Objective : To investigate the antidepressant effects and the underlying mechanisms of tetrahydrocurcumin(THC) and its nanoparticle formulation(THCN). Methods : Forty-six male ICR mice were randomly divided into Con group, LPS group, THC group, THCN group and SER group. A mouse depression model was established by intraperitoneal administration of LPS. The anxiety and depression-like behaviors of mice were evaluated by open field test(OFT) and forced swimming test(FST). Myelin staining was applied to assess the extent of demyelination in the prefrontal cortex of the mice. The prefrontal cortex and hippocampus were further examined for the expression levels of glial fibrillary acidic protein(GFAP) and Toll-like receptor 4(TLR4) through quantitative immunofluorescence assays. Results : Compared with the Con group, the LPS group showed increased anxiety-like and depressive-like behaviors in both the long-term and short-term experiments(P<0.05); the degree of demyelination increased in the LPS group of the long-term experiment(P<0.01); the expression of GFAP was reduced in the LPS group of the short-term experiment(P<0.01), while the expression of TLR4 increased(P<0.05); the expression of TLR4 decreased in the THC group(P<0.01); the expression of GFAP in the prefrontal cortex of the THCN group was reduced(P<0.01), while the expression of TLR4 increased(P<0.05). Compared with the LPS group, the THC group showed reduced depressive-like behaviors in the long-term experiment(P<0.05), while the anxiety-like and depressive-like behaviors of the THCN group and the SER group were reduced(P<0.05), and the anxiety-like and depressive-like behaviors of the THC group and the THCN group were reduced in the short-term experiment(P<0.05); the degree of demyelination was reduced in the THC group, THCN group and SER group in the long-term experiment(P<0.05); the expression of GFAP increased in the THC group of the short-term experiment(P<0.05), while the expression of TLR4 was reduced(P<0.05), and the expression of GFAP increased in the THCN group(P<0.05). Compared with the THC group, the THCN group and the SER group showed reduced anxiety-like behaviors in the long-term experiment(P<0.05); the expression of GFAP in the prefrontal cortex of the THCN group was reduced in the short-term experiment(P<0.05), while the expression of TLR4 in the hippocampal DG area increased in the short-term experiment(P<0.01). Conclusion Tetrahydrocurcumin and its nanoparticle formulation both exert significant ameliorative effects on depression-like behaviors and demyelination in mice induced by lipopolysaccharide. The antidepressant mechanism of THC appears to be mediated through the down-regulation of TLR4 and the up-regulation of GFAP. The mechanism underlying the antidepressant action of THCN seems predominantly focused on the enhancement of GFAP expression.

Objective : To investigate the therapeutic effects and underlying mechanisms of cannabidiol(CBD) and its nano-formulations on depression-like behaviors in mice. Methods : A murine model of acute anxiety and depression was established by intraperitoneal administration of lipopolysaccharide(LPS). A total of 55 mice were randomly assigned into several groups: for the long-term study, a control group(Con), a model group(LPS), a cannabidiol group(CBD), a nano-cannabidiol group(NCBD), and a sertraline(SER) group, each consisting of 7 mice. In the short-term study, mice were divided into four groups: the Con group, LPS group, CBD group, and NCBD group, with 5 mice in each group. Except for the Con group and LPS group, which were given distilled water, the remaining groups were administered 25 and 50 mg/kg of cannabidiol and its nano-formulationviaoral gavage. The open field and forced swimming tests were employed to assess anxiety-and depression-like behaviors inmice. Luxol Fast Blue myelin staining was employed to evaluate myelin sheath morphology in the prefrontal cortex, and immunofluorescence staining was utilized to quantify the protein expression levels of silencing information regulator(SIRT2), ionized calcium binding adaptor molecule-1(Iba-1), and interleukin-1β(IL-1β) in the prefrontal cortex. Results : In the long-term experiment, the LPS group exhibited a significant reduction in shuttle times(P<0.05), an increase in immobility time(P<0.01), and a decrease in the number and length of myelin sheaths(P<0.05) compared to the Con group. Compared to the LPS group, the depressive behaviors in the CBD, NCBD, and SER groups were significantly alleviated(P<0.01), and the number and length of myelin sheaths increased(P<0.05). In the short-term experiment, compared to the Con group, the LPS group exhibited significantly increased anxiety-and depression-like behaviors(P<0.05), downregulated SIRT2 expression(P<0.01), and upregulated Iba-1 and IL-1β expression(P<0.01). The CBD and NCBD groups demonstrated a reduction in anxiety and depression-like behaviors(P<0.05), an increase in SIRT2 expression(P<0.01), and a decrease in Iba-1 and IL-1β expressions(P<0.05) compared to the LPS group. Conclusion CBD and its nano-formulations effectively mitigate anxiety and depression-like behaviors in mice. The underlying mechanisms may be associated with the reversal of SIRT2 protein expression, demyelination changes, microglial activation, and the levels of inflammatory factors in the prefrontal cortex.

Atypical sensory responsivity is widely reported in autistic individuals and is related to elevated functional difficulties. Dynamically, altered initial responses and/or habituation rates could underlie their atypical averaged responses to repeated sensory stimuli. In this study we aimed to measure the arousal level in response to different types of auditory stimuli and the dynamic change of atypical arousal level using pupillometry in autistic children. In Experiment 1, 43 autistic children and 49 neurotypical (NT) children were asked to passively listen to a mild sound and an aversive sound repeatedly. In Experiment 2, 39 autistic children and 44 NT children who went through Experiment 1 listened to a gradually emerging non-startling sound and a suddenly emerging startling sound in a random order. We found that the autistic group showed hyper-arousal in response to the aversive sound and the startling sound as reflected by their larger change in pupil area. In comparison, these autistic children demonstrated normal arousal in response to the mild sound and the non-startling sound. Dynamically, the autistic group had a larger peak pupil area change than the NT group in the first trial and a normal habituation rate to the aversive sound. In summary, our results suggest hyper-arousal to aversive and startling stimuli and the role of larger initial responses in hyper-arousal in autism. Minimizing aversive and startling sensory stimuli or gradually increasing the volume of aversive auditory stimuli to allow autistic children to adapt using the principle of habituation is recommended to reduce the arousal level and problematic behaviors of autistic children.
Humans ; Male ; Child ; Female ; Acoustic Stimulation ; Autistic Disorder/physiopathology* ; Arousal/physiology* ; Pupil/physiology* ; Habituation, Psychophysiologic/physiology* ; Auditory Perception ; Child, Preschool

【Objective】 To investigate the effects of miR-29b-3p on congenital heart disease and its mechanism. 【Methods】 The expression level of miR-29b-3p in serum from CHD patients and normal individuals， and in cells was detected by RT-qPCR. Dimethylsulfoxide （DMSO） was used to induce P19 cells to differentiate into cardiomyocytes. Western blot was used to measure the expression levels of cardiogenesis-associated genes， and phosphatase and tensin homolog （PTEN） level in cells. The proliferation and migration of cardiomyocytes were measured by CCK-8 and Transwell assay， respectively. Dual-luciferase gene reporter assay was used to verify the targeted relationship between miR-29b-3p and PTEN. 【Results】 Compared with that of normal individuals， the expression of miR-29b-3p in CHD patients was decreased. During differentiation， miR-29b-3p level was higher at late stage than that at early stage. Downregulated miR-29b-3p inhibited the differentiation of P19 cells into cardiomyocytes， and inhibited cell proliferation and migration. miR-29b-3p targeted PTEN. The increased PTEN level induced by miR-29b-3p knockdown inhibited the differentiation of P19 cells， and proliferation and migration of cardiomyocytes. 【Conclusion】 miR-29b-3p was downregulated in the serum of CHD patients. The downregulation of miR-29b-3p inhibited the differentiation of P19 cells， proliferation and migration of cardiomyocytes by targeting and regulating PTEN.

Objective Based on the observation of the changes of symptoms, histopathology, visceral sensitivity, mast cell activation, autophagy, and Beclin-1 and Claudin-2 expression in rats, we established and evaluated a new rat model of diarrhea-predominant irritable bowel syndrome (D-IBS) induced by restraint-stress combined with capsaicin (CAP) administration.Methods Forty healthy 5-week old male Sprague Dawley (SD) rats were randomly divided into normal group, model group I, model group II and model group III, with 10 rats in each group.The D-IBS model was established by restraint-stress combined with intragastric administration of CAP (2 mL/100 g body weight, 0.125% in group I, 0.250% in group II, 0.500% in group III), tail clipping and forelimb restriction for 30 minutes every day for 2 weeks.The rats in the control group were treated with saline for 2 weeks.The number of contraction of abdominal wall and arched back were measured by Power Lab instrument.The mast cell activation was detected using aldehyde-magenta-orange G staining.Light and electron microscopic examinations were performed to detect the morphology and autophagy of colonic tissues.The expressions of Beclin-1 and Claudin-2 in the colonic mucosa were detected by streptavidin-biotin complex (SABC) immunohistochemical staining.Results All rats in the model group III died during the experiment.Compared with the control group and model group I, the stool frequency was increased and the visceral sensitivity threshold decreased in the model group II, and there were statistically significant differences between the model group II and the control and model groups I (P < 0.05).The colonic mucosa, mucosal epithelium and glands in each group showed normal morphology and there was no submucosal vasodilatation and diffuse inflammatory cell infiltration.Except for the control group, round purple-reddish staining spots were observed in the rat mucosal stroma or submucosa in the model groups I and II, indicating an increased expression of mast cells.The autophagy, expressions of Beclin-1 and Claudin-2 in the colonic epithelium were significantly increased in the model group II compared with control group and model group I (P< 0.05).Conclusions The model of D-IBS induced by restraint-stress combined with capsaicin is characterized by increased diarrhea, visceral hypersensitivity, increased mast cell expression and autophagy of intestinal epithelial cells, and disruption of the intestinal mucosal barrier.This model is simple to set up and shows similar symptoms of human irritable bowel syndrome.Therefore, it is worthy of popularization and application.

Objective To investigate the effect of hyperthermia on the expression of E6 and E7 genes of human papillomavirus (HPV) type 6 and 11 in HPV-infected human skin. Methods Tissue samples were obtained from the lesions of condyloma accuminatum (CA) in 6 patients after informed consent. Each sample was divided into 4 parts: one was embedded and directly stored at -80 ℃; the other 3 parts were placed in culture medium and the surface of the samples was irradiated for 30 minutes with a thermotherapy apparatus at 37℃, 42 ℃, 45 ℃, respectively, then the samples were taken out and stored at -80 ℃. RNA was extracted from the specimens, real time quantitative PCR (qPCR) was performed to detect the expression of E6 and E7 genes of HPV-6 and -11. Results Of the 6 patients, 2 were infected with HPV-6 and -11 respectively, 4 with both HPV-6 and HPV-11. The expression of E6 and E7 mRNA decreased with the increase in irradiation temperature. The relative mRNA expression levels at 37 ℃, 42 ℃ and 45 ℃ were 1.00 ± 0.00, 0.61 ± 0.17, 0.27 ± 0.15, respectively, for HPV-6 E6 gene, 1.00 ± 0.00, 0.56 ± 0.21, 0.16 ± 0.11 respectively, for HPV-6 E7 gene, 1.00 ± 0.00, 0.60 ± 0.22, 0.16 ± 0.08, respectively, for HPV-I1 E6 gene, 1.00 ± 0.00, 0.55 ± 0.15, 0.24 ± 0.06, respectively, for HPV-11 E7 gene; statistical difference was noted among them between the specimens irradiated at different temperature (all P < 0.01). Conclusion Hyperthermia can remarkably suppress the expression of HPV-6/I 1 E6 and E7 genes, which may be a possible mechanism under the regression of warts induced by local hyperthermia.

Objective To investigate the association between arterial compliance and fundus oculi arteriosclerosis in elderly people. Methods A total of 73 elderly subjects,including 61 elderly patients with fundus oculi arteriosclerosis and 12 healthy volunteers were recruited into the study.Capacitive arterial compliance(C1)and oscillatory arterial compliance(C2)were measured by DO2020 Cardiovascular Profiling Instrument.Moreover,fundus photographs were measured using Canon figure fundus camera. Results There were significant differences in systolic blood pressure(SBP),diastolic blood pressure(DBP),mean artery pressure,pulse pressure,capacitive arterial compliance (C1),and oscillatory arterial compliance(C2)between patients with fundus oculi arteriosclerosis and healthy volunteers(all P<0.05).In multiple regression analysis,the grade of fundus oculi arteriosclerosis was significantly correlated with SBP,DBP,mean artery pressure and pulse pressure (r=0.357,0.261,0.342,0.280,all P<0.05).Moreover,there were significant correlations between the grade of fundus oculi arteriosclerosis and Cl(r=-0.281,P<:0.05),and C2(r=-0.308,P<0.01). Conclusions These findings underscore the efficacy of C1 and C2 in identifying patients with fundus oculi arteriosclerosis.