Role of Cholesterol Metabolic Enzyme CYP46A1 and Its Metabolite 24S-Hydroxycholesterol in Ischemic Stroke.

Background: For several decades, it has been recognized that overactivation of the glutamate-gated N-methyl-D-aspartate receptors (NMDARs) and subsequent Ca toxicity play a critical role in ischemic brain injury. 24S-hydroxycholesterol (24S-HC) is a major cholesterol metabolite in the brain, which has been identified as a potent positive allosteric modulator of NMDAR in rat hippocampal neurons. We hypothesize that 24S-HC worsens ischemic brain injury via its potentiation of the NMDAR, and reducing the production of 24S-HC by targeting its synthetic enzyme CYP46A1 provides neuroprotection.

Cholestane-3β,5α,6β-Triol Inhibits Acid-Sensing Ion Channels and Reduces Acidosis-Mediated Ischemic Brain Injury.

Background: Activation of the acid-sensing ion channels (ASICs) by tissue acidosis, a common feature of brain ischemia, contributes to ischemic brain injury, while blockade of ASICs results in protection. Cholestane-3β,5α,6β-triol (Triol), a major cholesterol metabolite, has been demonstrated as an endogenous neuroprotectant; however, the mechanism underlying its neuroprotective activity remains elusive. In this study, we tested the hypothesis that inhibition of ASICs is a potential mechanism.

Using immune clusters for classifying Mycobacterium tuberculosis infection.

Background: The differential diagnosis between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) is still a challenge worldwide.

Methods: Immune indicators involved in innate, humoral, and cellular immune cells, as well as antigen-specific cells were simultaneously assessed in patients with ATB and LTBI.

Results: Of 54 immune indicators, no indicator could distinguish ATB from LTBI, likely due to an obvious heterogeneity of immune indicators noticed in ATB patients.

Inhibition of ASIC1a Improves Behavioral Recovery after Stroke.

Stroke continues to be a leading cause of death and long-term disabilities worldwide, despite extensive research efforts. The failure of multiple clinical trials raises the need for continued study of brain injury mechanisms and novel therapeutic strategies for ischemic stroke. The contribution of acid-sensing ion channel 1a (ASIC1a) to neuronal injury during the acute phase of stroke has been well studied; however, the long-term impact of ASIC1a inhibition on stroke recovery has not been established.

Mechanism of ShuiJingDan in Treating Acute Gouty Arthritis Flares Based on Network Pharmacology and Molecular Docking.

Purpose: This study examined the underlying mechanisms of SJD's anti-inflammatory and analgesic effects on acute GA flares.

Methods: This study used pharmacology network and molecular docking methods. The active ingredients of ShuiJingDan (SJD) were obtained from the Traditional Chinese Medicine Systems Pharmacology Analysis Platform (TCMSP), and the relevant targets of GA were obtained from the Online Mendelian Inheritance in Man (OMIM) database and Therapeutic Target Database (TTD).

Inhibition of Acid-Sensing Ion Channels by KB-R7943, a Reverse Na/Ca Exchanger Inhibitor.

KB-R7943, an isothiourea derivative, is widely used as a pharmacological inhibitor of reverse sodium-calcium exchanger (NCX). It has been shown to have neuroprotective and analgesic effects in animal models; however, the detailed molecular mechanisms remain elusive. In the current study, we investigated whether KB-R7943 modulates acid-sensing ion channels (ASICs), a group of proton-gated cation channels implicated in the pathophysiology of various neurological disorders, using the whole-cell patch clamp techniques.

Changes in NMDA Receptor Function in Rapid Ischemic Tolerance: A Potential Role for Tri-Heteromeric NMDA Receptors.

In this study, we characterize biophysical changes in NMDA receptor function in response to brief non-injurious ischemic stress (ischemic preconditioning). Electrophysiological studies show NMDA receptor function is reduced following preconditioning in cultured rat cortical neurons. This functional change is not due to changes in the reversal potential of the receptor, but an increase in desensitization.

Ultrasonography-Guided Combination with Elbow Arthrography-Assisted Minimally Invasive Treatment of Radial Neck Fractures in Young Children.

Background: A radius neck fracture in children is a common fracture that not only affects the growth and development of children but also has a certain impact on the function of children's elbow joints.

Objective: To probe into the application value of ultrasonography- (US-) guided combination with elbow arthrography in the minimally invasive treatment of radial neck fractures in young children, summarize its clinical effect and provide a minimally invasive, safe, effective, and reliable method for treating radial neck fractures in young children.

Methods: Seventy-three patients with type III or IV radial neck fractures were treated from June 2013 to December 2020 and were divided into the Métaizeau group ( = 31, treatment group) and Kirschner wire (-wire) -wire group ( = 42, control group).

pH and proton-sensitive receptors in brain ischemia.

Extracellular proton concentration is at 40 nM when pH is 7.4. In disease conditions such as brain ischemia, proton concentration can reach µM range.

The Dynamic Immunological Parameter Landscape in Coronavirus Disease 2019 Patients With Different Outcomes.

Objectives: The longitudinal and systematic evaluation of immunity in coronavirus disease 2019 (COVID-19) patients is rarely reported.

Methods: Parameters involved in innate, adaptive, and humoral immunity were continuously monitored in COVID-19 patients from onset of illness until 45 days after symptom onset.

Results: This study enrolled 27 mild, 47 severe, and 46 deceased COVID-19 patients.

Molecular Analysis and Antimicrobial Resistance Pattern of Tigecycline-Non-Susceptible Isolated from a Tertiary Care Hospital of East Asia.

Introduction: Tigecycline is one of the last resorts for carbapenem-resistant (CRKP) infections. Indeed, tigecycline-non-susceptible (TNSKP) strains are increasingly treated with the use of tigecycline. In this study, we attempted to better understand their epidemiological trends and characteristics.

Immunologic memory to SARS-CoV-2 in convalescent COVID-19 patients at 1 year postinfection.

Background: Understanding the complexities of immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to gain insights into the durability of protective immunity against reinfection.

Objective: We sought to evaluate the immune memory to SARS-CoV-2 in convalescent patients with longer follow-up time.

Methods: SARS-CoV-2-specific humoral and cellular responses were assessed in convalescent patients with coronavirus disease 2019 (COVID-19) at 1 year postinfection.

Acid-sensing ion channel 1 (ASIC1) mediates weak acid-induced migration of human malignant glioma cells.

Glioblastoma is the most aggressive and lethal tumor in the central nervous system in adult and has poor prognosis due to strong proliferation and aggressive invasion capacity. Acidic microenvironment is commonly observed in tumor tissues but the exact role of acidosis in the pathophysiology of glioblastoma and underlying mechanisms remain unclear. Acid-sensing ion channels (ASICs) are proton-gated cation channels activated by low extracellular pH.

Novel insights into ferroptosis: Implications for age-related diseases.

Rapid increase in aging populations is an urgent problem because older adults are more likely to suffer from disabilities and age-related diseases (ARDs), burdening healthcare systems and society in general. ARDs are characterized by the progressive deterioration of tissues and organs over time, eventually leading to tissue and organ failure. To date, there are no effective interventions to prevent the progression of ARDs.

Upregulation of acid sensing ion channel 1a (ASIC1a) by hydrogen peroxide through the JNK pathway.

Oxidative stress is intimately tied to neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis, and acute injuries, such as ischemic stroke and traumatic brain injury. Acid sensing ion channel 1a (ASIC1a), a proton-gated ion channel, has been shown to be involved in the pathogenesis of these diseases. However, whether oxidative stress affects the expression of ASIC1a remains elusive.

GPR68 Is a Neuroprotective Proton Receptor in Brain Ischemia.

Background And Purpose: Brain acidosis is prevalent in stroke and other neurological diseases. Acidosis can have paradoxical injurious and protective effects. The purpose of this study is to determine whether a proton receptor exists in neurons to counteract acidosis-induced injury.

Protein Kinase C Regulates ASIC1a Protein Expression and Channel Function via NF-kB Signaling Pathway.

Tissue acidosis is a common feature in many pathological conditions. Activation of acid-sensing ion channel 1a (ASIC1a) plays a key role in acidosis-mediated neurotoxicity. Protein kinase C (PKC) activity has been proved to be associated with many physiological processes and pathological conditions; however, whether PKC activation regulates ASIC1a protein expression and channel function remains ill defined.

The TRPM7 Channel in the Nervous and Cardiovascular Systems.

Transient receptor potential melastatin 7 (TRPM7), along with the closely related TRPM6, are unique channels that have dual operations: cation permeability and kinase activity. In contrast to the limited tissue distribution of TRPM6, TRPM7 is widely expressed among tissues and is therefore implicated in a variety of cellular functions physiologically and pathophysiologically. The discovery of TRPM7's unique structure imparting dual ion channel and kinase activities shed light onto novel and peculiar biological functions, such as Mg2+ homeostasis, cellular Ca2+ flickering, and even intranuclear transcriptional regulation by a cleaved kinase domain translocated to nuclei.

Hippocampal changes in mice lacking an active prohormone convertase 2.

Prohormone convertase 2 (PC2) is essential for the biosynthesis of many neuropeptides, including several of them in hippocampus. In mouse brain, lacking an enzymatically active PC2 (PC2-null) causes accumulation of many neuropeptides in their precursor or intermediate forms. Little is known about how a PC2-null state may affect the function of the hippocampus.

Gankyrin promotes osteosarcoma tumorigenesis by forming a positive feedback loop with YAP.

Background: Although gankyrin has been identified as a vital regulator of tumorigenesis, its role and regulatory mechanism in osteosarcoma (OS) remain unclear.

Methods: QRT-PCR, western blot and IHC staining were conducted to detect the expression of gankyrin in OS. Pearson's χ² test was adopted to examine the associations between gankyrin expression and clinicopathologic characteristics.

Percutaneous leverage reduction with two Kirschner wires combined with the Métaizeau technique versus open reduction plus internal fixation with a single Kirschner-wire for treating Judet IV radial neck fractures in children.

Objective: To compare the clinical effectiveness of a novel approach, percutaneous leverage reduction using two Kirschner-wires (k-wires) combined with the Métaizeau technique, versus open reduction plus internal fixation with k-wire for the treatment of Judet IV radial neck fractures in children.

Methods: Thirty-four patients with Judet IV radial neck fractures were treated either with percutaneous leverage reduction using two k-wires and the Métaizeau technique (n = 16) or open reduction plus internal fixation with k-wire (n = 18). Patient data including sex, age, time from trauma to surgery, fracture type, follow up, postoperative healing time, X-ray studies, elbow function, and complications were collected.

β-Estradiol Protects Against Acidosis-Mediated and Ischemic Neuronal Injury by Promoting ASIC1a (Acid-Sensing Ion Channel 1a) Protein Degradation.

Background and Purpose- Sex differences in the incidence and outcome of stroke have been well documented. The severity of stroke in women is, in general, significantly lower than that in men, which is mediated, at least in part, by the protective effects of β-estradiol. However, the detailed mechanisms underlying the neuroprotection by β-estradiol are still elusive.