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Glioblastoma (GBM) is the most universal and devastating primary intracranial neoplasm in the central nervous system. Urolithin A (UA) possesses many pharmacological and biological activities, but its function in GBM is not clear. CCK-8 and colony formation test were used to measure the anti-proliferative potency of UA against GBM cells. Flow cytometry was applied to evaluate cell cycle arrest and apoptosis of U251 and U118 MG cells upon UA incubation. Quantitative real-time PCR and western blotting were conducted to test the regulatory effect of UA on the expression of Sirt1 and FOXO1. Immunodeficient mice were implanted with GBM cells for in vivo validation of the anti-cancer effect of UA. We found UA repressed the proliferation, migration and invasion of glioblastoma cells, while also inhibiting the induction of colony formation ability and epithelial to mesenchymal transition (EMT) in a time- or dose-dependent manner. The does-dependent relationship of UA inducing the cell cycle arrest and apoptosis of glioblastoma cells was identified. Furthermore, UA could enhance the expression levels of Sirt1 and FOXO1 and the knockdown of Sirt1 blocked the inhibitory effects of UA on the proliferation and migration of glioblastoma cells and correspondingly modified the expression level of FOXO1. Overexpression of Sirt1 restored the despaired inhibitory effect of UA induced by Sirt1 knockout on the proliferation and migration of glioblastoma cells. In animal experiments, UA decreased the tumor size and weight of glioblastoma in xenograft nude mice and promoted the expression of Sirt1 and FOXO1 in transplanted tumors. Our findings presented in this study indicate that UA exerts a repressive effect on glioblastoma cells in vivo and in vitro by regulating the Sirt1-FOXO1 axis via the ERK and AKT pathways, indicating that UA is a new novel therapeutic candidate for the treatment of glioblastoma.

Major depressive disorder (MDD) is a serious and widespread mental illness worldwide. The abnormality of neuronal networks may contribute to the etiology of MDD. However, the neural connections underlying the main symptoms of MDD need further elucidation. Here, we found that GABAergic neurons in the lateral septum (LS) were activated by chronic unpredictable stress (CUS), with increased numbers of ΔFosB-labeled neurons. LS neuronal activity was modulated using a chemogenetic approach. Activation of LS neurons caused a depressive phenotype, as shown by increased immobility in the forced swim test, and induced increased susceptibility to subthreshold chronic stress, as indicated by decreased female urine sniffing time and preference for sucrose in depression-related behavior detection, whereas suppression of LS neuronal activity induced an antidepressant effect under basal and stressed conditions. Moreover, we found that the LS showed strong neuronal projections to the dorsal periaqueductal gray (dPAG); activation of dPAG-projecting GABAergic neurons in the LS produced the same depressive behaviors and stress susceptibility as induced by the activation of the majority of LS GABAergic neurons. Finally, we found that activation of neuronal fibers in the dPAG derived from the LS showed depression-related behaviors, as suggested by the decreased female urine sniffing time and sucrose preference in female urine sniffing and sucrose preference tests respectively. Our findings indicate that LS is a key depression-controlling nucleus, and that the LS-PAG projection is an essential effector circuit for morbidity and treatment in depression.

Objectives Cryptotanshinone (CPT), a natural quinoid diterpene, isolated from Salvia miltiorrhiza, has shown various pharmacological properties. However, its effect on chronic unpredictable stress (CUS)-induced depression phenotypes and the underlying mechanism remain unclear. Therefore, the aim of this study was to investigate whether CPT could exert an antidepressant effect. Methods We investigated the effects of CPT in a CUS-induced depression model and explored whether these effects were related to the anti-inflammatory and neurogenesis promoting properties by investigating the expression levels of various signaling molecules at the mRNA and protein levels. Results Administration of CPT improved depression-like behaviors in CUS-induced mice. CPT administration increased the levels of doublecortin-positive cells and reversed the decrease in the expression levels of brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling transduction, as well as the downstream functional proteins, phosphorylated extracellular regulated protein kinases (p-ERK), and cyclic adenosine monophosphate (cAMP)-response element-binding protein levels (p-CREB) in hippocampus. CPT treatment also inhibited the activation of microglia and suppressed M1 microglial polarization, while promoting M2 microglial polarization by monitoring the expression levels of arginase 1 (Arg-1) and inducible nitric oxide synthase (iNOS), and further inhibited the expression of proinflammatory cytokines, including interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α), and increased the expression of the anti-inflammatory cytokine IL-10 by regulating nuclear factor-κB (NF-κB) activation. Conclusions CPT relieves the depressive-like state in CUS-induced mice by enhancing neurogenesis and inhibiting inflammation through the BDNF/TrkB and NF-κB pathways and could therefore serve as a promising candidate for the treatment of depression.

Anhedonia, inability to experience pleasure from rewarding or enjoyable activities, is the prominent symptom of depression that involves dysfunction of the reward processing system. Both genetic predisposition and life events are thought to increase the risk for depression, in particular life stress. The cellular mechanism underlying stress modulating the reward processing neural circuits and subsequently disrupting reward-related behaviors remains elusive. We identify the VTA-BLA-NAc pathway as being activated by sex reward. Blockade of this circuit induces depressive-like behaviors, while reactivation of VTA neurons associated with sexual rewarding experience acutely ameliorates the impairment of reward-seeking behaviors induced by chronic restraint stress. Our histological and electrophysiological results show that the VTA neuron subpopulation responding to restraint stress inhibits the responsiveness of the VTA dopaminergic neurons to sexual reward. Together, these results reveal the cellular mechanism by which stress influences the brain reward processing system and provide a potential target for depression treatment.

Coronovirus disease 2019 (COVID-19) first broke out in Wuhan, Hubei Province, China in 2019, and now it spreads in more than 100 countries around the world. On January 30th, the World Health Organization (WHO) declared COVID-19 a public health emergency (PHEIC) of international concern. It was classified as a pandemic by (WHO) of the World Health Organization on March 11, 2020. With the increase in the number of cases reported by various countries every day, the COVID-19 pandemic has attracted more and more attention around the world. At the same time, this public health emergency has caused a variety of psychological problems, such as panic disorder, anxiety and depression. In addition, the Wuhan Mental Health Center's analysis of 2144 calls from the psychological hotline from February 4 to February 20, 2020 showed that general public accounted for 70%, medical workers accounted for 2.2%, patients with mental disorders accounted for 19.5%, and other personnel accounted for 8.3% (https://mp.weixin.qq.com/s/kmff1vnaLsT2d9xQkK5pwg). Therefore, while controlling the pandemic, the government should also pay attention to the mental health of the general public, medical workers and patients with mental disorders. Community mental health service system, online mental health service, telemedicine and other measures for patients with mental disorders may play a vital role during the pandemic.

The dysregulation of neuronal networks may contribute to the etiology of major depressive disorder (MDD). However, the neural connections underlying the symptoms of MDD have yet to be elucidated. Here, we observed that glutamatergic neurons in the paraventricular thalamus (PVT) were activated by chronic unpredictable stress (CUS) with higher expression numbers of ΔFosB-labeled neurons and protein expression levels, activation of PVT neurons caused depressive-like phenotypes, whereas suppression of PVT neuronal activity induced an antidepressant effect in male, but not female mice, which were achieved by using a chemogenetic approach. Moreover, we found that PVT glutamatergic neurons showed strong neuronal projections to the central amygdala (CeA), activation of the CeA-projecting neurons in PVT or the neuronal terminals of PVT-CeA projection neurons induced depression-related behaviors or showed enhanced stress-induced susceptibility. These results suggest that PVT is a key depression-controlling nucleus, and PVT-CeA projection regulates depression-related behaviors in a sex-dependent manner, which could be served as an essential pathway for morbidity and treatment of depression.

Major depressive disorder (MDD) is a common, serious, debilitating mental illness. Protein phosphatase Mg2+/Mn2+-dependent 1F (PPM1F), a serine/threonine phosphatase, has been reported to have multiple biological and cellular functions. However, the effects of PPM1F and its neuronal substrates on depressive behaviors remain largely unknown. Here, we showed that PPM1F is widely distributed in the hippocampus, and chronic unpredictable stress (CUS) can induce increased expression of PPM1F in the hippocampus, which was correlated with depression-associated behaviors. Overexpression of PPM1F mediated by adeno-associated virus (AAV) in the dentate gyrus (DG) produced depression-related behaviors and enhanced susceptibility to subthreshold CUS (SCUS) in both male and female mice, while, knockout of PPM1F in DG produced antidepressant phonotypes under stress conditions. Whole-cell patch-clamp recordings demonstrated that overexpression of PPM1F increased the neuronal excitability of the granule cells in the DG. Consistent with neuronal hyperexcitability, overexpression of PPM1F regulated the expression of certain ion channel genes and induced decreased phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CAMKII) and Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in hippocampus. These results suggest that PPM1F in the DG regulates depression-related behaviors by modulating neuronal excitability, which might be an important pathological gene for depression or other mental diseases.

Aims We utilized multi-voxel proton magnetic resonance spectroscopy (1H-MRS) to detect biochemical abnormalities in dorsolateral prefrontal white matter and anterior cingulate gray matter and to determine the correlation of biochemical changes with memory function in depressed adolescents. Methods A total of 24 depressed patients and 23 healthy controls were enrolled in this study. MRS was performed to assess the N-acetylaspartate (NAA)/creatine Cr and choline (Cho)/Cr ratios in dorsolateral prefrontal white matter and anterior cingulate gray matter of participants. Memory function was measured on the basis of Wechsler Memory Scale scores, and depression was diagnosed on the basis of clinical observation, interview, and Hamilton Depression Rating Scale scores. Results Compared with controls, depressed patients had significantly lower NAA/Cr and Cho/Cr ratios in left dorsolateral prefrontal white matter and lower NAA/Cr ratios in right dorsolateral prefrontal white matter (P

Exposure to chronic constant light (CCL) influences circadian rhythms and evokes stress. Since hippocampus is sensitive to stress, which facilitates long-term depression (LTD) in the hippocampal CA1 area, we examined whether CCL exposure influenced hippocampus-dependent spatial memory and synaptic plasticity in Wistar rats. Here we report that CCL exposure (3 weeks) disrupted 24-h cycle of locomotion activity in open field test. These rats showed shorter escape latency during initial phase of spatial learning but impaired hippocampus-dependent spatial memory without affecting the visual platform learning task in Morris water maze (MWM) compared with control rats. This effect may be due to stress adaptation as reflected by reduced thigmotaxis and anxiety-like behaviors in CCL rats. Moreover, in CA1 area of the hippocampal slices, CCL rats failed to show LTD by low frequency stimulation (LFS, 900 pulses, 1 Hz), while showed decreased short-term depression compared with control rats indicating the induction of LTD was influenced by CCL exposure. Furthermore, additional acute stress enabled LFS to induce LTD in control rats but not in CCL rats. Thus, these results suggested that CCL exposure impaired spatial memory and influenced hippocampal LTD, which may be due to stress adaptation.

The antidepressive effects of the antidiabetic medicine, pioglitazone, were recently reported in several studies. These effects may ameliorate the depressive symptoms of patients with post-stroke depression (PSD). The present study aimed to evaluate the antidepressive effect of pioglitazone in patients with PSD combined with type 2 diabetes. A total of 118 consecutive patients with stroke who had depression were studied for an average of 3 months. The Diagnostic and Statistical Manual of Mental Disorders (fourth edition) was used to assess whether a patient was depressed or not. The severity of depression was evaluated by the Hamilton depression rating scale (HAMD). In accordance with their HAMD scores, the 118 patients were divided into a severe depression group (n=40) and a mild and moderate (MM) depression group (n=78). These subjects were then divided into pioglitazone [30 mg once daily (qd)] and metformin (0.5 g twice daily) subgroups. All patients were given fluoxetine (20 mg qd). Follow-up evaluations, which included HAMD scores, activities of daily living (ADL) scores, fasting blood glucose (FBG) levels and fasting insulin (FINS) levels, were conducted on the first and third month following the beginning of the treatment. In the MM depression group, the HAMD score in the pioglitazone subgroup was lower than that in the metformin subgroup following treatment for 1 or 3 months. In the severe depression group, the HAMD score in the pioglitazone subgroup was lower than that in the metformin subgroup following 3 months of treatment. The FINS levels of the pioglitazone subgroup gradually decreased in the 3 months of treatment. No noticeable improvement was observed in the ADL scores and FBG values. In conclusion, the results of the current study demonstrate that pioglitazone effectively decreased HAMD scores and FINS values in patients with PSD, suggesting that pioglitazone may be useful for the treatment of patients with PSD combined with type 2 diabetes.

Stress in early life is believed to cause cognitive and affective disorders, and to disrupt hippocampal synaptic plasticity in adolescence into adult, but it is unclear whether exposure to enriched environment (EE) can overcome these effects. Here, we reported that housing rats in cages with limited nesting/bedding materials on postnatal days 2-21 reduced body weight gain, and this type of early life stress impaired spatial learning and memory of the Morris water maze and increased depressive-like behavior of the forced swim test in young adult rats (postnatal days 53-57). Early life stress also impaired long-term potentiation in hippocampal CA1 area of slices of young adult rats. Remarkably, EE experience on postnatal days 22-52 had no effect on spatial learning/memory and depressive-like behavior, but it significantly facilitated LTP in control rats, and completely overcame the effects of early life stress on young adult rats. These findings suggest that EE experience may be useful for clinical intervention in preventing cognitive and affective disorders during development.

We utilized multi-voxel proton magnetic resonance spectroscopy ((1)H-MRS) to detect biochemical abnormalities in dorsolateral prefrontal white matter and anterior cingulate gray matter and to determine the correlation of biochemical changes with memory function in depressed adolescents.A total of 24 depressed patients and 23 healthy controls were enrolled in this study. MRS was performed to assess the N-acetylaspartate (NAA)/creatine Cr and choline (Cho)/Cr ratios in dorsolateral prefrontal white matter and anterior cingulate gray matter of participants. Memory function was measured on the basis of Wechsler Memory Scale scores, and depression was diagnosed on the basis of clinical observation, interview, and Hamilton Depression Rating Scale scores.Compared with controls, depressed patients had significantly lower NAA/Cr and Cho/Cr ratios in left dorsolateral prefrontal white matter and lower NAA/Cr ratios in right dorsolateral prefrontal white matter (P 0.05). No biochemical differences were identified in the bilateral anterior cingulate gray matter between the two groups. Nevertheless, the depressed patients showed significantly lower memory quotient than controls (P 0.05). The NAA/Cr ratio in dorsolateral prefrontal white matter positively correlated with memory quotient (left: P 0.01; right: P 0.05).These findings suggest that biochemical abnormalities in prefrontal white matter are involved in the pathophysiology of adolescent depression. In particular, such abnormalities are already present at the early stage of the disorder, and low NAA/Cr in bilateral anterior frontal white matter may be associated with memory impairment and related neuropathology.

The anesthetic, propofol, effectively suppresses excitatory synaptic transmission and facilitates long-term depression (LTD) in the CA1 region of the hippocampus. Here, we have examined whether these effects are different in the developing hippocampus. We found that propofol in suppressing whole-cell excitatory postsynaptic currents (EPSC) was more effective in 21 day old rats than either in 7 day old rats or under the condition of high intracellular chloride concentration in 21 day old rats. Furthermore, the propofol concentration to facilitate the NMDA receptor-dependent LTD was lower at postnatal day 21 than at postnatal day 7. Interestingly, the decay time of EPSC was decreased during the development from postnatal day 7 to 21, but it was increased by the recording condition of high intracellular chloride concentration or by propofol administration. All these effects of propofol were dependent on the chloride channel opening. These observations suggest that propofol may induce differential anesthetic effects in the developing hippocampus, at least partially, depending on the intracellular chloride concentration.

An experimental setup, a mini-cabinet with reflector at its top, has been designed to study the drying process of jujube fruit by the convection and the solar radiation with hot air convection. The research experimentally investigated the drying characteristics and behavior of heat and mass transfer. Also, drying curves were analyzed. It demonstrated that solar energy could play an important role in promoting heat and mass transfers and saves energy consumed. The optimum conditions of appropriated temperature and humidity were obtained to save energy in solar energy convection drying process.Copyright © 2004 by ASME