Biomedicines最新文献

Background: This study aimed to investigate the relationships between kymographic parameters derived from high-speed videoendoscopy (HSV) and simultaneously recorded acoustic signals. The research provides insights into the vibratory dynamics of various glottal pathologies, assessed across different glottal widths, and their mutual relations with audio data. Methods: The study included 192 participants categorized as normophonic or having functional or organic lesions (benign, premalignant, and malignant). Parameters describing vocal fold oscillations were calculated using HSV kymography for three glottal widths, along with corresponding acoustic data. Initially, linear correlations between these parameters were assessed. Next, the consistency in cycle detection and its influence on the correlation levels were evaluated. Results: The fundamental frequency (F0) and mean Jitter (Jita) showed the highest correlations between the HSV- and audio-determined parameters (F0: 0.97, Jita: 0.40-0.70), with even stronger correlations when the number of detected cycles was consistent (F0: 0.99, Jita: 0.68-0.98). The correlations for other parameters ranged from low to moderate, with no significant differences observed between the diagnostic subgroups (functional changes and benign and malignant glottal lesions). However, in the premalignant lesions group, high correlations (0.77-0.9) were observed between the HSV and audio parameters, but only for measures describing period perturbations. Beyond F0 and mean Jitter, consistency in cycle detection did not significantly affect correlation levels. Conclusions: The simultaneous audio signal proved useful in verifying the accuracy of HSV quantification measures, particularly for F0, which showed strong agreement between the methods. Discrepancies in other parameters and low correlations between HSV-derived kymography and audio data may suggest the influence of the throat, mouth, and nose resonators, which are added to the glottal signal. While the kymographic analysis based on HSV provides detailed descriptions of vocal fold oscillations, it does not fully capture the three-dimensional structure and complex functionality of the vocal folds.

Background: Fibromyalgia, depression, and autoimmune diseases represent a triad of interconnected conditions characterized by overlapping biological pathways, including chronic inflammation, immune dysregulation, and neurochemical imbalances. Understanding their shared mechanisms offers opportunities for innovative therapeutic approaches. Objective: This systematic review explores the common inflammatory- and immune-related pathways among these conditions, emphasizing their implications for biomarker development and novel therapeutic strategies. Methods: Following PRISMA guidelines, a comprehensive literature search was conducted in databases including PubMed, Scopus, Web of Science, and the Cochrane Library. Studies examining the relationship between fibromyalgia, depression, and autoimmune diseases with a focus on immune responses, inflammatory biomarkers, and therapeutic interventions were included. The quality of the selected studies was assessed using the Cochrane Risk of Bias tool. Results: From the 255 identified studies, 12 met the inclusion criteria. Evidence supports the role of pro-inflammatory cytokines (e.g., IL-6, TNF-α) and neurochemical dysregulation (e.g., serotonin, dopamine) as key factors in the pathophysiology of these conditions. Pilot studies highlight the potential of immune-modulating therapies, including low-dose IL-2 and anti-inflammatory agents such as N-acetylcysteine and minocycline, in alleviating both physical and psychological symptoms. Emerging biomarkers, including cytokine profiles and platelet serotonin activity, show promise for personalized treatment approaches. Conclusions: The shared inflammatory pathways linking fibromyalgia, depression, and autoimmune diseases underscore the need for integrated therapeutic strategies. Although pilot studies provide preliminary insights, validation through large-scale, multicenter trials is essential. Future research should focus on standardizing methodologies and leveraging biomarker-driven precision medicine to improve outcomes for patients with these complex, multifactorial conditions.

Perioperative neurocognitive disorders (PNDs), including postoperative delirium, delayed neurocognitive recovery, and long-term postoperative neurocognitive disorders, present significant challenges for older patients undergoing surgery. Inflammation is a protective mechanism triggered in response to external pathogens or cellular damage. Historically, the central nervous system (CNS) was considered immunoprivileged due to the presence of the blood-brain barrier (BBB), which serves as a physical barrier preventing systemic inflammatory changes from influencing the CNS. However, aseptic surgical trauma is now recognized to induce localized inflammation at the surgical site, further exacerbated by the release of peripheral pro-inflammatory cytokines, which can compromise BBB integrity. This breakdown of the BBB facilitates the activation of microglia, initiating a cascade of neuroinflammatory responses that may contribute to the onset of PNDs. This review explores the mechanisms underlying neuroinflammation, with a particular focus on the pivotal role of cytokines in the pathogenesis of PNDs.

Background. The molecular mechanisms underlying acute coronary syndrome (ACS) have been extensively investigated, with a particular focus on the role of circulating microvesicles (MVs) as carriers of regulatory elements that influence hemodynamic changes and coronary flow. Endothelial and platelet dysfunction during ACS alters MV composition, impacting clinical outcomes. This study explores the levels of miR-126-5p and miR-223-3p in circulating MVs and their association with the Thrombolysis in Myocardial Infarction (TIMI) coronary flow classification scale, proposing their potential as biomarkers. Methods. Bioinformatic tools identified miRNAs linked to ACS. Plasma MVs were isolated from ACS patients and healthy controls through high-speed centrifugation. miRNA levels were quantified using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and compared across TIMI 0 and TIMI 3 groups. Diagnostic efficacy was assessed via receiver operating characteristic (ROC) curve analysis. Results. The bioinformatic analysis identified miR-126 and miR-223 present in ACS. miR-126-5p and miR-223-3p were significantly reduced in MVs from TIMI 0 patients compared to TIMI 3. ROC analysis showed high diagnostic accuracy for miR-126-5p (AUC = 0.918; 95% CI: 0.818-1.00; p = 0.001) and miR-223-3p (AUC = 1.00; 95% CI: 1.00-1.00; p < 0.001). Conclusions. Reduced levels of miR-126-5p and miR-223-3p in circulating MVs are strongly associated with impaired coronary flow, positioning these miRNAs as potential biomarkers for ACS risk stratification and therapeutic targeting.

Objectives: This retrospective study examines midkine, an inflammatory cytokine, as a potential serological biomarker to distinguish dilated cardiomyopathy (DCM) and inflammatory dilated cardiomyopathy (DCMi). Identifying such a biomarker is crucial for effective treatment of these two entities. Methods: The study included 54 patients with heart failure, reduced left ventricular systolic function, and suspected cardiac inflammation. Endomyocardial biopsies were obtained from all 54 patients to differentiate between DCM and DCMi. Blood sera were collected from these patients the same day the endomyocardial biopsy was performed and compared with those of 13 age-matched healthy individuals for different measurements such as midkine and NT-proBNP. Patients were followed up to a median of 194 days after the baseline visit. Results: Endomyocardial biopsies from patients with DCMi were associated with more infiltrating immune cells such as CD68⁺ macrophages and CD3⁺ T cells and a more frequent presence of a viral genome than those from patients with DCM. Both groups showed similar improvements in LV function and dimensions over time. MK serum levels were significantly higher in DCM/ DCMi patients than in healthy individuals but did not differ significantly between DCM and DCMi. MK levels did not significantly correlate with NYHA class, NT-proBNP, LVEDD, or LVEF, except for a weak correlation with LVEF at follow-up. Conclusions: Midkine serum levels were significantly higher in patients with a DCM phenotype and severely reduced systolic function. However, these levels could not distinguish between DCM and DCMi and showed no correlation with baseline or follow-up parameters. Therefore, midkine cannot be used as a biomarker to distinguish between DCM and DCMi.

Knee osteoarthritis (OA) is a chronic, progressive, inflammatory, and degenerative whole-joint disease. Early-stage OA treatments typically include physiotherapy, weight-loss, pain relief medications, and intra-articular knee injections, such as corticosteroids, hyaluronic acid, or platelet-rich plasma. These treatments primarily provide symptomatic relief rather than reversing or halting disease progression. Recently, mesenchymal stromal cell (MSC) injections have garnered attention due to their immunomodulatory and regenerative capacities. MSCs, which can be derived from sources such as bone marrow, umbilical cord, or adipose tissue, and can be allogeneic or autologous, have demonstrated promising results in both animal models and several human studies. However, different protocols have been employed, presenting challenges for comparing outcomes. In this review, we address these variable settings, evaluate current practices, and identify key factors critical in optimizing MSC-based therapies by critically reviewing clinical trials of ex vivo expanded MSC therapies for OA undertaken between 2008 and 2023. Specific attention was given to two key aspects: (1) the cell culture process employed in manufacturing of autologous or allogeneic MSC products, and (2) the post-culture methods employed in storage, reconstitution and administration of the MSCs. Our findings suggest that standardizing MSC production for clinical applications remains a significant challenge, primarily due to variations in tissue sources, harvesting techniques, and manufacturing protocols, and due to broad discrepancies in reporting. Thus, we propose a set of minimal reporting criteria to guide future clinical trials. A common reporting guideline is a critical step towards a more standardized MSC production across different laboratories and clinical settings, thereby enhancing reproducibility and advancing the field of regenerative medicine for knee OA, as well as other disease settings.

Background: Surface-enhanced Raman spectroscopy (SERS) analysis of urine is a promising liquid biopsy technique for cancer detection. However, its clinical translation is hindered by two major challenges that impact classification efficacy. First, the SERS signal of urine is confounded by fluctuations induced by physiological differences in urine composition such as pH and dilution. Second, the molecular origin of the SERS signal of urine is incompletely understood, limiting the interpretability of machine learning classifiers in terms of specific biochemical markers. Methods: In this pilot study, we analyzed urine samples from breast cancer patients (n = 18) and control subjects (n = 10) at three pH levels (5, 7, and 9). Additionally, we analyzed simulated urine mixtures consisting of uric acid, hypoxanthine, xanthine, and creatinine in physiological concentrations to explain the variation in the SERS spectra at different pH values. Results: Urine at pH 9 yielded the most detailed spectral features. The SERS spectral pattern under alkaline pH reflected greater contributions from hypoxanthine, uric acid, and creatinine, while xanthine contributions diminished due to competitive interactions at the SERS substrate surface. Normalizing SERS signals to the creatinine band at 1420 cm^-1 effectively mitigated the confounding effects of urine dilution. Conclusions: Optimizing the pH to 9 and normalizing to creatinine significantly enhances the interpretability and accuracy of SERS-based urine analysis for cancer detection. These findings offer important theoretical and practical advancements for the development of SERS-based liquid biopsy tools for cancer detection.

Obesity has become one of the most critical health crises of the modern era, affecting millions of individuals worldwide [...].

Post-traumatic stress disorder (PTSD), a mental disorder caused by exposure to traumatic stress, affects 5-10% of the world's population. There is some evidence that PTSD is associated with accelerated cellular aging, leading to an increased risk of medical and neurodegenerative comorbidities. Alterations in telomere length (TL) and telomerase enzyme activity have been proposed as biomarkers of this process. This hypothesis was seemingly confirmed in preliminary research, but more recent studies have yielded mixed results. The current narrative review was conducted to provide a critical synthesis of existing research on telomere length and telomerase in PTSD. Data from 26 clinical studies suggest that TL in PTSD is highly variable and may be influenced by methodological, demographic, trauma-related, and psychosocial factors. There is no evidence for altered telomerase activity in PTSD. In contrast, animal research suggests that exposure to traumatic stress does lead to TL shortening. Overall, it is likely that TL is not, by itself, a reliable biomarker of cellular aging in PTSD. Other markers of cellular senescence, such as epigenetic changes, may prove to be more specific in measuring this process in patients with PTSD.

After 70 years of clinical practice with antipsychotics in the treatment of some specific serious mental disorders, much information has been accumulated considering their efficiency as a first-line evidence-based schizophrenia therapy, but also on their adverse effects within the range from minor to life-threatening issues. In this paper, we highlight motor impairment as a frequent limiting factor. Despite the diversity of side effects following antipsychotics usage, many of those who suffer share the same pathophysiological background issues, such as oxidative damage, neuroinflammation, apoptosis, and neurodegeneration (observed in the brain regions involved in motor control). The obvious need to solve these limitations is facing restraints in clinical studies due to the ethical issues. Therefore, it seems reasonable to address the importance of preclinical investigations to overcome the adverse effects of antipsychotics. For that purpose, we analyzed the antipsychotics-induced dyskinesia seen in rodent models, with a special focus on attempts to highlight the benefits of antioxidant supplementation. Our analysis has revealed that antioxidant supplementation, with various antioxidant-rich compounds, confirms the clear neuroprotective effects of the therapy of this iatrogenic dyskinesia. Given their accessibility and safety, it seems that the administration of antioxidant-rich compounds in various forms, as an adjuvant therapy, may be beneficial in patients by lowering the risk of secondary Parkinsonism. Also, it seems that the strategy for further investigations in this field of preclinical studies should be standardized and should include more antipsychotics employed in the clinical practice.