Search Results (12,882)

COVID-19, caused by the SARS-CoV-2 virus, has a wide spectrum of clinical presentations even among individuals with similar demographics. Disease severity has been linked with viral-mediated expression of interferons and interferon-stimulated genes. Among the interferon-stimulated genes are members of adenosine deaminases acting on the RNA (ADAR) family that contribute to transcriptome diversity and modulate immune response. Previous studies identified altered ADAR expression and editing patterns during SARS-CoV-2 infection, although it remains unclear whether ADAR expression and activity differ between patients with varying severities of COVID-19. We used whole-blood transcriptomes from individuals with critical or non-critical COVID-19 and matched for age, sex, and presence of comorbidities. Results show differential expression of numerous genes, including those involved in neutrophil degranulation, and upregulation of ADAR1 and its isoform ADARp110 in patients with critical COVID-19. We identified severity-specific editing events, including nonsynonymous edits, within distinct biological pathways. Differentially edited sites—that could serve as molecular markers for COVID-19 severity—were found within genes enriched in signal transduction, RNA and protein metabolism, and inflammatory pathways. Our results demonstrate differences in expression and editing patterns of ADARs between critical and non-critical patients, supporting a potential role of ADAR editing in COVID-19 pathogenesis. Full article

Titanium and titanium alloys have been widely used in clinical implants such as dental implants due to their high strength and corrosion resistance. However, their inherent biological inertness and mismatch with the elastic modulus of human bone tissue restrict bone healing and reconstruction. In this study, pure titanium was first modified by micro-arc oxidation (MAO), and then a biodegradable soybean protein isolate (SPI)/polylactic acid (PLA)–polycaprolactone (PCL) composite coating was prepared by using the spin-coating method. The coating was systematically characterized by scanning electron microscopy (SEM), an energy spectrometer (EDS), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and atomic force microscopy (AFM), confirming that the composite coating was successfully prepared. An evaluation of the physical and chemical properties showed that the introduction of SPI significantly improved the hydrophilicity, surface roughness and adhesion to the substrate of the coating, regulated the degradation rate, and reduced the elastic modulus to the range of 10–30 GPa, which matches human bone tissue. At the same time, it enhanced corrosion resistance. In vitro MC3T3-E1 osteoblast experiments showed that the coating containing 50% SPI showed better cell compatibility, adhesion ability and osteogenic inducibility, and all groups had good blood compatibility. The SPI/PLA–PCL composite coating effectively improves the biological activity of the pure titanium surface and provides a feasible strategy for the surface modification of titanium implants and bone defect repair. Full article

Limosilactobacillus reuteri is one of the common lactic acid bacteria in the chicken gastrointestinal tract. Our previous study revealed that L. reuteri abundance declined in White Leghorn chickens following infection with Eimeria tenella, E. maxima, and E. necatrix, suggesting a potential role of this species in gut homeostasis during coccidiosis. In this study, eight L. reuteri strains were isolated from the intestinal tract of White Leghorn chickens. Strain S3 was selected as the most promising candidate after screening for acid and bile tolerance, adhesion ability, antagonism against pathogens. Oral administration of S3 strain at dose of 4 × 10⁷ CFU/bird, 1.2 × 10⁸ CFU/bird or 2 × 10⁸ CFU/bird for 18 days improved average daily gain (ADG) in both White Leghorn chickens and Suqin laying hens. The ADG value in groups treated with 4 × 10⁷ CFU/bird was significantly higher compared to that in the control group (p < 0.05). This treatment did not cause adverse effects on hepatic or renal function, but significantly increased the thymus index in both breeds and the levels of total protein and globulin in Suqin laying hens (p < 0.05). S3 strain also modulated gut microbiota composition in White Leghorn chickens, promoting beneficial lactobacilli colonization in the jejunum and achieving persistent colonization in the cecum. S3 strain selectively increased the proportion of CD3⁺CD4⁺ T lymphocytes in peripheral blood of Suqin laying hens. The anticoccidial efficacy of S3 strain was evaluated in Suqin laying hens challenged with E. tenella, E. maxima, and E. necatrix. The results showed that S3 strain alleviated clinical signs, reduced lesion scores, decreased oocyst output, and attenuated body weight loss. Anticoccidial index (ACI) values were 130.67, 148.06, and 163.40 for E. tenella, E. maxima, and E. necatrix infection, respectively. These results suggest that L. reuteri S3 is a safe chicken-derived probiotic with immunomodulatory and anticoccidial properties, and may serve as a feed additive for coccidiosis control in poultry production. Full article

Vascular smooth muscle cells (VSMCs), the contractile cells in the tunica media of blood vessels, maintain vascular tone. The proliferation of VSMCs is an important feature of vascular remodeling that contributes to the regulation of blood pressure. Autophagy, an intracellular self-degrading process that delivers cytoplasmic constituents to lysosomes, plays a vital role in VSMC proliferation. This is regulated by the dopaminergic and renin–angiotensin systems but their interplay in their regulation of autophagy in VSMCs is not well-understood. In rat VSMCs, fenoldopam (Fen), a dopamine D1-like receptor agonist, increased autophagy, as determined by the increase in the protein expressions of microtubule-associated protein 1 light chain (LC)3-II and beclin-1 (BECN1), in a time- and concentration-dependent manner. Conversely, angiotensin II (Ang II), the endogenous Ang II type 1 receptor (AT₁R) agonist, decreased the protein expression of LC3-II and BECN1, also in a time- and concentration-dependent manner. The production of cyclic adenosine monophosphate (cAMP) and autophagic LC3-II puncta in VSMCs were increased by Fen and decreased by Ang II. Pre-treatment of VSMCs with Rp-cAMPS, a protein kinase A inhibitor, prevented the Fen-mediated increase and the Ang II-mediated decrease in LC3-II protein expression. Fen decreased, whereas Ang II increased the phosphorylation of P70S6K, a direct downstream mammalian target of rapamycin (mTOR). The inhibitory effect of Fen and stimulatory effect of Ang II on P70S6K phosphorylation were prevented by Rp-cAMPS. Ang II also decreased the Fen-mediated increase in cAMP production, while Fen attenuated the Ang II-mediated increase in cell proliferation, a response that occurs downstream of autophagy. Moreover, Ang II prevented the Fen-mediated inhibition of cell proliferation, an effect that was blocked by losartan, an AT₁R antagonist. These results demonstrate that Fen and Ang II counter-regulate autophagy and proliferation of VSMCs via the mTOR pathway, which is cAMP-dependent. Full article

Long-term implantable neural electrodes underpin brain–machine interfaces, deep brain stimulation, epilepsy monitoring, and closed-loop neuromodulation. Following chronic implantation, however, the foreign body response (FBR) at the electrode–tissue interface remains a major constraint on long-term performance, as reflected by increased interfacial impedance, lower signal-to-noise ratios, fewer resolvable units, and higher stimulation thresholds. This deterioration arises from interrelated events that include implantation injury, protein adsorption, blood–brain barrier disruption, complement activation, glial reactivity, oxidative stress, glial scar formation, and neuronal loss. It cannot be attributed solely to material ageing or encapsulation failure. This review examines the molecular mechanisms of neural-electrode FBR and relates them to surface-biofunctionalization strategies, including antifouling coatings, bioactive ligands, immobilized neurotrophic factors, drug-eluting electrodes, and emerging immunomodulatory interfaces. Establishing mechanistic links among molecular events, material interfaces, and functionalization strategies may guide the rational design of durable neural electrodes. Full article

Aortic dissection (AD) is a severe vascular condition marked by abrupt onset, rapid progression, and heightened mortality rates. Vascular smooth muscle cells (VSMCs), the predominant cellular component of the arterial media, are essential for maintaining the structural integrity and functionality of blood vessels. Recent studies have associated Cysteine-rich protein 2 (CSRP2) with the advancement of several vascular diseases. The involvement of CSRP2 in AD progression is unclear. Aortic tissues were collected from patients for RNA sequencing and histological analysis. A mouse model of AD was created using β-aminopropionitrile monofumarate (BAPN), while VSMC phenotypic switching was induced by platelet-derived growth factor BB (PDGF-BB). Adeno-associated virus vector was used to overexpress CSRP2 in aorta. A variety of histopathological assays and biochemical analyses were applied to determine gene and protein expression patterns as well as uncover underlying molecular mechanisms. CSRP2 was significantly downregulated in both human and murine AD, and CSRP2 gene overexpression dramatically reduced BAPN-induced AD incidence and prevented animal mortality. CSRP2 could preserve a contractile VSMC phenotype, even though under PDGF-BB stimulation. Mechanistically, our findings reveal that CSRP2 directly interacts with p130 Crk-associated substrate (p130Cas; also known as BCAR1) and reduces its phosphorylation, which in turn inhibits the activation of extracellular signal-regulated kinase (ERK) signaling pathways, thereby preventing VSMC phenotypic switching induced by PDGF-BB. Our findings identify CSRP2 as a novel regulator of VSMC phenotypic modulation and a significant modulator of AD development, suggesting its potential as a target for early intervention for AD. Full article

Background/Objectives: Recent advances in immunotherapy have revolutionized cancer treatment, as exemplified by multiple monoclonal antibodies against programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1). Nevertheless, immunotherapeutic antibodies exhibit certain limitations, which drives the development of alternative approaches, such as small interfering RNA (siRNA)-based therapeutics. The aim of this study was to design and produce new biological PD-L1 siRNA (BioRNA/PD-L1-siRNA) molecules and further define their immunotherapeutic efficacy against non-small cell lung cancer (NSCLC) in vitro. Methods: A novel RNA molecular bioengineering platform was employed to produce new BioRNA/PD-L1-siRNA agents. The functions of BioRNA/PD-L1-siRNAs were determined by quantitative PCR, Western blot, immunofluorescence confocal imaging, flow cytometry, and PD-1/PD-L1 blockade assays in human NSCLC cells, alone and co-cultured with human peripheral blood mononuclear cells (PBMCs). Results: After heterologous overexpression and purification of five BioRNA molecules, one siRNA named BioRNA/PD-L1-siRNA-1 was identified as the most effective to selectively suppress human PD-L1 mRNA and protein levels in H460 and H1975 cells. Disruption of PD-1/PD-L1 interactions by BioRNA/PD-L1-siRNA-1 was further demonstrated via a PD-1/PD-L1 blockade bioassay. In addition, the immunomodulatory effectiveness of BioRNA/PD-L1-siRNA-1 was established in co-culture models, as indicated by the induction of T-cell and natural killer cell populations and an increase in specific cytokines and cytotoxic granules, and subsequent enhancement of apoptosis and greater inhibition of NSCLC cell viability. Conclusions: Overall, these findings demonstrate the potential of bioengineered PD-L1 siRNA entities for NSCLC immunotherapy. Full article

The blood–brain barrier (BBB) carefully regulates the transport of molecules between the blood and the nervous tissue. Obstructive sleep apnea (OSA) is a chronic condition that induces structural and functional changes in the BBB. These include alterations in its permeability and in protein expression in the BBB capillary endothelium. Moreover, OSA alters blood levels of transcription factors, such as hypoxia-inducible factor 1 (HIF-1), which are suggested to be responsible for these changes. As a review article, this paper focuses on the most significant effects of OSA on the BBB, including deviations in barrier morphology, particularly changes in the expression of tight junction and adherens junction proteins and membrane channels, as well as their impact on transport across the barrier. Moreover, particular attention is given to emerging evidence for the differential regulation of major BBB efflux transporters, including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), as well as the role of the HIF-1 pathway. Additionally, we summarize the current state of knowledge regarding the contribution of these BBB alterations to the development of neurodegenerative diseases. At the same time, altered transport is being investigated as a possibility for delivering new drugs to the central nervous system. Thus, this review aims to summarize the current knowledge about OSA’s impact on the BBB. Full article

Background: Acute rheumatic fever (ARF) is a clinical syndrome triggered by group A streptococcal (GAS) infections and characterized by fever, carditis, and arthritis as its main manifestations. Diagnosis relies on the revised Jones criteria. We report a rare case of ARF diagnosed in Switzerland. Case Presentation: An 18-year-old woman presented to the emergency department five days after returning from a one-week stay in Egypt with intermittent fever and a transient sore throat, followed by migratory joint pain. Laboratory testing revealed leukocytosis, elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Chest X-ray, urine analysis, and (travel-associated) pathogen-testing (Epstein–Barr virus, Cytomegalovirus, human immunodeficiency virus, Malaria, Dengue, Zika, Chikungunya) were unremarkable. Blood cultures remained negative. Initially, a viral respiratory infection was suspected and symptomatic treatment established. Days later the patient was re-evaluated due to persistent symptoms. Leukocyte count (Lc) and CRP further increased and subcutaneous nodules appeared. The antistreptolysin-O (ASO)-titer was elevated more than three times higher than the normal upper limit and proofed serological evidence of a preceding streptococcal infection (GAS throat culture had not been performed). ARF was diagnosed according to the Jones criteria. Treatment with amoxicillin and a high dose of acetylsalicylic acid (ASA) led to a rapid clinical improvement. Secondary prophylaxis with depot penicillin (benzathine penicillin G; 1.2 million units; once monthly) was initiated to prevent rheumatic heart disease. Conclusions: This case highlights a rare occurrence of ARF following travel to Egypt, with probable acquisition of group A streptococcal infection during the trip. It emphasizes consideration of ARF even in Western countries with low ARF-prevalence if clinical history is suggestive. Early recognition and initiation of antimicrobial and anti-inflammatory therapy is crucial to prevent cardiac involvement. To the best of our knowledge, this represents one of the first cases diagnosed in Switzerland in the past 20 years. Full article

Mammary gland inflammation, clinically expressed as mastitis in dairy ruminants and lactating women, arises from a self-amplifying loop of pathogen sensing, oxidative stress and innate immune activation, and remains a leading driver of antibiotic use, milk-quality loss and morbidity. Mounting pressure to reduce antimicrobial dependence has refocused attention on flavonoids—structurally diverse plant polyphenols with multi-target bioactivity, derived mainly from in vitro and rodent mastitis models. This review integrates contemporary evidence on the six principal flavonoid subclasses within a unifying molecular framework. Across subclasses, flavonoids converge on shared targets: the TLR4–MyD88–NF-κB axis, MAPK cascades, the Keap1–Nrf2–ARE antioxidant pathway, the NLRP3 inflammasome and tight-junction proteins of the blood–milk barrier. Less canonical mechanisms—m⁶A epitranscriptomic regulation, ferroptosis suppression, AhR signalling, anti-virulence binding to bacterial enzymes such as IGPD, and gut-microbiota-driven remodelling of the gut–mammary axis—expand the pharmacological landscape. We additionally appraise the subclasses comparatively, identifying flavanones and the flavone baicalin as carrying the strongest translational evidence, and examine the conflicting findings, model limitations, and delivery, residue and regulatory barriers that currently separate mechanistic promise from on-farm application. We outline structure–activity considerations and translational priorities, and position flavonoids as mechanism-rich, antibiotic-sparing candidates for the prevention and adjunctive management of mammary gland inflammation in dairy ruminants. Full article

Background: Evidence regarding the impacts of magnesium (Mg) supplementation on cardiometabolic risk factors (CMRFs) remains inconsistent. Objectives: This systematic review and dose–response meta-analysis evaluated effects of Mg supplementation on anthropometric indices, liver and kidney function, lipid and glycemic profiles, blood pressure, and inflammatory biomarkers. Methods: A systematic search of electronic databases up to May 2026 identified 78 eligible randomized controlled trials. Results: Mg supplementation significantly reduced body weight (weighted mean difference [WMD]: −0.70 kg; 95% confidence interval [CI]: −1.30, −0.09), diastolic blood pressure (WMD: −1.58 mmHg; 95% CI: −2.50, −0.65), homeostasis model assessment of insulin resistance (WMD: −0.48; 95% CI: −0.79, −0.18), low-density lipoprotein cholesterol (WMD: −3.21 mg/dL; 95% CI: −5.27, −1.15), fasting blood glucose (WMD: −3.60 mg/dL; 95% CI: −6.13, −1.06), systolic blood pressure (WMD: −2.50 mmHg; 95% CI: −4.08, −0.91), glycated hemoglobin (WMD: −0.15%; 95% CI: −0.26, −0.03), triglycerides (WMD: −9.24 mg/dL; 95% CI: −16.87, −1.61), and interleukin-6 levels (WMD: −1.10 pg/mL; 95% CI: −1.93, −0.27) compared with controls. High-density lipoprotein cholesterol concentrations significantly increased (WMD: 1.45 mg/dL; 95% CI: 0.37, 2.54). No significant effects were identified on hip circumference, alanine aminotransferase, waist circumference, tumor necrosis factor-α, creatinine, C-reactive protein, body mass index, total cholesterol, fasting insulin, body fat percentage, and aspartate aminotransferase. Most RCTs (79.5%) administered Mg doses ≥ 300 mg/day, and 66.7% had intervention durations ≥ 12 weeks; however, evidence from higher-dose (≥500 mg/day) and longer-term (≥25 weeks) interventions remained limited. Conclusions: Mg supplementation was associated with significant improvements in several CMRFs, including body weight, lipid and glycemic profiles, blood pressure, and interleukin-6 levels. However, these effects were generally modest, and their clinical relevance remains uncertain given the variable certainty of evidence across outcomes. Full article

The mechanisms underlying neurodegenerative diseases (NDDs) involve multiple pathological processes, such as abnormal protein aggregation, oxidative stress, neuroinflammation, mitochondrial dysfunction, and the disruption of neurovascular unit homeostasis. The blood–brain barrier (BBB) restricts drug exposure in the brain, posing a significant challenge for central nervous system delivery and for improving therapeutic efficacy. In recent years, carbon dots derived from natural products (CDs) have emerged as candidate materials for brain delivery and theranostic applications due to their small size, modifiable surfaces, fluorescence-tracking capability, and potential neuroprotective activity. This narrative review summarizes their sources, physicochemical characteristics, biological basis, interactions with the BBB, delivery strategies, neuroprotective effects, and imaging applications. Current evidence suggests that these CDs can alleviate oxidative stress and inflammatory responses, influence abnormal protein aggregation, and support drug delivery and fluorescence tracking in certain cellular and animal models. However, BBB permeability, brain fluorescence signals, brain parenchymal exposure, and therapeutic efficacy represent distinct levels of evidence and should not be considered interchangeable. Future studies should focus on strengthening material standardization, ensuring batch-to-batch consistency, characterizing absorption, distribution, metabolism, and excretion (ADME), conducting long-term safety assessments, and validating using humanized BBB models. Full article

Background: Early hemodynamic deterioration may occur in patients with acute decompensated heart failure (ADHF) receiving inotropic therapy despite the absence of overt hypoperfusion at baseline. This study aimed to identify baseline factors associated with progression from Society for Cardiovascular Angiography and Interventions (SCAI) stage A or B to SCAI stage C–E at 72 h after initiation of inotropic therapy. Methods: This retrospective, single-center study included 375 adults with ADHF who received intravenous dobutamine or levosimendan and were classified as SCAI stage A or B at the time of inotrope initiation. The primary endpoint was progression to SCAI stage C, D, or E at the 72 h assessment. Baseline clinical, echocardiographic, laboratory, and hemodynamic variables were compared according to progression status. Univariable and multivariable logistic regression analyses were performed to identify factors associated with the primary endpoint. Results: Progression to SCAI stage C–E occurred in 30 patients (8.0%). Patients who progressed had lower diastolic blood pressure (DBP) and higher heart rate, white blood cell count (WBC), C-reactive protein, aspartate aminotransferase, lactate dehydrogenase, and N-terminal pro-B-type natriuretic peptide levels. The primary multivariable logistic regression model included 327 patients and all 30 outcome events. Higher WBC was independently associated with greater odds of progression (odds ratio: 1.099; 95% confidence interval: 1.030–1.174; p = 0.005), whereas higher DBP was independently associated with lower odds of progression to SCAI stage C–E (odds ratio: 0.963; 95% confidence interval: 0.934–0.992; p = 0.014). The model showed acceptable calibration and moderate discrimination, with a c-statistic of 0.731 (95% confidence interval: 0.630–0.832). In bootstrap analysis, the association remained significant for WBC, whereas the association with DBP was borderline. Conclusions: Higher WBC and lower DBP were associated with progression to SCAI stage C–E at 72 h in this exploratory single-center cohort of patients with ADHF receiving inotropic therapy. Full article

Existing diagnostic markers of sepsis indicate already developed inflammatory complications, whereas predictors enable preoperative identification of high-risk patients for preventive measures. This study aimed to evaluate the prognostic value of preoperative inflammatory biomarkers for postoperative complications in cardiac surgery patients. Preoperatively, we assessed age, body mass index, EuroSCORE II (European System for Cardiac Operative Risk Evaluation II), complete blood count with hematological indices including neutrophil-to-lymphocyte ratio (NLR), serum cytokines, HIF1A (hypoxia-inducible factor 1-alpha), and EPAS1 (endothelial PAS domain protein 1) expression in peripheral blood leukocytes. During surgery, cardiopulmonary bypass time, myocardial ischemia time, and blood loss were recorded. Postoperatively, complications, intensive care unit (ICU) stay, and total hospitalization were documented. No differences were found in non-modifiable risk factors or perioperative parameters between groups, except for longer ICU stay in the complications group. Preoperatively, absolute neutrophil count and NLR were higher in patients without complications, while eosinophil count, HIF1A expression, and HIF1A/EPAS1 ratio were higher in those with it. The HIF1A/EPAS1 ratio demonstrated the best diagnostic characteristics. Thus, preoperative predictors of postoperative inflammatory complications include low neutrophil count and NLR, as well as high HIF1A expression and HIF1A/EPAS1 ratio. These markers may facilitate early risk stratification and preventive strategies before surgery. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic disorder associated with an elevated risk of cardiovascular disease. Mac-2 binding protein glycosylation isomer (M2BPGi), a noninvasive serum biomarker of hepatic fibrosis, has also been linked to adverse metabolic and cardiovascular outcomes. However, the association between serum M2BPGi levels and subclinical coronary atherosclerosis in individuals with MASLD remains unclear. We investigated the association between serum M2BPGi levels and coronary artery calcium score (CACS), an established imaging marker of subclinical atherosclerosis, in individuals with MASLD. Methods: This retrospective cross-sectional study included 6514 adults with MASLD who underwent health screening examinations between 2020 and 2025. Participants were categorized into quartiles according to serum M2BPGi levels: Q1 (<0.48), Q2 (0.48–0.61), Q3 (0.62–0.80), and Q4 (≥0.81). Coronary artery calcification (CAC) was defined as CACS > 0. Multivariable logistic regression analysis was performed after adjustment for age, sex, smoking status, liver enzymes, adiposity, dysglycemia, blood pressure, and lipid profile. Multivariable ordinal logistic regression analysis was additionally performed to evaluate the association between M2BPGi levels and CAC severity. Results: The prevalence of CAC increased progressively across M2BPGi quartiles (39.4%, 45.3%, 48.5%, and 57.4% for Q1–Q4, respectively; p < 0.001). In multivariable logistic regression analysis, participants in the highest M2BPGi quartile had significantly higher odds of CAC presence than those in the lowest quartile (OR, 1.32; 95% CI, 1.10–1.58; p = 0.0035). Higher M2BPGi quartiles were also independently associated with greater CAC severity in multivariable ordinal logistic regression analysis (OR, 1.33; 95% CI, 1.13–1.57; p = 0.0007 for Q4 vs. Q1). Conclusions: Higher serum M2BPGi levels were independently associated with both the presence and severity of CAC in individuals with MASLD. These findings suggest that M2BPGi may serve as a potential biomarker for identifying individuals with MASLD at increased risk of subclinical atherosclerosis and may complement conventional cardiovascular risk assessment. Full article