Non-canonical signaling initiated by hormone-responsive G protein-coupled receptors from subcellular compartments.

G protein-coupled receptors (GPCRs), the largest family of membrane receptors in the mammalian genomes, regulate almost all known physiological processes by transducing numerous extracellular stimuli including almost two-thirds of endogenous hormones and neurotransmitters. The traditional view held that GPCR signaling occurs exclusively at the cell surface, where the receptors bind with the ligands and undergo conformational changes to recruit and activate heterotrimeric G proteins. However, with the application of advanced biochemical and biophysical techniques, this conventional model is challenged by the elucidation of spatiotemporal GPCR activation with the evidence that receptors can signal from subcellular compartments to exhibit various molecular and cellular responses with physiological and pathophysiological relevance.

Ancestral glycoprotein hormone and its cognate receptor present in primitive chordate ascidian: Molecular identification and functional characterization.

The glycoprotein hormone (GPH) system is fundamentally significant in regulating the physiology of chordates, such as thyroid activity and gonadal function. However, the knowledge of the GPH system in the primitive chordate ascidian species is largely lacking. Here, we reported an ancestral GPH system in the ascidian (Styela clava), which consists of GPH α subunit (Sc-GPA2), GPH β subunit (Sc-GPB5), and the cognate leucine-rich repeat-containing G protein-coupled receptor (Sc-GPHR).

Cyclophilin D-induced mitochondrial impairment confers axonal injury after intracerebral hemorrhage in mice.

The mitochondrial permeability transition pore is a nonspecific transmembrane channel. Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling, calcium overload, and axonal degeneration. Cyclophilin D is an important component of the mitochondrial permeability transition pore.

Edonerpic maleate regulates glutamate receptors through CRMP2- and Arc-mediated mechanisms in response to brain trauma.

Dysfunction of ionotropic glutamate receptors (iGluRs) is a key molecular mechanism of excitotoxic neuronal injury following traumatic brain injury (TBI). Edonerpic maleate is a low molecular-weight compound that was screened as a candidate neuroprotective agent. In this study, we investigated its effects on TBI and GluRs signaling.

Controlled Decompression Attenuates Compressive Injury following Traumatic Brain Injury via TREK-1-Mediated Inhibition of Necroptosis and Neuroinflammation.

Decompressive craniectomy is an effective strategy to reduce intracranial hypertension after traumatic brain injury (TBI), but it is related to many postoperative complications, such as delayed intracranial hematoma and diffuse brain swelling. Our previous studies have demonstrated that controlled decompression (CDC) surgery attenuates brain injury and reduces the rate of complications after TBI. Here, we investigated the potential molecular mechanisms of CDC in experimental models.

Inhibition of miR-134-5p protects against kainic acid-induced excitotoxicity through Sirt3-mediated preservation of mitochondrial function.

Epilepsy is a neurological disorder which is characterized by brain hyper-excitability and manifests as seizure. Due to its complicated pathogenesis, treatment for epilepsy still remains a huge challenge for neurology in the whole world. MciroRNA-134 (miR-134) is one kind of miRNAs which was firstly found abundant in synapses.

Chinese expert consensus on diagnosis and treatment of trauma-induced hypercoagulopathy.

Trauma-induced coagulopathy (TIC) is caused by post-traumatic tissue injury and manifests as hypercoagulability that leads to thromboembolism or hypocoagulability that leads to uncontrollable massive hemorrhage. Previous studies on TIC have mainly focused on hemorrhagic coagulopathy caused by the hypocoagulable phenotype of TIC, while recent studies have found that trauma-induced hypercoagulopathy can occur in as many as 22.2-85.

Forniceal deep brain stimulation in severe Alzheimer's disease: A case report.

Background: Forniceal deep brain stimulation (DBS) has been proposed as an alternative treatment for Alzheimer's disease (AD). Previous studies on mild to moderate AD patients demonstrated improvements in cognitive functions brought about by forniceal DBS. Here, we report our longitudinal findings in one severe AD patient for whom the activities of daily living (ADL) rather than cognitive function significantly improved after 3 mo of continuous stimulation.

Alanine Scanning Mutagenesis of the DRYxxI Motif and Intracellular Loop 2 of Human Melanocortin-4 Receptor.

The melanocortin-4 receptor (MC4R) is a member of the G-protein-coupled receptor (GPCR) superfamily, which has been extensively studied in obesity pathogenesis due to its critical role in regulating energy homeostasis. Both the Gs-cAMP and ERK1/2 cascades are known as important intracellular signaling pathways initiated by the MC4R. The DRYxxI motif at the end of transmembrane domain 3 and the intracellular loop 2 (ICL2) are thought to be crucial for receptor function in several GPCRs.

The AMPAR Antagonist Perampanel Regulates Neuronal Necroptosis via Akt/GSK3β Signaling After Acute Traumatic Injury in Cortical Neuron.

Background: Perampanel is a highly selective and non-competitive α-amino-3-hydroxy- 5 -methyl-4-isoxazole propionate (AMPA) receptor (AMPAR) antagonist, which has been licensed as an orally administered antiepileptic drug in more than 55 countries. Recently, perampanel was found to exert neuroprotective effects in hemorrhagic and ischemic stroke models.

Objective: In this study, the protective effect of perampanel was investigated.

Biased signaling in naturally occurring mutations of G protein-coupled receptors associated with diverse human diseases.

G protein-coupled receptors (GPCRs) play critical roles in transmitting a variety of extracellular signals into the cells and regulate diverse physiological functions. Naturally occurring mutations that result in dysfunctions of GPCRs have been known as the causes of numerous diseases. Significant progresses have been made in elucidating the pathophysiology of diseases caused by mutations.

NDRG2 attenuates ischemia-induced astrocyte necroptosis via the repression of RIPK1.

Cerebral ischemia results in severe brain damage, and is a leading cause of death and long-term disability. Previous studies have investigated methods to activate astrocytes in order to promote repair in injured brain tissue and inhibit cell death. It has previously been shown that N-myc downstream-regulated gene 2 (NDRG2) was highly expressed in astrocytes and associated with cell activity, but the underlying mechanism is largely unknown.

Striatal asymmetry index and its correlation with the Hoehn & Yahr stage in Parkinson's disease.

Purpose: Striatal asymmetry is a common feature in Parkinson's disease (PD), which changes with the progression of the disease. However, the correlation between the striatal asymmetry and severity of PD remains unclear. The present study aimed to investigate the characteristics of asymmetry in PD, and analyze the correlation between the striatal asymmetry index (SAI) and disease severity.

circ_BICD2 acts as a ceRNA to promote tumor progression and Warburg effect in oral squamous cell carcinoma by sponging miR-107 to enhance HK2.

Numerous studies have proved that the Warburg effect serves a vital role involved in regulating the progression of malignant tumors. Previous studies confirmed that circRNAs act as a novel biomarker for diagnostic and therapeutic in various tumors. However, the functional role and mechanism of circ_BICD2 for the regulation of tumor growth and metastasis in oral squamous cell carcinoma (OSCC) via mediating the Warburg effect are largely unknown.

Activation of SK/K Channel Attenuates Spinal Cord Ischemia-Reperfusion Injury via Anti-oxidative Activity and Inhibition of Mitochondrial Dysfunction in Rabbits.

Spinal cord ischemia-reperfusion injury (SCI/R) is a rare but devastating disorder with a poor prognosis. Small conductance calcium-activated K (SK/K) channels are a family of voltage-independent potassium channels that are shown to participate in the pathological process of several neurological disorders. The aim of this study was to investigate the role of SK/K channels in experimental SCI/R in rabbits.

Characterization of channel catfish (Ictalurus punctatus) melanocortin-3 receptor reveals a potential network in regulation of energy homeostasis.

The melanocortin-3 receptor (MC3R) is known to be involved in regulation of energy homeostasis, regulating feed efficiency and nutrient partitioning in mammals. Its physiological roles in non-mammalian vertebrates, especially economically important aquaculture species, are not well understood. Channel catfish (Ictalurus punctatus) is the main freshwater aquaculture species in North America.

Physiology and pathophysiology of the β-adrenergic receptor.

The β-adrenergic receptor (β-AR) is an important regulator of various physiological functions, such as thermogenesis in brown adipose tissue, lipolysis in white adipose tissue, negative inotropic effect in cardiomyocyte, and relaxation in blood vessel. The activation of β-AR by its agonists is shown to have metabolic (antiobesity and antidiabetic) and cardiovascular effects in animal models, highlighting β-AR as a potential therapeutic target in the treatment of several human diseases. Moreover, a substantial number of studies performed on different populations have identified some β-AR polymorphic variants associated with obesity, diabetes, cardiovascular diseases, and other disorders.

Expression signatures of long non-coding RNA and mRNA in human traumatic brain injury.

Long non-coding RNAs (lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury tissue from three patients of the 101 Hospital of the People's Liberation Army, China (specifically, a 36-year-old male, a 52-year-old female, and a 49-year-old female), who were diagnosed with traumatic brain injury and underwent brain contusion removal surgery. Tissue surrounding the brain contusion in the three patients was used as control tissue to observe expression characteristics of lncRNAs and mRNAs in human traumatic brain injury tissue.

Melanocortin-4 receptor in swamp eel (Monopterus albus): Cloning, tissue distribution, and pharmacology.

Melanocortin-4 receptor (MC4R) plays critical roles in the regulation of various physiological processes, such as energy homeostasis, reproduction and sexual function, cardiovascular function, and other functions in mammals. Although the functions of the MC4R in fish have not been extensively studied, the importance of MC4R in regulation of piscine energy expenditure and sexual functions is emerging. Swamp eel (Monopterus albus) is an economically and evolutionarily important fish widely distributed in tropics and subtropics.

A Hydrogel of Ultrathin Pure Polyaniline Nanofibers: Oxidant-Templating Preparation and Supercapacitor Application.

Although challenging, fabrication of porous conducting polymeric materials with excellent electronic properties is crucial for many applications. We developed a fast in situ polymerization approach to pure polyaniline (PANI) hydrogels, with vanadium pentoxide hydrate nanowires as both the oxidant and sacrifice template. A network comprised of ultrathin PANI nanofibers was generated during the in situ polymerization, and the large aspect ratio of these PANI nanofibers allowed the formation of hydrogels at a low solid content of 1.

Multimodal monitoring combined with hypothermia for the management of severe traumatic brain injury: A case report.

Traumatic brain injury (TBI) is a prominent public health issue that has a significant negative impact on patients and their family members. It is the leading cause of mortality and disability among young (below 50 years old) individuals. Intracranial hypertension (ICH) remains the single most difficult therapeutic challenge for the management of severe TBI.

Value of Ventricular Intracranial Pressure Monitoring for Traumatic Bifrontal Contusions.

Objective: To investigate clinical efficacy of and optimal therapeutic strategy for ventricular intracranial pressure monitoring (V-ICPM) in patients with traumatic bifrontal contusions (TBCs).

Methods: From 8760 patients with traumatic brain injury treated between January 2010 and January 2016, a retrospective analysis was performed on 105 patients with TBCs who underwent V-ICPM and 282 patients with TBCs who did not. All patients underwent treatment at the 101st Hospital of PLA, Wuxi, China.

Rational fabrication of silver-coated AFM TERS tips with a high enhancement and long lifetime.

Tip-enhanced Raman spectroscopy (TERS), known as nanospectroscopy, has received increasing interest as it can provide nanometer spatial resolution and chemical fingerprint information of samples simultaneously. Since Ag tips are well accepted to show a higher TERS enhancement than that of gold tips, there is an urgent quest for Ag TERS tips with a high enhancement, long lifetime, and high reproducibility, especially for atomic force microscopy (AFM)-based TERS. Herein, we developed an electrodeposition method to fabricate Ag-coated AFM TERS tips in a highly controllable and reproducible way.

Protective effects of atorvastatin on cerebral vessel autoregulation in an experimental rabbit model of subarachnoid hemorrhage.

The aim of the present study was to assess the therapeutic effects of atorvastatin on cerebral vessel autoregulation and to explore the underlying mechanisms in a rabbit model of subarachnoid hemorrhage (SAH). A total of 48 healthy male New Zealand rabbits (weight, 2‑2.5 kg) were randomly allocated into SAH, Sham or SAH + atorvastatin groups (n=16/group).