Chalcone is a plant metabolite widely found in fruits,vegetables,spices and tea,and has anti-tumor,anti-inflammation,immunomodulation,antibacterial and anti-oxidation activities,as well as many other pharmacological a...Chalcone is a plant metabolite widely found in fruits,vegetables,spices and tea,and has anti-tumor,anti-inflammation,immunomodulation,antibacterial and anti-oxidation activities,as well as many other pharmacological and biological effects.Our team has shown that its analogs have antioxidant activity,and oxidative stress is a pathological hallmark of retinal ischemia/reperfusion injury that can lead to retinal damage and visual loss.This investigation aims to identify a chalcone that protects retinal ganglion cells in vitro from the effects of oxidative stress and examine its mechanism.Rat retinal ganglion cell-5 cells were pretreated with chalcones and then exposed to tert-butyl hydroperoxide that causes oxidative damage.Controls received dimethyl sulfoxide only or tert-butyl hydroperoxide in dimethyl sulfoxide.Only（E）-3,4-dihydroxy-2′-methylether ketone（L2 H17）,of the five chalcone analogs,markedly increased the survival rate of oxidatively injured RGC-5 cells.Thus,subsequent experiments only analyzed the results of the L2 H17 intervention.Cell viability and apoptosis were measured.Intracellular superoxide dismutase and reactive oxygen species levels were used to assess induced oxidative stress.The mechanism of action by L2 H17 was explored by measuring the ER stress/UPR pathway and the expression and localization of Nrf2.All results demonstrated that L2 H17 could reduce the apoptosis of oxidatively injured cells,inhibit caspase-3 activity,increase Bcl-2 expression,decrease Bad expression,increase the activity of superoxide dismutase,inhibit the production of reactive oxygen species,increase Nrf2 immunoreactivity,and reduce the activating transcription factor 4,phospho-eukaryotic initiation factor 2 and CHOP expression.L2 H17 protects retinal ganglion cells induced by oxidative stress by regulating Nrf2,which indicates that it has the potential to become a drug for retinal ischemia/reperfusion.展开更多
A kind of novel electroluminescence polymer has been prepared by oxidative-coupling polymerization of N-alkyl carbazole and trans-stilbene. The structure of the copolymers was characterized by elemental analysis, UV-v...A kind of novel electroluminescence polymer has been prepared by oxidative-coupling polymerization of N-alkyl carbazole and trans-stilbene. The structure of the copolymers was characterized by elemental analysis, UV-vis and FTIR spectra. The copolymers have good solubility in chloroform and acetone. Fluorescence spectra showed that these polymers are blue-light emitting materials.展开更多
Objective:To detect serum contents of IgE, Eotaxin and explore the relationship between serum IgE, Eotaxin and asthma severity.Methods: 140 cases of asthma children diagnosed in our hospital during January 2017 to Mar...Objective:To detect serum contents of IgE, Eotaxin and explore the relationship between serum IgE, Eotaxin and asthma severity.Methods: 140 cases of asthma children diagnosed in our hospital during January 2017 to March 2018 were chosen as Asthma group, 100 cases of healthy children vaccinated in our hospital at the same time were chosen as Normal control group. Serum contents of IgE, Eotaxin, inflammatory mediators and airway remodeling indexes were detected in two groups. Correlation analysis was used to evaluate the relationship between serum IgE, Eotaxin content and severity of asthma.Results: Serum contents of IgE and Eotaxin in Asthma group were significantly higher than those in Normal control group, and contents of IL-9, IL-17, IL-18 and IL-33 were higher than those in Normal control group, IL-35 was lower than that in Normal control group;serum contents of MMP-2, MMP-9, TGF-β and VEGF in Asthma group were significantly higher than those in Normal control group (P<0.05). Pearson test found that serum contents of IgE, Eotaxin in asthma children were positively correlated with inflammatory mediators such as IL-9, IL-17, IL-18, IL-33, negatively correlated with IL-35;positively correlated with airway remodeling indexes such as MMP-2, MMP-9, TGF-β and VEGF.Conclusion: Serum contents of IgE, Eotaxin in asthma children are significantly higher than those in normal children, and the specific contents were closely related to the degree of systemic inflammatory response and airway remodeling.展开更多
Objective:To investigate the efficacy of botulinum toxin type A combined with nanofat in the treatment of facial rejuvenation.Methods:from January 2020 to January 2021,20 patients with facial wrinkles in our hospital(...Objective:To investigate the efficacy of botulinum toxin type A combined with nanofat in the treatment of facial rejuvenation.Methods:from January 2020 to January 2021,20 patients with facial wrinkles in our hospital(The First Affiliated Hospital of Dalian Medical University)were treated with botulinum toxin type A combined with nanofat,and the effect,duration and complications were observed.Results:After 1,3 and 6 months of injection,the effective rates were 90%,75%and 40%,respectively;there was no occurrence of postoperative infection,fat mass,granuloma,and other adverse reactions.Conclusion:Botulinum toxin type A combined with nanofat filling has a clear therapeutic effect in the facial rejuvenation treatment,and can improve the skin texture while improving wrinkles,which is worthy of further popularization and application in clinic.展开更多
Leucine-richα-2 glycoprotein 1(LRG1),a secreted glycoprotein,has been identified as significantly upregulated in renal fibrosis,potentially exacerbating the condition by enhancing TGF-β-Smad3-dependent signaling pat...Leucine-richα-2 glycoprotein 1(LRG1),a secreted glycoprotein,has been identified as significantly upregulated in renal fibrosis,potentially exacerbating the condition by enhancing TGF-β-Smad3-dependent signaling pathways.Herein,utilizing our developed LRG1-targeting peptide for LRG1 recruitment and lenalidomide for E3 ubiquitin ligase engagement,we developed an advanced proteolysis targeting chimera,^(ET)TAC-2,specifically designed for LRG1 degradation.Our cellular degradation assays validated that ^(ET)TAC-2 effectively degraded LRG1 through a proteasome-dependent mechanism,achieving halfmaximal degradation at a concentration of 8.38μM.Furthermore,anti-fibrotic experiments conducted both in vitro and in vivo revealed that ^(ET)TAC-2 efficiently induced LRG1 degradation in fibrotic kidneys.This action effectively inhibited the TGF-β-Smad3 signaling pathway and diminished the secretion of fibrosis-associated proteins,consequently attenuating the progression of renal fibrosis.Our study highlights the pivotal role of LRG1 in renal fibrosis and positions ^(ET)TAC-2 as a promising therapeutic candidate for targeted LRG1 intervention.展开更多
BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic ...BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia(VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process.METHODS A total of 48 rats were randomly divided into sham operation group(Sham group), CRF group, CRF + atorvastatin group(CRF + statin group), and CRF + etanercept group(CRF + rhTNFR-Fcgroup). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43(GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay.RESULTS Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay,immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fcgroup.CONCLUSIONS In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or inhibit its activity, thus inhibited the above effects, and reduced the occurrence of VA and sudden cardiac death.展开更多
基金supported by the National Natural Science Foundation of China,No.81473295(to ZMS),81373312(to XZ)and 81371028(to WCW)
文摘Chalcone is a plant metabolite widely found in fruits,vegetables,spices and tea,and has anti-tumor,anti-inflammation,immunomodulation,antibacterial and anti-oxidation activities,as well as many other pharmacological and biological effects.Our team has shown that its analogs have antioxidant activity,and oxidative stress is a pathological hallmark of retinal ischemia/reperfusion injury that can lead to retinal damage and visual loss.This investigation aims to identify a chalcone that protects retinal ganglion cells in vitro from the effects of oxidative stress and examine its mechanism.Rat retinal ganglion cell-5 cells were pretreated with chalcones and then exposed to tert-butyl hydroperoxide that causes oxidative damage.Controls received dimethyl sulfoxide only or tert-butyl hydroperoxide in dimethyl sulfoxide.Only（E）-3,4-dihydroxy-2′-methylether ketone（L2 H17）,of the five chalcone analogs,markedly increased the survival rate of oxidatively injured RGC-5 cells.Thus,subsequent experiments only analyzed the results of the L2 H17 intervention.Cell viability and apoptosis were measured.Intracellular superoxide dismutase and reactive oxygen species levels were used to assess induced oxidative stress.The mechanism of action by L2 H17 was explored by measuring the ER stress/UPR pathway and the expression and localization of Nrf2.All results demonstrated that L2 H17 could reduce the apoptosis of oxidatively injured cells,inhibit caspase-3 activity,increase Bcl-2 expression,decrease Bad expression,increase the activity of superoxide dismutase,inhibit the production of reactive oxygen species,increase Nrf2 immunoreactivity,and reduce the activating transcription factor 4,phospho-eukaryotic initiation factor 2 and CHOP expression.L2 H17 protects retinal ganglion cells induced by oxidative stress by regulating Nrf2,which indicates that it has the potential to become a drug for retinal ischemia/reperfusion.
基金National Natural Science Foundation of ChinaEducation Ministry of China.
文摘A kind of novel electroluminescence polymer has been prepared by oxidative-coupling polymerization of N-alkyl carbazole and trans-stilbene. The structure of the copolymers was characterized by elemental analysis, UV-vis and FTIR spectra. The copolymers have good solubility in chloroform and acetone. Fluorescence spectra showed that these polymers are blue-light emitting materials.
文摘Objective:To detect serum contents of IgE, Eotaxin and explore the relationship between serum IgE, Eotaxin and asthma severity.Methods: 140 cases of asthma children diagnosed in our hospital during January 2017 to March 2018 were chosen as Asthma group, 100 cases of healthy children vaccinated in our hospital at the same time were chosen as Normal control group. Serum contents of IgE, Eotaxin, inflammatory mediators and airway remodeling indexes were detected in two groups. Correlation analysis was used to evaluate the relationship between serum IgE, Eotaxin content and severity of asthma.Results: Serum contents of IgE and Eotaxin in Asthma group were significantly higher than those in Normal control group, and contents of IL-9, IL-17, IL-18 and IL-33 were higher than those in Normal control group, IL-35 was lower than that in Normal control group;serum contents of MMP-2, MMP-9, TGF-β and VEGF in Asthma group were significantly higher than those in Normal control group (P<0.05). Pearson test found that serum contents of IgE, Eotaxin in asthma children were positively correlated with inflammatory mediators such as IL-9, IL-17, IL-18, IL-33, negatively correlated with IL-35;positively correlated with airway remodeling indexes such as MMP-2, MMP-9, TGF-β and VEGF.Conclusion: Serum contents of IgE, Eotaxin in asthma children are significantly higher than those in normal children, and the specific contents were closely related to the degree of systemic inflammatory response and airway remodeling.
文摘Objective:To investigate the efficacy of botulinum toxin type A combined with nanofat in the treatment of facial rejuvenation.Methods:from January 2020 to January 2021,20 patients with facial wrinkles in our hospital(The First Affiliated Hospital of Dalian Medical University)were treated with botulinum toxin type A combined with nanofat,and the effect,duration and complications were observed.Results:After 1,3 and 6 months of injection,the effective rates were 90%,75%and 40%,respectively;there was no occurrence of postoperative infection,fat mass,granuloma,and other adverse reactions.Conclusion:Botulinum toxin type A combined with nanofat filling has a clear therapeutic effect in the facial rejuvenation treatment,and can improve the skin texture while improving wrinkles,which is worthy of further popularization and application in clinic.
基金supported by grants from the National Natural Science Foundation of China(32000998,32201240,and 81700638)The Young Elite Scientists Sponsorship Program by the Henan Association for Science and Technology(2022HYTP046)the China Postdoctoral Science Foundation(2021TQ0298).
文摘Leucine-richα-2 glycoprotein 1(LRG1),a secreted glycoprotein,has been identified as significantly upregulated in renal fibrosis,potentially exacerbating the condition by enhancing TGF-β-Smad3-dependent signaling pathways.Herein,utilizing our developed LRG1-targeting peptide for LRG1 recruitment and lenalidomide for E3 ubiquitin ligase engagement,we developed an advanced proteolysis targeting chimera,^(ET)TAC-2,specifically designed for LRG1 degradation.Our cellular degradation assays validated that ^(ET)TAC-2 effectively degraded LRG1 through a proteasome-dependent mechanism,achieving halfmaximal degradation at a concentration of 8.38μM.Furthermore,anti-fibrotic experiments conducted both in vitro and in vivo revealed that ^(ET)TAC-2 efficiently induced LRG1 degradation in fibrotic kidneys.This action effectively inhibited the TGF-β-Smad3 signaling pathway and diminished the secretion of fibrosis-associated proteins,consequently attenuating the progression of renal fibrosis.Our study highlights the pivotal role of LRG1 in renal fibrosis and positions ^(ET)TAC-2 as a promising therapeutic candidate for targeted LRG1 intervention.
基金supported by the Key Project of Tianjin Natural Science Foundation (No.21JCZDJC01080)the Tianjin Key Medical Discipline (Specialty) (TJYXZDX K-029A)+1 种基金the Academic Backbone of “Clinical Talent Training and Climbing Plan” of Tianjin Medical University and the Tianjin Health Research ProjectScience and Technology Development Fund of Nanjing Medical University (NMUB20210180)。
文摘BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia(VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process.METHODS A total of 48 rats were randomly divided into sham operation group(Sham group), CRF group, CRF + atorvastatin group(CRF + statin group), and CRF + etanercept group(CRF + rhTNFR-Fcgroup). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43(GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay.RESULTS Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay,immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fcgroup.CONCLUSIONS In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or inhibit its activity, thus inhibited the above effects, and reduced the occurrence of VA and sudden cardiac death.
