Search Results (46,024)

Background: Lattice Radiotherapy (LRT), a spatially fractionated stereotactic radiotherapy (SBRT) technique, has shown promising results in the palliative treatment of large tumors. The focus of our first analysis of 56 lesions >/=7cm was on the extent of shrinkage following palliative LRT (mean 50%) and assessment of its effect duration (: mean 6 months). Herewith we present an updated analysis of our single-center LRT cohort, with a focus on LRT outcome across diagnoses and applied LRT regimens. Methods: We assessed the clinical outcome following LRT in 66 patients treated for 81 lesions between 01.2022 and 05.2025. LRT protocols included simultaneous integrated boost (sib-) LRT in 49 lesions (5 × 4–5 Gy to the entire mass with sib of 9–13 Gy to lattice vertices). Alternatively mainly in pre-irradiated and/or very large lesions—a single-fraction stereotactic LRT (SBRT-LRT) of 1 × 20 Gy to vertices only was delivered to 26 lesions. In six cases with modest response to single fraction SBRT-LRT, the sib-LRT schedule was added 4–8 weeks later. Results: The median age was 68 years (18–93). Main tumor locations were abdomino-pelvic (n = 34) and thoracic (n = 17). Histopathological diagnoses included carcinoma (n = 34), sarcoma (n = 31), and melanoma (n = 16). 31% of all lesions have been previously irradiated. 73% of cases underwent concurrent or peri-LRT systemic therapy. The mean/median overall survival (OS) time of the cohort was 7.6/4.6 months (0.4–40.2), 11.9/5.8 months in 16/66 alive, and 6.4/4.3 months in deceased patients, respectively. 82% of symptomatic patients reported immediate subjective improvement (PROM), with a lifelong response duration in most cases. Progressive disease (PD: >10% increase in initial volume) was found in 9%, stable disease (SD +/−10% of initial volume) in 19% of scanned lesions, and shrinkage (>10% reduction in initial volume) in 75%, with a mean/median tumor volume reduction of 51/60%. The extent of shrinkage was found to be 11–30%/31–60%/61–100% in 38/24/38% of lesions. Response rates (PD, SD, shrinkage) following the two applied LRT regimens, as well as those related to sarcoma and carcinoma diagnoses, were found to be comparable. Treatment tolerance was excellent (G0-1). Conclusions: Palliative LRT provides rapid subjective relief in ~80% of symptomatic patients. Radiologic shrinkage was stated in 75% of FU-scanned lesions, with a lifelong effect duration in most patients. LRT was found effective across histologies, with a similar extent of shrinkage in carcinoma and sarcoma following 1F SBRT- and 5F sib-LRT regimens, respectively. Full article

Matrix metalloproteinases (MMPs) are a major group of proteases known to regulate the turnover of the extracellular matrix (ECM). We observed that induced MMP-12 promotes eosinophilic inflammation-related epithelial cell mesenchymal transition (EMT), bronchial fibrosis, and airway obstruction in an allergen-exposed mouse model of chronic airway diseases in allergen-exposed mice and in airway-specific CC10-IL-13-overexpressed mice. Our histological analysis showed that the parabronchial and perivascular accumulation of eosinophils, fibroblasts, and collagen is significantly decreased in MMP-12^−/− allergen-exposed mice and airway-specific rtTA-MMP-12^−/−CC-10-IL-13-overexpressed mice compared to allergen-exposed wild-type mice and rtTA-CC10-IL-13-overexpressed mice. ELISA and Western blot analyses validated these histological findings, demonstrating that EMT and profibrotic protein levels were significantly decreased in allergen-challenged MMP-12^−/− mice and rtTA-MMP-12^−/−CC10-IL-13-overexpressed mice in comparison to the allergen-exposed wild-type mice and rtTA-CC10-IL-13-overexpressed mice. In addition, we also observed that allergen-challenged MMP-12^−/− mice have improved resistance and compliance compared to allergen-challenged wild-type mice. Most importantly, we show that treatment with MMP-12 inhibitors (PF-00356231 and MMP408) restricts the induction and progression of bronchial fibrosis and airway restrictions in allergen-exposed mice and airway-specific rtTA-CC10-IL-13 mice compared to the respective control mice. Taken together, the novelty of these findings lie in the fact that induced MMP-12 regulates eosinophilic inflammation-induced bronchial fibrosis and associated airway restriction, which may be reduced by treatment with MMP-12 inhibitors. Full article

Strongyloidosis is a parasitic disease caused by Strongyloides stercoralis, a nematode with a complex life cycle that facilitates long-term persistence within the host. The infection affects millions of people in tropical and subtropical regions and poses a particular challenge in immunocompromised individuals. Although conventional treatments, such as ivermectin and albendazole, are generally effective, emerging concerns regarding drug resistance and adverse effects have prompted the search for alternative therapeutic options. In this context, natural products—including plant extracts, bioactive phytochemicals, and nanoparticle-based formulations derived from natural sources—are emerging as promising anti-Strongyloides potential. This review summarizes recent studies on natural products with anthelmintic activity against strongyloidiasis, with emphasis on their mechanisms of action, efficacy, and future perspectives. A systematic search of the literature was conducted using terms related to Strongyloides, plant species, extracts, and bioactive compounds with nematocidal activity. Eligible studies included those reporting the activity of plants, plant extracts, and their purified metabolites against Strongyloides spp. Data were compiled into a comprehensive table including year of publication, author, plant species, active principle, application conditions, and target nematode species. The pharmacological treatment of this parasite varies according to its life cycle stage. Various biomolecules, phytoactive compounds, and novel plant-based formulations have demonstrated promising activity and may be considered both for treatment and for inclusion in control programs for strongyloidiasis. This review highlights medicinal plants and phytochemicals with ethnopharmacological background and experimentally validated activity against Strongyloides spp., integrating evidence from in vitro, in vivo, and experimental models, as well as clinical trials. Full article

Since 2007, white-nose syndrome (WNS), caused by the fungus Pseudogymnoascus destructans, has killed millions of bats across North America by disrupting hibernation cycles, causing premature fat depletion and starvation. Little brown bats (Myotis lucifugus) from some populations persisting after WNS store larger pre-hibernation fat reserves than bats did before WNS, which may help bats survive winter starvation and mount an immune response to Pd in spring. MicroRNAs (miRNAs) are highly conserved, small, non-coding RNA molecules that regulate gene expression post-transcriptionally. Aberrant miRNA expression can affect metabolic pathways in mammals and has been linked to various diseases. If fat reserves and immune mechanisms influence survival from WNS, then miRNAs regulating metabolic and immune-related genes might affect WNS pathogenesis and bat survival. A previous study identified 43 miRNAs differentially expressed in bats with WNS. We analyzed these miRNAs for their roles in metabolism and immune-related pathways, using DIANA Tools and KEGG analysis, to determine a subset that could serve as biomarkers of pathophysiology or survival in WNS-affected bats. We identified miR-543, miR-27a, miR-92b, and miR-328 as particularly important because they regulate multiple pathways likely important for WNS (i.e., immune response, lipogenesis, insulin signaling, and FOXO signaling). As proof-of-concept, we used reverse transcription quantitative real-time PCR (RT-qPCR) to quantify the prevalence of these miRNAs in plasma samples of bats (n = 11) collected from a post-WNS population during fall fattening. All the selected miRNAs were detectable in at least some bats during fall fattening although prevalence varied among miRNAs. Future in vivo validation studies would help confirm functional roles and biomarker utility of these miRNAs for WNS-affected bats. Full article

Background: Children with inflammatory bowel disease (IBD) are at heightened risk for vaccine-preventable infections because of underlying immune dysregulation and long-term immunosuppressive therapy. Despite published guidelines affirming vaccine safety, real-world coverage remains suboptimal. It is a pilot, single-country survey designed to explore baseline knowledge and practices regarding vaccination in paediatric IBD within a specific local healthcare context. Objective: The objective of this study is to evaluate the knowledge, attitudes, and practices of paediatric gastroenterologists (PGs) regarding the immunisation of children with IBD. Methods: We conducted an exploratory pilot, cross-sectional survey of paediatric gastroenterologists in Russia, focusing on immunisation knowledge and practical barriers in routine care. A cross-sectional, anonymous online survey was distributed to PGs nationwide between January 2022 and April 2022. The online questionnaire explored demographic characteristics, awareness of international recommendations, perceptions of vaccine safety at various disease and treatment stages, and routine vaccination practices. Responses were analysed with non-parametric statistics (α = 0.05). In a parallel prospective cohort, the vaccination certificates of 98 paediatric IBD patients (January 2022–April 2023) were audited to quantify real-world coverage. Results: Fifty-one PGs completed the survey. Forty-one per cent agreed that vaccines do not provoke IBD flares, while 17.6% considered live vaccines acceptable during immunosuppressive remission. Nearly one-third (32%) did not personally oversee immunisation, and 18% occasionally discouraged vaccination during therapy. Only 35.3% deemed baseline serology essential before starting immunosuppression; 46.5% supported antibody checks immediately prior to vaccination. The certificate audit revealed a full schedule completion rate of 66.3% for measles–mumps–rubella and 74.2% for hepatitis B, contrasting with parental reports of 82.3% complete coverage. Conclusions: Knowledge gaps, limited guideline awareness, and parental concerns contribute to suboptimal vaccination of paediatric IBD patients. Targeted educational initiatives, clearer shared-care pathways, and routine certificate audits are needed to close the coverage gap and reduce infection-related morbidity. Findings are hypothesis-generating and reflect local practice; as a pilot study, results should be interpreted with caution and may not generalise beyond similar settings. Full article

Background: High-sensitivity cardiac troponin T serum concentration (hs-cTnT) measurement is a well-established tool in the diagnosis of acute cardiovascular (CV) disease. It remains unclear whether resting hs-cTnT could be useful for screening the status of the CV system. The purpose of this study was to compare the correlation between hs-cTnT, determined in patients without clinical symptoms of acute illness, and selected parameters of subclinical CV dysfunction in relation to the coexistence of arterial hypertension (AH). Methods: In total, 101 patients were included in the analysis. The following methods were used to assess the CV system: transthoracic echocardiography, Doppler ultrasonography of the carotid and lower extremity arteries with intima–media thickness (IMT) measurement, pulse wave velocity (PWV), central blood pressure measurement, ankle–brachial index (ABI), and toe–brachial index (TBI). Results: In patients with AH, significant correlations were found between hs-cTnT and maximal velocity of tricuspid regurgitation (R = 0.397; p = 0.003), left atrium volume index (LAVI) (R = 0.39; p = 0.002), and IMT in carotid arteries (cIMT) (R = 0.4; p = 0.001), common femoral arteries (cfIMT) (R = 0.384; p = 0.004), and superficial femoral arteries (sfIMT) (R = 0.352; p = 0.01), as well as PWV (R = 0.63; p < 0.001), central systolic blood pressure (cSBP) (R = 0.34; p = 0.006), central pulse pressure (cPP) (R = 0.354; p = 0.004), and ankle–brachial index (ABI) (R = −0.28; p = 0.024). In multivariate analysis, the relationship between subclinical CV dysfunction and hs-cTnT remained significant for LAVI, cSBP, cPP, and ABI, as well as showing borderline significance for sfIMT. In patients without AH, only the relationship between hs-cTnT and ABI was significant. According to interaction analysis, AH significantly influenced the relationship between hs-cTnT and cSBP, cPP, and sfIMT. Conclusions: Resting hs-cTnT correlates significantly with selected parameters of subclinical CV dysfunction in patients with AH. This relationship is clearly weaker in patients without AH. Further research is needed, especially prospective studies on a larger group of patients. Full article

The aim of this study was to evaluate whether combined administration of olive leaf extract (OLE) with standard antifungal therapy—nystatin (NYS) or miconazole (MIC) could be a more efficient alternative in reducing the number of Candida colonies, the presence of oral signs and symptoms and changes in salivary IL-17A level compared to standard therapy alone. The study included 59 subjects with a positive microbiological Candida colony number greater than 600 CFU/mL and at least one oral sign or symptom present. Subjects were randomly divided into four groups depending on applied therapy: OLE + NYS group (n = 15), OLE + MIC group (n = 15), NYS group (n = 14), MIC group (n = 15). Therapy duration and clinical monitoring were standardized across all groups. There was no significant difference between the tested groups in Candida spp. colony number or salivary IL-17A levels. In the OLE + NYS group, a significant increase in salivation rate was observed, while a significant decrease in tongue burning was reported in the OLE + MIC group. A significant reduction in burning of the oral mucosa and tongue was observed in the MIC group. No significant differences were found in other clinical signs or symptoms among treatment groups. OLE, as an adjunct to standard antifungal therapy, did not significantly reduce Candida spp. colony number or salivary IL-17A levels. However, in combination with NYS it increased salivation rate, while in combination with miconazole, it significantly decreased tongue burning. Both symptoms are common clinical findings in oral Candida-related disease and suggest that OLE may have supportive potential in the clinical management of these conditions. Further research is needed to explore its potential therapeutic benefits on oral health. Full article

The therapeutic landscape of adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is undergoing a paradigm shift, driven by the development of immunotherapy-based “chemo-free” and “chemo-light’ regimens. These strategies aim to achieve high efficacy with reduced toxicity, particularly in older adults who may not tolerate intensive chemotherapy. In Philadelphia chromosome-positive (Ph+) BCP-ALL, the incorporation of ABL tyrosine kinase inhibitors (TKIs) with blinatumomab (CD3/CD19 bispecific T-cell engager) has shown remarkable efficacy, with some studies reporting molecular response rates in the range of 90–100% and long-term survival exceeding 80% without the need for intensive chemotherapy or allogeneic hematopoietic cell transplantation (allo-HCT). In Philadelphia-negative (Ph−) BCP- ALL, an immunotherapy-based combination of blinatumomab and inotuzumab ozogamicin (anti-CD22 antibody-drug conjugate) has demonstrated high rates of complete remission and measurable residual disease (MRD) negativity, with manageable toxicity. While chimeric antigen receptor (CAR) T-cell therapy remains a transformative option for relapsed/refractory B-ALL, its integration into frontline treatment is still under investigation. Ongoing trials are evaluating the optimal sequencing and combinations of these agents and their potential to obviate the need for chemotherapy and/or allo-HCT in selected patients. As evidence continues to accumulate, chemo-free and chemo-light regimens, incorporating minimal chemotherapy with targeted agents to balance efficacy and reduced toxicity, are poised to redefine the standard of care for adults BCP-ALL, offering the possibility of durable remissions with reduced treatment-related morbidity. Full article

Background: Autoimmune diseases and other immune-mediated disorders are associated with an increased risk of malignancy, influenced by chronic inflammation, immune dysregulation, and treatment-related factors. Clarifying cancer risk patterns across specific conditions is essential to improve clinical vigilance and inform screening practices. Objective: The aim of this study was to synthesise current evidence on the association between autoimmune and immune-mediated diseases and cancer, with a focus on practical implications for clinicians. Methods: Recent cohort studies, meta-analyses, and expert consensus documents were analysed to describe cancer epidemiology, pathogenic mechanisms, high-risk phenotypes, and treatment considerations across major autoimmune diseases and other immune-mediated conditions. The review covers idiopathic inflammatory myopathies, Sjögren’s syndrome, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, ANCA-associated vasculitis, giant cell arteritis, polymyalgia rheumatica, sarcoidosis, mixed connective tissue disease, IgG4-related disease, VEXAS syndrome, and eosinophilic fasciitis. Special attention was given to identifying warning features for underlying malignancy and evaluating cancer screening strategies. Results: The magnitude and distribution of cancer risk vary across diseases. In some conditions such as dermatomyositis, systemic sclerosis or Sjögren’s syndrome, increased risk is well established, particularly for haematological and certain solid tumours. However, tumour patterns may differ across populations, and findings are not always consistent. Distinct clinical and serological features help stratify individual cancer risk and may guide the intensity of screening. The first years after disease onset often represent a window of higher vulnerability, during which intensified surveillance may be warranted in selected patients. Conclusions: Cancer risk in autoimmune diseases should be assessed on an individual basis. Awareness of disease-specific risk factors and clinical warning signs supports early recognition of malignancy and informs screening decisions in routine practice. Full article

Obesity represents a significant global public health challenge, which not only elevates the risk of mortality but also increases the likelihood of chronic diseases. The ongoing obesity epidemic has led to a growing recognition of the detrimental effects of excessive adipose tissue accumulation on male reproductive health. Substantial evidence indicates that obesity adversely affects sperm quality, thereby impairing male fertility. Specifically, obesity is associated with compromised spermatogenesis, erectile dysfunction, and detrimental effects on offspring fertility parameters. These effects are mediated through various mechanisms, including alterations in the hypothalamic–pituitary–gonadal axis, inflammation within the reproductive system, localized caloric excess in reproductive tissues, epigenetic modifications, disruptions in gut microbiota, and heightened oxidative stress levels. While the molecular alterations associated with obesity have been extensively documented, the precise mechanisms by which obesity influences male reproductive function remain inadequately understood. This article aimed to review the classification and distribution of adipose tissue in obesity, the impact of obesity on male fertility, and the potential mechanisms through which obesity affects male reproductive health, thereby offering insights into the prevention and treatment of obesity-related male fertility issues. Full article

Introduction. Chronic pain (CP) is a multidimensional condition that exerts a considerable impact on individuals’ quality of life and presents a wide range of clinical and psychological expressions. This study sought, firstly, to identify distinct clinical profiles among individuals with CP based on clinical indicators, and secondly, to examine the differences in psychological vulnerability and pain-related coping strategies according to the clinical profiles. Methods. A total of 251 adults diagnosed with CP and residing in Spain participated in the study. Participants completed the Purpose in Life Test, the Reflective Functioning Questionnaire, the Interpersonal Needs Questionnaire, the Beck Hopelessness Scale, the Difficulties in Emotion Regulation Scale, and the Pain Coping Questionnaire. A two-step cluster analysis was performed to identify subgroups within the sample, followed by independent samples t-tests to assess psychological differences between clusters. Results. This study identified two clinical profiles among individuals with CP, distinguished by diagnostic delay, disease progression, and functional impact. Cluster 1 exhibited greater functional impairment, lower quality of life, and higher emotional distress (uncertainty, perceived burdensomeness, emotional dysregulation, and hopelessness). In contrast, Cluster 2 showed lower functional impairment, better quality of life, greater use of distraction strategies, and a higher meaning in life. Discussion. These findings suggest that both medical and psychological aspects appear to be associated with each other and may influence the perception, evolution and adaptation to CP. Full article

Survivin, a pivotal member of the inhibitor of apoptosis proteins (IAP) family, plays critical roles in cell cycle regulation and division. Survivin is overexpressed in most malignancies, making it an attractive therapeutic target. Due to its high specificity and potency, siRNA-based RNA interference (RNAi) has emerged as a powerful therapeutic strategy for effectively downregulating disease-related genes such as survivin in cancer therapy. However, naked siRNA suffers from rapid enzymatic degradation, poor cellular uptake, and off-target effects, severely limiting its therapeutic efficacy in vivo. Development of polymer-based nanocarriers for tumor-targeted delivery of survivin siRNA (siSurvivin) holds great potential to address these challenges. In this review, we first described the structure and function of survivin and summarized the survivin-targeted therapeutic strategy. Then, the siRNA delivery systems, particularly the polymeric nanocarriers, were introduced. Furthermore, a plethora of polymer-based nanocarriers for tumor-targeted siSurvivin delivery, including synthetic polymers (branched polymers, dendritic polymers, polymeric micelles), natural polymers (polysaccharides, proteins, and others), lipid-polymer hybrid nanoparticles, and polymer composite nanoparticles, were elaborated. Promising results underscore the potential of polymer-based nanocarriers for survivin siRNA delivery to enhance cancer therapy, providing a roadmap for future clinical translation. Full article

Background/Objectives: Diabetes mellitus (DM) is an increasingly prevalent endocrine disorder affecting humans and companion animals. Type 1 DM (T1DM) and type 2 DM (T2DM) are well characterized in humans, and canine DM most often resembles T1DM, marked by insulin dependence and β-cell destruction. Conversely, feline DM shares key features with human T2DM, including insulin resistance, obesity-related inflammation, and islet amyloidosis. This review provides a comprehensive comparative analysis of antidiabetic therapies in humans, dogs, and cats, focusing on three core areas: disease pathophysiology, pharmacological and delivery strategies, and translational implications. In human medicine, a wide array of insulin analogs, oral hypoglycemic agents, and incretin-based therapies, including glucagon-like peptide-1 receptor agonists (liraglutide) and sodium-glucose cotransporter-2 inhibitors (empagliflozin), are available. Veterinary treatments remain limited to species-adapted insulin formulations and off-label use of human drugs. Interspecies differences in gastrointestinal physiology, drug metabolism, and behavioral compliance influence therapeutic efficacy and pharmacokinetics. Recent innovations, such as microneedle patches for insulin delivery and continuous glucose monitoring systems, show promise in humans and animals. Companion animals with naturally occurring diabetes serve as valuable models for preclinical testing of novel delivery platforms and long-acting formulations under real-world settings. While these technologies show potential, challenges remain in regulatory approval and behavioral adaptation in animals. Conclusions: Future research should prioritize pharmacokinetic bridging studies, veterinary-specific formulation trials, and device validation in animal models. By highlighting shared and species-specific characteristics of DM pathogenesis and treatment, this review advocates a One Health approach toward optimized antidiabetic therapies that benefit human and veterinary medicine. Full article

Objective: Lithospermum erythrorhizon has been extensively used for the clinical treatment of skin diseases, but its material basis and mechanism of action remain unclear. This study integrates network pharmacology, untargeted metabolomics, and in vitro experimental validation to elucidate the anti-inflammatory effects and underlying mechanisms of β-acetoxyisovalerylalkannin, a bioactive naphthoquinone compound isolated from Arnebiae Radix, using inflammatory skin disease models. Methods: Core targets for β-Acetoxyisovalerylalkannin and skin inflammation were identified via network pharmacology and validated through molecular docking. In vitro assays assessed β-Acetoxyisovalerylalkannin’s impact on keratinocyte proliferation, migration, apoptosis, and inflammatory factors (CXCL1, CXCL2, CXCL8, CCL20, IFN-γ, MCP-1, TNF-α, NF-κB). Non-targeted metabolomics identified differential metabolites and pathways. Results: Network pharmacology revealed 66 common targets significantly enriched in the MAPK/STAT3 signaling pathway. In vitro, β-Acetoxyisovalerylalkannin suppressed proliferative viability and hypermigration and induced apoptosis in HaCaTs. Moreover, it downregulated the mRNA levels of inflammatory markers (CXCL1, CXCL2, CXCL8, CCL20, IFN-γ, MCP-1, TNF-α, and NF-κB) by inhibiting the activation of the MAPK/STAT3 signaling pathway. Metabolomics identified 177 modified metabolites, associating them with the arginine/proline, glycine/serine/threonine, glutathione, and nitrogen metabolic pathways. Conclusions: β-Acetoxyisovalerylalkannin exerts protective effects against skin inflammation by reducing abnormal cell proliferation and inflammatory responses, promoting apoptosis, and effectively improving the metabolic abnormalities of HaCaTs. β-Acetoxyisovalerylalkannin is, therefore, a potential therapeutic option for mitigating skin inflammation-related damage. Full article

With the advancement of remote sensing imagery and multimodal sensing technologies, monitoring plant trait dynamics has emerged as a critical area of research in modern agriculture. Traditional approaches, which rely on handcrafted features and shallow models, struggle to effectively address the complexity inherent in high-dimensional and multisource data. In contrast, deep learning, with its end-to-end feature extraction and nonlinear modeling capabilities, has substantially improved monitoring accuracy and automation. This review summarizes recent developments in the application of deep learning methods—including CNNs, RNNs, LSTMs, Transformers, GANs, and VAEs—to tasks such as growth monitoring, yield prediction, pest and disease identification, and phenotypic analysis. It further examines prominent research themes, including multimodal data fusion, transfer learning, and model interpretability. Additionally, it discusses key challenges related to data scarcity, model generalization, and real-world deployment. Finally, the review outlines prospective directions for future research, aiming to inform the integration of deep learning with phenomics and intelligent IoT systems and to advance plant monitoring toward greater intelligence and high-throughput capabilities. Full article