Coffee Consumption and Incidence of Cardiovascular and Microvascular Diseases in Never-Smoking Adults with Type 2 Diabetes Mellitus.

The relationship between coffee consumption and diabetes-related vascular complications remains unclear. To eliminate confounding by smoking, this study assessed the relationships of coffee consumption with major cardiovascular disease (CVD) and microvascular disease (MVD) in never-smokers with type 2 diabetes mellitus (T2DM). Included were 9964 never-smokers with T2DM from the UK Biobank without known CVD or cancer at baseline (7781 were free of MVD). Participants were categorized into four groups according to daily coffee consumption (0, 0.5-1, 2-4, ≥5 cups/day). CVD included coronary heart disease (CHD), myocardial infarction (MI), stroke, and heart failure (HF). MVD included retinopathy, peripheral neuropathy, and chronic kidney disease (CKD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidential intervals (CIs) of total CVD and MVD and the component outcomes associated with coffee consumption. During a median of 12.7 years of follow-up, 1860 cases of CVD and 1403 cases of MVD were identified. Coffee intake was nonlinearly and inversely associated with CVD (P-nonlinearity = 0.023) and the component outcomes. Compared with no coffee intake, HRs (95% CIs) associated with a coffee intake of 2 to 4 cups/day were 0.82 (0.73, 0.93) for CVD, 0.84 (0.73, 0.97) for CHD, 0.73 (0.57, 0.92) for MI, 0.76 (0.57, 1.02) for stroke, and 0.68 (0.55, 0.85) for HF. Higher coffee intake (≥5 cups/day) was not significantly associated with CVD outcomes. Coffee intake was linearly and inversely associated with risk of CKD (HR for ≥5 vs. 0 cups/day = 0.64; 95% CI: 0.45, 0.91; P-trend = 0.0029) but was not associated with retinopathy or peripheral neuropathy. Among never-smoking individuals with T2DM, moderate coffee consumption (2-4 cups/day) was associated with a lower risk of various CVD outcomes and CKD, with no adverse associations for higher consumption.

Oleanolic Acid Inhibiting the Differentiation of Neural Stem Cells into Astrocyte by Down-Regulating JAK/STAT Signaling Pathway.

To investigate the effect of oleanolic acid (OA) on the differentiation of neural stem cells (NSCs) induced by A[Formula: see text] via regulating the JAK/STAT signaling pathway, a neurotoxicity cell model involving the induction of NSCs by soluble A[Formula: see text] (5 [Formula: see text]M) was used. The WST-1 method and immunofluorescence tests were used respectively to detect the activity of cell model and the expression of GFAP[Formula: see text]/DAPI and Tubulin[Formula: see text]/DAPI. Western blotting and real-time PCR analyses were used to observe the effects of OA on NSCs differentiation by examining key targets of the JAK/STAT signal transduction pathway. Compared with normal NSCs, A[Formula: see text]-induced NSCs had down-regulated expression of Ngn1 and up-regulated STAT3 expression and phosphorylation, and inhibited neuronal differentiation. OA treatment effectively inhibited the A[Formula: see text]-induced activation of JAK/STAT signaling, with a significant increase in Ngn1 expression and a significant decrease in p-STAT3/STAT3. These results indicate that OA could inhibit the excessive differentiation of NSCs into astrocytes by down-regulating JAK/STAT signaling which might retard the progress of AD.

[Effective Components of three kinds of shen-supplementing Chinese medicine on self-renewal and neuron-like differentiation of NSCs in AD mouse embryos: an experimental research].

OBJECTIVE: To observe the regulatory effects of psoralen, oleanolic acid, and stilbene glucoside, three active components of psoralea fruit, glossy privet fruit and tuber fleeceflower root respectively, on Aß25-35induced self-renewal and neuron-like differentiation of neural stem cells (NSCs). METHODS: Embryonic NSCs werein vitro isolated and cultured from Kunming mice of 14-day pregnancy, and randomly divided into the control group, the Aß25-35 group, the Aß25-35 +psoralen group, the Aß25-35 +oleanolic acid group, and the Aß25-35 + stilbene glucoside group. The intervention concentration of Aß25-35 was 25 µmol/L, and the intervention concentration of three active components of Chinese medicine was 10(-7)mol/L. The effect of three active components of Chinese medicine on the proliferation of NSCs was observed by counting method. The protein expression of Tubulin was observed by Western blot and immunofluorescence. The ratio of Tubulin+/DAPI was caculated. Results Compared with the control group, the sperical morphology of NSCs was destroyed in the Aß25-35 group, the counting of NSCs, the expression of Tubulin protein, and the ratio of Tubulin /DAPI all decreased (P <0.01, P <0.05). Compared with the Aß25-35 group, the counting of NSCs, the expression of Tubulin protein, and the ratio of Tubulin + /DAPI all increased in the three Chinese medicine treated groups (P <0. 01, P <0. 05). CONCLUSIONS: 25 µmol/L Aß25-35 could inhibit self-renewal and neuron-like differentiating of NSCs. But psoralen, oleanolic acid, and stilbene glucoside could promote self-renewal of NSCs and neuron-like differentiation.