AIMFor further investigating of heat shock transcription factor 1 (HSF1) action in thermoregulation and its physiological mechanism.

METHODSThe relationship among the expression of HSF1 and interleukin 1beta (IL-1beta) mRNA and tumor necrosis factor alpha (TNF-alpha) mRNA in monocytes was studied during the different fever stages in rabbit fever model induced by LPS. The expressions of IL-1beta and TNF-alpha mRNA were measured by RT-PCR assay; HSF1 expression was measured by Western blot.

RESULTS(1) Intravenous injection of LPS produced a double-peak temperature arisen at 60 min and 180 min. (2) The expression of IL-1beta mRNA in monocytes had a peak at 160 min, while the peak of TNF-alpha mRNA expression occurred at 80 min after intravenous injection of LPS. (3) The content of the HSF1 trimer increased gradually after 160 min intravenous injection of LPS. The results indicated that the content of the HSF1 trimer was negative correlation with the expressions of IL-1beta mRNA and TNF-alpha mRNA, and the change in body temperature was a positive correlation with IL-1beta mRNA.

CONCLUSIONIt is possible that HSF1 limits the rise in body temperature by repressing the gene expressions of the endogenous pyrogen, IL-1beta and TNF-alpha.

Animals ; DNA-Binding Proteins ; metabolism ; Fever ; metabolism ; Heat Shock Transcription Factors ; Interleukin-1beta ; metabolism ; Male ; Monocytes ; metabolism ; RNA, Messenger ; genetics ; Rabbits ; Transcription Factors ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

ObjectiveTo explore the application value of individualized surgical treatment based on the CT portal venograpy (CTPV) classiifcation in cirrhotic portal hypertension.MethodsOne hundred and iffty-six patients with cirrhotic portal hypertension who received surgical treatment in Anhui Province Hospital between June 2010 and December 2014 were enrolled in this prospective study. According to different surgical procedures, the patients were divided into two groups: the individualized surgery based on CTPV classiifcation group (classification group) and traditional surgery group (traditional group). Among the 84 patients in the classiifcation group, 56 were males and 28 were females with the age ranging from 19 to 67 years old and the median of 45 years old. Among the 72 patients in the traditional group, 47 were males and 25 were females with the age ranging from 23 to 62 years old and the median of 43 years old. The informed consents of all patients were obtained and the local ethical committee approval was received. The patients in the classiifcation group underwent individualized surgery according to the pre-operative CTPV classiifcation, while the patients in the traditional group underwent splenectomy + pericardial devascularization. The effects of two surgical procedures on the portal hypertension, intraoperative and postoperative conditions and postoperative survival rate of the patients were observed. The observation indexes of two groups were compared usingt test and survival analysis was conducted using Kaplan-Meier method and Log-rank test.ResultsThe postoperative free portal pressure (FPP) in the classiifcation group was (27±3) cmH2O (1 cmH2O=0.098 kPa), signiifcantly lower than (33±8) cmH2O in the traditional group (t=-3.355,P<0.05). The FPP decrease range before and after surgery in the classiifcation group was (13±6) cmH2O, signiifcantly higher than (9±5) cmH2O in the traditional group (t=3.016,P<0.05). The length of surgery and intraoperative blood loss in the classiifcation group were respectively (188±84) min and (378±49) ml, significantly less than (240±76) min and (463±57) ml in the traditional group (t=-2.687,-3.015;P<0.05). The postoperative length of stay and hospitalization expense in the classiifcation group were respectively (12±4) d and (31 000 ± 15 000) yuan, signiifcantly lower than (15±5) d and (36 000±15 000) yuan in the traditional group (t=-2.061,-2.104;P<0.05). The 1, 3-year accumulative survival rate were respectively 94.05% and 85.71% in the classiifcation group, and were respectively 87.50% and 68.05% in the traditional group. The overall survival rate in the classiifcation group was signiifcantly higher than that in the traditional group (χ2=7.000,P<0.05).ConclusionsPre-operative CTPV classification and individualized surgical treatment for patients with cirrhotic portal hypertension can effectively reduce the portal vein pressure and has the advantages of smaller injury and better prognosis.

Background: Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods. In this study, we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain. Methods: Sixty-four adolescent, male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group, n = 32) or normal housing conditions (control group, n = 32). At 15 months of age, 16 mice were randomly selected from each group for a series of behavioral tests, including two depression-related tasks (the sucrose preference test and the tail suspension test). Three days following the last behavioral test, eight mice were randomly selected from each group for immunohistochemical analyses to measure the cell density of parvalbumin (PV⁺)- and calretinin (CR⁺)-positive gamma-aminobutyric-acid (GABA)ergic inhibitory inter-neurons, and the expression levels of vesicular transporters of glutamate-1 (VGluT1) and vesicular GABA transporter (VGAT) in three stress-sensitive regions of the brain (the medial pre-frontal cortex [mPFC], hippocampus, and amygdala). Results: Behaviorally, compared with the control group, adolescent chronic stress increased depression-like behaviors as shown in decreased sucrose preference (54.96 ± 1.97% vs. 43.11 ± 2.85%, t₍₂₂₎ = 3.417, P = 0.003) and reduced latency to immobility in the tail suspension test (92.77 ± 25.08 s vs. 33.14 ± 5.95 s, t₍₂₅₎ = 2.394, P = 0.025), but did not affect anxiety-like behaviors and pre-pulse inhibition. At the neurobiologic level, adolescent stress down-regulated PV⁺, not CR⁺, inter-neuron density in the mPFC (F_{(1, 39)} = 19.30, P < 0.001), and hippocampus (F_{(1, 42)} = 5.823, P = 0.020) and altered the CR⁺, not PV⁺, inter-neuron density in the amygdala (F_{(1, 28)} = 23.16, P < 0.001). The VGluT1/VGAT ratio was decreased in all three regions (all F > 10.09, all P < 0.004), which suggests stress-induced hypoexcitability in these regions. Conclusions Chronic stress during adolescence increased depression-like behaviors in aged mice, which may be associated with the E/I imbalance in stress-sensitive brain regions.

Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.
Animals ; Mice ; Corticotropin-Releasing Hormone/metabolism* ; Nucleus Accumbens/metabolism* ; Receptors, Corticotropin-Releasing Hormone/metabolism* ; Sleep ; Sleep Wake Disorders ; Stress, Psychological/complications*