protein, the role of UPS in protein degradation, and the possible function of FBK genes involved in plant growth, development, secondary metabolism, and stress response, which provides a systematic and comprehensive understanding of the mechanism of ubiquitination and potential function of FBKs in plant species.

Intermittent enteral nutrition shortens the time to achieve nutritional goals in critically ill patients

Nutritional support is associated with improved clinical outcomes in critically ill patients; however, loss of muscle mass during critical illness leads to weakness, delayed return to work, and increased healthcare consumption. Animal data have suggested that intermittent feeding decreases protein catabolism. This study was aimed at determining whether the mode of enteral nutrition administration might lead to differences in meeting nutritional goals, tolerance, and complications. A prospective, randomized, single-center clinical trial was conducted in four intensive care units in the Czech Republic. Critically ill adult patients with high nutritional risk were randomized to continuous or intermittent enteral nutrition administration through a tolerance-driven protocol. The primary outcome was the time to reach the energetic target. Secondary outcomes included assessment of tolerance (high gastric residual volume, vomitus, and diarrhea), complications (aspiration or ventilator-associated pneumonia), and 28-day mortality. A total of 300 patients were randomized, and 294 were analyzed: 148 in the continuous arm and 146 in the intermittent arm. Regarding the primary outcome, log-rank test indicated that the intermittent group, compared with continuous group, had a statistically significantly shorter time (p = 0.009) and greater diarrhea occurrence (7 (4.7%) vs. 16 (11%), p = 0.049). No statistically significant differences in ventilator-associated pneumonia incidence (18 (12.2%) vs. 18 (12.3%), p = 0.965), 28-day mortality (46 (31.1%) vs. 40 (27.4%), p = 0.488), and other secondary outcomes were observed between groups. Thus, intermittent enteral nutrition was superior to continuous enteral nutrition in terms of time to reach the energetic target with the tolerance-driven administration protocol but was associated with higher diarrhea incidence. No statistically significant differences in the other secondary outcomes were observed.

Unlocking Platelet Mechanisms through Multi-Omics Integration: A Brief Review.

Platelets, tiny cell fragments measuring 2-4 μm in diameter without a nucleus, play a crucial role in blood clotting and maintaining vascular integrity. Abnormalities in platelets, whether genetic or acquired, are linked to bleeding disorders, increased risk of blood clots, and cardiovascular diseases. Advanced proteomic techniques offer profound insights into the roles of platelets in hemostasis and their involvement in processes such as inflammation, metastasis, and thrombosis. This knowledge is vital for drug development and identifying diagnostic markers for platelet activation. Platelet activation is an exceptionally rapid process characterized by various posttranslational modifications, including protein breakdown and phosphorylation. By utilizing multiomics technologies and biochemical methods, researchers can thoroughly investigate and define these posttranslational pathways. The absence of a nucleus in platelets significantly simplifies mass spectrometry-based proteomics and metabolomics, as there are fewer proteins to analyze, streamlining the identification process. Additionally, integrating multiomics approaches enables a comprehensive examination of the platelet proteome, lipidome, and metabolome, providing a holistic understanding of platelet biology. This multifaceted analysis is critical for elucidating the complex mechanisms underpinning platelet function and dysfunction. Ultimately, these insights are crucial for advancing therapeutic strategies and improving diagnostic tools for platelet-related disorders and cardiovascular diseases. The integration of multi-omics technologies is paving the way for a deeper understanding of platelet mechanisms, with significant implications for biomedical research and clinical applications.

Comparative response of casein protein hydrolysate fed young and older human serum on in vitro muscle protein metabolism and myotube size.

In this study we used an ex vivo-in vitro model to assess the effect of feeding older (50 - 70 y) adults a casein protein hydrolysate (CPH) compared with non-bioactive non-essential amino acid (NEAA) supplement on muscle protein synthesis (MPS) and markers of muscle protein breakdown (MPB). As a secondary objective, to assess any attenuation with aging, we compared the anabolic response to CPH-fed serum from older and young adults. Serum from seven healthy older and seven young men following overnight fast and 60 min postprandial ingestion of CPH or NEAA (0.33 g.kg-1 body mass) was used to condition C2C12 myotube media. Analysis by 2-way ANOVA of the fed relative to fasted MPS response revealed a main effect for protein type in pmTOR (p=0.009), p70S6K (p=0.031), p4E-BP1 (p=0.047) and MPS (p=0.041) with a greater response to CPH-fed serum, and interaction effects (AgeXProtein) between young and old serum for pmTOR (p=0.009) and p70S6K (p=0.016). In addition, significant changes in myotube diameter (p=0.049), Atrogin-1 (p=0.004) and MuRF-1 (p=0.012) in response to CPH-fed compared to fasted serum were observed with no differences between young and old serum. In conclusion, this study demonstrated that CPH-fed serum from both young and older (50 - 70 y) adults can stimulate MPS, muscle growth and suppress biomarkers of muscle protein breakdown processes.

Activators of the 26S proteasome when protein degradation increases.

In response to extra- and intracellular stimuli that constantly challenge and disturb the proteome, cells rapidly change their proteolytic capacity to maintain proteostasis. Failure of such efforts often becomes a major cause of diseases or is associated with exacerbation. Increase in protein breakdown occurs at multiple steps in the ubiquitin-proteasome system, and the regulation of ubiquitination has been extensively studied. However, the activities of the 26S proteasome are also stimulated, especially under highly catabolic conditions such as those associated with atrophying skeletal muscle, proteotoxic stress such as heat shock and arsenite, or hormonal cues such as cAMP or cGMP agonists. Among the proteins that enhance proteasomal degradation are the PKA, PKG, UBL-UBA proteins and the Zn finger AN1-type domain (ZFAND) family proteins. ZFAND proteins are of particular interest because of their inducible expression in response to various stimuli and their abilities to control protein quality by stimulating the 26S proteasome and p97/VCP. The regulatory roles of ZFAND proteins appear to be important not only for the control of protein degradation but also for other cellular processes, such as mRNA stability and signaling pathways. This review summarizes the known functions of proteasome activators and discusses their possible roles in regulating proteostasis and other cellular processes.

Transcriptomic Insights into Post-Spawning Death and Muscle Atrophy in Ayu (Plecoglossus altivelis).

In semelparous species like the ayu (Plecoglossus altivelis), spawning is followed by rapid physiological decline and death; yet, the underlying molecular mechanisms remain largely unexplored. This study examines transcriptomic changes in ayu skeletal muscle before and after spawning, with a focus on key genes and pathways contributing to muscle atrophy and metabolic dysfunction. Through RNA sequencing and DEG analysis, we identified over 3000 DEGs, and GSEA and KEGG pathway analysis revealed significant downregulation of energy metabolism and protein degradation. In post-spawning ayu, a rapid decrease in body weight was observed, accompanied by a decline in the expression of myosin heavy chain genes, which are major muscle protein genes, and gene expression changes indicative of muscle atrophy. Decreased expression of AP-1 transcription factors associated with muscle development and aging was also evident. PPI network analysis identified carbohydrate catabolism protein gapdh may be the key factor that led to muscle atrophy and accelerated aging in ayu. Our study revealed that after spawning, the ayu muscle tissue undergoes strong metabolic disorders and cellular stress responses, providing special insights into the mechanisms through the post-spawning death of ayu.

Diversity in chemotherapy-induced cachexia.

Preclinical and clinical studies suggest that chronic administration of cytotoxic drugs (e.g., chemotherapy) may contribute to the occurrence of skeletal muscle wasting and weakness/fatigue (i.e., cachexia). Doxorubicin, folfiri, and cisplatin are known to promote cachexia by triggering common alterations such as skeletal muscle atrophy, protein breakdown, and mitochondrial dysfunction, whereas each also possesses distinguishing features in terms of the activated molecular pathways. Similarly, commonalities exist between different cancer types including the development of muscle wasting early in treatment that can persist for years. The impact of treatment for gastrointestinal, head and neck, and nonsmall cell lung cancers (NSCLCs) on the development of cachexia and survival outcomes is well documented. However, a disconnect occurs between preclinical studies on cachexia, which are often performed on younger mice, and clinical studies on cachexia, which are focused on patients over 60 yr old. Yet, several preclinical studies have examined the impact of age on chemotherapy-induced cachexia. Finally, sex differences have been identified in both preclinical and clinical studies focused on the onset of cachexia consequential to chemotherapy administration and raise the question of whether treatments for this condition should be based on sex specificities. In conclusion, although cancer cachexia has been widely studied for its impact on patients affected by various malignancies, the effects of chemotherapy on the development of cachexia are less explored. Here, we examine diversity in chemotherapy-induced cachexia with respect to specific types of chemotherapy regimens and cancer, and differences based on age and sex.

Astaxanthin ameliorates dexamethasone-induced skeletal muscle atrophy and disorders of glucolipid metabolism

Long-term use of glucocorticoids, such as dexamethasone, can lead to skeletal muscle atrophy and disturbances in glucolipid metabolism. Astaxanthin, a ketocarotenoid, has a variety of physiological activities. In this study, we investigated the effects of astaxanthin on dexamethasone-induced skeletal muscle atrophy and disorders of glycolipid metabolism. Male C57Bl/6J mice were administered dexamethasone alone or supplemented with different doses of astaxanthin (30mg/kg/d, 60mg/kg/d, 120mg/kg/d) for 4 weeks. The results showed that astaxanthin improved locomotor performance and attenuated dexamethasone-induced reductions in skeletal muscle mass and cross-sectional area in mice. Further exploration of the mechanism revealed that astaxanthin was able to balance the catabolism and synthesis of skeletal muscle proteins and protect mitochondria by reducing the expression of the mitochondrial autophagy-associated proteins Lc3B and BNIP3. In addition, astaxanthin reduced the accumulation of fatty acid metabolites and visceral fat and improved the ability of skeletal muscle to utilize sugars, suggesting that astaxanthin may alleviate dexamethasone-induced disturbances in glycolipid metabolism. This study illustrates that astaxanthin can alleviate skeletal muscle atrophy and metabolic disturbances induced by long-term dexamethasone treatment. This suggests that astaxanthin may be a functional dietary supplement to reduce the side effects of glucocorticoid therapy.

Effect of Short-Term Stress and Interaction of Salinity and Ammonia-N Levels, Associated With Food Deprivation on Fatty Acid Profile and Body Composition in Nile Tilapia (Oreochromis niloticus).

High levels of nitrogen compounds can lead to acute toxicity in aquatic organisms. Ammonia, a by-product of protein breakdown, is the most prevalent contaminant in freshwater environments. Increasing salinity in water sources can cause fluctuations in salinity levels within breeding ponds. The interaction of these elements can occur in breeding ponds, significantly impacting the physiology and quality of the aquatic products. The purpose of this study was to examine the relationship between salinity and ammonia-N stress and their effects on the quality and fatty acid profile of tilapia fish (Oreochromis niloticus). The fish were divided into 12 distinct treatment groups, each characterized by varying salinity levels (0, 4, 8, and 12 ppt) and different concentrations of ammonia-N (0, 50% of 50% lethal concentration [LC50]-96 h, and 30% of LC50-96 h) arranged in a factorial design. The calculated LC50-96 h for ammonia-N was 0.86 mg/L. Significant increases were observed in cortisol and glucose levels associated with various salinity treatments and ammonia levels. The levels of carcass protein in the salinity treatments (4, 8, and 12 ppt) did not show any significant differences when compared to the control treatment. However, the protein percentage at 50% of LC50-96 h of ammonia-N was lower than that of the control treatment. In salinity treatments and ammonia levels (50% and 30% of LC50-96 h of ammonia-N), a significant increase in the percentage of lipid, highly unsaturated fatty acids (HUFA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) was observed. To draw the conclusion, our assessment indicates that a salinity concentration of 8 ppt over a 96-h period without feeding has produced positive effects on the quality of tilapia carcasses.

THE IMPACT OF EARLY ENTERAL NUTRUTION ON THE POSTOPERATIVE COURSE IN PATIENTS WITH LIVER CIRRHOSIS AND BLEEDING FROM ESOPHAGEAL AND GASTRIC VARICES

Aim. To determine the effectiveness and safety of early enteral protein nutrition (ЕEPN) using the clinical nutrition «FontActiv Forte Protein» to correct dysproteinemia and hypoalbuminemia in patients with esophageal variceal bleeding, gastric variceal bleeding in the context of liver cirrhosis during the post-hemorrhagic and postoperative periods. Materials and methods. The results of treatment of 71 patients who were treated in the Kyiv City Clinical Emergency Hospital were retrospectively analyzed. The first group of the study consisted of 34 patients who were treated between 2020-2024. The second control group of the study consisted of 37 patients treated between 2015 and 2019. All patients were admitted on an emergency basis for bleeding from esophageal varices in the setting of liver cirrhosis and were operated on after stabilization of hemodynamic parameters. Surgical treatment included porto-azigal disconnection: devascularization of the proximal stomach, distal esophagus, and hardware transection of the esophagus with or without splenectomy. Patients in the first study group received early enteral protein nutrition (EEРN) with protein mixtures (FontActive Forte Protein). Patients of the second control group received parenteral nutrition with Hepasol A, Hepasol Neo, enteral nutrition was started on day 6 of the postoperative period. Results. The intergroup comparison showed that all laboratory parameters, including the levels of total protein and albumin in the posthemorrhagic and early postoperative periods, decreased significantly in all patients of both groups and recovered slowly. Patients in the first group of the study who received REPX had a faster recovery of total protein and albumin, fewer complications, and shorter hospital stay after surgery (p&lt;0.05). Conclusions. The administration of early enteral protein nutrition (FontActive Forte Protein) does not increase the risk of recurrent bleeding compared to delayed enteral nutrition. Nutritional support of protein homeostasis with liquid protein mixtures (FontActive Forte Protein) in patients with bleeding from esophageal/ gastric varices in the post-hemorrhagic/postoperative period is a safe method of correcting amino acid imbalance, reducing protein catabolism, maintaining protein synthesis function of the liver and serum albumin synthesis, which improves the results of surgical treatment, reduces the number of postoperative complications and the length of hospital stay.

Part II. Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?

Creatine monohydrate supplementation (CrM) is a safe and effective intervention for improving certain aspects of sport, exercise performance, and health across the lifespan. Despite its evidence-based pedigree, several questions and misconceptions about CrM remain. To initially address some of these concerns, our group published a narrative review in 2021 discussing the scientific evidence as to whether CrM leads to water retention and fat accumulation, is a steroid, causes hair loss, dehydration or muscle cramping, adversely affects renal and liver function, and if CrM is safe and/or effective for children, adolescents, biological females, and older adults. As a follow-up, the purpose of this paper is to evaluate additional questions and misconceptions about CrM. These include but are not limited to: 1. Can CrM provide muscle benefits without exercise? 2. Does the timing of CrM really matter? 3. Does the addition of other compounds with CrM enhance its effectiveness? 4. Does CrM and caffeine oppose each other? 5. Does CrM increase the rates of muscle protein synthesis or breakdown? 6. Is CrM an anti-inflammatory intervention? 7. Can CrM increase recovery following injury, surgery, and/or immobilization? 8. Does CrM cause cancer? 9. Will CrM increase urine production? 10. Does CrM influence blood pressure? 11. Is CrM safe to consume during pregnancy? 12. Does CrM enhance performance in adolescents? 13. Does CrM adversely affect male fertility? 14. Does the brain require a higher dose of CrM than skeletal muscle? 15. Can CrM attenuate symptoms of sleep deprivation? 16. Will CrM reduce the severity of and/or improve recovery from traumatic brain injury? Similar to our 2021 paper, an international team of creatine research experts was formed to perform a narrative review of the literature regarding CrM to formulate evidence-based responses to the aforementioned misconceptions involving CrM.

Microbial Ecology of Local Cheese: A Focus on Lactic Acid Bacteria

The microbial ecology of local cheese is a complex and dynamic interplay of microorganisms that profoundly influences its flavor, texture, safety, and preservation. This article delves into the intricate relationships within the cheese microbiota, with a specific focus on lactic acid bacteria (LAB). LAB, as the predominant group in cheese ecosystems, play pivotal roles in acidification, flavor development, and safety. Their production of lactic acid contributes to the acidity and tanginess of the cheese, while also creating an environment that inhibits the growth of pathogenic microorganisms. Beyond LAB, yeasts and molds contribute to the texture and flavor complexity of cheese through enzymatic breakdown of proteins and lipids. The microbial community's impact on cheese characteristics extends to the creation of complex flavor compounds and the inhibition of undesirable microbes, enhancing safety. Research findings underscore the correlation between specific LAB strains and the production of unique flavors, as well as the inhibitory effects of LAB-produced bacteriocins on pathogenic bacteria, emphasizing the safety-enhancing mechanisms inherent in the microbial ecology of local cheese. Furthermore, the article highlights the extended shelf life of cheese with well-established LAB populations, showcasing the practical implications of microbial interactions in ensuring cheese quality over time. Understanding the microbial ecology of local cheese, especially the roles of LAB, is vital for both traditional cheese-making practices and exploring innovative approaches in cheese production. This comprehensive exploration underscores the significance of microbial dynamics in shaping the distinctive characteristics and ensuring the safety and quality of local cheeses.

Pathway mapping of exhaled volatile organic compounds associated with blood and ruminal fluid metabolites to describe the nutritional and metabolic status of lactating dairy cows.

Exhaled breath offers an interesting matrix of low invasive sampling of potentially relevant information about the organism's metabolism in the form of volatile organic compounds (VOC). The VOC can be exhaled by the ructus (Islam et al., 2023) or passed the blood-lung barrier for expiration through the lungs. In this work, we consider exhaled breath as a mixture of VOC derived from the lungs and from the upper gastrointestinal tract. However, the informative value of exhaled breath in ruminants remains largely unstudied. The aim of this study was to identify exhaled VOC that could be used to assess the nutritional and metabolic status of dairy cows. To do so, we performed untargeted analysis of exhaled VOC from dairy cows, investigated their correlations with commonly analyzed blood and ruminal fluid metabolites and the calculated energy balance (EB), and explored the underlying pathways of correlated exhaled VOC. This was done as part of a feeding experiment in which 32 lactating Holstein dairy cows were assigned to 2 basal diets for 12 weeks. Half of the cows were fed a hay-based diet, and the other half were fed a silage-based diet. During experimental wk 1-8, half of the cows in each basal diet group were supplemented with a control concentrate, and the other half received an experimental concentrate containing essential oils. During experimental wk 9-12, all cows received the control concentrate. Exhaled breath, blood, and ruminal fluid samples were collected every 4 experimental weeks (W4, 8, and 12) on 3 consecutive sampling days. Exhaled breath was analyzed for VOC, ruminal fluid for VFA and ammonia, and serum samples for albumin, total protein, urea, glucose, cholesterol, BHB, and nonesterified fatty acid (NEFA) concentrations. Pearson correlations were calculated to assess the associations between exhaled VOC and concentrations of blood and ruminal fluid metabolites and the calculated EB. Fifteen correlations were found between exhaled VOC (tetradecanal and γ-hydroxybutyrate (GHB), 3-penten-2-one, 4-hydroxy-4-methylpentan-2-one, 2-ethylhexanal, 2-ethylhexan-1-ol, p-cymene) and ruminal fluid (acetate, butyrate, valerate, and ammonia) and blood metabolite concentrations (BHB, NEFA, glucose, urea, and cholesterol) across the cow groups. The underlying pathways of 3-penten-2-one, GHB, and tetradecanal were mainly related to fat and protein catabolism and therefore to the actual animal metabolism. The correlations with the other 4 exhaled VOC, 4-hydroxy-4-methylpentan-2-one, p-cymene, 2-ethyl-hexan-1-ol, and 2-ethylhexanal, were diet- or time-related, specifically due to differences in feed ingredients. The results demonstrate the associations of single exhaled VOC with the nutritional and metabolic status of healthy dairy cows. Their potential as new biomarkers should be further investigated in cows in various nutritional and metabolic states.

Chaperone Proteins: The Rising Players in Muscle Atrophy.

Despite significant progress in understanding the molecular aetiology of muscle atrophy, there is still a great need for new targets and drugs capable of counteracting muscle wasting. The role of an impaired proteostasis as the underlying causal mechanism of muscle atrophy is a well-established concept. From the earliest work on muscle atrophy and the identification of the first atrogenes, the hyper-activation of the proteolytic systems, such as autophagy and the ubiquitin proteasome system, has been recognized as the major driver of atrophy. However, the role of other key regulators of proteostasis, the chaperone proteins, has been largely overlooked. Chaperone proteins play a pivotal role in protein folding and in preventing the aggregation of misfolded proteins. Indeed, some chaperones, such as αB-crystallin and Hsp25, are involved in compensatory responses aimed at counteracting protein aggregation during sarcopenia. Chaperones also regulate different intracellular signalling pathways crucial for atrogene expression and the control of protein catabolism, such as the AKT and NF-kB pathways, which are regulated by Hsp70 and Hsp90. Furthermore, the downregulation of certain chaperones causes severe muscle wasting per se and experimental strategies aimed at preventing this downregulation have shown promising results in mitigating or reversing muscle atrophy. This highlights the therapeutic potential of targeting chaperones and confirms their crucial anti-atrophic functions. In this review, we summarize the most relevant data showing the modulation and the causative role of chaperone proteins in different types of skeletal muscle atrophies.