Facile strategy for gelatin-based hydrogel with multifunctionalities to remodel wound microenvironment and accelerate healing of acute and diabetic wounds.

Chronic diabetic wounds represent the most common diabetes complication. Wound healing depends on scavenging reactive oxygen species (ROS), neovascularization, and controlling infection. A naturally derived gelatin-based hydrogel is biocompatible, biodegradable, does not promote inflammation, and can remove ROS, but strategies for developing a gelatin-based hydrogel currently require careful chemical modification of gelatin and time-consuming purification and post-crosslinking processing. Herein, a facile method of combining zirconium (Zr4+), gelatin, and quercetin (QCN) to generate an injectable gelatin-based hydrogel (QCN@Gel-Zr) for diabetic wound treatment was presented. Adding QCN improved the mechanical, injection, and adhesive performance of the Gel-Zr hydrogel and conferred antibacterial and free radical-scavenging abilities. These properties induced cellular proliferation and migration, protection against oxidative stress, and reduction in inflammatory expression. In vivo models of acute and chronic diabetic skin wounds were used to demonstrate biocompatibility and the ability of the gelatin hydrogels to promote wound healing. The histological analysis showed that the QCN@Gel-Zr hydrogel promoted angiogenesis, collagen deposition, and hair follicle regeneration with no detectable cytotoxicity. This study demonstrates the preparation of gelatin-based hydrogel with various flexible functions to address the complex biological requirements of diabetic wound repair.

Subtle distinction in molecular structure of flavonoids leads to vastly different coating efficiency and mechanism of metal-polyphenol networks with excellent antioxidant activities.

Metal-polyphenol networks (MPNs) are of immense scientific interest because of their simple and rapid process to deposit on various substrates or particles with different shapes. However, there are rare reports on the effect of polyphenol molecular structure on coating efficiency and mechanism of MPNs. Herein, three typical flavonoid polyphenols, catechin (Cat), epigallocatechin (EGC) and procyanidin (PC), with the same skeleton (C6-C3-C6) but subtle distinction in molecular structure, were selected to build MPN coatings with ferric ions (Fe3+). And various techniques combined with the density functional theory (DFT) were applied to deeply reveal the roles of coordinative phenolic hydroxyl groups as well as noncovalent interactions (hydrogen bonding and π - π stacking) in the formation of flavonoid-based MPNs. We found that more accessible numbers of coordinative phenolic hydroxyl groups, the higher coating efficiency. In these flavonoid-based MPNs, the single-complex is the predominant during the coordinative modes between phenolic hydroxyl and Fe3+, not the previously reported mono-complex, bis-complex and/or tris-complex. Besides coordinative interaction, noncovalent interactions also contribute to MPNs formation, and hydrogen bonds prevail in the noncovalent interaction compared with π-π stacking. And these engineered MPN coatings can endow the substrate with excellent antioxidant activities. This study contributes to in-depth understanding the building mechanism of flavonoid-based MPNs, and increasing coating efficiency by choosing proper polyphenols.

Hematopoietic progenitor kinase 1 inhibits the development and progression of pancreatic intraepithelial neoplasia.

Ras plays an essential role in the development of acinar-to-ductal metaplasia (ADM) and pancreatic ductal adenocarcinoma (PDAC). However, mutant Kras is an inefficient driver for PDAC development. The mechanisms of the switching from low Ras activity to high Ras activity that are required for development and progression of pancreatic intraepithelial neoplasias (PanINs) are unclear. In this study, we found that hematopoietic progenitor kinase 1 (HPK1) was upregulated during pancreatic injury and ADM. HPK1 interacted with the SH3 domain and phosphorylated Ras GTPase-activating protein (RasGAP) and upregulated RasGAP activity. Using transgenic mouse models of HPK1 or M46, a kinase-dead mutant of HPK1, we showed that HPK1 inhibited Ras activity and its downstream signaling and regulated acinar cell plasticity. M46 promoted the development of ADM and PanINs. Expression of M46 in KrasG12D Bac mice promoted the infiltration of myeloid-derived suppressor cells and macrophages, inhibited the infiltration of T cells, and accelerated the progression of PanINs to invasive and metastatic PDAC, while HPK1 attenuated mutant Kras-driven PanIN progression. Our results showed that HPK1 plays an important role in ADM and the progression of PanINs by regulating Ras signaling. Loss of HPK1 kinase activity promotes an immunosuppressive tumor microenvironment and accelerates the progression of PanINs to PDAC.

Progresses, Challenges, and Prospects of CRISPR/Cas9 Gene-Editing in Glioma Studies.

Glioma refers to a tumor that is derived from brain glial stem cells or progenitor cells and is the most common primary intracranial tumor. Due to its complex cellular components, as well as the aggressiveness and specificity of the pathogenic site of glioma, most patients with malignant glioma have poor prognoses following surgeries, radiotherapies, and chemotherapies. In recent years, an increasing amount of research has focused on the use of CRISPR/Cas9 gene-editing technology in the treatment of glioma. As an emerging gene-editing technology, CRISPR/Cas9 utilizes the expression of certain functional proteins to repair tissues or treat gene-deficient diseases and could be applied to immunotherapies through the expression of antigens, antibodies, or receptors. In addition, some research also utilized CRISPR/Cas9 to establish tumor models so as to study tumor pathogenesis and screen tumor prognostic targets. This paper mainly discusses the roles of CRISPR/Cas9 in the treatment of glioma patients, the exploration of the pathogenesis of neuroglioma, and the screening targets for clinical prognosis. This paper also raises the future research prospects of CRISPR/Cas9 in glioma, as well as the opportunities and challenges that it will face in clinical treatment in the future.

Profile of Remimazolam in Anesthesiology: A Narrative Review of Clinical Research Progress.

Remimazolam is a novel short-acting γ-aminobutyric acid (GABA) receptor agonist with typical characteristics of benzodiazepine sedative drugs, nonorgan-dependent metabolism, long-term infusion without accumulation, and no injection pain. It is quite different from the other current sedative drugs and has broad prospects for application. It has been established that the metabolites of remimazolam are inactive, and the interactions with other drugs are weak with slight cardiopulmonary suppressive effects, showing good effectiveness and safety. During the 2-year period that it has been on the market, remimazolam has been used in multiple clinical scenarios, such as the induction and maintenance of general anesthesia and sedation in outpatient minor procedures or examinations. However, it's use has also prompted widespread concern around the world. Therefore, given its short- and rapid-acting, controllable characteristics remimazolam deserves in-depth study in order for it to be used in fast-track surgery, comfort diagnosis and treatment. Notably, such agents might be of great significance, especially in elderly individuals, patients with critical diseases or patients with liver and kidney insufficiency. The current study reviews recent clinical studies (2015-2022) on remimazolam and summarizes the characteristics of its applications. Specifically, the use of remimazolam in some specific populations are described. This study attempts to provide scientific support for the clinical application of this novel sedative drug in the field of anesthesia.

Therapeutic Effects of Retinoic Acid in Lipopolysaccharide-Induced Cardiac Dysfunction: Network Pharmacology and Experimental Validation.

Purpose: Sepsis, which is deemed as a systemic inflammation reaction syndrome in the face of infectious stimuli, is the primary cause of death in ICUs. Sepsis-induced cardiomyopathy (SIC) may derive from systemic inflammation reaction and oxidative stress. Retinoic acid (RA) is recognized by its beneficial roles in terms of the immunoresponse to infections and antioxygen actions. However, the treatment efficacy and potential causal links of RA in SIC are still elusive. Methods: By virtue of the STITCH database, we identified the targets of RA. Differentially expressed genes in SIC were acquired from the GEO database. The PPI network of intersected targets was established. GO and KEGG pathway enrichment analysis was completed. Hub genes were analyzed by cytoHubba plug-in. In the process of experimental validation, a mouse sepsis model was established by lipopolysaccharide (LPS), and the treated mice were intraperitoneally injected with RA or Dexamethasone (DEX) 60 min prior to LPS injections. Survival conditions, cardiac functions and antioxidant levels of the mice were assessed. Cardiac inflammation and injury were detected by HE and TUNEL. The levels of key genes and signal pathway expression were analyzed by RT-PCR and Western blot. Results: PPARA, ITGAM, VCAM-1, IGF-1 and IL-6 were identified as key therapeutic targets of RA by network pharmacology. PI3K-Akt signaling pathway is the main regulatory pathway of RA. In vivo researches unraveled that RA can improve the survival rate and cardiac function of LPS-treated mice, inhibit inflammatory factors and myocardial injury, and regulate the expression of key therapeutic targets and key pathways, which is PI3K-Akt signaling pathway. Conclusion: Network pharmacological method offers a predicative strategy to explore the treatment efficacy and causal links of RA in endotoxemic myocarditis. Through experimental verification, we discover that RA can reduce lipopolysaccharide-induced cardiac dysfunction by regulating the PI3K-Akt signaling pathway and key genes.

Recent Advances in Nanomaterials for Diagnosis, Treatments, and Neurorestoration in Ischemic Stroke.

Stroke is a major public health issue, corresponding to the second cause of mortality and the first cause of severe disability. Ischemic stroke is the most common type of stroke, accounting for 87% of all strokes, where early detection and clinical intervention are well known to decrease its morbidity and mortality. However, the diagnosis of ischemic stroke has been limited to the late stages, and its therapeutic window is too narrow to provide rational and effective treatment. In addition, clinical thrombolytics suffer from a short half-life, inactivation, allergic reactions, and non-specific tissue targeting. Another problem is the limited ability of current neuroprotective agents to promote recovery of the ischemic brain tissue after stroke, which contributes to the progressive and irreversible nature of ischemic stroke and also the severity of the outcome. Fortunately, because of biomaterials' inherent biochemical and biophysical properties, including biocompatibility, biodegradability, renewability, nontoxicity, long blood circulation time, and targeting ability. Utilization of them has been pursued as an innovative and promising strategy to tackle these challenges. In this review, special emphasis will be placed on the recent advances in the study of nanomaterials for the diagnosis and therapy of ischemic stroke. Meanwhile, nanomaterials provide much promise for neural tissue salvage and regeneration in brain ischemia, which is also highlighted.

Molecular Profiles of Serum-Derived Extracellular Vesicles in High-Grade Serous Ovarian Cancer.

Patients with high-grade serous ovarian cancer (HGSC) who have no visible residual disease (R0) after primary surgery have the best clinical outcomes, followed by patients who undergo neoadjuvant chemotherapy (NACT) and have a response enabling interval cytoreductive surgery. Clinically useful biomarkers for predicting these outcomes are still lacking. Extracellular vesicles (EVs) have been recognized as liquid biopsy-based biomarkers for early cancer detection and disease surveillance in other disease settings. In this study, we performed extensive molecular characterization of serum-derived EVs and correlated the findings with therapeutic outcomes in patients with HGSC. Using EV-DNA whole-genome sequencing and EV-RNA sequencing, we identified distinct somatic EV-DNA alterations in cancer-hallmark genes and in ovarian cancer genes, as well as significantly altered oncogenic pathways between the R0 group and NACT groups. We also found significantly altered EV-RNA transcriptomic variations and enriched pathways between the groups. Taken together, our data suggest that the molecular characteristics of EVs could enable prediction of patients with HGSC who could undergo R0 surgery or respond to chemotherapy.

Identification of Potential Biomarkers for Ryanodine Receptor 1 (RYR1) Mutation-Associated Myopathies Using Bioinformatics Approach.

Background: Myopathies related to Ryanodine receptor 1 (RYR1) mutation are the most common nondystrophy muscle disorder in humans. Early detection and diagnosis of RYR1 mutation-associated myopathies may lead to more timely treatment of patients, which contributes to the management and preparation for malignant hyperthermia. However, diagnosis of RYR1 mutation-associated myopathies is delayed and challenging. The absence of diagnostic morphological features in muscle biopsy does not rule out the possibility of pathogenic variations in RYR1. Accordingly, it is helpful to seek biomarkers to diagnose RYR1 mutation-associated myopathies. Methods: Skeletal muscle tissue microarray datasets of RYR1 mutation-associated myopathies or healthy persons were built in accordance with the gene expression synthesis (GEO) database. Differentially expressed genes (DEGs) were identified on the basis of R software. Genes specific to tissue/organ were identified through BioGPS. An enrichment analysis of DEGs was conducted in accordance with the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). We also built protein-protein interaction (PPI) networks to explore the function and enrichment pathway of DEGs and the identification of hub genes. Lastly, the ROC curve was drawn for hub genes achieving specific expressions within skeletal muscle. Moreover, the area under the curve (AUC) was obtained to calculate the predictive value of key genes. The transcription factors of hub genes achieving specific expressions within skeletal muscle were predicted with the use of the iRegulon plugin. Results: We identified 170 DEGs among 11 muscle biopsy samples of healthy subjects and 17 muscle biopsy samples of RYR1 mutation-associated myopathy patients in the dataset. Among the above DEGs, 30 genes achieving specific expressions within tissues/organs were found. GO and KEGG enrichment analysis of DEGs mainly focused on muscle contraction, actin-mediated cell contraction, actin filament-based movement, and muscular sliding. 12 hub genes were identified with the use of Cytoscape. Four hub genes were specifically expressed in skeletal muscle tissue, including MYH1 (AUC: 0.856), TNNT3 (AUC: 0.840), MYLPF (AUC: 0.786), and ATP2A1 (AUC: 0.765). The iRegulon predicted results suggested that the transcription factor MYF6 was found with the highest reliability. Conclusions: Four skeletal muscle tissue-specific genes were identified, including MYH1, TNNT3, MYLPF, and ATP2A1, as the potential biomarkers for diagnosing and treating RYR1 mutation-associated myopathies, which provided insights into the transcriptome-level development mechanism. The transcription factor MYF6 may be a vital upstream regulator of the above biomarkers.

Research Progress on the Ability of Astragaloside IV to Protect the Brain Against Ischemia-Reperfusion Injury.

Stroke, a disease with a sudden onset and high morbidity and mortality rates, is difficult to treat in the clinic. Traditional Chinese medicine has become increasingly widely used in clinical practice. Modern pharmacological studies have found that Radix Astragali has a variety of medicinal properties, i.e., immunoregulatory, antioxidative, anti-cancer, anti-diabetes, myocardial protective, hepatoprotective, and antiviral functions. This article reviews the protective effect and mechanism of astragaloside IV, which is extracted from Radix Astragali, on stroke, discusses the cerebroprotective effect of astragaloside IV against ischemia-reperfusion-related complications, offers insight into research prospects, and expands the idea of integrating traditional Chinese and Western medicine treatment strategies and drugs to provide a theoretical reference for the clinical treatment of cerebral ischemia-reperfusion injury and the improvement of stroke prognosis.

MK8722, an AMPK activator, inhibiting carcinoma proliferation, invasion and migration in human pancreatic cancer cells.

BACKGROUND: MK8722 is a potent and systemic pan-AMPK activator. It is an effective, direct, allosteric activator of AMPK complex in many mammals. This study tried to explore the underlying anti-cancer molecular mechanism of MK8722 in human pancreatic cancer cells (PCCs). METHODS: The anti-proliferation, invasion and migration functions of MK8722 in human pancreatic cancer analyzed by real time cellular analysis, colony formation assay, cell migration assay, transwell assay and flow cytometery analysis. Moreover, the potential targeted signaling pathway was tested via RNA-seq and pathway enrichment analysis. RESULTS: In the present study, we investigated the anti-PCCs effects of MK8722 on two different human pancreatic cancer cell lines (PANC-1 and Patu8988). The results showed that MK8722 significantly inhibited human tumor cells proliferation and migration/invasion in a dose-dependent manner. Additionally, the influence of MK8722 was examined by analyzing the expression of potential key genes and pathways, which may provide novel insights to the mechanism of MK8722. CONCLUSION: The inhibition of pancreatic cancer by MK8722 through a number of pathways that inhibit carcinoma proliferation, invasion and migration. The potential effect of MK8722 might be determined by regulating the expression of AL162151, IER2, REPIN1, KRT80 to inhibit cycle arrest and migration.

Paeoniflorin improves functional recovery through repressing neuroinflammation and facilitating neurogenesis in rat stroke model.

BACKGROUND: Microglia, neuron, and vascular cells constitute a dynamic functional neurovascular unit, which exerts the crucial role in functional recovery after ischemic stroke. Paeoniflorin, the principal active component of Paeoniae Radix, has been verified to exhibit neuroprotective roles in cerebralischemic injury. However, the mechanisms underlying the regulatory function of Paeoniflorin on neurovascular unit after cerebral ischemia are still unclear. METHODS: In this study, adult male rats were treated with Paeoniflorin following transient middle cerebral artery occlusion (tMCAO), and then the functional behavioral tests (Foot-fault test and modified improved neurological function score, mNSS), microglial activation, neurogenesis and vasculogenesis were assessed. RESULTS: The current study showed that Paeoniflorin treatment exhibited a sensorimotor functional recovery as suggested via the Foot-fault test and the enhancement of spatial learning as suggested by the mNSS in rat stroke model. Paeoniflorin treatment repressed microglial cell proliferation and thus resulted in a significant decrease in proinflammatory cytokines IL-1ß, IL-6 and TNF-α. Compared with control, Paeoniflorin administration facilitated von Willebrand factor (an endothelia cell marker) and doublecortin (a neuroblasts marker) expression, indicating that Paeoniflorin contributed to neurogenesis and vasculogenesis in rat stroke model. Mechanistically, we verified that Paeoniflorin repressed JNK and NF-κB signaling activation. CONCLUSIONS: These results demonstrate that Paeoniflorin represses neuroinflammation and facilitates neurogenesis in rat stroke model and might be a potential drug for the therapy of ischemic stroke.

Research progress on the mechanism of orexin in pain regulation in different brain regions.

Orexin is a neuropeptide that is primarily synthesized and secreted by the lateral hypothalamus (LH) and includes two substances derived from the same precursor (orexin A [OXA] and orexin B [OXB]). Studies have shown that orexin is not only involved in the regulation of eating, the sleep-wake cycle, and energy metabolism, but also closely associated with various physiological functions, such as cardiovascular control, reproduction, stress, reward, addiction, and the modulation of pain transmission. At present, studies that have been performed both domestically and abroad have confirmed that orexin and its receptors are closely associated with pain regulation. In this article, the research progress on acute pain regulation involving orexin is reviewed.

Recent Advances in Immune Cell Therapy for Glioblastoma.

Glioblastoma (GBM) is the most malignant form of astrocytoma with short survival and a high recurrence rate and remains a global problem. Currently, surgery, chemotherapy, radiotherapy, and other comprehensive treatments are the main treatment modalities, but patients still have a poor prognosis mainly due to the infiltrative growth of GBM and the protective effect of the blood-brain barrier on tumor cells. Therefore, immunotherapy is expected to be a good option for GBM. In the immune system, different cells play varying roles in the treatment of GBM, so understanding the roles played by various immune cells in treating GBM and considering how to combine these effects to maximize the efficacy of these cells is important for the selection of comprehensive and optimal treatment plans and improving GBM prognosis. Therefore, this study reviews the latest research progress on the role of various types of immune cells in the treatment of GBM.

Ubiquitination of IGF2BP3 by E3 ligase MKRN2 regulates the proliferation and migration of human neuroblastoma SHSY5Y cells.

Neuroblastoma (NB) is a paediatric tumour that shows great biomolecule and clinical heterogeneity, and patients with NB often develop various neurological complications. Currently, the disease is mainly treated by surgery and still lacks specific therapeutic drugs; therefore, targets are urgently needed. Makorin ring finger protein 2 (MKRN2) is an E3 ligase whose effects on neuroblastoma have not been illustrated. shRNAs for MKRN2 have been designed, and MKRN2-knockdown human neuroblastoma SHSY5Y cells were established. MKRN2 knockdown promotes the proliferation and migration of SHSY5Y cells. Because MKRN2 is an E3 ligase, we performed a series of experiments, and Insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) was identified as a new substrate for MKRN2. IGF2BP3 is an RNA-binding protein that regulates the stability of many mRNAs, including CD44 and PDPN, and our study demonstrated that MKRN2 regulates the expression of CD44 and PDPN in an IGF2BP3-dependent manner. These results suggest that MKRN2 might be a potential therapeutic target for neuroblastoma.

Risk Factors for Emergence Agitation in Adults Undergoing Thoracoscopic Lung Surgery: A Case-Control Study of 1,950 Patients.

OBJECTIVE: The present study investigated the incidence of and risk factors for emergence agitation (EA) in adult patients after thoracoscopic lung surgery. DESIGN: A retrospective case-control study. SETTING: Single-center university hospital. PARTICIPANTS: The study comprised 1,950 adult patients who underwent elective lung surgery from January to December 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preoperative, surgical, and anesthesia-related data were collected. EA was assessed with the Riker Sedation-Agitation Scale and defined as a Riker score ≥5. Univariate analyses and multivariate logistic regression analysis were used to identify risk factors for EA. The incidence of EA was 14.1%. The results of the multivariate analysis showed that male sex (odds ratio [OR] 1.877, 95% confidence interval [CI] 1.341-2.627), age ≥65 years (OR 1.424, 95% CI 1.074-1.889), body mass index ≥24 kg/m2 (OR 1.409, 95% CI 1.070-1.856), American Society of Anesthesiologists physical status Ⅲ or Ⅳ (OR 2.654, 95% CI 1.189-5.924), cigarette smoking (OR 1.553, 95% CI 1.108-2.177), duration of surgery (OR 1.006, 95% CI 1.003-1.009), intraoperative tachycardia (OR 1.721, 95% CI 1.058-2.802), intraoperative hypotension (OR 1.636, 95% CI 1.064-2.514), intraoperative hypertension (OR 1.608; 95% CI 1.056-2.448), and rescue analgesia (OR 1.810, 95% CI 1.235-2.653) were independent risk factors for EA. However, wound infiltration (OR 0.679, 95% CI 0.507-0.908) and the use of dexmedetomidine (OR 0.663, 95% CI 0.490-0.869) appeared to be protective factors against EA. CONCLUSION: EA is a common complication after thoracoscopic lung surgery, especially within a certain population. Adequate perioperative management, which comprises wound infiltration, the maintenance of intraoperative hemodynamic stability, sufficient analgesia, and the use of dexmedetomidine, should be adopted to reduce the incidence of EA.

The effects of emission trading system on corporate innovation and productivity-empirical evidence from China's SO2 emission trading system.

Emission trading system is a significant market-based environmental regulation tool worldwide. This study fills existing knowledge gap on whether ETSs have "weak" and "strong" version of Porter hypothesis effects in China, by examining the effects of the Chinese SO2 emission trading on corporate innovation and productivity. Using the micro-data of domestic-listed manufacturing companies from 2004 to 2015, this study regarded China's SO2 emission trading system as a quasi-natural experiment by applying a difference-in-difference framework to eliminate endogenous problems. It was found that the SO2 emission trading system significantly promoted corporate innovation but did not have a significant effect on corporate productivity. The cause analysis showed that suboptimal institutional context and lack of corporate dynamic response led to the failure of strong Porter hypothesis effect. In addition, small- and medium-sized enterprises and non-state-owned enterprises gained greater innovation compensation effects of the emission trading system. This research believed that, the design, institutional context, and market incentives of emission trading systems need to be improved from the top down, to achieve the dual goal of environmental sustainability and economic growth.

Electroacupuncture Pretreatment Alleviates Cerebral Ischemia-Reperfusion Injury by Increasing GSK-3ß Phosphorylation Level via Adenosine A1 Receptor.

OBJECTIVE: To observe the effect of adenosine A1 receptor in the hippocampus of mice on GSK-3ß phosphorylation level and elucidate the underlying mechanisms of electroacupuncture pretreatment by activating Α1 receptor mediating cerebral ischemia-reperfusion injury. METHOD: The model of middle cerebral artery occlusion (MCAO) was established and grouped into electroacupuncture pretreatment group (EA group), MCAO group, and sham-operated group (Sham group). The neurobehavioral manifestation, the volume of cerebral infarction, and its related protein changes in mice in each group were observed. Then, adenosine Α1 receptor antagonist and agonist were injected intraperitoneally to observe the effects of A1 receptor on the phosphorylation level of GSK-3ß phosphorylation level and elucidate the underlying mechanisms of electroacupuncture pretreatment by activating Α1 receptor mediating cerebral ischemia-reperfusion injury. RESULTS: (1) Compared with the MCAO group (24 hours after reperfusion), the infarct size in the EA group decreased significantly, and the Garcia neurological score and phosphorylation level of GSK-3ß phosphorylation level and elucidate the underlying mechanisms of electroacupuncture pretreatment by activating Α1 receptor mediating cerebral ischemia-reperfusion injury. ß phosphorylation level and elucidate the underlying mechanisms of electroacupuncture pretreatment by activating Α1 receptor mediating cerebral ischemia-reperfusion injury. ß phosphorylation level and elucidate the underlying mechanisms of electroacupuncture pretreatment by activating Α1 receptor mediating cerebral ischemia-reperfusion injury. CONCLUSIONS: Electroacupuncture pretreatment can increase GSK-3ß phosphorylation level via activating A1 receptor, to protect neurons in ischemia-reperfusion injury.ß phosphorylation level and elucidate the underlying mechanisms of electroacupuncture pretreatment by activating Α1 receptor mediating cerebral ischemia-reperfusion injury.

JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke.

C-Jun N-terminal kinase (JNK) is a pivotal MAPK (mitogen-activated protein kinase), which activated by ischemia brain injury and plays a fairly crucial function in cerebral ischemic injury. Emerging studies demonstrated that JNK-IN-8 (a JNK inhibitor with high specificity) regulates traumatic brain injury through controlling neuronal apoptosis and inflammation. However, the function of JNK-IN-8 in ischemic stroke and the mechanisms underlying of JNK-IN-8 about neuroprotection are not well understood. In this work, male rats were treated with JNK-IN-8 after transient middle cerebral artery occlusion, and then the modified improved neurological function score (mNSS), the foot-fault test (FFT), interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) levels were assessed. We found that JNK-IN-8-treated rats with MCAO exerted an observable melioration in space learning as tested by the improved mNSS, and showed sensorimotor functional recovery as measured by the FFT. JNK-IN-8 also played anti-inflammatory roles as indicated through decreased activation of microglia and decreased IL-6, IL-1ß, and TNF-α expression. Furthermore, JNK-IN-8 suppressed the activation of JNK and nuclear factor-κB (NF-κB) signaling as indicated by the decreased level of phosphorylated-JNK and p65. All data demonstrate that JNK-IN-8 inhibits neuroinflammation and improved neurological function by inhibiting JNK/NF-κB and is a promising agent for the prevention of ischemic brain injury.

Progress of Research on Exosomes in the Protection Against Ischemic Brain Injury.

Exosomes, as a type of extracellular vesicle (EV), are lipid bilayer vesicles 20-100 nm in diameter that can cross the blood-brain barrier. Exosomes are important transport vesicles in the human body that participate in many conduction pathways and play an important physiological role. Because of their high biocompatibility and low immunogenicity and toxicity, exosomes have attracted increasing attention as an attractive drug delivery system. This article reviews the relevant studies that have shown that exosomes play an important role in protective mechanisms against ischemic brain injury.