A review of the mechanisms of abnormal ceramide metabolism in type 2 diabetes mellitus, Alzheimer's disease, and their co-morbidities.

The global prevalence of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is rapidly increasing, revealing a strong association between these two diseases. Currently, there are no curative medication available for the comorbidity of T2DM and AD. Ceramides are structural components of cell membrane lipids and act as signal molecules regulating cell homeostasis. Their synthesis and degradation play crucial roles in maintaining metabolic balance in vivo, serving as important mediators in the development of neurodegenerative and metabolic disorders. Abnormal ceramide metabolism disrupts intracellular signaling, induces oxidative stress, activates inflammatory factors, and impacts glucose and lipid homeostasis in metabolism-related tissues like the liver, skeletal muscle, and adipose tissue, driving the occurrence and progression of T2DM. The connection between changes in ceramide levels in the brain, amyloid ß accumulation, and tau hyper-phosphorylation is evident. Additionally, ceramide regulates cell survival and apoptosis through related signaling pathways, actively participating in the occurrence and progression of AD. Regulatory enzymes, their metabolites, and signaling pathways impact core pathological molecular mechanisms shared by T2DM and AD, such as insulin resistance and inflammatory response. Consequently, regulating ceramide metabolism may become a potential therapeutic target and intervention for the comorbidity of T2DM and AD. The paper comprehensively summarizes and discusses the role of ceramide and its metabolites in the pathogenesis of T2DM and AD, as well as the latest progress in the treatment of T2DM with AD.

Interaction of hemoglobin, transfusion, and acute kidney injury in patients undergoing cardiopulmonary bypass: a group-based trajectory analysis.

Anemia is a risk factor for acute kidney injury (AKI) following cardiopulmonary bypass (CPB). Whether red blood cell (RBC) transfusion-enhanced hemoglobin levels contribute to low AKI rates remains unclear. We investigated the interaction between hemoglobin, RBC transfusion, and AKI after CPB. Hemoglobin trajectories within 72 h were analyzed using group-based trajectory analysis. Multivariable logistic analysis and inverse probability-weighted regression were adopted to evaluate the associations between hemoglobin and AKI in RBC and non-RBC transfusion subgroups. We analyzed 6226 patients' data. In the transfusion subgroup, three hemoglobin trajectories were identified. The AKI incidence was lowest in the trajectory with the lowest hemoglobin level (trajectory 1, less transfusion), and it was comparable in trajectories 2 and 3 (20.7% vs. 32.7% vs. 29.4%, p < 0.001, respectively). In four logistic models, the odds ratio for AKI with trajectory 1 as the reference ranged from 1.44 to 1.85 for trajectory 2 (p < 0.001) and 1.45 to 1.66 for trajectory 3 (p < 0.050). The average treatment effect on AKI was 5.6% (p = 0.009) for trajectory 2 and 7.5% (p = 0.041) for trajectory 3, with trajectory 1 as the reference. In the non-RBC transfusion subgroup, three approximately linear hemoglobin trajectories (9, 10, and 12 g/dL) were observed; however, both the crude and adjusted AKI incidence were similar within the three trajectories. In patients undergoing CPB, hemoglobin level >9 g/dL was not associated with decreased AKI incidence in the subgroup without RBC transfusion. However, in patients with RBC transfusion, maintaining hemoglobin level >9 g/dL by RBC transfusion was associated with increased AKI incidence.

Qianjinweijing Decoction Protects Against Fine Particulate Matter Exposure-mediated Lung Function Disorder.

Fine particulate matter (PM2.5) is well known to impair lung function. Strategies protecting against PM2.5-exerted lung dysfunction have been less investigated. Qianjinweijing decoction (QJWJ), a decoction of a herbal medicine of natural origin, has been used to treat lung disorders as it inhibits oxidation and inflammation. However, no clinical trial has yet evaluated the role of QJWJ in PM2.5-induced lung dysfunction. Therefore, we conducted a randomized, double-blind, placebo-controlled trial to assess whether QJWJ provided lung benefits against the adverse effects of PM2.5 exposure among adults. Eligible participants (n = 65) were recruited and randomized to receive QJWJ decoction (n = 32) or placebo (n = 33) for 4 weeks. The restrictive ventilatory defect (RVD), lung function parameters, and induced sputum were analyzed. The PM2.5 exposure concentration was significantly associated with the vital capacity (VC), peak expiratory flow (PEF), and forced expiratory flow at 75% of the forced vital capacity (FEF75). The negative associations between PM2.5 and the lung function parameters were eliminated in response to the QJWJ intervention. Additionally, the percentage of RVD (P = 0.018) and the proportion of eosinophils (Eo%) in induced sputum (P = 0.014) in the QJWJ group was significantly lower than that in the placebo group. This study demonstrated that QJWJ could alleviated PM2.5-induced lung dysfunction and could be a potential treatment for air pollution-related chronic respiratory disease.

Impact of partial pressure of oxygen trajectories on the incidence of acute kidney injury in patients undergoing cardiopulmonary bypass.

BACKGROUND: To investigate the impact of the dynamic oxygenation status on the incidence of acute kidney injury (AKI) in patients undergoing cardiopulmonary bypass. METHODS: This retrospective study was performed using data extracted from the Medical Information Mart for Intensive Care III database. A group-based trajectory approach was used to identify partial pressure of oxygen (PaO2) trajectories using dynamic change in PaO2 within 48 hours after intensive care unit admission. RESULTS: In total, 5,824 patients were included. Four PaO2 trajectories were identified: Trajectory 1 (Traj-1), hyperoxia and rapid decrease; Trajectory 2 (Traj-2), hyperoxia and rapid decrease similar to that of Traj-1; Trajectory 3 (Traj-3), normoxemia and rapid increase in PaO2; and Trajectory 4 (Traj-4), hyperoxia and gradual decrease. Compared with the Traj-1 group, the Traj-3 group had a significantly lower initial Sequential Organ Failure Assessment score, similar vasopressor use rate, and a higher fraction of inspired oxygen. However, the risk of developing AKI was significantly higher in the Traj-3 [adjusted odds ratio (OR): 1.7, 95% confidence interval (CI): 1.1-2.7] and Traj-4 groups (OR: 1.9, 95% CI: 1.4-2.5) than in the Traj-1 group. CONCLUSIONS: Patients with persistent hyperoxia had a higher incidence of AKI than those with transient hyperoxia. Further studies are required to determine potential underlying mechanisms.

Radix Paeoniae Rubra Ameliorates Lupus Nephritis in Lupus-Like Symptoms of Mrl Mice by Reducing Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and Platelet Endothelial Cell Adhesion Molecule-1 Expression.

OBJECTIVE: Vasculitis is the basic pathological change of systemic lupus erythematosus (SLE). Radix Paeoniae Rubra (RPR), a traditional Chinese herb with the function of reducing blood stasis, has anti-inflammatory and immunoregulatory properties. This study explored the effects of RPR on the kidneys of lupus-like symptoms of mrl (MRL/lpr) mice from the perspective of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1). METHODS: Eighteen MRL/lpr lupus model mice were randomly divided into three groups, the model control group, prednisone-treated group, and RPR-treated group, and 6 C57BL/ 6 mice were classified as a control group. After the mice had been treated for 12 weeks, the expression of ICAM-1, VCAM-1 and PECAM-1in the kidney was determined by immunohistochemistry and Reverse Transcription-Polymerase Chain Reaction (RT-PCR). RESULTS: After 12 weeks, there were significant differences in body weight in the model, prednisone and RPR groups compared with the normal group (P <0.05). Pathological observation: Compared with the model group, the proliferation of inflammatory cells infiltrated glomeruli and interstitial cells in prednisone and RPR groups were reduced, and renal pathological damage was reduced. Compared with the model group, urine protein level of prednisone and RPR groups were reduced with no significance (P> 0.05). The mRNA expression levels of ICAM-1 and VCAM-1 were significantly reduced in the prednisone group and RPR group compared with the model group (P <0.05 or P <0.01). Meanwhile, the immunohistochemistry expressions of ICAM-1 and VCAM- 1 expressed in the kidney were significantly reduced in the prednisone group and RPR group (P <0.01 or P <0.05). However, The mRNA expression level and the immunohistochemistry expressions of PECAM-1 expressed in the kidney were reduced in each treatment group (prednisone group and RPR group), but these differences were not significant (P>0.05). CONCLUSIONS: ICAM-1, VCAM-1 and PECAM-1 expression in the model group was found to be significantly increased. In addition, RPR could reduce the expression of ICAM-1, VCAM-1 and PECAM-1 in MRL/lpr lupus mice as effectively as prednisone, which may result in the dosage reduction of prednisone, thus decreasing the toxicity and improving the efficacy of prednisone - based treatment of SLE.

Characterization of viral genomic mutations in novel influenza A (H7N9)-infected patients: the association between oseltamivir-resistant variants and viral shedding duration.

Since February 2013, human infections with the novel influenza A H7N9 virus have occurred in eastern China. It is important to detect mutations in viral genes and analyze the clinical features of patients and viral shedding duration related to neuraminidase inhibitor (NAI) resistance. We collected clinical specimens from 31 hospitalized H7N9 patients and sequenced NA, PB2, HA, and M gene fragments. Of the 31 identified patients, 7 (22.6%) carried the R292K substitution in NA, 30 (96.8%), 3 (9.7%), and 5 (16.1%) carried E627K, Q591K, and D701N mutations in PB2, respectively, and 2 (6.5%) carried both E627K and D701N mutations in PB2. All 26 identified patients harbored Q226L mutations and possessed only a single arginine (R) at cleavage sites in the HA and a S31N mutation in M2. Among 7 NA-R292K mutated patients, 3 died and 4 were discharged. There was no significant difference in the days that patients started oseltamivir treatment after symptom onset between NA-R292K mutant and NA-R292 wild-type patients (median days, 7 vs 6, P = 0.374). NA-R292K mutant patients had a significantly longer duration of viral shedding than NA-R292 wild-type patients after oseltamivir treatment (median days, 10 vs 5, P = 0.022). The mutation of R292K in NA conferring the potential ability of oseltamivir resistance resulted in prolonged viral duration and poor outcome and should be taken into consideration in the clinical management of infected patients.