Search Results (855)

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

Lumbar spinal stenosis (LSS) is caused by multiple degenerative changes including the hypertrophy of the ligamentum flavum (LFH). Inflammation and fibrosis contribute to LFH and glucocorticoid drugs (GCDs) are generally used to manage LSS symptoms. However, a thorough understanding of the molecular mechanisms exerted by GCD in ligamentum flavum (LF) cells remains incomplete. Primary human LF cells were isolated from surgical specimens and stimulated with pro-inflammatory agents (IL-1α, IL-1β, LPS) or the profibrotic cytokine TGFβ1, in the presence or absence of dexamethasone. Gene and protein expression levels of inflammatory, fibrotic, and ossification-related markers were analysed using RT-qPCR and Western blotting. Dexamethasone significantly suppressed the expression of key pro-inflammatory, fibrotic, and ossification markers (IL-6, COX2, COL3A1, MMPs, TNFRSF11b) in both acute and prolonged models of LF inflammation. However, under TGFβ1 stimulation, dexamethasone attenuated inflammatory gene expression but failed to reduce the expression of major fibrosis-associated genes, such as COL3A1, bFGF, and POSTN. Dexamethasone effectively suppresses inflammation-mediated fibrosis in LF-derived cells, indicating its potential to both prevent and reverse LFH progression in the context of LSS. However, its limited efficacy against TGFβ1-driven fibrotic pathways highlights the need for combination therapies targeting both inflammation and fibrosis for more comprehensive management of LFH. These findings support further exploration of corticosteroids as therapeutic agents for hypertrophic ligament disorders. Full article

Background: Precise staging of prostate cancer is vital for treatment planning and prognosis. While [⁶⁸Ga]Ga-PSMA-11 PET-CT has demonstrated high diagnostic accuracy in detecting metastatic disease, the interpretation of indeterminate or potentially benign PSMA-avid bone lesions remains a clinical challenge in routine practice. Methods: We conducted a retrospective single-centre study involving 214 patients who underwent [⁶⁸Ga]Ga-PSMA-11 PET-CT between January 2021 and January 2024. Patients with prior known bone metastases or alternative PSMA radiotracers were excluded. Only those with follow-up imaging were included for diagnostic accuracy analysis. Follow-up modalities included PSMA PET-CT, CT, MRI, and bone scintigraphy. Final classification (metastatic or benign) was based on radiological and clinical assessment. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using follow-up imaging as the reference standard. Lesions classified as indeterminate were analysed separately and excluded from diagnostic performance calculations. Results: Of the 214 included patients, 142 had follow-up imaging. Among 80 patients with bone lesions initially reported as metastatic, 74 (92.5%) were confirmed. Among 28 patients initially reported as having benign bone lesions, 26 (92.9%) remained benign on follow-up. Thirty-four patients with indeterminate lesions were reviewed; four were ultimately metastatic. Excluding indeterminate cases, sensitivity, specificity, PPV, and NPV were 97.4%, 86.7%, 94.9%, and 92.9%, respectively. Diagnostic discordance was primarily associated with benign uptake in the ribs, iliac bones, pubic rami and degenerative changes. Conclusions: [⁶⁸Ga]Ga-PSMA-11 PET-CT shows excellent sensitivity and positive predictive value for detecting metastatic bone disease in prostate cancer. However, benign lesions may also exhibit uptake, emphasising the importance of integrating imaging results with PSA levels, Gleason scores, and TNM staging. Prospective studies are needed to validate these findings and assess their impact on long-term outcomes. Full article

The in vivo effect of platelet-rich plasma (PRP) on supraspinatus tendon morphology and subacromial bursa cell gene expression in degenerative rotator cuff tears remains unclear. This randomized controlled trial evaluated the effect of preoperative leukocyte-poor PRP (LP-PRP) subacromial injection on supraspinatus tendon histology and subacromial bursa gene expression. Sixteen patients with full-thickness supraspinatus tears were randomized to receive an ultrasound-guided LP-PRP injection (n = 8) or no injection (n = 8) six weeks before arthroscopic repair. Tendon biopsies were assessed using the modified Movin score. Gene expression of collagen type I, II and III, metalloproteinase 3 and 13, and interleukin 1β and 6 genes from subacromial bursa cells was quantified using quantitative real-time PCR. The results of the two groups were compared to determine any statistically significant difference regarding all the examined parameters. The PRP group demonstrated a significantly lower total modified Movin score than controls (6.5 vs. 12.1, p = 0.002), with lower scores for fiber structure, fiber arrangement, nuclear rounding, inflammation and cell density (all p < 0.003), while angiogenesis did not differ (p = 0.149), indicating an architecture closer to that of normal tendon. No statistically significant differences in gene expression were observed (all p > 0.05), although collagen II and metalloproteinase 3 and 13 showed biologically relevant downregulation [fold change 0.23 (95%CI 0.05–1.09), 0.24 (95%CI 0.002–26.10), and 0.26 (95%CI 0.02–2.76), respectively]. The LP-PRP injection was associated with improved supraspinatus tendon histological characteristics and biologically relevant reductions in selected bursal genes, in the setting of supraspinatus tendon tear. Full article

Osteoarthritis (OA) represents a degenerative joint disease which advances through cartilage breakdown, synovial inflammation, and subchondral bone transformation until it causes persistent pain and mobility loss. The scientific community lacks complete knowledge about OA disease mechanisms and post-operative healing processes despite arthroplasty surgery providing effective symptom relief. This study investigated plasma proteomic changes in OA patients before and after arthroplasty. The cohort included eight OA patients undergoing knee or hip arthroplasty and ten age-, sex-, and body mass index-matched healthy controls. Plasma proteins were analyzed using liquid chromatography–tandem mass spectrometry following enzymatic digestion and depletion of high-abundance components. The bioinformatic analysis together with quantitative methods showed that OA patients experienced changes in inflammatory pathways, extracellular matrix remodeling, immune system regulation and coagulation processes. A total of 93 proteins were differentially abundant in the pre-operative comparison. Among these, 63 proteins were consistently up-regulated and 23 were consistently down-regulated across both pre- and post-operative time points. In addition, 20 proteins exhibited post-operative-specific changes. These findings highlight both persistent disease-associated alterations and transient proteomic shifts linked to post-operative recovery. Overall, this study identifies candidate plasma proteomic signatures associated with OA and surgical intervention, providing exploratory insights into disease monitoring and potential personalized therapeutic strategies. Full article

Duropathies represent a spectrum of disorders associated with spinal dural tears and cerebrospinal fluid (CSF) leaks. Diagnosis and treatment is often complicated by overlapping clinical manifestations. This review aims to synthesize current literature on duropathies, focusing on their clinical, neuroradiological, and pathophysiological features. A comprehensive literature review was conducted, analyzing various conditions classified as duropathies, including spontaneous intracranial hypotension (SIH), superficial siderosis (SS), spinal cord herniation, and, as added issue, arachnoid webs. The review emphasized the importance of imaging techniques such as MRI and CT myelography in diagnosing these conditions. Duropathies can arise from congenital anomalies, trauma, and degenerative changes, with SIH being characterized by orthostatic headaches and neurological deficits. Imaging typically reveals specific patterns, such as a widened dorsal subarachnoid space and ventral displacement of the spinal cord. Syringomyelia was frequently associated with arachnoid webs, and complications like SS and bibrachial amyotrophy were noted in patients with persistent ventral spinal CSF leaks. The unifying concept of duropathies is proposed, emphasizing the need for timely intervention to mitigate long-term neurological consequences. Enhanced diagnostic strategies are crucial for improving patient outcomes, and a multidisciplinary approach is recommended for the management of these complex disorders. Further research is warranted to clarify the pathophysiological mechanisms underlying duropathies and to establish standardized treatment protocols. Full article

Chronic osteoarthritis (COA) is a progressive and degenerative condition that causes joint inflammation and pain, often requiring long-term pharmacological management. Conventional treatments may lead to adverse effects, tolerance, and limited analgesic efficacy. This randomized, double-blind clinical trial evaluated the analgesic potential of a full-spectrum Cannabis sativa oil extract administered orally twice daily over six weeks in dogs with COA. Subjects were assigned to three groups: Cannabis, Placebo, and Control. Pain was assessed using the Canine Brief Pain Inventory (CBPI) and the Canine Osteoarthritis Staging Tool (COAST), which ranges from 0 to 4. The Cannabis extract (46.4 mg/mL) total cannabinoids: Cannabidiol (CBD), Cannabidiolic acid (CBDA), Delta-9-Tetrahydrocannabinol (Δ⁹-THC), and Tetrahydrocannabinolic acid (THCA), were administered using a cautious dose escalation protocol. Treatment began at ~0.1 mg/kg every 12 h, increasing by one drop (1.16 mg) every 72 h. This gradual titration continued until reaching the maximum tolerated dose (2 mg/kg every 12 h), which was maintained for the final two weeks. The protocol was designed to minimize adverse effects and allow close monitoring, especially in geriatric or clinically fragile dogs. By day 28, when the DMT was reached, the Cannabis group showed a 39.6% reduction in CBPI scores, compared to 24.7% in the Placebo group and a 1.6% increase in the Control group. COAST scores improved from level 4 to level 3 in 55.5% of dogs in the Cannabis group, with no changes observed in the other groups. We hypothesize that the co-administration of carprofen, meloxicam, or pregabalin with a full-spectrum Cannabis sativa extract—rich in acidic cannabinoids and terpenes—enhances pain relief and mobility in dogs with COA more effectively than conventional therapies alone. This study aimed to assess the efficacy of an oily full-spectrum Cannabis sativa extract as an adjunctive treatment to NSAIDs in twenty-seven dogs diagnosed with COA, and to compare pain intensity across three treatments groups. Full article

The choroid plexus (CP) has traditionally been regarded as a cerebrospinal fluid-producing structure; however, increasing evidence indicates that it functions as a dynamic regulatory interface involved in immune surveillance, metabolic homeostasis, and brain clearance. Neuroimaging studies consistently report CP enlargement across aging and diverse neurological and neuropsychiatric disorders, yet the underlying cellular mechanisms remain poorly integrated. In this review, we synthesize morphological, molecular, and imaging evidence to propose a sequential degenerative model of the CP epithelium. This model comprises: (1) regulated epithelial cell loss via apical extrusion, (2) compensatory hypertrophy of residual cells, (3) mitochondrial remodeling with oncocytic-like change, and (4) progressive blood–cerebrospinal fluid barrier dysfunction. At the molecular level, alterations in epithelial adhesion systems—particularly SPINT1-mediated protease regulation and E-cadherin–based adherens junction stability—may initiate epithelial instability. Hypertrophic epithelial cells exhibit increased mitochondrial burden, reflected by Tom20 expression, which may initially support metabolic adaptation but ultimately contribute to oxidative stress and functional decline. At the macroscopic level, the cumulative effects of cell loss, hypertrophy, and mitochondrial remodeling likely underlie CP enlargement detectable by magnetic resonance imaging. This framework positions CP enlargement as an imaging-visible manifestation of epithelial stress and provides a structural–molecular basis for interpreting CP alterations in brain aging and neurodegenerative disorders. Full article

Major orthopedic limb surgery is often accompanied by external coaptation; the combined effect of these interventions can lead to muscle atrophy and functional impairment. Large animal models, including goats, are commonly used to study orthopedic interventions, yet longitudinal data on muscle changes after such interventions are limited. This study quantified gastrocnemius muscle adaptations in adult Boer-cross goats undergoing a clinically representative unilateral tibial segmental ostectomy and external coaptation protocol. Muscles on the operated side exhibited statistically significant decreases in mass, length, optimal fiber length, and CSA, and increases in nucleus density compared to muscles on the contralateral, non-operated side (p < 0.05). Although muscle properties showed partial recovery over time, mass and CSA remained 20–30% lower on the operated side than on the non-operated side at 12 months post-surgery despite cast removal at about 2 months post-surgery. Muscle CSA was positively correlated with bone mineral density and peak vertical ground reaction forces measured during the in vivo study. The extent of muscle recovery in the goat model was less than that observed for other mammalian models of hindlimb remobilization. More research is needed to understand the complex interaction between surgery, external coaptation, and muscle properties in the goat model. Full article

Lumbar intervertebral disc herniation is a common cause of low back and radicular leg pain, traditionally managed with a combination of conservative therapies and, when indicated, surgical discectomy. An intriguing phenomenon observed in many patients is the spontaneous resorption of herniated disc material over time, often correlating with significant symptom improvement. This article is presented as a narrative review synthesizing experimental, imaging, and clinical literature relevant to spontaneous disc resorption and its implications for clinical decision-making. This paper provides a comprehensive overview of spontaneous disc herniation resorption, exploring the underlying pathophysiological mechanisms and the factors that predict which herniations are likely to regress without surgery. Key mechanisms include inflammatory-mediated degradation of disc fragments, neovascularization with macrophage infiltration and phagocytosis of extruded nucleus pulposus tissue, and biological processes such as enzymatic matrix breakdown and cellular apoptosis that collectively lead to shrinkage of the herniated mass. Patient and disc characteristics that favour spontaneous resorption are identified, such as younger age, extruded or sequestered fragment type, larger initial herniation size, and robust inflammatory response on imaging, whereas certain chronic degenerative changes may reduce this likelihood. We also review current clinical guidelines and expert recommendations on when surgical intervention is warranted versus when conservative management and observation are appropriate. Understanding the probability of natural disc fragment resolution is critical in guiding treatment decisions. In the absence of severe neurological deficits or intractable pain, a period of non-operative management can often be pursued safely, given that the majority of patients experience substantial relief within a few months as discs regress. Conversely, timely surgery is advised for those with neurological compromise or refractory symptoms. By synthesizing the latest evidence on spontaneous disc herniation resorption and its predictors, this review aims to assist neurosurgeons and spine specialists in optimizing patient selection for conservative care and identifying the proper timing for surgical intervention to achieve the best clinical outcomes. Given the narrative design, conclusions are based on synthesis of heterogeneous evidence rather than formal comparative analysis. Full article

Background and Objectives: Intertrochanteric hip fractures (ITFs) are common in older adults and frequently coexist with knee osteoarthritis (KOA). Although both conditions share key biomechanical risk factors, the specific relationship between KOA severity and ITF stability has not been well defined. Recent evidence suggests that degenerative knee changes may alter lower-limb load distribution and increase susceptibility to unstable fracture patterns. This study evaluated whether KOA severity, graded using the Kellgren–Lawrence (KL) system, is associated with ITF stability according to the 2018 AO/OTA classification. Materials and Methods: A retrospective observational study was conducted on 138 patients with IHFs treated between 2018 and 2023. KOA severity was assessed using KL grades I–IV on non-weight-bearing anteroposterior knee radiographs. Lateral wall thickness (LWT) was measured using the Hsu method, with <20.5 mm indicating fracture instability. Statistical analyses included correlation, linear regression, logistic regression, and receiver operating characteristic (ROC) curve analysis to examine the association between KL grade and fracture stability. Results: Among 138 patients, 98 (71.0%) had unstable ITFs. Advanced KOA was significantly more common in the unstable group (KL III 45.9%, KL IV 48.0%; p < 0.001). KL grade showed a significant inverse correlation with LWT (Pearson’s r = −0.394, p < 0.001). Each one-grade increase in KL severity was associated with a 3.8 mm reduction in LWT (p < 0.001). In multivariable logistic regression, KL grade remained an independent predictor of fracture instability (adjusted OR = 4.9, 95% CI: 2.8–8.8, p < 0.001), whereas age and comorbidities were not significant. ROC analysis demonstrated good discriminatory power (AUC = 0.79). A KL ≥ III threshold achieved 95% sensitivity and 56% specificity for predicting instability. Conclusions: Higher KOA severity is strongly associated with unstable ITF patterns. KL grade independently predicts instability and may serve as a simple, accessible radiographic indicator of biomechanical vulnerability and fracture risk in older adults. Incorporating KOA severity into the preoperative evaluation may enhance risk stratification, guide selection of fixation strategy, and support individualized rehabilitation planning. Full article

Background/Objectives: Atlantoaxial posterior fusion has unique characteristics, and it is anticipated that adjacent segment degenerative changes following fusion surgery may present distinctive findings. This study aims to analyze the risk factors for degenerative changes in subaxial levels following the increasingly common atlantoaxial posterior fusion procedure. Methods: A total of 58 patients (19 males, 39 females) who had neutral, flexion, and extension plain lateral radiographs taken and a follow-up record of approximately two years post-surgery were included in the final study cohort. The study analyzed surgical methods, patient demographics, hospitalization-related factors, visual analog scale (VAS) for neck pain, and radiologic parameters. Patients were classified into the radiologic subaxial pathology (RSP) group (n = 34) and the non-RSP group (n = 24) using several radiologic indicators of spinal instability or arthritic changes, and the risk factors for RSP were analyzed. Results: The RSP group showed a significantly higher proportion of females and prevalence of rheumatoid arthritis (RA). At 3 months postoperatively, the C1-7 sagittal vertical axis (SVA) was significantly lower in the RSP group. Multivariate regression analysis using significant variables (p < 0.05) such as sex, RA and 3-month C1-7 SVA showed that RA and 3-month C1-7 SVA were significantly associated with RSP. Among radiologic parameters related to surgery, multivariate analysis identified 3-month C1-7 SVA as the sole risk factor for RSP. To explore its correlation with other radiologic parameters at 3 months postoperatively, linear logistic regression analysis was conducted. Significant positive correlations were observed with the C1-2 Cobb angle. Conclusions: This study identified RA and C1-7 SVA as the most significant risk factors for RSP in atlantoaixal posterior fusion. Full article

Background and Objectives: The biological state of anterior cruciate ligament (ACL) remnant tissue may influence postoperative healing, yet the molecular changes associated with injury chronicity remain poorly defined. This study evaluated MMP-13 and TGF-β1 expression in human ACL remnants to characterize their regenerative or fibrotic potential. Materials and Methods: ACL remnants from acute (<3 months) and chronic (>6 months) injuries were analyzed using histology, immunohistochemistry, and QuPath-based digital quantification. Clinical outcomes were correlated with marker expression. Protein–protein interaction and KEGG enrichment analyses were performed to identify extracellular matrix (ECM)-related pathways associated with MMP-13 and TGF-β1. Results: Chronic ACL remnants exhibited disorganized ECM structure with significantly higher MMP-13 and TGF-β1 expression across all digital metrics, including DAB-positive area, cell density, optical density, and H-score (p < 0.01). Higher expression of both markers correlated with lower IKDC and Lysholm scores and greater residual pivot-shift positivity. Bioinformatic analysis identified 39 shared proteins enriched in ECM-receptor interaction, TGF-β signaling, and fibrosis-related pathways, aligning with the degenerative phenotype observed in chronic tissue. Conclusions: ACL remnant biology evolves from a reparative profile in acute injuries to a fibrotic, matrix-degradative state in chronic injuries. MMP-13 and TGF-β1 serve as indicators of remnant quality and may help guide timing of surgery and future biologic strategies aimed at improving ACL reconstruction outcomes. Full article

Background: Children’s behavior and lifestyle are changing rapidly, potentially exceeding the capacity of physiological adaptation. Contemporary lifestyles may negatively affect spinal development and contribute to dysfunction and premature degeneration. Despite the increasing prevalence of postural changes, cervical spine disorders in adolescents remain under-researched. Methods: This narrative review is based on a comprehensive search of PubMed/MEDLINE and Scopus. The search strategy included a broad review of anatomical and biomechanical literature from the past 25 years and a focused review of studies from the last 15 years to reflect recent generational changes. Results: The immature spine has distinct structural and biomechanical characteristics that increase susceptibility to maladaptive responses to unbalanced forces. High screen time is associated with sedentary behavior and increased consumption of ultra-processed foods, which may affect metabolic health and musculoskeletal development. Childhood and adolescent obesity are increasingly prevalent and may influence spinal development, including through myosteatosis. Data on the consequences of cervical and lumbar lordosis loss in adolescents remain limited. Although degenerative spinal disorders are well recognized in adults, their identification in younger populations may be inadequate. Conclusions: Modern lifestyle factors pose a growing risk to children’s spinal health through complex interactions among behavioral, metabolic, and biomechanical mechanisms. The developing spine’s vulnerability and the coexistence of multiple, interrelated risk factors support the need for integrated preventive strategies rather than single-factor interventions. Future studies should focus on models capturing these interactions and their long-term consequences. Full article

Osteoarthritis is the most common musculoskeletal disorder. It primarily affects people in their mid-40s and older. As the disease progresses, degenerative changes occur in the synovial membrane, subchondral bone, and cartilage. Ultimately, the entire joint and its surrounding tissues become structurally and functionally impaired. Several sets of biochemical markers have been proposed to enable timely diagnosis and anticipate disease progression. However, only a few of these markers are routinely used to evaluate disease activity in subgroups. We conducted a cross-sectional, single-center cohort study of 72 patients with knee osteoarthritis. Diagnoses were established based on clinical data and radiological findings. We examined two Wnt/β-catenin signaling inhibitors, serum DKK-1 and sclerostin, and two bone/cartilage metabolic regulatory factors, RANKL and OPG, correlating these with disease activity and pain scores (WOMAC, VAS, and KOFUS), radiographic stage, inflammatory molecules and indices, and bone mineral density. DKK-1 levels were higher in the intensive pain group (VAS > 5) and positively correlated with the KOFUS throughout the study. This correlation was stronger in individuals with a BMI < 30. Serum DKK-1 levels were higher in patients with lower bone mineral density. No significant modifications in SOST, RANKL, or OPG levels were found in any of the above settings. In our patient cohort with mild-to-moderate knee osteoarthritis (OA), sclerostin, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) were not related to pain or disease activity. In contrast, DKK-1 was an indicator of pain and low-grade flare-ups. Furthermore, DKK-1 was associated with the KOFUS and impaired bone turnover in non-obese subgroups. Confirming these relationships in larger groups of patients would contribute to more efficient use of DKK-1 in disease stratification algorithms. Full article