A switch in the pathway of TRPC3-mediated calcium influx into brain pericytes contributes to capillary spasms after subarachnoid hemorrhage.

Calcium influx and subsequent elevation of the intracellular calcium concentration ([Ca]) induce contractions of brain pericytes and capillary spasms following subarachnoid hemorrhage. This calcium influx is exerted through cation channels. However, the specific calcium influx pathways in brain pericytes after subarachnoid hemorrhage remain unknown.

Contactin-6-deficient male mice exhibit the abnormal function of the accessory olfactory system and impaired reproductive behavior.

Introduction: Contactin-6 (CNTN6), also known as NB-3, is a neural recognition molecule and a member of the contactin subgroup of the immunoglobulin superfamily. Gene encoding CNTN6 is expressed in many regions of the neural system, including the accessory olfactory bulb (AOB) in mice. We aim to determine the effect of CNTN6 deficiency on the function of the accessory olfactory system (AOS).

p38 MAPK Endogenous Inhibition Improves Neurological Deficits in Global Cerebral Ischemia/Reperfusion Mice.

Cerebral ischemia/reperfusion (I/R) injury is a complex pathophysiological process that can lead to neurological function damage and the formation of cerebral infarction. The p38 MAPK pathway has attracted considerable attention in cerebral I/R injury (IRI), but little research has been carried out on its direct role in vivo. In this study, to observe the effects of p38 MAPK endogenous inhibition on cerebral IRI, p38 heterozygous knockdown (p38) mice were used.

Negative regulation by proBDNF signaling of peripheral neurogenesis in the sensory ganglia of adult rats.

Neurogenesis in the adult brain is well recognized and plays a critical role in the maintenance of brain function and homeostasis. However, whether neurogenesis also occurs in the adult peripheral nervous system remains unknown. Here, using sensory ganglia (dorsal root ganglia, DRGs) as a model, we show that neurogenesis also occurs in the peripheral nervous system, but in a manner different from that in the central nervous system.

A Genetically Encoded F-19 NMR Probe Reveals the Allosteric Modulation Mechanism of Cannabinoid Receptor 1.

Due to the lack of genetically encoded probes for fluorine-19 nuclear magnetic resonance spectroscopy (F NMR), its utility for probing eukaryotic membrane protein dynamics is limited. Here we report an efficient method for the genetic incorporation of an unnatural amino acid (UAA), 3'-trifluoromenthyl-phenylalanine (mtfF), into cannabinoid receptor 1 (CB1) in the Baculovirus Expression System. The probe can be inserted at any environmentally sensitive site, while causing minimal structural perturbation to the target protein.

Cryo-EM analysis of the HCoV-229E spike glycoprotein reveals dynamic prefusion conformational changes.

Coronaviruses spike (S) glycoproteins mediate viral entry into host cells by binding to host receptors. However, how the S1 subunit undergoes conformational changes for receptor recognition has not been elucidated in Alphacoronavirus. Here, we report the cryo-EM structures of the HCoV-229E S trimer in prefusion state with two conformations.

Umbilical Cord Mesenchymal Stem Cells for Inflammatory Regulation After Excision and Grafting of Severe Burn Wounds in Rats.

Severe burns predispose to shock and necessitate escharectomy and skin grafting. Previous studies show that mesenchymal stem cells are effective for burn wound healing and immune regulation. In this study, we combined escharectomy and skin grafting after burn injury with stem cell application, so as to examine the immune regulation of stem cells and the effect on the transplanted skin graft.

Resina Draconis Reduces Acute Liver Injury and Promotes Liver Regeneration after 2/3 Partial Hepatectomy in Mice.

Aim: To investigate the protective effects and possible mechanisms of action of resina draconis (RD) on acute liver injury and liver regeneration after 2/3 partial hepatectomy (PH) in mice.

Methods: 2/3 PH was used to induce acute liver injury. Mice were divided into three groups: sham, vehicle + 2/3 PH, and RD + 2/3 PH.

Wip1 phosphatase deficiency impairs spatial learning and memory.

Spatial learning and memory are typically assessed to evaluate hippocampus-dependent cognitive and memory functions in vivo. Protein phosphorylation and dephosphorylation by kinases and phosphatases play critical roles in spatial learning and memory. Here we report that the Wip1 phosphatase is essential for spatial learning, with knockout mice lacking Wip1 phosphatase exhibiting dysfunctional spatial cognition.

Total Saponins from Paris forrestii Reverse Multidrug Resistance of MCF-7/ADM Cells by Suppression of P-gp via ERK Signaling Pathway.

Our previous study demonstrated that the total saponins from Paris forristii (PCT3) had obvious inhibitory effect on the proliferation of adriamycin-resistant human breast adenocarcinoma cells (MCF-7/ADM), and this effect was significantly stronger than that in parental cells (MCF-7). This study was designed to test the reversal effect of PCT3 on MCF-7/ADM cells and to understand its mechanism of action. Results demonstrated that low cytotoxic concentrations of PCT3 (0.

Distinct Residential and Infiltrated Macrophage Populations and Their Phagocytic Function in Mild and Severe Neonatal Hypoxic-Ischemic Brain Damage.

Neonatal brain injury, especially severe injury induced by hypoxia-ischemia (HI), causes mortality and long-term neurological impairments. Our previous study demonstrated activation of CD11b myeloid cells, including residential microglial cells (MGs) and infiltrating monocyte-derived macrophages (MDMs) in a murine model of hypoxic-ischemic brain damage (HIBD), with unknown functions. Here, we study the differences in the phagocytic function of MGs and MDMs to clarify their potential roles after HIBD.

Prognostic Significance of the Modified Glasgow Prognostic Score in Patients With Pancreatic Cancer: A Meta-Analysis.

Background: The prognostic value of the modified Glasgow prognostic score (mGPS) in patients with pancreatic cancer is controversial, based on previous studies. Therefore, this meta-analysis aimed to explore the relationship between mGPS and prognosis in pancreatic cancer.

Methods: The databases PubMed, Web of Science, Embase, and the Cochrane Library were searched to identify eligible studies.

Endocrine Dysfunction Following Stroke.

Endocrine dysfunction is known to occur after traumatic brain injury. The purpose of this study was to examine the incidence of various endocrine dysfunctions after a stroke. The Taiwan National Health Insurance Research Database (NHIRD) was searched from 2001 to 2011 for patients with a diagnosis of stroke.

Exploring cisplatin resistance in ovarian cancer through integrated bioinformatics approach and overcoming chemoresistance with sanguinarine.

Ovarian cancer is refractory in response towards platinum-based chemotherapy, and resistance frequently develops. We attempted to identify the driving pathways in cisplatin-resistant ovarian cancer and develop targeted therapies to overcome this resistance. Using an integrated bioinformatics approach, a GSE15372 database from NCBI's Gene Expression Omnibus database was obtained for identifying differentially expressed genes (DEGs), in which 535 DEGs were found (407 up-regulated and 128 down-regulated) in association with ovarian cancer cisplatin-resistance.

Breviscapine exerts neuroprotective effects through multiple mechanisms in APP/PS1 transgenic mice.

Alzheimer's disease (AD) is one of the most serious neurodegenerative diseases and is characterized by progressive cognitive impairment and multiple neurological changes. To date, there are no effective drugs to delay or cure AD. Breviscapine (Bre) is an active ingredient of flavonoids extracted from breviscapus.

Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-G Complex Structures.

Human endocannabinoid systems modulate multiple physiological processes mainly through the activation of cannabinoid receptors CB1 and CB2. Their high sequence similarity, low agonist selectivity, and lack of activation and G protein-coupling knowledge have hindered the development of therapeutic applications. Importantly, missing structural information has significantly held back the development of promising CB2-selective agonist drugs for treating inflammatory and neuropathic pain without the psychoactivity of CB1.

Self-capping of nucleoprotein filaments protects the Newcastle disease virus genome.

Non-segmented negative-strand RNA viruses, such as measles, ebola and Newcastle disease viruses (NDV), encapsidate viral genomic RNAs into helical nucleocapsids, which serve as the template for viral replication and transcription. Here, the clam-shaped nucleocapsid structure, where the NDV viral genome is sequestered, was determined at 4.8 Å resolution by cryo-electron microscopy.

Paeoniflorin attenuates impairment of spatial learning and hippocampal long-term potentiation in mice subjected to chronic unpredictable mild stress.

Rationale And Objective: Paeoniflorin has been reported to exhibit antidepressant-like effects in several animal model depression; and it also exerts a neuroprotective effect. In the present study, we investigated the effects of paeoniflorin administration on depression-like behaviors and cognitive abilities in mice subjected to chronic unpredictable mild stress (CUMS), an animal model associated with depressive disorders and cognitive deficits.

Methods: We administered paeoniflorin (20 mg/kg), which is the main active constituent extracted from Paeonia lactiflora Pall.

Increased TRPM4 Activity in Cerebral Artery Myocytes Contributes to Cerebral Blood Flow Reduction After Subarachnoid Hemorrhage in Rats.

Cerebral blood flow (CBF) reduction underlies unfavorable outcomes after subarachnoid hemorrhage (SAH). Transient receptor potential melastatin-4 (TRPM4) has a pivotal role in cerebral artery myogenic tone maintenance and CBF regulation under physiological conditions. However, the role of TRPM4 in CBF reduction after SAH is unclear.

Post-stroke gastrodin treatment ameliorates ischemic injury and increases neurogenesis and restores the Wnt/β-Catenin signaling in focal cerebral ischemia in mice.

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide, and the only available drug treatment is limited to a short window following the ischemic event. Gastrodin is the major bioactive constituent extracted from thetuberGastrodia elata, and is currently used to treat dizziness in the clinic. "Early" application of gastrodin (before modeling or immediately after ischemic injury) has shown antioxidative and neuroprotective effects in a transient focal brain ischemia model in rodents; however, it is not known whether the delayed administration of gastrodin after permanent focal cerebral ischemia ameliorates neural injury and increases neurogenesis.

MicroRNA-128 Protects Dopamine Neurons from Apoptosis and Upregulates the Expression of Excitatory Amino Acid Transporter 4 in Parkinson's Disease by Binding to AXIN1.

Background/aims: Parkinson's disease (PD) is a frequently occurring condition that resulted from the loss of midbrain neurons, which synthesize the neurotransmitter dopamine. In this study, we established mouse models of PD to investigate the expression of microRNA-128 (miR-128) and mechanism through which it affects apoptosis of dopamine (DA) neurons and the expression of excitatory amino acid transporter 4 (EAAT4) via binding to axis inhibition protein 1 (AXIN1).

Methods: Gene expression microarray analysis was performed to screen differentially expressed miRNAs that are associated with PD.