Search Results (332)

Aesthetic medicine is shifting from symptomatic correction to biological structural restoration. Regenerative aesthetics represents a frontier in dermatology, focusing on the restoration of the skin microenvironment to enhance cellular vitality and tissue resilience. Central to this approach is the concept of “skin bed preparation”, a strategic priming phase designed to optimize the physiological terrain before the delivery of advanced aesthetic interventions. This review explores the molecular and cellular mechanisms by which skin bed preparation modulates the extracellular matrix (ECM) and the dermal niche to maximize the efficacy of subsequent treatments and promote long-term skin longevity. Evidence suggests that biostimulatory priming utilizing senolytics, senomorphics, mitochondrial, and/or epigenetic rejuvenators rehabilitates the fibroblast–collagen interactome. By reducing oxidative stress and chronic low-grade inflammation, these preparatory steps transition the skin from a catabolic to an anabolic state. This metabolic reset ensures that subsequent procedures, such as laser therapy, injectable fillers, encounter a responsive cellular environment, resulting in superior collagen induction and prolonged clinical outcomes. Optimizing the skin microenvironment via regenerative aesthetics is not merely an adjunctive step but a fundamental requirement for therapeutic success. Integrating skin bed preparation into clinical protocols provides a synergistic framework that enhances immediate procedural results while addressing the underlying hallmarks of skin aging, ultimately redefining the trajectory of skin health and longevity. Full article

Background/Objectives: Serum 25-hydroxyvitamin D (25OHD) is a key determinant of calcium-phosphorus homeostasis and bone metabolism; however, its role as a modifier of the bone mineral density (BMD) response to romosozumab, a dual-action anabolic agent for osteoporosis, remains poorly characterized, particularly across different levels of renal function. This study investigated whether the renal function category and prior treatment history modified the association between baseline 25OHD and romosozumab BMD response. Methods: We conducted a retrospective cohort study of 315 consecutive Japanese patients treated with romosozumab (210 mg subcutaneously monthly for 12 months) at Mutsu General Hospital, Aomori, Japan (2019–2025; IRB approval RO7-5; date of approval: 20 January 2026). Patients were stratified by eGFR-based renal function category: preserved renal function (eGFR ≥ 60 mL/min/1.73 m², n = 199) and moderately reduced renal function (eGFR 30–59 mL/min/1.73 m², n = 86). Patients with severely reduced renal function (eGFR 15–29, n = 11) were excluded from the comparative analyses. Spearman rank correlations (Rs) were computed between baseline 25OHD and (i) baseline TRACP-5b and (ii) 12-month lumbar spine BMD changes. Mediation analysis was performed to examine TRACP-5b as a potential mediator. Results: In the preserved renal function group, baseline 25OHD was significantly and inversely correlated with TRACP-5b (Rs = −0.246, p = 0.0007). This correlation was absent in the moderately reduced renal function group (Rs = +0.036, p = 0.74), and the interaction was statistically significant (z = −2.38, p = 0.017). Among treatment-experienced patients, lower 25OHD levels were correlated with greater LS-BMD response (Rs = −0.197, p = 0.036), whereas no such correlation was observed in treatment-naïve patients (Rs = −0.009, p = 0.902). Mediation analysis did not identify TRACP-5b as a significant mediator. Conclusions: The association between serum 25OHD and romosozumab BMD response appears to be context-dependent across renal function categories and prior treatment history. These findings are hypothesis-generating and require prospective validation before they can be applied to clinical practice. Full article

Background: Peripheral muscle electrostimulation (PME), encompassing neuromuscular electrical stimulation (NMES) and functional electrical stimulation (FES), has been increasingly acknowledged as an effective adjunctive or complementary treatment to voluntary exercise in elderly cardiac patients who cannot perform sufficient amounts of exercise, for whom there is limited research on optimal protocols. Sarcopenia, defined as a progressive decrease in muscle mass, strength and function, affects approximately 34% of heart failure (HF) patients and considerably worsens their prognosis. The objective of this systematic review is to summarize current evidence on the theoretical mechanisms, physiological pathways, safety and efficacy of PME in older adults within a cardiac rehabilitation (CR) setting, with a specific emphasis on sarcopenia reversal. Methods: We performed a systematic review following the PRISMA 2020 guidelines. A systematic search was conducted on the PubMed, Embase, Cochrane Library, CINAHL and PEDro databases from inception until December 2025. We searched for randomized controlled trials (RCTs) and controlled clinical trials focusing on PME in patients with cardiac diseases aged 65 years or older. The main outcomes were physical function (assessed with the Short Physical Performance Battery [SPPB] and 6 min walk distance [6MWD]), muscle strength, muscle mass and safety. The Cochrane Risk of Bias tool was used to evaluate the quality of the studies. Results: Eight studies were included, with 387 participants and a mean age between 78 and 85 years. PME consistently improved lower-extremity muscle strength (MD: 5.2% body weight, 95% CI = 1.2–9.1, p = 0.013) along with SPPB scores, which ranged from +2.3 to +2.67 points (all p < 0.05). Home-based PME (NMES) achieved 100% adherence rates, and no cardiovascular adverse events were reported. The mechanisms by which PME is beneficial involve peripheral skeletal muscle adaptations without eliciting central hemodynamic stress, increased endothelial function, aerobic enzyme activity, protein anabolism stimulation or muscle proteolysis inhibition. No significant effects were observed on BNP levels, hospital readmissions or mortality. PME has been shown to attenuate the progression of sarcopenia through hypertrophy of type I and II muscle fibers, as well as mitochondrial biogenesis. Conclusions: PME is a safe, feasible adjunct to conventional CR in frail, elderly cardiac patients, particularly those with exercise intolerance and sarcopenia. It improves peripheral muscle function, physical performance, and muscle protein balance without cardiovascular stress. Larger multicenter trials are needed to establish optimal protocols and long-term clinical outcomes. Full article

Chemotherapy-induced metabolic reprogramming of glioblastoma multiforme (GBM) cells increases intracellular levels of reductive and energetic carriers, thereby fueling drug-relocation and retention systems and enhancing GBM drug-resistance. We have previously shown the role of this process in the adaptation of poly(morpho)nuclear “giant” cells (PGCs) in T98G populations to doxorubicin (DOX)-induced stress. Here, we addressed the role of a “resistance triad”, which coordinates metabolic T98G reprogramming with the activation of the drug-relocation and drug-retention axis, in the recovery of GBM populations from chemotherapeutic stress. A combination of proteomic analyses with metabolic and phenotypic profiling of pulse DOX-treated T98G cells revealed the significance of mitochondrial dynamics for the efficiency of the T98G “resistance triad”. DOX-induced mobilization of ATP-generating systems and ATP-dependent anabolic pathways was accompanied by the formation of DOX-negative, “mosaic” mitochondrial networks and the upregulation of mitofusin-2 (MFN2) in T98G PGCs. Transient MFN2 down-regulation correlated with the respiratory capacity of T98G cells, while impairing cell welfare in the absence and presence of DOX. However, minute fractions of PGCs, which withstood combined MFN2 down-regulation and pulse DOX treatment, retained mitochondrial networks and displayed efficient ABC transporter-/V-type channel-dependent lysosomal DOX retention. Collectively, a “triad” of mitochondrial activation, ABC transporter-dependent perinuclear redistribution and V-type channel-mediated lysosomal DOX compartmentalization determines DOX resistance of T98G cells. Whereas MFN2-dependent mitochondrial rearrangements may contribute to these processes, complementary adaptative mechanisms can compensate MFN2 dysfunction, limiting its potential as a therapeutic target. Full article

Prediabetes is increasingly recognized as a risk factor for sarcopenia, driven by chronic low-grade inflammation, insulin resistance, and impaired anabolic signaling. Nutritional interventions containing whey protein, hydroxymethylbutyrate (HMB), glucosamine, and micronutrients may offer a multi-target strategy to counteract muscle deterioration. This study aimed to evaluate the efficacy of HiLo Platinum™ supplementation in attenuating muscle strength decline in a prediabetic rat model, with integrated analysis of metabolic biomarkers and gut microbiome profiles. A randomized preclinical trial was conducted using male Sprague Dawley rats assigned to four groups: normal diet (ND), prediabetic control induced by cholesterol- and fat-enriched diet with fructose (CFEDF), and two treatment groups receiving low-dose (0.63 g/kg BW) or high-dose (1.26 g/kg BW) HiLo Platinum™. The intervention lasted six weeks. Muscle strength was assessed via a four-limb grip strength test (reverse hang time and holding impulse). Biomarkers related to inflammation, mitochondrial function, and anabolic signaling (TNF-α, IL-10, PGC-1α, IGF-1, SIRT-1, AMPK, mTOR, and myostatin), lipid profile, and blood glucose were analyzed. Gut microbiome composition and diversity were evaluated using taxonomic profiling and multivariate analyses. HiLo Platinum™ supplementation significantly improved muscle strength, evidenced by increased reverse hang time and holding impulse (p < 0.001). Both doses reduced blood glucose and improved lipid profiles, including increased HDL and decreased LDL, triglycerides, and total cholesterol. Anti-inflammatory effects were observed with reduced TNF-α and elevated IL-10 levels. Mitochondrial and metabolic regulators (PGC-1α, SIRT-1, AMPK) and anabolic mediators (IGF-1) were significantly upregulated, while mTOR levels decreased. Gut microbiome analysis revealed increased genus richness (Chao1 index) and distinct microbial shifts associated with improved metabolic and inflammatory markers. HiLo Platinum™ effectively mitigates prediabetes-induced muscle strength decline through integrated modulation of inflammatory pathways, mitochondrial function, metabolic homeostasis, and gut microbiome composition. These findings support its potential as a nutritional therapeutic strategy for preventing sarcopenia in prediabetic conditions, although further studies are needed to evaluate long-term effects and implications on muscle hypertrophy. Full article

Background and Objectives: Low back pain (LBP) is a leading cause of disability worldwide and is frequently associated with intervertebral disc degeneration (IVDD). Current therapeutic strategies are primarily symptomatic and do not restore native disc biology, largely due to the avascular nature of the intervertebral disc and the hostile inflammatory and mechanical microenvironment that characterizes degeneration. The aim of this study is to provide an updated and clinically oriented overview of the pathophysiology of IVDD and to evaluate the current evidence on mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP)-based therapies. Materials and Methods: A focused narrative literature review was performed to evaluate current evidence on MSC- and PRP-based therapies for intervertebral disc degeneration (IVDD). The search was conducted in PubMed. Only studies in English were considered eligible. Results: Mesenchymal stem cells (MSCs) demonstrated regenerative and immunomodulatory effects primarily through paracrine mechanisms, enhancing extracellular matrix synthesis and reducing inflammation and apoptosis. MSC-derived extracellular vesicles emerged as a promising cell-free alternative, potentially overcoming limitations related to cell survival and safety. Platelet-rich plasma (PRP) showed anabolic and anti-inflammatory properties, promoting disc cell proliferation and matrix production, particularly in early-stage degeneration. Clinical studies, including randomized trials, reported significant improvements in pain and function for both MSC and PRP therapies, with favourable safety profiles. However, heterogeneity in treatment protocols and limited long-term data remain significant limitations. Orthobiologic therapies represent a minimally invasive option for patients with discogenic low back pain refractory to conservative treatment. Patient selection is crucial and should consider degeneration stage, disc viability, and clinical presentation. PRP is primarily indicated in early-stage degeneration (Pfirrmann II–III), whereas MSC-based therapies may be considered in selected patients with more advanced but still viable discs. Based on current evidence, a stepwise approach is proposed, progressing from conservative management to PRP, MSCs, and ultimately surgery. Orthobiologics should be integrated within a multimodal strategy including rehabilitation. Conclusions: MSCs and PRP represent a promising and, eventually, complementary orthobiologic therapies for IVDD. PRP is primarily effective in early degenerative stages as a biologic stimulator, whereas MSCs may provide regenerative benefits in more advanced but still viable discs. Further studies are necessary to standardize protocols and confirm long-term efficacy and safety. Full article

Background/Objectives: Carbohydrate-restricted diets (CHRs) are increasingly employed in the treatment of obesity. We aimed to investigate the effects of a CHR on hepatic lipid anabolism and its association with changes in the proinflammatory environment and insulin signaling. Methods: Forty-eight C57BL/6J female mice were used in this study. We aimed to analyze the impact of a CHR on the hepatic proinflammatory profile and its relationship with changes in insulin signaling and fatty acid anabolism in obese female mice after two months on a high-fat diet. We also examined the impact of a one-month chow diet after CHR. Blood samples were collected, and the liver was processed during all-time study periods for analyses of biochemical, hormonal, and inflammatory markers, as well as possible changes in leptin and insulin signaling pathways. Results: Compared with chow-fed mice, CHR mice showed increased interleukin (IL)-1β and IL-2 levels, as well as leptin-related signaling in the liver. There was also a decrease in the expression of fatty acid synthase and the phosphorylation of ATP-citrate lyase, which was associated with a reduction in the activation of the insulin receptor, Akt, the mammalian target of rapamycin, cAMP-response element-binding protein, and glycogen synthase kinase 3β. The subsequent reintroduction of a chow diet after CHR resulted in lower hepatic free fatty acid and triglyceride levels than in obese mice without previous CH restriction. Conclusions: This study suggests that CHR inhibits de novo hepatic lipogenesis in obese mice by attenuating insulin signaling in a low-grade proinflammatory state. Full article

Background and Objectives: Individuals classified as having very high fracture risk remain vulnerable to imminent fractures even when treated with antiresorptive therapies. This meta-analysis evaluated whether initiating treatment with anabolic agents, including teriparatide, abaloparatide, and romosozumab, provides superior fracture protection in this high-risk population. Materials and Methods: A systematic review and meta-analysis of randomized controlled trials was conducted following PRISMA standards. Eligible studies included adults at very high fracture risk, defined by recent or multiple fragility fractures or markedly low bone mineral density, who received anabolic therapy as initial treatment compared with placebo or antiresorptive agents. Outcomes of interest were new vertebral, non-vertebral, hip, and clinical fractures. Effect estimates were pooled using random-effects models. Results: Six randomized trials encompassing 17,872 participants were analyzed. Initiation with anabolic therapy was associated with a marked reduction in incident vertebral fractures. The labeled pooled summary estimate for vertebral fractures was 0.43 (95% confidence interval 0.34–0.54). Significant risk reductions were also observed for clinical fractures (hazard ratio 0.62, 95% confidence interval 0.51–0.75), non-vertebral fractures (pooled effect estimate 0.71, 95% confidence interval 0.59–0.85), and hip fractures (risk ratio 0.65, 95% confidence interval 0.45–0.96). Exploratory subgroup analyses suggested greater vertebral fracture protection versus placebo and persistent benefit versus active antiresorptive comparators. Sequential therapy using an anabolic agent followed by an antiresorptive reduced spinal fracture risk by approximately half. Considerable heterogeneity was noted for vertebral fracture outcomes. Conclusions: Starting osteoporosis treatment with anabolic agents results in faster and more-pronounced fracture risk reduction across all major fracture categories in patients at very high fracture risk. These findings support a shift toward anabolic-first treatment sequencing in this particularly vulnerable group. Full article

Glucocorticoids (GCs) are widely used for their potent anti-inflammatory and immunosuppressive effects, but their use is strongly associated with negative impacts on bone health. Rapid bone loss and an increased risk of fragility fractures are characteristics of glucocorticoid-induced osteoporosis (GIOP), the most common type of secondary osteoporosis. While oral GCs are a well-known cause of GIOP, growing evidence suggests that non-oral routes of administration may also negatively affect the skeleton. This review summarizes current knowledge on the pathophysiology of GIOP, highlighting the complex relationship between direct and indirect mechanisms. It examines the effects of various routes of GC administration—oral, intravenous, inhaled, topical, and epidural—on bone mineral density, microarchitecture, and fracture. While parenteral GCs may have fewer systemic effects than oral therapy, long-term exposure or high cumulative doses may still cause clinically significant skeletal deterioration. This review also discusses current methods for assessing, preventing, and treating the fracture risk associated with GIOP. These strategies include lifestyle modifications, calcium and vitamin D supplements, and medications such as denosumab, bisphosphonates, and anabolic agents. Reducing the incidence of glucocorticoid-associated fractures and improving prevention and treatment requires an understanding of how GCs impact bone. Full article

Background: Obesity is traditionally defined by excess fat mass; however, the preservation of fat-free mass (FFM), particularly skeletal muscle, has gained increasing relevance due to its metabolic, endocrine, and functional roles. Weight loss interventions, including hypocaloric diets, pharmacological treatments, and bariatric surgery, are frequently associated with unintended loss of skeletal mass, increasing the risk of sarcopenic obesity and related complications. Objective: This study aimed to systematically evaluate the effectiveness of whey protein supplementation in preserving fat-free mass and muscle-related outcomes in adults with obesity undergoing weight loss interventions. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Randomized controlled trials published in English were identified through searches of PubMed/MEDLINE, CENTRAL, Embase, Scopus, ClinicalTrials.gov, and WHO ICTRP, searched up to September 2025. Eligible studies included adults (>18 years) with obesity receiving whey protein supplementation as part of a hypocaloric diet, compared with placebo or standard interventions. Primary outcomes were changes in fat-free mass assessed by validated methods (DXA, BIA, MRI), while secondary outcomes included body weight, fat mass, metabolic parameters, adherence, and safety. Risk of bias was assessed using the Cochrane RoB 2.0 tool, and certainty of evidence was evaluated with GRADE. The abstract was registered in PROSPERO with code CRD420251069996. There was no funding and no conflicts of interest. Results: Fourteen randomized controlled trials were included. Whey protein supplementation generally supported the maintenance or modest improvement of fat-free mass, particularly when combined with resistance exercise or anabolic-enriched formulations such as leucine or vitamin D. Several trials, however, reported neutral effects, especially in the absence of structured physical activity. Overall, effect estimates ranged from small gains to null or uncertain differences, and the certainty of evidence was frequently downgraded due to limited sample sizes, wide confidence intervals, heterogeneity across interventions and assessment methods, short follow-up periods, and methodological limitations including open-label designs and inconsistent adherence monitoring. Conclusions: Whey protein supplementation may support fat-free mass preservation during weight loss in adults with obesity, particularly as part of a multimodal intervention. Further high-quality trials are needed to define optimal dosing strategies and target populations. Full article

Given the multi-faceted nature of cancer cachexia, a combination of pharmacologic and supportive measures such as exercise and nutrition seems intuitive to most clinicians. Clinical trials have also suggested that a multimodal approach to cancer cachexia (CC) is feasible and potentially effective. However, past trials have been limited by medications that were partially effective or had the potential for serious adverse events such as thromboembolism. We review new agents that have demonstrated efficacy in phase II trials or are involved in multi-center phase III studies. The advent of several recent phase II studies indicate that consistently effective, well-tolerated medications may soon be available for CC. These new agents target several mechanisms involved in CC, including food aversion, catabolism, and decreased anabolism. Several multi-center studies are expected to be actively recruiting this year. If these agents prove to be effective, individualized treatment may be possible, guided by individuals’ phenotype and/or clinical biomarkers. Future research should also determine whether combination therapy (pharmacologic and/or non-pharmacologic) produces additive or synergistic benefits. Full article

Penaeus monodon is a major marine aquaculture species; however, production intensification has increased water-quality deterioration and disease pressure. Copper-loaded montmorillonite (Cu-MMT) is a functional clay additive with adsorption and antimicrobial properties, yet the optimal application mode remains unclear. We compared a control (KZ), water application (PZ), and dietary inclusion (BZ) of Cu-MMT in P. monodon. BZ was associated with higher survival and a numerically higher specific growth rate, whereas final body weight did not differ among treatments. Antioxidant status improved in BZ, with higher catalase (CAT) and total superoxide dismutase (T-SOD) activities (both p < 0.05). Hepatopancreas RNA-seq identified 949 differentially expressed genes (DEGs) for KZ vs. PZ and 814 DEGs for KZ vs. BZ. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that PZ was enriched for redox processes, transporter activity, and amino-acid biosynthesis—indicative of a stress-defense state—whereas BZ was enriched for proteolysis, endoplasmic-reticulum protein processing, and proteasome pathways, consistent with an anabolic, protein-quality-control–oriented mode. Intestinal 16S rRNA profiling indicated higher diversity and reduced putative pathogens in BZ. Overall, dietary Cu-MMT is the preferred application, shifting shrimp from an energy-consuming stress response to efficient anabolism and thereby improving performance and survival. Full article

Systemic mastocytosis comprises a group of clonal mast cell disorders characterized by multisystem involvement. Bone involvement represents a major source of morbidity, particularly in young men affected by indolent systemic mastocytosis. This review provides an integrated and up-to-date overview of SM-related bone disease. We dissect the dual and context-dependent role of mast cells in bone remodeling, detailing how they promote osteoclastogenesis, suppress osteoblast function, and, in advanced disease, drive osteosclerosis. We critically appraise available treatments, including classic anti-resorptive therapy and emerging anabolic strategies. We further discuss the transformative impact of KIT-directed tyrosine kinase inhibitors, particularly avapritinib, which has demonstrated for the first time the ability to reverse not only osteoporosis but also osteosclerosis. Finally, we explore the emerging role of machine learning models in SM, proposing their application to individualized prediction of osteoporosis and fracture risk in SM. By bridging clinical care, bone biology, and therapeutic advances, this review underscores the need for a paradigm shift in which SM-related bone disease is recognized as a dynamic process requiring early identification, integrated risk stratification, and coordinated use of anti-resorptive, disease-modifying, and data-driven precision approaches to prevent fractures and improve long-term outcomes and quality of life in this delicate category of patients. Full article

Background: Fragility fractures of the pelvis (FFPs) are increasingly prevalent given ageing populations. Conservative management is often primarily utilised due to its initial minimal displacement and the high risks of surgery in this vulnerable population. However, this can lead to rapid deconditioning, especially with non-weight-bearing protocols. Parathyroid hormone (PTH), as a bone anabolic agent, has the potential to improve clinical and radiological outcomes in FFPs, but the evidence remains limited. Methods: A systematic review and meta-analysis following PRISMA guidelines was undertaken. Database search results were independently screened by two authors, and data were extracted. The primary outcome measure was time to fracture healing as assessed by imaging, with the secondary outcome measure of pain levels (VAS/NRS). Results: There were 1230 articles screened, and 893 unique results identified. Six studies were included in the final analysis. These compared the use of PTH and its analogues with standard care, placebo, or sacroplasty. The findings suggest that PTH may accelerate fracture healing and reduce pain in this patient population, although evidence is limited and at high risk of bias. Conclusions: Treatment with PTH may improve bone healing and visual analogue pain scores, although the evidence is limited. There may be a benefit from adjunctive PTH treatment for patients with FFPs; however, larger methodologically robust studies are required to confirm this. Full article

Background: Hemodialysis (HD) patients frequently develop muscle wasting and chronic inflammation, conditions associated with functional decline and reduced quality of life (QoL). Nutritional strategies that provide targeted anabolic support without increasing nitrogen load may offer clinical benefits. The aim of this study was to evaluate the possible impact of a food for special medical purposes (FFSMP), composed of free-form branched-chain amino acids, β-hydroxy-β-methylbutyrate, and zinc, on muscle mass and strength, laboratory parameters, physical performance (PP), and QoL in HD patients. Methods: in this randomized double-blind crossover study, 24 adult HD patients received the FFSMP (10 g/day; two sachets) supplementation or placebo for 12 weeks, separated by an 8-week wash-out (protocol code RS 29.23). Measured outcomes included quadriceps rectus femoris thickness (QRFT) muscle, body composition analysis, inflammatory markers, oxidative stress indices, other routine biochemical parameters, PP, and QoL (SF-36 questionnaire). Results: FFSMP supplementation resulted in significant increases in QRFT and in fat-free mass percentage. Reductions in oxidative stress and inflammatory biomarkers were observed. Routine biochemical parameters remained stable, with the exception of a decrease in pre-dialysis urea. Functional performance measures did not differ between treatment periods. Improvements were noted in selected SF-36 domains, specifically energy/fatigue and general health. No major adverse events occurred during the study. Conclusions: In HD patients, this FFSMP produced favorable changes in markers of muscle mass and systemic inflammation without affecting short-term physical performance. These findings support the potential clinical utility of targeted amino acid supplementation in this patient population, highlighting the need for larger, longer-term trials. Full article