A Neural Circuit from the Paraventricular Thalamus to the Bed Nucleus of the Stria Terminalis for the Regulation of States of Consciousness during Sevoflurane Anesthesia in Mice.

BACKGROUND: The neural circuitry underlying sevoflurane-induced modulation of consciousness is poorly understood. This study hypothesized that the paraventricular thalamus bed nucleus of the stria terminalis pathway plays an important role in regulating states of consciousness during sevoflurane anesthesia. METHODS: Rabies virus-based transsynaptic tracing techniques were employed to reveal the neural pathway from the paraventricular thalamus to the bed nucleus of the stria terminalis. This study investigated the role of this pathway in sevoflurane anesthesia induction, maintenance, and emergence using chemogenetic and optogenetic methods combined with cortical electroencephalogram recordings. Both male and female mice were used in this study. RESULTS: Both γ-aminobutyric acid-mediated and glutamatergic neurons in the bed nucleus of the stria terminalis receive paraventricular thalamus glutamatergic projections. Chemogenetic inhibition of paraventricular thalamus glutamatergic neurons prolonged the sevoflurane anesthesia emergence time (mean ± SD, hM4D-clozapine N-oxide vs. mCherry-clozapine N-oxide, 281 ± 88 vs. 172 ± 48 s, P < 0.001, n = 24) and decreased the induction time (101 ± 32 vs. 136 ± 34 s, P = 0.002, n = 24), as well as the EC5 0 for the loss or recovery of the righting reflex under sevoflurane anesthesia (mean [95% CI] for the concentration at which 50% of the mice lost their righting reflex, 1.16 [1.12 to 1.20] vs. 1.49 [1.46 to 1.53] vol%, P < 0.001, n = 20; and for the concentration at which 50% of the mice recovered their righting reflex, 0.95 [0.86 to 1.03] vs. 1.34 [1.29 to 1.40] vol%, P < 0.001, n = 20). Similar results were observed during suppression of the paraventricular thalamus bed nucleus-stria terminalis pathway. Optogenetic activation of this pathway produced the opposite effects. Additionally, transient stimulation of this pathway efficiently induced behavioral arousal during continuous steady-state general anesthesia with sevoflurane and reduced the depth of anesthesia during sevoflurane-induced burst suppression. CONCLUSIONS: In mice, axonal projections from the paraventricular thalamic neurons to the bed nucleus of the stria terminalis contribute to regulating states of consciousness during sevoflurane anesthesia.

Influence of glucuronidation and reduction modifications of resveratrol on its biological activities.

Resveratrol (3,5,4'-trihydroxystilbene, RES), a star among dietary polyphenols, shows a wide range of biological activities, but it is rapidly and extensively metabolized into its glucuronide and sulfate conjugates as well as to the corresponding reduced products. This begs the question of whether the metabolites of RES contribute to its in vivo biological activity. To explore this possibility, we synthesized its glucuronidation (3-GR and 4'-GR) and reduction (DHR) metabolites, and evaluated the effect of these structure modifications on biological activities, including binding ability with human serum albumin (HSA), antioxidant activity in homogeneous solutions and heterogeneous media, anti-inflammatory activity, and cytotoxicity against various cancer cell lines. We found that 1) 4'-GR, DHR and RES show nearly equal binding to HSA, mainly through hydrogen bonding, whereas 3-GR adopts a quite different orientation mode upon binding, thereby resulting in reduced ability; 2) 3-GR shows comparable (even equal) ability to RES in FRAP- and AAPH-induced DNA strand breakage assays; DHR, 3-GR, and 4'-GR exhibit anti-hemolysis activity comparable to that of RES; additionally, 3-GR and DHR retain some degree activity of the parent molecule in DPPH.-scavenging and cupric ion-initiated oxidation of LDL assays, respectively; 3) compared to RES, 4'-GR displays equipotent ability in the inhibition of COX-2, and DHR presents comparable activity in inhibiting NO production and growth of SMMC-7721 cells. Relative to RES, its glucuronidation and reduction metabolites showed equal, comparable, or some degree of activity in the above assays, depending on the specific compound and test model, which probably supports their roles in contributing to the in vivo biological activities of the parent molecule.

Vascular exclusion by preserving tumor-contralateral branch of hepatic artery in hepatectomy in treatment liver cancer with cirrhosis.

BACKGROUND/AIMS: To investigate the effectiveness and safety of vascular exclusion by preserving tumor-contralateral branch of hepatic artery in hepatectomy in treatment liver cancer with cirrhosis. METHODOLOGY: The clinical data of 10 cases treated with hepatectomy for liver cancer were analyzed retrospectively. Vascular exclusion by preserving tumor-contralateral branch of hepatic artery was applied to control bleeding. Blood loss, operative time and postoperative hepatic function were observed. RESULTS: The average blood loss was 515mL, the operative time was 191 minutes and the mean time of exclusion was 30.20 minutes. There is no significant difference between hepatic function (serum total bilirubin, alanine transaminase) of postoperative day 7 and that of pre-operation. CONCLUSIONS: Vascular exclusion by preserving tumor-contralateral branch of hepatic artery could effectively control bleeding and preserve hepatic function and is proved to be applicable to patients of liver cancer with cirrhosis.

Corrigendum: The association between metabolic disturbance and cognitive impairments in early-stage schizophrenia.

[This corrects the article DOI: 10.3389/fnhum.2020.599720.].

The Association Between Metabolic Disturbance and Cognitive Impairments in Early-Stage Schizophrenia.

Background: Cognitive impairment is one of the core symptoms of schizophrenia, which is considered to be significantly correlated to prognosis. In recent years, many studies have suggested that metabolic disorders could be related to a higher risk of cognitive defects in a general setting. However, there has been limited evidence on the association between metabolism and cognitive function in patients with early-stage schizophrenia. Methods: In this study, we recruited 172 patients with early-stage schizophrenia. Relevant metabolic parameters were examined and cognitive function was evaluated by using the MATRICS Consensus Cognitive Battery (MCCB) to investigate the relationship between metabolic disorder and cognitive impairment. Results: Generally, the prevalence of cognitive impairment among patients in our study was 84.7% (144/170), which was much higher than that in the general population. Compared with the general Chinese setting, the study population presented a higher proportion of metabolic disturbance. Patients who had metabolic disturbance showed no significant differences on cognitive function compared with the other patients. Correlation analysis showed that metabolic status was significantly correlated with cognitive function as assessed by the cognitive domain scores (p < 0.05), while such association was not found in further multiple regression analysis. Conclusions: Therefore, there may be no association between metabolic disorder and cognitive impairment in patients with early-stage schizophrenia. Trial Registration: Clinicaltrials.gov, NCT03451734. Registered March 2, 2018 (retrospectively registered).

Altered functional connectivity strength and its correlations with cognitive function in subjects with ultra-high risk for psychosis at rest.

AIMS: Evidence of altered structural and functional connectivity in the frontal-occipital network is associated with cognitive deficits in patients with schizophrenia. However, the altered patterns of functional connectivity strength (FCS) in individuals with ultra-high risk (UHR) for psychosis remain unknown. In this study, whole-brain FCS was assessed to examine the altered patterns of FCS in UHR subjects. METHODS: A total of 34 UHR subjects and 37 age- and sex-matched healthy controls were enrolled to undergo resting-state functional magnetic resonance imaging. The imaging data were analyzed using the graph theory method. RESULTS: Compared with healthy controls, UHR subjects showed significantly decreased FCS in the left middle frontal gyrus and significantly increased FCS in the left calcarine cortex. The FCS values in the left middle frontal gyrus were positively correlated to the scores of the Brief Assessments of Cognitionin Schizophrenia Symbol Coding Test (r = 0.366, P = 0.033) in the UHR subjects. A negative correlation was found between the FCS values in the left calcarine cortex and the scores of the Stroop color-naming test (r = -0.475, P = 0.016) in the UHR subjects. A combination of the FCS values in the 2 brain areas showed an accuracy of 87.32%, a sensitivity of 73.53%, and a specificity of 100% for distinguishing UHR subjects from healthy controls. CONCLUSIONS: Significantly altered FCS in the frontal-occipital network is observed in the UHR subjects. Furthermore, decreased FCS in the left middle frontal gyrus and increased FCS in the left calcarine have significant correlations with the cognitive measures of the UHR subjects and thus improve our understanding of the underlying pathophysiological mechanisms of schizophrenia. Moreover, a combination of the FCS values in the 2 brain areas can serve as a potential image marker to distinguish UHR subjects from healthy controls.

MicroRNA-34a functions as a tumor suppressor by directly targeting oncogenic PLCE1 in Kazakh esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the frequent malignant tumors with poor prognosis worldwide. Identifying the prognostic biomarkers and potential mechanisms of such tumors has attracted increasing interest in esophageal cancer biology. Our previous study showed that phospholipase C elipson 1 (PLCE1) expression is up-regulated and associated with disease progression in esophageal carcinoma. MicroRNAs (miRNAs) play vital roles in regulating its target gene expression. However, studies on miRNA-regulated PLCE1 expression and its cellular function are still very few. We found that miR-34a is significantly expressed lower in ESCC tissues. We further showed that PLCE1 is a direct functional target gene of miR-34a, and the functional roles of miR-34a in ESCC cell lines in vitro were also determined through gain- and loss-of-function analyses. Results revealed that miR-34a functions as a tumor suppressor by inhibiting the proliferation, migration, and EMT phenotype, as well as promoting apoptosis of ESCC cell lines. Moreover, PLCE1 is overexpressed in ESCC tumors and promotes tumorigenicity in vivo and vitro. PLCE1 expression is negatively correlated with miR-34a profiles in ESCC tissues. Our data suggest that miR-34a exerts its anti-cancer function by suppressing PLCE1. The newly identified miR-34a/PLCE1 axis partially illustrates the molecular mechanism of ESCC metastasis and represents a new candidate therapeutic target for ESCC treatment.

Finding more active antioxidants and cancer chemoprevention agents by elongating the conjugated links of resveratrol.

Resveratrol is the subject of intense research as a natural antioxidant and cancer chemopreventive agent. There has been a great deal of interest and excitement in understanding its action mechanism and developing analogs with antioxidant and cancer chemoprevention activities superior to that of the parent compound in the past decade. This work delineates that elongation of the conjugated links is an important strategy to improve the antioxidant activity of resveratrol analogs, including hydrogen atom- or electron-donating ability in homogeneous solutions and antihemolysis activity in heterogeneous media. More importantly, C3, a triene bearing 4,4'-dihydroxy groups, surfaced as an important lead compound displaying remarkably increased antioxidant, cytotoxic, and apoptosis-inducing activities compared with resveratrol.