Search Results (2,449)

Background/Objectives: Altered lumbar sagittal alignment is associated with degenerative and mechanical musculoskeletal disorders. However, conventional angle-based measurements, such as the Cobb angle, may not fully reflect the overall curvature pattern of the lumbar spine. This pilot study investigated whether curvature distribution profiling on sagittal lumbar radiographs is associated with clinically confirmed lumbar musculoskeletal disorders. Methods: This retrospective pilot study included 50 adults who underwent standing sagittal lumbar radiography. Patients were classified as disease-positive or disease-negative according to radiographic findings, short-term clinical follow-up, and chart review. Vertebral body centroids from T12 to S1 were manually identified to construct continuous lumbar curvature profiles. Curvature height was normalized to a standardized baseline for cross-case comparison. Distribution patterns of curvature deviation were analyzed between groups. Total curvature was also calculated as a quantitative descriptor of overall lumbar bending, and group-wise comparisons were performed using the Kruskal–Wallis test. Results: The disease-negative group showed a predominantly unimodal and symmetric curvature distribution, whereas the disease-positive group showed greater dispersion at both hypo-lordotic and hyper-lordotic extremes. The hypo-lordosis subgroup demonstrated a more consistent deviation pattern, whereas the hyper-lordosis subgroup partially overlapped with the disease-negative distribution. These pattern-based findings suggest that deviation from a central curvature profile, rather than lordosis magnitude alone, may be associated with lumbar musculoskeletal disorders. In exploratory quantitative analysis, total curvature showed a distributional shift in the disease-positive group, although the overall between-group difference did not reach statistical significance (p = 0.096). Conclusions: Curvature distribution profiling may provide complementary morphological information in conjunction with conventional angle-based assessment. Both reduced and exaggerated lumbar curvature patterns were observed in association with lumbar musculoskeletal disorders. Larger studies are needed to validate these preliminary findings and to determine the clinical relevance of this approach. Full article

Astaxanthin (ASX) is a xanthophyll carotenoid widely studied for its beneficial properties in humans, mainly related to its local or systemic antioxidant, cytoprotective and immunomodulatory effects. Particularly, ASX can donate electrons to neutralize reactive oxygen species (ROS), thereby mitigating oxidative stress, a key factor in the onset of several chronic and degenerative diseases. Thanks to these valuable properties, ASX has attracted considerable interest in the pharmaceutical, nutraceutical and cosmetic sectors. Despite its promising biological potential, the application of ASX is limited by several physicochemical factors. It is a highly lipophilic molecule, unstable when exposed to light, heat and oxygen, which leads to rapid degradation, and is characterized by low bioavailability. To overcome these limitations, various formulation strategies have been developed, particularly encapsulation-based approaches aimed at improving stability, solubility and therapeutic applications. This review provides an overview of the conventional and innovative dosage forms of ASX developed to enhance bioavailability and preserve the chemical and biological properties of this powerful antioxidant, by focusing on the different administration routes. Special attention is given to the advantages and limitations of the different formulation strategies and their implications for human health according to the different administration routes. Although oral administration remains the most explored route, further studies are needed to develop formulations suitable for alternative routes of administration. Full article

Platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) are promising regenerative treatments for lumbar degenerative disc disease (DDD), but their comparative efficacy is unclear. This systematic review and indirect meta-analysis, conducted according to PRISMA guidelines and the PICOS framework, evaluated their effects on pain, function, and safety. PubMed, Scopus, and Web of Science were systematically searched, yielding 1694 records, of which 21 studies (nine randomized controlled trials [RCTs] and 12 prospective studies) were included. Data were analyzed qualitatively and quantitatively, and risk of bias was assessed using RoB 2 and ROBINS-I. Meta-analyses of randomized controlled trials (RCTs) examined pain and disability at 6 and 12 months using a random-effects model. Indirect comparisons were performed using the Bucher method. Qualitative synthesis showed that PRP consistently reduced pain (often > 50%) and improved function, frequently outperforming corticosteroids. MSCs provided sustained benefits, with follow-up extending up to 72 months in some studies. Quantitative meta-analysis of five RCTs demonstrated that PRP significantly reduced pain at 6 months (mean difference [MD] −16.4 mm) and disability (ODI −12.7), with effects persisting at 12 months in one study. In contrast, MSCs showed a modest but significant reduction in pain (MD −4.3 mm) and minimal functional improvement. Indirect comparisons favored PRP over MSCs at 6 months. Both treatments exhibited favorable safety profiles, with mostly mild and transient adverse events. Overall, PRP appears more effective than MSCs in the short to mid-term, although both therapies are safe. Further high-quality head-to-head RCTs are needed to confirm these findings and define optimal clinical indications. Full article

Background: Risk stratification of patients with mitral regurgitation (MR), including both primary (degenerative) and secondary (functional) forms, remains challenging, particularly in asymptomatic or minimally symptomatic stages, as clinical assessment and resting echocardiography may underestimate disease severity and functional impairment. Exercise stress echocardiography (ESE) enables dynamic evaluation of regurgitation severity, ventricular performance, and cardiopulmonary response, potentially improving prognostic assessment. Methods: A systematic review was conducted according to PRISMA guidelines. PubMed, Scopus, and EMBASE were searched from inception to March 2026. Studies including adult patients with primary or secondary MR undergoing exercise-based stress echocardiography and reporting clinical outcomes were selected. Studies using exclusively pharmacological stress were excluded. Data were qualitatively synthesized, and continuous variables were summarized as weighted medians and interquartile ranges. In addition, emerging and non-conventional prognostic markers, including anatomical indices such as the modified Haller index (MHI), were explored to provide a more comprehensive risk stratification framework. Results: Nineteen studies were included, encompassing a heterogeneous population in terms of MR etiology, severity, and clinical presentation. During follow-up, a substantial proportion of patients experienced adverse events, including heart failure, mitral valve intervention, or death. Exercise-derived parameters consistently showed strong prognostic value. In particular, exercise-induced worsening of MR severity (increase in effective regurgitant orifice area and regurgitant volume), absence of contractile reserve, elevated filling pressures (E/e’), and exercise-induced pulmonary hypertension were associated with worse outcomes. Reduced functional capacity and impaired right ventricular–pulmonary arterial coupling provided additional prognostic information. Emerging markers, including chest wall configuration assessed by MHI, appeared to further refine risk stratification in selected patient subsets. In contrast, resting parameters were less consistently predictive. Conclusions: ESE provides incremental prognostic information in patients with MR by identifying dynamic abnormalities not evident at rest. Its integration into clinical evaluation, together with novel anatomical and functional markers, may improve risk stratification and support earlier identification of high-risk patients who could benefit from timely intervention. Further studies are needed to standardize methodologies and define clinically relevant thresholds. Full article

Epidemiological studies have demonstrated that kidney aging is a risk factor for acute kidney injury (AKI) and chronic kidney disease (CKD). Therefore, understanding the mechanisms of kidney aging is key to designing novel anti-kidney aging strategies. In this regard, animal models of kidney aging are essential tools. In this review article, we focus on D-galactose (D-gal)-induced accelerated aging in rodents. This animal aging model is a popular and widely used experimental method in the field of aging and aging-related degenerative disorders. It has been shown that the major characteristics of the D-gal-induced aging process are increased oxidative stress, decreased antioxidant enzymes, elevated cell death, increased tissue fibrosis, and accumulation of inflammatory mediators. This review focuses on D-gal-induced kidney aging in mice and rats, with discussions on both kidney aging mechanisms and anti-kidney aging regimens using this model. It is our belief that D-gal induction of accelerated kidney aging will continue to be used as a convenient platform for elucidating kidney aging mechanisms and exploring novel anti-kidney aging targets that may slow down kidney aging and retard the development of aging-related renal disorders. Full article

Deposits of insoluble protein plaques, which are mostly composed of fibrils from disease-specific amyloid proteins, are histological markers of various human disorders. These range from non-neuropathic amyloidosis such as light chain amyloidosis or type II diabetes to well-known neuro-degenerative diseases such as Alzheimer’s Disease and Parkinson’s Disease. There are indications that these types of fibrillar suprastructures display biological activity distinct from the individual fibrils they are composed of. Yet, little is known about the mechanisms underlying the assembly of fibrillar suprastructures. An understanding of secondary fibril self-assembly into mesoscopic and macroscopic suprastructures is also critical for their application as novel biomaterial. The paucity of experimental data and theoretical models on fibrillar supra-assembly likely relates to the experimental and conceptual challenges in following this type of assembly on multiple length- and timescales, and in characterizing the distinct morphologies formed. Here, we report that the amyloid dye thioflavin T (ThT) is augmented during self-assembly of isolated lysozyme fibrils. We provide evidence that this augmentation of ThT fluorescence results from the unquenching of fibril-bound ThT during fibril binding. Combining ThT fluorescence, optical density, and fluorescence quenching kinetics with optical and electron microscopy, we propose that fibril self-assembly is driven by a transition from reaction-limited ordered assembly to diffusion-limited random cross-linking of fibrils. Full article

Multiple sclerosis (MS) reflects a dynamic interplay between peripheral immune activation and compartmentalized inflammation within the central nervous system (CNS). While current disease-modifying therapies effectively reduce relapse activity driven by transient peripheral immune infiltration, their impact on progressive disability remains limited, prompting interest in strategies targeting CNS-resident immune mechanisms. Bruton’s tyrosine kinase (BTK), expressed in B cells and myeloid-derived cells, including microglia, serves as a shared intracellular signaling node linking adaptive and innate immune pathways. Second-generation BTK inhibitors, including evobrutinib, tolebrutinib, fenebrutinib, remibrutinib, and orelabrutinib, have advanced through Phase II-III development in MS. These agents differ in binding mode, selectivity, pharmacokinetics, CNS penetration, and safety profiles, distinctions that may influence stage-specific therapeutic performance. Recent trials across relapsing and progressive phenotypes have yielded heterogeneous outcomes. Divergent signals in primary and secondary progressive MS reflect underlying biological heterogeneity and suggest that therapeutic responsiveness may depend on residual inflammatory activity, lesion biology, and pharmacologic characteristics. Emerging biomarker frameworks further emphasize the importance of stratifying inflammatory activity and degenerative progression when interpreting trial data. This review integrates molecular pharmacology and the most recent clinical evidence available through 2026 to examine how pharmacologic properties translate into stage-dependent therapeutic positioning. We also consider safety constraints within a disease-stage-specific benefit-risk framework, aiming to clarify the evolving role of BTK inhibition in MS. Full article

Background and objectives: Articular cartilage provides low-friction articulation across joint surfaces, distributes loads, and absorbs stress, all of which are crucial mechanical functions of joints. Changes in the mechanical characteristics of cartilage are among the first signs of degenerative joint disease, and they are especially important for athletes who are subjected to high-impact, high-magnitude loading on a regular basis. The objective of this study was to: (i) compare the mechanical characteristics of tibiofemoral cartilage in healthy and osteoarthritic conditions across medial and lateral anatomical compartments; and (ii) use nonlinear phenomenological viscoelastic modeling in conjunction with unconfined compression testing to characterize compartment-specific viscoelastic behavior. Materials and Methods: Forty-six human tibiofemoral cartilage samples were collected during knee surgeries and classified as healthy (n = 17) or osteoarthritic (n = 29) and as medial (n = 26) or lateral (n = 20). Quasi-static unconfined compression tests were performed at 1 mm/min to obtain stress–strain responses, Young’s modulus, maximum compressive stress, and energy absorption. Viscoelastic behavior was analyzed using a nonlinear phenomenological viscoelastic model. Appropriate parametric or non-parametric statistical tests and effect size measures were applied. Results: Osteoarthritic cartilage’s stiffness and energy absorption were significantly higher than those of healthy tissue (p < 0.05). Medial cartilage exhibited significantly greater stiffness and stress than lateral cartilage (p < 0.001). The nonlinear phenomenological viscoelastic model provided an excellent fit (R² > 0.999). Conclusions: The mechanical profile of osteoarthritic tibiofemoral cartilage is characterized by pathological mechanical remodeling and increased stiffness. Greater mechanical susceptibility in the medial compartment supports the significance of cartilage biomechanical properties as sensitive indicators of early degeneration and osteoarthritis risk in athletic populations. Full article

Osteoarthritis (OA) is a complex degenerative joint disease for which early diagnosis and clear molecular characterization remain limited. DNA methylation has been increasingly recognized as an important regulatory factor in OA pathogenesis. In this study, we proposed an integrative computational framework combining statistical analysis, machine learning, deep learning, and functional genomics to identify and validate OA-associated genes and methylation biomarkers for diagnostic and biological interpretation. Candidate CpG sites were obtained using two complementary strategies: differential methylation analysis and selection of loci located near transcription start sites of previously reported OA-related genes. Key features were further refined using support vector machine recursive feature elimination and random forest algorithms. Based on the selected loci, we developed a feature-fusion diagnostic model that combines Transformer and convolutional neural networks with adaptive weighting to capture both global dependency structures and local methylation patterns. A panel of 220 methylation sites demonstrated stable and reproducible diagnostic performance in an independent cohort. Functional annotation and pathway analysis highlighted several established OA-associated genes, including TGFBR2, SMAD3, PPARG, and MAPK3, and suggested INHBB as a potential novel effector gene, with additional support for AMH and INHBE involvement. Overall, this study presents a robust methylation-based framework for identifying key OA-associated genes and provides new insights into the epigenetic mechanisms underlying OA. Full article

Objective: To evaluate the prognostic utility of the five-item modified Frailty Index (mFI-5) for postoperative outcomes in older adults undergoing posterior lumbar interbody fusion (PLIF) for degenerative lumbar disease and to develop an interpretable preoperative risk model for medical complications (CxME). Methods: We retrospectively reviewed consecutive patients aged ≥65 years who underwent PLIF for lumbar spondylosis at a single tertiary institution. Baseline demographics, comorbidities, symptoms, American Society of Anesthesiologists (ASA) physical status, bone mineral density, antithrombotic use, perioperative laboratory findings, and operative variables were collected. CxME were defined as Clavien–Dindo grade ≥ II complications occurring during index hospitalization or within 30 days postoperatively. mFI-5 was calculated from five preoperative variables and stratified as 0, 1, and ≥2. Multivariable logistic regression was used to identify independent predictors of CxME. Results: Among 255 patients (mean age 72.6 years), 53 (20.8%) developed CxME. Patients with CxME were older and had higher rates of diabetes mellitus and preoperative dependency. mFI-5 ≥ 2 was more frequent in patients with CxME than in those without (66.0% vs. 27.3%, p < 0.001). Higher frailty was associated with older age, greater comorbidity burden, higher ASA class, lower preoperative hemoglobin, greater transfusion exposure, longer hospital stay, and a higher incidence of CxME (14.0%, 9.6%, and 38.9% for mFI-5 scores 0, 1, and ≥2, respectively; p < 0.001). In multivariable analysis, age (OR 1.133, 95% CI 1.055–1.216; p < 0.001) and mFI-5 (OR 2.103, 95% CI 1.387–3.188; p < 0.001) independently predicted CxME. The Age + mFI-5 model showed fair discrimination (optimism-corrected area under ROC 0.734). Conclusions: Preoperative frailty and age independently predicted postoperative medical complications after PLIF in older adults. The Age + mFI-5 model may support risk stratification, counselling, and perioperative optimization. Full article

Regenerative medicine is becoming more widely integrated with longevity-oriented and preventive care as populations age and chronic degenerative diseases burden healthcare systems. Mesenchymal stem cell (MSC) therapies have progressed from experimental interventions to approved products, yet scalability, safety, cost, and regulatory complexity constrain widespread implementation in medical wellness contexts. The predominant therapeutic effects of MSCs are mediated via paracrine mechanisms, leading to cell-free approaches based on the MSC secretome—a complex mixture of bioactive factors including all types of biomolecules and assemblies thereof, such as exosomes. These acellular products offer compelling advantages: multiple batches from single-donor sources, standardized dosing, reduced allogeneic cell risks, and shorter outpatient-compatible administration. Preclinical and clinical data indicate that secretome-based products exert potent regenerative effects in osteoarthritis, chronic wounds, stroke, traumatic brain injury, and neurodegenerative diseases. This review examines the evolution from cell-based to cell-free regenerative strategies, focusing on human umbilical cord Wharton’s jelly MSC secretome for precision longevity medicine. It compares MSC therapies with secretome- and exosome-based formulations across mechanistic, manufacturing, safety, practical and regulatory dimensions. Regional perspectives highlight Southeast Asia, and especially Thailand, as an emerging regenerative-longevity hub. Finally, it outlines the preventive patient journey integrating cell-free interventions within multi-modal programs aimed at extending healthspan. Full article

Ionizing radiation therapy has undergone a clear paradigm shift in veterinary oncology and inflammatory disease management, moving from mainly palliative use toward structured, curative treatment programs. This review synthesizes current evidence on key modalities used in veterinary practice, including external beam radiotherapy, brachytherapy, systemic targeted radionuclide therapy, stereotactic radiosurgery, stereotactic body radiotherapy, radiosynoviorthesis, and low-dose radiotherapy. Each modality is discussed in relation to its physical and biological basis, major isotopes or beam types, routes of delivery, target species such as dogs, cats, and horses, clinical indications, and global availability. Comparative analysis highlights differences in clinical acceptance, evidence strength, access, and cost. External beam radiotherapy and stereotactic techniques support curative tumor management, whereas radiosynoviorthesis and low-dose radiotherapy are effective for inflammatory and degenerative disorders. Despite ongoing progress, challenges remain in access, dosimetry standardization, and prospective evidence. Companion animals are also emphasized as valuable translational models, guiding future innovation and collaboration internationally. Full article

Sestrins are an evolutionarily conserved family of stress-responsive proteins that regulate cellular metabolism, redox balance, and survival. Their expression is induced by diverse cellular stresses through activation of transcription factors such as p53, NRF2, and FOXO. Through antioxidant activity and modulation of mTORC1 and mTORC2 signalling, Sestrins limit the accumulation of reactive oxygen species, regulate metabolic pathways, and promote autophagy. In this review, we analyse published studies reporting SESN1, SESN2, and SESN3 expression in human tissues, circulation, and experimental disease models. The available evidence indicates that Sestrin levels are dynamically regulated across multiple pathologies, including metabolic, ageing, cardiovascular, inflammatory, neurodegenerative, and degenerative disorders. Notably, changes in tissue Sestrin expression are often mirrored in circulation. These observations suggest that Sestrins may serve as informative biomarkers of cellular stress and disease states, and that monitoring their expression in tissues or blood could provide insight into disease progression and therapeutic response. Full article

Background: Psidium guajava L. (Psidium guajava) is an edible plant; its parts are widely used to cure and prevent many health disorders. Psidium guajava leaves contain a wide array of polyphenols that inhibit peroxidation and may play a role in the prevention and treatment of common, degenerative chronic disorders such as diabetes, cardiovascular disease, and cancer. Colon cancer is the third most common type of cancer diagnosed and the second most common cause of cancer-related deaths globally. In contrast, prostate cancer is the second most diagnosed cancer and the fifth leading cause of cancer-related death worldwide. This study aims to evaluate the pharmacological potential of the Psidium guajava plants cultivated in Romania on colon and prostate cancer cell lines. Methods: Phenolic compounds extraction was made using an average sample of all nine Psidium guajava varieties. Analyses were carried out using a HP-1200 liquid chromatograph. The effect of the alcoholic extract of Psidium guajava leaves was tested on two colon cancer and one prostate cancer cell line as in vitro models. Results: The Psidium guajava leaf extract exhibited anticancer activity against the tested cell lines, with decreased proliferation, increased apoptosis, and cell cycle arrest. The extract reduced the cancer cell line’s migration and invasion capacity, demonstrating greater selectivity for the colon cancer cell line than for the prostate cancer cell lines. Conclusions: This study provides further proof of the Psidium guajava plant’s anticancer properties against colon cancer cell lines. Further studies are needed to confirm its use either alone or in conjunction with conventional cancer treatments as an alternate treatment for certain kinds of malignancies. Full article

Notably, certain ginsenoside components exhibit distinct bidirectional and context-dependent regulatory effects on ferroptosis depending on the disease setting. In aberrantly proliferating or activated cells, ginsenosides function as ferroptosis inducers, whereas in damaged quiescent cells of normal tissues, they act as ferroptosis inhibitors. The pro-ferroptotic effect is predominantly observed in cells characterized by abnormal proliferation or activation, such as cancer cells and activated hepatic stellate cells in liver fibrosis. In this context, ginsenosides modulate key iron metabolism proteins and suppress antioxidant defense systems (e.g., GPX4, SLC7A11), thereby triggering intracellular iron overload and explosive lipid peroxidation, ultimately culminating in ferroptosis. Conversely, the anti-ferroptotic effect primarily targets damaged non-proliferative cells in normal tissues subjected to pathological insults (e.g., ischemia–reperfusion, inflammation). In this setting, the regulatory focus of ginsenosides shifts toward maintaining iron homeostasis through mechanisms including upregulation of iron storage proteins (e.g., FTH1), downregulation of iron uptake proteins (e.g., TFRC), and inhibition of labile Fe²⁺ accumulation, thereby blocking ferroptosis initiation. This review systematically elucidates the pharmacological effects and underlying mechanisms by which different ginsenoside components regulate ferroptosis across various disease contexts and cell types, with particular emphasis on their disease- and cell type-dependent bidirectional regulatory characteristics. By highlighting these context-specific effects, we aim to provide novel potential therapeutic targets and mechanistic insights for the precision treatment of diverse pathological conditions, including malignant proliferative disorders, non-malignant aberrantly activated/proliferative diseases such as liver fibrosis, and cell injury/degenerative diseases. Full article