Beneficial effects of metformin supplementation in hypothalamic paraventricular nucleus and arcuate nucleus of type 2 diabetic rats.

Background Oxidative stress and inflammation play important roles in the development of diabetes. Metformin (MET) is considered as the first-line therapy for patients with type 2 diabetes (T2D). Hypothalamic paraventricular nucleus (PVN) and hypothalamic arcuate nucleus (ARC) are vital in obesity and diabetes. However, there have been few studies on the effects of MET on inflammatory reaction and oxidative stress in the PVN and ARC of T2D diabetic rats. Methods Male Sprague-Dawley (SD) rats were fed with high-fat diet (HFD), and intraperitoneally injected with low-dose streptozotocin (STZ, 30 mg/kg) at 6th week to induce T2D diabetes. After injection of STZ, they were fed with HFD continually. Starting from the 8th week of HFD feeding, T2D rats received intragastrical administration of MET (150 mg/kg/day) in addition to the HFD for another 8 weeks. At the end of the 15th week, the rats were anaesthetized to record the sympathetic nerve activity and collect blood and tissue samples. Results In comparison with control rats, T2D diabetic rats had higher levels of pro-inflammatory cytokines (PICs) and excessive oxidative stress in the PVN and ARC, accompanied with more activated astrocytes. The renal sympathetic nerve activity (RSNA) and the plasma norepinephrine (NE) increased in T2D diabetic rats. The expression of tyrosine hydroxylase (TH) increased and the expression of 67-kDa isoform of glutamate decarboxylase (GAD67) decreased in T2D diabetic rats. Supplementation of MET decreased blood glucose, suppressed RSNA, decreased PICs (TNF-α, IL-1ß and IL-6) in PVN and ARC, attenuated oxidative stress and activation of astrocytes in ARC and PVN of T2D diabetic rats, as well as restored the balance of neurotransmitter synthetase. The number of Fra-LI (chronic neuronal excitation marker) positive neurons in the ARC and PVN of T2D diabetic rats increased. Chronic supplementation of MET also decreased the number of Fra-LI positive neurons in the ARC and PVN of T2D diabetic rats. Conclusion These findings suggest that the PVN and ARC participate in the beneficial effects of MET in T2D diabetic rats, which is possibly mediated via down-regulating of inflammatory molecules, attenuating oxidative stress and restoring the balance of neurotransmitter synthetase by MET in the PVN and ARC.

Is vanishing twin syndrome associated with adverse obstetric outcomes of ART singletons? A systematic review and meta-analysis.

PURPOSE: The objective of our meta-analysis was to estimate the effect of VTS on obstetric outcomes of ART singletons. METHODS: PubMed, Embase, MEDLINE, and ClinicalTrials.gov were searched up to January 2019 to find studies reporting the obstetric outcomes of ART singletons with VTS. Dichotomous data were expressed as odds ratios (OR) with 95% confidence intervals (CI). Continuous data were expressed as weighted mean difference (WMD) with 95% CI. RESULTS: A total of 17 observational studies encompassing more than 60,000 ART singletons were included in this meta-analysis. The impact of VTS on singletons was highly dependent on the definition of VTS, precisely, the vanishing timing and intrauterine growth stage. When VTS happened at or before 14 weeks, regardless of intrauterine growth stage, there were no differences in terms of gestational age (GA) [WMD = - 0.08, 95% CI = - 0.27, 0.10], preterm birth (< 37 weeks) (PTB) [OR = 1.23, 95% CI = 0.89, 1.70], and low birth weight (< 2.5 kg) (LBW) [OR = 1.56, 95% CI = 1.00, 2.43] in original singletons versus singleton with VTS. On the contrary, VTS occurred after 14 weeks was associated with significantly shorter GW and lower BW, as well as higher risks of PTB and LBW. When the sac reduced in VTS was an empty gestational sac, there would be no differences in GW, PTB, and LBW between singletons versus singletons with VTS, whereas the loss of a fetus with cardiac-activity was associated with adverse obstetric outcomes. CONCLUSIONS: This meta-analysis suggests whether or not VTS is harmful to obstetric outcomes is highly dependent on the vanishing timing and intrauterine growth stage.

Effects of seawater immersion on open traumatic brain injury in rabbit model.

We emulated instances of open traumatic brain injuries (TBI) in a maritime disaster. New Zealand rabbit animal models were used to evaluate the pathophysiological changes in open TBI with and without the influence of artificial seawater. New Zealand rabbits were randomly divided into 3 groups. Control group consisted of only normal animals. Animals in TBI and TBI + Seawater groups underwent craniotomy with dura mater incised and brain tissue exposed to free-fall impact. Afterward, only TBI + Seawater group received on-site artificial seawater infusion. Brain water content (BWC) and permeability of blood-brain barrier (BBB) were assessed. Reactive oxygen species levels were measured. Western blotting and immunofluorescence were employed to detect: apoptosis-related factors Caspase-3, Bax and Bcl-2; angiogenesis-related factors CD31 and CD34; astrogliosis-related factor glial fibrillary acidic protein (GFAP); potential neuron injury indicator neuron-specific enolase (NSE). Hematoxylin & eosin, Masson-trichrome and Nissl stainings were performed for pathological observations. Comparing to Control group, TBI group manifested abnormal neuronal morphology; increased BWC; compromised BBB integrity; increased ROS, Bax, CD31, CD34, Caspase-3 and GFAP expressions; decreased Bcl-2 and NSE expression. Seawater immersion caused all changes, except BWC, to become more significant. Seawater immersion worsens the damage inflicted to brain tissue by open TBI. It aggravates hypoxia in brain tissue, upregulates ROS expression, increases neuron sensitivity to apoptosis-inducing factors, and promotes angiogenesis as well as astrogliosis.

Pregnancy outcomes after day 5 versus day 6 blastocyst-stage embryo transfer: A systematic review and meta-analysis.

AIM: To compare the pregnancy outcomes after day 5 blastocyst-stage embryo transfers (BET) versus day 6 BET following vitrified-warmed cycle and to evaluate whether the number of embryos transferred and the chromosomal status of embryo influence effect estimates. METHODS: A literature search (PubMed, Embase and MEDLINE) up to January 2019 was conducted to identify studies where women with day 6 BET were compared to women with day 5 BET. Only studies published in English language, on peer-reviewed journal were considered eligible. The following subgroup analyses were performed: (i) number of embryos transferred and (ii) chromosomal status of embryo. RESULTS: From a total of 1956 articles identified, 23 observational studies were included in the meta-analysis. We observed that day 6 BET were associated with lower implantation rate (risk ratio, RR: 1.17, 95% confidence interval, CI: 1.10-1.24), clinical pregnancy rate (RR: 1.17, 95% CI: 1.10-1.24), ongoing pregnancy rate (RR: 1.15, 95% CI: 1.07-1.24) and live birth rate (RR: 1.22, 95% CI: 1.11-1.33) than day 5 BET following vitrified-warmed cycle. The subgroup analysis found that the superiority of day 5 BET compared with day 6 BET is influenced by the number of embryos transferred and chromosomal status of embryos. CONCLUSION: Current evidence shows that day 5 BET is superior to day 6 BET following vitrified-warmed cycle in clinical practice. Due to the overall low quality of available evidence, more larger and well-conducted studies are needed to compare the pregnancy outcomes between day 5 and day 6 BET before drawing a clear conclusion.

Inhibition of Hypothalamic Inhibitor κB Kinase ß/Nuclear Transcription Factor κB Pathway Attenuates Metabolism and Cardiac Dysfunction in Type 2 Diabetic Rats.

BACKGROUND: Inflammation and oxidative stress play important roles in energy imbalance and its complications. Recent research indicates that hypothalamic inflammation may contribute to the pathogenesis of metabolic syndrome and cardiac dysfunction, but the mechanisms remain unclear. We hypothesized that suppression of the proinflammatory IKKß/NF-κB pathway in the hypothalamus can improve energy balance and cardiac function in type 2 diabetic (T2D) rats. METHODS: Normal and T2D rats received bilateral hypothalamic arcuate nucleus (ARC) infusions of the IKKß inhibitor SC-514 or vehicle via osmotic minipump. Metabolic phenotyping, immunohistochemical analyses, and biochemical analyses were used to investigate the outcomes of inhibition of the hypothalamic IKKß. Echocardiography and glucometer were used for measuring cardiac function and blood glucose, respectively. Blood samples were collected for the evaluation of circulating proinflammatory cytokines. Heart was harvested for cardiac morphology evaluations. The ARC was harvested and analyzed for IKKß, NF-κB, proinflammatory cytokines, reactive oxygen species (ROS), and NAD(P)H (gp91phox, p47phox) oxidase activity levels and neuropeptides. RESULTS: Compared with normal rats, T2D rats were characterized by hyperglycemia, hyperinsulinemia, glucose intolerance, cardiac dysfunction, as well as higher ARC levels of IKKß, NF-κB, proinflammatory cytokines, ROS, gp91phox, and p47phox. ARC infusion of the IKKß inhibitor SC-514 attenuated all these changes in T2D rats, but not in normal rats. CONCLUSIONS: Our results indicate that the hypothalamic IKKß/NF-κB pathway plays a key role in modulating energy imbalance and cardiac dysfunction, suggesting its potential therapeutic role during type 2 diabetes mellitus.