Background A variety of inflammatory mediators and effector cells participate together in acute lung injury,and lead to secondary injury that is due to an inflammatory cascade and secondary diffuse lung parenchyma inj...Background A variety of inflammatory mediators and effector cells participate together in acute lung injury,and lead to secondary injury that is due to an inflammatory cascade and secondary diffuse lung parenchyma injury.Inflammation is associated with an oxidative stress reaction,which is produced in the development of airway inflammation,and which has positive feedback on inflammation itself.Resolvin D1 can reduce the infiltration of neutrophils,regulate cytokine levels and reduce the inflammation reaction,and thereby promote the resolution of inflammation.The purpose of this study is to investigate the effects of resolvin D1 on an inflammatory response and oxidative stress during lipopolysaccharide （LPS）-induced acute lung injury.Methods LPS （3 mg/kg） was used to induce the acute lung injury model.Pretreatment resolvin D1 （100 ng/mouse） was given to mice 30 minutes before inducing acute lung injury.Mice were observed at 6 hours,12 hours,1 day,2 days,3 days,4 days and 7 days after LPS was administrated,then they were humanely sacrificed.We collected bronchoalveolar lavage fluid （BALF） and the lung tissues for further analysis.Paraffin section and HE staining of the lung tissues were made for histopathology observations.Parts of the lung tissues were evaluated for wet-to-dry （W/D） weight ratio.tumor necrosis factor （TNF）-α,inter leukin （IL）-1β,IL-10 and myeloperoxidase （MPO） were detected by enzyme-linked immunosorbent assay （ELISA）.A lipid peroxidation malondialdehyde （MDA） assay kit was used to detect MDA.A total superoxide dismutase assay kit with WST-1 was used to analyze superoxide dismutase （SOD）.We determined the apoptosis of neutrophils by Flow Cytometry.A real-time quantitative PCR Detecting System detected the expression of mRNA for heme oxygenase （HO）-1.Results Pretreatment with resolvin D1 reduced the pathological damage in the lung,decreased the recruitment of neutrophils and stimulated their apoptosis.It markedly decreased the expressions of TNF-α,展开更多
Background Cigarette smoke induced airway inflammation plays a role in pathogenesis of airway inflammation.Resolvin-D1 derived from omega-3 polyunsaturated fatty acids is an endogenous anti-inflammatory and proresolvi...Background Cigarette smoke induced airway inflammation plays a role in pathogenesis of airway inflammation.Resolvin-D1 derived from omega-3 polyunsaturated fatty acids is an endogenous anti-inflammatory and proresolving lipid mediator.Resolvin-D1 ameliorated inflammatory responses in lung injury,asthma,peritonitis and atherosclerosis.We investigated whether resolvin-D1 suppressed the productions of chemokines and oxidative stress induced by cigarette smoke extract （CSE） in vitro and its possible mechanism.Methods We examined the proinfiammatory chemokine interleukin-8 and hydrogen peroxide （H2O2）productions induced by CSE in 16 human bronchial epithelial （16HBE）cells after resolvin-D1 treatment and their mechanisms.16HBE cells were treated with resolvin-D1 at up to 10 nmol/L,for 30 minutes before CSE up to 16％ （v/v） exposure.Release of interlukin-8 proteins was assessed by enzyme linked immunosort assay （ELISA） and its mRNA level by RT-PCR.We evaluated extracellular H2O2 expression in the supematant.Phosphorylation of NF-KB/p65 and degradation of Ⅰ-KB in 16HBE cells were determined by Westem blotting analysis and NF-KB DNA binding activity by electrophoretic mobility shift assay （EMSA）.Results 16HBE cells treated with 8％ CSE showed significantly higher interlukin-8 production.Resolvin-D1 pretreatment inhibited CSE induced intedukin-8 production （mRNA and protein） in a dose and time dependent manner.Extracellular H2O2 level decreased after resolvin-D1 treatment.Resolvin-D1 attenuated CSE triggered Ⅰ-KB degradation and NF-KB/p65 activation dose dependently and inhibited NF-KB DNA binding activity.Conclusion Resolvin-D1 inhibits CSE induced interlukin-8 and H2O2 production in 16HBE cells by modulating NF-KB activation and has therapeutic potential for pulmonary inflammation.展开更多
Non-alcoholic fatty liver disease (NAFLD) is a low-grade systemic inflammatory condition, since liver and adipose tissue tumor necrosis factor-α (TNF-α) and TNF receptor 1 transcripts and serum TNF-α levels are inc...Non-alcoholic fatty liver disease (NAFLD) is a low-grade systemic inflammatory condition, since liver and adipose tissue tumor necrosis factor-α (TNF-α) and TNF receptor 1 transcripts and serum TNF-α levels are increased and IL-6-/-mice are less prone to NAFLD. Fatty liver damage caused by high-fat diets is associated with the generation of pro-inflammatory prostaglandin E2 (PGE2). A decrease in the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the usefulness of EPA and DHA both in the prevention and management of NAFLD has been reported. AA, EPA and DHA and their anti-inflammatory products lipoxins (LXs), resolvins and protectins suppress IL-6 and TNF-α and PGE2 production. These results suggest that the activities of △6 and △5 desaturases are reduced in NAFLD and hence, the dietary essential fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) are not metabolized to their long-chain products AA, EPA and DHA, the precursors of anti-inflammatory molecules, LXs, resolvins and protectins that could prevent NAFLD. This suggests that an imbalance between proand anti-inflammatory bioactive lipids contribute to NAFLD. Hence, it is proposed that plasma and tissue levels of AA, EPA, DHA and LXs, resolvins and protectins could be used as predictors and prognostic biomarkers of NAFLD. It is suggested that the synthesis and use of more stable analogues of LXs, resolvins and protectins need to be explored in the prevention and management of NAFLD.展开更多
Type 2 diabetes mellitus(T2DM)increases the risk of many lethal and debilitating conditions.Among them,foot ulceration due to neuropathy,vascular disease,or trauma affects the quality of life of millions in the United...Type 2 diabetes mellitus(T2DM)increases the risk of many lethal and debilitating conditions.Among them,foot ulceration due to neuropathy,vascular disease,or trauma affects the quality of life of millions in the United States and around the world.Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase.Despite advanced treatment,diabetic foot ulcers(DFUs)are associated with a risk of amputation.Thus,there is a need for novel therapies to address chronic inflammation,decreased angiogenesis,and impaired granulation tissue formation contributing to the non-healing of DFUs.Studies have shown promising results with resolvins(Rv)and anti-inflammatory therapies that resolve inflammation and enhance tissue healing.But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency,tissue targetability,and immunogenicity.This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs.The articles discussing the T2DM disease state,current research on Rv for treating inflammation,the role of Rv in enhancing wound healing,and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy.The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with antiinflammatory agents as promising therapeutic agents in ulcer healing.展开更多
Aim: Resolvins, maresins and lipoxins are lipid mediators issued from essential polyunsaturated fatty acids which are the first anti-inflammatory and pro-resolving signals identified during the resolution phase of inf...Aim: Resolvins, maresins and lipoxins are lipid mediators issued from essential polyunsaturated fatty acids which are the first anti-inflammatory and pro-resolving signals identified during the resolution phase of inflammation. As borage oil and/or borage seed extracts have shown beneficial action in treatment of atopic dermatitis or eczema in human and canine, we have modified a borage oil component by using biotechnology in order to get a compound structurally related to a polyunsaturated fatty acid, and we have studied its ability to reduce inflammation mediators production through the generation of resolvins, maresins and/or lipoxins. Additionally, we have demonstrated the potent anti-inflammatory effect of this new compound which consists in borage seed oil aminopropanediol amides, through an in vivo study concerning subjects suffering from psoriasis or atopic dermatitis. Study Design/Methods: For the in vitro study, inflammation was induced in co-cultures of human dendritic cells and normal keratinocytes by the addition of PMA and the calcium ionophore A23187. Ability of our borage seed oil aminopropanediol amides to increase resolvin D2, maresin 1 and lipoxins A4 and B4 synthesis was then measured. Pro-inflammatory cytokines (IL-1β, IL-6, IL-8) and PGE2 productions were also quantified. For the in vivo study, 36 subjects suffering from psoriasis or atopic dermatitis have used twice a day during 30 days, a formulation containing borage seed oil aminopropanediol amides. Before the beginning of the study and after 30 days’ treatment, the severity of psoriasis and of atopic dermatitis was evaluated by using the PGA and the SCORAD scoring scales, respectively. Results: Borage seed oil aminopropanediol amides were able to significantly increase the resolvin D2, maresin 1 and lipoxins A4 and B4 synthesis. Concomitantly, they were also able to significantly inhibit the production of IL-1β, IL-6, IL-8 and PGE2 induced by the PMA and the calcium ionophore A23187 in the in vitro co-culture model used. Introduced 展开更多
Background： Resolvin D1 （RvD1） is a newly found anti-inflammatory bioactive compound derived from polyunsaturated fatty acids. The current study aimed to explore the protective effect of RvD1 on lipopolysaccharide ...Background： Resolvin D1 （RvD1） is a newly found anti-inflammatory bioactive compound derived from polyunsaturated fatty acids. The current study aimed to explore the protective effect of RvD1 on lipopolysaccharide （LPS）-induced acute kidney injury （AKI） and its possible mechanism. Methods： Both in vivo and in vitro studies were conducted. Male BALB/c mice were randomly divided into control group （saline）, LPS group （LPS 5 mg/kg）, RvD1 group （RvD1 5 μg/kg ＋ LPS 5 mg/kg）, and blockage group （Boc-MLP 5 gg/kg ＋ RvD1 5 gg/kg ＋ LPS 5 mg/kg）. Boc-MLP is a RvD 1 receptor blocker. The mice were intraperitoneally injected with these drugs and recorded for general condition for 48 h, while the blood and kidneys were harvested at 2, 6, 12, 24, and 48 h time points, respectively （n = 6 in each group at each time point）. Human proximal tubule epithelial cells （HK-2） were randomly divided into control group （medium only）, LPS group （LPS 5 μg/ml）, RvD1 group （RvD1 10 ng/ml ＋ LPS 5 μg/ml）, and blockage group （Boc-MLP 10 ng/ml ＋ RvD1 10 ng/ml ＋ LPS 5 μg/ml）. The cells were harvested for RNA at 2, 4, 6, 12, and 24 h time points, respectively （n = 6 in each group at each time point）. Blood creatinine was tested by using an Abbott i-STAT portable blood gas analyzer. Tumor necrosis factor-α （TNF-α level was detected by EL1SA. Kidney pathology was observed under hematoxylin and eosin （HE） staining and transmission electron microscope （TEM）. We hired immune-histological staining, Western blotting, and fluorescence quantitative polymerase chain reaction to detect the expression of RvD1 receptor ALX, nuclear factor-kappa B （NF-KB） signaling pathway as well as caspase-3. Kidney apoptosis was evaluated by TUNEL staining. Results： RvD 1 receptor ALX was detected on renal tubular epithelials. Kaplan-Meier analysis indicated that RvD 1 improved 48 h animal survival （80%） compared with LPS group （40%） and RvDI blockage group （60%）, while Rv展开更多
Objective： To investigate the effect of combined application of Xuebijing Injection（血必净注射液, XBJ） and resolvin D1（RvD1） on survival rate and the underlying mechanisms in mice with sepsisinduced lung injury. ...Objective： To investigate the effect of combined application of Xuebijing Injection（血必净注射液, XBJ） and resolvin D1（RvD1） on survival rate and the underlying mechanisms in mice with sepsisinduced lung injury. Methods： The cecal ligation and puncture（CLP） method was used to develop a mouse sepsis model. Specific pathogen free male C57 BL/6 mice were randomly divided into 5 groups（n=20 each）： sham, CLP, CLP＋XBJ, CLP＋RvD1 and CLP＋XBJ＋RvD1. After surgery, mice in the CLP＋XBJ, CLP＋RvD1 and CLP＋XBJ＋RvD1 groups were given XBJ（25 μL/g body weight）, RvD1（10 ng/g body weight）, and their combination（the same dose of XBJ and RvD1）, respectively. In each group, 12 mice were used to observe 1-week survival rate, while the rest were executed at 12 h. Whole blood was collected for flow cytometric analysis of leukocyte adhesion molecules CD18, lung tissues were harvested for observing pathological changes, and testing the activity of myeloperoxidase（MPO） and the expression of intercellular cell adhesion molecule 1（ICAM-1）. Results： Compared with the CLP group, the histopathological damage of the lung tissues was mitigated, MPO activity was decreased in the CLP＋XBJ and CLP＋RvD1 groups（P〈0.05）. In addition, the 1-week survival rate was improved, proportion of CD18-expressing cells in whole blood and ICAM-1 protein expression in lung tissue were decreased in the CLP＋XBJ＋RvD1 group（P〈0.05 or P〈0.01）. Conclusion： XBJ together with RvD1 could effectively inhibit leukocyte adhesion, reduce lung injury, and improve the survival rate of mice with sepsis.展开更多
Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that ...Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.展开更多
Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity.β3-adrenoceptor(β3-AR),a type of G protein-coupled receptor(GPCR),is believed to mediate the thermogenesis of br...Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity.β3-adrenoceptor(β3-AR),a type of G protein-coupled receptor(GPCR),is believed to mediate the thermogenesis of brown fat in mice.However,β3-AR has low expression in human adipose tissue,precluding its activation as a standalone clinical modality.This study aimed at identifying a potential GPCR target to induce beige fat.We found that chemerin chemokine-like receptor 1(CMKLR1),one of the novel GPCRs,mediated the development of beige fat via its two ligands,chemerin and resolvin E1(RvE1).The RvE1 levels were decreased in the obese mice,and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat markers.Inversely,despite sharing the same receptor as RvE1,the chemerin levels were increased in obesogenic conditions,and chemerin treatment led to an augmented obese phenotype and a decline of beige fat markers.Moreover,RvE1 and chemerin induced or restrained the development of beige fat,respectively,via the mechanistic target of rapamycin complex 1(mTORC1)signaling pathway.We further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of CMKLR1.In conclusion,our study showed that RvE1 and chemerin affected metabolic homeostasis differentially,suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.展开更多
基金This study by grants from the National Natural Science Foundation of China
文摘Background A variety of inflammatory mediators and effector cells participate together in acute lung injury,and lead to secondary injury that is due to an inflammatory cascade and secondary diffuse lung parenchyma injury.Inflammation is associated with an oxidative stress reaction,which is produced in the development of airway inflammation,and which has positive feedback on inflammation itself.Resolvin D1 can reduce the infiltration of neutrophils,regulate cytokine levels and reduce the inflammation reaction,and thereby promote the resolution of inflammation.The purpose of this study is to investigate the effects of resolvin D1 on an inflammatory response and oxidative stress during lipopolysaccharide （LPS）-induced acute lung injury.Methods LPS （3 mg/kg） was used to induce the acute lung injury model.Pretreatment resolvin D1 （100 ng/mouse） was given to mice 30 minutes before inducing acute lung injury.Mice were observed at 6 hours,12 hours,1 day,2 days,3 days,4 days and 7 days after LPS was administrated,then they were humanely sacrificed.We collected bronchoalveolar lavage fluid （BALF） and the lung tissues for further analysis.Paraffin section and HE staining of the lung tissues were made for histopathology observations.Parts of the lung tissues were evaluated for wet-to-dry （W/D） weight ratio.tumor necrosis factor （TNF）-α,inter leukin （IL）-1β,IL-10 and myeloperoxidase （MPO） were detected by enzyme-linked immunosorbent assay （ELISA）.A lipid peroxidation malondialdehyde （MDA） assay kit was used to detect MDA.A total superoxide dismutase assay kit with WST-1 was used to analyze superoxide dismutase （SOD）.We determined the apoptosis of neutrophils by Flow Cytometry.A real-time quantitative PCR Detecting System detected the expression of mRNA for heme oxygenase （HO）-1.Results Pretreatment with resolvin D1 reduced the pathological damage in the lung,decreased the recruitment of neutrophils and stimulated their apoptosis.It markedly decreased the expressions of TNF-α,
基金This study was supported by grants from the National Natural Science Foundation of China and China Medical Board of New York to Dr.Wen Fuqiang （No.31171103,No.81230001 and No.06834）.
文摘Background Cigarette smoke induced airway inflammation plays a role in pathogenesis of airway inflammation.Resolvin-D1 derived from omega-3 polyunsaturated fatty acids is an endogenous anti-inflammatory and proresolving lipid mediator.Resolvin-D1 ameliorated inflammatory responses in lung injury,asthma,peritonitis and atherosclerosis.We investigated whether resolvin-D1 suppressed the productions of chemokines and oxidative stress induced by cigarette smoke extract （CSE） in vitro and its possible mechanism.Methods We examined the proinfiammatory chemokine interleukin-8 and hydrogen peroxide （H2O2）productions induced by CSE in 16 human bronchial epithelial （16HBE）cells after resolvin-D1 treatment and their mechanisms.16HBE cells were treated with resolvin-D1 at up to 10 nmol/L,for 30 minutes before CSE up to 16％ （v/v） exposure.Release of interlukin-8 proteins was assessed by enzyme linked immunosort assay （ELISA） and its mRNA level by RT-PCR.We evaluated extracellular H2O2 expression in the supematant.Phosphorylation of NF-KB/p65 and degradation of Ⅰ-KB in 16HBE cells were determined by Westem blotting analysis and NF-KB DNA binding activity by electrophoretic mobility shift assay （EMSA）.Results 16HBE cells treated with 8％ CSE showed significantly higher interlukin-8 production.Resolvin-D1 pretreatment inhibited CSE induced intedukin-8 production （mRNA and protein） in a dose and time dependent manner.Extracellular H2O2 level decreased after resolvin-D1 treatment.Resolvin-D1 attenuated CSE triggered Ⅰ-KB degradation and NF-KB/p65 activation dose dependently and inhibited NF-KB DNA binding activity.Conclusion Resolvin-D1 inhibits CSE induced interlukin-8 and H2O2 production in 16HBE cells by modulating NF-KB activation and has therapeutic potential for pulmonary inflammation.
基金Supported by Ramalingaswami Fellowship of the Department of Biotechnology, Indiaa grant from the Defense Research and Development Organisation, New Delhi, India
文摘Non-alcoholic fatty liver disease (NAFLD) is a low-grade systemic inflammatory condition, since liver and adipose tissue tumor necrosis factor-α (TNF-α) and TNF receptor 1 transcripts and serum TNF-α levels are increased and IL-6-/-mice are less prone to NAFLD. Fatty liver damage caused by high-fat diets is associated with the generation of pro-inflammatory prostaglandin E2 (PGE2). A decrease in the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the usefulness of EPA and DHA both in the prevention and management of NAFLD has been reported. AA, EPA and DHA and their anti-inflammatory products lipoxins (LXs), resolvins and protectins suppress IL-6 and TNF-α and PGE2 production. These results suggest that the activities of △6 and △5 desaturases are reduced in NAFLD and hence, the dietary essential fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) are not metabolized to their long-chain products AA, EPA and DHA, the precursors of anti-inflammatory molecules, LXs, resolvins and protectins that could prevent NAFLD. This suggests that an imbalance between proand anti-inflammatory bioactive lipids contribute to NAFLD. Hence, it is proposed that plasma and tissue levels of AA, EPA, DHA and LXs, resolvins and protectins could be used as predictors and prognostic biomarkers of NAFLD. It is suggested that the synthesis and use of more stable analogues of LXs, resolvins and protectins need to be explored in the prevention and management of NAFLD.
基金Supported by the Intramural Grant IMR Rai 12397B from the Western University of Health Sciences,Pomona,Californiathe Grants from the National Institutes of Health,United States,R01 HL144125 and R01 HL147662.
文摘Type 2 diabetes mellitus(T2DM)increases the risk of many lethal and debilitating conditions.Among them,foot ulceration due to neuropathy,vascular disease,or trauma affects the quality of life of millions in the United States and around the world.Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase.Despite advanced treatment,diabetic foot ulcers(DFUs)are associated with a risk of amputation.Thus,there is a need for novel therapies to address chronic inflammation,decreased angiogenesis,and impaired granulation tissue formation contributing to the non-healing of DFUs.Studies have shown promising results with resolvins(Rv)and anti-inflammatory therapies that resolve inflammation and enhance tissue healing.But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency,tissue targetability,and immunogenicity.This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs.The articles discussing the T2DM disease state,current research on Rv for treating inflammation,the role of Rv in enhancing wound healing,and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy.The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with antiinflammatory agents as promising therapeutic agents in ulcer healing.
文摘Aim: Resolvins, maresins and lipoxins are lipid mediators issued from essential polyunsaturated fatty acids which are the first anti-inflammatory and pro-resolving signals identified during the resolution phase of inflammation. As borage oil and/or borage seed extracts have shown beneficial action in treatment of atopic dermatitis or eczema in human and canine, we have modified a borage oil component by using biotechnology in order to get a compound structurally related to a polyunsaturated fatty acid, and we have studied its ability to reduce inflammation mediators production through the generation of resolvins, maresins and/or lipoxins. Additionally, we have demonstrated the potent anti-inflammatory effect of this new compound which consists in borage seed oil aminopropanediol amides, through an in vivo study concerning subjects suffering from psoriasis or atopic dermatitis. Study Design/Methods: For the in vitro study, inflammation was induced in co-cultures of human dendritic cells and normal keratinocytes by the addition of PMA and the calcium ionophore A23187. Ability of our borage seed oil aminopropanediol amides to increase resolvin D2, maresin 1 and lipoxins A4 and B4 synthesis was then measured. Pro-inflammatory cytokines (IL-1β, IL-6, IL-8) and PGE2 productions were also quantified. For the in vivo study, 36 subjects suffering from psoriasis or atopic dermatitis have used twice a day during 30 days, a formulation containing borage seed oil aminopropanediol amides. Before the beginning of the study and after 30 days’ treatment, the severity of psoriasis and of atopic dermatitis was evaluated by using the PGA and the SCORAD scoring scales, respectively. Results: Borage seed oil aminopropanediol amides were able to significantly increase the resolvin D2, maresin 1 and lipoxins A4 and B4 synthesis. Concomitantly, they were also able to significantly inhibit the production of IL-1β, IL-6, IL-8 and PGE2 induced by the PMA and the calcium ionophore A23187 in the in vitro co-culture model used. Introduced
基金This research was supported by a grant of the National Natural Science Foundation of China
文摘Background： Resolvin D1 （RvD1） is a newly found anti-inflammatory bioactive compound derived from polyunsaturated fatty acids. The current study aimed to explore the protective effect of RvD1 on lipopolysaccharide （LPS）-induced acute kidney injury （AKI） and its possible mechanism. Methods： Both in vivo and in vitro studies were conducted. Male BALB/c mice were randomly divided into control group （saline）, LPS group （LPS 5 mg/kg）, RvD1 group （RvD1 5 μg/kg ＋ LPS 5 mg/kg）, and blockage group （Boc-MLP 5 gg/kg ＋ RvD1 5 gg/kg ＋ LPS 5 mg/kg）. Boc-MLP is a RvD 1 receptor blocker. The mice were intraperitoneally injected with these drugs and recorded for general condition for 48 h, while the blood and kidneys were harvested at 2, 6, 12, 24, and 48 h time points, respectively （n = 6 in each group at each time point）. Human proximal tubule epithelial cells （HK-2） were randomly divided into control group （medium only）, LPS group （LPS 5 μg/ml）, RvD1 group （RvD1 10 ng/ml ＋ LPS 5 μg/ml）, and blockage group （Boc-MLP 10 ng/ml ＋ RvD1 10 ng/ml ＋ LPS 5 μg/ml）. The cells were harvested for RNA at 2, 4, 6, 12, and 24 h time points, respectively （n = 6 in each group at each time point）. Blood creatinine was tested by using an Abbott i-STAT portable blood gas analyzer. Tumor necrosis factor-α （TNF-α level was detected by EL1SA. Kidney pathology was observed under hematoxylin and eosin （HE） staining and transmission electron microscope （TEM）. We hired immune-histological staining, Western blotting, and fluorescence quantitative polymerase chain reaction to detect the expression of RvD1 receptor ALX, nuclear factor-kappa B （NF-KB） signaling pathway as well as caspase-3. Kidney apoptosis was evaluated by TUNEL staining. Results： RvD 1 receptor ALX was detected on renal tubular epithelials. Kaplan-Meier analysis indicated that RvD 1 improved 48 h animal survival （80%） compared with LPS group （40%） and RvDI blockage group （60%）, while Rv
基金Supported by the Tianjin Science and Technology Project,China(No.13RCGFSY19300)
文摘Objective： To investigate the effect of combined application of Xuebijing Injection（血必净注射液, XBJ） and resolvin D1（RvD1） on survival rate and the underlying mechanisms in mice with sepsisinduced lung injury. Methods： The cecal ligation and puncture（CLP） method was used to develop a mouse sepsis model. Specific pathogen free male C57 BL/6 mice were randomly divided into 5 groups（n=20 each）： sham, CLP, CLP＋XBJ, CLP＋RvD1 and CLP＋XBJ＋RvD1. After surgery, mice in the CLP＋XBJ, CLP＋RvD1 and CLP＋XBJ＋RvD1 groups were given XBJ（25 μL/g body weight）, RvD1（10 ng/g body weight）, and their combination（the same dose of XBJ and RvD1）, respectively. In each group, 12 mice were used to observe 1-week survival rate, while the rest were executed at 12 h. Whole blood was collected for flow cytometric analysis of leukocyte adhesion molecules CD18, lung tissues were harvested for observing pathological changes, and testing the activity of myeloperoxidase（MPO） and the expression of intercellular cell adhesion molecule 1（ICAM-1）. Results： Compared with the CLP group, the histopathological damage of the lung tissues was mitigated, MPO activity was decreased in the CLP＋XBJ and CLP＋RvD1 groups（P〈0.05）. In addition, the 1-week survival rate was improved, proportion of CD18-expressing cells in whole blood and ICAM-1 protein expression in lung tissue were decreased in the CLP＋XBJ＋RvD1 group（P〈0.05 or P〈0.01）. Conclusion： XBJ together with RvD1 could effectively inhibit leukocyte adhesion, reduce lung injury, and improve the survival rate of mice with sepsis.
基金National Key R&D Program of China,Nos.2019YFA0110300 (to LZ),2021YFA1201400 (to LZ)Natural Science Foundation of Shanghai,No.21ZR1468600 (to LZ)Open Fund of the Key Laboratory of Cellular Physiology (Shanxi Medical University),Ministry of Education,No.KLMEC/SXMU-201910 (to XJ)。
文摘Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.
基金funded by the National Natural Science Foundation of China(81570764)Guangzhou Science and Technology Project(201807010069)+2 种基金Shenzhen Science and Technology Project(JCYJ20190807154205627)Guangdong Natural Science Fund(2020A1515010365)Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translation Research of Hakka Population(2018B030322003KF01)received by Zhonghan Yang。
文摘Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity.β3-adrenoceptor(β3-AR),a type of G protein-coupled receptor(GPCR),is believed to mediate the thermogenesis of brown fat in mice.However,β3-AR has low expression in human adipose tissue,precluding its activation as a standalone clinical modality.This study aimed at identifying a potential GPCR target to induce beige fat.We found that chemerin chemokine-like receptor 1(CMKLR1),one of the novel GPCRs,mediated the development of beige fat via its two ligands,chemerin and resolvin E1(RvE1).The RvE1 levels were decreased in the obese mice,and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat markers.Inversely,despite sharing the same receptor as RvE1,the chemerin levels were increased in obesogenic conditions,and chemerin treatment led to an augmented obese phenotype and a decline of beige fat markers.Moreover,RvE1 and chemerin induced or restrained the development of beige fat,respectively,via the mechanistic target of rapamycin complex 1(mTORC1)signaling pathway.We further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of CMKLR1.In conclusion,our study showed that RvE1 and chemerin affected metabolic homeostasis differentially,suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.
