A nanoparticle vaccine targeting glycoprotein D induces immune protection against pseudorabies virus.

We aimed to examine the association between insulin resistance (IR) and target organ damage (TOD) in patients with hypertension. Three indices of IR (Triglyceride-Glucose index: TyG; triglyceride-to-HDL ratio: TG/HDL-C; Metabolic Score for Insulin Resistance: METS-IR) were examined for their association with TOD in 614 newly diagnosed patients with hypertension. Left ventricular mass index (LVMI), the intima-media thickness of the common carotid artery (IMT-CCA) and estimated Glomerular Filtration Rate (eGFR) were used as indices of cardiac, artery and renal damage. Receiver Operating Characteristic (ROC) analysis performed to estimate optimal cut-off for each index, while simple and multiple logistic regression models were applied to examine the indices as binary predictors of organ damage. Linear and non-linear associations were examined with continuous variables using linear regression and restricted cubic splines (RCS) models. After adjusting for confounders, logistic regression showed that high TG/HDL-C (OR:1.50, 95%CI:1.03-2.18) and METS-IR (OR:2.17, 95%CI:1.50-3.13) were associated with increased risk of left ventricular hypertrophy, while only high METS-IR was associated with increased risk of carotid plaque (OR:2.07, 95%CI:1.17-3.68) and only high TG/HDL-C was associated with renal damage (OR:2.33, 95%CI:1.02-5.36). Adjusted linear regression showed that none of the indices were significantly associated with LVMI. However, all indices were associated with CCA-IMT (p<0.05), but none with eGFR (p>0.05). Adjusted RCS models showed a significant non-linear association between TyG and CCA-IMT (p for non-linearity = 0.009). In conclusion, IR biomarkers are of clinical value in newly diagnosed patients with hypertension.

Antibody-drug conjugates (ADCs) are constrained by limited tumor penetration of IgG formats and heterogeneity from stochastic conjugation. We addressed these challenges by engineering a compact trastuzumab Fab-based ADC with site-specific installation of DM1 using the peptide ligase butelase-1 and by extending serum persistence via genetic fusion of an albumin-binding domain (ABD). Butelase-1 ligation proceeded rapidly under mild conditions to afford a homogeneous product with a defined drug-to-antibody ratio. The conjugate selectively killed HER2-positive cells in vitro while sparing HER2-negative controls. ABD fusion increased serum albumin binding and improved in vivo exposure; the resulting T-Fab-ABD(H + L)-DM1 produced superior tumor growth inhibition in HER2-positive xenografts compared with its non-ABD analogue. The ADC showed no significant body weight loss or organ damage in mice, indicating good tolerability. These findings validate a modular strategy combining a Fab scaffold, enzymatic site-specific conjugation, and ABD-mediated half-life extension to generate potent, homogeneous ADCs and nominate T-Fab-ABD(H + L)-DM1 as a promising candidate for HER2-positive cancer therapy.

Sepsis is a clinical syndrome marked by a dysregulated host response to infection, impairing oxygen delivery and utilization and causing organ dysfunction. Hypoxemia, which can cause significant tissue and organ damage, commonly occurs in sepsis. Thus, oxygen therapy is essential in patients with sepsis. However, the optimal oxygenation target for these patients remains controversial. To evaluate the effects of different oxygenation targets on short- and medium-term outcomes in patients with sepsis. A prospective, single-center, randomized controlled trial was conducted. The primary outcome was 28-day mortality. Secondary outcomes included 90-day mortality and intergroup comparisons of mechanical ventilation and vasopressor use during hospitalization. In total, 270 patients were randomly assigned to the conservative oxygenation, conventional oxygenation, and hyperoxygenation target groups (n = 86, 93, and 91), of whom 35 (40.7%), 32 (34.4%), and 17 (18.7%) died by day 28, respectively. The 28-day mortality significantly differed between these groups ( P = 0.005). Pairwise comparison revealed a significant difference between the conservative oxygenation and hyperoxygenation target groups (χ 2 = 10.132, P = 0.001). Kaplan-Meier analysis showed significant differences in survival distributions among the groups (χ 2 = 10.340, P = 0.006). The 90-day mortality rates were 50.0%, 41.9%, and 36.3% in the conservative oxygenation, conventional oxygenation, and hyperoxygenation target groups, respectively, exhibiting no significant difference. Compared with conservative oxygen therapy, hyperoxygenation (PaO 2 : 100-150 mmHg) reduced 28-day mortality in patients with sepsis. However, no significant differences were observed among oxygenation targets regarding 90-day outcomes.

Electrically controlled hyaluronic acid-based hydrogel for sustained and repeatable metronomic chemotherapy.

Esketamine attenuated sepsis-induced organ injury in mice via the TGF-β-Smad3 signaling pathway.

Preeclampsia (PE) is a complex hypertensive disorder resulting from placental insufficiency during pregnancy. PE contributes to maternal and fetal morbidity and mortality and often co-occurs with fetal growth restriction (FGR); these two are both considered placental insufficiency syndromes. Alterations in mitochondrial function levels due to placental insufficiency play an important role in the pathophysiology of PE and FGR. Changes in these processes can lead to maternal and fetal organ damage with subsequent risk to develop cardiovascular disease. This review therefore investigates the effects of placental insufficiency syndromes, including PE and FGR, on mitochondrial function and its underlying mechanisms, using a perinatal approach including maternal heart and kidney, placenta, and fetal heart and kidney. This review also explores the potential of mitochondrial-targeted therapies in mitigating these effects. We provide an overview of the literature at hand and demonstrate the critical role of mitochondrial function in different organ systems. Subsequently, we also discuss the need for mitochondrial-targeted therapies, in particular, focused on oxidative stress, metabolic pathways, mitochondrial quality control, and mitochondrial calcium handling. This knowledge provides guidance for future studies and potential therapies to improve PE and FGR and their consequences for maternal and fetal outcomes during pregnancy and cardiovascular health later in life.

The impact of ultra-high pressure processing on crayfish tropomyosin allergenicity and microstructure preservation: Insights into texture and flavors.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with well-recognized female predominance; however, disease expression and severity may differ by gender. Data on gender-based differences in SLE from Bangladesh remain limited. This study aimed to compare sociodemographic characteristics, clinical manifestations, immunological profiles and disease activity indicators between male and female patients with SLE. This cross-sectional study was conducted at the Lupus Clinic, Department of Rheumatology, Bangladesh Medical University (BMU), Dhaka, Bangladesh, from December 2019 to January 2021. A total of 140 patients who fulfilled the classification criteria for SLE were enrolled, including 130 females and 10 males. Demographic data, clinical features, immunological and serological parameters, Safety of Estrogens in Systemic Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) were analyzed and compared by gender. The female-to-male ratio was approximately 13:1. Male patients presented at younger ages (p=0.002) and had earlier disease onset than females (p=0.011). Lupus nephritis was significantly more frequent among male patients (p=0.037). Anti-dsDNA levels were higher in male patients, though not statistically significant; complement (C3) levels were significantly lower in male patients (p=0.014). Male patients had significantly higher disease activity (SELENA-SLEDAI) scores than females (p=0.044), whereas cumulative organ damage was comparable. Despite lower prevalence, male SLE patients exhibited more severe disease manifestations and higher activity. These findings underscore the importance of heightened clinical vigilance and gender-sensitive management strategies in SLE.

Elevated lipoprotein(a) [Lp(a)] levels have been strongly related to cardiovascular (CV) risk. However, its association with Hypertension Mediated Organ Damage (HMOD) and CV events in the primary prevention setting remains unclear. To evaluate in these patients, the correlation between Lp(a) levels and: (i) heart, vessels and kidney HMOD and; (ii) CV events and all-cause mortality in a primary prevention setting. 747 low CV risk subjects were recruited between 2009 and 2014. HMOD was assessed through Pulse Wave Velocity, carotid Intima-Media Thickness (IMT), presence of carotid plaques, Left Ventricular Hypertrophy (LVH) and Ejection Fraction and glomerular filtration rate. All-cause mortality and CV events up to 2021 were retrieved by electronic health records, for a median follow-up time of 10 years (I-III quartiles 9.6-11.1). Mean age was 50.8 ± 13.0 years and 63.5% of the subjects were men. The prevalence of hypertension was 37.9%, dyslipidemia 67.2%, smoking 17.8%, and diabetes mellitus 8.7%. Median Lp(a) value was 17 mg/dL (5.9-56.0), and 26.5% of patients had values above 50 mg/dL. Regarding HMOD, 10.3% subjects had arterial stiffness, 7.2% increased IMT, 19.8% carotid plaques while only 0.7% had LVH. No significant correlation was found between Lp(a) levels and indices of subclinical HMOD. Furthermore, no relationship was found between CV events and all-cause mortality and Lp(a) levels. In this primary prevention cohort, elevated Lp(a) levels were not associated with significant structural damage to the heart, carotid arteries, or increased aortic stiffness and were not associated with CV events and all-cause mortality.

Erchen decoction promotes inguinal white adipose tissue browning via the M2 macrophage-sympathetic axis to ameliorate obesity in mice.

Encephalopathy is a heterogeneous clinical syndrome with numerous neurological and systemic etiologies. We report the case of a 67-year-old man, a chronic ethanol consumer, admitted with a one-week history of confusional syndrome. Initial laboratory tests revealed severe hypercalcemia, acute kidney injury, mild anemia, and hyperproteinemia. Serum ammonia levels were within normal limits, reducing the likelihood of hepatic encephalopathy despite the patient's chronic ethanol use. Cerebral imaging excluded acute cerebrovascular events, while abdominal ultrasound demonstrated splenomegaly and normal-sized kidneys. Serum protein electrophoresis and immunofixation identified a monoclonal IgG-kappa component, strongly suggestive of multiple myeloma. The patient's neurocognitive symptoms improved rapidly following systemic corticosteroid therapy and fluid-electrolyte rebalancing, confirming hypercalcemia as the primary mechanism of encephalopathy. Hypercalcemic encephalopathy as an initial manifestation of multiple myeloma is exceedingly rare. This case highlights the diagnostic complexity in elderly patients with multiple potential contributors to altered mental status, including chronic ethanol exposure and renal dysfunction. The presence of normal renal dimensions, unexplained hypercalcemia, and a monoclonal component should prompt evaluation for plasma cell malignancy. Early recognition of hypercalcemia-induced encephalopathy and prompt investigation for underlying hematologic malignancy are essential to prevent irreversible organ damage and to ensure timely initiation of specific therapy.

This study aimed to quantify the temporal evolution of multiple organ dysfunction syndrome (MODS) following trauma with secondary sepsis and to validate a rodent-specific MODS scoring system over 6-72 hours. A total of 168 male Sprague-Dawley rats (8 weeks old, SPF grade) were randomly divided into four groups: the normal control group (NC group), limb crush injury group (Fx group), cecal ligation and puncture group (CLP group), and limb crush injury combined with CLP group (Fx+CLP group). A stepwise CLP surgery was performed in the Fx+CLP group 24 hours after closed tibial and fibular fracture surgery to mimic the clinical window of high infection incidence. Five observation time points were set: 6, 12, 24, 48, and 72 hours. Hematological parameters were detected, and tissues of rats were examined histopathologically before a diagnostic scoring system for MODS in experimental animals was constructed. The mortality rate of the Fx+CLP group was 58.33%, significantly higher than in the other groups ( P < 0.01). The levels of white blood cells, interleukin (IL)-6, and IL-10 in the Fx+CLP group, which peaked at 24 hours, were notably higher than those of the CLP group at each time point ( P < 0.01). During the organ-function assessment, the Fx+CLP group started to present with cardiac and hepatic dysfunction 12 hours after the first onset, and pulmonary and renal dysfunction 24 hours after the first onset. The pathological damage to the organs worsened with time. Particularly, the brain tissue pathology suggested that the pathological score of the Fx+CLP group exceeded 2 at 24 hours after the first onset. Moreover, coagulation dysfunction started 12 hours after the first onset. In general, the timing features of organ damage were distinct, and the overall damage was much more severe than in the single-factor damage groups. A consecutive 6- to -72-hour quantitative profile of MODS across six organ systems was established, demonstrating that cardiac and hepatic dysfunction emerged at 12 hours, followed by pulmonary, renal, neurological, and coagulatory failure at 24 hours. The validated MODS score was expected to offer a robust translational tool for timing therapeutic interventions.

Patients with difficult to control hypertension (HTN) are often referred by general practitioners to specialized centers to estimate global cardiovascular (CV) risk profile, evaluate hypertension-mediated organ damage (HMOD), and optimize antihypertensive therapy. This referral provides a unique opportunity to analyse patients with high CV risk and HTN in a real-world setting, characterized by the rigorous adoption of uniform and state-of-the-art procedures by expert personnel. To examine (1) global CV risk profile, office and out-of-office blood pressure (BP) levels, and markers of HMOD in adult patients referred to a high-volume European Hypertension center; (2) to evaluate how these clinical parameters impact on the choice of different antihypertensive therapies. An observational, cross-sectional study was conducted in adult patients of both sexes, aged ≥ 18 years, with essential treated hypertension, who were consecutively evaluated at the Excellence Hypertension Center at Sant'Andrea Hospital in Rome, Italy. Office and out-of-office BP levels were measured, and different hypertension phenotypes were set according to European guidelines. CV risk profile was estimated according using SCORE2. Only patients with treated HTN were selected for the analysis and stratified according to antihypertensive therapies: (1) angiotensin receptor blockers (ARBs); (2) angiotensin converting enzyme (ACE) inhibitors; (3) other drugs (including diuretics, beta-blockers, calcium channel blockers, alpha-blockers, mineralocorticoid receptor antagonists). From an overall database of 11,168 outpatients, a total of 5,677 patients with treated HTN were analysed (46.3% females, age 63.6 ± 13.1 years, BMI 27.4 ± 4.8kg/m2, office BP 140.6 ± 17.5/85.5 ± 11.5 mmHg, 24-hour BP 128.7 ± 13.7/77.2 ± 9.7 mmHg, SCORE2 5.4 ± 4.3%). Among these, 52.9% were treated with ARBs, 30.2% with ACE inhibitors and 17.0% with other drugs. Patients treated with ARBs were more frequently males, and significantly older, had more frequently obesity (P < 0.001), dyslipidaemia (p < 0.001), and diabetes (p < 0.001) than those treated with other drug classes. They also had more frequently CV comorbidities (P < 0.001) and resistant HTN (P < 0.001). They received more BP lowering agents (P < 0.001), being more frequently treated with triple (P < 0.001), quadruple (P < 0.001), or more complex (P < 0.001) combination therapies. Comparable office and out-of-office BP control were recorded between patients treated with ARBs and those patients managed with either ACE inhibitors or other drugs. Among adult outpatients referred to an excellence hypertension center, the majority were treated with ARBs, alone or in combination therapies. ARB-treated patients presented more frequently CV risk factors, comorbidities, and difficult-to-treat HTN.

Rapid detection of Shiga toxin-producing Escherichia coli via multiplex gastrointestinal pathogen polymerase chain reaction in a 5-year-old girl with hemorrhagic enterocolitis and rotavirus coinfection preceding influenza A infection for minimizing organ damage in hemolytic uremic syndrome.

Blood pressure (BP) is a dynamic trait associated with cardiovascular disease. We aimed to estimate age-specific BP levels and rates of change from childhood to mid-adulthood and to examine their associations with subsequent subclinical target organ damage. We included 2508 participants from the Hanzhong Adolescent Hypertension Study with BP measured ≥4× from 1987 to 2023. Surrogate markers of target organ damage were assessed, including arterial stiffness, left ventricular hypertrophy, and albuminuria. Growth models were used to construct BP trajectories and estimate age-specific BP levels and rates of change (slopes). Rates of change in BP at each age point from childhood to mid-adulthood were positively associated with arterial stiffness and albuminuria in mid-adulthood, independent of corresponding BP levels. The magnitude of the associations rose from childhood, peaked in adolescence, and declined thereafter. For example, odds ratios (95% CIs) per 1 SD increase in systolic BP change rates for arterial stiffness increased from 1.94 (1.69-2.24) at age 6 to 2.11 (1.82-2.44) at age 13, then declined to 1.13 (1.01-1.28) by age 52. Faster BP increases were more strongly associated with arterial stiffness and albuminuria than concurrent BP levels during childhood and adolescence, whereas the opposite trend was observed in young and mid-adulthood. Similar age-dependent trends were identified for left ventricular hypertrophy, with minor variations in the ages at which associations reached statistical significance. Accelerated BP increases during childhood and adolescence show a stronger association with mid-adult subclinical target organ damage than increases occurring in adulthood.

A novel bilirubin-lowering mechanism of Ginkgo Biloba terpene lactones discovered in safety assessment.

Hypertension-mediated organ damage (HMOD) represents a critical and dynamic stage on the cardiovascular continuum, serving as the primary mechanistic link between sustained arterial pressure elevation and major adverse cardiovascular and renal events. HMOD is often subclinical at first occurrence and is a systemic, cumulative process, representing structural and functional injury of the heart, brain, kidneys, and vasculature. This narrative review synthesises current evidence on the pathogenesis and clinical sequelae of HMOD, specifically focusing on the interplay between chronic haemodynamic load, endothelial dysfunction, oxidative stress, neurohormonal activation, inflammation, and microvascular remodelling. Key manifestations such as left ventricular hypertrophy, hypertensive nephrosclerosis, cerebral small vessel disease, and arterial stiffness can be regarded as dynamic and partly modifiable phenomena of subclinical injury rather than inevitable sequelae of long-standing hypertension. This review aims to summarise contemporary detection and risk stratification approaches, drawing on the 2023 European Society of Hypertension (ESH) and 2024 European Society of Cardiology (ESC) guidelines, combining imaging and biomarker-based assessment. Evidence supporting organ protection as an important therapeutic objective is also reviewed, with particular attention to regression of left ventricular mass and reduction in albuminuria as treatment endpoints associated with improved prognosis beyond blood pressure reduction alone. Finally, unresolved issues such as causal versus associative properties of candidate biomarkers, comparative validity of vascular indices, and heterogeneity in organ-specific response to therapy are critically analysed. The overarching goal of this review is to support a clinically applicable framework for early HMOD detection and organ-protective treatment strategies in routine hypertension care.

Metabolic syndrome and uric acid in pediatric hypertension: implications for early target organ damage risk stratification.

Hypertension and diabetes mellitus are both known risk factors for atrial fibrillation (AF). Whether coexisting hypertension exacerbates AF risk among individuals with diabetes remains unclear. This study aims to investigate the association between hypertension and incident AF in this population. We studied participants in the prospective Kailuan Study, including 18,084 adults diagnosed with diabetes between 2006 and 2011 and free of AF at baseline. Hypertension was defined by a previous diagnosis, use of antihypertensive medications, or systolic/diastolic blood pressure ≥140/90 mmHg. Incident AF was identified via biennial electrocardiograms and hospital records. Cox proportional hazards models adjusted for demographic, lifestyle, metabolic, and clinical covariates were used to estimate hazard ratios (HRs). Over a median follow-up of 14.8 years (interquartile range 12.7-16.8), 275 participants with diabetes developed AF, and 5,265 died from any cause. Hypertension was associated with a higher risk of AF (adjusted HR, 1.48; 95% confidence interval [CI], 1.05-2.07) compared to those without hypertension. Compared to participants with normal blood pressure, the adjusted HRs for AF were 1.54 (95% CI, 1.11-2.13) for grade 1 hypertension and 1.61 (95% CI, 1.06-2.44) for grade 2 hypertension. Among those with hypertension, target organ damage-particularly prior myocardial infarction or ischemic stroke-further elevated AF risk (HR, 2.66; 95% CI, 1.26-5.60). Hypertension independently increases AF risk in individuals with diabetes, especially with higher blood pressure levels and target organ damage. Early hypertension control is crucial for the prevention of AF in this high-risk population.