SIRT1 alleviates insulin resistance and respiratory distress in late preterm rats by activating QKI5-mediated PPARγ/PI3K/AKT pathway.

Neonatal respiratory distress syndrome (NRDS) is a common complication of gestational diabetes mellitus (GDM) and late preterm births. Research suggests that SIRT1 was involved in LPS-induced acute respiratory distress syndrome, but its mechanism remains to be further explored. Here, pregnant rats were intraperitoneally injected with 45 mg/Kg streptozotocin at day 0 of gestation to induce GDM and injected with LPS at day 17 of gestation to induce late preterm birth. Pioglitazone (a PPARγ agonist) was administered from day 17 to parturition in GDM group, and it was administered for 3 days before LPS injection in late preterm birth group. SRT1720 (a SIRT1 activator) was administered by oral gavage from day 0 to day 17 in both groups. Our data showed that activation of SIRT1 or PPARγ alleviated the abnormal blood glucose metabolism and lung tissue injury, downregulated expression of surfactant proteins (SP-B and SP-C), and decreased activation of the PI3K/AKT pathway induced by GDM and late preterm birth in neonatal rats. Moreover, an insulin resistance model was established by treating primary AT-II cells with insulin. Activation of SIRT1 reversed insulin-induced reduction in cell proliferation, glucose consumption, SP-B and SP-C expression, and the activity of the PI3K/AKT pathway and increase in cellular inflammation and apoptosis. Mechanistically, SIRT1 upregulated PPARγ expression via deacetylation of QKI5, an RNA binding protein that can stabilize its target mRNA molecules, and then activated the PI3K/AKT pathway. In conclusion, SIRT1 promotes the expression of PPARγ via upregulation of QKI5 and activates the PI3K/AKT pathway, thus mitigating NRDS caused by GDM and late preterm birth.

White Blood Cell Count Predicts Mortality in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The association between white blood cell (WBC) counts and mortality in patients with intracerebral hemorrhage (ICH) has not been established. The aim of this study is to determine whether higher WBC is associated with mortality at 90 days. METHODS: A retrospective observational study was conducted at two medical hospitals in China. Baseline WBC count on admission served as the primary predictor variable. Longitudinal WBC counts within the first week after admission were collected to assess the effects of WBC trajectory and the median and maximum WBC counts on outcomes following ICH. Associations of WBC count with outcomes were evaluated in multivariable regression analyses. RESULTS: We identified 3613 patients with ICH who met the inclusion criteria. After adjusting primary confounding variables, patients with increased WBC count had a significantly higher risk of 90-day mortality (p < 0.001 for trend). In the receiver operating characteristic analyses, the capacity for all-cause mortality prediction by WBC count on admission (area under the ROC curve (AUC) = 0.65) was superior to other important inflammatory markers, including neutrophil (AUC = 0.64) , lymphocyte (AUC = 0.57), albumin (AUC = 0.57), and platelet count (AUC = 0.53), p < 0.001 for WBC vs. neutrophil, and the median WBC count (AUC = 0.66) within the first week after admission was a better marker than admission WBC count (p = 0.02). CONCLUSIONS: In patients with ICH, WBC count on admission was associated with all-cause mortality at 90 days. Additionally, the median and maximum WBC counts within the first week after admission showed better predictive ability for the 90-day mortality compared with the WBC count on admission.

Tribbles Homolog 3-Mediated Vascular Insulin Resistance Contributes to Hypoxic Pulmonary Hypertension in Intermittent Hypoxia Rat Model.

This study aimed to investigate the role of vascular insulin resistance (VIR) and Tribbles homolog 3 (TRIB3) in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH). Rats were subjected to low air pressure and low oxygen intermittently for 4 weeks to induce HPH. The mean right ventricular pressure (mRVP), mean pulmonary arterial pressure (mPAP), and right ventricular index (RVI) were significantly increased in HPH rats. Pulmonary arteries from HPH rats showed VIR with reduced vasodilating effect of insulin. The protein levels of peroxisome proliferator-activated receptor gamma (PPARγ), phosphoinositide 3-kinase (PI3K), phosphorylations of Akt, and endothelial nitric oxide (NO) synthase (eNOS) were decreased, and TRIB3 and phosphorylated extracellular signal-regulated protein kinases (ERK1/2) were increased in pulmonary arteries of HPH rats. Early treatment of pioglitazone (PIO) partially reversed the development of HPH, improved insulin-induced vasodilation, and alleviated the imbalance of the insulin signaling. The overexpression of TRIB3 in rat pulmonary arterial endothelial cells (PAECs) reduced the levels of PPARγ, PI3K, phosphorylated Akt (p-Akt), and phosphorylated eNOS (p-eNOS) and increased p-ERK1/2 and the synthesis of endothelin-1 (ET-1), which were further intensified under hypoxic conditions. Moreover, TRIB3 knockdown caused significant improvement in Akt and eNOS phosphorylations and, otherwise, a reduction of ERK1/2 activation in PAECs after hypoxia. In conclusion, impaired insulin-induced pulmonary vasodilation and the imbalance of insulin-induced signaling mediated by TRIB3 upregulation in the endothelium contribute to the development of HPH. Early PIO treatment improves vascular insulin sensitivity that may help to limit the progression of hypoxic pulmonary hypertension.

[Breeding of a new cultivar "Chuanjianghuang 1" of Sichuan Dao-di herbs Curcumae Longae Rhizoma and Curcumae Radix].

The systematic breeding method was adopted to breed a new good cultivar of Curcuma longa, named "Chuanjianghuang 1". From 2014 to 2015, two consecutive years of multi-point test were carried out in Shuangliu, Chongzhou and Wenjiang. The biological characters, phenology, agronomic characters, yield and quality indexes of "Chuanjianghuang 1" were comprehensively evaluated. The results showed that compared with local traditional species, the rhizome yield of the new cultivar "Chuanjianghuang 1" increased by 20.61%.The average content of volatile oil was higher than 24.17% and the average content of curcumin in root tuber was higher than 26.62%. The yield of root tuber increased by 54.59%.The average content of volatile oil is higher than 36.28% and the average content of curcuminoids is higher than 25.31%. Compared with "Huangsi Yujin 1", "Chuanjianghuang 1" increased the average yield of rhizome by 123.68%,the volatile oil increased by an average of 7.69%and the curcumin content increased by an average of 58.23%. The average content of volatile oil is higher than 52.82% and the average content of curcuminoids in root tuber was higher than 38.34%. The new variety "Chuanjianghuang 1" has better yield than the local traditional species, and the internal quality of rhizome and root tuber is better. Compared with "Huangsi Yujin 1", the yield of rhizome is significantly increased, and the internal quality of rhizome and root tuber is better, especially the content of curcumin in rhizome and curcuminoids in root tuber is significantly higher than that of "Huangsi Yujin 1". "Chuanjianghuang 1" is high yield, good quality, good stability and strong adaptability, which is suitable for cultivation and promotion in Chengdu Jinma River Basin, such as Shuangliu, Chongzhou, Wenjiang.

Magnolol administration in normotensive young spontaneously hypertensive rats postpones the development of hypertension: role of increased PPAR gamma, reduced TRB3 and resultant alleviative vascular insulin resistance.

Patients with prehypertension are more likely to progress to manifest hypertension than those with optimal or normal blood pressure. However, the mechanisms underlying the development from prehypertension to hypertension still remain largely elusive and the drugs for antihypertensive treatment in prehypertension are absent. Here we determined the effects of magnolol (MAG) on blood pressure and aortic vasodilatation to insulin, and investigated the underlying mechanisms. Four-week-old male spontaneous hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) control rats were used. Our results shown that treatment of young SHRs with MAG (100 mg/kg/day, o.g.) for 3 weeks decreased blood pressure, improved insulin-induced aorta vasodilation, restored Akt and eNOS activation stimulated by insulin, and increased PPARγ and decreased TRB3 expressions. In cultured human umbilical vein endothelial cells (HUVECs), MAG incubation increased PPARγ, decreased TRB3 expressions, and restored insulin-induced phosphorylated Akt and eNOS levels and NO production, which was blocked by both PPARγ antagonist and siRNA targeting PPARγ. Improved insulin signaling in HUVECs by MAG was abolished by upregulating TRB3 expression. In conclusion, treatment of young SHRs with MAG beginning at the prehypertensive stage decreases blood pressure via improving vascular insulin resistance that is at least partly attributable to upregulated PPARγ, downregulated TRB3 and consequently increased Akt and eNOS activations in blood vessels in SHRs.