Search Results (2,265)

Hepatic ischemia–reperfusion injury (IRI) is a critical clinical condition associated with liver transplantation and acute liver injury. This study investigated the role of sulfide quinone oxidoreductase (SQOR) and its downstream product, supersulfides, in hepatic IRI. C57BL/6NJ mice were subjected to 45 min of partial hepatic ischemia, followed by reperfusion lasting 4 h. Control of shRNA mediated knockdown of SQOR expressing adeno-associated viral vectors were administered 3 weeks prior to liver ischemia. In the shRNA-mediated knockdown of SQOR group, the hydro-trisulfide donor sodium trisulfide was administered daily for 1 week prior to the induction of liver ischemia. SQOR played a crucial protective role during hepatic IRI by facilitating electron transport to the mitochondrial respiratory chain and maintaining the oxidized and reduced nicotinamide adenine dinucleotide ratio. Administration of sodium trisulfide, exhibited protective effects against hepatic IRI. Sodium trisulfide restored the oxidized and reduced nicotinamide adenine dinucleotide ratio, reduced oxidative stress, and preserved the expression of key enzymes involved in the sulfide oxidation pathway. SQOR and supersulfides contribute to hepatic protection against IRI, likely through their potent antioxidative and redox-regulating functions, and highlight sodium trisulfide as a potential therapeutic agent. Full article

Glaesserella parasuis (G. parasuis) is a key pathogen responsible for swine respiratory disease, and the development of broadly protective vaccines is hampered by its high antigenic diversity. The iron-acquisition protein TbpB is a conserved vaccine candidate, but the cellular immune responses it elicits, particularly T-cell subset dynamics during immunization and challenge, remain insufficiently defined. This study characterized these responses after oral immunization of colostrum-deprived piglets with the TbpB^Y167A mutant. Ten colostrum-deprived piglets were allocated to immunized and non-immunized (PBS) groups, immunized at days 15 and 30 of life and subsequently challenged with G. parasuis (45 days old); peripheral blood mononuclear cells were collected at baseline, after each immunization, and at 1 and 3 days post-infection. Multiparametric flow cytometry was used to quantify major leukocyte subsets and T-cell phenotypes defined by sIgM, CD172a, CD3, TCRγδ, CD8α/β, CD4 and CD27 expression. Booster immunization induced significant expansion of B cells (p < 0.01), TCRγδ T cells (p < 0.01), CD8⁺ αβ T cells (p < 0.001) and CD4⁺ memory T cells (p < 0.01) in immunized piglets compared with controls. After challenge, CD8⁺ cytotoxic T cells in immunized animals rapidly shifted from naïve to memory phenotypes, peaking at 48–72 h (p < 0.01). These biphasic T-cell dynamics are consistent with the protective efficacy previously demonstrated for this vaccine in colostrum-deprived piglets, and support a key contribution of TCRγδ, CD8⁺ cytotoxic and CD4⁺ memory T cells to immunity against G. parasuis and to the design of next-generation vaccines. Full article

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the global COVID-19 pandemic, which led to hundreds of millions of human infections and more than seven million deaths worldwide. Major variants of concern, particularly the Omicron variant and its associated subvariants, can escape the vaccines developed so far to target previous strains/subvariants. Therefore, effective vaccines that broadly neutralize different Omicron subvariants and show good protective efficacy are needed to prevent further spread of Omicron. The spike (S) protein, including its receptor-binding domain (RBD), is a key vaccine target. Methods: Here, we designed a unique mRNA vaccine encoding Omicron-KP.3 RBD based on RBD-truncated S protein backbone of an earlier Omicron subvariant EG.5 (KP3 mRNA), and evaluated its stability, immunogenicity, neutralizing activity, and protective efficacy in a mouse model. Results: Our data showed that the nucleoside-modified, lipid nanoparticle-encapsulated mRNA vaccine was stable at various temperatures during the period of detection. In addition, the vaccine elicited potent antibody responses with broadly neutralizing activity against multiple Omicron subvariants, including KP.2, KP.3, XEC, and NB.1.8.1. This mRNA vaccine protected immunized transgenic mice from challenge with SARS-CoV-2 Omicron-KP.3. Immune serum also protected against subsequent virus challenge, with the level of protection associating positively with the serum neutralizing antibody titer. Conclusions: Taken together, the data presented herein suggest that this newly designed mRNA vaccine has potential against current and future Omicron subvariants. Full article

Background: Pharmacotherapy is the therapeutic mainstay in epilepsy, but in about 30% of patients, the epilepsy is pharmacoresistant. A ketogenic diet (KD) is an alternative therapeutic option. The mechanisms underlying the anti-seizure effect of KD are not fully understood. An enhanced energy metabolism may have a protective effect; C8 and C10 fatty acids were previously shown to activate mitochondrial function in vitro. In the present study, we investigated whether ß-hydroxybutyrate (HOB), C8, C10 or a combination of C8 and C10 fatty acids, which all increase under KD, could activate mitochondrial respiratory chain enzymes in murine hippocampal neurons (HT22). Methods: Cells were incubated for one week in the presence of the different metabolites. Respiratory chain enzyme activities as well as citrate synthase as a mitochondrial marker enzyme were determined spectrophotometrically in these cells. We observed that enzyme activities of complexes I and III, II and III, and IV (cytochrome c-oxidase) and V (ATP synthase) significantly increased in response to incubation with C8 and C10 fatty acids and a combination of both. Results: This activation of the respiratory chain enzymes was not inferior to an incubation with HOB, the key metabolite in KD. The activity of the mitochondrial marker enzyme citrate synthase increased under incubation with the fatty acids, showing that the mitochondrial content increased. Conclusions: In murine hippocampal cells, C8, C10 and combined C8 and C10 fatty acids led to variable increases in activities of mitochondrial respiratory chain enzymes and citrate synthase. This indicates that both C8 and C10 fatty acids may be important for the antiepileptic effect of KD, as they enhance energy production. Full article

Tris(1-chloro-2-propyl) phosphate (TCIPP) is an emerging environmental pollutant associated with adverse respiratory effects, yet whether niacin has a protective effect on lung function remains unclear. Data from 1031 participants in the 2011–2012 National Health and Nutrition Examination Survey (NHANES) were analyzed using multiple linear regression to assess associations between urinary bis(1,3-dichloro-2-propyl) phosphate (BCIPP), dietary niacin intake, and pulmonary function. Animal models were established to investigate TCIPP-induced lung injury and the protective effects of niacin. Lung injury was assessed by histopathology, lung function, inflammation, and oxidative stress-related indicators. Comparative Toxicogenomics Database (CTD), molecular docking, and Western blot were performed to explore underlying mechanisms. Higher urinary BCIPP concentration was associated with reduced lung function, whereas higher dietary niacin intake was associated with improved lung function. Notably, BCIPP levels showed positive associations between dietary niacin intake and FEV₁ [β (95% CI) = 0.11 (0.06, 0.16), p_adj < 0.001] and FVC [β (95% CI) = 0.09 (0.05, 0.13), p_adj < 0.001] in males with lower BCIPP exposure. In male mice, TCIPP exposure caused dose-dependent lung injury, inflammation, and oxidative stress, while niacin supplementation alleviated lung damage, improved lung function, and restored antioxidant defenses by inhibiting NF-κB phosphorylation. Niacin supplementation alleviated TCIPP-induced lung injury in males by inhibiting oxidative stress and NF-κB activation, suggesting niacin as a potential nutritional strategy to improve lung function. Full article

Background/Objective: The influenza virus remains one of the most prevalent respiratory pathogens, posing significant global health and economic challenges. According to the World Health Organization, the seasonal influenza virus infects up to 1 billion people and causes up to 650,000 deaths, annually. Despite influenza vaccination is the most effective available preventive strategy, its reliance on strain predictions and yearly updates limits its effectiveness. The virus’ ability to cause both epidemics and pandemics, driven by zoonotic transmissions, underscores its continuous threat. The ongoing H5N1 avian influenza outbreak is the perfect example, renewing concerns due to its ability to infect over 70 mammalian species and sporadically transmit to humans. This study aims to evaluate the protective potential of two human monoclonal antibodies against diverse and recent influenza virus strains. Method: PN-SIA28 and PN-SIA49 monoclonal antibodies were previously isolated from an individual undergoing seasonal influenza vaccination and with no known recent influenza virus exposure. Their breadth of recognition, neutralization, and conferred in vivo protection were assessed against multiple influenza viruses, including pre-pandemic strains. Structural analyses were performed to characterize antibody–antigen interactions for epitope identification. Results: Both antibodies recognize a broad range of strains and neutralize pre-pandemic avian influenza viruses, including the currently circulating H5N1 clade. Moreover, a structural analysis revealed that PN-SIA49 binds a conserved HA stem region, overlapping with epitopes recognized by other broadly neutralizing antibodies. Conclusions: These findings underscore the potential of broadly neutralizing antibodies as a basis for universal influenza countermeasures against both seasonal and pandemic threats. Additionally, they provide guidance for the design of targeted vaccine strategies to steer immune responses toward broadly protective epitopes. Full article

Background/Objectives: Cigarette smoke (CS) drives pathogenesis across the spectrum of chronic respiratory disorders, exerting its detrimental effects primarily through oxidative stress and programmed cell death. Scutellarein (Scu), a botanical-origin flavonoid enriched in respiratory therapeutics-oriented Chinese medicinal herbs, demonstrates established anti-inflammatory applications. This study systematically evaluated the protective roles of Scu against CS-induced lung injury and explored the underlying mechanisms. Methods: Subacute CS-exposed mice were used to evaluate the therapeutic effects of Scu on lung injury. Immunofluorescence and quantitative PCR were used to examine the expression levels of junctional proteins and proinflammatory mediators. Apoptotic cell death was quantified using Annexin V-FITC/7-AAD staining. Transepithelial electrical resistance and dextran permeability assay were used to access the barrier integrity in alveolar epithelial MLE-12 cells. Western blotting was used to detect the changes in the signal pathway. Results: In CS-exposed mice, Scu administration dose-dependently reduced histopathological scores, pulmonary edema, changes in the alveolar structure, and inflammatory cell infiltration. In MLE-12 cells, Scu significantly suppressed cigarette smoke condensate (CSC)-induced inflammatory mediators, oxidative stress, caspase-3 activation, and apoptosis and preserved CSC-suppressed tight junction protein expression and barrier disruption. Scu also rescued CSC-altered expression levels of Hrk, Ecscr, and Myo5b and mitigated the CSC-suppressed PI3K/AKT/mTOR pathway. Conclusions: Scu alleviates CS-induced subacute lung injury through its antioxidant, anti-apoptotic effects to maintain epithelial barrier integrity likely via the mitigation of the CSC-suppressed PI3K/AKT/mTOR pathway. Full article

Background: Children and adolescents are pivotal in the transmission of influenza, and vaccination remains the most effective preventive measure. Cell-based influenza vaccines offer advantages over traditional egg-based vaccines by reducing egg-adapted mutations and improving antigenic match. SKYCellflu^® quadrivalent influenza vaccine (QIV; SK bioscience, Korea), the first cell-based QIV licensed in Korea for individuals aged 6 months and older, offers potential advantages; however, its real-world effectiveness in the Korean pediatric population remains limited. Objective: This study aimed to estimate the real-world effectiveness of SKYCellflu^® QIV, a cell-based QIV, in preventing laboratory-confirmed influenza among children and adolescents aged 6 months to 18 years in Korea during the 2024–2025 influenza season. Methods: A multicenter, prospective, test-negative case–control study was conducted from October 2024 to May 2025 across 25 institutions in Korea. Children and adolescents aged 6 months to 18 years who presented within 7 days of the onset of influenza-like illness (fever ≥ 38 °C and at least one respiratory symptom) were enrolled. Influenza infection was confirmed using rapid antigen tests or polymerase chain reaction; participants who tested positive were classified as cases, and those who tested negative for influenza served as controls. All participants were further categorized as vaccinated or unvaccinated based on receipt of SKYCellflu^® QIV. Those who received other influenza vaccines during the season were excluded. Vaccination status was verified through medical records and the national immunization registry. Results: A total of 1476 participants were included (751 cases, 725 controls). The overall adjusted vaccine effectiveness (aVE) was 45.57% (95% CI, 29.38–58.04). The vaccine demonstrated the highest effectiveness in children aged 6–35 months (aVE: 88.55%; 95% CI, 60.39–96.11). Effectiveness was higher against influenza B (aVE: 61.28%; 95% CI, 35.76–76.30) than influenza A (aVE: 41.63%; 95% CI, 22.55–56.01). The vaccine’s effectiveness in adolescents was not statistically significant due to the small sample size in this age group. Conclusions: This multicenter test-negative study provides the first real-world effectiveness of SKYCellflu^® QIV in a Korean pediatric population. The results suggest substantial protection in younger children, particularly against influenza B, and support the continued use of annual influenza vaccination in this population. Further studies with larger adolescent cohorts are needed to confirm these findings in older age groups. Full article

Acute respiratory distress syndrome (ARDS) is a fatal inflammatory lung disorder with few effective treatments. Hyaluronan (HA), a major extracellular matrix component, exhibits diverse biological activities depending on its molecular weight. This study aimed to evaluate the therapeutic potential of HA of various molecular weights in a rat model of ARDS. ARDS was induced in rats via the intratracheal instillation of 5 mg of bleomycin. Seven days later, when ARDS symptoms developed, low (LHA), medium (MHA), high (HHA), and mixed (MIX HA) hyaluronan were intratracheally administered seven times from Days 7 to 28. On Day 7, arterial oxygen saturation (SpO₂) and the partial pressure of oxygen (PaO₂) decreased, carbon dioxide levels increased, the respiratory rate increased, and extensive lung cell infiltration was observed, confirming successful ARDS induction. LHA and MIX HA improved the SpO₂ and PaO₂, and the latter increased lung and alveolar volume, reduced infiltration, and normalized breathing. All HA types attenuated collagen deposition and M1 macrophage activity, while MIX HA enhanced M2 polarization and upregulated MMP-2, MMP-9, and TLR-4. LHA increased VEGF and EGF expression. These findings demonstrate that different-weight HAs provide partial ARDS protection via distinct mechanisms. MIX HA shows synergistic effects, restoring and improving lung structure and function, respectively, representing a promising ARDS therapy. Full article

Background/Objectives: COVID-19 mRNA vaccines protect against hospitalization, but less is known about real-world vaccine effectiveness (VE) against other severe outcomes. Methods: We enrolled adults hospitalized with acute respiratory illness at two hospitals in Atlanta, Georgia, USA from May 2021 to January 2023. Participants were eligible if they had standard-of-care COVID-19 testing or provided an upper respiratory swab for analysis. Vaccination status was confirmed through the state registry. mRNA COVID-19 VE among those with severe outcomes was determined using a test-negative case–control design with stepwise logistic regression adjusting for confounding variables. Results: Of 1973 participants eligible for analysis, 886 (44.9%) were unvaccinated, 641 (32.5%) received a primary series, and 446 (22.6%) received a primary series plus ≥ 1 booster. A total of 734 (37.2%) were positive for COVID-19. During the pre-Delta/Delta (2 May 2021–19 December 2021) vs. Omicron (20 December 2021–31 January 2023) eras, adjusted COVID-19 mRNA VE of a primary series compared to no vaccination was 85.5% (95% CI: 77.0%, 90.8%) vs. 38.2% (95% CI: 11.5%, 56.8%) overall, 90.0% (95% CI: 82.6%, 94.2%) vs. 54.4% (95% CI: 9.0%, 77.1%) among those with radiographic pneumonia, and 94.4% (95% CI: 80.5%, 98.4%) vs. 62.5% (95% CI: 19.0%, 82.7%) among those admitted to the ICU. VE against severe outcomes was highest within the 6 months following vaccination and during the pre-Delta/Delta era. A booster dose partially restored VE against Omicron-associated hospitalization and pneumonia. Conclusions: COVID-19 mRNA vaccines were effective at preventing hospitalization and other severe outcomes in adults during periods of pre-Delta/Delta and Omicron variant circulation. Full article

Introduction: Patients with an intracerebral hemorrhage (ICH) have been shown to have a high incidence of acute respiratory distress syndrome (ARDS). We aimed to determine the incidence of ARDS following ICH in the era of lung-protective ventilation. We also examined risk factors associated with ARDS following ICH. Materials and Methods: A retrospective cohort study of adults admitted to a single health system’s intensive care units with acute, spontaneous ICH from 1 March 2015 to 28 February 2018, using univariate and multivariable logistic regression models to evaluate the associations of patient characteristics with the diagnosis of ARDS. Results: In total, 269 patients were included, with 155 patients requiring invasive mechanical ventilation. The overall incidence of ARDS was 6.7% (18/269), and the incidence in intubated patients was 10% (16/155), as the median time of ventilation with >8 cc/mL of ideal body weight was low. For the entire ICH population, severity of hypoxemia on initial arterial blood gas (ABG; Odds Ratio [OR] per 10 mmHg 0.855 [95% Confidence Interval [CI] 0.74–0.987]) and total minutes of mechanical ventilation (OR per 60 min 1.018 [95% CI 1.007–1.029]) were both associated with the diagnosis of ARDS. In intubated patients, ventilation, younger age (OR per 10 years 0.655 [95% CI 0.431–0.997]), and total minutes of mechanical ventilation (OR per 60 min 1.028 [95% CI 1.006–1.049] increased the odds of developing ARDS. Conclusions: ARDS was found to be significantly lower in the present cohort of ICH patients when compared to prior studies, with younger age and hypoxemia associated with an increasing risk. Full article

Background: Molar–Incisor Hypomineralization (MIH) represents a developmental enamel defect of systemic origin, typically affecting the first permanent molars and often the incisors. Within the limitations of this study, several associations were observed between perinatal factors and MIH-related outcomes. However, most of these connections were not retained in adjusted analyses. Febrile illness during the first year of life showed a significant association with hypersensitivity. Methods: A structured 30-item questionnaire was distributed to mothers of 50 children diagnosed with MIH between February and March 2024. Data was analyzed using chi-square tests, with p < 0.05 considered significant, and univariate and multivariate logistic regressions at 95% confidence interval. Clinical diagnosis followed the Weerheijm (EAPD) criteria. Results: Maternal medication during pregnancy (antibiotics, antiepileptics, asthma drugs) was significantly associated with preterm birth (p = 0.01). Low birth weight correlated with tooth eruption disorders (p = 0.009) and perinatal complications such as hypoxia and respiratory distress (p = 0.0001). Fluoride application demonstrated a protective effect against discolorations (p = 0.005), caries (p = 0.002), and hypersensitivity (p = 0.01). In the multivariate model, febrile illness during the first year of life may be associated with hypersensitivity in MIH-affected teeth (aOR = 5.71, 95% CI: 1.01–32.27, p = 0.049). Conclusions: Maternal medication and perinatal complications, particularly low birth weight, were associated with MIH occurrence. Preventive strategies emphasizing maternal health, early screening, and remineralization-based therapies can mitigate long-term oral health impacts. Full article

The recent literature has debunked the widespread hypothesis that viruses are primarily transmitted via droplets and not beyond 1.5 m, and transmission via contact has been downplayed. Hence, an evidence-based revision of the existing isolation guidelines for respiratory viruses was needed. Therefore, a completely new protocol for respiratory virus isolation in terms of personal protective equipment and patient room air purification was evaluated. Isolation relief criteria based on Ct values in follow-up sampling were assessed. A Ct value of <28 was employed as a proxy for potential active replication and associated transmissibility. Between 25% and 50% of patients who tested positive for RSV, HRV, hMPV, or SARS-CoV-2 continued to exhibit high viral loads on day 7 post-initial diagnosis, underscoring the potential for sustained infectivity. Hence, the discontinuation of isolation measures for these patients without follow-up testing may carry a considerable risk of ongoing viral transmission. On the contrary, only 7% of patients positive for Flu and 14% for PIV had a follow-up sample on day 7 with a Ct value of less than 28. Ct values increased more rapidly in influenza, indicating faster viral clearance compared to other respiratory viruses. Based on these results, the policy of a standard 7-day isolation period without follow-up testing could be adopted for influenza-positive patients. Full article

Urban heat waves are intensifying under climate change, posing growing public health risks, particularly in rapidly urbanizing cities. Green infrastructure is widely promoted as a nature-based solution for heat mitigation, yet its health benefits may vary across urban contexts. This study examines how neighborhood-level green infrastructure modifies heat-related health risks in Tabriz, Iran—a historically cold city experiencing increasing heat stress. The Normalized Difference Vegetation Index (NDVI) was derived from Landsat 8 imagery for 190 neighborhoods and classified into quartiles. Heat waves were defined as two or more consecutive days with mean temperatures at or above the 95th percentile. Emergency department visits for cardiovascular, respiratory, and all-cause conditions (2018–2020) were analyzed using Distributed Lag Non-linear Models with quasi-Poisson regression. Neighborhoods with low-to-moderate greenness (second and third NDVI quartiles) consistently exhibited lower relative risks of heat-related cardiovascular and all-cause visits, while both the lowest and highest NDVI quartiles showed elevated risk estimates. Risk patterns varied by lag period and demographic subgroup, with higher vulnerability observed among males and younger adults in highly vegetated areas, though estimates were imprecise. These findings suggest a non-linear relationship between urban greenness and heat-related health risks. Moderate green infrastructure appears most protective, underscoring the importance of context-sensitive and equitable greening strategies for climate adaptation in heat-vulnerable cities. Full article

Background: Hospital-acquired influenza remains a persistent threat that amplifies morbidity, mortality, length of stay, and operational strain, particularly among older and immunocompromised inpatients. The COVID-19 era reshaped control norms—normalizing N95 use during surges, ventilation improvements, and routine multiplex PCR—creating an opportunity to strengthen hospital outbreak management. Methods: We conducted a targeted narrative review of WHO/CDC/Infectious Diseases Society of America (IDSA) guidance and peer-reviewed studies (January 2015–August 2025), emphasizing adult inpatient care. This narrative review synthesizes recent evidence and discusses theoretical implications for practice, rather than establishing formal guidelines. Evidence was synthesized into pragmatic practice statements on detection, diagnostics, isolation/cohorting, antivirals, chemoprophylaxis, vaccination, surveillance, and communication. Results: Early recognition and test-based confirmation are pivotal. For inpatients, nucleic-acid amplification tests are preferred; negative antigen tests warrant PCR confirmation, and lower-respiratory specimens improve yield in severe disease. A practical outbreak threshold is ≥2 epidemiologically linked, laboratory-confirmed cases within 72 h on the same ward. Effective control may require immediate isolation or cohorting with dedicated staff, strict droplet/respiratory protection, and daily active surveillance. Early oseltamivir (≤48 h from onset or on admission) reduces mortality and length of stay; short-course post-exposure prophylaxis for exposed patients or staff lowers secondary attack rates. Integrated vaccination efforts for healthcare personnel and high-risk patients reinforce workforce resilience and reduce transmission. Conclusions: A standardized, clinician-led bundle—early molecular testing, do-not-delay antivirals, decisive cohorting and Personal protective equipment (PPE), targeted chemoprophylaxis, vaccination, and disciplined communication— could help curb transmission, protect vulnerable patients and staff, and preserve capacity. Hospitals should codify COVID-era layered controls for seasonal influenza and rehearse unit-level outbreak playbooks to accelerate response and recovery. These recommendations target clinicians and infection-prevention leaders in acute-care hospitals. Full article