Abstract Background Although vitamin D deficiency has been linked to adverse outcomes in critically ill patients, its impact on sepsis-related short- and long-term complications, particularly skeletal sequelae, remains poorly understood. This study aimed to investigate the long-term bone metabolism outcomes in patients with sepsis and its association between vitamin D status. Methods A retrospective baseline data collection and two prospective cohort analyses (with 5-year follow-ups) were conducted using data from 400 adults (18–70 years) admitted to the ICU (2008–2018) at the First Affiliated Hospital of Xi’an Jiaotong University in China. We first compared septic patients and non-septic patients, observing the relationship between sepsis and vitamin D levels. Next, we identified the long-term outcomes (osteoporosis) of patients after sepsis. Additionally, patients with sepsis were stratified into two cohorts based on baseline vitamin D levels. The outcomes in this cohort included all-cause 60-day mortality, and bone loss (osteoporosis). We conducted a statistical analysis using a 1:1 propensity score matching (PSM) to adjust for potential confounding variables. Results A total of 400 patients were included in the study, of whom 214 were diagnosed with sepsis. Patients with sepsis were more likely to have lower serum 25(OH)D levels than non-sepsis subjects (12.6 ± 7.5 vs. 15.5 ± 7.7 ng/mL, P = 0.01). In assessing long-term outcomes, sepsis patients reflected a higher risk of developing osteoporosis than non-sepsis patients (62.2% vs. 16.6%, P = 0.01). Lower vitamin D levels after sepsis were also associated with a higher incidence of osteoporosis (P < 0.01). Conclusions Vitamin D deficiency was a common finding during sepsis. In terms of long-term outcomes, the incidence of osteoporosis within 5 years of hospitalization was higher in sepsis patients, especially in patients with lower Vitamin D levels.

Ethnopharmacological relevance: Ischemic stroke (IS) is a major cause of mortality. Inflammation exerts an essential part of brain-heart communication after IS. Naoxintong capsule (NXT), derived from the classical Traditional Chinese Medicine (TCM) formulation Bu-Yang-Huan-Wu-Tang, are extensively employed in China to manage IS, myocardial infarction (MI), and atherosclerosis. Previous clinical studies have demonstrated the protective effects of NXT in anti-atherosclerosis, cerebral infarction, angina, and acute coronary syndrome. However, the potential therapeutic mechanism of NXT for IS remains unknown. Aim of the study: This study aims to investigate a potential mechanism for enhancing brain-heart interaction following an ischemic stroke. Materials and methods: C57BL/6J mice underwent permanent middle cerebral artery occlusion (MCAO) for durations of 6, 12, and 24 h. The effects of NXT on the brain were observed via TTC, Nissl and TUNEL staining, immunofluorescence staining, and Zea-Longa scores. Simultaneously, the effects of NXT on the heart were evaluated via H&E staining and echocardiography. Inflammatory factors in heart and serum were determined via ELISA orluminex liquid suspension chip detection. Network pharmacology predicted the targets and signaling pathways of NXT. The binding affinity between potential targets and active compounds of NXT was assessed through molecular docking. The expression levels of I kappa B alpha, IKK(3, NF-kappa B, NLRP3, and caspase-1 were evaluated via Western blotting. Results: The Zea-Longa scores, infarct rate, and the rate of apoptosis in the brain at 6, 12, and 24 h of MCAO mice were markedly decreased by NXT. Additionally, they clearly enhanced the NeuN positive rate and prevented microglia from activating at 24 h. NXT significantly reduced the level of myocardial injury biomarkers (Lactate

Ethnopharmacological relevance: Ischemic stroke (IS) is a leading cause of long-term disability and mortality worldwide. The Chinese Pharmacopeia 2020 lists Naoxintong Capsule (NXT), a traditional Chinese medicine prescription, as having demonstrated substantial therapeutic efficacy for IS. Aim of the study: Our study aimed to evaluate the mechanism by which NXT treats IS by integrating the microbiome, transcriptome, and metabolomics. Materials and methods: In a middle cerebral artery occlusion (MCAO) mouse model, the infarction rate, neurological scores, lipopolysaccharide (LPS) levels, inflammatory factor levels (IL-1(3, IL-17A, and IL-6), and intestinal permeability proteins (ZO-1, MUC2, and MUC4) were measured to confirm the effect of NXT on the brain and colon. 16S rRNA sequencing, transcriptomics analysis, and targeted amino acid (AA) metabolism were employed to evaluate the mechanism by which NXT treats IS. Furthermore, the neuroprotective effects of specific AAs, identified through targeted AA metabolism, were assessed in PC12 cells following oxygen-glucose deprivation (OGD) injury. In addition, the TLR4/NF-kappa B pathway was evaluated by Western blot (WB). Results: NXT administration substantially alleviated brain damage and colon injury by decreasing the infarction rate, neurological scores, LPS levels, and inflammatory factors, and increasing the expression of intestinal permeability protein. Transcriptomic analysis revealed that NXT regulated "inflammatory response," "Toll-like receptor signaling pathway,", and "NF-kappa B signaling pathway." Furthermore, WB confirmed that NXT inhibited the brain TLR4/NF-kappa B pathway. 16S rRNA sequencing indicated that NXT adjusted the intestinal microbiota composition and decreased the abundance of pathogenic bacteria, including Parasutterella_massiliensis and Ihubacter_excrementihominis. Targeted AA metabolism analysis demonstrated that NXT regulated the serum levels of serine, lysine, and proline in MCAO mice. Furthermore, serine, lysine, and proline inhibited the TLR4/NF-kappa B pathway to protect against OGD injury in PC12 cells. Conclusion: Our study indicates that NXT reduces the abundance of Parasutterella_massiliensis and Ihubacter_excrementihominis, while increasing the levels of serine, lysine, and proline. These changes are significantly associated with neuroinflammation. Furthermore, NXT alleviates IS-induced neuroinflammation by inhibiting the TLR4/NF-kappa B pathway. Importantly, our study provides novel insights into the mechanisms underlying NXT's therapeutic effects on IS.

Studying how single nucleotide polymorphisms (SNPs) crosstalk with non-autologous factors to cause complex autoimmune diseases is challenging. An amino acid replacement in the neutrophil cytosolic factor 1 (NCF1-339/NCF1R90H) leading to lower reactive oxygen species induction has been reported as the major SNP for systemic lupus erythematosus (SLE). Here we show that infection with the murine norovirus (MNV) contributes to the induction of lupus in Ncf190H mice. Mutant NCF190H upregulates the IFN-α/JAK1/STAT1 pathway in macrophages and anti-MNV-antibody production. In parallel, the MNV infection of NCF190H mice upregulates Toll-like receptor 7 in macrophages, plasmacytoid dendritic cells and B220+ splenocytes, thereby promoting germinal center formation and lupus-associated autoantibodies production. These compounded effects lead to protection against MNV infection but also glomeruloneph ritis with proteinuria and lupus arthritis in the absence of chemical inducers such as pristane. Our data thus suggest that this SLE-associated SNP, NCF190H, synergizes with MNV infection to induce the development of mouse lupus.

Endogenous endorphin (EETs) accumulation plays a neuroprotective role after cerebral ischemia-reperfusion injury, but the regulatory mechanism of its degradation remains unclear. With the deepening understanding of the role of sEH proteinin the metabolism of EETs, it has been suggested that depletion of sEH protein (encoded by EPHX2 gene) macromolecules may reduce the degradation of EETs, which is of great significance for improving cerebral ischemic injury. In this paper, we used CRISPR/Cas9 technique to construct EPHX2 gene knockout rat model and evaluate its role in MCAO. Primary microglia were isolated and transfected, cell viability analysis, ELISA, qPCR and immunohistochemistry were performed to systematically evaluate the effects of sEH on EETs degradation, neural function and inflammatory response. It was found that sEH depletion significantly alleviated the pathological changes and reduced the degradation of EETs in MCAO rats. Antagonistic EETs could reverse the neuroprotective effects of sEH depletion. Further analysis showed that sEH depletion inhibited the inflammatory response by regulating the phenotypic transition of microglia. Specific mechanisms include inhibition of IFN-γ-induced microglial inflammatory responses via EETs and inhibition of p-p38/NF-κB signaling pathways. Studies have revealed that sEH protein is a key regulator of EETs degradation, and sEH protein macromolecule depletion can effectively reduce the metabolic degradation of EETs, thereby alleviating cerebral ischemic injury and relieving inflammation.

Aldosterone-producing adenoma is a subtype of primary aldosteronism. Recent advancements in multi-omics research have led to significant progress in understanding primary aldosteronism at the genetic level. Among the various genes associated with the development of aldosterone-producing adenomas, the KCNJ5 (potassium inwardly rectifying channel, subfamily J, member 5) gene has received considerable attention due to its prevalence as the most common somatic mutation gene in primary aldosteronism. This paper aims to integrate the existing evidence on the involvement of KCNJ5 gene in the pathogenesis of aldosterone-producing adenomas, to enhance the understanding of the underlying mechanisms of aldosterone-producing adenomas from the perspective of genetics, and to provide novel insights for the clinical diagnosis and treatment of aldosterone-producing adenomas.

RNA imaging in live cells can provide comprehensive information on the expression, localization, degradation, storage, and regulation of RNA in cells, which is crucial for basic biology and clinical research. Our previous research finds that slicing the facilitated crRNA in the typical CRISPR/Cas12a system at a fitted site did not affect its trans-cleavage activity, which was previously reported to be triggered by targeted ssDNA or dsDNA, and a mini crRNA-mediated CRISPR/Cas12a (MCM-CRISPR/Cas12a) system was proposed. Here, we further apply it to enhanced imaging of MicroRNAs in cells by designing the activator in the system as a molecular beacon (MB), which can form a hybrid double-stranded structure of DNA/RNA with the targeted MicroRNA. When targeted MicroRNA is present, the hairpin structure of the MB is opened and the system emits fluorescence. Simultaneously, the DNA-RNA formed by the targeted MicroRNA and MB activates the trans-cleavage activity of LbCas12a, partially cleaving the single-stranded DNA extended from the MB and further enhancing the fluorescence intensity of the system. We designed the MCM-CRISPR/Cas12a system for miRNA-21, miRNA-155, and miRNA-10b and successfully applied it for sensitive and specific imaging of these MicroRNAs both inside and outside cells. This study provides a new idea for the sensitive and specific imaging of multiple MicroRNAs within cells, which is important for studying the distribution and dynamic changes of MicroRNAs in cells.

The microbiome-gut-brain axis plays a crucial role in many neurological diseases, including mild cognitive impairment. Sleep deprivation (SD) induces cognitive decline accompanied by alterations in the gut microbiota. However, the role of gut microbiota alterations in SD-induced cognitive dysfunction and the underlying mechanisms remain unclear. Here, we found that dysbiosis of the gut microbiota following pretreatment with broad-spectrum antibiotics worsens SD-induced cognitive impairment in mice. Fecal microbiota transplantation from SD mice to healthy mice induced cognitive impairment. Additionally, the abundance of Akkermansia muciniphila (A. muciniphila) in the mouse gut microbiota was significantly reduced after 7 days of SD. A. muciniphila pretreatment alleviated cognitive dysfunction and prevented synaptic reduction in the hippocampus in SD mice. A. muciniphila pretreatment inhibited extensive microglial activation and synaptic engulfment in the hippocampus of SD mice. Metabolomics analysis revealed that A. muciniphila pretreatment increased the serum acetate and butanoic acid levels in SD mice. Finally, pretreatment with short-chain fatty acids (SCFAs) inhibited microglial synaptic engulfment and prevented neuronal synaptic loss in SD mice and primary microglia-neuron co-culture following LPS stimulation. Together, our findings illustrate that gut dysbiosis plays an essential role in SD-induced cognitive impairment by activating microglial engulfment at synapses. A. muciniphila supplementation may be a novel preventative strategy for SD-induced cognitive dysfunction, by increasing SCFAs production and maintaining microglial homeostasis.

Solasonine (SS), the main active ingredient of Solanum nigrum L., has been reported to possess a variety of pharmacological properties. A recent study demonstrated a neuroprotective effect of SS in a mouse nerve injury model. However, its protective effects on cerebral ischemia/reperfusion injury (CIRI) remain to be elucidated. We investigated herein the in vitro and in vivo neuroprotective effects of SS. Primary hippocampal neurons were exposed to oxygen and glucose deprivation/reoxygenation (OGD/R) to construct an in vitro model while rats were treated with middle cerebral artery occlusion/reperfusion (MCAO/R) to establish an in vivo CIRI model. The results showed that SS reduced OGD/R-induced inflammatory responses of neurons by blocking secretion of TNF & alpha;, IL-1 & beta; and IL-6. Moreover, SS ameliorated OGD/R-induced oxidative stress in neurons by decreasing the level of ROS and MDA and increasing the activity of SOD and GPx. We also found that SS protected neurons from OGD/Rinduced apoptosis by down-regulating bax and cleaved caspase-3 and up-regulating bcl-2. The in vivo results revealed that SS administration reduced the infarct volume and alleviated the neurological deficit of MCAO/R rats as well as diminished neuronal damages in these rats. Our investigation on the underlying mechanisms indicated that the neuroprotective effect of SS on CIRI may be associated with the TLR4/MyD88/NF-& kappa;B and AMPK/Nrf2/HO-1 pathways. Taken together, these findings demonstrate that SS ameliorates CIRI via suppressing TLR4/MyD88/NF-& kappa;B pathway and activating AMPK/Nrf2/HO-1 pathway.

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine and metabolic disorder that is closely associated with the proliferation and apoptosis of ovarian granulosa cells (GCs). Ampelopsis japonica (AJ) is the dried tuberous root of Ampelopsis japonica (Thunb.) Makino (A. japonica), with anti-inflammatory, antioxidant, antibacterial, antiviral, wound-healing, and antitumor properties; however, it is unclear whether this herb has a therapeutic effect on PCOS. Therefore, this study aimed to investigate the pharmacological effect of AJ on PCOS and reveal its potential mechanism of action. A PCOS rat model was established using letrozole. After establishing the PCOS model, the rats received oral treatment of AJ and Diane-35 (Positive drug: ethinylestradiol + cyproterone tablets) for 2 weeks. Lipidomics was conducted using liquid-phase mass spectrometry and chromatography. AJ significantly regulated serum hormone levels and attenuated pathological variants in the ovaries of rats with PCOS. Furthermore, AJ significantly reduced the apoptotic rate of ovarian GCs. Lipidomic analysis revealed that AJ modulated glycerolipid and glycerophospholipid metabolic pathways mediated by lipoprotein lipase (Lpl), diacylglycerol choline phosphotransferase (Chpt1), and choline/ethanolamine phosphotransferase (Cept1). Therefore, we established that AJ may reduce ovarian GC apoptosis by modulating lipid metabolism, ultimately improving ovulatory dysfunction in PCOS. Therefore, AJ is a novel candidate for PCOS treatment.

Fracture in acute stage of ischemic stroke can increase inflammatory response and enhance stroke injury. Loganin alleviates the symptoms of many inflammatory diseases through its anti-inflammatory effect, but its role in ischemic stroke and fracture remains to be explored. Here, mice were handled with permanent middle cerebral artery occlusion (pMCAO) followed by tibial fracture 1 day later to establish a pMCAO+fracture model. Loganin or Methyllycaconitine (MLA, a specific a7nAchR inhibitor) were intragastrically administered 2 or 0.5 h before pMCAO, respectively. And mouse motor function and infarct volume were evaluated 3 days after pMCAO. We found that loganin alleviated the neurological deficit, cerebral infarction volume, and neuronal apoptosis (NeuN+ TUNEL+ ) in mice with pMCAO+fracture. And loganin suppressed pMCAO+fracture-induced neuroinflammation by promoting M2 microglia polarization (Iba1+ CD206+ ) and inhibiting M1 microglia polarization (Iba1+ CD11b+ ). While administration with MLA reversed the protective effect of loganin on pMCAO+fracture-induced neurological deficit and neuroinflammation. Next, LPS was used to stimulate BV2 microglia to simulate pMCAO+fracture-induced inflammatory microenvironment in vitro. Loganin facilitated the transformation of LPS-stimulated BV2 cells from M1 pro-inflammatory state (CD11b+ ) to M2 anti-inflammatory state (CD206+ ), which was antagonized by treatment with MLA. And loganin induced autophagy activation in LPS-stimulated BV2 cells by activating a7nAchR. Moreover, treatment with rapamycin (an autophagy activator) neutralized the inhibitory effect of MLA on loganin induced transformation of BV2 cells to M2 phenotype. Furthermore, BV2 cells were treated with LPS, LPS + loganin, LPS + loganin+MLA, or LPS + loganin+MLA+ rapamycin to obtain conditioned medium (CM) for stimulating primary neurons. Loganin reduced the damage of primary neurons caused by LPS-stimulated BV2 microglia through activating a7nAchR and inducing autophagy activation. In conclusion, loganin played anti-inflammatory and neuroprotective roles in pMCAO + fracture mice by activating a7nAchR, enhancing autophagy and promoting M2 polarization of microglia.

BackgroundSerum exosomes play important roles in intercellular communication and are promising biomarkers of several autoimmune diseases. However, the biological functions and potential clinical importance of long non-coding RNAs (lncRNAs) and mRNAs from serum exosomes in rheumatoid arthritis (RA) have not yet been studied.MethodsSerum exosomal lncRNAs and mRNAs were isolated from patients with RA and osteoarthritis (OA) and healthy controls. The differentially expressed lncRNAs (DE-lncRNAs) and mRNA profiles in the serum exosomes of patients with RA were analysed using high-throughput sequencing, and their functions were predicted using Gene Ontologyenrichment, Kyoto Encyclopedia of Genes and Genomes pathway, and gene set enrichment analysis. We constructed a DE-lncRNA-mRNA network and a protein-protein interaction network of differentially expressed mRNAs (DE-mRNAs) in RA using the Cytoscape software. The expression of several candidate a DE-lncRNAs and DE-mRNAs in the serum of patients with RA, patients with OA, and healthy controls was confirmed by qRT-PCR. We assessed the diagnostic ability of DE-lncRNAs and DE-mRNAs in patients with RA using receiver operating characteristic analysis. Furthermore, we analysed the characteristics of immune cell infiltration in RA by digital cytometry using the CIBERSORT algorithm and determined the correlation between immune cells and several DE-lncRNAs or DE-mRNAs in RA.ResultsThe profiles of serum exosomal lncRNAs and mRNAs in patients with RA were different from those in healthy controls and patients with OA. The functions of both DE-lncRNAs and DE-mRNAs in RA are associated with the immune response and cellular metabolic processes. The RT-PCR results show that NONHSAT193357.1, CCL5, and MPIG6B were downregulated in patients with RA. The combination of three DE-mRNAs, CCL5, MPIG6B, and PFKP, had an area under the curve of 0.845 for differentiating RA from OA. Digital cytometry using the CIBERSORT algorithm showed that the neutrophil counts were higher in patients with RA than those in healthy controls and patients with OA.ConclusionsThese findings help to elucidate the role of serum exosomal lncRNAs and mRNAs in the specific mechanisms underlying RA.

Sleep loss is commonplace nowadays and profoundly impacts cognition. Dopamine receptor D2 (DRD2) makes a specific contribution to cognition, although the precise mechanism underlying how DRD2 affects the cognitive process after sleep deprivation remains unclear. Herein, we observed cognitive impairment and impaired synaptic plasticity, including downregulation of synaptophysin and PSD95, decreased postsynaptic density thickness, neuron complexity, and spine density in chronic sleep restriction (CSR) mice. We also observed downregulated hippocampal DRD2 and Cryab expression in the CSR mice. Meanwhile, NF-κB translocation from the cytoplasm to the nucleus occurred, indicating that neuroinflammation ensued. However, hippocampal delivery of the DRD2 agonist quinpirole effectively rescued these changes. In vitro, quinpirole treatment significantly decreased the release of proinflammatory cytokines in microglial supernatant, indicating a potential anti-neuroinflammatory effect of Drd2/Cryab/NF-κB in CSR mice. Our study provided the evidence that activation of the Drd2 may relieve neuroinflammation and improve sleep deprivation-induced cognitive deficits.

Aims: NCF1, a subunit of the NADPH oxidase 2 (NOX2), first described the expression in neutrophils and macrophages and participated in the pathogenesis from various systems. However, there are controversial findings on the role of NCF1 in different kinds of kidney diseases. In this study, we aim to pinpoint the specific role of NCF1 in the progression of renal fibrosis induced by obstruction. Results: In this study, NCF1 expression was upregulated in kidney biopsies of chronic kidney disease patients. The expression level of all subunits of the NOX2 complex was also significantly increased in the unilateral ureteral obstruction (UUO) kidney. Then, we used wild-type mice and Ncf1 mutant mice (Ncf1m1j mice) to perform UUO-induced renal fibrosis. Results demonstrated that Ncf1m1j mice exhibited mild renal fibrosis but increased macrophages count and CD11b+Ly6Chi macrophage proportion. Next, we compared the renal fibrosis degree between Ncf1m1j mice and Ncf1 macrophage-rescued mice (Ncf1m1j.Ncf1Tg-CD68 mice). We found that rescuing NCF1 expression in macrophages further alleviated renal fibrosis and decreased macrophage infiltration in the UUO kidney. In addition, flow cytometry data showed fewer CD11b+Ly6Chi macrophages in the kidney of the Ncf1m1j.Ncf1Tg-CD68 group than the Ncf1m1j group. Innovation: We first used the Ncf1m1j mice and Ncf1m1j.Ncf1Tg-CD68 mice to detect the role of NCF1 in the pathological process of renal fibrosis induced by obstruction. Also, we found that NCF1 expressed in different cell types exerts opposing effects on obstructive nephropathy. Conclusion: Taken together, our findings support that systemic mutation of Ncf1 ameliorates renal fibrosis induced by obstruction, and rescuing NCF1 in macrophages further alleviates renal fibrosis.

Type 2 diabetes mellitus (T2DM) is characterized by chronic low-grade systemic inflammation. Tissue infiltration by monocyte migration contributes to the pathogenesis of vascular complications in T2DM. We studied the role of intermediate-conductance Ca2+-activated K+ (KCa3.1) channels in the palmitic acid (PA)-induced migration of peripheral blood mononuclear cells (PBMCs) from T2DM patients and the influence of advanced glycation endproducts (AGEs). A total of 49 T2DM patients and 33 healthy subjects was recruited into this study. Using flow cytometry and Western blotting analysis as well as cell migration assay, we found that there was a significant decrease in frequency of T lymphocytes and monocytes in CD45+ leukocyte population. PA at 100 μM stimulated migration of PBMCs from T2DM individuals, which was inhibited by the specific KCa3.1 channel blocker TRAM-34 (1 μM). The PBMC migration was positively correlated with glycosylated hemoglobin A1 chain (HbA1c) level of T2DM patients, an indicator of AGEs, and PBMCs with higher level of HbA1c showed upregulated expression of toll-like receptor (TLR) 2/4 and KCa3.1 channels. In THP-1 cells, AGEs at 200 μg/ml increased protein expression of TLR 2/4 and KCa3.1 channels, and were synergistically involved in PA-induced migration through receptors of AGEs (RAGE)-mediated KCa3.1 upregulation. In conclusion, in PBMCs of T2DM patients, AGEs promotes PA-induced migration via upregulation of TLR2/4 and KCa3.1 channels.

Allergic asthma is a common chronic inflammation of the airways and causes airway remodeling eventually. For a long time, investigators have been focusing on the immunological mechanism of asthma. However, in recent years, the role of neuro-regulation in the occurrence of asthma has gradually attracted investigators’ attention. In this review, we firstly describe neuro-immune regulation in inflammation of allergic asthma from two aspects: innate immunity and adaptive immunity. Secondly, we introduce neuro-immune regulation in airway remodeling of asthma. Finally, we prospect the role of pulmonary neuroendocrine cells in the development of asthma. In general, the amount of researches is limited. Further researches on the neural regulation during the occurrence of asthma will help us clarify the mechanism of asthma more comprehensively and find more effective ways to prevent and control asthma.

本文以微博平台中的明星超级话题为观察场域,聚焦其中的粉丝及所属圈群——"饭圈"的追星实践,勾勒和阐释饭圈内部的权力关系生成及权力运作过程.研究着重考察饭圈内部的大粉、产出粉和普通粉丝三种粉丝类型,研究以线上、线下民族志相结合为主要研究方法,得出以下结论:饭圈内部秩序的建构,是以牧领权力及其治理术为核心的权力关系实践;在饭圈的数字实践中,"袒露与服从"是实现情感满足、群体认同和数字生活"自我救赎"的前提;饭圈的运行机制成为数字牧领的显现,出现了再中心化、制度化和数字劳动异化的新型权力生产特征.

BackgroundPerilipin 5 (Plin5) acts as a pivotal mediator of oxidative stress and inflammation and is associated with the progression of relevant diseases. Cerebral ischemic stroke is a severe pathological condition that involves excess oxidative stress and inflammation. However, whether Plin5 plays a role in the progression of cerebral ischemic stroke remains unaddressed. This work focused on the investigation of Plin5 in oxygen-glucose deprivation/reoxygenation (OGD/R)-injured neurons, an in vitro model for studying cerebral ischemic stroke.MethodsThe primary neuronal cells were isolated from the hippocampus of newborn mice. Neurons were subjected to OGD/R treatment to establish an in vitro model for studying cerebral ischemic stroke. Neurons were infected with recombinant adenovirus expressing Plin5 to upregulate Plin5 expression. The mRNA levels were measured by real-time quantitative PCR (RT-qPCR). Protein levels were determined by immunoblotting. Cell viability was assessed via cell counting kit-8 (CCK-8) assay. Cell apoptosis was evaluated via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Annexin V-Allophycocyanin/7-Amino Actinomycin D (Annexin V-APC/7-AAD) apoptotic assays. Oxidative stress was monitored by dichlorofluorescein diacetate (DCFH-DA) probe. Inflammatory cytokine release was detected by enzyme-linked immunosorbent assay (ELISA).ResultsA decreased level of Plin5 was observed in neurons challenged with OGD/R. Plin5 overexpression remarkably subdued OGD/R-elicited apoptosis, oxidative stress and proinflammatory response. Plin5 overexpression led to an enhancement of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway associated with regulation of the Akt-glycogen synthase kinase-3β (GSK-3β). The blocking of Akt was able to reverse the enhancing effect of Plin5 on Nrf2 activation. The restraining of Akt or silencing of Nrf2 diminished the protective effects of Plin5 in OGD/R-injured neurons.ConclusionsPlin5 confers neuroprotection for neurons against OGD/R damage via effects on the Nrf2-Akt-GSK-3β pathway. This work indicates a possible role of Plin5 in cerebral ischemic stroke and the up-regulation of Plin5 is a sort of survival strategy for neurons suffering from ischemic injury.

文章探究在媒体融合的时代背景之下,我国媒体在内容生产过程中关注的版权问题,以及学术界对版权问题的关注、版权理论和实践.文章在梳理当前版权研究的议题与方向时发现,中国版权研究主要聚焦于制度建设、技术应用以及版权运营三个层面,并在数字化背景下进一步丰富了版权的内涵与外延,针对当前实践探索中存在的诸多问题提出法理层面的解决思路和措施,但总体上缺乏对版权商品化及其贸易背后权力关系运作等更深层面的探讨.