Search Results (2,383)

Intra-articular injections form a substantial element of the temporomandibular joint disorder (TMD) therapy. Given the role played by IL-1β in pathology, the use of autologous conditioned serum (ACS) is well-founded. Despite years of effective use in different locations, data regarding the intra-articular administration of ACS in TMD is scarce, and the strategy itself is not routinely applied. This study aims to provide preliminary evidence on the therapeutic efficacy of administering intra-articular ACS in treating TMD. Patients with TMD who received intra-articular ACS were included. More invasive co-interventions, such as arthroscopy, were excluded. Final searches were conducted on 17 June 2025, using five databases (ACM, BASE, DOAJ, PubMed, and SciELO). Risk of bias was evaluated using the RoB 2 tool. The results were tabulated. Only one study met the inclusion criteria. When compared to dextrose prolotherapy in internal TMD, ACS therapy resulted in greater improvement in mouth opening, pain, and joint-sound reduction. The small sample size, head-to-head design, and limited blinding suggest a highly cautious interpretation of the findings. ACS is a promising, but still experimental, therapeutic strategy addressing critical mechanisms in TMD. However, the currently available data is insufficient to confirm the effectiveness and safety of such an approach, and further high-quality studies are needed. This study received no funding. PROSPERO registration number: CRD420251069310. Full article

In addition to its well-recognized roles in immunomodulation and calcium phosphate homeostasis, growing evidence shows that Vitamin D (Vit. D) presents a wide range of other properties, including antioxidant and anticancer effects. However, the action of Vit. D is not fully recognized in pancreatic cancer (PC) cells exposed to oxidative stress. Therefore, the aim of the present study was to investigate whether vitamin D₃ (Vit. D₃) protects PC cells from death induced by oxidative stress. PC cells are suggested to be resistant to oxidative stress since they demonstrate overexpression of superoxide dismutase (SOD) 1–3. The study measured PC cell viability, DNA damage level, the mRNA and protein expression of antioxidant enzymes, reactive oxygen species (ROS) level and activity of antioxidant enzymes after exposure to H₂O₂, Vit. D₃ and their combinations. N-Acetyl-L-Cysteine (NAC), a well-known direct ROS scavenger, was used as a positive control. Vit. D₃ exposure alone had no effect on PC cell viability, ROS level and DNA damage. Its impact on the mRNA and protein expression of antioxidant enzymes was also scarce. However, Vit. D₃ protected PC cells against H₂O₂-induced death, similarly to NAC. It also diminished the increase in ROS and DNA damage caused by H₂O₂. In addition, Vit. D₃ enhanced the mRNA expression of catalase (CAT), SOD 1–3 and glutathione peroxidase (Gpx)3, but did not affect their protein levels in PC cells exposed to oxidative stress. Interestingly, Vit. D₃ increased CAT activity after 24 h in 1.2B4 cells and elevated the activity of both CAT and Gpx after 2 h in PANC-1 cells, which could contribute to the observed reduction of H₂O₂-induced ROS level. To conclude, our findings show that antioxidant properties of Vit. D₃ may protect PC cells from oxidative stress-induced death. Therefore, further studies are needed to understand the action of Vit. D₃ in PC cells. Full article

(1) Background: The use of cancer therapy is one of the most challenging arguments in cancer research and is in constant development. One of the principal problems connected with tumor therapy arises from the potential side effects connected with the classical chemotherapeutic treatment but also with molecular target therapy. The identification of novel molecules useful for the reduction of potential side effects but also as a new therapeutic opportunity is one of the hottest topics. (2) Methods: We identified castalin from chestnut shells by using NRM and LC-MS/MS. We treated different cancer cell lines with castalin alone or in combination with a CHK1 inhibitor. Finally, we performed an RNA-seq analysis of HeLa cells treated with castalin. (3) Results: We demonstrated the ability of castalin to induce DNA damage, probably by increasing ROS production. Consistently, antioxidant treatment, with ascorbic acid, reduced the DNA damage induced by castalin. Finally, we demonstrated the potential synergistic effect of castalin with SRA737, a CHK1 inhibitor currently used in clinical trials. (4) Conclusions: We demonstrated the ability of castalin to induce DNA damage favoring NHEJ repair. Moreover, the use of castalin in combination with SRA737 increased the efficacy of the CHK1 inhibitor, reducing its possible side effects. Full article

Relevance of the problem and aim of the work: Ankylosis of the temporomandibular joint (TMJ) affects physical, psychological, and social well-being and quality of life. One of the most frequently used surgical interventions for the treatment of temporomandibular joint ankylosis is interpositional arthroplasty, particularly in cases where joint preservation is feasible, with different autologous fats: dermis fat, buccal fat pad, and full thickness skin-subcutaneous fat. The aim of the work was to evaluate the efficiency of using different autologous fats in temporomandibular joint ankylosis treatment with interposition arthroplasty method. Materials and Methods: This systematic literature review was conducted according to PRISMA guidelines and registered in the PROSPERO database (CRD420251038325). A comprehensive search was performed in PubMed, the Cochrane Library, and ScienceDirect databases using combinations of keywords: (temporomandibular joint disorders OR temporomandibular joint) AND (adipose tissue or autologous) AND (ankylosis OR arthroplasty). Inclusion criteria were clinical studies conducted on human subjects, written in English, that evaluated the use of autologous fat in interpositional arthroplasty for TMJ ankylosis. The main outcome measures included postoperative maximum mouth opening (MMO), pain intensity, and relative fat volume contraction. Risk of bias was assessed using the Cochrane RoB 2 tool for randomized controlled trials and the Newcastle–Ottawa Scale for cohort studies. Most included studies were of moderate to high quality. Results: A total of 20 publications were selected, including a total of 369 patients. In a qualitative analysis, the best results for maximal opening of mouth (MOM) at 3, 6, 12, and more than 12 months were obtained with dermal fat. After 3 months, the MOM was 40.0 ± 2.7 mm, after 6 months—40.80 ± 4.26 mm, after 12 months—41.9 ± 4.0 mm, after more than 12 months—43.5 mm. The lowest pain intensity was observed using dermal fat taken from the iliac crest region. The rate of volumetric fat shrinkage was greater using buccal fat pad than dermis fat. Conclusions: The most commonly used types of autologous fat in interposition arthroplasty in ankylosis are the following: dermal fat from the abdominal region (iliac crest, subumbilical area, groin), buccal fat pad and full-thickness subcutaneous fat. The best results after the surgical treatment of TMJ ankylosis with interposition arthroplasty are obtained using dermis fat. Full article

(1) Background: This study investigates the impact of digital device usage on the visual system, with a focus on binocular vision. It also highlights the importance of objective assessment in accurately diagnosing and guiding therapeutic approaches for Digital Eye Strain Syndrome (DESS). (2) Methods: A comprehensive narrative review was conducted to synthesize existing evidence. The methodological quality of observational and case–control studies was assessed using the Newcastle–Ottawa scale, while randomized controlled trials (RCTs) were evaluated using the Cochrane risk-of-bias (RoB 2) tool. (3) Results: Fifteen articles were included in this review, with a predominant focus on binocular vision anomalies, particularly accommodative and vergence dysfunctions, as well as ocular surface anomalies related to DESS. Clinical assessments relied primarily on symptom-based questionnaires, which represent a significant limitation. The included studies were largely observational, with a lack of longitudinal and RCTs. In contrast, research in dry eye disease has been more comprehensive, with multiple RCTs already conducted. (4) Therefore, it is essential to develop validated objective metrics that support accurate clinical diagnosis and guide evidence-based interventions. Conclusions: It remains unclear whether changes in binocular vision are a cause or consequence of DESS. However, prolonged screen time can exacerbate pre-existing binocular vision anomalies due to continuous strain on convergence and accommodation, leading to symptoms. Future research should prioritize prospective longitudinal studies and well-designed RCTs that integrate objective clinical measures to elucidate causal relationships and improve diagnostic and therapeutic frameworks. Full article

The maturation of testicular Leydig cells during the prepubertal stage is crucial for establishing male fertility. While diabetes is recognized as a significant detrimental factor affecting male testicular function, its impact specifically during the prepubertal period remains largely unknown. We hypothesized that prepubertal diabetes may impair testicular development by disrupting Leydig cell maturation. Using streptozotocin (STZ) administration, we established a prepubertal diabetic rat model and investigated the effects of diabetes on testicular development 2 and 4 weeks post-STZ treatment. Diabetes significantly hampered testicular development, manifesting as a decreased testicular weight, structural abnormalities, reduced testosterone levels, and increased inflammatory responses. As anticipated, prepubertal diabetes stagnated Leydig cell maturation and increased Leydig cell apoptosis. Mechanistic studies revealed that autophagy is essential for maintaining homeostasis and facilitating differentiation in immature Leydig cells but is significantly inhibited by hyperglycemia. Dysregulation of autophagy impaired the mitochondrial network, triggering inflammatory responses, suppressing steroidogenic capacity, and accumulating reactive oxygen species (ROS). Elevated ROS levels exacerbated the inflammatory response in the Leydig cells in an NLRP3-dependent manner. Inhibition of NLRP3 ameliorated the hyperglycemia-induced inflammation and decline in steroidogenic ability. Collectively, these findings demonstrate that hyperglycemia suppresses autophagy induction and enhances ROS accumulation in Leydig cells. This cascade promotes inflammation and inhibits steroidogenesis, thereby impeding testicular development in prepubertal diabetic rats. Full article

Endothelial function plays a key role in tissue repair. Reactive Oxygen Species (ROS) production impairs tissue renewal and homeostasis. Complex Magnetic Fields (CMFs) have been attracting attention as a non-invasive tool to promote tissue regeneration, especially through angiogenic stimulation. The present study aims to investigate CMF effect in an in vitro model of oxidative stress-stimulated Endothelial Cells (ECs). Cells were pre-treated with H₂O₂ to mimic an oxidative environment, followed by the application of three CMF programs repeated in two experimental sets: two consecutive cycles (two cycles) or two cycles spaced 24 h apart (T0+T24). Flow cytometry investigation shows that both CMF applications reduce ROS production, presumably promoting SODs proteins expression. Specifically, two cycles affect mitochondrial SOD-2 expression, which may promote cellular turnover by upregulating pro-apoptotic proteins, leading to mild cell death balanced with increased cell viability. T0+T24 application promotes cytosolic SOD-1 expression, which may influence the expression and release of antioxidant molecules, as evidenced by the increased protein levels of Akt/Nrf2 and the overall antioxidant activity measured post-treatment. In conclusion, ROS-induced EC dysfunction can be reverted by CMF application: 2 cycles could be applied when cellular renewal is required (such as in pathological wounds) while T0+T24 could be useful when an antioxidant and anti-inflammatory effect is needed (e.g., in edema or muscular lesions). Full article

Selenium (Se) and silicon (Si) have been demonstrated to mitigate the adverse effects of cadmium (Cd) stress on the growth of various higher plants. However, the distinct mechanisms by which Se and Si, when applied to soil, alleviate the toxicity of Artemisia argyi under Cd stress remain unclear. This study employed A. argyi as the experimental material and simulated a Cd stress environment in soil pot experiments by adding CdCl₂·2.5H₂O at concentrations of 4 mg kg⁻¹ and 10 mg kg⁻¹. Exogenous Se in the form of Na₂SeO₃ (2 mg kg⁻¹) or Si in the form of Na₂SiO₃ (20 mg kg⁻¹) was applied simultaneously. After 90 days of combined exposure, the study investigated the differential mechanisms by which Se and Si application influenced Cd uptake by roots, its translocation within aboveground and underground tissues, and the antioxidant system of A. argyi under two levels of Cd stress. The results indicate that under Cd stress conditions, the application of Se significantly promotes the growth of A. argyi. Under both Cd concentration treatments, the application of Se or Si alone markedly reduces the Cd content in the aboveground parts of A. argyi. This reduction may be attributed to alterations in the subcellular distribution of Cd, decreased Cd content in organelles, and increased Cd sequestration in cell walls and soluble components. Furthermore, the application of Se or Si in soil can enhance the content of osmoregulatory substances, chlorophyll, and plant chelating agents in A. argyi leaves while reducing the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), particularly at high Cd concentrations. The findings suggest that the alleviation of Cd toxicity by exogenous Se is primarily due to its role in inhibiting Cd uptake and translocation to shoots, as well as strengthening Cd compartmentalization in root cell walls and enhancing the antioxidant defense system. In contrast, exogenous Si primarily mitigates Cd toxicity by restricting Cd translocation from underground to aboveground plant tissues. Full article

Background and Objectives: Osteoarthritis (OA) is a chronic, degenerative joint disease. The main symptoms include pain that can cause loss of function and stiffness, as well as swelling, reduced range of motion, crepitus, joint deformity, and muscle weakness. It leads to irreversible structural changes, that in advanced stages can require surgical interventions. The aim of this review was to summarize the current literature about the role of virtual reality (VR), exergames and digital technologies in patients with knee osteoarthritis before or after total knee arthroplasty, to understand if it is possible to prevent and reduce the symptoms and if these new technologies are more effective than conventional rehabilitation therapies. Materials and Methods: We conducted a systematic search of PubMed, Cochrane Library, Scopus, and PEDro from inception to November 2024. The review adhered to the PRISMA 2020 guidelines, and the protocol was prospectively registered in PROSPERO (registration number: CRD42024541890). We included randomized controlled trials (RCTs) enrolling participants aged 60 years or older, in which VR or telerehabilitation programs were compared with conventional rehabilitation approaches. Eligible studies had to report at least one of the following outcomes: pain, functionality, stability, or adherence. Two independent reviewers screened titles and abstracts, assessed full-text eligibility, extracted data, and evaluated the risk of bias using the Cochrane Risk of Bias 2 (RoB 2) tool. Results: Fourteen randomized controlled trails (RCTs) (1123 participants; mean age 68.2 years) were included. VR and telerehabilitation generally outperformed conventional rehabilitation for pain (8/13 studies, −0.9 to −2.3 VAS points) and functionality (7/13 studies, WOMAC improvement 8–15%, TUG −1.2 to −2.8 s). Compliance was higher in most technology-assisted programs (6/7 studies, 70–100% adherence). Stability outcomes were less consistent, with only 1/4 studies showing clear benefit. One study favored conventional rehabilitation for functionality. Overall risk of bias was low-to-moderate, with heterogeneity mainly driven by intervention duration, platform type, and supervision level. Conclusions: Structured telerehabilitation, non-immersive VR, and interactive online exercise programs, especially those offering real-time feedback, show comparable or superior benefits to conventional rehabilitation in older adults with knee OA or after TKA, particularly for pain reduction, functional gains, and adherence. These approaches enhance accessibility and home-based care, supporting their integration into clinical practice when in-person therapy is limited. Full article

Our previous research has demonstrated the role of optimal temperatures and reactive oxygen species (ROS) in maintaining symptomless nonhost resistance (NHR) of barley to powdery mildews. However, the exact functions of temperature and ROS in NHR of plants, including barley, to viral infections are not known. Although barley is a nonhost for Tobacco mosaic virus (TMV), this virus can replicate in barley leaves at temperatures of ca. 30 °C. Here we elucidated the influence of short-term heat stress pre-treatments (30 °C, 3 h; heat shock at 49 °C, 20 s) on the symptomless NHR of barley to TMV and the role of the ROS superoxide (O₂^.−) in maintaining NHR. Heat stress and antioxidant (superoxide dismutase and catalase, SOD + CAT) treatments resulted in 50–100% higher TMV levels, while combined heat shock and SOD + CAT application caused further increases in TMV and appearance of cell and tissue death resembling a hypersensitive response (HR). An early (from 2 h after inoculation) burst of O₂^.− was essentially absent in TMV-infected barley exposed to short-term heat stress pre-treatments. Expression of barley genes regulating ROS (O₂^.−) metabolism (HvRBOHF2, HvSOD1) and cell death (HvBI-1) displayed an inverse correlation with TMV levels even at later time points (1–4 days after inoculation), implying a role in symptomless NHR, while increased levels of the antioxidant glutathione marked heat stress-induced suppression of NHR. We demonstrated that short-term heat stress and antioxidant treatments result in compromised NHR of barley to TMV, pointing to the role of optimal temperatures and ROS (O₂^.−) in symptomless NHR to virus infections. Full article

Objective: this systematic review with a meta-analysis aimed to evaluate the available body of published peer-reviewed randomized controlled trial (RCT) studies on the effects of different doses and types of strength training (ST) on body composition, physical performance, and protein or calcium intake in older people with osteosarcopenia. Method: a systematic literature search was conducted between July 2024 and August 2025 using five databases: PubMed, Medline, CINAHL Complete, Scopus, and Web of Science. PRISMA, TESTEX, RoB 2, and GRADE tools assessed methodological quality and certainty of evidence. Hedge’s g effect sizes were calculated for the abovementioned variables for the meta-analysis. Results: the protocol was registered in PROSPERO (code: CRD42025643858). Of 141 registers, seven RCTs with 349 participants were included. Seven overall and two subgroup meta-analyses showed significant increases in skeletal muscle mass index (SMMI; p < 0.01), maximal isometric handgrip strength (MIHS; p = 0.03), and protein intake (p = 0.03). There were no significant differences in bone mineral density (BMD), body fat percentage (BFP), gait speed, and calcium intake. However, meta-analysis by subgroups showed significant decreases in BFP (p = 0.01) in favor of elastic band training versus resistance training, with no significant differences in BMD. Conclusions: ST in older people with osteosarcopenia conditions increases SMMI, MIHS, and protein intake. Full article

This paper explores different approaches to harmony tokenization in symbolic music for transformer-based models, focusing on two tasks: masked language modeling (MLM) and melodic harmonization generation. Four tokenization strategies are compared, each varying in how chord information is encoded: (1) as full chord symbols, (2) separated into root and quality, (3) as sets of pitch classes, and (4) as sets of pitch classes where one is designated as a root. A dataset of over 17,000 lead sheet charts is used to train and evaluate RoBERTa for MLM and GPT-2/BART for harmonization. The results show that chord spelling methods—those breaking chords into pitch-class tokens—achieve higher accuracy and lower perplexity, indicating more confident predictions. These methods also produce fewer token-level errors. In harmonization tasks, chunkier tokenizations (with more information per token) generate chords more similar to the original data, while spelling-based methods better preserve structural aspects such as harmonic rhythm and melody–harmony alignment. Audio evaluations reveal that spelling-based models tend toward more generic pop-like harmonizations, while chunkier tokenizations more faithfully reflect the dataset’s style. Overall, while no single tokenization method dominates across all tasks, different strategies may be preferable for specific applications, such as classification or generative style transfer. Full article

Curcumin, the principal active component of turmeric, is a polyphenol that has been used in various countries for the treatment of numerous conditions due to its wide range of health benefits. Curcumin exhibits bifunctional antioxidant properties: the first is attributed to its chemical structure, which enables it to directly neutralize reactive oxygen species (ROS); the second is related to its ability to induce the expression of antioxidant enzymes via the transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2). Both ROS and Nrf2 are closely associated with mitochondrial function and metabolism, and their dysregulation may lead to mitochondrial dysfunction, potentially contributing to the development of various pathological conditions. Therefore, curcumin treatment appears highly promising and is strongly associated with the preservation of mitochondrial function. The aim of this review is to summarize the current literature on the impact of curcumin’s antioxidant properties on mitochondrial function. Specifically, studies conducted in different biological models are included, with emphasis on aspects such as mitochondrial respiration, antioxidant enzyme activity, interactions with mitochondrial membranes, and the role of curcumin in the regulation of intrinsic apoptosis. Full article

Micronutrients and nutraceuticals play crucial roles in wound healing and tissue regeneration, supporting various physiological processes. This review aims to synthesize and evaluate the functions of various micronutrients and nutraceuticals, emphasizing the synergistic interactions among different nutrients that facilitate wound healing processes. A thorough literature review was performed using electronic databases, including PubMed, Scopus, Web of Science, Embase, Google Scholar, and Cochrane Library, to identify molecular studies, animal models, randomized controlled trials, and observational human studies published up to January 2000. Two independent reviewers screened the articles, extracted data, and evaluated the Risk of Bias using the Risk of Bias 2 (RoB 2) tool for the 190 studies that met the inclusion criteria. Evidence suggests that bioactive compounds found in functional foods and dietary supplements can help prevent chronic conditions and promote wellness beyond basic nutrition. Vitamins A, C, and E, as well as minerals such as zinc, selenium, and iron, are essential for cell proliferation and the formation of new tissues. Additionally, nutraceuticals, including omega-3 fatty acids, glutamine, arginine, and polyphenols, exhibit anti-inflammatory and antioxidant properties, which promote healing and reduce the risk of infection. Probiotics and other bioactive compounds in nutraceuticals contribute to maintaining the balance of microbiota, reducing inflammation, and stimulating cell regeneration. Significant variability was noted in study design, sample size, intervention dosage, and outcome measures. This evidence underscores the necessity for further well-designed clinical trials to determine the optimal dosages and combinations for specific wound types across diverse patient populations. This systematic review was prospectively registered in PROSPERO (ID: 1072091). Full article

Background: While insulin is the standard of care for feline diabetes mellitus (FDM), non-insulin antidiabetic drugs (NIADs) are emerging as alternatives. This systematic review aims to synthesize and critically appraise the current evidence for the efficacy and safety of NIADs in cats. Methods: A systematic review was conducted following PRISMA guidelines. Major databases were searched for studies evaluating NIADs in diabetic cats or at-risk/experimental models. Risk of bias was assessed using RoB 2 and ROBINS-I tools. Results: Twenty studies were included. In diabetic cats (10 studies), traditional agents (glipizide, metformin, acarbose) showed limited efficacy based on evidence with a high risk of bias. Newer SGLT2 inhibitors (bexagliflozin, velagliflozin) demonstrated high treatment success rates and non-inferiority to insulin but were associated with a significant risk of euglycemic diabetic ketoacidosis (eDKA). In at-risk/experimental models (10 studies), thiazolidinediones consistently improved insulin sensitivity, while glipizide was shown to accelerate islet amyloidosis. Conclusions: The evidence supports a paradigm shift towards SGLT2 inhibitors as a viable oral monotherapy for select cases of FDM. This alters the clinical risk–benefit discussion from preventing hypoglycemia to mitigating eDKA. Significant evidence gaps remain, particularly the lack of high-quality RCTs and data in cats with common comorbidities. Full article