The effectiveness and safety of linagliptin within elderly type 2 diabetes mellitus: a meta-analysis and systematic review.

BACKGROUND: Linagliptin is a convenient and effective drug approved for glycemic management in type 2 diabetes mellitus (T2DM). However, the effectiveness and safety evidence of linagliptin remains unclear with the increasing prevalence of T2DM in elderly patients. OBJECTIVE: For evaluating the effectiveness and safety of linagliptin within T2DM cases who aged ≥60 years. METHODS: The researchers pooled 4903 cases aged ≥60 years with T2DM from 5 published randomized clinical trials obtained from multiple databases. The safety was evaluated by the incidence and severity of adverse events (AEs) which mainly focused on hypoglycaemia. The major effectiveness end point was the change of glycated haemoglobin (HbA1c). Then the researchers made the qualitative and quantitative assessments of the investigation. RESULTS: The level of HbA1c and FPG was significantly reduced by linagliptin (WMD=-0.63%, 95% CI: -0.81, -0.44; p<0.00001; Z=6.70) and (WMD=-15.58 mg/dL, 95% CI: -22.34, -8.82; p<0.00001; Z=4.52) relative to that in the placebo cohort. The incidences of overall (OR=1.01, 95% CI: 0.82, 1.25; p=0.91) and severe negative events (OR=0.88, 95% CI: 0.61, 1.25; p=0.46) were not significant increased in linagliptin cohorts compared to the placebo cohorts. There is insignificant difference in hypoglycaemia between linagliptin and placebo cohorts for the 24 weeks' study(OR=1.12, 95% CI: 0.85, 1.48; p=0.41). Severe hypoglycemia had slightly descended incidence, whereas insignificant difference was shown in the linagliptin cohorts in contrast to placebo cohorts (OR=0.95, 95 % CI: 0.68, 1.32, p=0.76). CONCLUSIONS: Linagliptin is an effective drug with excellent safety for elderly T2DM.

Interleukin-11 treatment protected against cerebral ischemia/reperfusion injury.

OBJECTIVE: Inflammation and immune responses are crucial factors associated with the onset and progression of stroke. Interleukin-11 (IL-11) is a hematopoietic IL-6 family cytokine that functions as an anti-inflammatory agent against various inflammatory diseases. However, its roles in stroke remain unknown. In this study, we investigated the effects of IL-11 on cerebral ischemia-reperfusion injury in a model of focal cerebral ischemia. METHODS: Mice were randomly divided into five groups the vehicle group, the middle cerebral artery occlusion (MCAO) group, the MCAO plus adenosine monophosphate-activated protein kinase (AMPK) inhibitor compound C group, the MCAO plus IL-11 treatment group, and the MCAO plus IL-11 treatment and compound C group. Focal cerebral ischemia was induced by occluding the left middle cerebral artery, and reperfusion was achieved by withdrawing the suture 2 h after ischemia. The protein expression levels of IL-11 were measured using Western blot analysis, and its location was detected using immunohistochemistry and immunofluorescence staining. The infarct volume was examined using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and the neurobehavioral progression was assessed using the neurological scoring system. The expression of astrocytes and microglia was detected using immunochemistry, and real-time quantitative PCR was used for the gene quantification of inflammatory cytokines. The extent of cerebral ischemia-reperfusion injury was tested using Nissl staining and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. The expression of the apoptotic proteins Bax, Bcl-2 and cleaved caspase-3 were detected using Western blot analysis, and the oxidative stress was also measured. RESULTS: The expression of IL-11 mRNA and protein significantly decreased after cerebral ischemia. Immunohistochemical staining showed a large amount of IL-11 in the cerebral cortex of the mice in the vehicle group, whereas the immunoreactivity of IL-11 remained weak for 24 h in the MCAO group. Immunofluorescent staining further confirmed that IL-11 was mainly expressed in the neurons. It was suggested that IL-11 (20 µg/kg) treatment ameliorated infarction and reduced neurological scores. In addition, IL-11 proved to reduce neuropathic damage, glial activation, and the expression of proinflammatory cytokines and increase the expression of anti-inflammatory cytokines after cerebral ischemia. IL-11 was also able to alleviate oxidative stress caused by cerebral ischemia, and AMPK inhibition enhanced the alleviation. Moreover, IL-11 was found to inhibit apoptosis caused by cerebral ischemia, which could also be facilitated by AMPK inhibitors. SIGNIFICANCE: Our research suggests that IL-11 is decreased during cerebral ischemia-reperfusion injury, but IL-11 treatment can improve neurological function and reduce the cerebral infarct volume, which can trigger stroke in mice. AMPK inhibition can further promote the protective effect of IL-11 in stroke. Overall, we demonstrate that IL-11 is of therapeutic interest in controlling stroke and managing cerebral ischemia-reperfusion injury.

[A study on expression of HIF-1alpha and EPO in the hippocampus of rats with vascular dementia].

OBJECTIVE: To observe the expression rule of hypoxia inducible factor-1 (HIF-1alpha) and erythropoietion (EPO) in the formation of vascular dementia (VD) and investigate the possible pathogenesis of VD. METHODS: Rats of experimental group were treated with a permanent bilateral common carotid arteries (CCA) occlusion (2-VO) for establishing vascular dementia model. Rats were evaluated on learning-memory ability by Y-type water maze test. The dynamic expression of HIF-1alpha and EPO in hippocampal CA1 region were measured by immunohistochemical assay method. RESULTS: (1) The learning-memory ability of rats in VD groups was progressively decreased as the ischemic duration prolonged (P < 0.05); (2) In VD group, the expression of HIF-1alpha and EPO in hippocampal CA1 region were most obvious at 1 w, and then declined progressively but still above the normal level (P < 0.01); (3) In VD group, the expression of HIF-1alpha and EPO at each ischemic point and their corresponding learning-memory ability were in significant correlation at the 0.01 level. CONCLUSION: Both HIF-1alpha and EPO contribute to the formation of VD, and HIF-1/EPO anoxic signal transduction may play a protecting role in this process.