Publications by authors named "Xulin Xu"

Aims: Dedicator of Cytokinesis 2 (DOCK2), a member of the DOCK family of Guanine nucleotide exchange factors that specifically act on the Rho GTPases including Rac and Cdc42, plays pivotal roles in the regulation of leukocyte homeostasis. However, its functions in platelets remain unknown.

Methods And Results: Using mice with genetic deficiency of DOCK2 (Dock2-/-), we showed that Dock2-/-mice exhibited a macrothrombocytopenic phenotype characterized as decreased platelet count and enlarged platelet size by transmission electron microscopy.

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Aquaculture water with antibiotic resistance genes (ARGs) is escalating due to the horizontal gene transfer. Non-antibiotic stressors specifically found, including those from fishery feed and disinfectants, are potential co-selectors. However, the mechanisms underlying this process remains unclear.

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The essence of difference between hemostasis and thrombosis is that the clotting reaction is a highly fine-tuned process. Vascular protein disulfide isomerase (PDI) represents a critical mechanism regulating the functions of hemostatic proteins. Herein we show that histidine-rich glycoprotein (HRG) is a substrate of PDI.

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Background: Integrins mediate the adhesion, crawling, and migration of neutrophils during vascular inflammation. Thiol exchange is important in the regulation of integrin functions. ERp72 (endoplasmic reticulum-resident protein 72) is a member of the thiol isomerase family responsible for the catalysis of disulfide rearrangement.

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Extracellular protein disulfide isomerase (PDI) is a promising target for thrombotic-related diseases. Four potent PDI inhibitors with unprecedented chemical architectures, piericones A-D (), were isolated from . Their structures were elucidated by spectroscopic data analysis, chemical methods, quantum C nuclear magnetic resonance DP4+ and electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis.

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Background And Purpose: Thrombosis is a major cause of morbidity and mortality worldwide. Platelet activation by exposed collagen through glycoprotein VI (GPVI) and formation of neutrophil extracellular traps (NETs) are critical pathogenic factors for arterial and venous thrombosis. Both events are regulated by spleen tyrosine kinase (Syk)-mediated signalling events.

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Protein disulfide isomerase (PDI) is the prototypic member of the thiol isomerase family that catalyses disulfide bond rearrangement. Initially identified in the endoplasmic reticulum as folding catalysts, PDI and other members in its family have also been widely reported to reside on the cell surface and in the extracellular matrix. Although how PDI is exported and retained on the cell surface remains a subject of debate, this unique pool of PDI is developing into an important mechanism underlying the redox regulation of protein sulfhydryls that are critical for the cellular activities under various disease conditions.

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Classical antithrombotics and antiplatelets are associated with high frequencies of bleeding complications or treatment failure when used as single agents. The platelet-independent fibrin generation by activated endothelium highlights the importance of vascular protection in addition to platelet inhibition in thrombosis prevention. Dihydromyricetin (DHM), the most abundant flavonoid in Ampelopsis grossedentata, has unique vasoprotective effects.

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Background: It has been shown that chronic stress-induced depression is associated with exaggerated inflammatory response in the brain. Alpha7 nicotinic acetylcholine receptors (α7nAChRs) regulate the cholinergic anti-inflammatory pathway, but the role of cholinergic signaling and α7nAChR in chronic stress has not yet been examined.

Methods: In this study, we used a well-documented model of depression in which mice were exposed to 6 h of restraint stress for 21 consecutive days.

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Anxiety is an affective disorder that is commonly observed after irreversible brain damage induced by cerebral ischemia and can delay the physical and cognitive recovery, which affects the quality of life of both the patient and family members. However, anxiety after ischemia has received less attention, and mechanisms underlying anxiety-like behaviours induced by chronic cerebral ischemia are under-investigated. In the present study, the chronic cerebral hypoperfusion model was established by the permanent occlusion of the bilateral common carotid arteries (two-vessel occlusion, 2VO) in rats, and anxiety-related behaviours were evaluated.

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The selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride (ZD7288) blocks the induction of long-term potentiation in the perforant path-CA3 region in rat hippocampus in vivo. To explore the mechanisms underlying the action of ZD7288, we recorded excitatory postsynaptic potentials in perforant path-CA3 synapses in male Sprague-Dawley rats. We measured glutamate content in the hippocampus and in cultured hippocampal neurons using high performance liquid chromatography, and determined intracellular Ca(2+) concentration [Ca(2+)]i) using Fura-2.

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Chronic cerebral hypoperfusion (CCH) causes memory deficits and increases the risk of vascular dementia (VD) through several biologically plausible pathways. However, whether CCH causes prefrontal cortex (PFC)-dependent spatial working memory impairments and Baclofen, a GABAB receptor agonist, could ameliorate the impairments is still not clear especially the mechanisms underlying the process. In this study, rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) to induce CCH.

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Chronic cerebral hypoperfusion (CCH) causes cognitive impairments and increases the risk of Alzheimer's disease (AD) and vascular dementia (VD) through several biologically plausible pathways, yet the underlying neurobiological mechanisms are still poorly understood. In this study, we investigated whether fluoxetine, a selective serotonin reuptake inhibitor (SSRI), could play a neuroprotective role against chronic cerebral hypoperfusion injury and to clarify underlying mechanisms of its efficacy. Rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO).

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Aims: Brain ischemia activates astrocytes in a process known as astrogliosis. Although this process has beneficial effects, excessive astrogliosis can impair neuronal recovery. Polyinosinic-polycytidylic acid (Poly IC) has shown neuroprotection against cerebral ischemia-reperfusion injury, but whether it regulates reactive astrogliosis and glial scar formation is not clear.

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Chronic cerebral hypoperfusion (CCH) causes learning and memory impairments and increases the risk of Alzheimer disease (AD) and vascular dementia (VD) through several biologically plausible pathways, yet the mechanisms underlying the disease process remained unclear particularly in a temporal manner. We performed permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) to induce CCH. To determine whether hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are altered at different stages of cognitive impairment caused by CCH, adult male SD rats were randomly distributed into sham-operated 4, 8 and 12weeks group, 2VO 4, 8 and 12weeks group.

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Chronic restraint stress (CRS) causes hippocampal neurodegeneration and hippocampus-dependent cognitive deficits. Flupirtine represents neuroprotective effects and we have previously shown that flupirtine can protect against memory impairment induced by acute stress. The present study aimed to investigate whether flupirtine could alleviate spatial learning and memory impairment and hippocampal apoptosis induced by CRS.

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M-type (Kv7) K(+) channels, encoded by KCNQ2-KCNQ5 genes, play a pivotal role in controlling neuronal excitability. However, precisely how neuronal activity regulates Kv7 channel translocation has not yet been fully defined. Here we reported activity-dependent changes in Kv7 channel subunits Kv7.

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Chronic cerebral hypoperfusion may cause cognitive impairment, but the underlying neurobiological mechanism is poorly understood. In this study, we investigated whether clonidine, an α-adrenergic receptor agonist, could play neuroprotective role against chronic ischemic brain injury and the potential mechanism. Rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO).

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The hyperpolarization-activated cyclic-nucleotide-gated non-selective cation (HCN) channels play a vital role in the neurological basis underlying nervous system diseases. However, the role of HCN channels in drug addiction is not fully understood. In the present study, we investigated the expression of HCN1 and HCN2 subunits in hippocampal CA1 and the potential molecular mechanisms underlying the modulation of HCN channels in rats with chronic morphine exposure with approaches of electrophysiology, water maze, and Western blotting.

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Background: Cerebral ischemic preconditioning (IPC) protects brain against ischemic injury. Activation of Toll-like receptor 3 (TLR3) signaling can induce neuroprotective mediators, but whether astrocytic TLR3 signaling is involved in IPC-induced ischemic tolerance is not known.

Methods: IPC was modeled in mice with three brief episodes of bilateral carotid occlusion.

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Hyperpolarization-activated cyclic-nucleotide-gated cation nonselective (HCN) channels are involved in the pathology of nervous system diseases. HCN channels and γ-aminobutyric acid (GABA) receptors can mutually co-regulate the function of neurons in many brain areas. However, little is known about the co-regulation of HCN channels and GABA receptors in the chronic ischemic rats with possible features of vascular dementia.

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Focal cerebral ischemia can impair the induction of activity-dependent long-term potentiation (LTP) in the hippocampus. This impairment of hippocampal synaptic plasticity can be caused by excitotoxicity and subsequent perturbation of hippocampal LTP-relevant transmitter systems, which include NR2B and PSD-95. It has been suggested that hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels may play an important role in the control of membrane excitability and rhythmic neuronal activity.

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Activation of alpha2-adrenoceptors inhibits long-term potentiation and long-term depression in many brain regions. However, effectiveness and mechanism of alpha2-adrenoceptors for synaptic plasticity at the Schaffer collateral-CA1 synapses in rat in vivo is unclear. In the present study, we investigated the effects of alpha2-adrenoceptors agonist clonidine on high-frequency stimulation (HFS)-induced long-term potentiation (LTP) and paired-pulse facilitation (PPF) at the Schaffer collateral-CA1 synapse of rat hippocampus in vivo.

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Article Synopsis
  • The study investigates how the TLR3 agonist Poly I:C provides neuroprotection in acute ischemic conditions using both in vitro (astrocyte cultures) and in vivo (mouse models) approaches.
  • Poly I:C treatment before simulated ischemia significantly improves cell viability, decreases cell damage, and reduces inflammation indicators like TNFα and IL-6.
  • The findings suggest that the neuroprotective effects of Poly I:C are linked to the activation of the TLR3-TRIF signaling pathway, highlighting its potential as a therapeutic strategy for ischemic brain injuries.
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