- Stress Responses and Cortisol
- Neuroinflammation and Neurodegeneration Mechanisms
- Circadian rhythm and melatonin
- Traditional Chinese Medicine Analysis
- Neuroendocrine regulation and behavior
- Neurological Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Telomeres, Telomerase, and Senescence
- Neurogenesis and neuroplasticity mechanisms
- Tryptophan and brain disorders
- Neurotransmitter Receptor Influence on Behavior
- Birth, Development, and Health
- Genetics, Aging, and Longevity in Model Organisms
- Epilepsy research and treatment
- Advanced Drug Delivery Systems
- RNA Interference and Gene Delivery
- Autophagy in Disease and Therapy
- Hormonal Regulation and Hypertension
- Anesthesia and Neurotoxicity Research
- RNA modifications and cancer
- Pharmacological Effects and Assays
- Metabolomics and Mass Spectrometry Studies
- Phytochemistry and biological activity of medicinal plants
- Metalloenzymes and iron-sulfur proteins
- Glioma Diagnosis and Treatment
Nanjing Medical University
2014-2024
Jiangsu Province Hospital
2024
Cleveland Clinic Lerner College of Medicine
2014-2018
Nanjing Drum Tower Hospital
2016
The molecular mechanisms underlying the behavioral effects of glucocorticoids are poorly understood. We report here that hippocampal neuronal nitric oxide synthase (nNOS) is a crucial mediator. Chronic mild stress and exposures caused nNOS overexpression via activating mineralocorticoid receptor. In turn, nNOS-derived (NO) significantly downregulated local glucocorticoid receptor expression through both soluble guanylate cyclase (sGC)/cGMP peroxynitrite (ONOO − )/extracellular...
Major depressive disorder (MDD) is one of the most common mental disorders. We designed a fast-onset antidepressant that works by disrupting interaction between serotonin transporter (SERT) and neuronal nitric oxide synthase (nNOS) in dorsal raphe nucleus (DRN). Chronic unpredictable mild stress (CMS) selectively increased SERT-nNOS complex DRN mice. Augmentation interactions caused depression-like phenotype accounted for CMS-induced behaviors. Disrupting produced effect enhancing signaling...
Abstract Cognitive deficits, including spatial memory impairment, are very common after ischemic stroke. Neurogenesis in the dentate gyrus (DG) contributes to forming brain. Fluoxetine, a selective serotonin reuptake inhibitor, can enhance neurogenesis hippocampus physiological situations and some neurological diseases. However, whether it has effects on ischemia‐induced cognitive impairment hippocampal not been determined. Here we report that fluoxetine treatment (10 mg kg −1 , i.p.) for 4...
Telomere and telomerase alterations have been reported in mood disorders. However, the role of depression remains unclear. Here we show that chronic mild stress (CMS) led to a significant decrease reverse transcriptase (TERT) level activity hippocampus. Treatment with antidepressant fluoxetine reversed CMS-induced TERT changes. Inhibiting by systemic administration (100 mg · kg −1 d , i.p., for 14 d), intrahippocampal microinjection (0.7 μmol, 2 μl), or infusion (using an osmotic minipump,...
Abstract Whether microRNAs (miRNAs) from plasma exosomes might be dysregulated in patients with depression, especially treatment-resistant depression (TRD), remains unclear, based on study of which novel biomarkers and therapeutic targets could discovered. To this end, a small sample was performed by isolation TRD diagnosed Hamilton scale. In study, 4 peripheral samples healthy controls were collected for extraction exosomes. Exosomal miRNAs analyzed miRNA sequencing, followed image...
Temozolomide (TMZ) is a standard treatment for glioblastoma (GBM) patients. However, TMZ has moderate therapeutic effects due to chemoresistance of GBM cells through less clarified mechanisms. Here, we demonstrate that TMZ-derived 5-aminoimidazole-4-carboxamide (AICA) converted AICA ribosyl-5-phosphate (AICAR) in cells. This conversion catalyzed by hypoxanthine phosphoribosyl transferase 1 (HPRT1), which highly expressed human GBMs. As the bona fide activator AMP-activated protein kinase...
Background Stroke is a leading cause of long‐term disability worldwide. However, current therapies that promote functional recovery from stroke are limited to physical rehabilitation. No pharmacological therapy available. Thus, understanding the role histone deacetylase 2 (HDAC2) in pathophysiological process stroke‐induced loss may provide novel strategy for recovery. Methods and Results Focal was induced by photothrombosis. LV‐HDAC2‐shRNA‐GFP, LV‐GFP, Ad‐HDAC2‐Flag, or...
Glioblastoma, the most lethal primary brain tumor, harbors glioma stem cells (GSCs) that not only initiate and maintain malignant phenotypes but also enhance therapeutic resistance. Although frequently mutated in glioblastomas, function regulation of PTEN PTEN-intact GSCs are unknown. Here, we found directly interacted with MMS19 competitively disrupted MMS19-based cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) machinery differentiated cells. was specifically succinated at cysteine (C)...
Summary In neurons, increased protein–protein interactions between neuronal nitric oxide synthase ( nNOS ) and its carboxy‐terminal PDZ ligand CAPON contribute to excitotoxicity abnormal dendritic spine development, both of which are involved in the development Alzheimer's disease. models disease, – interaction was detected after treatment with amyloid‐β vitro, a similar change found hippocampus APP / PS 1 mice (a transgenic mouse model disease), compared age‐matched background vivo . After...
Abstract Anxiety disorders are associated with a high social burden worldwide. Recently, increasing evidence suggests that nuclear factor kappa B (NF‐κB) has significant implications for psychiatric diseases, including anxiety and depressive disorders. However, the molecular mechanisms underlying role of NF‐κB in stress‐induced behaviors poorly understood. In this study, we show chronic mild stress (CMS) glucocorticoids dramatically increased expression subunits p50 p65, phosphorylation...
Sucrose preference test (SPT) is a most frequently applied method for measuring anhedonia, core symptom of depression, in rodents. However, the SPT still remains problematic mainly due to primitive, irregular, and inaccurate various types home-made equipment laboratories, causing imprecise, inconsistent, variable results. To overcome this issue, we devised novel automatic detection anhedonia mice using an electronic apparatus with its program automated detecting behavior drinking instead...
Glucocorticoids (GCs) are steroidal hormones produced by the adrenal cortex. A physiological-level GCs have a crucial function in maintaining many cognitive processes, like cognition, memory, and mood, however, both insufficient excessive impair these functions. Although this phenomenon could be explained U-shape of GC effects, underlying mechanisms still not clear. Therefore, understanding may provide insight into treatments for mood-related disorders.
Sinisan has been widely used to treat depression. However, its pharmacologically-effective constituents are largely unknown, and the pharmacological effects clinical efficacies of Sinisan-containing processed medicinal herbs may change. To address these important issues, we developed an ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) method multiple statistical strategies analyze compound...
Abstract In response to stressful events, the hypothalamic-pituitary-adrenal (HPA) axis is activated, and consequently glucocorticoids are released by adrenal gland into blood circulation. A large body of research has illustrated that excessive in hippocampus exerts negative feedback regulation HPA through glucocorticoid receptor (GR), which critical for homeostasis axis. Maternal prenatal stress causes dysfunction mechanism their offspring adulthood. Here we report telomerase reverse...
Common chemotherapeutic agents such as oxaliplatin often cause neuropathic pain during cancer treatment in patients. Such is difficult to treat and responds poorly common analgesics, which represents a clinical challenge. (+)-Borneol, bicyclic monoterpene present the essential oil of plants, used for analgesia anesthesia traditional Chinese medicine. Although borneol has an antinociceptive effect on acute models, little known about its chemotherapy-induced mechanism. We found that...
As for traditional Chinese medicine (TCM) prescription, what puzzled researchers most was how to select proper chemical markers represent the whole pharmacological action system. In this paper, an integrated metabolomic method presented a systematic discovery of potential active components in Fangji Huangqi Tang (FHT), well-known TCM prescription nephrotic syndrome treatment, based on "correlations between and metabolic profiles." Firstly, metabolomics study carried out representative...
Proparacaine (PPC) is a previously discovered topical anesthetic for ophthalmic optometry and surgery by blocking the central Nav1.3. In this study, we found that proparacaine hydrochloride (PPC-HCl) exerted an acute robust antiepileptic effect in pilocarpine-induced epilepsy mice. More importantly, chronic treatment with PPC-HCl totally terminated spontaneous recurrent seizure occurrence without significant toxicity. Chronic did not cause obvious cytotoxicity, neuropsychiatric adverse...
ABSTRACT Major depressive disorder is a severe, life‐threatening and highly prevalent psychiatric disorder. A high percentage of people suffering from depression are characterized by hyperactivity the hypothalamic–pituitary–adrenal axis, resulting in plasma glucocorticoid (cortisol human corticosterone rodent) elevations. Glucocorticoid critical molecule onset pathology depression. simple, sensitive specific method based on ultra‐fast liquid chromatography–tandem mass spectrometry has been...