Background: TREM2 expressed on microglia plays an important role in modulating inflammation in neurodegenerative diseases. It remains unknown whether TREM2 modulates hyperglycemia-induced microglial ...inflammation. Methods: We investigated the molecular function of TREM2 in high glucose-induced microglial inflammation using western blotting, qPCR, ELISA, pulldown, and co-IP methods. Results: Our data showed that in high glucose-induced BV2 cells, TREM2 was increased, and the proinflammatory cytokine IL-1β was increased. TREM2 knockout (KO) attenuated the proinflammatory cytokine IL-1β; conversely, TREM2 overexpression (OE) exacerbated IL-1β expression. Furthermore, we found that high glucose promoted the interaction of TREM2 with NLRP3. TREM2 KO abolished the interaction of TREM2 with NLRP3, while TREM2 OE enhanced the interaction. Moreover, TREM2 KO reduced high glucose-induced NLRP3 inflammasome activation, and TREM2 OE augmented high glucose-induced NLRP3 inflammasome activation, indicating that high glucose enhances the expression of TREM2, which activates the NLRP3 inflammasome. To further clarify whether the NLRP3 signaling pathway mediates the TREM2-regulated inflammatory response, we blocked the NLRP3 inflammasome by knocking out NLRP3 and treating cells with a caspase1 inhibitor, which decreased the levels of the IL-1β proinflammatory cytokine but did not affect the high glucose-induced expression of TREM2. Conclusions: TREM2 modulates high glucose-induced microglial inflammation via the NLRP3 signaling pathway.
Luteolin, a common flavonoid in our daily diet, has potent anti-diabetic effects. However, its prognostic impact on type 2 diabetes mellitus (T2DM) is still uncertain. This study aimed to clarify ...this association.
In this prospective cohort study, 2,461 patients with T2DM were included from the National Health and Nutrition Examination Survey. Dietary luteolin intake was estimated by the type and amount of food consumed in a 24-hour dietary recall. All-cause and cardiac mortality were ascertained by National Death Index Mortality data (as of December 31, 2019). The association of luteolin intake with mortality risk was estimated by Cox proportional hazards model.
The median (interquartile range) luteolin intake was 0.355 (0.130, 0.835) mg/day. During the follow-up (median, 8.4 years), 561 all-cause deaths (including 136 cardiac deaths) were documented. Per-unit increment of luteolin intake (natural logarithm transformed) was found to reduce all-cause mortality by 7.0% (P = 0.024) and cardiac mortality by 22.6% (P = 0.001) in patients with T2DM. An inverse dose-response association was identified between luteolin intake (range: 0.005-9.870 mg/day) and mortality risk. The consistent result was also shown when stratified by age, gender, race, body mass index, HbA1c level, and T2DM duration. Moreover, luteolin intake increment was also shown to be associated with a lower C-reactive protein level at baseline (β =-0.332; 95% CI =-0.541, -0.122).
The current study confirmed that the dietary luteolin intake increment reduced all-cause mortality (especially cardiac mortality) in patients with T2DM, which may be attributed to the anti-inflammatory property of luteolin.
Identifying high-risk patients for contrast-associated acute kidney injury (CA-AKI) helps to take early preventive interventions. The current study aimed to establish and validate an online ...pre-procedural nomogram for CA-AKI in patients undergoing coronary angiography (CAG).
In this retrospective dataset, 4,295 patients undergoing CAG were enrolled and randomized into the training or testing dataset with a split ratio of 8:2. Optimal predictors for CA-AKI were determined by Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) algorithm. Nomogram was developed and deployed online. The discrimination and accuracy of the nomogram were evaluated by receiver operating characteristic (ROC) and calibration analysis, respectively. Clinical usefulness was estimated by decision curve analysis (DCA) and clinical impact curve (CIC).
A total of 755 patients (17.1%) was diagnosed with CA-AKI. 7 pre-procedural predictors were identified and integrated into the nomogram, including age, gender, hemoglobin, N-terminal of the prohormone brain natriuretic peptide, neutrophil-to-lymphocyte ratio, cardiac troponin I, and loop diuretics use. The ROC analyses showed that the nomogram had a good discrimination performance for CA-AKI in the training dataset (area under the curve, AUC = 0.766, 95%CI 0.737 to 0.794) and testing dataset (AUC = 0.737, 95%CI 0.693 to 0.780). The nomogram was also well-calibrated in both the training dataset (
= 0.965) and the testing dataset (
= 0.789). Good clinical usefulness was identified by DCA and CIC. Finally, this model was deployed in a web server for public use (https://duanbin-li.shinyapps.io/DynNomapp/).
An easy-to-use pre-procedural nomogram for predicting CA-AKI was established and validated in patients undergoing CAG, which was also deployed online.
Glasgow prognostic score (GPS) is a reliable scoring system reflecting both nutritional and inflammatory factors. The association of inflammation and nutrition with contrast-associated acute kidney ...injury (CA-AKI) has been validated. This study set out to determine the impact of GPS and its derived scores on CA-AKI incidence.
Populations treated with coronary angiography with/without percutaneous coronary intervention were screened retrospectively. According to C-reactive protein and albumin, three kinds of GPSs were involved: GPS, modified GPS (mGPS), and the cutoff-based GPS (cGPS) which was derived by calculating the optimal cutoff values of two parameters. Primary endpoint was CA-AKI. Pearson’ r correlation, linear/logistic regression, receiver operating characteristic curve as well as subgroup analyses were conducted.
Totally, 3150 patients were valid for analysis, and the mean age was 67.5 years old, with 66.4 % male. Of these, 610 patients suffered CA-AKI. All three kinds of GPSs were independently associated with the SCr elevation proportion (GPS: β = 4.850, 95%CI 3.700 to 8.722, P < 0.001; mGPS: β = 3.450, 95%CI 1.896 to 6.888, P = 0.001; cGPS: β = 3.992, 95%CI 2.368 to 6.940, P < 0.001). GPS, mGPS and cGPS were proved to be the independent risk factors for CA-AKI risk (all P for trend <0.05). Compared with GPS and mGPS, cGPS was of greater prognostic value for predicting CA-AKI incidence (cGPS: AUC = 0.633; mGPS: AUC = 0.567; GPS: AUC = 0.611). Main findings were also consistent in all subgroup analysis.
Preprocedural GPS and its derived scores (mGPS and cGPS), especially cGPS, were correlated with the incidence of CA-AKI, which might assist in clinical decision making in treating CA-AKI.
Caffeine is widely consumed not only in coffee but also in soft drinks and tea. However, the long-term health effects of caffeine are still controversial, especially in people with high ...cardiovascular risk such as elderly patients with hypertension.
This study analyzed data from the National Health and Nutrition Examination Survey 2003-2018. Caffeine intake was calculated by two 24-h dietary recall interviews. Complex sampling-weighted multivariable Cox proportional hazards models were used to compare the hazard ratios (HRs) of all-cause and cardiovascular mortality in elderly hypertensive patients with different caffeine intake (<10, 10 to <100, 100 to <200, 200 to <300, and ≥300 mg/day).
This study included 6,076 elderly hypertensive patients. The mean ± standard error follow-up duration was 6.86 ± 0.12 years. During this period, a total of 2,200 all-cause deaths occurred, of which 765 were cardiovascular deaths. Taking patients with caffeine intake < 10 mg/day as a reference, patients with moderate caffeine intake (200 to <300 mg/day) had a lower risk of all-cause (HR, 0.70 95% CI, 0.56-0.87) and cardiovascular (HR, 0.55 95% CI, 0.39-0.77) mortality. The benefit of reducing all-cause mortality risk was significant in female patients (HR, 0.65 95% CI, 0.50-0.85) or patients with well-controlled blood pressure (HR, 0.63 95% CI, 0.46-0.87), but not in male patients or patients with poorly controlled blood pressure. In addition, non-linear relationship analysis also showed that moderate caffeine intake had the lowest HRs of all-cause (Non-linear
= 0.022) and cardiovascular mortality (Non-linear
= 0.032) in the present study.
Moderate caffeine intake is associated with reduced risk of all-cause and cardiovascular mortality in elderly hypertensive patients.
Increasing evidence has pointed to the connection between pre-mRNA splicing and the circadian clock; however, the underlying mechanisms of this connection remain largely elusive. In the filamentous ...fungus
, the core circadian clock elements comprise White Collar 1 (WC-1), WC-2 and FREQUENCY (FRQ), which form a negative feedback loop to control the circadian rhythms of gene expression and physiological processes. Previously, we have shown that in
, the pre-mRNA splicing factors Pre-mRNA-processing ATP-dependent RNA helicase 5 (PRP5), protein arginine methyl transferase 5 (PRMT5) and snRNA gene
are involved in the regulation of splicing of
transcripts, which encode the negative component of the circadian clock system. In this work we further demonstrated that repression of spliceosomal component sRNA genes,
,
, and
, affected the circadian conidiation rhythms. In a
knockdown strain, the molecular rhythmicity was dampened. The expression of a set of snRNP genes including
was up-regulated in a mutant strain lacking the clock component
, suggesting that the function of spliceosome might be under the circadian control. Among these snRNP genes, the levels of
RNA and PRP5 protein oscillated. The distribution of PRP5 in cytosol was rhythmic, suggesting a dynamic assembly of PRP5 in the spliceosome complex in a circadian fashion. Silencing of
caused changes in the transcription and splicing of NCU09649, a clock-controlled gene. Moreover, in the clock mutant
, the rhythmicity of
I-6 splicing was abolished. These data shed new lights on the regulation of circadian clock by the pre-RNA splicing, and PRP5 may link the circadian clock and pre-RNA splicing events through mediating the assembly and function of the spliceosome complex.
We aimed to investigate cohort differences in age trajectories of hospitalization due to non-communicable conditions, and if these varied by paternal socioeconomic position. We used the Uppsala Birth ...Cohort Multigenerational Study—including virtually complete information on medical diagnoses.
Our sample constituted 28,448 individuals (103,262 observations). The outcome was five-year prevalence of hospitalization due to major non-communicable conditions in 1989–2008. The exposures were age (19–91), year-of-birth (1915–1929; 1938–1972), gender (man vs woman), and parental socioeconomic position (low, medium, and high). We used multilevel logit models to examine associations between exposures and the hospitalization outcome.
Younger cohorts had a higher prevalence of hospitalization at overlapping ages than those born earlier, with inter-cohort differences emerging from early-adulthood and increasing with age. For instance, at age 40 predicted probability of hospitalization increased across birth-cohorts—from 1.2% (born in 1948-52) to 2.0% (born in 1963-67)—whereas at age 50 it was 2.9% for those born in 1938-42 compared with 4.6% among participants born in 1953-57. Those with medium and low socioeconomic position had 13.0% and 20.0% higher odds of experiencing hospitalization during the observation period, respectively—when age, year-of-birth and gender were accounted for.
We found that no progress was made in reducing the socioeconomic inequalities in hospitalization across cohorts born between 1915 and 1972. Hence, more effective policies and interventions are needed to reduce the overall burden of morbidity—particularly among the most vulnerable.
•What is already known on this subject?•The evidence on trends in morbidity in Sweden is mainly cross-sectional and focused on individual conditions.•Rates of various indicators of morbidity (e.g. poor mobility, psychological distress, disability) have increased over time.•What this study adds.•Successively younger birth cohorts had a higher prevalence of hospitalization, with differences emerging in early-adulthood.•Those in medium and low parental socioeconomic position (vs high) had 13% and 20% higher odds of hospitalization.•No progress was made in reducing the socioeconomic inequalities across cohorts born between 1915 and 1972.
An integration hydrogen adsorption benign component such as a metal with an oxygen-containing reactant adsorption benign component such as metal oxide allows for efficient overall water splitting in ...alkaline solutions and yet remains a considerable challenge. Herein, 5d transition metal oxide WO2 and WO3 (denoted as WO x ) nanoparticles are purposely integrated with a porous Ni nanosheet array grown on nickel foam (NF) to design a strongly coupled Ni/WO x /NF porous nanosheet array electrocatalyst. Through the anion exchange of Ni(OH)2 nanosheets with tungstate, followed by hydrogenation treatment, abundant Ni/WO x interfaces with strong coupling interaction are generated. Benefiting from the strong synergies between Ni and WO x and the unique nanostructure, Ni/WO x /NF only requires the overpotentials of 42 mV for hydrogen evolution reaction (HER) and 395.7 mV for oxygen evolution reaction (OER) to achieve the current densities of 10 and 100 mA cm–2, respectively. Furthermore, the Ni/WO x /NF can achieve a current density of 10 mA cm–2 at a low cell voltage of 1.54 V in a two-electrode system. This work opens a novel avenue for the design of high-performance but low-cost electrocatalysts for overall water splitting.
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