Endoplasmic reticulum stress and the unfolded protein response: emerging regulators in progression of traumatic brain injury.

Traumatic 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. In recent decades, abundant evidence has highlighted the significance of endoplasmic reticulum stress (ERS) in advancing central nervous system (CNS) disorders, including TBI. ERS following TBI leads to the accumulation of unfolded proteins, initiating the unfolded protein response (UPR). Protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6) are the three major pathways of UPR initiation that determine whether a cell survives or dies. This review focuses on the dual effects of ERS on TBI and discusses the underlying mechanisms. It is suggested that ERS may crosstalk with a series of molecular cascade responses, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, autophagy, and cell death, and is thus involved in the progression of secondary injury after TBI. Hence, ERS is a promising candidate for the management of TBI.

Mitochondrial transport in neurons and evidence for its involvement in acute neurological disorders.

Ensuring mitochondrial quality is essential for maintaining neuronal homeostasis, and mitochondrial transport plays a vital role in mitochondrial quality control. In this review, we first provide an overview of neuronal mitochondrial transport, followed by a detailed description of the various motors and adaptors associated with the anterograde and retrograde transport of mitochondria. Subsequently, we review the modest evidence involving mitochondrial transport mechanisms that has surfaced in acute neurological disorders, including traumatic brain injury, spinal cord injury, spontaneous intracerebral hemorrhage, and ischemic stroke. An in-depth study of this area will help deepen our understanding of the mechanisms underlying the development of various acute neurological disorders and ultimately improve therapeutic options.

Armcx1 attenuates secondary brain injury in an experimental traumatic brain injury model in male mice by alleviating mitochondrial dysfunction and neuronal cell death.

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. An in vivo TBI model was established in male C57BL/6 mice via controlled cortical impact (CCI). Adeno-associated viruses (AAVs) with Armcx1 overexpression and knockdown were constructed and administered to mice via stereotactic cortical injection. Exogenous miR-223-3p mimic or inhibitor was transfected into cultured cortical neurons, which were then scratched to simulate TBI in vitro. It was found that Armcx1 expression decreased significantly, while miR-223-3p levels increased markedly in peri-lesion tissues after TBI. The overexpression of Armcx1 significantly reduced TBI-induced neurological dysfunction, neuronal cell death, mitochondrial dysfunction, and axonal injury, while the knockdown of Armcx1 had the opposite effect. Armcx1 was potentially a direct target of miR-223-3p. The miR-223-3p mimic obviously reduced the Armcx1 protein level, while the miR-223-3p inhibitor had the opposite effect. Finally, the miR-223-3p inhibitor dramatically improved mitochondrial membrane potential (MMP) and increased the total length of the neurites without affecting branching numbers. In summary, our results suggest that the decreased expression of Armcx1 protein in neurons after experimental TBI aggravates secondary brain injury, which may be regulated by miR-223-3p. Therefore, this study provides a potential therapeutic approach for treating TBI.

Supramolecular Photonic Hydrogel for High-Sensitivity Alkaline Phosphatase Detection via Synergistic Driving Force.

Structurally-colored photonic hydrogels which are fabricated by introducing hydrogels into thin films or photonic crystal structures are promising candidates for biosensing. Generally, the design of photonic hydrogel biosensors is based on the sensor-analyte interactions induced charge variation within the hydrogel matrix, or chemically grafting binding sites onto the polymer chains, to achieve significant volume change and color variation of the photonic hydrogel. However, relatively low anti-interference capability or complicated synthesis hinder the facile and low-cost fabrication of high-performance photonic hydrogel biosensors. Here, a facilely prepared supramolecular photonic hydrogel biosensor is developed for high-sensitivity detection of alkaline phosphatase (ALP), which is an extensively considered clinical biomarker for a variety of diseases. Responding to ALP results in the broken supramolecular crosslinking and thus increased lattice distancing of the photonic hydrogel driven by synergistic repulsive force between nanoparticles embedded in photonic crystal structure and osmotic swelling pressure. The biosensor shows sensitivity of 7.3 nm spectral shift per mU mL-1 ALP, with detection limit of 0.52 mU mL-1 . High-accuracy colorimetric detection can be realized via a smartphone, promoting point-of-care sensing and timely diagnosis of related pathological conditions.

SARS-CoV-2 Pattern Provides a New Scoring System and Predicts the Prognosis and Immune Therapeutic Response in Glioma.

OBJECTIVE: Glioma is the most common primary malignancy of the adult central nervous system (CNS), with a poor prognosis and no effective prognostic signature. Since late 2019, the world has been affected by the rapid spread of SARS-CoV-2 infection. Research on SARS-CoV-2 is flourishing; however, its potential mechanistic association with glioma has rarely been reported. The aim of this study was to investigate the potential correlation of SARS-CoV-2-related genes with the occurrence, progression, prognosis, and immunotherapy of gliomas. METHODS: SARS-CoV-2-related genes were obtained from the human protein atlas (HPA), while transcriptional data and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Glioma samples were collected from surgeries with the knowledge of patients. Differentially expressed genes were then identified and screened, and seven SARS-CoV-2 related genes were generated by LASSO regression analysis and uni/multi-variate COX analysis. A prognostic SARS-CoV-2-related gene signature (SCRGS) was then constructed based on these seven genes and validated in the TCGA validation cohort and CGGA cohort. Next, a nomogram was established by combining critical clinicopathological data. The correlation between SCRGS and glioma related biological processes was clarified by Gene set enrichment analysis (GSEA). In addition, immune infiltration and immune score, as well as immune checkpoint expression and immune escape, were further analyzed to assess the role of SCRGS in glioma-associated immune landscape and the responsiveness of immunotherapy. Finally, the reliability of SCRGS was verified by quantitative real-time polymerase chain reaction (qRT-PCR) on glioma samples. RESULTS: The prognostic SCRGS contained seven genes, REEP6, CEP112, LARP4B, CWC27, GOLGA2, ATP6AP1, and ERO1B. Patients were divided into high- and low-risk groups according to the median SARS-CoV-2 Index. Overall survival was significantly worse in the high-risk group than in the low-risk group. COX analysis and receiver operating characteristic (ROC) curves demonstrated excellent predictive power for SCRGS for glioma prognosis. In addition, GSEA, immune infiltration, and immune scores indicated that SCRGS could potentially predict the tumor microenvironment, immune infiltration, and immune response in glioma patients. CONCLUSIONS: The SCRGS established here can effectively predict the prognosis of glioma patients and provide a potential direction for immunotherapy.

Role of hydrogen sulfide in subarachnoid hemorrhage.

Subarachnoid 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 (H2 S), as the third gas signaling molecule after carbon monoxide and nitric oxide, has been widely studied recently. There is growing evidence that H2 S has a promising future in the treatment of central nervous system diseases. In this review, we focus on the effects of H2 S in experimental SAH and elucidate the underlying mechanisms. We demonstrate that H2 S has neuroprotective effects and significantly reduces secondary damage caused by SAH via antioxidant, antiinflammatory, and antiapoptosis mechanisms, and by alleviating cerebral edema and vasospasm. Based on these findings, we believe that H2 S has great potential in the treatment of SAH and warrants further study to promote its early clinical application.

A novel chemiluminescence system for the determination of daidzein and its hydroxyl radical-scavenging capacity.

A novel chemiluminescence (CL) system was established for the determinations of daidzein in pharmaceutical preparations and to assess its ability to scavenge hydroxyl radicals. It was shown that a strong CL signal generated when eosin Y was mixed with Fenton reagent was decreased significantly when daidzein was added to the reaction system due to partial scavenging of the hydroxyl radicals in the solution. The extent of decrease in the CL intensity had a good stoichiometric relationship with the daidzein concentration. Based on this, we developed a new method for the determination of daidzein, using a flow-injection chemiluminescence (FI-CL) technique. Under the optimal conditions, the linear range of daidzein concentration was 8.0 × 10(-8) -3.0 × 10(-6) mol/L (R = 0.9982), with a detection limit of 9.0 × 10(-9) mol/L (S:N = 3), and the RSD was 5.8% for 1.0 × 10(-6) mol/L daidzein (n = 11). This method was successfully used in the determination of daidzein in tablets and for evaluation of the hydroxyl radical-scavenging capacity of daidzein. The possible reaction mechanism of the CL system is discussed.