Search Results (33,691)

Accumulating evidence suggests that exposure to pollution from environmental cadmium (Cd) contributes to diabetic kidney disease as indicated by albuminuria and a progressive decrease in the estimated glomerular filtration rate (eGFR). This study examined the effects of Cd exposure on eGFR and the excretion rates of albumin (E_alb) and β₂-microglobulin (E_β2M) in 65 diabetics and 72 controls. Excretion of Cd (E_Cd) was a measure of exposure, while excretion of N-acetylglucosaminidase (E_NAG) reflected the extent of kidney tubular cell injury. In participants with an elevated excretion of E_β2M, the prevalence odds ratios (POR) for a reduced eGFR rose 6.4-fold, whereas the POR for albuminuria rose 4.3-fold, 4.1-fold, and 2.8-fold in those with a reduced eGFR, diabetes, and hypertension, respectively. Using covariance analysis, which adjusted for the interactions, 43% of the variation in E_alb among diabetics could be explained by female gender (η² = 0.176), E_NAG (η² = 0.162), hypertension (η² = 0.146), smoking (η² = 0.107), and body mass index (η² = 0.097), while the direct contribution of E_Cd to E_alb variability was minimal (η² = 0.005). Results from a mediating-effect analysis imply that Cd could contribute to albuminuria and a falling eGFR through inducing tubular cell injury, leading to reduced reabsorption of albumin and β₂M. Full article

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition that progressively impairs cognitive processes, particularly learning and memory. A key pathological feature of AD involves senile plaques mainly composed of β-amyloid (Aβ) peptides, generated via the amyloidogenic pathway from amyloid precursor protein (APP) through sequential β-secretase (BACE1) and γ-secretase cleavage, positioning BACE1 inhibition as a prime therapeutic target. In this study, we applied bioassay-guided fractionation of the butanol-soluble fraction from Dryopteris crassirhizoma rhizomes, previously reported to inhibit Aβ production, to isolate and characterize Aβ-lowering constituents. Through successive chromatographic steps, nine compounds were isolated and structurally classified into flavonoids, chromones, and phloroglucinols, including epicatechin (1), β-carboxymethyl-(-)-epicatechin (2), 7-methoxy-isobiflorin (3), biflorin (4), eriodictyol (5), noreugenin (6), phloroglucinols (butyrylphloroglucinol (7), 2-propionyl-4-methylphloroglucinol (8), and 2-butyryl-4-methylphloroglucinol (9) by comprehensive spectroscopic analysis (NMR, MS, UV, IR). These compounds were assessed for effects on sAPPβ and BACE1 (β-secretase) levels by Western blot, with Aβ production quantified via ELISA in a cellular AD model (APP-CHO cells). Compounds 5–9 significantly reduced sAPPβ and BACE1 expression while potently suppressing Aβ generation. These results demonstrate that diverse constituents from D. crassirhizoma rhizomes inhibited Aβ production through BACE1 suppression, highlighting their potential as natural lead compounds for AD prevention or therapy. Full article

Atherosclerosis (AS) is a disease characterized by chronic vascular wall inflammation and lipid deposition. Although lipid-lowering drugs such as statins have significantly reduced cardiovascular event rates, “residual inflammatory risk” remains a key factor driving disease progression and plaque rupture. As a central regulator of the inflammatory response, the nuclear factor-κappaB (NF-κB) signaling network comprises both canonical pro-inflammatory pathways and functionally more complex non-canonical pathways. Increasing evidence in recent years indicates that abnormal and sustained activation of the non-canonical NF-κB signaling pathway plays a pivotal role in driving plaque rupture. This review first elaborates on the shift in AS strategies from “lipid-lowering” to “anti-inflammatory” approaches, followed by an in-depth analysis of the molecular activation mechanisms of the NF-κB signaling pathway and its distinctiveness in the AS pathological process, along with its epigenetic regulation. It emphasizes how this pathway drives pathological angiogenesis and regulates vascular smooth muscle cell (VSMC) phenotypic switching and macrophage function, thereby forming a vicious cycle that amplifies inflammation and structural damage, ultimately leading to acute cardiovascular events. Finally, we systematically summarize current progress and challenges in drug development targeting the NF-κB pathway (e.g., targeting key kinases like NIK and IKKα), aiming to provide theoretical foundations and future directions for novel therapeutic strategies to stabilize coronary plaques and prevent acute coronary syndromes. Full article

Background: Primary fibula tumours are rare, representing approximately 0.25% of all primary bone tumours. While benign lesions are often asymptomatic, malignant ones typically present with pain and functional impairment. Most tumours arise in the proximal third of the fibula, yet the literature regarding their epidemiology and clinicopathological features remains limited. This systematic review aims to synthesise current evidence on presentation, diagnosis, management, and prognosis of primary malignant tumours of the proximal fibula. Methods: A systematic review was conducted following PRISMA guidelines. PubMed, Scopus, and the Cochrane Register were searched on 28 October 2025 for English-language case reports and case series on primary malignant tumors of the proximal fibula. Two reviewers independently performed study selection and data extraction, collecting information on demographics, tumor characteristics, diagnostic approaches, treatments, and outcomes, with disagreements resolved by a third reviewer. Results: Thirty-three papers involving 228 patients (78 females, 128 males, 22 unknown) were included. The mean age at diagnosis was 22.8 years (range 4–79). The most common symptoms were painful mass and neurological complaints. Osteosarcoma and Ewing’s sarcoma were predominant histological types. Limb-sparing surgeries were most common, although 16 patients underwent amputation. At mean follow-up of 48.9 months, local recurrence occurred in 44 cases, and 12 developed distant metastases, most commonly in the lungs. Overall, 38 patients died, 37 due to disease progression. Conclusions: Primary malignant tumours of the proximal fibula, while rare, pose significant therapeutic challenges. Accurate diagnosis, appropriate multimodal treatment, and careful surgical planning are crucial to optimise oncological control and functional outcomes. Full article

Ulcerative colitis (UC) is a chronic progressive inflammatory bowel disease, with evolutive potential for extension to the entire colon, development of complications and need for colectomy. Therapeutic goals in UC have moved from symptom control to more stringent outcomes such as endoscopic and histologic remission, which have been observed to correlate with improved long-term outcomes. Disease clearance, a composite endpoint simultaneously including clinical remission, endoscopic and histologic healing, has been recently proposed as the ultimate target. A treat-to-target approach, as endorsed by the STRIDE II consensus, with a tight monitoring and treatment escalation when predefined endpoints are not reached, is proposed as a strategy to achieve complete disease control. However, unlike Crohn’s disease (CD), the evidence supporting this approach for the management of UC is limited and its implementation in routine clinical practice is not widely diffused. Recent real-life data show that almost half of UC patients are not adequately controlled with current therapies according to STRIDE II criteria, due to steroid overuse, persistent signs of inflammation, active extra-intestinal manifestations and impaired quality of life. This perspective paper explores current evidence and future directions on treat-to-target strategies in UC for clinical research and practice. Full article

Background and Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disease, and the only approved pharmacological therapy shown to slow disease progression is tolvaptan. This study presents a long-term observation of ADPKD patients treated at our center, focusing on changes in eGFR approximately one year before and at least 1 year after the initiation of tolvaptan therapy. Materials and Methods: A retrospective analysis of a cohort of ADPKD patients who have received tolvaptan treatment in our center. Results: In total, 20 patients were enrolled in the analysis. Their median time of observation since tolvaptan introduction was 23.5 months. No statistically significant difference was noted in the median monthly decrease in eGFR between the time prior to tolvaptan introduction and during tolvaptan therapy. Analysis of trajectories of eGFR in particular patients enabled the division of the cohort into three subgroups: beneficiaries (n = 7, 35%), stable (n = 8, 40%), and progressors (n = 5, n = 25%). Conclusions: Despite the low number of patients, together with a relatively short observation period, which are the main limitations of our study, our results suggest that, in real-world settings, the efficacy of tolvaptan may be lower than previously reported. There is an urgent need to identify factors responsible for the suboptimal effect of the medicine. Our findings underscore the need to re-evaluate the current inclusion criteria for tolvaptan, particularly in real-world settings where patient variability is broader than in controlled clinical trials. Tailoring treatment qualification to include more practical and region-specific factors may enhance therapeutic outcomes. Full article

Background/Objectives: We investigated the association between leisure-time physical activity (LTPA) and liver fibrosis, and whether this relationship differs by obesity and diabetes status. Methods: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2017–March 2020 cycle. LTPA was assessed using the Global Physical Activity Questionnaire (GPAQ) and classified as physically active if engaging in ≥600 metabolic equivalent (MET)-minutes per week of moderate-to-vigorous activity, or inactive. Clinically significant liver fibrosis was defined as liver stiffness measurement (LSM) ≥ 8.0 kPa on transient elastography. Multivariable logistic and linear regression models estimated adjusted odds ratios (ORs) for significant liver fibrosis, with additional subgroup analyses according to obesity and diabetes status. Results: In 7662 U.S. adults, physically active participants (n = 2721) had a lower prevalence of significant fibrosis than inactive individuals (5.4% vs. 11.4%, p < 0.001). In multivariable analysis, Participants who were physically active were associated with 42% lower odds of having fibrosis (OR 0.58, 95% confidence interval [CI] 0.41–0.82; p = 0.004). This association remained consistent in subgroup analyses stratified by obesity and diabetes status, even in the non-obese subgroup with body mass index (BMI) < 30 kg/m² (OR 0.54, 95% CI 0.32–0.91; p = 0.022) and the non-diabetic subgroup (OR 0.59, 95% CI 0.39–0.90; p = 0.016). Conclusions: Regular moderate-to-vigorous LTPA was independently associated with lower likelihood of clinically significant liver fibrosis. This beneficial association was significant regardless of obesity or diabetes status, suggesting that LTPA may play a clinically meaningful role in populations at high risk for progressive liver disease. Full article

Background: Cardiac amyloidosis is characterized by progressive myocardial and atrial infiltration, leading to atrial mechanical dysfunction, atrial fibrillation, and thromboembolic complications. Left atrial (LA) strain is an established marker of atrial function; however, data on triplane LA strain in cardiac amyloidosis are limited. Methods: We evaluated transthoracic echocardiographic examinations of 24 patients with cardiac amyloidosis and 24 age-, sex-, rhythm-, and ejection fraction-matched control subjects (9 with atrial fibrillation in each group). Among amyloidosis patients, 21 had transthyretin and 3 had light-chain cardiac amyloidosis. All examinations were performed during 2025. Triplane and biplane LA reservoir strain were assessed using speckle-tracking echocardiography. Two-way analysis of variance tested the effects of disease (amyloidosis vs. control) and rhythm (sinus rhythm vs. atrial fibrillation). Agreement between triplane and biplane measurements was evaluated using Pearson correlation and Bland–Altman analyses. Results: Triplane LA reservoir strain was significantly lower in patients with cardiac amyloidosis compared with controls (6.7 ± 2.7% vs. 16.2 ± 8.3%, p < 0.001). Even in sinus rhythm, amyloidosis patients demonstrated markedly impaired LA strain, with mean values similar to those observed in control subjects with atrial fibrillation. Two-way ANOVA revealed significant main effects of disease (F = 68.9, p < 0.0001) and rhythm (F = 45.0, p < 0.0001), as well as a significant disease–rhythm interaction (F = 26.5, p < 0.0001). Triplane and biplane LA strain showed strong correlation (r = 0.90, p < 0.0001) with good agreement. Reproducibility was excellent (intra-observer ICC = 0.97; inter-observer ICC = 0.94). Conclusions: Triplane LA reservoir strain is markedly reduced in cardiac amyloidosis and enables comprehensive visualization of atrial mechanical dysfunction. The technique demonstrates high reproducibility and strong agreement with biplane analysis, supporting its use as a complementary tool for characterizing amyloid atriopathy. Full article

The progression of neoplastic diseases is driven by a complex interplay of biological processes, including uncontrolled proliferation, enhanced invasion, metastasis, and profound metabolic reprogramming. Among the hallmarks of cancer, as revised by Hanahan and Weinberg, the reprogramming of energy metabolism has emerged as a critical feature that enables cancer cells to meet their heightened bioenergetic and biosynthetic demands. One significant aspect of this metabolic adaptation is the accumulation of lipid droplets (LDs) dynamic, cytoplasmic organelles primarily involved in lipid storage and metabolic regulation. LDs serve as reservoirs of neutral lipids and play a multifaceted role in cancer cell physiology. Their accumulation is increasingly recognized as a marker of tumor aggressiveness and poor prognosis. By storing lipids, LDs provide a readily accessible source of energy and essential building blocks for membrane synthesis, supporting rapid cell division and growth. Moreover, LDs contribute to cellular homeostasis by modulating oxidative stress, maintaining redox balance, and regulating autophagy, particularly under nutrient-deprived or hypoxic conditions commonly found in the tumor microenvironment. Importantly, LDs have been implicated in the development of resistance to cancer therapies. They protect cancer cells from the cytotoxic effects of chemotherapeutic agents by buffering endoplasmic reticulum (ER) stress, inhibiting apoptosis, and facilitating survival pathways. The presence of LDs has been shown to correlate with increased resistance to a variety of chemotherapeutic drugs, although the precise molecular mechanisms underlying this phenomenon remain incompletely understood. Emerging evidence suggests that chemotherapy itself can induce changes in LD accumulation, further complicating treatment outcomes. Given their central role in cancer metabolism and therapy resistance, LDs represent a promising target for therapeutic intervention. Strategies aimed at disrupting lipid metabolism or inhibiting LD biogenesis have shown potential in sensitizing cancer cells to chemotherapy and overcoming drug resistance. In this review, we comprehensively examine the current understanding of LD biology in cancer, highlight studies that elucidate the link between LDs and drug resistance, and discuss emerging approaches to target lipid metabolic pathways to enhance therapeutic efficacy across diverse cancer types. Full article

Background: Alzheimer’s disease (AD) features progressive cognitive decline and amyloid-beta (Aβ) accumulation. Insulin resistance in type 2 diabetes mellitus (T2DM) is increasingly recognised as a mechanistic link between metabolic dysfunction and neurodegeneration. Although sodium–glucose cotransporter-2 inhibitors (SGLT2is) have established glycaemic and cardioprotective benefits, their neuroprotective role remains less well defined. Objectives: This systematic review examines animal studies on the neuroprotective effects of SGLT2i in T2DM and AD models. Methods: A literature search was conducted across the Web of Science, Scopus, and PubMed databases, covering January 2014 to November 2024. Heterogeneity was assessed with I², and data were pooled using fixed-effects models, reported as standardised mean differences with 95% confidence intervals. We focus on spatial memory performance as measured by the Morris Water Maze (MWM) test, including escape latency and time spent in the target quadrant, as the primary endpoints. The secondary endpoints of Aβ accumulation, oxidative stress, and inflammatory markers were also analysed and summarised. Results: Twelve studies met the inclusion criteria for this review. A meta-analysis showed that SGLT2i treatment significantly improved spatial memory by reducing the escape latency in both T2DM and AD models. In addition, SGLT2i yielded a significant improvement in spatial memory, as indicated by an increased target quadrant time for both T2DM and AD. Furthermore, SGLT2i reduced Aβ accumulation in the hippocampus and cortex, which met the secondary endpoint; the treatment also lessened oxidative stress and inflammatory markers in animal brains. Conclusions: Our findings indicate that SGLT2is confer consistent neuroprotective benefits in experimental T2DM and AD models. Full article

The emergence of SARS-CoV-2 posed a great global threat and emphasized the urgent need for diagnostic tools that are rapid, reliable, sensitive and capable of real-time monitoring of SARS-CoV-2 infections. Recent investigations have identified a potential connection between SARS-CoV-2 infection and gut dysbiosis, highlighting the sophisticated interplay between the virus and the host microbiome. This review article discusses the eminence of nanobiosensors, as state-of-the-art tools, to investigate and clarify the connection between SARS-CoV-2 pathogenesis and gut microbiome imbalance. Nanobiosensors are uniquely advantageous owing to their sensitivity, selectivity, specificity, and reliable monitoring capabilities, making them well-suited for identifying both viral particles and microbial markers in biological samples. We explored a range of nanobiosensor platforms and their potential use for concurrently monitoring the gut dysbiosis induced by different pathological conditions. Additionally, we explore how advanced sensing technologies can shed light on the mechanisms driving virus-induced dysbiosis, and the implications for disease progression and patient outcomes. The integration of nanobiosensors with microfluidic devices and artificial intelligence algorithms has also been explored, highlighting the potential of developing point-of-care diagnostic tools that provide comprehensive insights into both viral infection and gut health. Utilizing nanotechnology, scientists and healthcare professionals may gain a more profound insight into the complex interaction dynamics between SARS-CoV-2 infection and the gut microenvironment. This could pave the way for enhanced diagnostic and prognostic approaches, treatment courses, and patient care for COVID-19. Full article

Oral lichen planus (OLP) is a chronic immune-mediated disorder affecting the mucous membranes of the oral cavity, characterized by inflammation caused by T-cell-mediated destruction of basal keratinocytes with the potential for malignant transformation. The exact etiology of the disease remains unclear, but as its symptoms may reduce patient quality of life, various treatment modalities have been proposed, generally based on managing symptoms and controlling disease progression. In this narrative review, we examine both conventional therapies (corticosteroids, immunosuppressants, retinoids) and emerging treatment options (photodynamic therapy, low-level laser therapy, and biologics) in terms of their efficacy and limitations. Although corticosteroid therapy remains a cornerstone of treatment, it is not effective in all cases, demonstrating the need to investigate alternative methods; hence, we also present possible future directions for OLP treatment in this study. Full article

Liver fibrosis, the progressive accumulation of scar tissue resulting from chronic liver disease, is increasingly recognized as a multi-system condition, the effects of which extend beyond the liver, affecting brain health. Dementia, characterized by progressively impaired cognition sufficient to impede daily functioning, is a major global health issue with incompletely defined risk factors and pathogenic precursors. To examine the relationship between liver fibrosis and cognitive outcomes, we conducted a comprehensive PubMed literature search, and human studies published in English were included. Evidence is synthesized on the pathophysiology and clinical significance of liver fibrosis, types of dementia, and studies supporting the association between liver fibrosis and cognitive impairment. Meta-analytic data indicate that liver fibrosis is associated with an approximately 30% increased risk of incident dementia (pooled hazard ratio ~1.3), with progressively higher risks across more advanced fibrosis stages. Putative pathomechanisms, potentially modulated by age and sex, include chronic systemic and neuro-inflammation, insulin resistance, vascular dysfunction, and a perturbed intestinal microbiota–liver–brain axis. Non-invasive liver fibrosis diagnostics, advanced neuroimaging, and biomarkers represent key tools for assessing risk. In conclusion, liver fibrosis is a systemic condition that can affect brain health. Early detection, thorough risk assessment and interventions, such as lifestyle changes, metabolic therapies, and antifibrotic treatments, may help protect neural function. Key research gaps are identified, with suggestions for improving understanding of liver fibrosis’s connection to dementia or cognitive impairment. Full article

Objective: Alzheimer’s disease (AD) and other forms of dementia are a heterogeneous group of neurodegenerative diseases characterized by progressive cognitive decline. Differential diagnosis between AD and other dementias is crucial for choosing the optimal treatment strategy. Currently, cerebrospinal fluid (CSF) analysis remains the most accurate diagnostic method, but its invasiveness limits its use. In this regard, the search for reliable biomarkers in the blood is an urgent task. Methods: The study included 31 dementia patients (23 women and 8 men) diagnosed via interdisciplinary consultations and neuropsychological testing (MMSE ≤ 24). CSF and blood plasma samples were collected and analyzed using Luminex technology. Biomarker concentrations were measured, and statistical analyses (ANOVA, Kruskal–Wallis, and Pearson correlation) were performed to compare groups and assess correlations. Results: Levels of Aβ40 and Aβ42 in CSF were significantly lower in patients with AD compared with non-AD dementia (p = 0.02 and p < 0.001, respectively). The Aβ42/40 ratio in CSF was higher in patients with non-AD dementia (p = 0.048). The concentration of Aβ42 in blood plasma was increased in patients with AD (p = 0.001). Positive correlations were found between Aβ42 in CSF and TDP-43 in plasma in non-AD dementia (r = 0.97, p < 0.001), as well as between neurogranin and TDP-43 in plasma in AD (r = 0.845, p < 0.001). Conclusions: The study demonstrates the potential of blood biomarkers, in particular Aβ42, for the differential diagnosis of AD and other forms of dementia. The discovered correlations between CSF and plasma biomarkers deepen the understanding of neurodegenerative processes and contribute to the development of noninvasive diagnostic methods. Full article

Background: The introduction of tyrosine kinase inhibitors has revolutionised the treatment of gastrointestinal stromal tumours (GISTs), yet the role of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal GISTosis remains controversial. Methods: A retrospective analysis was conducted on patients with peritoneal GISTosis who underwent CRS plus HIPEC in an 18-year period. We analysed the clinicopathological characteristics and evaluated the perioperative and long-term outcomes based on the extent of disease (peritoneal cancer index, PCI), the resection (completeness of cytoreduction score) and the IM-administration. The survival factors were also analysed and the Kaplan–Meier estimator to model and estimate overall (OS) and progression-free survival (PFS). The median follow-up period was 72 months (range, 12–146). Results: A total of 25 patients (M:F = 15:10) with a median age of 57 years (range, 32–69) underwent CRS with HIPEC for peritoneal GIST metastases, detected either synchronously (n = 11) or metachronously (n = 14). The media PCI score was 9 (range, 4–20) and complete cytoreduction was achieved in 80%. Grade III complications were observed in two patients, whereas there was no postoperative mortality. Neoadjuvant imatinib-mesylate (IM) therapy was administered in 60% of patients who detected with metachronous metastases (n = 8/14), whereas adjuvant IM therapy was administered in 19 of 25 patients. Median OS was 62 months (95% CI = 22.8–101.2). Median OS and DFS for patients with PCI scores ≤ 10 were significantly longer compared to those with PCI scores > 10 (p = 0.009 and p = 0.024, respectively). Patients with CC scores of 0–1 had a significantly longer OS compared to those with CC scores of 2 (p = 0.005) and 3 (p = 0.002) and longer PFS compared to those with CC scores of 3 (p = 0.005). The need for imatinib did not significantly impact OS (p = 0.240) or PFS (p = 0.243). Conclusions: CRS combined with HIPEC shows promising results in peritoneal GISTosis, especially in patients with lower PCI and CC scores. Until larger studies validate its safety and efficacy, it should be primarily performed in expert hands in specialised peritoneal surface oncology centres. Full article