Search Results (33)

Background: Soft tissue sarcomas (STSs) are a rare and heterogeneous group of mesenchymal tumors with limited response to current therapies, particularly in advanced stages. STS tumors were traditionally considered “cold” tumors, characterized by limited immune infiltration and low immunogenicity. However, emerging evidence is challenging this perception, highlighting a potentially critical role for the immune system in STS biology. Objective: Building on our previous findings suggesting impaired natural killer (NK) cell activity in STS patients, we aimed to perform an in-depth characterization of peripheral NK cells in STS. Methods: Peripheral blood samples from STS patients and sex- and age-matched healthy donors were analyzed to assess NK cell degranulation, IFNγ production, and receptor repertoire. Results: Functional assays revealed a notable reduction in both degranulation and IFNγ production in NK cells from STS patients. STS patients also exhibited dysregulated expression of activating and inhibitory NK cell receptors. Principal component analysis (PCA) identified CD27 and NKp44 as critical markers for distinguishing STS patients from healthy donors. Increased CD27 expression represents a shift towards a more regulatory NK cell phenotype, and we found that CD27 expression was negatively correlated with NK cell degranulation and IFNγ production. ROC curve analysis demonstrated strong potential to distinguish between the groups for both CD27 (AUC = 0.85) and NKp44 (AUC = 0.94). Conclusion: In conclusion, STS patients exhibited impaired NK cell function, altered receptor repertoire, and a shift towards a less cytotoxic and more regulatory phenotype. Full article

Knee osteoarthritis (OA) is a chronic articular disease characterized by the progressive degeneration of cartilage and bone tissue, leading to the appearance of subchondral cysts, osteophyte formation, and synovial inflammation. Conventional treatments consist of non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, and glucocorticoids. However, the prolonged use of these drugs causes adverse effects. NSAIDs, for instance, are known to be nephrotoxic, increasing the damage to articular cartilage. New therapies capable of accelerating the process of tissue regeneration and repair are being discussed, such as the use of orthobiologics that are naturally found in the body and obtained through minimally invasive collection and/or laboratory manipulations. Bone marrow aspirate (BMA) and bone marrow aspirate concentrate (BMAC) are both rich in hematopoietic stem cells, mesenchymal stem cells (MSCs), and growth factors (GFs) that can be used in the healing process due to their anabolic and anti-inflammatory effects. The aim of this literature review is to assess the efficacy of BMA and BMAC in the treatment of knee OA based on the favorable results that researchers have obtained with the use of both orthobiologics envisaging an accelerated healing process and the prevention of OA progression. Full article

Bone marrow cellular therapy has undergone a remarkable evolution, significantly impacting the treatment of musculoskeletal disorders. This review traces the historical trajectory from early mythological references to contemporary scientific advancements. The groundbreaking work of Friedenstein in 1968, identifying fibroblast colony-forming cells in bone marrow, laid the foundation for future studies. Caplan’s subsequent identification of mesenchymal stem cells (MSCs) in 1991 highlighted their differentiation potential and immunomodulatory properties, establishing them as key players in regenerative medicine. Contemporary research has focused on refining techniques for isolating and applying bone marrow-derived MSCs. These cells have shown promise in treating conditions like osteonecrosis, osteoarthritis, and tendon injuries thanks to their ability to promote tissue repair, modulate immune responses, and enhance angiogenesis. Clinical studies have demonstrated significant improvements in pain relief, functional recovery, and tissue regeneration. Innovations such as the ACH classification system and advancements in bone marrow aspiration methods have standardized practices, improving the consistency and efficacy of these therapies. Recent clinical trials have validated the therapeutic potential of bone marrow-derived products, highlighting their advantages in both surgical and non-surgical applications. Studies have shown that MSCs can reduce inflammation, support bone healing, and enhance cartilage repair. However, challenges remain, including the need for rigorous characterization of cell populations and standardized reporting in clinical trials. Addressing these issues is crucial for advancing the field and ensuring the reliable application of these therapies. Looking ahead, future research should focus on integrating bone marrow-derived products with other regenerative techniques and exploring non-surgical interventions. The continued innovation and refinement of these therapies hold promise for revolutionizing the treatment of musculoskeletal disorders, offering improved patient outcomes, and advancing the boundaries of medical science. Full article

Traumatic damage to the spinal cord (SCI) frequently leads to irreversible neurological deficits, which may be related to apoptotic neurodegeneration in nerve tissue. The MLC901 treatment possesses neuroprotective and neuroregenerative activity. This study aimed to explore the regenerative potential of MLC901 and the molecular mechanisms promoting neurogenesis and functional recovery after SCI in rats. A calibrated forceps compression injury for 15 s was used to induce SCI in rats, followed by an examination of the impacts of MLC901 on functional recovery. The Basso, Beattie, and Bresnahan (BBB) scores were utilized to assess neuronal functional recovery; H&E and immunohistochemistry (IHC) staining were also used to observe pathological changes in the lesion area. Somatosensory Evoked Potentials (SEPs) were measured using the Nicolet^® Viking Quest™ apparatus. Additionally, we employed the Western blot assay to identify PI3K/AKT/GSK-3β pathway-related proteins and to assess the levels of GAP-43 and GFAP through immunohistochemistry staining. The study findings revealed that MLC901 improved hind-limb motor function recovery, alleviating the pathological damage induced by SCI. Moreover, MLC901 significantly enhanced locomotor activity, SEPs waveform, latency, amplitude, and nerve conduction velocity. The treatment also promoted GAP-43 expression and reduced reactive astrocytes (GFAP). MLC901 treatment activated p-AKT reduced p-GSK-3β expression levels and showed a normalized ratio (fold changes) relative to β-tubulin. Specifically, p-AKT exhibited a 4-fold increase, while p-GSK-3β showed a 2-fold decrease in T rats compared to UT rats. In conclusion, these results suggest that the treatment mitigates pathological tissue damage and effectively improves neural functional recovery following SCI, primarily by alleviating apoptosis and promoting neurogenesis. The underlying molecular mechanism of this treatment mainly involves the activation of the PI3K/AKT/GSK-3β pathway. Full article

The present review provides a comprehensive examination of the intricate dynamics between α-synuclein, a protein crucially involved in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease and multiple system atrophy, and endogenously-produced bioactive lipids, which play a pivotal role in neuroinflammation and neurodegeneration. The interaction of α-synuclein with bioactive lipids is emerging as a critical factor in the development and progression of neurodegenerative and neuroinflammatory diseases, offering new insights into disease mechanisms and novel perspectives in the identification of potential biomarkers and therapeutic targets. We delve into the molecular pathways through which α-synuclein interacts with biological membranes and bioactive lipids, influencing the aggregation of α-synuclein and triggering neuroinflammatory responses, highlighting the potential of bioactive lipids as biomarkers for early disease detection and progression monitoring. Moreover, we explore innovative therapeutic strategies aimed at modulating the interaction between α-synuclein and bioactive lipids, including the development of small molecules and nutritional interventions. Finally, the review addresses the significance of the gut-to-brain axis in mediating the effects of bioactive lipids on α-synuclein pathology and discusses the role of altered gut lipid metabolism and microbiota composition in neuroinflammation and neurodegeneration. The present review aims to underscore the potential of targeting α-synuclein-lipid interactions as a multifaceted approach for the detection and treatment of neurodegenerative and neuroinflammatory diseases. Full article

Background/Objectives: Bariatric surgery candidates require presurgical physical training, therefore, we compared the metabolic effects of a constant moderate-intensity training program (MICT) vs. a high-intensity interval training (HIIT) in this population. Methods: Seventeen participants performed MICT (n = 9, intensity of 50% of heart rate reserve (HRR) and/or 4–5/10 subjective sensation of effort (SSE)) or HIIT (n = 8, 6 cycles of 2.5 min at 80% of the HRR and/or 7–8/10 of SSE, interspersed by 6 cycles of active rest at 20% of the FCR) for 10 sessions for 4 weeks. After training, tissue samples (skeletal muscle, adipose tissue, and liver) were extracted, and protein levels of adiponectin, GLUT4, PGC1α, phospho-AMPK/AMPK, collagen 1 and TGFβ1 were measured. Results: Participants who performed MICT showed higher protein levels of PGC-1α in skeletal muscle samples (1.1 ± 0.27 vs. 0.7 ± 0.4-fold change, p < 0.05). In the liver samples of the people who performed HIIT, lower protein levels of phospho-AMPK/AMPK (1.0 ± 0.37 vs. 0.52 ± 0.22-fold change), PGC-1α (1.0 ± 0.18 vs. 0.69 ± 0.15-fold change), and collagen 1 (1.0 ± 0.26 vs. 0.59 ± 0.28-fold change) were observed (all p < 0.05). In subcutaneous adipose tissue, higher adiponectin levels were found only after HIIT training (1.1 ± 0.48 vs. 1.9 ± 0.69-fold change, p < 0.05). Conclusions: Our results show that both MICT and HIIT confer metabolic benefits in candidates undergoing bariatric surgery; however, most of these benefits have a program-specific fashion. Future studies should aim to elucidate the mechanisms behind these differences. Full article

Toxicological studies have shown that the American cockroach Periplaneta americana (Linnaeus) is a classical model for studying the mode of action of commonly used insecticides. In a previous study, we demonstrated that thiamethoxam and clothianidin decreased locomotor activity in an open-field-like apparatus. Here, we tested the effect of the neonicotinoid acetamiprid when applied orally, topically, or injected into the haemolymph. We found that acetamiprid was also able to impair locomotor activity in the open-field-like apparatus. When treated with acetamiprid, a strong alteration in locomotor activity was observed 1 h, 24 h, and 48 h after haemolymph and topical applications. Oral application induced an impairment of locomotor activity at 24 h and 48 h. A comparison of the present data with our previously published results showed that neonicotinoids were more active when injected into the haemolymph compared to oral and topical applications. These findings increased our understanding of the effect of neonicotinoid insecticides on insect locomotor activity, and demonstrated that the cyano-substituted neonicotinoid, acetamiprid, was able to alter cockroach locomotor activity. Full article

Leiomyosarcomas (LMSs) are malignant neoplasms of soft muscle differentiation that can be classified into five distinct groups according to site-related origin: intra-abdominal, subcutaneous or deep soft tissue of the limbs, cutaneous, external genitalia, and vascular. This distinction reflects different biological behaviors as well as molecular changes, thus reflecting different prognoses and therapeutic options. Vascular LMSs are the least frequent, arising from the walls of the blood vessels, most commonly from the inferior vena cava. Due to its deep location, symptoms are non-specific, and the disease presents at an advanced stage, sometimes with metastases. Surgery is the treatment of choice, associated with chemo- and radiotherapy. Due to its rarity, most departments have minimal experience handling this disease. This article reviews the current knowledge on vascular leiomyosarcomas, particularly the inferior vena cava leiomyosarcoma. Full article

This study evaluated the changes in the composition of oral–gut microbiota in patients with rheumatoid arthritis (RA) caused by methotrexate (MTX) and non-surgical periodontal treatment (NSPT). Assessments were performed at baseline (T0), 6 months after MTX treatment (T1), and 45 days after NSPT (T2). The composition of the oral and gut microbiota was assessed by amplifying the V4 region of the 16S gene from subgingival plaques and stools. The results of the analysis of continuous variables were presented descriptively and non-parametric tests and Spearman’s correlation were adopted. A total of 37 patients (27 with periodontitis) were evaluated at T0; 32 patients (24 with periodontitis) at T1; and 28 patients (17 with periodontitis) at T2. MTX tended to reduce the alpha diversity of the oral–gut microbiota, while NSPT appeared to increase the number of different species of oral microbiota. MTX and NSPT influenced beta diversity in the oral microbiota. The relative abundance of oral microbiota was directly influenced by periodontal status. MTX did not affect the periodontal condition but modified the correlations that varied from weak to moderate (p < 0.05) between clinical parameters and the microbiota. MTX and NSPT directly affected the composition and richness of the oral–gut microbiota. However, MTX did not influence periodontal parameters. Full article

The neonicotinoid imidacloprid is a widely used insecticide worldwide. We assessed the effects of acute and chronic imidacloprid exposure on the social behavior of adult zebrafish. We assembled simple apparatus to detect 2D locomotion: a single camera capture system and two specially designed water tanks. We then used the tracking and heat maps of the behavior trajectories of zebrafish subjected to sham and imidacloprid exposure and compared their social behavior. Furthermore, histomorphology and immunohistochemistry of their brain tissue sections were performed to clarify possible neurotoxicity due to imidacloprid exposure in our adult zebrafish. Our results showed that imidacloprid exposure significantly reduced the zebrafish’s swimming speed, distance traveled, acceleration, and deceleration. The longer the imidacloprid exposure, the more severe the locomotor behavior disability. Furthermore, imidacloprid exposure significantly reduced heterosexual attractive behavior between the different sexes, as well as defensive alert behavior among males. Our histomorphology and immunohistochemistry evidence showed imidacloprid exposure may lead to neuronal oxidative stress, inflammation, apoptosis, and damage in the telencephalon of adult zebrafish. Thus, we suggested that neonicotinoid imidacloprid exposure can damage the telencephalon neurons of adult zebrafish through oxidative stress, inflammation, and apoptosis and then affect the social behavior of adult zebrafish. Full article

The use of blended learning strategies is increasingly common in health sciences, including veterinary medicine; however, there are very few descriptions of these methods being applied to practicals. We describe here the application of blended learning based on the implementation of flipped classrooms with collaborative learning and gamification to the 2020–2021 veterinary medicine gross anatomy practicals at CEU Cardenal Herrera University (Spain). Students prepared for the sessions by pre-viewing videos and taking a quiz before the start. The sessions were conducted in small groups where students learned through collaborative work and reviewed their learning with a card game. A small but significant increase was observed when comparing the scores of practical exams of the locomotor apparatus with those of 2018–2019 (6.79 ± 2.22 vs. 6.38 ± 2.24, p < 0.05), while the scores were similar (7.76 ± 1.99 vs. 7.64 ± 1.92) for the organ system exams. Students’ responses in a satisfaction survey were mostly positive (>80%) regarding the motivating and learning-facilitating effect of this educational method. Our work shows that the application of blended learning in anatomy practicals based on a flipped classroom and with elements of gamification and collaborative work can be an effective way to improve the learning experience of students. Full article

CD56+ T cells are generally recognized as a distinct population of T cells and are categorized as NKT-like cells. Although our understanding of NKT-like cells is far from satisfactory, it has been shown that aging and a number of disease situations have impacted these cells. To construct an overview of what is currently known, we reviewed the literature on human NKT-like cells. NKT-like cells are highly differentiated T cells with “CD1d-independent” antigen recognition and MHC-unrestricted cell killing. The genesis of NKT-like cells is unclear; however, it is proposed that the acquisition of innate characteristics by T cells could represent a remodeling process leading to successful aging. Additionally, it has been shown that NKT-like cells may play a significant role in several pathological conditions, making it necessary to comprehend whether these cells might function as prognostic markers. The quantification and characterization of these cells might serve as a cutting-edge indicator of individual immune health. Additionally, exploring the mechanisms that can control their killing activity in different contexts may therefore result in innovative therapeutic alternatives in a wide range of disease settings. Full article

The prevalence of anxiety has increased dramatically due to COVID-19, so effective preventive interventions are welcome. The main objective of our study was to compare the acute relaxation response (RR) induced by Tibetan singing bowl (TSB) sound-based treatment against progressive muscle relaxation (PMR) and a control waiting list group (CWL) in a single treatment session in an adult nonclinical anxious population. In this cross-sectional randomized control trial, 50 participants selected based on high state anxiety were randomly assigned to one of the experimental groups. Pre/post self-reported anxiety, electroencephalographic activity (EEG), and heart rate variability (HRV) were recorded at baseline (T1), minute 15 (T2), minute 30 (T3), and minute 45 (T4). The TSB group showed significant reductions in alpha power (from T2 to T4) and increased HRV (from T3 to T4) compared with the PMR and CWL groups. Moreover, TSB and PMR both showed significant reductions in self-reported anxiety compared with CWL, with this effect being more evident in the TSB group. We concluded that a single session of TSB treatment was able to induce a more evident psychological/physiological relaxation response compared with PMR and CWL. TSB could be a relevant acute intervention in stressful situations or crisis intervention and while waiting for conventional interventions. Full article

O’Donoghue’s triad is an extremely debilitating condition. Although there are many conventional treatments available, there is still no consensus regarding the most effective rehabilitation protocol for a full recovery. Surgical interventions have become an ordinary consideration, but problems may still persist even after the surgical procedure. Orthobiologics, however, have gained considerable popularity in regenerative medicine. Notable autologous alternatives, such as bone marrow aspirate (BMA), are often utilized in clinical settings. To our knowledge, the administration of BMA products for the management of O’Donoghue’s triad has not been thoroughly investigated in the literature. In this case report we describe a full recovery from O’Donoghue’s triad with BMA matrix in a patient who was recalcitrant to surgical intervention due to fear of complications. Our patient received three BMA matrix injections with four-week intervals, exhibiting significant recovery according to pain scores, functional assessment outcomes, and magnetic resonance imaging (MRI) results. The patient returned to normal activities with no complaints and MRI evidence at follow-up showed significant signs of structural restoration of the musculoskeletal tissues. Here, we demonstrate that autologous BMA products are a feasible alternative for the accelerated recovery of musculoskeletal tissue injury with safety and efficacy. Full article