Search Results (159)

Background/Objectives: Resistance exercise under hypoxic conditions induces various metabolic and hormonal responses, yet the relationship between hypoxia severity and anabolic hormone responses remains unclear. This study aimed to assess the effects of a single bout of resistance exercise on metabolic and hormonal responses in normoxia and three levels of hypoxia in both men and women. Methods: The study involved 16 physically active individuals with at least two years of experience in recreational resistance training. The participants completed resistance exercise sessions in normoxia and normobaric hypoxia at simulated altitudes of 3000 m (H3000), 4000 m (H4000), and 5000 m (H5000). Blood levels of total testosterone (T), cortisol (C), growth hormone (GH), and metabolic variables were measured before and after exercise. Results: In women, severe hypoxia (H4000 and H5000) was found to significantly enhance post-exercise increases in T and GH compared to H3000 (p < 0.05), without affecting C levels. In men, hypoxia (regardless of intensity) did not significantly augment post-exercise changes in T and GH compared to normoxia. In H4000 conditions, an increase in C levels was observed (p < 0.05), leading to an unfavorable reduction in the T/C ratio. Additionally, a reduction in the total number of repetitions performed during the training session and a weakened metabolic response (lactate and creatine kinase) were observed in men at H5000. Conclusions: In women, severe hypoxia (H5000) was found to induce a pronounced hormonal response, particularly in GH levels. The use of severe hypoxia during resistance exercise appears unfavorable in men due to a reduced metabolic response, and diminished exercise capacity, coupled with a failure to induce more favorable changes in the secretion of anabolic hormones than in normoxic conditions. Full article

Background: Malnutrition and muscle weakness are highly prevalent in critically admitted patients. To overcome sarcopenia and muscle weakness, physical activity and neuromuscular electric stimulation have been introduced with limited efficacy. Thus, several anabolic remedies have been introduced. An adequate increase in protein support according to indirect calorimetry and body composition and methyl hydroxybutyrate (HMB) is emerging. Therefore, we wanted to investigate the impact of HMB-enriched whey formula on the nutritional status, muscle weakness, and clinical course of critically ill patients undergoing nutritional status multimodal assessment and physical rehabilitation. Methods: We consecutively enrolled critically ill adult patients admitted to the intensive care unit (ICU) of “Santa Maria Hospital”, Terni, Italy. All patients underwent preliminary anthropometric, laboratory tests, nutritional (bioimpedance vector analysis and indirect calorimetry), and ultrasound muscle assessment at admission (T0). Laboratory tests monitoring continued throughout the ICU stay. Nutritional and muscle strength assessment was taken weekly throughout the patient’s ICU stay. All patients were enterally administered with a whey protein-enriched formula. Ten days after admission (during the physical rehabilitation period), patients were randomly administered a mixture of essential amino acids and methyl hydroxybutyrate (HMB). Results: We consecutively enrolled 54 ICU patients. At the baseline, survivors (n = 46) were significantly younger than non-survivors. The latter had a worse SAPS II score, nutritional status, and risk, with no significant difference in basal metabolism. Prealbumin values significantly correlated with improved nutritional status and metabolism. Starting from 10 days upon ICU admission, the pennation angle (used as a measure of muscle strength) significantly correlated with the improvement in nutritional status. Whey proteins were well tolerated. Its administration showed a tendency to improve the pennation angle. No specific effect of the mixture containing essential amino acids and methyl hydroxybutyrate was observed. Nutritional status improvement and the rise of basal metabolism were significantly correlated with the extubation time. On the other hand, the reduction in muscle weakness was not significantly correlated with the timing of extubation. Conclusions: Whey protein formula administration can significantly improve nutritional status and basal metabolism in ICU patients. This is reflected in improved muscle strength. Whey protein administration shows a tendency toward a rise in pennation angle. A similar and non-specific trend was observed upon HMB mixture add-one. Further prospective large-scale controlled studies are needed to confirm these promising results. Full article

The role of mitochondria as the electric engine of cells is well established. Over the past two decades, accumulating evidence has pointed out that, despite the presence of a highly active glycolytic pathway (Warburg effect), a functional and even upregulated mitochondrial respiration occurs in cancer cells to meet the need of high energy and the biosynthetic demand to sustain their anabolic growth. Mitochondria are also the primary source of intracellular ROS. Cancer cells maintain moderate levels of ROS to promote tumorigenesis, metastasis, and drug resistance; indeed, once the cytotoxicity threshold is exceeded, ROS trigger oxidative damage, ultimately leading to cell death. Based on this, mitochondrial metabolic functions and ROS generation are considered attractive targets of synthetic and natural anticancer compounds. Tocotrienols (TTs), specifically the δ- and γ-TT isoforms, are vitamin E-derived biomolecules widely shown to possess striking anticancer properties since they regulate several intracellular molecular pathways. Herein, we provide for the first time an overview of the mitochondrial metabolic reprogramming and redox homeostasis perturbation occurring in cancer cells, highlighting their involvement in the anticancer properties of TTs. This evidence sheds light on the use of these natural compounds as a promising preventive or therapeutic approach for novel anticancer strategies. Full article

Reprogramming of energy metabolism to support cellular growth is a “hallmark” of cancer, allowing cancer cells to balance the catabolic demands with the anabolic needs of producing the nucleotides, amino acids, and lipids necessary for tumor growth. Metabolic alterations, or “addiction”, are promising therapeutic targets and the focus of many drug discovery programs. Asparagine metabolism has gained much attention in recent years as a novel target for cancer therapy. Asparagine is widely used in the production of other nutrients and plays an important role in cancer development. Nutritional inhibition therapy targeting asparagine has been used as an anticancer strategy and has shown success in the treatment of leukemia. However, in solid tumors, asparagine restriction alone does not provide ideal therapeutic efficacy. Tumor cells initiate reprogramming processes in response to asparagine deprivation. This review provides a comprehensive overview of asparagine metabolism in cancers. We highlight the physiological role of asparagine and current advances in improving survival and overcoming therapeutic resistance. Full article

Background: Anabolic resistance accelerates muscle loss in aging and obesity, thus predisposing to sarcopenic obesity. Methods: In this retrospective analysis of a randomized clinical trial, we examined baseline predictors of the adaptive response to three months of home-based resistance exercise, daily physical activity, and protein-based, multi-ingredient supplementation (MIS) in a cohort of free-living, older males (n = 32). Results: Multiple linear regression analyses revealed that obesity and a Global Risk Index for metabolic syndrome (MetS) were the strongest predictors of Δ% gains in lean mass (TLM and ASM), LM/body fat ratios (TLM/%BF, ASM/FM, and ASM/%BF), and allometric LM (ASMI, TLM/BW, TLM/BMI, ASM/BW), with moderately strong, negative correlations to the adaptive response to polytherapy r = −0.36 to −0.68 (p < 0.05). Kidney function, PA level, and chronological age were only weakly associated with treatment outcomes (p > 0.05). Next, we performed a subgroup analysis in overweight/obese participants with at least one other MetS risk factor and examined their adaptive response to polytherapy with two types of protein-based MIS (PLA; collagen peptides and safflower oil, n = 8, M5; whey/casein, creatine, calcium, vitamin D₃, and fish oil, n = 12). The M5 group showed greater improvements in LM (ASM; +2% vs. −0.8%), LM/body fat ratios (ASM/FM; +3.8% vs. −5.1%), allometric LM (ASM/BMI; +1.2% vs. −2.5%), strength (leg press; +17% vs. −1.4%), and performance (4-Step-Stair-Climb time; −10.5% vs. +1.1%) vs. the PLA group (p < 0.05). Bone turnover markers, indicative of bone accretion, were increased pre-to-post intervention in the M5 group only (P1NP; p = 0.036, P1NP/CTX ratio; p = 0.088). The overall anabolic response, as indicated by ranking low-to-high responders for Δ% LM (p = 0.0079), strength (p = 0.097), and performance (p = 0.19), was therefore significantly higher in the M5 vs. PLA group (p = 0.013). Conclusions: Our findings confirm that obesity/MetS is a key driver of anabolic resistance in old age and that a high-quality, whey/casein-based MIS is more effective than a collagen-based alternative for maintaining musculoskeletal health in individuals at risk for sarcopenic obesity, even when total daily protein intake exceeds current treatment guidelines. Full article

Renal cell carcinoma (RCC) is the most common type of kidney cancer arising from renal tubular epithelial cells and is characterized by a high aggressive behavior and invasiveness that lead to poor prognosis and high mortality rate. Diagnosis of RCC is generally incidental and occurs when the stage is advanced and the disease is already metastatic. The management of RCC is further complicated by an intrinsic resistance of this malignancy to chemotherapy and radiotherapy, which aggravates the prognosis. For these reasons, there is intense research focused on identifying novel biomarkers which may be useful for a better prognostic assessment, as well as molecular markers which could be utilized for targeted therapy. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that has been identified as a key modulator of oxidative stress response, and its overexpression is considered a negative prognostic feature in several types of cancers including RCC, since it is involved in various key cancer-promoting functions such as proliferation, anabolic metabolism and resistance to chemotherapy. Given the key role of Nrf2 in promoting tumor progression, this enzyme could be a promising biomarker for a more accurate prediction of RCC course and it can also represent a valuable therapeutic target. In this review, we provide a comprehensive literature analysis of studies that have explored the role of Nrf2 in RCC, underlining the possible implications for targeted therapy. Full article

Background/Objectives: The sucrose non-fermentation-related kinase 1 (SnRK1) protein complex in plants plays an important role in energy metabolism, anabolism, growth, and stress resistance. SnRK1 is a heterotrimeric complex. The SnRK1 complex is mainly composed of α, β, βγ, and γ subunits. Studies on plant SnRK1 have primarily focused on the functional α subunit, with the β regulatory subunit remaining relatively unexplored. The present study aimed to elucidate the evolutionary relationship, structural prediction, and interaction with the core α subunit of peach SnRK1β3 (PpSnRK1) subunit. Methods: Bioinformatics analysis of PpSnRK1 was performed through software and website. We produced transgenic tomato plants overexpressing PpSnRK1 (OEPpSnRK1). Transcriptome analysis was performed on OEPpSnRK1 tomatoes. We mainly tested the growth index and drought resistance of transgenic tomato plants. Results: The results showed that PpSnRK1 has a 354 bp encoded protein sequence (cds), which is mainly located in the nucleus and cell membrane. Phylogenetic tree analysis showed that PpSnRK1β3 has similar domains to other woody plants. Transcriptome analysis of OEPpSnRK1β3 showed that PpSnRK1β3 is widely involved in biosynthetic and metabolic processes. Functional analyses of these transgenic plants revealed prolonged growth periods, enhanced growth potential, improved photosynthetic activity, and superior drought stress tolerance. Conclusions: The study findings provide insight into the function of the PpSnRK1 subunit and its potential role in regulating plant growth and drought responses. This comprehensive analysis of PpSnRK1 will contribute to further enhancing our understanding of the plant SnRK1 protein complex. Full article

Cancer-associated cachexia (CAC) is a severe wasting syndrome, marked by involuntary weight loss and muscle wasting. It is a leading cause of cancer-related morbidity and mortality, and is driven by systemic, chronic low-grade inflammation. Key cytokines, such as IL-6 and GDF15, activate catabolic pathways in many organs. This study examined the role of inflammation and metabolic disruption in the liver during CAC, focusing on its dual role as both a target and a source of inflammatory factors. The analysis covered protein and lipid metabolism disturbances, including the hepatic production of acute-phase proteins and insulin resistance. Hepatic inflammation contributes to systemic dysfunction in CAC. The increased production of C-Reactive Protein (CRP) impacts muscle wasting, while liver inflammation leads to insulin resistance and hepatic steatosis, aggravating the cachectic state. Therefore, understanding the molecular mechanisms of liver metabolism in CAC is essential for developing effective therapies. Potential interventions include anti-inflammatory treatments, anabolic strategies, and restoration of lipid metabolism. Further research is necessary to explore the liver’s full contribution to CAC and its systemic effects, allowing to the development of liver-targeted therapeutic strategies. Full article

Although low-protein diets can improve the nitrogen utilization efficiency and alleviate economic pressures in ruminants, they may also negatively impact dairy performance. Rumen-protected lysine (RPL) supplementation can improve the health status and growth performance of ruminants without compromising nitrogen utilization efficiency and feed intake. In this study, a total of thirty-three multiparous dairy goats in the late-lactation period were randomly divided into three groups that were separately fed the control diet (namely the protein-adequacy group), the low-protein diet (namely the protein-deficient group), and the RPL-supplemented protein-deficient diet (namely RPL-supplementation group) for five weeks. Here, we investigated the molecular mechanisms regarding how low-protein diets with RPL supplementation compromise lactation phenotypes in dairy goats through cross-tissue transcriptomic analyses. Dietary protein deficiency caused an imbalance in amino acid (AA) intake, disrupted hepatic function, and impaired milk synthesis. Transcriptomic analyses further showed that RPL supplementation exhibited some beneficial effects, like mitigating abnormal lipid and energy metabolism in the liver, elevating hepatic resistance to oxidative stress, improving the mammary absorption of AAs, as well as activating mammary lipid and protein anabolism primarily through peroxisome proliferator-activated receptor (PPAR) and janus kinase-signal transducer (JAK)—signal transducer and activator of transcription (STAT) signaling, respectively. RPL supplementation of a low-protein diet contributes to maintaining late lactation in dairy goats primarily through mitigating hepatic energy disturbances and activating both lipid and protein metabolism in the mammary glands. Since RPL supplementation initiated a series of comprised events on mammary protein and lipid metabolism as well as the hepatic function and energy generation in dairy goats under protein deficiency during late lactation, these findings thus provide some insights into how RPL supplementation helps maintain milk production and health in dairy mammals especially at late lactation. Full article

Background: Nutrition significantly impacts the outcomes of critically ill children in intensive care units (ICUs). Due to the evolving metabolic, neuroendocrine, and immunological disorders associated with severe illness or trauma, there are dynamically changing phases of energy needs requiring tailored macronutrient intake. Objectives: This study aims to assess the changing dietary needs from the acute phase through recovery, provide recommendations for implementing evidence-based strategies to ensure adequate energy and nutrient provision in pediatric ICUs, and optimize patient outcomes. Methods: A comprehensive search of the MEDLINE-PubMed database was conducted, focusing on randomized controlled trials, meta-analyses, and systematic reviews related to the nutrition of critically ill children. The study highlights recent guidelines using the GRADE approach, supplemented by relevant adult studies, current clinical practices, challenges, gaps in knowledge, and future directions for research aimed at improving nutritional interventions. Results: Early personalized, incremental enteral feeding helps mitigate the negative energy balance during the acute phase, aids organ function restoration in the stabilization phase, and supports growth during the recovery phase and beyond. Conversely, early full nutritional support, high protein doses, or isolated micronutrient administration have not demonstrated benefits due to anabolic resistance in these patients. Moreover, early parenteral nutrition during the acute phase may suppress autophagy and lead to worse outcomes. Accurate assessment of nutritional status and monitoring of daily energy and protein needs are crucial. Conclusions: Strong evidence supports the establishment of a dedicated nutritional team and the implementation of individualized nutritional protocols in the ICU to reduce morbidity and mortality in critically ill children. Full article

Background: Acute sarcopenia refers to the swift decline in muscle function and mass following acute events such as illness, surgery, trauma, or burns that presents significant challenges in hospitalized older adults. Methods: narrative review to describe the mechanisms and management of acute sarcopenia. Results: The prevalence of acute sarcopenia ranges from 28% to 69%, likely underdiagnosed due to the absence of muscle mass and function assessments in most clinical settings. Systemic inflammation, immune–endocrine dysregulation, and anabolic resistance are identified as key pathophysiological factors. Interventions include early mobilization, resistance exercise, neuromuscular electrical stimulation, and nutritional strategies such as protein supplementation, leucine, β-hydroxy-β-methyl-butyrate, omega-3 fatty acids, and creatine monohydrate. Pharmaceuticals show variable efficacy. Conclusions: Future research should prioritize serial monitoring of muscle parameters, identification of predictive biomarkers, and the involvement of multidisciplinary teams from hospital admission to address sarcopenia. Early and targeted interventions are crucial to improve outcomes and prevent long-term disability associated with acute sarcopenia. Full article

Background: Sarcopenia is characterized by the progressive loss of skeletal muscle mass, strength, and function, significantly impacting overall health and quality of life in older adults. This narrative review explores emerging targets and potential treatments for sarcopenia, aiming to provide a comprehensive overview of current and prospective interventions. Methods: The review synthesizes current literature on sarcopenia treatment, focusing on recent advancements in muscle regeneration, mitochondrial function, nutritional strategies, and the muscle–microbiome axis. Additionally, pharmacological and lifestyle interventions targeting anabolic resistance and neuromuscular junction integrity are discussed. Results: Resistance training and adequate protein intake remain the cornerstone of sarcopenia management. Emerging strategies include targeting muscle regeneration through myosatellite cell activation, signaling pathways, and chronic inflammation control. Gene editing, stem cell therapy, and microRNA modulation show promise in enhancing muscle repair. Addressing mitochondrial dysfunction through interventions aimed at improving biogenesis, ATP production, and reducing oxidative stress is also highlighted. Nutritional strategies such as leucine supplementation and anti-inflammatory nutrients, along with dietary modifications and probiotics targeting the muscle–microbiome interplay, are discussed as potential treatment options. Hydration and muscle–water balance are emphasized as critical in maintaining muscle health in older adults. Conclusions: A combination of resistance training, nutrition, and emerging therapeutic interventions holds potential to significantly improve muscle function and overall health in the aging population. This review provides a detailed exploration of both established and novel approaches for the prevention and management of sarcopenia, highlighting the need for further research to optimize these strategies. Full article

The prevalence of sarcopenia (loss of muscle strength, mass and function) in individuals with heart failure (HF) stands at a considerable level (approximately 20%), contributing to heightened mortality rates and diminished quality of life. The underlying pathophysiological mechanisms involve the presence of low-grade inflammation and a disturbance of the anabolic–catabolic protein balance. The nutritional assessment of patients with HF is a key aspect, and diverse diagnostic tools are employed based on patient profiles (outpatient, inpatient and nursing home). The Global Leadership Initiative on Malnutrition (GLIM) criteria serves as a consensus for diagnosing malnutrition. Given that edema can impact body mass index (BMI) in patients with HF, alternative body assessment technical methods, such as bioelectrical vector impedance (BiVA), BIA (without vector mode), computer tomography (CT) or clinical ultrasound (US), are useful. Scientific evidence supports the efficacy of both aerobic and resistance physical exercises in ameliorating and preventing muscle wasting associated with HF. Dietary strategies emphasize the importance of protein intake, while certain micronutrients like coenzyme Q10 or intravenous iron may offer benefits. This narrative review aims to present the current understanding of the pathogenesis, diagnosis and treatment of muscle loss in individuals with heart failure and its consequential impact on prognosis. Full article

Background: The vegan diet (VEG_D) has gained popularity in recent years for ecological and ethical reasons, as well as for its health benefits. In addition to the type of diet, the resistance training program (RT_P) plays a fundamental role as one of the main natural anabolic stimuli to increase musculoskeletal mass and reduce fat mass. Methods: The study was a 16-week non-randomized controlled clinical trial consisting of three RT_P sessions per week. The sample included 70 Chilean individuals, aged between 18 and 59 years, who had been following a VEG_D or omnivorous diet (OMN_D) for the past 6 months. Four groups were established: Vegan Diet Resistance Training Program (VEG_D-RT_P), Vegan Diet Control (VEG_D-C), Omnivorous Diet Resistance Training Program (OMN_D-RT_P), and Omnivorous Diet Control (OMN_D-C). Results: The sample consisted of 47 women and 23 men, with a mean age of 30.1 (±8.6) years. A reduction of 1.20% in the percentage of fat mass (%FM) was observed in the VEG_D-RT_P group (r = 0.554, p = 0.016), as well as a reduction of 0.70 kg in kilograms of fat mass (KFM) (r = 0.480, p = 0.036). The OMN_D-RT_P group decreased %FM by 0.90% (r = 0.210, p = 0.432) and KFM by 0.50 kg (r = 0.109, p = 0.683). Conclusions: RT_P combined with VEG_D or OMN_D significantly reduced the percentage of fat mass, although its effect was more significant in the VEG_D-RT_P participants. Full article

A coenzyme A (CoA-SH)-responsive dual electrochemical and fluorescence-based sensor was designed utilizing an MnO₂-immobilized-polymer-dot (MnO₂@D-PD)-coated electrode for the sensitive detection of osteoarthritis (OA) in a peroxisomal β-oxidation knockout model. The CoA-SH-responsive MnO₂@D-PD-coated electrode interacted sensitively with CoA-SH in OA chondrocytes, triggering electroconductivity and fluorescence changes due to cleavage of the MnO₂ nanosheet on the electrode. The MnO₂@D-PD-coated electrode can detect CoA-SH in immature articular chondrocyte primary cells, as indicated by the significant increase in resistance in the control medium (R_24h = 2.17 MΩ). This sensor also sensitively monitored the increase in resistance in chondrocyte cells in the presence of acetyl-CoA inducers, such as phytol (Phy) and sodium acetate (SA), in the medium (R_24h = 2.67, 3.08 MΩ, respectively), compared to that in the control medium, demonstrating the detection efficiency of the sensor towards the increase in the CoA-SH concentration. Furthermore, fluorescence recovery was observed owing to MnO₂ cleavage, particularly in the Phy- and SA-supplemented media. The transcription levels of OA-related anabolic (Acan) and catabolic factors (Adamts5) in chondrocytes also confirmed the interaction between CoA-SH and the MnO₂@D-PD-coated electrode. Additionally, electrode integration with a wireless sensing system provides inline monitoring via a smartphone, which can potentially be used for rapid and sensitive OA diagnosis. Full article