Seaweed has been used in traditional cosmetics and as a herbal medicine in treatments for cough,boils,goiters,stomach ailments,and urinary diseases,and for reducing the incidence of tumors,ulcers,and headaches.Despite...Seaweed has been used in traditional cosmetics and as a herbal medicine in treatments for cough,boils,goiters,stomach ailments,and urinary diseases,and for reducing the incidence of tumors,ulcers,and headaches.Despite the fact that seaweeds are frequently used in the practice of human health,little is known about the role of seaweed in the context of inflammation.This study aimed to investigate the influence of Jeju endemic seaweed on a mouse macrophage cell line(RAW 264.7) under the stimulation of lipopolysaccharide(LPS).Ethyl acetate extracts obtained from 14 different kinds of Jeju seaweeds were screened for inhibitory effects on pro-inflammatory mediators.Our results revealed that extracts from five seaweeds,Laurencia okamurae,Grateloupia elliptica,Sargassum thun-bergii,Gloiopeltis furcata,and Hizikia fusiformis,were potent inhibitors of the production of pro-inflammatory mediators such as nitric oxide(NO),prostaglandin E2(PGE2),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α).Based on these results,the anti-inflammatory effects and low cell toxicity of these seaweed extracts suggest potential thera-peutic applications in the regulation of the inflammatory response.展开更多
Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim...Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim to control the spread of neuroinflammation during the acute phase but later hinder axon regeneration in later stages.Recent studies have enhanced our understanding of immunomodulation,revealing that injury-associated inflammation involves various cell types and molecules with positive and negative effects.This review employs bibliometric analysis to examine the literature on inflammatory mediators in spinal cord injury,highlighting recent research and providing a comprehensive overview of the current state of research and the latest advances in studies on neuroinflammation related to spinal cord injury.We summarize the immune and inflammatory responses at different stages of spinal cord injury,offering crucial insights for future research.Additionally,we review repair strategies based on inflammatory mediators for the injured spinal cord.Finally,this review discusses the current status and future directions of translational research focused on immune-targeting strategies,including pharmaceuticals,biomedical engineering,and gene therapy.The development of a combined,precise,and multitemporal strategy for the repair of injured spinal cords represents a promising direction for future research.展开更多
Regulating the interfacial charge transfer is pivotal for elucidating the kinetics of engineering the interface between the light-harvesting semiconductor and the substrate/catalyst for photoelectrocatalytic water spl...Regulating the interfacial charge transfer is pivotal for elucidating the kinetics of engineering the interface between the light-harvesting semiconductor and the substrate/catalyst for photoelectrocatalytic water splitting.In this study,we constructed a superior Ti-doped hematite photoanode(TiFeO)by employing SnOx as an electron transfer mediator,partially oxidized graphene(pGO)as a hole transfer mediator,and molecular Co cubane as a water oxidation catalyst.The Co/pGO/TiFeO/SnO_(x)integrated system achieves a photocurrent density of 2.52 mA cm^(-2) at 1.23 VRHE,which is 2.4 times higher than bare photoanode(1.04 mA cm^(-2)),with operational stability up to 100 h.Kinetic measurements indicate that pGO can promote charge transfer from TiFeO to the Co cubane catalyst.In contrast,SnOx reduces charge recombination at the interface between TiFeO and the fluorinated tin oxide substrate.In-situ infrared spectroscopy shows the formation of an O–O bonded intermediate during water oxidation.This study highlights the crucial role of incorporating dual charge-transfer mediators into photoelectrodes for efficient solar energy conversion.展开更多
All-solid-state Li-S batteries(ASSLSBs)are more attractive owing to their achievable superior energy density at a reasonable cost and the solid electrolyte(SE)utilization mitigating the widely recognized polysulfide s...All-solid-state Li-S batteries(ASSLSBs)are more attractive owing to their achievable superior energy density at a reasonable cost and the solid electrolyte(SE)utilization mitigating the widely recognized polysulfide shuttle problem.While the volume expansion(~80%)that occurs during the initial transformation of sulfur to lithium sulfide induces mechanical stress,this can be avoided by using Li_(2)S as a cathode,which also permits the anode-free cell design.However,the high oxidation energy barrier of Li_(2)S cathode during the charging step limits its application in commercial devices.Redox mediators have been extensively used to reduce the oxidation energy barrier of Li_(2)S to the sulfur conversation and boost the reversible kinetics of the conversion reaction.In this review,we have summarized the available redox mediators for Li_(2)S cathode in ASSLSBs and its working mechanism.Moreover,we have proposed novel strategies and guidelines for designing effective redox mediators to boost the reversible conversion reaction.展开更多
While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the assoc...While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence.Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline,we employed structural equation modeling to assess the mediating effects of systolic(SBP)and diastolic(DBP)blood pressure.During the follow-up,2811 incident stroke cases were identified.A healthy lifestyle was significantly associated with a reduced risk of stroke,with SBP mediating 44.70%(β=-0.0014,95%confidence interval[CI]:-0.0016 to-0.0012)and DBP mediating 37.81%(β=-0.0012,95%CI:-0.0015 to-0.0009)of this association.The mediating effects were attenuated but remained significant for ischemic stroke(SBP:33.21%;DBP:27.24%).In conclusion,approximately two-fifths of the protective association between a healthy lifestyle and stroke may be mediated by BP.These findings suggest that BP control may serve as an important early indicator for evaluating the effectiveness of lifestyle interventions in reducing stroke risk.展开更多
Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabo...Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabolites mediating the associations ofα-diversity with blood pressure(BP)and BP variability(BPV).Methods Metagenomics and plasma targeted metabolomics were conducted on 523 Chinese participants from the MetaSalt study.The 24-hour,daytime,and nighttime BP and BPV were calculated based on ambulatory BP measurements.Linear mixed models were used to characterize the relationships betweenα-diversity(Shannon and Chao1 index)and BP indices.Mediation analyses were performed to assess the contribution of metabolites to the observed associations.The influence of key metabolites on hypertension was further evaluated in a prospective cohort of 2,169 participants.Results Gut microbial richness(Chao1)was negatively associated with 24-hour systolic BP,daytime systolic BP,daytime diastolic BP,24-hour systolic BPV,and nighttime systolic BPV(P<0.05).Moreover,26 metabolites were strongly associated with richness(Bonferroni P<0.05).Among them,four key metabolites(imidazole propionate,2-hydroxy-3-methylbutyric acid,homovanillic acid,and hydrocinnamic acid)mediated the associations between richness and BP indices(proportions of mediating effects:14.1%–67.4%).These key metabolites were also associated with hypertension in the prospective cohort.For example,each 1-standard deviation unit increase in hydrocinnamic acid significantly reduced the risk of prevalent(OR[95%CI]=0.90[0.82,0.99];P=0.03)and incident hypertension(HR[95%CI]=0.83[0.71,0.96];P=0.01).Conclusion Our results suggest that gut microbial richness correlates with lower BP and BPV,and that certain metabolites mediate these associations.These findings provide novel insights into the pathogenesis and prevention of hypertension.展开更多
BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, li...BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, liver, kidney and lung. Microcirculatory disturbance in AP has attracted widespread attention. In order to provide a theoretical basis for clinical therapy of AP, it is very important to explore the effect of inflammatory mediators on microcirculatory disturbance in this disease. DATA SOURCES: In this review, the impact of inflammatory mediators on microcirculatory disturbance in AP was reviewed according to the literature, especially the articles indexed in PubMed and books published in China and reports from websites. RESULTS: At present, inflammatory mediation and microcirculatory disturbance are the two major hypotheses to explain the development of AP. Although experimental studies have shown that inflammatory mediators induce or aggravate microcirculatory disturbance, the clinical application of these findings is still difficult because the inflammatory mediators are diverse and their research is not comprehensive and thorough. CONCLUSION: It is very important to explore the influence of inflammatory mediators on microcirculatory disturbance in AP.展开更多
Intracerebral hemorrhage （ICH） leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated tha...Intracerebral hemorrhage （ICH） leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage （ICH）. The results showed that fingolimod decreased the numbers of circulating CD4~ T, CD8~ T, CD19~ B, NK, and NKT cells and they recovered quickly after the drug＇ was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced rT1%. In conclusion, modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability.展开更多
OBJECTIVE: To investigate the influence of spleen deficiency on the epithelial barrier of jejunum and lungs in a rat model of spleen-deficiency and the effect and potential specialized pro-resolving mediators (SPMs) m...OBJECTIVE: To investigate the influence of spleen deficiency on the epithelial barrier of jejunum and lungs in a rat model of spleen-deficiency and the effect and potential specialized pro-resolving mediators (SPMs) mechanism of chiropractic manipulation. METHODS: Three-week-old male Sprague-Dawley rats were divided randomly into normal control group (n = 6), spleen-deficiency group (n = 5) and chiropractic group (n = 6). Spleen-deficiency model was induced in spleen-deficiency group and chiropractic group. Moreover, chiropractic manipulation was performed in chiropractic group. Four weeks later, systemic Th1/Th2 balance was evaluated by the ratio of plasma interferon (IFN)-γ/interleukin (IL)-4 levels by enzyme-linked immunosorbent assay (ELISA). Epithelial barrier integrity were assessed by the observation of morphological changes by hematoxylin-eosin staining and zonula occludens (ZO)-1 gene expressions by quantitative real time polymerase chain reaction in jejunum and lungs. Plasma resolvin D1 (RvD1) and lipoxin A4 (LXA4) levels were measures by ELISA for endogenous SPMs production. The levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in jejunum and lungs were also measured by HPLC-MS/ MS. RESULTS: Comparing with normal control group, spleen-deficiency group showed disrupted mucosa in jejunum, inflammatory condition in lungs, significantly decreased ratio of plasma IFN-γ/IL-4 levels and lower expressions of ZO-1 mRNA in both jejunum and lung tissues. Comparing with spleen-deficiency group, chiropractic group had less disrupted mucosa in jejunum and inflammatory condition in lungs, significantly increased systemic ratio of IFN-γ/IL-4 and expressions of ZO-1 mRNA in both jejunum and lung tissues. Chiropractic group had significantly enhanced plasma levels of RvD1 and LXA4, but had no significantly higher levels of DHA and AA in jejunum and lungs when comparing with spleen-deficiency group. CONCLUSION: Spleen deficiency caused systemic Th1/Th2 imbalance towards Th2 polarization and epithelial barrier disruption in jejunum and lungs.Chiropractic manipulation helped enhance endogenous SPMs production, which might be one of the action mechanism of chiropractic manipulation on the improvement of epithelial barrier disruption.展开更多
AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and tre...AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality,ascite volumes,ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3,6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α),phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared,terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated. RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α,PLA2 and IL-6 in serum,ascite volumes,ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points P < 0.05,58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-α content,8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P < 0.01,0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content,7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content,1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio,8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001,3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content,4.50 (2.00) vs 7.20 (2.00),4.20 (1.60) vs 6.40 (2.30),3.40 (2.70) vs 7.90 (1.70) in ascite volumes,respectively. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h P < 0.01,0.00 (2.00)% vs 0.00 (0.00)%,0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes,respectively. CONCLUSION: The mechanism of dexamethasone treatment in acute pancreatitis is related to its inhibition of inflammatory mediator generation and induction of pancreatic acinar cell apoptosis.展开更多
OBJECTIVE: To investigate the effect of glucocorticoids on systemic inflammatory mediator release in rats with acute pancreatitis and the outcome of dexamethasone in treatment of acute pancreatitis. METHODS: Sixty-eig...OBJECTIVE: To investigate the effect of glucocorticoids on systemic inflammatory mediator release in rats with acute pancreatitis and the outcome of dexamethasone in treatment of acute pancreatitis. METHODS: Sixty-eight Wistar rats were divided into sham, acute pancreatitis, and treatment (intravenous dexamethasone 0.5 mg/kg) groups. Experimental acute pancreatitis was induced by the injection of 5% sodium taurocholate (0.1 ml/100 mg body weight) into the pancreatic-biliary duct. The bIood samples were obtained and examined for 6-keto-PGI_1α, TXB_2 and IL-6 postoperatively at 3,6 and 12 hours, respectively. The pancreatic samples were evaluated by a blinded method. Twelve-hour survival rate was determined and compared between the groups. RESULTS: The high serum concentrations of 6-keto-PGI_1α, TXB_2 and IL-6 were noted in the rats with acute pancreatitis associated with pancreatic hemorrhage and necrosis. Their 12-hour survival rate was 42.9%. The rats in the treatment group survived with significantly reduced serum concentrations of 6-keto-PGI_1α, TXB_2 and IL-6 (P<0.05). Their pancreatic morphology was normal. CONCLUSION: Dexamethasone may reduce the serum concentration of 6-keto-PGI_1α, TXB_2, and IL-6, and the severity of acute pancreatitis while increasing the survival rate of rats with acute pancreatitis.展开更多
Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation;however, the precise mechanisms remain un...Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation;however, the precise mechanisms remain unclear. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cell treatment on expression profiles of multiple cytokines in the brain after cardiac arrest and cardiopulmonary resuscitation. Cardiac arrest was induced in rats by asphyxia and cardiopulmonary resuscitation was initiated 6 minutes after cardiac arrest. One hour after successful cardiopulmonary resuscitation, rats were injected with either phosphate-buffered saline(control) or 1 × 10~6 bone marrow-derived mesenchymal stem cells via the tail vein. Serum S100 B levels were measured by enzyme-linked immunosorbent assay and neurological deficit scores were evaluated to assess brain damage at 3 days after cardiopulmonary resuscitation. Serum S100 B levels were remarkably decreased and neurological deficit scores were obviously improved in the mesenchymal stem cell group compared with the phosphate-buffered saline group. Brains were isolated from the rats and expression levels of 90 proteins were determined using a RayBio Rat Antibody Array, to investigate the cytokine profiles. Brain levels of the inflammatory mediators tumor necrosis factor-α, interferon-γ, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, macrophage inflammatory protein-3α, macrophage-derived chemokine, and matrix metalloproteinase-2 were decreased ≥ 1.5-fold, while levels of the anti-inflammatory factor interleukin-10 were increased ≥ 1.5-fold in the mesenchymal stem cell group compared with the control group. Donor mesenchymal stem cells were detected by immunofluorescence to determine their distribution in the damaged brain, and were primarily observed in the cerebral cortex. These results indicate that bone marrow-derived mesenchymal stem cell transplantation attenuates brain damage induced by cardiac arrest and cardiopulmonary resuscitation, possibly via regulation of inflammatory mediators. This experimental protocol was approved by the Institutional Animal Care and Use Committee of Fujian Medical University, China in January 2016(approval No. 2016079).展开更多
Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro...Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.展开更多
The development of efficient photocatalytic H2-evolution materials requires both rapid electron transfer and an effective interfacial catalysis reaction for H2 production. In addition to the well-known noble metals, l...The development of efficient photocatalytic H2-evolution materials requires both rapid electron transfer and an effective interfacial catalysis reaction for H2 production. In addition to the well-known noble metals, low-cost and earth-abundant non-noble metals can also act as electron- transfer mediators to modify photocatalysts. However, as almost all non-noble metals lack the interfacial catalytic active sites required for the H2-evolution reaction, the enhancement of the photocatalytic performance is limited. Therefore, the development of new interfacial active sites on metal-modified photocatalysts is of considerable importance. In this study, to enhance the photocatalytic evolution of H2 by Ni-modified TiO2, the formation of NiSx as interfacial active sites was promoted on the surface of Ni nanoparticles. Specifically, the co-modified TiO2/Ni-NiSx photocatalysts were prepared via a two-step process involving the photoinduced deposition of Ni on the TiO2 surface and the subsequent formation of NiSx on the Ni surface by a hydrothermal reaction method. It was found that the TiO2/Ni-NiSx photocatalysts exhibited enhanced photocatalytic H2-evolution activity. In particular, TiO2/Ni-NiSx(30%) showed the highest photocatalytic rate (223.74 μmol h.1), which was greater than those of TiO2, TiO2/Ni, and TiO2/NiSx by factors of 22.2, 8.0, and 2.2, respectively. The improved H2-evolution performance of TiO2/Ni-NiSx could be attributed to the excellent synergistic effect of Ni and NiSx, where Ni nanoparticles function as effective mediators to transfer electrons from the TiO2 surface and NiSx serves as interfacial active sites to capture H+ ions from solution and promote the interfacial H2-evolution reaction. The synergistic effect of the non-noble metal cocatalyst and the interfacial active sites may provide new insights for the design of highly efficient photocatalytic materials.展开更多
Mesenchymal stromal/stem cells(MSCs)are adult stem cells of stromal origin that possess self-renewal capacity and the ability to differentiate into multiple mesodermal cell lineages.They play a critical role in tissue...Mesenchymal stromal/stem cells(MSCs)are adult stem cells of stromal origin that possess self-renewal capacity and the ability to differentiate into multiple mesodermal cell lineages.They play a critical role in tissue homeostasis and wound healing,as well as in regulating the inammatory microenvironment through interactions with immune cells.Hence,MSCs have garnered great attention as promising candidates for tissue regeneration and cell therapy.Because the inflammatory niche plays a key role in triggering the reparative and immunomodulatory functions of MSCs,priming of MSCs with bioactive molecules has been proposed as a way to foster the therapeutic potential of these cells.In this paper,we review how soluble mediators of the inflammatory niche(cytokines and alarmins)influence the regenerative and immunomodulatory capacity of MSCs,highlighting the major advantages and concerns regarding the therapeutic potential of these inflammatory primed MSCs.The data summarized in this review may provide a significant starting point for future research on priming MSCs and establishing standardized methods for the application of preconditioned MSCs in cell therapy.展开更多
AIM：To investigate the effect of anti-vascular epithelial growth factor（VEGF）agents on the expression of fibrosisrelated inflammatory mediators under normoxic and hypoxic conditions,and to further clarify the mecha...AIM：To investigate the effect of anti-vascular epithelial growth factor（VEGF）agents on the expression of fibrosisrelated inflammatory mediators under normoxic and hypoxic conditions,and to further clarify the mechanism underlying fibrosis after anti-VEGF therapy. METHODS：Human retinal pigment epithelial（RPE）cells were incubated under normoxic and hypoxic conditions.For hypoxia treatment,CoCl_2 at 200μmol/L was added to the media. ARPE-19 cells were treated as following：1）control group：no treatment; 2）bevacizumab group：bevacizumab at 0.25 mg/mL was added to the media; 3）hypoxia group：CoCl_2 at 200 μmol/L was added to the media; 4）hypoxia＋bevacizumab group：CoCl_2 at 200 μmol/L and bevacizumab at 0.25 mg/mL were added to the media.The expression of interleukin（IL）-1β,IL-6,IL-8 and tumor necrosis factor（TNF）-α were evaluated using real-time polymerase chain reaction（RT-PCR）and enzyme-linked immunosorbent assay（ELISA）at 6,12,24 and 48 h. RESULTS：Both m RNA and protein levels of IL-1β,IL-6 and IL-8 were statistically significantly higher in the bevacizumab group than in the control group at each time point,and TNF-α gene and protein expression was only significantly higher only at 24 and 48h（P〈0.05）. Under hypoxic conditions,bevacizumab significantly increased the expression of IL-1β,IL-6,IL-8 and TNF-α at 6,12,24 and 48h（P〈0.05）. IL-1β,IL-8 and TNF-α peaked at 24 h and IL-6 peaked at 12 h after the bevacizumab treatment under both normoxic and hypoxic conditions. CONCLUSION：Treatment of ARPE-19 cells with bevacizumab can significantly increase the expression of fibrosis-related inflammatory mediators under bothnormoxic and hypoxic conditions. Inflammatory factors might be involved in the process of fibrosis after antiVEGF therapy,and the up-regulation of inflammatory factors induced by anti-VEGF drugs might promote the fibrosis process.展开更多
Rechargeable lithium-oxygen(Li-O_(2))batteries are the next generation energy storage devices due to their ultrahigh theoretical capacity.Redox mediators(RMs)are widely used as a homogenous electrocatalyst in non-aque...Rechargeable lithium-oxygen(Li-O_(2))batteries are the next generation energy storage devices due to their ultrahigh theoretical capacity.Redox mediators(RMs)are widely used as a homogenous electrocatalyst in non-aqueous Li-O_(2)batteries to enhance their discharge capacity and reduce charge overpotential.However,the shuttle effect of RMs in the electrolyte solution usually leads to corrosion of the Li metal anode and uneven Li deposition on the anode surface,resulting in unwanted consumption of electrocatalysts and deterioration of the cells.It is therefore necessary to take some measures to prevent the shuttle effect of RMs and fully utilize the soluble electrocatalysts.Herein,we summarize the strategies to suppress the RM shuttle effect reported in recent years,including electrolyte additives,protective separators and electrode modification.The mechanisms of these strategies are analyzed and their corresponding requirements are discussed.The electrochemical properties of Li-O_(2)batteries with different strategies are summarized and compared.The challenges and perspectives on preventing the shuttle effect of RMs are described for future study.This review provides guidance for achieving shuttle-free redox mediation and for designing Li-O_(2)cells with a long cycle life,high energy efficiency and highly reversible electrochemical reactions.展开更多
AIM:To compare the short-term impacts of femtosecond lenticule extraction(FLEx)and femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)on ocular surface measures and tear inflammatory mediators.METHODS:Th...AIM:To compare the short-term impacts of femtosecond lenticule extraction(FLEx)and femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)on ocular surface measures and tear inflammatory mediators.METHODS:This prospective comparative nonrandomized clinical study comprised 75 eyes(75 patients).Totally 20 male and 15 female patients(age 21.62±3.25 y)with 35 eyes underwent FLEx,and 26 male and 14 female patients(age 20.18±3.59 y)with 40 eyes underwent FS-LASIK.Central corneal sensitivity,noninvasive tear breakup time,corneal fluorescein staining,Schirmer I test,tear meniscus height,and ocular surface disease index were evaluated in all patients.Tear concentrations of nerve growth factor(NGF),interleukin-1α(IL-1α),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),and matrix metalloproteinase-9(MMP-9)were assessed by multiplex antibody microarray.All measurements were performed preoperatively,and 1 d,1 wk,and 1 mo postoperatively.RESULTS:Patients who underwent FLEx exhibited a more moderate reduction in central corneal sensation and less corneal fluorescein staining than those in the FS-LASIK group 1 wk after the procedure(P<0.01).NGF was significantly higher 1 d and 1 wk after surgery in the FS-LASIK group than in the FLEx group(P<0.01).By contrast,compared to those in the FLEx group,higher postoperative values and slower recovery of tear TGF-β1,IL-1α,and TNF-αconcentrations were observed in the FS-LASIK group(P<0.01).Tear concentrations of NGF,TGF-β1,TNF-α,and IL-1αwere correlated with ocular surface changes after FLEx or FS-LASIK surgery.CONCLUSION:There is less early ocular surface disruption and a reduced inflammatory response after FLEx than after FS-LASIK.NGF,TGF-β1,TNF-α,and IL-1αmay contribute to the process of ocular surface recovery.展开更多
Summary:In this study,we investigated the effects of nucleolin on lipopolysaccharide(LPS)-induced activation of MAPK and NF-KappaB(NF-kB)signaling pathways and secretion of TNF-a,IL-1βand HMGB1 in THP-1 monocytes.Imm...Summary:In this study,we investigated the effects of nucleolin on lipopolysaccharide(LPS)-induced activation of MAPK and NF-KappaB(NF-kB)signaling pathways and secretion of TNF-a,IL-1βand HMGB1 in THP-1 monocytes.Immunofluorescence assay and Western blotting were used to identify the nucleolin expression in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Inactivation of nucleolin was induced by neutralizing antibody against nucleolin.THP-1 monocytes were pretreated with anti-nucleolin antibody for 1 h prior to LPS challenge.The irrelevant IgG group was used as control.Secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1)and activation of MAPK and NF-kB/I-kB signaling pathways were examined to assess the effects of nucleolin on LPS-mediated inflammatory response.Nucleolin existed in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Pretreatment of anti-nucleolin antibody significantly inhibited the LPS-induced secretion of TNF-a,IL-1β and HMGB1.P38,JNK,ERK and NF-κB subunit p65 inhibitors could significantly inhibit the secretion of IL-1β,TNF-a and HMGB1 induced by LPS.Moreover,the phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65)was significantly increased after LPS challenge.In contrast,pretreatment of anti-nucleolin antibody could significantly inhibit the LPS-induced phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).However,the irrelevant IgG,as a negative control,had no effect on LPS-induced secretion of TNF-a and IL-Iβ and phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).We demonstrated that nucleolin mediated the LPS-induced activation of MAPK and NF-κB signaling pathways,and regulated the secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1).展开更多
Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2 is a global pandemic and poses a major threat to human health worldwide.In addition to respiratory symptoms,COVID-19 is usual...Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2 is a global pandemic and poses a major threat to human health worldwide.In addition to respiratory symptoms,COVID-19 is usually accompanied by systemic inflammation and liver damage in moderate and severe cases.Nuclear factor erythroid 2-related factor 2(NRF2)is a transcription factor that regulates the expression of antioxidant proteins,participating in COVID-19-mediated inflammation and liver injury.Here,we show the novel reciprocal regulation between NRF2 and inflammatory mediators associated with COVID-19-related liver injury.Additionally,we describe some mechanisms and treatment strategies.展开更多
基金supported by the Jeju Sea-green Program for the Regional Innovation Systemthe Regional Technology Innovation Program (No RTI04-02-07) of the Ministry of Knowledge and Economy,Korea
文摘Seaweed has been used in traditional cosmetics and as a herbal medicine in treatments for cough,boils,goiters,stomach ailments,and urinary diseases,and for reducing the incidence of tumors,ulcers,and headaches.Despite the fact that seaweeds are frequently used in the practice of human health,little is known about the role of seaweed in the context of inflammation.This study aimed to investigate the influence of Jeju endemic seaweed on a mouse macrophage cell line(RAW 264.7) under the stimulation of lipopolysaccharide(LPS).Ethyl acetate extracts obtained from 14 different kinds of Jeju seaweeds were screened for inhibitory effects on pro-inflammatory mediators.Our results revealed that extracts from five seaweeds,Laurencia okamurae,Grateloupia elliptica,Sargassum thun-bergii,Gloiopeltis furcata,and Hizikia fusiformis,were potent inhibitors of the production of pro-inflammatory mediators such as nitric oxide(NO),prostaglandin E2(PGE2),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α).Based on these results,the anti-inflammatory effects and low cell toxicity of these seaweed extracts suggest potential thera-peutic applications in the regulation of the inflammatory response.
基金supported by the National Natural Science Foundation of China,Nos.82272470 (to GN),82072439 (to GN),81930070 (to SF)the Tianjin Health Key Discipline Special Project,No.TJWJ2022XK011 (to GN)+2 种基金the Outstanding Youth Foundation of Tianjin Medical University General Hospital,No.22ZYYJQ01 (to GN)Tianjin Key Medical Disciplines,No.TJYXZDXK-027A (to SF)National Key Research and Development Program-Stem Cells and Transformation Research,No.2019YFA0112100 (to SF)
文摘Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim to control the spread of neuroinflammation during the acute phase but later hinder axon regeneration in later stages.Recent studies have enhanced our understanding of immunomodulation,revealing that injury-associated inflammation involves various cell types and molecules with positive and negative effects.This review employs bibliometric analysis to examine the literature on inflammatory mediators in spinal cord injury,highlighting recent research and providing a comprehensive overview of the current state of research and the latest advances in studies on neuroinflammation related to spinal cord injury.We summarize the immune and inflammatory responses at different stages of spinal cord injury,offering crucial insights for future research.Additionally,we review repair strategies based on inflammatory mediators for the injured spinal cord.Finally,this review discusses the current status and future directions of translational research focused on immune-targeting strategies,including pharmaceuticals,biomedical engineering,and gene therapy.The development of a combined,precise,and multitemporal strategy for the repair of injured spinal cords represents a promising direction for future research.
文摘Regulating the interfacial charge transfer is pivotal for elucidating the kinetics of engineering the interface between the light-harvesting semiconductor and the substrate/catalyst for photoelectrocatalytic water splitting.In this study,we constructed a superior Ti-doped hematite photoanode(TiFeO)by employing SnOx as an electron transfer mediator,partially oxidized graphene(pGO)as a hole transfer mediator,and molecular Co cubane as a water oxidation catalyst.The Co/pGO/TiFeO/SnO_(x)integrated system achieves a photocurrent density of 2.52 mA cm^(-2) at 1.23 VRHE,which is 2.4 times higher than bare photoanode(1.04 mA cm^(-2)),with operational stability up to 100 h.Kinetic measurements indicate that pGO can promote charge transfer from TiFeO to the Co cubane catalyst.In contrast,SnOx reduces charge recombination at the interface between TiFeO and the fluorinated tin oxide substrate.In-situ infrared spectroscopy shows the formation of an O–O bonded intermediate during water oxidation.This study highlights the crucial role of incorporating dual charge-transfer mediators into photoelectrodes for efficient solar energy conversion.
基金supported by the“Regional Innovation Strategy(RIS)”through the National Research Foundation of Korea(NRF),funded by the Ministry of Education(MOE)(2021RIS-003),South Koreasupported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.RS-2023-00241916),South Korea+4 种基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(IRIS RS-2024-00352303),South Koreathe results of a study on the“Leaders in Industry-university Cooperation 3.0”project,supported by the Ministry of Education and National Research Foundation of Korea,South Koreasupported by the Basic Science Research Program through the National Research Foundation of Korea(NRF),funded by the Ministry of Education(2020R1A6A03038697),South Koreasupported by Learning&Academic research institution for Master’s PhD students,and Postdocs(LAMP)Program of the National Research Foundation of Korea(NRF)grant funded by the Ministry of Education(No.RS-2023-00301974),South Koreasupported by the Technology Innovation Program(RS-2024-00432013)funded By the Ministry of Trade,Industry&Energy(MOTIE,South Korea)。
文摘All-solid-state Li-S batteries(ASSLSBs)are more attractive owing to their achievable superior energy density at a reasonable cost and the solid electrolyte(SE)utilization mitigating the widely recognized polysulfide shuttle problem.While the volume expansion(~80%)that occurs during the initial transformation of sulfur to lithium sulfide induces mechanical stress,this can be avoided by using Li_(2)S as a cathode,which also permits the anode-free cell design.However,the high oxidation energy barrier of Li_(2)S cathode during the charging step limits its application in commercial devices.Redox mediators have been extensively used to reduce the oxidation energy barrier of Li_(2)S to the sulfur conversation and boost the reversible kinetics of the conversion reaction.In this review,we have summarized the available redox mediators for Li_(2)S cathode in ASSLSBs and its working mechanism.Moreover,we have proposed novel strategies and guidelines for designing effective redox mediators to boost the reversible conversion reaction.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82192900,82192901,82192904,81390540,and 91846303 to L.L.)the National Key Research and Development Program of China(Grant No.2016YFC0900500 to Y.G.)the Kadoorie Charitable Foundation in Hong Kong,and the Wellcome Trust in the UK(Grant/Award Nos.088158/Z/09/Z,104085/Z/14/Z,and 202922/Z/16/Z to Z.C.).
文摘While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence.Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline,we employed structural equation modeling to assess the mediating effects of systolic(SBP)and diastolic(DBP)blood pressure.During the follow-up,2811 incident stroke cases were identified.A healthy lifestyle was significantly associated with a reduced risk of stroke,with SBP mediating 44.70%(β=-0.0014,95%confidence interval[CI]:-0.0016 to-0.0012)and DBP mediating 37.81%(β=-0.0012,95%CI:-0.0015 to-0.0009)of this association.The mediating effects were attenuated but remained significant for ischemic stroke(SBP:33.21%;DBP:27.24%).In conclusion,approximately two-fifths of the protective association between a healthy lifestyle and stroke may be mediated by BP.These findings suggest that BP control may serve as an important early indicator for evaluating the effectiveness of lifestyle interventions in reducing stroke risk.
基金supported by the National Science and Technology Major Program for Noncommunicable Chronic Diseases(2023ZD0503500)the National Natural Science Foundation of China(82030102,12126602,91857118)+1 种基金the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-010,2019-I2M-2-003)the National High Level Hospital Clinical Research Funding(2022-GSP-GG-1,2022-GSP-GG-2)。
文摘Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabolites mediating the associations ofα-diversity with blood pressure(BP)and BP variability(BPV).Methods Metagenomics and plasma targeted metabolomics were conducted on 523 Chinese participants from the MetaSalt study.The 24-hour,daytime,and nighttime BP and BPV were calculated based on ambulatory BP measurements.Linear mixed models were used to characterize the relationships betweenα-diversity(Shannon and Chao1 index)and BP indices.Mediation analyses were performed to assess the contribution of metabolites to the observed associations.The influence of key metabolites on hypertension was further evaluated in a prospective cohort of 2,169 participants.Results Gut microbial richness(Chao1)was negatively associated with 24-hour systolic BP,daytime systolic BP,daytime diastolic BP,24-hour systolic BPV,and nighttime systolic BPV(P<0.05).Moreover,26 metabolites were strongly associated with richness(Bonferroni P<0.05).Among them,four key metabolites(imidazole propionate,2-hydroxy-3-methylbutyric acid,homovanillic acid,and hydrocinnamic acid)mediated the associations between richness and BP indices(proportions of mediating effects:14.1%–67.4%).These key metabolites were also associated with hypertension in the prospective cohort.For example,each 1-standard deviation unit increase in hydrocinnamic acid significantly reduced the risk of prevalent(OR[95%CI]=0.90[0.82,0.99];P=0.03)and incident hypertension(HR[95%CI]=0.83[0.71,0.96];P=0.01).Conclusion Our results suggest that gut microbial richness correlates with lower BP and BPV,and that certain metabolites mediate these associations.These findings provide novel insights into the pathogenesis and prevention of hypertension.
基金supported by grants from the Technological Foundation Project of Traditional Chinese Medical Science of Zhejiang Province(No.2003C130No.2004C142)the Foundation Project for Medical Science and Technology of Zhejiang Province(No.2003B134).
文摘BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, liver, kidney and lung. Microcirculatory disturbance in AP has attracted widespread attention. In order to provide a theoretical basis for clinical therapy of AP, it is very important to explore the effect of inflammatory mediators on microcirculatory disturbance in this disease. DATA SOURCES: In this review, the impact of inflammatory mediators on microcirculatory disturbance in AP was reviewed according to the literature, especially the articles indexed in PubMed and books published in China and reports from websites. RESULTS: At present, inflammatory mediation and microcirculatory disturbance are the two major hypotheses to explain the development of AP. Although experimental studies have shown that inflammatory mediators induce or aggravate microcirculatory disturbance, the clinical application of these findings is still difficult because the inflammatory mediators are diverse and their research is not comprehensive and thorough. CONCLUSION: It is very important to explore the influence of inflammatory mediators on microcirculatory disturbance in AP.
基金supported by the National Basic Research Development Program of China (2013CB966900)the National Natural Science Foundation of China (81241144, 81371372)the National Key Clinical Specialty Construction Program of China
文摘Intracerebral hemorrhage （ICH） leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage （ICH）. The results showed that fingolimod decreased the numbers of circulating CD4~ T, CD8~ T, CD19~ B, NK, and NKT cells and they recovered quickly after the drug＇ was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced rT1%. In conclusion, modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability.
基金Supported by the National Natural Science Foundationfunded Project:the Mechanism of Spine-pinching Manipulation via Inflammation Regulation of SPMs on Prevention and Treatment of Spleen-deficiency Asthma(No.81774446)
文摘OBJECTIVE: To investigate the influence of spleen deficiency on the epithelial barrier of jejunum and lungs in a rat model of spleen-deficiency and the effect and potential specialized pro-resolving mediators (SPMs) mechanism of chiropractic manipulation. METHODS: Three-week-old male Sprague-Dawley rats were divided randomly into normal control group (n = 6), spleen-deficiency group (n = 5) and chiropractic group (n = 6). Spleen-deficiency model was induced in spleen-deficiency group and chiropractic group. Moreover, chiropractic manipulation was performed in chiropractic group. Four weeks later, systemic Th1/Th2 balance was evaluated by the ratio of plasma interferon (IFN)-γ/interleukin (IL)-4 levels by enzyme-linked immunosorbent assay (ELISA). Epithelial barrier integrity were assessed by the observation of morphological changes by hematoxylin-eosin staining and zonula occludens (ZO)-1 gene expressions by quantitative real time polymerase chain reaction in jejunum and lungs. Plasma resolvin D1 (RvD1) and lipoxin A4 (LXA4) levels were measures by ELISA for endogenous SPMs production. The levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in jejunum and lungs were also measured by HPLC-MS/ MS. RESULTS: Comparing with normal control group, spleen-deficiency group showed disrupted mucosa in jejunum, inflammatory condition in lungs, significantly decreased ratio of plasma IFN-γ/IL-4 levels and lower expressions of ZO-1 mRNA in both jejunum and lung tissues. Comparing with spleen-deficiency group, chiropractic group had less disrupted mucosa in jejunum and inflammatory condition in lungs, significantly increased systemic ratio of IFN-γ/IL-4 and expressions of ZO-1 mRNA in both jejunum and lung tissues. Chiropractic group had significantly enhanced plasma levels of RvD1 and LXA4, but had no significantly higher levels of DHA and AA in jejunum and lungs when comparing with spleen-deficiency group. CONCLUSION: Spleen deficiency caused systemic Th1/Th2 imbalance towards Th2 polarization and epithelial barrier disruption in jejunum and lungs.Chiropractic manipulation helped enhance endogenous SPMs production, which might be one of the action mechanism of chiropractic manipulation on the improvement of epithelial barrier disruption.
基金Supported by Grants for Traditional Chinese Medicine Science of Zhejiang Province,and Medical Science and Technology of Zhejiang Province and Hangzhou
文摘AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality,ascite volumes,ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3,6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α),phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared,terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated. RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α,PLA2 and IL-6 in serum,ascite volumes,ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points P < 0.05,58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-α content,8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P < 0.01,0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content,7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content,1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio,8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001,3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content,4.50 (2.00) vs 7.20 (2.00),4.20 (1.60) vs 6.40 (2.30),3.40 (2.70) vs 7.90 (1.70) in ascite volumes,respectively. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h P < 0.01,0.00 (2.00)% vs 0.00 (0.00)%,0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes,respectively. CONCLUSION: The mechanism of dexamethasone treatment in acute pancreatitis is related to its inhibition of inflammatory mediator generation and induction of pancreatic acinar cell apoptosis.
文摘OBJECTIVE: To investigate the effect of glucocorticoids on systemic inflammatory mediator release in rats with acute pancreatitis and the outcome of dexamethasone in treatment of acute pancreatitis. METHODS: Sixty-eight Wistar rats were divided into sham, acute pancreatitis, and treatment (intravenous dexamethasone 0.5 mg/kg) groups. Experimental acute pancreatitis was induced by the injection of 5% sodium taurocholate (0.1 ml/100 mg body weight) into the pancreatic-biliary duct. The bIood samples were obtained and examined for 6-keto-PGI_1α, TXB_2 and IL-6 postoperatively at 3,6 and 12 hours, respectively. The pancreatic samples were evaluated by a blinded method. Twelve-hour survival rate was determined and compared between the groups. RESULTS: The high serum concentrations of 6-keto-PGI_1α, TXB_2 and IL-6 were noted in the rats with acute pancreatitis associated with pancreatic hemorrhage and necrosis. Their 12-hour survival rate was 42.9%. The rats in the treatment group survived with significantly reduced serum concentrations of 6-keto-PGI_1α, TXB_2 and IL-6 (P<0.05). Their pancreatic morphology was normal. CONCLUSION: Dexamethasone may reduce the serum concentration of 6-keto-PGI_1α, TXB_2, and IL-6, and the severity of acute pancreatitis while increasing the survival rate of rats with acute pancreatitis.
基金supported by the Natural Science Foundation of Fujian Province of China,No.2015J01375(to QML)Fujian Provincial Hospital Foundation of China,No.2014070(to QML)
文摘Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation;however, the precise mechanisms remain unclear. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cell treatment on expression profiles of multiple cytokines in the brain after cardiac arrest and cardiopulmonary resuscitation. Cardiac arrest was induced in rats by asphyxia and cardiopulmonary resuscitation was initiated 6 minutes after cardiac arrest. One hour after successful cardiopulmonary resuscitation, rats were injected with either phosphate-buffered saline(control) or 1 × 10~6 bone marrow-derived mesenchymal stem cells via the tail vein. Serum S100 B levels were measured by enzyme-linked immunosorbent assay and neurological deficit scores were evaluated to assess brain damage at 3 days after cardiopulmonary resuscitation. Serum S100 B levels were remarkably decreased and neurological deficit scores were obviously improved in the mesenchymal stem cell group compared with the phosphate-buffered saline group. Brains were isolated from the rats and expression levels of 90 proteins were determined using a RayBio Rat Antibody Array, to investigate the cytokine profiles. Brain levels of the inflammatory mediators tumor necrosis factor-α, interferon-γ, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, macrophage inflammatory protein-3α, macrophage-derived chemokine, and matrix metalloproteinase-2 were decreased ≥ 1.5-fold, while levels of the anti-inflammatory factor interleukin-10 were increased ≥ 1.5-fold in the mesenchymal stem cell group compared with the control group. Donor mesenchymal stem cells were detected by immunofluorescence to determine their distribution in the damaged brain, and were primarily observed in the cerebral cortex. These results indicate that bone marrow-derived mesenchymal stem cell transplantation attenuates brain damage induced by cardiac arrest and cardiopulmonary resuscitation, possibly via regulation of inflammatory mediators. This experimental protocol was approved by the Institutional Animal Care and Use Committee of Fujian Medical University, China in January 2016(approval No. 2016079).
基金supported by the National Natural Science Foundation of China,Nos.81971870,82172173(both to MCL)。
文摘Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.
基金supported by the National Natural Science Foundation of China(21477094)the Fundamental Research Funds for the Central Universities(WUT 2017IB002)~~
文摘The development of efficient photocatalytic H2-evolution materials requires both rapid electron transfer and an effective interfacial catalysis reaction for H2 production. In addition to the well-known noble metals, low-cost and earth-abundant non-noble metals can also act as electron- transfer mediators to modify photocatalysts. However, as almost all non-noble metals lack the interfacial catalytic active sites required for the H2-evolution reaction, the enhancement of the photocatalytic performance is limited. Therefore, the development of new interfacial active sites on metal-modified photocatalysts is of considerable importance. In this study, to enhance the photocatalytic evolution of H2 by Ni-modified TiO2, the formation of NiSx as interfacial active sites was promoted on the surface of Ni nanoparticles. Specifically, the co-modified TiO2/Ni-NiSx photocatalysts were prepared via a two-step process involving the photoinduced deposition of Ni on the TiO2 surface and the subsequent formation of NiSx on the Ni surface by a hydrothermal reaction method. It was found that the TiO2/Ni-NiSx photocatalysts exhibited enhanced photocatalytic H2-evolution activity. In particular, TiO2/Ni-NiSx(30%) showed the highest photocatalytic rate (223.74 μmol h.1), which was greater than those of TiO2, TiO2/Ni, and TiO2/NiSx by factors of 22.2, 8.0, and 2.2, respectively. The improved H2-evolution performance of TiO2/Ni-NiSx could be attributed to the excellent synergistic effect of Ni and NiSx, where Ni nanoparticles function as effective mediators to transfer electrons from the TiO2 surface and NiSx serves as interfacial active sites to capture H+ ions from solution and promote the interfacial H2-evolution reaction. The synergistic effect of the non-noble metal cocatalyst and the interfacial active sites may provide new insights for the design of highly efficient photocatalytic materials.
基金Supported by the Ministry of Education,Science and Technological Development,Republic of Serbia,No.451-03-68/2020-14/200015.
文摘Mesenchymal stromal/stem cells(MSCs)are adult stem cells of stromal origin that possess self-renewal capacity and the ability to differentiate into multiple mesodermal cell lineages.They play a critical role in tissue homeostasis and wound healing,as well as in regulating the inammatory microenvironment through interactions with immune cells.Hence,MSCs have garnered great attention as promising candidates for tissue regeneration and cell therapy.Because the inflammatory niche plays a key role in triggering the reparative and immunomodulatory functions of MSCs,priming of MSCs with bioactive molecules has been proposed as a way to foster the therapeutic potential of these cells.In this paper,we review how soluble mediators of the inflammatory niche(cytokines and alarmins)influence the regenerative and immunomodulatory capacity of MSCs,highlighting the major advantages and concerns regarding the therapeutic potential of these inflammatory primed MSCs.The data summarized in this review may provide a significant starting point for future research on priming MSCs and establishing standardized methods for the application of preconditioned MSCs in cell therapy.
基金Supported by Shandong Provincial Natural Science Foundation,China(No.ZR2014HM029)
文摘AIM：To investigate the effect of anti-vascular epithelial growth factor（VEGF）agents on the expression of fibrosisrelated inflammatory mediators under normoxic and hypoxic conditions,and to further clarify the mechanism underlying fibrosis after anti-VEGF therapy. METHODS：Human retinal pigment epithelial（RPE）cells were incubated under normoxic and hypoxic conditions.For hypoxia treatment,CoCl_2 at 200μmol/L was added to the media. ARPE-19 cells were treated as following：1）control group：no treatment; 2）bevacizumab group：bevacizumab at 0.25 mg/mL was added to the media; 3）hypoxia group：CoCl_2 at 200 μmol/L was added to the media; 4）hypoxia＋bevacizumab group：CoCl_2 at 200 μmol/L and bevacizumab at 0.25 mg/mL were added to the media.The expression of interleukin（IL）-1β,IL-6,IL-8 and tumor necrosis factor（TNF）-α were evaluated using real-time polymerase chain reaction（RT-PCR）and enzyme-linked immunosorbent assay（ELISA）at 6,12,24 and 48 h. RESULTS：Both m RNA and protein levels of IL-1β,IL-6 and IL-8 were statistically significantly higher in the bevacizumab group than in the control group at each time point,and TNF-α gene and protein expression was only significantly higher only at 24 and 48h（P〈0.05）. Under hypoxic conditions,bevacizumab significantly increased the expression of IL-1β,IL-6,IL-8 and TNF-α at 6,12,24 and 48h（P〈0.05）. IL-1β,IL-8 and TNF-α peaked at 24 h and IL-6 peaked at 12 h after the bevacizumab treatment under both normoxic and hypoxic conditions. CONCLUSION：Treatment of ARPE-19 cells with bevacizumab can significantly increase the expression of fibrosis-related inflammatory mediators under bothnormoxic and hypoxic conditions. Inflammatory factors might be involved in the process of fibrosis after antiVEGF therapy,and the up-regulation of inflammatory factors induced by anti-VEGF drugs might promote the fibrosis process.
基金financially supported by the Tsinghua-Foshan Innovation Special Fund(Grant No.2018THFS0409)the China Postdoctoral Science Foundation(Grant No.2019M650668)the National Key Research and Development Program of China(Grant No.2016YFA0201003)。
文摘Rechargeable lithium-oxygen(Li-O_(2))batteries are the next generation energy storage devices due to their ultrahigh theoretical capacity.Redox mediators(RMs)are widely used as a homogenous electrocatalyst in non-aqueous Li-O_(2)batteries to enhance their discharge capacity and reduce charge overpotential.However,the shuttle effect of RMs in the electrolyte solution usually leads to corrosion of the Li metal anode and uneven Li deposition on the anode surface,resulting in unwanted consumption of electrocatalysts and deterioration of the cells.It is therefore necessary to take some measures to prevent the shuttle effect of RMs and fully utilize the soluble electrocatalysts.Herein,we summarize the strategies to suppress the RM shuttle effect reported in recent years,including electrolyte additives,protective separators and electrode modification.The mechanisms of these strategies are analyzed and their corresponding requirements are discussed.The electrochemical properties of Li-O_(2)batteries with different strategies are summarized and compared.The challenges and perspectives on preventing the shuttle effect of RMs are described for future study.This review provides guidance for achieving shuttle-free redox mediation and for designing Li-O_(2)cells with a long cycle life,high energy efficiency and highly reversible electrochemical reactions.
基金Supported by the National Natural Science Foundation of China(No.81870681)Key Program of the Department of Science and Technology of Hainan Province(No.ZDYF2020151)+1 种基金Huaxia Translational Medicine Fund For Young Scholars(No.2017-D-001)Medical Science and Technology Research Foundation of Guangdong Province(No.A2020406)。
文摘AIM:To compare the short-term impacts of femtosecond lenticule extraction(FLEx)and femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)on ocular surface measures and tear inflammatory mediators.METHODS:This prospective comparative nonrandomized clinical study comprised 75 eyes(75 patients).Totally 20 male and 15 female patients(age 21.62±3.25 y)with 35 eyes underwent FLEx,and 26 male and 14 female patients(age 20.18±3.59 y)with 40 eyes underwent FS-LASIK.Central corneal sensitivity,noninvasive tear breakup time,corneal fluorescein staining,Schirmer I test,tear meniscus height,and ocular surface disease index were evaluated in all patients.Tear concentrations of nerve growth factor(NGF),interleukin-1α(IL-1α),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),and matrix metalloproteinase-9(MMP-9)were assessed by multiplex antibody microarray.All measurements were performed preoperatively,and 1 d,1 wk,and 1 mo postoperatively.RESULTS:Patients who underwent FLEx exhibited a more moderate reduction in central corneal sensation and less corneal fluorescein staining than those in the FS-LASIK group 1 wk after the procedure(P<0.01).NGF was significantly higher 1 d and 1 wk after surgery in the FS-LASIK group than in the FLEx group(P<0.01).By contrast,compared to those in the FLEx group,higher postoperative values and slower recovery of tear TGF-β1,IL-1α,and TNF-αconcentrations were observed in the FS-LASIK group(P<0.01).Tear concentrations of NGF,TGF-β1,TNF-α,and IL-1αwere correlated with ocular surface changes after FLEx or FS-LASIK surgery.CONCLUSION:There is less early ocular surface disruption and a reduced inflammatory response after FLEx than after FS-LASIK.NGF,TGF-β1,TNF-α,and IL-1αmay contribute to the process of ocular surface recovery.
基金This work was supported by grants from Bureau of Science and Technology of Changsha,China(No.Kq 1701007)Hunan Natural Science Foundation,China(No.2018JJ6127).
文摘Summary:In this study,we investigated the effects of nucleolin on lipopolysaccharide(LPS)-induced activation of MAPK and NF-KappaB(NF-kB)signaling pathways and secretion of TNF-a,IL-1βand HMGB1 in THP-1 monocytes.Immunofluorescence assay and Western blotting were used to identify the nucleolin expression in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Inactivation of nucleolin was induced by neutralizing antibody against nucleolin.THP-1 monocytes were pretreated with anti-nucleolin antibody for 1 h prior to LPS challenge.The irrelevant IgG group was used as control.Secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1)and activation of MAPK and NF-kB/I-kB signaling pathways were examined to assess the effects of nucleolin on LPS-mediated inflammatory response.Nucleolin existed in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Pretreatment of anti-nucleolin antibody significantly inhibited the LPS-induced secretion of TNF-a,IL-1β and HMGB1.P38,JNK,ERK and NF-κB subunit p65 inhibitors could significantly inhibit the secretion of IL-1β,TNF-a and HMGB1 induced by LPS.Moreover,the phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65)was significantly increased after LPS challenge.In contrast,pretreatment of anti-nucleolin antibody could significantly inhibit the LPS-induced phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).However,the irrelevant IgG,as a negative control,had no effect on LPS-induced secretion of TNF-a and IL-Iβ and phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).We demonstrated that nucleolin mediated the LPS-induced activation of MAPK and NF-κB signaling pathways,and regulated the secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1).
基金Supported by National Natural Science Foundation of China,No.82070632.
文摘Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2 is a global pandemic and poses a major threat to human health worldwide.In addition to respiratory symptoms,COVID-19 is usually accompanied by systemic inflammation and liver damage in moderate and severe cases.Nuclear factor erythroid 2-related factor 2(NRF2)is a transcription factor that regulates the expression of antioxidant proteins,participating in COVID-19-mediated inflammation and liver injury.Here,we show the novel reciprocal regulation between NRF2 and inflammatory mediators associated with COVID-19-related liver injury.Additionally,we describe some mechanisms and treatment strategies.
