Investigating the impact of remnant cholesterol on new-onset stroke across diverse inflammation levels: Insights from the China Health and Retirement Longitudinal Study (CHARLS).

BACKGROUND: Prior research underscores the significant impact of remnant cholesterol (RC) on stroke occurrence due to its proatherogenic and proinflammatory traits. This study aims to explore diverse risks of new-onset stroke associated with RC, considering distinct inflammation levels in the middle-aged and senior population in China. METHODS: We analyzed 6509 participants from the China Health and Retirement Longitudinal Study (CHARLS) across four waves (2011-2018). We employed a multivariable Cox proportional hazards regression model, incorporated restricted cubic spline techniques, and conducted sensitivity analyses to evaluate the association among RC, high-sensitivity C-reactive protein (hsCRP), and the risk of new-onset stroke. RESULTS: Over 7 years, 540 new-onset strokes occurred. Individuals in the highest quartile of RC levels exhibited a heightened risk of new-onset stroke, with a multivariable-adjusted hazard ratio (HR) peaking at 1.50 (95% confidence interval 1.12-2.00, P for trend = 0.021), showing a non-linear correlation (P nonlinearity = 0.049). High hsCRP alone had an adjusted HR of 1.10 (95% CI 0.87-1.39), compared to 1.40 (95% CI 1.00-1.96) for high RC alone. Additionally, concurrent high RC and hsCRP showed an adjusted HR of 1.43 (95% CI 1.05-1.96). Consistency persisted across various hsCRP thresholds, after adjusting for additional parameters, or excluding chronic diseases in the primary model, reinforcing result robustness. CONCLUSION: Our findings reveal a substantial and non-linear association between higher baseline RC levels and an elevated risk of new-onset stroke. Moreover, elevated levels of both RC and hsCRP jointly pose the highest risk for new-onset stroke, surpassing the risk associated with each factor individually.

Investigation of Stroke Risk Factors and Prognostic Indicators in NVAF Patients with Low CHA2DS2-VASc Scores.

The prognosis of patients with nonvalvular atrial fibrillation (NVAF) with a low CHA2DS2-VASc score (0-1) following a stroke is not well studied. In this investigation, stroke risk factors and prognostic markers in low-risk NVAF patients who are nonetheless at risk for stroke were examined.From January 2012 to January 2022, we retrospectively assessed atrial fibrillation (AF) patients at Xiamen University's Zhongshan Hospital for ischemic stroke. Along with a control group of patients with CHA2DS2-VASc scores of 0-1 who weren't suffering from a stroke, patients with CHA2DS2-VASc scores of 0-1 at the time of stroke were included in the study. Using multivariate logistic regression, independent risk factors were identified. To assess the cumulative occurrences of in-hospital mortality in patients with NVAF-related stroke, the Kaplan-Meier method was used.The study included 156 out of 3.237 inpatients with AF-related stroke who had CHA2DS2-VASc ratings of 0-1. Left atrial diameter (LAD) (odds ratio [OR]: 1.858, 95% confidence interval (CI) 1.136-3.036, P = 0.013), D-dimer (OR: 2.569, 95% CI 1.274-5.179, P = 0.008), and NT-proBNP (OR: 4.558, 95% CI 2.060-10.087, P = 0.000) were found to be independent risk factors for stroke in NVAF patients with a low CHA2DS2-VASc score. During hospitalization, nine patients with NVAF-related stroke died. In patients with NVAF-related stroke, NT-proBNP (hazard ratio: 3.504, 95% CI 1.079-11.379, P = 0.037) was an indicator of mortality risk.Patients with NVAF and CHA2DS2-VASc scores of 0-1 had independent risk factors for stroke in the form of LAD, D-dimer, and NT-proBNP. Notably, in low-risk NVAF patients with stroke, NT-proBNP was discovered to be a potent predictor of in-hospital death.

Recent advances in optical aptasensors for biomarkers in early diagnosis and prognosis monitoring of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver cancers and is one of the main malignant tumor types globally. It is essential to develop rapid, ultrasensitive, and accurate strategies for the diagnosis and surveillance of HCC. In recent years, aptasensors have attracted particular attention owing to their high sensitivity, excellent selectivity, and low production costs. Optical analysis, as a potential analytical tool, offers the advantages of a wide range of targets, rapid response, and simple instrumentation. In this review, recent progress in several types of optical aptasensors for biomarkers in early diagnosis and prognosis monitoring of HCC is summarized. Furthermore, we evaluate the strengths and limitations of these sensors and discuss the challenges and future perspectives for their use in HCC diagnosis and surveillance.

Urinary Creatinine Concentrations and Its Explanatory Variables in General Chinese Population: Implications for Creatinine Limits and Creatinine Adjustment.

Objective: The study aimed to analyze the applicability of the World Health Organization's exclusionary guidelines for Urinary creatinine (Ucr) in the general Chinese population, and to identify Ucr related factors. Methods: We conduct a cross-sectional study using baseline data from 21,167 participants in the China National Human Biomonitoring Program. Mixed linear models and restricted cubic splines (RCS) were used to analyze the associations between explanatory variables and Ucr concentration. Results: The geometric mean and median concentrations of Ucr in the general Chinese population were 0.90 g/L and 1.01 g/L, respectively. And 9.36% samples were outside 0.3-3.0 g/L, including 7.83% below the lower limit and 1.53% above the upper limit. Middle age, male, obesity, smoking, higher frequency of red meat consumption and chronic kidney disease were associated significantly with higher concentrations of Ucr. Results of the RCS showed Ucr was positively and linearly associated with body mass index, inversely and linearly associated with systolic blood pressure, diastolic blood pressure, triglycerides level, and glomerular filtration rate, and were non-linearly associated with triiodothyronine. Conclusion: The age- and gender-specific cut-off values of Ucr that determine the validity of urine samples in the general Chinese population were recommended. To avoid introducing bias into epidemiologic associations, the potential predictors of Ucr observed in the current study should be considered when using Ucr to adjust for variations in urine dilution.

Prostaglandin E2 attenuates synergistic bactericidal effects between COX inhibitors and antibiotics on Staphylococcus aureus.

PGE2 is found to attenuate the bactericidal effects of kanamycin or ampicillin in Staphylococcus aureus, as well as the methicillin-resistant S. aureus (MRSA). Co-treatment with cyclooxygenase (COX) inhibitors (celecoxib, aspirin or naproxen) synergistically enhances kanamycin or ampicillin-induced cell death of S. aureus and MRSA. COX inhibitors repressed bacterial multidrug resistance through down-regulating efflux pump activity in antibiotics-treated S. aureus and MRSA. However, this synergistic bactericidal effects are reduced by the treatment with PGE2. PGE2 restores the efflux pump activity as well as increases biofilm formation in S. aureus and MRSA. Collectively, the enhancement of efflux pump activity and biofilm formation with PGE2 might partially explain the resistance to synergistic bactericidal effects between COX inhibitors and antibiotics in PGE2-treated S. aureus.

Concentration-dependent dual effects of silibinin on kanamycin-induced cells death in Staphylococcus aureus.

Silibinin has dual effects on bacteria, depending on the concentrations or living contexts. The mechanism of either action has not yet been elucidated. Present study suggests that silibinin has yinyang impacts on the growth of Staphylococcus aureus depending on doses. S. aureus treated with low concentration of silibinin (L, 6.2 µM) showed enhanced resistance to kanamycin through increased level of hydrogen peroxide (H2O2). However, S. aureus treated with medium concentration of silibinin (M, 50 µM) showed increased susceptibility to kanamycin through reduced level of H2O2. These findings suggested that dual effects of silibinin were concentration-dependent and apparently related to the levels of H2O2 that assist bacterial survival at higher concentrations. Interestingly, treatment with high concentration of silibinin (H, 400 µM) alone without kanamycin exhibited cytotoxicity to S. aureus regardless of H2O2 levels. Based on the findings in vitro, we moved to examine the influence of silibinin on S. aureus-induced mouse peritonitis model. Silibinin at high concentration was shown to enhance the survival of peritonitis mice and protected them from S. aureus-induced tissue injury presumably by antibacterial effect of high concentration of silibinin. When the infected mice were co-treated with kanamycin, bacterial burden and H2O2 levels in lung, liver and spleen were all increased by treatment with a low dose of silibinin, while decreased with a medium dose of silibinin. Thus, the findings highlighted the potential of silibinin to be as a modifying agent in case of antibiotic resistance.

Salicylate induces reactive oxygen species and reduces ultraviolet C susceptibility in Staphylococcus aureus.

This study demonstrates that growth of Staphylococcus aureus in the presence of salicylate reduces ultraviolet C (UVC)-induced cell death and increases the generation of reactive oxygen species (ROS). In addition, compounds that scavenge ROS (N-acetylcysteine, glutathione, catalase and superoxide dismutase) reverse the increased UVC survival induced by growth in the presence of salicylate, while ROS donors (tert-butylhydroperoxide, H2O2 and NaClO) enhance survival of salicylate challenged cultures. Collectively, these findings suggest that ROS production induced by growth in the presence of salicylate protects S. aureus from UVC-induced cell death.

A preliminary study on epigenetic regulation of Acanthopanax senticosus in leukemia cell lines.

Conventional chemotherapy for leukemia inevitably causes systemic toxicity. Acanthopanax senticosus, a naturally occurring herb used in traditional Chinese medicine, has been found to be a multipotent bioflavonoid with great potential in the prevention and treatment of malignant diseases. However, the mechanism underlying the action of A. senticosus in epigenetic regulation is poorly understood. In the study described here, we focused on the efficacy of A. senticosus in inducing apoptosis of leukemia cells and a possible mechanism. By evaluating the inhibition ratio and morphologic changes, we found that A. senticosus can inhibit growth and induce apoptosis of human leukemia HL-60 and HL60/ADM cells in a dose- and time-dependent manner. Furthermore, A. senticosus induced Fas ligand (FasL) expression and blocked the cell cycle in S phase. In addition, A. senticosus exhibited a potential for inhibition of histone deacetylase (HADC), which contributes to histone acetylation. It possibly resulted in the promotion of the expression of FasL. It is suggested that A. senticosus could be recognized as a new HDAC inhibitor which was able to reactivate aberrantly silenced genes. We discuss the clinical aspects of using A. senticosus for treatment of leukemia.

Quercetin enhances adriamycin cytotoxicity through induction of apoptosis and regulation of mitogen-activated protein kinase/extracellular signal-regulated kinase/c-Jun N-terminal kinase signaling in multidrug-resistant leukemia K562 cells.

Multidrug resistance (MDR) has become a significant challenge in chemotherapeutic treatment of cancer. Quercetin, a naturally occurring flavonoid, has been found to possess anti-proliferative, anti-inflammatory and immunoregulatory bioactivities. The present study was performed to examine the effect of quercetin on human leukemic MDR K562/adriamycin (ADR) cells. Treatment of K562/ADR cells with a combination of quercetin and ADR resulted in potentiation of cytotoxicity, which was measured using a cell counting kit-8 assay. Flow cytometric analysis revealed that quercetin dose-dependently promoted cell apoptosis and treatment with a combination of quercetin and ADR caused synergistic enhancement of the apoptotic effect. In addition, treatment of K562/ADR cells with quercetin alone or in combination with ADR resulted in loss of mitochondrial membrane potential, activation of caspase-8, -9 and -3, reduced expression of the anti-apoptotic proteins B-cell lymphoma (Bcl)-2 and Bcl-extra large and enhanced expression of the pro-apoptotic proteins Bcl-2-interacting mediator of cell death, Bcl-2-associated death promoter and Bcl-2-associated X protein in the cells. Furthermore, the combined treatment of quercetin and ADR synergistically increased the expression of phosphorylated (p-)c-Jun N-terminal kinase and p-p38 mitogen-activated protein kinase and decreased the expression of p-extracellular signal-regulated kinase in the K562/ADR cells. In addition, the expression of P-glycoprotein was significantly decreased following treatment with quercetin alone or in combination with ADR. These findings demonstrated that quercetin is important in MDR and may be developed into a new reversal agent for cancer chemotherapy.

[Expression of alternatively spliced human tissue factor in acute leukemia cells].

The high expression of tissue factor (TF) is related to the coagulation disorder in acute leukemia. TF in blood circulation is mainly expressed in cells, microparticles (MP) and alternatively spliced human tissue factor (asHTF). To elucidate the role of TF in the coagulation disorder of acute myeloid leukemia (AML), RT-PCR was performed on 6 common AML cell lines NB4, HL-60, Kasumi-1, U937, K562 and THP-1. The results showed that only NB4 and U937 cells expressed baseline full-length TF and asHTF which were proved by sequencing. The flow cytometric detection, TF activity and TF antigen tests in NB4 and U937 cells revealed that the asHTF was expressed in trace amount and almost had no activity, while the TF antigen and activity in microparticles were significantly higher than that in asHTF. It is concluded that asHTF may play an unimportant role in the coagulation disorder of AML. Microparticle associated tissue factor (MP-TF) is the predominant source of TF activity released from AML cells.