Search Results (119,565)

Background: This study aimed to evaluate the effects of NP associated with LDD on balance, gait and foot pressure distribution. Methods: This prospective controlled study was conducted on 42 individuals aged between 40-70 years. There were 3 groups in the study: individuals diagnosed with NP associated with LDD (n=14), individuals with LDD without NP(n=14), and the control group (n=14). The Force Plate system and Core Balance System measured static and dynamic postural balance and stability limits. Gait and dynamic plantar pressure distribution analyses were performed with a computerized gait evaluation system. Results: The Leeds Assessment of Neuropathic Signs and Symptoms (LANSS), VAS during gait, and Oswestry Disability Index (ODI)scores were higher in LDD with NP group than in LDD without NP group (p<0. 05). It was found that LDD with NP group had backward dynamic balance control (p<0. 05). There was no significant difference in balance control, dynamic plantar pressure distribution, and spatiotemporal gait parameters between the groups (p>0. 05). Conclusion: Although participants with NP had higher levels of pain severity in gait and disability, there was no difference in postural balance, dynamic plantar pressure distribution, and spatiotemporal gait parameters compared to participants with LDD without NP and healthy individuals. All participants with LDD were unilaterally affected. Therefore, postural balance and gait tasks would be able to compensate for the unaffected limb. Full article

Background: Closing extraction spaces with clear aligners remains a significant biomechanical challenge, frequently involving difficulties in sagittal control, torque expression, and intra-arch anchorage. Although various sequential or phased retraction strategies exist, the Caterpillar Motion protocol has not yet been formally defined. This clinical report describes the Caterpillar Motion staging protocol and illustrates its application through representative extraction cases, rather than providing a systematic review or experimental comparison. Case Presentation: Two adult patients with extraction-based malocclusions were treated using the Caterpillar Motion staging protocol. Case 1 involved bimaxillary first-premolar extractions with maximum anchorage requirements and periodontal limitations in the mandibular incisors. Case 2 presented as a full Class II malocclusion requiring maxillary first-premolar extractions with moderate anchorage for sagittal camouflage. In both cases, tooth movement was organized into alternating functional groups, with waves limited to 2 mm of sagittal closure. Discussion: The Caterpillar Motion protocol reduces the risk of aligner bowing effect, increases effective crown engagement, and redistributes anchorage demands by preventing simultaneous shortening of both arch extremities. Both cases demonstrated controlled anterior retraction, stable posterior anchorage, and favorable root parallelism. Conclusions: Caterpillar Motion offers a biomechanically coherent and clinically reproducible staging strategy for clear aligner extraction therapy. Further controlled studies are needed to validate its advantages over traditional linear and en-masse protocols. Full article

Background: The long-term cardiovascular safety of high-dose intravenous mesenchymal stem cell (MSC) therapy remains insufficiently characterized in real-world clinical settings. Methods: We conducted a single-center retrospective observational study of patients who received high-dose intravenous MSC therapy. Cardiovascular events were identified through follow-up records. Observed event incidence was compared descriptively with age-adjusted population reference data. Statistical analyses were performed using two-sided Poisson methods. Results: Among treated patients, a total of four cardiovascular events were recorded during follow-up. The observed incidence did not demonstrate an excess signal compared with reference population data. No clustering of events was observed in the early post-infusion period. Sensitivity analyses yielded consistent findings. Conclusions: In this real-world cohort, high-dose intravenous MSC therapy was not associated with an apparent increase in cardiovascular event incidence. Given the observational design and limited event number, larger prospective studies are warranted to further characterize long-term cardiovascular safety. Full article

Healing skin wounds is still difficult in many clinical situations, especially when the wounds are chronic or infected. These wounds often stay inflamed for long periods, and the risk of bacterial invasion is high. Oxidative stress tends to increase as well, while the formation of new blood vessels is often inadequate. Because of these factors, wound repair depends on the proper coordination of several biological events. These include basic antimicrobial activities, the control and resolution of inflammation, protection against oxidative damage, the rebuilding of collagen structures, and the development of new vascular networks. Traditional Chinese Medicine (TCM) provides many active compounds. These compounds work on many targets and through different pathways. They show good potential in wound treatment. But many TCM compounds have poor solubility in water. They are also unstable, have low bioavailability, and do not pass through the skin easily. These problems limit their use in clinical settings. Nanotechnology offers new ways to solve these problems. Nanodelivery systems can improve the solubility and stability of active compounds. They can also help the compounds enter the skin and stay in the wound area. Many types of nanocarriers have been developed, such as liposomes, polymer nanoparticles, nanogels, and inorganic nanomaterials. These systems can also provide controlled release or release that responds to the wound environment. This can make the treatment more accurate. In this review, we summarize how major TCM-derived compounds support wound repair and describe the biological mechanisms behind their effects. We also discuss recent nanodelivery approaches that aim to strengthen these therapeutic actions. These combinations can improve antibacterial performance, shape the immune response, reduce reactive oxygen species, and help the skin close more quickly. We also point out several challenges, such as concerns about material safety, the need for more consistent herbal extraction methods, gaps in mechanistic understanding, and the difficulty of producing these formulations on a large scale. Taken together, these points suggest that nanodelivery approaches using TCM-derived compounds still need more careful study and steady improvement before they can be used more widely in wound care. Full article

This review evaluates the emerging role of circulating tumour cells (CTCs) as clinically meaningful, minimally invasive biomarkers for oral squamous cell carcinoma (OSCC). Despite advances in management, OSCC continues to demonstrate high morbidity and mortality, largely due to late diagnosis and the absence of validated biomarkers for early detection or real-time monitoring. Conventional diagnostic tools, tissue biopsy, and imaging provide only static snapshots and fail to capture tumour heterogeneity or evolving biological behaviour. CTCs offer a novel and significant opportunity to address these limitations. Key findings from recent studies highlight that CTC enumeration correlates with tumour burden, nodal metastasis, recurrence, and overall prognosis. Molecular and phenotypic characterisation further reveals dynamic traits such as epithelial–mesenchymal transition, stemness, and therapy resistance, providing insights into metastatic potential and treatment failure. Technological advances, including immunocytochemistry, microfluidic capture platforms, PCR-based assays, and next-generation sequencing, have enhanced the sensitivity and specificity of CTC detection and enabled detailed multi-omic profiling. Collectively, evidence suggests that integrating CTC analysis into OSCC clinical workflows could improve early detection, refine risk stratification, personalise therapeutic strategies, and support longitudinal monitoring of disease dynamics. As research progresses, CTC-based diagnostics represent a promising frontier in shifting OSCC management toward more precise, adaptive, and biologically informed care. Full article

Herein, we have identified the polyfunctionalized 1-(phenylsulfonyl)-1H-indole-2-carboxylic acid derivative MTP150 for the treatment of neurodegenerative diseases owing to its efficacy in reducing protein aggregation, modulating matrix metalloproteinase activity, mitigating neuroinflammation, and enhancing DNA damage repair pathways across in vivo Caenorhabditis elegans models of Alzheimer’s disease, Parkinson’s disease (PD), and Huntington’s disease. Further experiments in an in vivo Drosophila model of PD showed that MTP150 increased motor performance, reduced oxidative stress levels, and restored mitochondrial function in model flies. In addition, MTP150 exhibited neuroprotective effects in PD model cells, thereby supporting its therapeutic potential for this disease. Full article

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a clinically significant side effect related to antiresorptive therapies, such as denosumab and bisphosphonates. MRONJ may develop following oral surgical procedures or spontaneously. Although the pathophysiological processes underlying MRONJ are not well clarified, infections, commonly occurring after oral surgery, seem to have an important contribution in its development. Consequently, the role of the oral microbiota warrants investigation. This study investigates the possible contribution of the salivary microbiota to the onset of osteonecrosis in subjects treated with zoledronate or denosumab. Methods: Three groups of subjects were analyzed: patients treated with zoledronate or denosumab who had developed MRONJ (cases); those who did not (controls) and healthy subjects. Oral microbioma was evaluated through next-generation sequencing. Results: A total of 55 individuals were enrolled: 16 healthy subjects (29.1%), 21 controls (38.2%), and 18 cases (32.7%). Differences in the abundance of certain bacterial taxa were observed both among the three groups and in pairwise comparisons. Furthermore, a cut-off value of 5.51% for Streptococcus spp. was identified as being associated with the development of MRONJ. Conclusions: For the first time, this preliminary study highlights differences in the salivary microbiota among healthy subjects, controls, and cases, suggesting a potential cut-off value for Streptococcus spp. Despite the limited sample size, these findings provide initial insights. Further studies in larger cohorts are warranted. Full article

Viral hemorrhagic fevers (VHFs) comprise a heterogeneous group of severe infectious diseases that continue to represent a major global health concern. Although many VHFs remain endemic to regions of Africa, Asia, and the Americas, their wide geographic distribution, together with increasing international travel and global trade, facilitates the importation of cases into non-endemic areas and raises the risk of secondary transmission under favorable ecological and epidemiological conditions. These infections are frequently associated with high case-fatality rates and impose a substantial social and economic burden, including pressure on healthcare systems, disruption of essential services, and long-term physical and psychological sequelae among survivors. Despite notable advances in recent years, therapeutic options for VHFs remain limited. Supportive care continues to represent the cornerstone of clinical management for most infections, while pathogen-targeted therapies are available only for a restricted number of diseases. Monoclonal antibody-based therapies have achieved the most significant regulatory success to date, particularly for Ebola virus disease. In parallel, several small-molecule antivirals have been investigated in preclinical and clinical settings, including during outbreak responses, although inconsistent efficacy and safety concerns have limited widespread approval. Vaccine development has progressed further, with licensed vaccines available for selected VHFs, including Ebola, yellow fever, and dengue, and multiple candidates based on diverse technological platforms advancing through clinical evaluation. In addition to summarizing current therapeutic and vaccine strategies, this review highlights pharmaceutical development considerations relevant to biologic therapeutics and selected vaccine platforms, including formulation stability, pharmacokinetic behavior, delivery routes, storage requirements, and logistical constraints affecting deployment during outbreak responses. Using a comparative cross-pathogen framework, the review synthesizes recent literature to identify translational gaps, regulatory challenges, and future priorities for the development of safer and more effective medical countermeasures against VHFs. Full article

Raman spectroscopy offers unique molecular fingerprinting capability for cancer diagnosis and monitoring, yet its biomedical application is fundamentally limited by weak intrinsic signals and complex biological backgrounds. Composite Raman probes, particularly surface-enhanced Raman scattering (SERS)—based systems, overcome these limitations through synergistic electromagnetic and chemical enhancement combined with functional integration. By engineering plasmonic nanostructures, interfacial electronic states, and molecular architectures, composite Raman probes achieve synergistic electromagnetic and chemical enhancement while incorporating biorecognition units, reporter molecules, and protective coatings to improve stability, specificity, and biocompatibility. In recent years, these probes have evolved from simple signal tags into multifunctional platforms capable of ultrasensitive tumor biomarker detection, high-contrast imaging, surgical guidance, therapy monitoring, and dynamic analysis of the tumor microenvironment (TME). This review systematically summarizes recent advances in composite Raman probes for oncological applications, with an emphasis on material design strategies, enhancement mechanisms, and stimulus-responsive regulation. Representative applications at both molecular and tissue levels are highlighted, including nucleic acid, protein, and exosome detection, as well as in vivo imaging and microenvironmental sensing. Finally, current challenges and future perspectives toward clinical translation are discussed, aiming to provide guidance for the rational design of next-generation Raman probes for precision oncology. Full article

Infective endocarditis (IE) is a severe infectious disease affecting cardiac valves (either native or prosthetic) or implantable cardiac devices, and it is associated with high rates of morbidity and mortality. Recent data from the Global Burden of Disease study have shown a significant increase in both the incidence and mortality of IE. One-year mortality following diagnosis can reach up to 30%. IE can present with a wide range of clinical manifestations, and its course may be complicated by systemic embolic events or intracardiac complications such as abscess formation or prosthetic valve dehiscence. Echocardiography remains the first-line imaging modality; however, an integrated multimodality imaging approach is increasingly adopted in contemporary practice, incorporating both cardiac computed tomography and positron emission tomography. A multidisciplinary approach involving cardiologists, cardiac surgeons, internists, infectious disease specialists, and nuclear medicine physicians is often required to ensure accurate diagnosis and effective treatment of IE. The prognosis of infective endocarditis depends on early diagnosis, appropriate antimicrobial therapy, and timely surgical intervention when indicated. This review aims to summarize the current knowledge on IE, from pathophysiological insights to surgical strategies. It also focuses on practical recommendations to address the most pressing unmet clinical needs through a multidisciplinary approach. Full article

Acute coronary syndromes (ACS) are a major cause of mortality worldwide, and although interventional treatment has significantly improved mortality and morbidity related to ischemic heart disease, there is constant concern about optimizing drug treatment. In this regard, multiple studies have been conducted on inflammation in myocardial infarction (MI), starting from its implications in the atherosclerosis process. The aim of this review is to analyse the current evidence related to the subject and the correlation between the inflammatory state at presentation and the prognosis of patients with MI, identifying key points, possible therapeutic limitations, and future research directions. Both innate and acquired immune components are involved in the inflammatory cascade, with an increase in inflammatory cell and cytokine levels. To analyse the degree of inflammation and determine when it is excessive, numerous inflammatory markers have been studied, from acute phase proteins such as high-sensitivity C-reactive protein (hsCRP) and fibrinogen, to the ratios between inflammatory cells and interleukins involved in the main inflammatory pathways. Their association with post-infarction mortality and morbidity has been observed, but they must be integrated into the clinical context for the selection of patients who would benefit most from their reduction. New anti-inflammatory therapies are being studied in light of these findings, and progress is expected. Early trials with non-selective anti-inflammatory drugs have highlighted the importance of selective inhibition so as not to disrupt healing, and drugs are now being studied that target specific pathways that are exacerbated in infarction and lead to excessive remodelling. Several inflammatory pathways have been investigated but the results are inconclusive in terms of improving prognosis, requiring further studies to formulate future therapeutic indications. Full article

Skin and hair follicles regenerate through coordinated stem cell niches and cyclic signaling associated with transitions among anagen, catagen, and telogen phases. In alopecia and chronic skin diseases, follicular miniaturization, immune dysregulation, persistent inflammation, impaired vascularization, and a compromised stratum corneum barrier limit the effectiveness of conventional topical and systemic therapies. Bio-nanovesicles (BNVs), including natural extracellular vesicles such as exosomes and microvesicles, as well as engineered artificial or hybrid nanovesicles, offer a targeted, cell-free delivery platform for miRNAs, proteins, and growth factors. By modulating key pathways—Wnt/β-catenin, PI3K/AKT, MAPK/ERK, and TGF-β/BMP—BNVs have the potential to restore regenerative crosstalk, enhance angiogenesis, and help initiate hair and skin repair. Full article

Background: Breast cancer (BC) is one of the most diagnosed malignancies and a leading cause of cancer-related mortality among women worldwide, thereby posing a substantial threat to women’s health worldwide. However, clinically robust diagnostic biomarkers with high sensitivity and specificity, as well as well-validated molecular targets for targeted therapy, remain limited. Methods: BC transcriptomic data from seven GEO datasets and the TCGA-BRCA cohort (n = 1231) were integrated for analysis. After batch-effect correction, candidate genes were screened through DEA, WGCNA, and PPI networks analysis. An ensemble machine learning (ML) framework incorporating 127 algorithmic combinations was constructed, and SHAP analysis was applied to identify hub genes. Further analyses included functional enrichment, immune infiltration, miRNA regulatory network analysis, and SMR analysis. The expression patterns were validated using single-cell transcriptome data. Drug repositioning analysis and AI-assisted virtual screening were performed to prioritize compounds with favorable drug-like properties. The predicted binding modes of candidate compounds with CHEK1 were assessed by molecular docking. Results: Thirty core genes were obtained through differential expression, WGCNA, and PPI screening. Integrated ML (127 algorithms) determined the optimal model (AUC = 0.919), and SHAP identified nine feature genes, among which CHEK1 and KIF23 showed preliminary diagnostic potential across four external cohorts (AUC: 0.625–0.938). Functional enrichment indicated that both are enriched in the cell cycle and p53 pathways, closely associated with BRCA1/ATR; immune infiltration revealed significant correlations with macrophages and CD8⁺ T cells, with hsa-miR-15a-5p and hsa-miR-607 being common upstream regulatory miRNAs. SMR analysis supported a causal relationship between CHEK1 expression and BC genetic susceptibility (p_SMR < 0.05, p_HEIDI > 0.05); single-cell analysis confirms its heterogeneous expression. AI-assisted virtual screening identified 25 A-grade computational candidate compounds from 171 candidates. Molecular docking suggested that Olaparib and LY294002 can form favorable interactions with the CHEK1 active pocket. Conclusions: The study identified CHEK1 as a key diagnostic gene for BC through 127 ML algorithms and SMR causal inference. By combining AI-assisted virtual screening and molecular docking, computational candidate compounds targeting CHEK1 were prioritized. These findings represent hypothesis-generating in silico predictions and require experimental validation before any therapeutic conclusions can be drawn. Full article

Background: Non-invasive intrauterine resuscitation measures, such as maternal repositioning and intravenous fluid therapy, are used in the presence of suspicious or pathological cardiotocographic (CTG) patterns during labor. However, evidence regarding their link with CTG abnormalities, amniotic fluid color, and immediate neonatal outcomes is limited. Objectives: To analyze the link between maternal repositioning and intravenous fluid therapy and the occurrence of suspicious or pathological intrapartum CTG patterns, as well as their relationship with amniotic fluid color and immediate neonatal effects. Methods: An analytical, observational, prospective study was conducted in women in labor with continuous monitoring. Changes in maternal position, administration of intravenous fluid therapy, CTG patterns, amniotic fluid color, and immediate neonatal outcomes were analyzed. Links were evaluated using appropriate statistical tests, considering maternal positions in isolation and in combination. Results: Maternal repositioning, both alone and in combination, was associated with the presence of suspicious or pathological CTG and with statistically significant differences in the 5 min Apgar score when analyzed as a continuous variable. No significant association was observed between intravenous fluid therapy and CTG patterns or neonatal outcomes. The presence of meconium-stained amniotic fluid was associated with a higher frequency of suspicious or pathological CTG. Conclusions: Maternal repositioning was most frequently applied as a clinical response to a suspicious CTG. Intravenous fluid therapy showed no link with CTG abnormalities or adverse neonatal outcomes. These findings reinforce the need to interpret intrapartum CTG in an integrated manner with the overall clinical context and support the use of maternal repositioning as a non-invasive measure in intrapartum management. Full article