Search Results (1,989)

Alzheimer’s disease (AD), a degenerative condition affecting the central nervous system, has witnessed a notable rise in prevalence along with the increasing aging population. In recent years, the integration of cutting-edge medical imaging technologies with forefront theories in artificial intelligence has dramatically enhanced the efficiency of identifying and diagnosing brain diseases such as AD. This paper presents an innovative two-stage automatic auxiliary diagnosis algorithm for AD, based on an improved 3D DenseNet segmentation model and an improved MobileNetV3 classification model applied to brain MR images. In the segmentation network, the backbone network was simplified, the activation function and loss function were replaced, and the 3D GAM attention mechanism was introduced. In the classification network, firstly, the CA attention mechanism was added to enhance the model’s ability to capture positional information of disease features; secondly, dilated convolutions were introduced to extract richer features from the input feature maps; and finally, the fully connected layer of MobileNetV3 was modified and the idea of transfer learning was adopted to improve the model’s feature extraction capability. The results of the study showed that the proposed approach achieved classification accuracies of 97.85% for AD/NC, 95.31% for MCI/NC, 93.96% for AD/MCI, and 92.63% for AD/MCI/NC, respectively, which were 3.1, 2.8, 2.6, and 2.8 percentage points higher than before the improvement. Comparative and ablation experiments have validated the proposed classification performance of this method, demonstrating its capability to facilitate an accurate and efficient automated auxiliary diagnosis of AD, offering a deep learning-based solution for it. Full article

Osteoarthritis (OA) is a degenerative joint disease characterized by the breakdown of cartilage and the subsequent inflammation of joint tissues, leading to pain and reduced mobility. Despite advancements in symptomatic treatments, disease-modifying therapies for OA remain limited. This narrative review examines the dual role of autophagy in OA, emphasizing its protective functions during the early stages and its potential to contribute to cartilage degeneration in later stages. By delving into the molecular pathways that regulate autophagy, this review highlights its intricate interplay with oxidative stress and inflammation, key drivers of OA progression. Emerging therapeutic strategies aimed at modulating autophagy are explored, including pharmacological agents such as AMP kinase activators, and microRNA-based therapies. Preclinical studies reveal encouraging results, demonstrating that enhancing autophagy can reduce inflammation and decelerate cartilage degradation. However, the therapeutic benefits of autophagy modulation depend on precise, stage-specific approaches. Excessive or dysregulated autophagy in advanced OA may lead to chondrocyte apoptosis, exacerbating joint damage. This review underscores the promise of autophagy-based interventions in bridging the gap between experimental research and clinical application. By advancing our understanding of autophagy’s role in OA, these findings pave the way for innovative and effective therapies. Nonetheless, further research is essential to optimize these strategies, address potential off-target effects, and develop safe, targeted treatments that improve outcomes for OA patients. Full article

Background: The accurate diagnosis of degenerative joint diseases (DJDs) of the temporomandibular joint (TMJ) presents a significant clinical challenge due to their progressive nature and the complexity of associated structural changes. These conditions, characterized by cartilage degradation, subchondral bone remodeling, and eventual joint dysfunction, necessitate reliable and efficient imaging techniques for early detection and effective management. Cone-beam computed tomography (CBCT) is widely regarded as the gold standard for evaluating osseous changes in the TMJ, offering detailed visualization of bony structures. However, ultrasonography (US) has emerged as a promising alternative, offering a non-invasive and radiation-free option for assessing TMJ disorders. This study aims to evaluate the diagnostic accuracy of US in identifying degenerative changes in the TMJ, with CBCT serving as the definitive diagnostic reference. By analyzing the sensitivity, specificity, and predictive values of US in detecting key degenerative markers—such as subchondral erosion, osteophytes, and joint space narrowing—this investigation seeks to assess its utility as a screening tool and its potential integration into clinical workflows. Methods: Forty adult patients presenting temporomandibular joint disorders were included in our cross-sectional study. Each patient underwent a clinical examination and was subjected to cone-beam computed tomography (CBCT) and ultrasonography (US). A statistical analysis was performed to compare the imaging results from CBCT and US. Results: The results are summarized in three tables. The first table presents a comparative analysis of radiological outcomes in patients with temporomandibular joint disorders using different imaging techniques. CBCT demonstrated higher sensitivity in detecting osteophytes in the right mandibular head (27.50% vs. 7.50%, p = 0.027) and higher detection rates for erosions, though without a significant advantage over US. The second table analyzes the consistency of diagnostic results between CBCT and US. A moderate agreement was observed for detecting normal bone structures, with AC1 values of 0.58 for the right and 0.68 for the left mandibular head (p < 0.001). The third table evaluates the diagnostic accuracy of US compared to CBCT. US demonstrated a positive predictive value (PPV) of 90% for detecting normal conditions, indicating its high reliability as a screening tool for normal findings. US demonstrates higher effectiveness in ruling out certain issues due to its high specificity and negative predictive value. However, its lower sensitivity in detecting abnormalities may lead to both false-positive and false-negative results. Conclusions: US holds significant promise as a screening modality for detecting normal anatomical features of the temporomandibular joint, its limitations in identifying more complex degenerative changes necessitate a cautious and integrated approach to TMJ diagnostics. Full article

The prototype of a biomimetic multi-spiked connecting scaffold (MSC-Scaffold) represents an essential innovation in the fixation in subchondral trabecular bone of components for a new generation of entirely cementless hip resurfacing arthroplasty (RA) endoprostheses. In designing such a functional biomaterial scaffold, identifying the microstructural and mechanical properties of the host bone compromised by degenerative disease is crucial for proper post-operative functioning and long-term maintenance of the endoprosthesis components. This study aimed to explore, depending on the occurrence of obesity, changes in the microstructure and mechanical properties of the subchondral trabecular bone in femoral heads of osteoarthritis (OA) patients caused by the MSC-Scaffold embedding. Computed microtomography (micro-CT) scanning of femoral heads from OA patients was conducted before and after the mechanical embedding of the MSC-Scaffold. Bone morphometric parameters such as bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) for regions surrounding the MSC-Scaffold were computed, and the mechanical properties such as bone density (ρ_B), bone compressive strength (S), and the Young’s modulus (E) within these regions were calculated. A statistically significant increase in BV/TV (by 15.0% and 24.9%) and Tb.Th (by 13.1% and 42.5%) and a decrease in Tb.N (by 15.2% and 23.6%) were observed, which translates to an increase in ρ_B (by 15.0% and 24.9%), S (by 28.8% and 49.5%), and E (by 18.0% and 29.8%) in non-obese patients and obese patients, respectively. These changes in properties are favorable for the mechanical loads’ transfer from the artificial joint surface via the MSC-Scaffold to the periarticular trabecular bone of the OA femoral head in the postoperative period. Full article

The retinal pigment epithelium (RPE) contributes to retinal homeostasis, and its metabolic dysfunction is implied in the development of retinal degenerative disease. The isoform M2 of pyruvate kinase (PKM2) is a key factor in cell metabolism, and its function may be affected by insulin-like growth factor 1 (IGF-1). This study aims to investigate the effect of IGF-1 on PKM2 modulation of RPE cells and whether co-treatment with klotho may preserve it. ARPE-19 cells, an ex vivo model of human pigmented epithelium, were exposed to IGF-1. Then, we evaluated PKM2 expression, dimerization and subcellular localization, energy metabolism, and redox balance, and whether pre-treatment with Klotho may antagonize the effects of IGF-1. The results show that IGF-1 favors PKM2 dimerization, thus reducing the activity of PKM2 and leading to an altered cellular energy status coupled with reduced oxidative stress. In conclusion, PKM2 plays a pivotal role in the modulation of RPE metabolism and redox balance and could explain the mechanisms through which IGF-1 participates in the pathogenesis of some retinal diseases. Klotho may exert protective effects by mitigating the IGF-1 signal and its effect on mitochondrial function. Full article

Background: Degenerative aortic valve disease (DAVD) is a multifactorial process. We developed an animal model to analyze the isolated, local effect of reactive oxygen species (ROS) on its pathophysiology. Methods: We utilized a photodynamic reaction (PDR) as a source of ROS in the aortic valve by aiming a laser at the aortic valve for 60 min after the administration of a photosensitizer 24 h prior. ROS, laser, and sham groups (n = 7 each) for every observation period (t = 0; t = 8 d; t = 84 d; t = 168 d) were established. The amount of ROS generation; morphological changes; inflammatory, immune, and apoptotic reactions; and hemodynamic changes in the aortic valves were assessed using appropriate histological, immunohistological, immunohistochemical, and echocardiographic methods. Results: The ROS group displayed an increased amount of ROS (p < 0.01) and increased inflammatory activation of the endothelium (p < 0.05) at t = 0. In the ROS group, aortic valves were calcified (p < 0.05) and the transvalvular gradient was increased (p < 0.01) at t = 168 d. Conclusion: The small animal model employed here may serve as a platform for analyzing ROS’s isolated role in the DAVD context. Full article

Knee osteoarthritis (OA) is a prevalent degenerative joint disease globally, causing pain, stiffness, and disability. Intravascular laser irradiation of blood (ILIB) has been used for chronic pain and musculoskeletal disease. However, evidence on the clinical benefits and serum biomarkers post-ILIB therapy in knee OA is insufficient. We designed a double-blind randomized controlled trial to evaluate the clinical and biological outcomes of ILIB therapy for knee OA. Seventeen patients with knee OA were randomly assigned to the ILIB and control groups. The outcomes included the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Scale, visual analog scale, and biomarker analysis of interleukin (IL)-6, IL-13, IL-1β, epidermal growth factor, macrophage inflammatory protein-1β, and eotaxin. The measurements were performed at baseline and three days, one month, and three months post-intervention. The ILIB group showed a significant improvement in the WOMAC-pain score at one month of follow-up than the control group. IL-1β levels reduced significantly on day three, one month, and three months, and IL-13 levels reduced on day three and three months during follow-up in the ILIB group. ILIB therapy reduced knee OA pain for one month and significantly reduced serum IL-1β and IL-13 levels, suggesting potential for pain management. Full article

Degenerative retinal diseases can lead to blindness if left untreated. At present, there are no curative therapies for retinal diseases. Therefore, effective treatment strategies for slowing the progression of retinal diseases and thus improving patients’ life standards are urgently needed. The present study aimed to assess the effect of sinusoidal electromagnetic field (EMF) (50 Hz, 1.3 mT) treatment for 15 and 30 min on spontaneously arising retinal pigment epithelial cells (ARPE-19) and retinal ganglion cells (RGC-5) and its short-term post-treatment significance. Our study indicated the beneficial impact of EMF treatment on the proliferative and migratory capacity of the tested cells. ARPE-19 and RGC-5 cells exposed to an EMF exhibited elevated levels of HO-1, increased N6-methyladenosine (m⁶A) and N5-methylcytosine (m⁵C) status mediated by METTL3 and NSUN2, respectively, and changes in levels of DNA damage repair factors, which may contribute to the regenerative properties of ARPE-19 and RGC-5 cells. Overall, this analysis showed that EMF (sinusoidal, 50 Hz, 1.3 mT) treatment may serve as a potential therapeutic strategy for retinal diseases. Full article

Background/Objectives: Cyclophosphamide (CP) is widely used for treating various cancers and autoimmune diseases, but it causes damage to reproductive organs due to oxidative stress (OS) and inflammation. Boric acid (BA) has antioxidant properties that may help reduce OS, which is critical for preserving uterine functionality, particularly for cancer patients considering pregnancy after cryopreservation. This study aimed to determine whether BA could diminish CP-induced toxicity in the uterus and fallopian tubes (FT) using CP-induced toxicity in a rat model. Methods: Forty female Wistar rats, aged 18–20 weeks, were divided into four groups as follows: control, oral BA (OBR), CP, and CP plus OBR (CP + OBR). The toxicity was induced in the CP and CP + OBR groups with an initial dose of 200 mg/kg CP, followed by 8 mg/kg daily for 14 days. Rats in the OBR and CP + OBR groups received 20 mg/kg/day of BA. After the 16-day experiment, tissues were collected for analysis. Results: Histopathological and immunohistochemical assessments of IL-6 and HIF-1α expressions were used to evaluate inflammation and OS. The control, OBR, and CP + OBR groups maintained normal tissue features, while the CP group showed epithelial cell shedding, vacuolization, degenerative endometrial glands, lymphocyte infiltration, and reduced collagen fiber density. Elevated HIF-1α and IL-6 expressions in the uterus and FT indicated significant OS and inflammation. Conclusions: The study concluded that BA supplementation in CP-treated rats effectively reduced CP-induced uterine and FT damage, suggesting the potential protective role of BA in managing CP-associated toxicity. Full article

Pain and disability secondary to degenerative disc disease continue to burden the healthcare system, creating an urgent need for effective, disease-modifying therapies. Contemporary research has identified potential therapies that include protein-, cellular- and/or matrix-related approaches; however, none have yet achieved a meaningful clinical impact. The tissue-specific realities of the intervertebral disc create considerable therapeutic challenges due to the disc’s location, compartmentalization, hypovascularization and delicate physiological environment. Furthermore, the imaging modalities currently used in practice are largely unable to accurately identify sources of pain ostensibly discogenic in origin. These obstacles are considerable; however, recent research has begun to shed light on possible breakthrough technologies. Such breakthroughs include revolutionary imaging to better identify tissue sources of pain. Furthermore, novel molecular therapies have been shown to be able to mediate the progression of degenerative disc disease in some large animal studies, and even provide some insight into suppressing the development of tissue sources of discogenic pain. These potential breakthrough technologies have yet to be translated for clinical use. Full article

Osteochondrosis and apophysitis are common causes of pain in the growing skeleton, each with different causes and treatment approaches. Osteochondrosis involves degenerative processes affecting the epiphyseal ossification centers of the developing bones, while apophysitis results from repetitive traction injuries to the tendon insertions and affects both the cartilage and the underlying bone. Raising awareness of these conditions is crucial to facilitate the recovery of young athletes and prevent their sporting careers from being jeopardized early on. This review presents six known lower limb conditions that occur in young athletes, including three apophysitis such as Osgood–Schlatter disease, Sinding–Larsen–Johansson syndrome, and Sever’s disease, and three osteochondroses, including Perthes’ disease, Köhler’s disease, and Freiberg’s disease. The aim of this review is to outline the pathophysiology, clinical presentation, and treatment strategies for each of these conditions to provide a comprehensive understanding of their impact on young athletes. This review will provide clinicians, coaches, and physiotherapists with essential, evidence-based insights to increase their awareness of these conditions and refine treatment strategies for young athletes. Full article

Nicotinamide mononucleotide (NMN) possesses a variety of physiological functions and has therapeutic effects on cardio-cerebral diseases, senile degenerative diseases, neurodegenerative diseases, delayed aging, etc. However, its ability to cross the blood–brain barrier (BBB) and the mechanism of its transport have not been reported. In this study, we used the immortalized hCMEC/D3 cell line to construct an in vitro monolayer cell BBB model, evaluated its ability to cross the blood–brain barrier, and explored the mechanism by carrying out transport and efflux experiments on NMN. The ability of NMN to cross the BBB was investigated by preparing NMN-loaded liposomes conjugated with ANG peptide and RVG peptide. The results showed that the transmembrane transport ability of NMN was moderate, and the transport mechanism was passive transport relying on the concentration difference. The trans-BBB ability of ANG peptide coupled with NMN could be highly significantly improved. Full article

Retinal degenerative diseases lead to irreversible vision loss due to photoreceptor cell death, driven by complex genetic and environmental factors. Ceramide, a sphingolipid metabolite, emerges as a critical mediator in the apoptotic cascade associated with retinal degeneration. Our previous work demonstrated L-Cycloserine’s ability to protect photoreceptor-derived cells from oxidative stress by inhibiting the de novo ceramide pathway and thus prompting further investigation on its effect in the in vivo retina. This study investigates the potential of L-Cycloserine to protect albino BALB/c mice against light-induced retinal degeneration (LIRD). L-Cycloserine, in an optimal dose, administered systemically 30 min before LIRD, was found to prevent photoreceptor cell death significantly from light-induced degeneration. We further determined the retinal bioavailability and pharmacokinetic behavior of L-Cycloserine, its effect on sphingolipid profile, expression of sphingolipid biosynthetic, and cell death-promoting genes and proteins from the retina to understand the underlying mechanisms. This study lays the groundwork for further preclinical and clinical investigations into L-Cycloserine’s potential as a novel therapeutic in treating retinal degenerative diseases. Full article

Osteoarthritis (OA) is among the most prevalent degenerative joint disorders worldwide, particularly affecting the aging population and imposing significant disability and economic burdens. The disease is characterized by progressive degradation of articular cartilage and chronic inflammation, with no effective long-term treatments currently available to address the underlying causes of its progression. Conventional therapies primarily manage symptoms such as pain and inflammation but fail to repair damaged tissues. Emerging biotherapies and regenerative medicine approaches offer promising alternatives by addressing cartilage repair and inflammation control at the molecular level. This review explores the recent advancements in biotherapeutic strategies, including mesenchymal stem cell (MSC) therapy, growth factors, and tissue engineering, which hold the potential for promoting cartilage regeneration and modulating the inflammatory microenvironment. Additionally, the integration of nanotechnology has opened new avenues for targeted drug delivery systems and the development of innovative nanomaterials that can further enhance the efficacy of biotherapies by precisely targeting inflammation and cartilage damage. This article concludes by discussing the current clinical applications, the ongoing clinical trials, and the future research directions necessary to confirm the safety and efficacy of these advanced therapies for OA management. With these advancements, biotherapies combined with nanotechnology may revolutionize the future of OA treatment by offering precise and effective solutions for long-term disease management and improved patient outcomes. Full article

Background: Kappa free light chains (KFLCs) are emerging as promising biomarkers for intrathecal B cell activity for diagnosing multiple sclerosis (MS) through cerebrospinal fluid (CSF) analysis. In this study, we evaluated the ability of KFLC formulas to identify the presence of MS and their agreement with the ‘gold standard’ of CSF IgG oligoclonal bands (OCBs). Methods: A total of 233 patients were included in this study: 149, comprising 43 males and 106 females, had MS, and the remainder, 40 males and 44 females, had other neurological diseases (ONDs). We evaluated the potential of KFLCs in terms of sensitivity, specificity, and accordance. All analyses were conducted using a sex-disaggregated approach. Results: KFLCs showed a high sensitivity for both sexes with respect to the diagnosis of MS, with values between 74.42% and 93.03%. The specificity of the various formulas was much lower for females when compared to males, with values between 45.45% and 59.09%, with a significant difference between the two sexes for the K Index > 5.9 (p = 0.0451). Cohen’s kappa showed substantial agreement for men and moderate agreement for women between the KFLC indices and OCB. Conclusions: This study highlights the potential of KFLCs as a biomarker for MS but emphasises the need for sex-specific thresholds to improve diagnostic accuracy. Full article