In the present study, pleckstrin homology domain‑containing family A member 4 (PLEKHA4) was identified as being upregulated in renal cell carcinoma, particularly within the kidney renal clear cell carcinoma (KIRC) subtype. The present study conducted bioinformatics analysis, Cell Counting Kit‑8 and cell migration assays, flow cytometry, western blotting and experiments with the aim of uncovering the role of PLEKHA4 in β‑catenin signaling in KIRC cells. Notably, PLEKHA4 upregulation was revealed to be associated with enhanced cell proliferation, indicating its potential role as an oncogene in KIRC.
View Article and Find Full Text PDFThe amygdaloid complex consists of multiple nuclei and is a key node in controlling temporal lobe epilepsy (TLE) in both human and animal model studies. However, the specific nucleus in the amygdaloid complex and the neural circuitry governing seizures remain unknown. Here, it is discovered that activation of glutamatergic neurons in the posterior basolateral amygdala (pBLA) induces severe seizures and even mortality.
View Article and Find Full Text PDFEthnopharmacological Relevance: Alcoholic depression, a disorder of the central nervous system, is characterized by alcohol abuse, which causes blood-brain barrier disruption and oxidative damage in the brain. The rhizome of Rhodiola crenulate, from which Dazhu Hongjingtian Injection (DZHJTI) is derived, has been traditionally employed in ethnopharmacology to treat neurological disorders due to its neuroprotective, anti-inflammatory, and antioxidant properties. However, the exact mechanism by which DZHJTI alleviates alcoholic depression remains unclear.
View Article and Find Full Text PDFSalidroside (SAL), a phenylpropanoid bioactive compound, has various pharmacological properties, including antioxidant, anti-inflammatory, and hepatoprotective effects. However, the pharmacological effects and mechanisms of action of SAL on cholestatic liver injury are unclear. This study investigated the mechanism and effects of salidroside (SAL) on intestinal flora distribution and hepatic stellate cell (HSC) activation in cholestatic hepatic fibrosis.
View Article and Find Full Text PDFComplement activation and prefrontal cortical dysfunction both contribute to the pathogenesis of major depressive disorder (MDD), but their interplay in MDD is unclear. We here studied the role of complement C3a receptor (C3aR) in the medial prefrontal cortex (mPFC) and its influence on depressive-like behaviors induced by systematic lipopolysaccharides (LPS) administration. C3aR knockout (KO) or intra-mPFC C3aR antagonism confers resilience, whereas C3aR expression in mPFC neurons makes KO mice susceptible to LPS-induced depressive-like behaviors.
View Article and Find Full Text PDFThe NaOAc-assisted aerobic oxidation reaction of pentacoordinate hydrospirophosphoranes and dichalcogenyl compounds with open air as a green oxidant has been developed under mild conditions. A series of novel pentacoordinate spirophosphoranes with P-Se/P-S bonds were synthesized in excellent yields. The reaction mechanism was determined by P nuclear magnetic resonance tracing experiments, high-resolution mass spectrometry tracing experiments, and X-ray diffraction analysis.
View Article and Find Full Text PDFFear-related disorders (for example, phobias and anxiety) cause a substantial public health problem. To date, studies of the neural basis of fear have mostly focused on the amygdala. Here we identify a molecularly defined amygdala-independent tetra-synaptic pathway for olfaction-evoked innate fear and anxiety in male mice.
View Article and Find Full Text PDFBackground: The ability to differentiate stimuli that predict fear is critical for survival; however, the underlying molecular and circuit mechanisms remain poorly understood.
Methods: We combined transgenic mice, in vivo transsynaptic circuit-dissecting anatomical approaches, optogenetics, pharmacological methods, and electrophysiological recording to investigate the involvement of specific extended amygdala circuits in different fear memory.
Results: We identified the projections from central lateral amygdala (CeL) protein kinase C δ (PKCδ)-positive neurons and somatostatin (SST)-positive neurons to GABAergic (gamma-aminobutyric acidergic) and glutamatergic neurons in the ventral part of the bed nucleus of stria terminalis (vBNST).
Glutamine (Gln) is an immunomodulatory protein that mediates oxidative stress, inflammation, and apoptosis, but has not been reported in the treatment of hyperoxia (Hyp)-induced brain injury. The aim of this study was to determine whether Gln could improve hyp-induced brain injury in neonatal rats to and later learning and memory dysfunction, and to explore its possible mechanisms. We prepared a model of neonatal rat brain injury caused by normobaric hyperoxia while administered with Gln for 7 days for evaluation.
View Article and Find Full Text PDFBackgrounds: Botulinum toxin type A (BoNT/A) is extensively applied in spasticity and dystonia as it cleaves synaptosome-associated protein 25 (SNAP25) in the presynaptic terminals, thereby inhibiting neurotransmission. An increasing number of randomized clinical trials have suggested that glabellar BoNT/A injection improves depressive symptoms in patients with major depressive disorder (MDD). However, the underlying neuronal circuitry of BoNT/A-regulated depression remains largely uncharacterized.
View Article and Find Full Text PDFPentacoordinated bisaminoacyl hydrospirophosphoranes were first found to induce the asymmetric addition reactions as a novel chiral organic framework. Asymmetric addition reactions of bisaminoacyl hydrospirophosphoranes with aromatic aldehyde and in situ generated imine were investigated, and the corresponding α-hydroxyspirophosphonates and α-amino spirophosphonates were obtained. The addition reaction of hydrospirophosphoranes with Δ configuration showed better stereoselectivity than that with Λ configuration, not only for the addition reaction to aromatic aldehyde but also to in situ generated imine.
View Article and Find Full Text PDFNeutrophil extracellular traps (NETs) are special web-like structures that can be generated in both infectious and noninfectious diseases. Previous studies showed that reactive oxygen species (ROS) were crucial in the formation of NETs (NETosis). The purpose of this study is to evaluate the effect of (+)-borneol, an antioxidant, on NETosis.
View Article and Find Full Text PDFAtrial natriuretic peptide (ANP) plays a pivotal role in the regulation of the cardiovascular system. The ANP level increases during atrial fibrillation (AF), suggesting that AF may provoke ANP secretion, but its potential mechanism is still unclear. In the present study, the potential mechanisms of rapid atrial pacing (RAP) regulating ANP secretion was explored.
View Article and Find Full Text PDFChronic stress is a major risk factor for depression onset. However, it remains unclear how repeated stress sculpts neural circuits and finally elicits depression. Given the essential role of lateral habenula (LHb) in depression, here, we attempt to clarify how LHb-centric neural circuitry integrates stress-related information.
View Article and Find Full Text PDFBackground: Malignant melanoma (MM) is highly metastatic and has the highest mortality rate in patients with skin cancer. The ERBB3 binding protein 1 (Ebp1) has been linked to the onset and progression of a number of malignancies. However, the role of Ebp1 in MM has not yet been reported.
View Article and Find Full Text PDFThe prediction of schizophrenia-related psychopathologic deficits is exceedingly important in the fields of psychiatry and clinical practice. However, objective association of the brain structure alterations to the illness clinical symptoms is challenging. Although, schizophrenia has been characterized as a brain dysconnectivity syndrome, evidence accounting for neuroanatomical network alterations remain scarce.
View Article and Find Full Text PDFImidazo[1,2-a] pyridine is one of the pharmaceutically important scaffolds and has been widely studied due to its extensive biological activities. In this work, electrospray ionization tandem mass spectrometry (ESI-MS/MS) in positive mode was used to study the gas-phase fragmentation behavior of a series of 3-phenoxy imidazo[1,2-a] pyridines. Proposed fragmentation pathways were supported by ESI-MS/MS data and computational thermochemistry.
View Article and Find Full Text PDFThe stereochemical mechanism of the nucleophilic substitution reaction at pentacoordinate phosphorus (P-V) atom is rarely studied. Here, we report the Atherton-Todd-type reaction of pentacoordinate hydrospirophosphorane with phenolic compounds in detail. The stereochemical mechanism of nucleophilic substitution at P-V atom was proposed by P NMR tracing experiment, X-ray diffraction analysis, and density functional theory calculations.
View Article and Find Full Text PDFPain is a source of substantial discomfort. Abnormal activity in both the zona incerta (ZI) and posterior complex of the thalamus (Po) are implicated in neuropathic pain, but their exact roles remain unclear. In particular, the precise cell types and molecular mechanisms of the ZI-Po circuit that regulate nociception are largely uncharacterized.
View Article and Find Full Text PDFMethyl-CpG-binding protein 2 (MeCP2) encoded by the gene is a transcriptional regulator whose mutations cause Rett syndrome (RTT). -deficient mice show fear regulation impairment; however, the cellular and molecular mechanisms underlying this abnormal behavior are largely uncharacterized. Here, we showed that gene deficiency in cholinergic interneurons of the nucleus accumbens (NAc) dramatically impaired fear learning.
View Article and Find Full Text PDFDysfunction of the noradrenergic (NE) neurons is implicated in the pathogenesis of bipolar disorder (BPD). ErbB4 is highly expressed in NE neurons, and its genetic variation has been linked to BPD; however, how ErbB4 regulates NE neuronal function and contributes to BPD pathogenesis is unclear. Here we find that conditional deletion of ErbB4 in locus coeruleus (LC) NE neurons increases neuronal spontaneous firing through NMDA receptor hyperfunction, and elevates catecholamines in the cerebrospinal fluid (CSF).
View Article and Find Full Text PDFThe central cholinergic nervous system plays an important role in cognition, with acetylcholine hypofunction considered to be a major factor of dementia. Botulinum toxin type A (BoNT/A), a potent poison secreted by Clostridium botulinum, is used widely for dystonia treatment and facial cosmesis. BoNT/A injection inhibits acetylcholine release in the neuromuscular junction through cleavage of synaptosomal-associated protein of 25 kDa in cholinergic terminals.
View Article and Find Full Text PDF