Objective: Gliomas are the most common intracranial tumors with the highest degree of malignancy. Disturbed cholesterol metabolism is one of the key features of many malignant tumors, including gliomas. This study aimed to investigate the significance of cholesterol metabolism-related genes in prognostic prediction and in guiding individualized treatment of patients with gliomas.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
March 2025
Background: Traumatic brain injury (TBI) is a major public health concern with high morbidity and mortality rates. Secondary brain injury, marked by inflammatory responses and apoptosis, worsens TBI outcomes. The endoplasmic reticulum stress (ERS) response has been implicated in secondary brain injury, with Glutamine Rich 1 Gene (QRICH1) emerging as a potential mediator.
View Article and Find Full Text PDFTraumatic brain injury (TBI) has the highest incidence of all common neurological disorders, along with high mortality and disability rates. Pathological conversion of excess nitric oxide (NO) to S-nitrosoglutathion (GSNO) after TBI leads to high S-nitrosylation of intracellular proteins, causing nitrative stress. GSNO reductase (GSNOR) plays an important role by regulating GSNO and SNO-proteins (PSNOs) and as a redox regulator of the nervous system.
View Article and Find Full Text PDFBackground: Armadillo Repeat Containing X-Linked 1 (ARMCX1), a member of the ARM Repeat X-linked protein family, exerts inhibitory function in various tumors. However, its biological role in lung adenocarcinoma (LUAD) and the underlying molecular mechanisms require further exploration.
Methods: LUAD tissue microarrays and bioinformatic databases were used to evaluate the relationship between ARMCX1 and clinicopathological features.
Development of subtype-selective drugs for G protein-coupled receptors poses a significant challenge due to high similarity between subtypes, as exemplified by the three β-adrenergic receptors (βARs). The βAR agonists show promise for treating the overactive bladder or preterm birth, but their potential is hindered by off-target activation of βAR and βAR. Interestingly, several β-blockers, which are antagonists of the βARs and βARs, have been reported to exhibit agonist activity at the βAR.
View Article and Find Full Text PDFPrevious studies have identified metabolites as biomarkers or potential therapeutic targets for traumatic brain injury (TBI). However, the causal association between them remains unknown. Therefore, we investigated the causal effect of serum metabolites and cerebrospinal fluid (CSF) metabolites on TBI susceptibility through Mendelian randomization (MR).
View Article and Find Full Text PDFThe µ-opioid receptor (µOR) is an important target for pain management and molecular understanding of drug action on µOR will facilitate the development of better therapeutics. Here we show, using double electron-electron resonance and single-molecule fluorescence resonance energy transfer, how ligand-specific conformational changes of µOR translate into a broad range of intrinsic efficacies at the transducer level. We identify several conformations of the cytoplasmic face of the receptor that interconvert on different timescales, including a pre-activated conformation that is capable of G-protein binding, and a fully activated conformation that markedly reduces GDP affinity within the ternary complex.
View Article and Find Full Text PDFDue to aging populations and changes in lifestyle, cardiovascular diseases including cardiomyopathy, hypertension, and atherosclerosis, are the leading causes of death worldwide. The heart is a complicated organ composed of multicellular types, including cardiomyocytes, fibroblasts, endothelial cells, vascular smooth muscle cells, and immune cells. Cellular specialization and complex interplay between different cell types are crucial for the cardiac tissue homeostasis and coordinated function of the heart.
View Article and Find Full Text PDFThe human organic cation transporter 1 (hOCT1), also known as SLC22A1, is integral to hepatic uptake of structurally diversified endogenous and exogenous organic cations, influencing both metabolism and drug pharmacokinetics. hOCT1 has been implicated in the therapeutic dynamics of many drugs, making interactions with hOCT1 a key consideration in novel drug development and drug-drug interactions. Notably, metformin, the frontline medication for type 2 diabetes, is a prominent hOCT1 substrate.
View Article and Find Full Text PDFFront Aging Neurosci
February 2024
Background: Disorders associated with cognitive impairment impose a significant burden on both families and society. Previous studies have indicated that gait characteristics under dual-task as reliable markers of early cognitive impairment. Therefore, digital gait detection has great potential for future cognitive screening.
View Article and Find Full Text PDFTraumatic brain injury (TBI) is a common trauma with high mortality and disability rates worldwide. However, the current management of this disease is still unsatisfactory. Therefore, it is necessary to investigate the pathophysiological mechanisms of TBI in depth to improve the treatment options.
View Article and Find Full Text PDFProstaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application.
View Article and Find Full Text PDFAim: Stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) have a substantial role in neuronal formation, differentiation, remodeling, and maturation and participate in multiple physiological and pathological events. In this study, we investigated the role of SDF-1/CXCR4 in neural functional injury and neuroprotection after intracerebral hemorrhage (ICH).
Methods: Western blot, immunofluorescence and immunoprecipitation were used to detect SDF-1/CXCR4 expression and combination respectively after ICH.
Armcx1 is highly expressed in the brain and is located in the mitochondrial outer membrane of neurons, where it mediates mitochondrial transport. Mitochondrial transport promotes the removal of damaged mitochondria and the replenishment of healthy mitochondria, which is essential for neuronal survival after traumatic brain injury (TBI). This study investigated the role of Armcx1 and its potential regulator(s) in secondary brain injury (SBI) after TBI.
View Article and Find Full Text PDFBackground: Minocycline, an antibiotic with anti-inflammatory, antioxidant, and neuroprotective properties, has been used for treating psychiatric disorders in research. This systematic review aimed to evaluate the efficacy and tolerability of minocycline in patients having depression with or without treatment-resistance.
Methods: Electronic databases including Embase, PubMed, and the Cochrane library were searched for relevant studies published up to October 17, 2022.
The αadrenergic receptor (αAR) belongs to the family of G protein-coupled receptors that respond to adrenaline and noradrenaline. αAR is involved in smooth muscle contraction and cognitive function. Here, we present three cryo-electron microscopy structures of human αAR bound to the endogenous agonist noradrenaline, its selective agonist oxymetazoline, and the antagonist tamsulosin, with resolutions range from 2.
View Article and Find Full Text PDFThe μ-opioid receptor (μOR) is an important target for pain management and the molecular understanding of drug action will facilitate the development of better therapeutics. Here we show, using double electron-electron resonance (DEER) and single-molecule fluorescence resonance energy transfer (smFRET), how ligand-specific conformational changes of the μOR translate into a broad range of intrinsic efficacies at the transducer level. We identify several cytoplasmic receptor conformations interconverting on different timescales, including a pre-activated receptor conformation which is capable of G protein binding, and a fully activated conformation which dramatically lowers GDP affinity within the ternary complex.
View Article and Find Full Text PDFAdvances in structural biology have provided important mechanistic insights into signaling by the transmembrane core of G-protein coupled receptors (GPCRs); however, much less is known about intrinsically disordered regions such as the carboxyl terminus (CT), which is highly flexible and not visible in GPCR structures. The β adrenergic receptor's (βAR) 71 amino acid CT is a substrate for GPCR kinases and binds β-arrestins to regulate signaling. Here we show that the βAR CT directly inhibits basal and agonist-stimulated signaling in cell lines lacking β-arrestins.
View Article and Find Full Text PDFObjective: Status epilepticus (SE) is a common neurological emergency that is defined as a prolonged seizure or a series of seizures which often leads to irreversible damage. Levetiracetam (LEV) and valproate (VPA) are second-line anti-seizure drugs that are frequently used in patients with established SE (ESE). This meta-analysis compared the efficacy and safety of LEV and VPA for the treatment of ESE.
View Article and Find Full Text PDFMicrotubules, a highly dynamic cytoskeleton, participate in many cellular activities including mechanical support, organelles interactions, and intracellular trafficking. Microtubule organization can be regulated by modification of tubulin subunits, microtubule-associated proteins (MAPs) or agents modulating microtubule assembly. Increasing studies demonstrate that microtubule disorganization correlates with various cardiocerebrovascular diseases including heart failure and ischemic stroke.
View Article and Find Full Text PDFIsosteviol sodium (STVNa) is a beyerane diterpene synthesized via acid hydrolysis of stevioside, which can improve glucose and lipid metabolism in animals with diabetes. However, it remains unknown whether STVNa can exhibit a therapeutic effect on nonalcoholic fatty liver disease (NAFLD) and its underlying mechanism. We hypothesize that autophagic initiation may play a key role in mediating the development of NAFLD.
View Article and Find Full Text PDFBiochem Biophys Res Commun
September 2022
A fat-rich diet triggers obesity, and promotes cardiomyocyte injury. Till now, no prior investigations suggested a beneficial role of Isosteviol Sodium (STVNa) in cardiac activity in high fat diet (HFD)-exposed obese rats. However, there is evidence that STVNa accelerates healing of multiple tissue injuries.
View Article and Find Full Text PDFSubarachnoid hemorrhage (SAH) is a common acute and severe disease worldwide, which imposes a heavy burden on families and society. However, the current therapeutic strategies for SAH are unsatisfactory. Hydrogen sulfide (H S), as the third gas signaling molecule after carbon monoxide and nitric oxide, has been widely studied recently.
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