Search Results (6,291)

In addition to its role in angiotensin II (Ang II) production, chymase exhibits various functions, including activation of latent transforming growth factor beta 1 (TGF-β1) and pro-matrix metalloproteinases (MMPs). However, the extent to which these Ang II-independent functions contribute to pathological conditions remains unclear. In this study, we investigated the Ang II-independent roles of chymase in cardiac remodeling and dysfunction. Eighteen male Syrian hamsters, aged 6 weeks and weighing 90–110 g, were used. Exogenous Ang II was administered to a hamster model that mirrors the human chymase-dependent Ang II production pathway, via subcutaneous osmotic mini pumps (2 mg/kg/day) for 4 weeks. A chymase-specific inhibitor, TY-51469 (10 mg/kg/day), was given daily starting 1 day after commencement of Ang II infusion. Evaluation showed that while systolic blood pressure increased significantly, only diastolic dysfunction developed over time. Ang II treatment led to elevated cardiac expression of chymase, TGF-β1, and MMP-2, and increased the number of chymase-positive mast cells, resulting in notable cardiac hypertrophy and fibrosis. TY-51469 effectively suppressed these molecular changes and improved both cardiac structure and diastolic dysfunction, despite continued Ang II exposure. These results suggest that chymase promotes cardiac remodeling and dysfunction not only through Ang II generation but also by activating profibrotic and matrix-degrading factors, such as TGF-β1 and MMP-2. Full article

Rheumatoid arthritis (RA) is one of the most common chronic autoimmune diseases which global prevalence is approximately 0.3–2%. Numerous studies provide evidence that the elevated levels of reactive oxygen species (ROS) contribute to the pathogenesis and progression of RA. In response to redox imbalance, several intrinsic antioxidant defence mechanisms are activated to counteract oxidative stress and scavenge ROS. The aim of the present study is to analyse whether the levels of lactoferrin and thioredoxin, two proteins which are part of the antioxidant defence of the body, are associated with fibrinogen and other acute phase proteins such as CRP and ferritin in RA. Serum lactoferrin, thioredoxin, ferritin, and CRP levels were measured using ELISA. Significant positive correlations of lactoferrin and thioredoxin with fibrinogen were observed in RA patients, r = 0.394, p < 0.0001 and r = 0.410, p = 0.002, respectively. These positive correlations were also observed in females, r = 0.375, p < 0.0001 and r = 0.447, p = 0.001, in the subgroup of patients with DAS28 < 5.1, r = 0.689, p < 0.0001 and r = 0.604, p = 0.001 and in the subgroup of patients with normal CRP, r = 0.488, p < 0.0001 and r = 0.414, p = 0.005, respectively. These findings help clarify the pathogenetic interplay between oxidative stress, inflammation, and coagulation in RA and indicate the need for further studies to elucidate the potential of lactoferrin and thioredoxin as biomarkers that capture pathological disease changes. Full article

Background/Objectives: Recurrent meningiomas remain difficult to manage due to the absence of effective systemic therapies and comparatively high treatment failure rates, particularly in high-grade tumors. Stereotactic radiosurgery (SRS) offers a minimally-invasive and precise option, particularly for tumors in surgically complex locations. However, the risks associated with re-irradiation, and recent changes in the WHO classification of CNS tumors highlight the need for more personalized and strategic treatment approaches. This systematic review evaluates the safety, efficacy, and clinical considerations for use of SRS for recurrent meningiomas. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search was conducted using the PubMed, Scopus, and Web of Science databases for studies reporting outcomes of SRS in recurrent, pathologically confirmed intracranial meningiomas. Studies were excluded if they were commentaries, reviews, case reports with fewer than three cases, or had inaccessible full text. The quality and risk of bias of the included studies were assessed using the modified Newcastle-Ottawa Scale. Data on patient and tumor characteristics, SRS treatment parameters, clinical outcomes, adverse effects, and statistical analysis results were extracted. Results: Sixteen studies were included. For WHO Grade I tumors, 3- to 5-year progression-free survival (PFS) ranged from 85% to 100%. Grade II meningiomas demonstrated more variable outcomes, with 3-year PFS ranging from 23% to 100%. Grade III tumors had consistently poorer outcomes, with reported 1-year and 2-year PFS rates as low as 0% and 46%, respectively. SRS performed after surgery alone was associated with superior outcomes, with local control rates of 79% to 100% and 5-year PFS ranging from 40.4% to 91%. In contrast, tumors previously treated with radiotherapy, with or without surgery, showed substantially poorer outcomes, with 3- to 5-year PFS ranging from 26% to 41% and local control rates as low as 31%. Among patients with prior radiotherapy, outcomes were particularly poor in Grade II and III recurrent tumors. Toxicity rates ranged from 3.7% to 37%, and were generally higher for patients with prior radiation. Predictors of worse PFS included prior radiation, older age, and Grade III histology. Conclusions: SRS may represent a reasonable salvage option for carefully selected patients with recurrent meningioma, particularly following surgery alone. Outcomes were notably worse in high-grade recurrent meningiomas following prior radiotherapy, emphasizing the prognostic significance of both histological grade and treatment history. Notably, the lack of molecular and genetic data in most existing studies represents a key limitation in the current literature. Future prospective studies incorporating molecular profiling may improve risk stratification and support more personalized treatment strategies. Full article

Background: Magnetic Resonance Cholangiopancreatography (MRCP) has continuously evolved to enhance visualization capabilities. However, diagnosing biliary ductal system pathology, particularly early primary sclerosing cholangitis (PSC), remains challenging. This study investigates the influence of intramuscular glucagon (IMG) administration on final image quality and pancreatobiliary ductal system diameter in MRCP. Methods: Forty patients (57.5% female; average age 34.45 ± 8.2) referred for Magnetic Resonance Enterography (MRE) underwent MRCP before and 8–12 min after IMG administration. Two independent MRI specialists analyzed Coronal T2-weighted fast spin-echo high-resolution 3D MRCP images quantitatively and qualitatively. Quantitative assessments involved measuring the transverse diameter of five specific biliary duct structures (inferior, mid, and upper common bile duct; right and left hepatic ducts) and three pancreatic duct segments (head, body, and tail). The qualitative evaluation used a five-point Likert-type scale (1 = perfect visualization; 5 = not visible) for the predefined segments. Interobserver variation was assessed using the Intraclass Correlation Coefficient (ICC). Results: Following IMG administration, the diameters of all corresponding biliary and pancreatic segments significantly increased, with consistently strong interobserver agreement demonstrated pre- and post-IMG administration. Moreover, in qualitative analysis, post-IMG administration scores indicated a significant decrease (p < 0.01) in visualization scores, signifying improved visualization at all corresponding points for both radiologists compared to the pre-glucagon administration scores. The ICC scores pre- and post-IMG administration demonstrated moderate to strong agreement. Conclusions: IMG administration improves MRCP imaging parameters by increasing ductal diameters and enhancing biliary tree visualization, underscoring its potential to detect subtle or early pathological changes. Full article

Background: Cellulosimicrobium, formerly known as the Oerskovia genus, is a Gram-positive organism known for its characteristic bright yellow colonies. While abundant in nature, it is very rarely linked to pathogenesis in humans. While there is no classical presentation for Cellulosimicrobium-associated infections, cases tend to be foreign body-related or involve immunocompromised patients. Rates of Cellulosimicrobium-associated infections have been hypothesised to rise in the future, due to rising numbers of immunocompromised patients in the community and increasing usage of foreign bodies such as prostheses and long-term catheters. Existing technical difficulties regarding misidentifying cultures as other species (often other coryneforms) may also play a significant role in the low number of documented cases, and this may change in the near future with diagnostic advancements such as whole genomic sequencing. Case Presentation: A 57-year-old immunocompetent Irish male presented with concomitant neck and lung masses. Notably, this was found to be directly following a recent dental procedure. During extensive investigations, Cellulosimicrobium was isolated from biopsied lung tissue using 16S ribosomal ribonucleic acid gene-sequencing analysis. The patient was treated with long-term oral amoxicillin and safely discharged, with both masses showing measurable reductions in size on subsequent imaging. Conclusions: Should Cellulosimicrobium represent the causative pathological organism in this case, then we believe this to represent a potential novel documented presentation of the organism’s pathogenesis in humans. We provide detailed discussion surrounding the successful management of this patient and the evaluation of the evolving differential diagnosis throughout this case. Full article

Background: Edentulism, or toothlessness, is a significant public health issue with profound implications for physical and systemic health, especially during pregnancy, when hormonal and behavioral changes increase the risk of oral diseases. Indigenous populations are particularly vulnerable due to socioeconomic and cultural factors that limit access to dental care. Methods: This pilot study assessed the oral microbiota of nine women, both pregnant and non-pregnant, aged 18–35 from the Salasaca indigenous community in Ecuador, using 16S rRNA gene sequencing. Samples were collected from dentin, saliva, and oral mucosa, and analyzed for alpha and beta diversity levels, taxonomic composition, and ecological metrics using the DADA2 pipeline and a canonical correspondence analysis. Results: Pregnant participants exhibited significantly lower microbial diversity compared to non-pregnant individuals, with notable differences in species richness and community structure. Dominant phyla included Bacillota, Bacteroidota, and Pseudomonadota. Prevotella sp., Neisseria sp., and Haemophilus sp. were among the prevalent genera, with the canonical correspondence analysis highlighting associations between microbial profiles and variables such as gestational status, marital status, and BMI. Conclusion: The findings suggest that pregnancy influences the oral microbiota composition, potentially predisposing women to dysbiosis and dental pathology. This study highlights the need for targeted oral health strategies during pregnancy and serves as a foundation for larger studies in underserved indigenous populations. Full article

Urinary incontinence (UI) is a widespread worldwide gynecological pathology with a negative impact on women’s quality of life. We performed a narrative review and present a general, descriptive, and comprehensive perspective about surgical techniques for urinary incontinence in young women. Even though parity and vaginal births represent important risk factors for the occurrence of UI, it is also common among young women who are nulliparous. Lifestyle, obesity, smoking, alcohol consumption, and excessive stretching exercises can contribute to the occurrence of UI. Correct diagnosis and treatment may reduce the negative effects of UI on daily activities. Disease management varies depending on the three types of UI: stress, urge, and mixed. Conservative treatment involves lifestyle changes, pharmacological therapy, and pelvic floor muscle training. If symptoms persist, surgical techniques such as midurethral/suburethral slings, anterior colporrhaphy, and retropubic/laparoscopic colposuspension are necessary. Transvaginal tension-free vaginal tape obturator (TVT-O) is the most common surgical technique for the treatment of UI. Its effectiveness has been proven by reducing symptoms and improving quality of life. Alternative modern treatment methods are vaginal laser therapy, periurethral bulking agents injection, or local injection with autologous platelet-rich plasma. Surgical techniques for the treatment of UI are in continuous development and improvement considering the increased incidence of this pathology and the need of patients to improve symptoms and quality of life. Full article

Renocardiac syndrome type 4 (RCS4) is a common comorbid pathology, but the mechanisms of kidney dysfunction-induced cardiac remodeling and the involvement of cardiac progenitor cells (CPCs) in this process remain unclear. The aim of this study was to investigate the structural and functional changes in the cardiac muscle in RCS4 induced by unilateral ureteral obstruction (UUO) and the role of nestin⁺ CPCs in these. Heart function and localization of nestin⁺ cells in the myocardium were assessed using nestin-GFP transgenic mice subjected to UUO for 14 and 28 days. UUO resulted in cardiac hypertrophy, accompanied by an elongation of the QRS wave on the ECG, decreased expression of Cxcl1, Cxcl9, and Il1b, reduced the number of CD11b⁺ cells, and increased in titin isoform parameters, such as T1/MHC and TT/MHC ratios, without changes in fibrosis markers. The number of nestin⁺ cells increased in the myocardium with increased duration of UUO and displayed an SCA-1⁺TBX5⁺ phenotype, consistent with CPCs. Thus, cardiac pathology in RCS4 was manifested by cardiomyocyte hypertrophy with changes in the electrophysiological phenotype of the heart, not accompanied by fibrosis or inflammation. Nestin⁺ cardiac cells retained the CPC phenotype during UUO, and their number increased, which suggests their participation in regenerative processes in the heart. Full article

Environmental pollution with microplastics (MPs) can have a negative impact on human health. Certain findings point to the relationship between MP and the development of inflammatory bowel diseases (IBD). We investigated the effect of MP consumption on the severity of chronic colitis in male C57BL/6 mice. The MP effect was modeled by drinking water consumption with a suspension of 5 μm PS particles at a concentration of 10 mg/L replacement for 12 weeks. Chronic colitis was induced by three seven-day cycles of 1% DSS consumption (starting from the 8th, 29th and 50th days of the experiment). We investigated inflammatory infiltration, the goblet cell volume fraction and the highly sulfated and neutral mucins content in them, the endocrine cell number, the ulcerative-inflammatory process prevalence, changes in the gene’s expression encoding tight junction proteins, glycocalyx components proapoptotic factor Bax and proliferation marker Mki67 in the colon, and TNFα, IL-1β, IL-6 and IL-10 cytokines content in the serum. In healthy mice, MP did not cause pathological changes in the colon; however, indirect data indicate an increase in colon permeability. In chronic colitis, MP leads to higher prevalence of all pathological changes in general, and ulcers in particular, in a greater number of crypt abscesses and enteroendocrine cells. MP consumption leads to a more severe chronic colitis course. Full article

Background/Objectives: Heart disease affects 0.1% to 4% of pregnant women, with congenital heart defects being the leading cause in developed countries. While maternal mortality is generally low, pre-existing cardiac conditions substantially increase adverse outcome risks. This report describes the multidisciplinary management of a pregnant patient with a bicuspid aortic valve, severe aortic stenosis, and ascending aortic ectasia. Case Presentation: A 34-year-old pregnant woman, asymptomatic but at high risk (World Health Organization Class III) for hemodynamic decompensation, was closely monitored throughout gestation. At 36 weeks, intrauterine growth restriction was detected, prompting an elective cesarean delivery at 38 weeks. Postpartum, the patient developed pre-eclampsia, which was managed successfully. Imaging revealed progressive aortic dilation, leading to surgical aortic valve replacement and ascending aorta reduction plasty. Post-operatively, atrioventricular reentrant tachycardia from an unrecognized accessory pathway developed; medical therapy effectively controlled the arrhythmia after failed catheter ablation. One year later, both mother and child remained in good health. Discussion: This case illustrates the complexity of managing pregnancy in women with congenital heart disease and significant aortic pathology. The physiological changes of pregnancy can exacerbate underlying lesions, necessitating individualized risk assessment, vigilant monitoring, and timely intervention. Conclusions: A multidisciplinary approach involving cardiology, obstetrics, anesthesiology, and genetics is essential to optimize outcomes for pregnant women with significant heart disease. As advances in care allow more women with congenital heart defects to reach childbearing age, structured care pathways remain vital for ensuring safe pregnancies and long-term cardiovascular health. Full article

Stem cell therapies, including mesenchymal (MSCs) and haematopoietic stem cells (HSCs), have shown promise in neurodegenerative diseases. Here, we investigated the therapeutic effects of a defined combination of unmanipulated MSCs and CD34⁺ HSCs, termed Neuro-Cells (NC), in a murine model of Alzheimer’s disease (AD), the APPswe/PS1dE9 mouse. At 12 months of age, mice received intracisternal injections of NC (1.39 × 10⁶ MSCs + 5 × 10⁵ HSCs) or vehicle. After 45 days, behavioural testing, immunohistochemical analyses of amyloid plaque density (APD), and cortical gene expression profiling were conducted. NC-treated APP/PS1 mice exhibited preserved object recognition memory and reduced anxiety-like behaviours, contrasting with deficits observed in untreated transgenic controls. Histologically, NC treatment significantly reduced the density of small amyloid plaques (<50 μm²) in the hippocampus and thalamus, and total plaque burden in the thalamus. Gene expression analysis revealed that NC treatment normalised or reversed disease-associated changes in insulin receptor (IR) signalling and neurotrophic pathways. Specifically, NC increased expression of Bdnf, Irs2, and Pgc-1α, while attenuating aberrant upregulation of Insr, Igf1r, and markers of ageing and AD-related pathology (Sirt1, Gdf15, Arc, Egr1, Cldn5). These findings indicate that NC therapy mitigates behavioural and molecular hallmarks of AD, potentially via restoration of BDNF and insulin receptor-mediated signalling. Full article

Fenofibrate (FF), a lipid-lowering drug, may decrease the risk of cardiovascular diseases in some pathological settings, yet data on its cardiac effects in physiological aging is scarce. To determine FF and age effects on the heart’s morphology and expression of metabolism-related genes, we treated young and old male rats for 30 days with 0.1% or 0.5% FF. FF did not affect serum activities of LDH and creatine kinase in both age groups. Upon FF treatment the structure of the heart muscle did not change in young rats; however, 0.5% FF increased the abundance of collagen fibers in old rats, and lipid accumulation in cardiomyocytes in young and old animals. FF increased immunoreactivity of the hypertrophy marker NPPA that was more pronounced in old than in young rats, while VEGFB immunoreactivity did not change. FF upregulated phospho-AMPK and PGC1α protein levels only in the cardiac muscle of old rats, while in both age groups it mildly increased the expression of selected fatty acid oxidation genes. We conclude that the cardiac muscle response to FF is dose-dependent and influenced by age. The observed negative impact of high-dose FF in the hearts of aged rats underscores the importance of dose optimization in the elderly. Full article

Background/Objectives: Pompe disease (PD) is a rare autosomal recessive disorder caused by a deficiency of the lysosomal acid α-1,4-glucosidase (GAA) encoded by the GAA gene, leading to muscular dysfunctions due to pathological accumulation of glycogen in skeletal and cardiac muscles. PD has been reported in several animals and Japanese quails (JQ; Coturnix japonica), but a causative mutation has yet to be found in JQs with PD. Here, we aimed to identify a pathogenic mutation in JQs associated with PD. Methods: Paraffin-embedded skeletal muscle blocks from four JQs stored since the 1970s were used in this study. After confirming the histopathological phenotypes of PD, Sanger sequencing was performed to identify a pathological mutation in the GAA I gene of JQs. A genotyping survey was conducted using a real-time polymerase chain reaction assay targeting a candidate mutation using DNA samples extracted from 70 new-hatched JQs and 10 eggs from commercial farms. Results: Microscopic analysis confirmed the presence of the PD phenotype in three affected JQs based on abnormal histopathological changes and accumulated glycogen in the affected muscles, while one JQ was unaffected and served as a control. Sanger sequencing revealed that the three affected JQs were homozygous for the deletion of guanine at position 1096 in the open reading frame (c.1096delG). A genotyping survey of 70 JQs and 10 eggs from commercial farms showed that none carried this deletion mutation. Conclusions: This study identified c.1096delG as the pathogenic mutation for PD in JQs. This mutation induces a frameshift and substitution of amino acids at position 366 (alanine to histidine), resulting in premature termination at the 23rd codon (p.A366Hfs*23). This suggests that this mutation causes the deficient activity of GAA in JQs with PD. The identification of the c.1096delG mutation enabled the systematic maintenance of the flock colony in the PD model. Furthermore, this PD model can be used to clarify unknown aspects of PD pathogenesis and develop therapeutic strategies. Full article

Background: Anemia is a common comorbidity in heart failure (HF) and has been associated with adverse clinical consequences. This retrospective, descriptive cohort study examined phenotype-specific differences in anemia severity, clinical presentation, comorbid burden, and in-hospital management across HF subtypes classified by left ventricular ejection fraction (LVEF). Methods: We retrospectively analyzed 443 adult patients hospitalized with concurrent HF and anemia from January 2022 to December 2024. Patients were stratified by LVEF into HFrEF (<40%), HFmrEF (40–49%), and HFpEF (≥50%). All patients included met WHO criteria for anemia. Demographic, clinical, paraclinical, and therapeutic data were extracted, and descriptive statistical methods were used to evaluate intergroup differences. No formal time-to-event analyses (e.g., Kaplan–Meier curves) were performed; instead, exploratory cumulative readmission analyses using fixed follow-up windows were conducted. In-hospital mortality was recorded and stratified by HF phenotype. Results: The cohort comprised 213 (48.0%) HFrEF, 118 (26.6%) HFmrEF, and 112 (25.3%) HFpEF patients. The distribution of anemia severity, management strategies, and comorbidity profiles varied significantly across phenotypes. Severe anemia predominated in the HFmrEF cohort (54.2%), whereas mild anemia was most common in HFpEF (52.1%) and HFrEF (52.1%). Mean hemoglobin concentrations were 8.39 ± 1.79 g/dL (HFmrEF), 9.07 ± 2.47 g/dL (HFpEF), and 8.62 ± 1.94 g/dL (HFrEF). Rates of atrial fibrillation (48.2% in HFpEF), hypertensive ECG changes (63.4% in HFpEF), and ischemic-lesion patterns (>50% in HFrEF) differed by cohort. Echocardiographically, grade III mitral regurgitation and severe pulmonary hypertension each affected 25.4% of HFmrEF patients, whereas HFpEF patients most often exhibited grade II mitral regurgitation (42.9%) and moderate pulmonary hypertension (42.9%). HFrEF patients had severe pulmonary hypertension. Intravenous (IV) iron was the primary treatment modality, with highest utilization in HFmrEF. IV iron use ranged from 69.9% (HFrEF) to 84.8% (HFmrEF), with transfusion rates of 5.6% (HFrEF)–16.1% (HFpEF). Comorbid burdens differed by phenotype: HFrEF was associated with structural heart disease, HFmrEF with vascular and hepatic pathology, and HFpEF with metabolic and degenerative comorbidities. Discharge pharmacotherapy reflected phenotype-specific treatment patterns. Conclusions: This real-world descriptive analysis highlights substantial variation in anemia burden and management across the HF spectrum. While limited to descriptive findings, our analysis highlights the heterogeneity of anemia in HF and describes observed associations across phenotypes, without implying causality. These findings should be interpreted as hypothesis-generating. These findings are observational, exploratory, and cannot establish a causal relationship between intravenous iron use and survival. Full article

Backgroud: The aim of this study was to create an accessible, simple and reliable method for assessing the relative density of bone tissue in dentistry based on the analysis of digital panoramic radiographs. Methods: Measurement of average gray values on orthopantomograms was carried out using ImageJ Version 1.54i software. To estimate the relative bone density, functions for selecting regions of interest (ROI), calculating the area of selection, and statistics of the selected area were used. Statistical characteristics of samples and testing of hypotheses using statistical criteria were performed using Microsoft Excel. Results: we found that when manually selecting the reference and comparison areas for areas without signs of pathological changes in bone tissue, the average standard deviation was 0.058, and the coefficient of variation was 0.055 ± 0.011%, which makes the choice of the jaw angle as a reference more preferable. The average relative bone density of the assessed defective areas to the jaw angle was 0.64 ± 0.11, and the average relative bone density of the areas without pathology to the jaw angle was 1.052 ± 0.058. Conclusions: a research protocol was developed and justified using the ImageJ software package, which establishes a strict procedure for quantitative assessment of relative bone density based on the results of digital panoramic radiography. The proposed protocol can be used to monitor the condition of bone tissue after all types of dental treatment over time. Full article