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Depressive symptoms, such as anhedonia, decreased social interaction, and lack of motivation, implicate brain reward systems in the pathophysiology of depression. Exposure to chronic stress impairs the function of brain reward circuits and is well-known to be involved in the etiology of depression. A transcriptomic analysis found that stress alters the expression of Rasd2 in mice prefrontal cortex (PFC). Similarly, in our previous study, acute fasting decreased Rasd2 expression in mice PFC, and RASD2 modulated dopamine D2 receptor (DRD2)-mediated antidepressant-like effects in ovariectomized mice. This research suggests the role of RASD2 in stress-induced depression and its underlying neural mechanisms that require further investigation. Here, we show that 5-day unpredictable mild stress (5-d UMS) exposure reduces RASD2 expression in both the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) of mice, while overexpression (but not knock-down) of Rasd2 in the NAc core (NAcc) alleviates 5-d UMS-induced depression-like behaviors and activates the DRD2-cAMP-PKA-DARPP-32 signaling pathway. Further studies investigated neuronal projections between the mPFC (Cg1, PrL, and IL) and NAcc, labeled by the retrograde tracer Fluorogold. Depression-like behaviors induced by 5-d UMS were only related to inhibition of the PrL-NAcc circuit. DREADD (Designer receptors exclusively activated by designer drug) analysis found that the activation of PrL-NAcc glutaminergic projection alleviated depression-like behaviors and increased DRD2- and RASD2-positive neurons in the NAcc. Using Drd2-cre transgenic mice, we constructed mice with Rasd2 overexpression in DRD2PrL-NAcc neurons, finding that Rasd2 overexpression ameliorated 5-d UMS-induced depression-like behaviors. These findings demonstrate a critical role for RASD2 modulation of DRD2PrL-NAcc neurons in 5-d UMS-induced depression-like behaviors. In addition, the study identifies a new potential strategy for precision medical treatment of depression.
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Developing from transient absorption (TA) spectroscopy, two-dimensional (2D) spectroscopy with pump-probe geometry has emerged as a versatile approach for alleviating the difficulty in implementing 2D spectroscopy with other geometries. However, the presence of cross-phase modulation (XPM) in TA spectroscopy introduces significant spectral distortions, particularly when the pump and probe pulses overlap. We demonstrate that this phenomenon is extended to the 2D spectroscopy with pump-probe geometry and the XPM is induced by the interference of the two pump pulses. We present the oscillatory behavior of XPM in the 2D spectrum and its displacement with respect to the waiting time delay through both experimental measurements and numerical simulations. Additionally, we explore the influence of probe pulse chirp on XPM and discover that by compressing the chirp, the impact of XPM on the desired signal can be reduced.
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BACKGROUND: Previous studies have shown that estrogen and acute fasting for 9 hours have antidepressant-like effects by reducing immobility time in the forced swimming test. Estrogen and acute fasting share a common regulatory gene, Rasd2. RASD2 regulates dopamine D2 receptor (DRD2) transmission, but the role of Rasd2 in the DRD2-mediated antidepressant-like effect of acute fasting has not been examined. METHODS: In this study, open field test, forced swimming test, tail suspension test and sucrose preference test were used for behavioral assessments. RNA-seq, western blot, enzyme-linked immunosorbent assay, and co-immunoprecipitation were used to explore the role of Rasd2 in a depression model induced by ovariectomy and the antidepressant-like effects of 9-hour fasting. RESULTS: The RNA seq results showed that acute fasting induced a significant change in Rasd2 gene expression. Depression-like behaviors induced by ovariectomy were associated with decreased RASD2 and DRD2 protein levels in the hippocampus, and Rasd2 overexpression in the hippocampus alleviated depression-like behaviors and increased DRD2 expression. Nine-hour fasting had antidepressant-like effects in ovariectomized mice by upregulating the protein levels of RASD2, DRD2, CREB-BDNF, Akt, and estrogen receptor beta, and these effects can be blocked by DRD2 antagonists. CONCLUSIONS: Our results suggest that Rasd2 and DRD2 play pivotal roles in depression-like behavior induced by ovariectomy. Rasd2 regulates DRD2-mediated antidepressant-like effects of acute fasting in ovariectomized mice. Rasd2 can therefore be postulated to be a potential therapeutic target for depression and perhaps also a potential predictive marker for depression.
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Antidepressivos , Natação , Feminino , Camundongos , Animais , Antidepressivos/uso terapêutico , Estrogênios/farmacologia , Estrogênios/metabolismo , Jejum , Receptores de Dopamina D2/metabolismo , Depressão/tratamento farmacológico , Depressão/genética , Hipocampo , Modelos Animais de Doenças , Fator Neurotrófico Derivado do Encéfalo/metabolismoRESUMO
Benzoxazole alkaloids exhibit a diverse array of structures and interesting biological activities. Herein we report the identification of a benzoxazole alkaloid-encoding biosynthetic gene cluster (mich BGC) in the marine-derived actinomycete Micromonospora sp. SCSIO 07395 and the heterologous expression of this BGC in Streptomyces albus. This approach led to the discovery of five new benzoxazole alkaloids microechmycin A-E (1-5), and a previously synthesized compound 6. Their structures were elucidated by HRESIMS and 1D and 2D NMR data. Microechmycin A (1) showed moderate antibacterial activity against Micrococcus luteus SCSIO ML01 with the minimal inhibitory concentration (MIC) value of 8 µg mL-1.
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Alcaloides , Micromonospora , Micromonospora/genética , Micromonospora/química , Antibacterianos/farmacologia , Antibacterianos/química , Alcaloides/farmacologia , Alcaloides/química , Espectroscopia de Ressonância Magnética , Genômica , Estrutura MolecularRESUMO
Optogenetics is a biological technique, which involves controlling the biological functions of target cells using light. In recent years, optogenetics has become one of the most advanced experimental techniques in neuroscience. It provides precise control on target cells in addition to rapidly and specifically altering the neuronal activity both in vivo and ex vivo. The emergence of optogenetic technology enabled researchers to study the pathogenesis of diseases at the level of neurons and explore new ideas for the treatment of brain diseases. Depression is a highly prevalent and disabling mental disorder, which seriously impacts people's work and life. Currently, our understanding of the occurrence, development, and treatment of depression has made great progress, but the exact pathogenesis of depression is still unclear. In this article, we summarize the applications of optogenetics in improving our understanding of depression and provide new insight for uncovering the potential pathways of depression.
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Encéfalo/fisiopatologia , Depressão/genética , Depressão/fisiopatologia , Optogenética , Animais , HumanosRESUMO
Depression is a common neurological disease that seriously affects human health. There are many hypotheses about the pathogenesis of depression, and the most widely recognized and applied is the monoamine hypothesis. However, no hypothesis can fully explain the pathogenesis of depression. At present, the brain-derived neurotrophic factor (BDNF) and neurogenesis hypotheses have highlighted the important role of plasticity in depression. The plasticity of neurons and glial cells plays a vital role in the transmission and integration of signals in the central nervous system. Plasticity is the adaptive change in the nervous system in response to changes in external signals. The hippocampus is an important anatomical area associated with depression. Studies have shown that some antidepressants can treat depression by changing the plasticity of the hippocampus. Furthermore, caloric restriction has also been shown to affect antidepressant and hippocampal plasticity changes. In this review, we summarize the latest research, focusing on changes in the plasticity of hippocampal neurons and glial cells in depression and the role of BDNF in the changes in hippocampal plasticity in depression, as well as caloric restriction and mitochondrial plasticity. This review may contribute to the development of antidepressant drugs and elucidating the mechanism of depression.
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Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtorno Depressivo/tratamento farmacológico , Hipocampo/fisiopatologia , Neuroglia/fisiologia , Neurônios/fisiologia , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Transtorno Depressivo/metabolismo , Transtorno Depressivo/fisiopatologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Neuroglia/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Neurônios/efeitos dos fármacosRESUMO
Foam flotation is generally recognized as a low-cost and efficient technology for the harvesting of microalgae for food, feed and fuel production, as well as environmental remediation. However, the harvesting efficiency of microalgae using foam flotation is restricted by the residual metal cations in the medium, and the corresponding inhibition mechanism has not yet been revealed. This study investigated the effects of metal cations in the medium on the harvesting efficiency and concentration factor during the foam flotation of Scenedesmus acuminatus. The interface interaction of cell-collector-bubble effected by metal cations was revealed by quantifying the amount of collector (cetyl trimethylammonium bromide, CTAB) between cells and bubbles, as well as the response of bubble interface characteristics. Results showed that the harvesting efficiency dropped linearly as the increase of cationic concentrations. Under the CTAB dose of 20 mg L-1, the harvesting efficiency decreased from 98.65% to 56.77% with a decrease of concentration factor from 25.41 to 9.05 in the presence of metal cations. The Na+ and Mg2+ in the medium were the major inhibitors. The inhibitory mechanisms revealed that metal cations obviously impeded the adsorption of CTAB onto the cells by competing adsorption site, resulting in a low harvesting efficiency. The presence of metal cations also inhibited the bubble coalescence and slowed down drainage velocity in the plateau channel of foam layer, forming foam with higher water content, thus reducing the concentration factor. A schematic illustration is proposed to better understand the effect mechanism of metal cations on microalgal foam flotation. This study might facilitate the process development in an effort to overcome the inhibition of cations during microalgal foam flotation.
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Microalgas , Cetrimônio , Metais , CátionsRESUMO
Two-dimensional electronic spectroscopy (2DES) can be implemented with different geometries, e.g., BOXCARS, collinear, and pump-probe geometries. The pump-probe geometry has the advantage of overlapping only two beams and reducing phase cycling steps. However, its applications are typically limited to observing the dynamics with single-quantum coherence and population, leaving the challenge to measure the dynamics of the double-quantum (2Q) coherence, which reflects the many-body interactions. We demonstrate an experimental technique in 2DES under pump-probe geometry with a designed pulse sequence and the signal processing method to extract 2Q coherence. In the designed pulse sequence, with the probe pulse arriving earlier than the pump pulses, our measured signal includes the 2Q signal as well as the zero-quantum signal. With phase cycling and data processing using causality enforcement, we extract the 2Q signal. The proposal is demonstrated with rubidium atoms. We observe the collective resonances of two-body dipole-dipole interactions in both the D1 and D2 lines.
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Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test. However, whether 9-hour fasting has therapeutic effects in female mice with depressive symptoms has not been established. Therefore, in this study, we simulated perimenopausal depression via an ovariectomy in mice, and subjected them to a single 9-hour fasting 7 days later. We found that the ovariectomy increased the time spent immobile in the forced swimming test, inhibited expression of the mammalian target of rapamycin complex 1 signaling pathway in the hippocampus and prefrontal cortex, and decreased the density of dendritic spines in the hippocampus. The 9-hour acute fasting alleviated the above-mentioned phenomena. Furthermore, all of the antidepressant-like effects of 9-hour fasting were reversed by an inhibitor of the mammalian target of rapamycin complex 1. Electrophysiology data showed a remarkable increase in long-term potentiation in the hippocampal CA1 of the ovariectomized mice subjected to fasting compared with the findings in the ovariectomized mice not subjected to fasting. These findings show that the antidepressant-like effects of 9-hour fasting may be related to the activation of the mammalian target of the rapamycin complex 1 signaling pathway and synaptic plasticity in the mammalian hippocampus. Thus, fasting may be a potential treatment for depression.
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Dopamine and its receptors are currently recognized targets for the treatment of several neuropsychiatric disorders, including Parkinson's disease, schizophrenia, some drug use addictions, as well as depression. Dopamine receptors are widely distributed in various regions of the brain, but their role and exact contribution to neuropsychiatric diseases has not yet been thoroughly studied. Based on the types of dopamine receptors and their distribution in different brain regions, this paper reviews the current research status of the molecular, cellular and circuit mechanisms of dopamine and its receptors involved in depression. Multiple lines of investigation of these mechanisms provide a new future direction for understanding the etiology and treatment of depression and potential new targets for antidepressant treatments.
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Depression has an alarmingly high prevalence worldwide. A growing body of evidence indicates that environmental factors significantly affect the neural development and function of the central nervous system and then induce psychiatric disorders. Early life stress (ELS) affects brain development and has been identified as a major cause of depression. It could promote susceptibility to stress in adulthood. Recent studies have found that ELS induces epigenetic changes that subsequently affect transcriptional rates of differentially expressed genes. The epigenetic modifications involved in ELS include histone modifications, DNA methylation, and non-coding RNA. Understanding of these genetic modifications may identify mechanisms that may lead to new interventions for the treatment of depression. Many reports indicate that different types of ELS induce epigenetic modifications of genes involved in the neurotransmitter systems, such as the dopaminergic system, the serotonergic system, the gamma-aminobutyric acid (GABA)-ergic system, and the glutamatergic system, which further regulate gene expression and ultimately induce depression-like behaviors. In this article, we review the effects of epigenetic modifications on the neurotransmitter systems in depression-like outcomes produced by different types of ELS in recent years, aiming to provide new therapeutic targets for patients who suffer from depression.
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Two new piericidins A5 (1) and G1 (2), a previously synthesized piericidin G2 (3), and two known piericidins A1 (4) and A2 (5) were isolated from the marine-derived Streptomyces sp. SCSIO 40063. The structures of 1-5 were elucidated by HRESIMS, 1 D, 2 D NMR data analyses and comparisons with the known compounds. Compound 2 showed moderate cytotoxicities against four human tumor cell lines SF-268, MCF-7, HepG2 and A549 with IC50 values between 10.0 and 12.7 µM.
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Antineoplásicos , Streptomyces , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Streptomyces/químicaRESUMO
BACKGROUND: Shenfu decoction (SFD) is a classic Chinese medicine prescription that has a strong cardiotonic effect. The combination of ginseng (the dried root of Panax ginseng C. A. Meyer) and Fuzi (processed product of sub-root of Aconitum carmichaeli Debx), the main constituents of SFD, has been reported to improve the pharmacological effect of each other. Moreover, research has shown that the main active components of SFD, ginseng total saponins (GTS) and Fuzi total alkaloids (FTA), have antidepressant activity. However, the effects of these ingredients on depressive-like behavior induced by ovariectomy, a model of menopausal depression, have not been studied. PURPOSE: Our research aims to elucidate the antidepressant-like effects of GTS and FTA compatibility (GF) in ovariectomized mice and the potential mechanisms. METHODS: To elucidate the antidepressant-like effects of GF in mice in ovariectomy condition, behavioral tests were performed after 7 days of intragastric administration of different doses of GF. Underlying molecular mechanisms of CREB-BDNF, BDNF-mTORC1 and autophagy signaling were detected by western blotting, serum metabolites were examined by UPLC-QE plus-MS and dendritic spine density was determined by Golgi-Cox staining. RESULTS: GF remarkably decreased the immobility time in the forced swim test. GF also increased levels of pCREB/CREB, BDNF, Akt, mTORC1 and p62 in the prefrontal cortex and hippocampus, as well as decreased LC3-II/LC3-I in the prefrontal cortex and hippocampus of ovariectomized mice. Furthermore, 15 serum differential metabolites (9 of which are lipids and lipid molecules) were identified by metabonomics. Next, the antidepressant-like effects of GF was blocked by rapamycin, an inhibitor of mTORC1. The antidepressant actions of GF on levels of pCREB, mTORC1, LC3-â ¡/LC3-â and p62 in the prefrontal cortex and the levels of BDNF, Akt, mTORC1 and p62 in the hippocampus were inhibited by rapamycin, and the dendritic spines density was also regulated. CONCLUSION: GF has antidepressant effects in ovariectomized mice, and like other antidepressants, these effects involve activation of BDNF-mTORC1, autophagy regulation and consequent effects on hippocampal synaptic plasticity. Moreover, metabolomic results suggest that GF also has effects on peripheral lipid profiles that may provide potential biomarkers for these antidepressant-like effects. These results indicate that GF is worthy of further exploration as a promising pharmaceutical treatment for depression. This study provides a new direction for the development of new indications for traditional Chinese medicine compounds.
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Alcaloides , Panax , Saponinas , Alcaloides/farmacologia , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Autofagia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cardiotônicos/farmacologia , Depressão/metabolismo , Diterpenos , Medicamentos de Ervas Chinesas , Feminino , Hipocampo , Lipídeos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Redes e Vias Metabólicas , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/metabolismo , Saponinas/farmacologia , Sirolimo/farmacologiaRESUMO
The objective of this work was to investigate the chemical compositions of the essential oil (EO) extracted from Senecio scandens by hydrodistillation and their insecticidal activities against Tribolium castaneum, Lasioderma serricorne and Liposceis bostrychophila. The chemical profile of the EO were analyzed by gas chromatography-mass spectrometry (GC-MS), and 20 compounds were identified which accounted for 88.03% of the total EO. Five major compounds identified in the EO were assayed against the three stored product insects. The EO showed strong contact toxicity to T. castaneum (LD50 = 18.01 µg/adult), L. serricorne (LD50 = 20.11 µg/adult) and L. bostrychophila (LD50 = 72.14 µg/cm2). Among all compounds, geraniol showed the contact toxicity against L. serricorne and L. bostrychophila with LD50 values of 15.82 µg/adult and 26.64 µg/cm2. The EO and its five chemical compounds also exhibited different level of potential repellence to the three stored product insects.
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Repelentes de Insetos , Inseticidas , Óleos Voláteis , Senécio , Tribolium , Animais , Repelentes de Insetos/química , Repelentes de Insetos/farmacologia , Insetos , Inseticidas/química , Óleos Voláteis/químicaRESUMO
Berberine, as a natural alkaloid compound, is characterized by a diversity of pharmacological effects. In recent years, many researches focused on the role of berberine in central nervous system diseases. Among them, the effect of berberine on neurodegenerative diseases has received widespread attention, for example Alzheimer's disease, Parkinson's disease, Huntington's disease, and so on. Recent evidence suggests that berberine inhibits the production of neuroinflammation, oxidative, and endoplasmic reticulum stress. These effects can further reduce neuron damage and apoptosis. Although the current research has made some progress, its specific mechanism still needs to be further explored. This review provides an overview of berberine in neurodegenerative diseases and its related mechanisms, and also provides new ideas for future research on berberine.
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KLF4 is a zinc-finger transcription factor that plays an essential role in many biological processes, including neuroinflammation, neuron regeneration, cell proliferation, and apoptosis. Through effects on these processes, KLF4 has likely roles in Alzheimer's disease, Parkinson's disease, and traumatic brain injury. However, little is known about the role of KLF4 in more immediate behavioral processes that similarly depend upon broad changes in brain excitability, such as the sleep process. Here, behavioral approaches, western blot, and immunohistochemical experiments were used to explore the role of KLF4 on sedation and the potential mechanisms of those effects. The results showed that overexpression of KLF4 prolonged loss of righting reflex (LORR) duration in pentobarbital-treated mice and increased c-Fos expression in the lateral hypothalamus (LH) and the ventrolateral preoptic nucleus (VLPO), while it decreased c-Fos expression in the tuberomammillary nucleus (TMN). Moreover, overexpression of KLF4 reduced the expression of p53 in the hypothalamus and increased the expression of STAT3 in the hypothalamus. Therefore, these results suggest that KLF4 exerts sedative effects through the regulation of p53 and STAT3 expression, and it indicates a role of KLF4 ligands in the treatment of sleep disorders.
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Hipnóticos e Sedativos/farmacologia , Hipotálamo/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Pentobarbital/farmacologia , Animais , Hipotálamo/efeitos dos fármacos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Reflexo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Depression is one of the most common disorders causing mortality around the world. Although electroconvulsive therapy (ECT) is, along with antidepressants and psychotherapy, one of the three major treatments of depression, it is still considered as the last resort for depressed patients. This situation is partially due to limited studies and uncertainty regarding its mechanism. However, decades of increased research have focused on the effects of ECT on depression and its potential mechanism. Furthermore, these investigations may suggest that ECT should be a first-line therapy for depression due to its profound effects in relieving desperation in certain situations. Here, we outline recent clinical and preclinical studies and summarize the advantages and disadvantages of ECT. Thus, this review may provide some hints for clinical application.
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Krüppel-like factor 4 (KLF4), a member of the family of zinc-finger transcription factors, is widely expressed in range of tissues that play multiple functions. Emerging evidence suggest KLF4's critical regulatory effect on the neurophysiological and neuropathological processes of Alzheimer's disease (AD), indicating that KLF4 might be a potential therapeutic target of neurodegenerative diseases. In this review, we will summarize relevant studies and illuminate the regulatory role of KLF4 in the neuroinflammation, neuronal apoptosis, axon regeneration and iron accumulation to clarify KLF4's status in the pathogenesis of AD.
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Herbal medicines, as an important part of traditional Chinese medicine (TCM), have been used to treat digestive system malignancies (DSM) for many years, and have gradually gained recognition worldwide. The role of herbal medicines in the comprehensive treatment of DSM is being improved from adjuvant treatment of the autologous immune function in cancer patients, to the treatment of both the symptoms and disease, direct inhibition of tumor cell growth and proliferation, and induction of tumor cell autophagy and apoptosis. Their specific mechanisms in these treatments are also being explored. The paper reviews the current anti-tumor mechanisms of TCM, including single herbal medicines, Chinese herbal formulations, Chinese medicine preparations and TCM extract, and their application in the comprehensive treatment of digestive system tumors, providing a reference for clinical application of TCM.