Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell e...Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.展开更多
The build-up of misfoldedα-synuclein(α-syn)in the central nervous system is the pathological hallmark of a number of neurodegenerative diseases that are known asα-synucleinopathies.These include Parkinson’s diseas...The build-up of misfoldedα-synuclein(α-syn)in the central nervous system is the pathological hallmark of a number of neurodegenerative diseases that are known asα-synucleinopathies.These include Parkinson’s disease(PD),Parkinson’s disease with dementia(PDD),dementia with Lewy body(LB),multiple system atrophy(MSA),and a subset of Alzheimer’s disease.Growing evidence underscores that the intercellular transmission and amplification of pathologicalα-syn are critical processes underlying the progression ofα-synucleinopathies(Peng et al.,2020),and as such,the study of these processes could lead to the identification of promising therapeutics to mitigate disease progression.Most previous studies have focused solely on pathological seeds in relation to disease progression.展开更多
Perovskite nanocrystals(PNCs)have recently become promising optoelectronic materials due to their excellent photophysical properties.However,the highly dynamic binding state between ligands and the surface of PNCs has...Perovskite nanocrystals(PNCs)have recently become promising optoelectronic materials due to their excellent photophysical properties.However,the highly dynamic binding state between ligands and the surface of PNCs has severely restricted their luminescent properties and stabilities.In this work,1,3-bisbenzyl-2-oxoimidazolidine-4,5-dicarboxylic acid(cycle acid,CA)is introduced as both an etchant and a ligand upon post-synthetic surface treatment of PNCs.By removing the imperfect octahedrons[Pb X_(6)]^(4-)and passivating the surface defects synergistically,this treatment improves photoluminescence quantum yields from 76%to 95%and enhances the stability of PNCs against polar solvent,moisture,heat,and illumination.Meanwhile,CA can effectively and instantly recover the luminescence emission for aged PNCs.As a result,the CA-Cs Pb Br_(3)PNCs and CA-Cs Pb IxBr_(3-x)PNCs are applied as color-converting layers on a blue LED chip for warm white light-emitting diodes(WLEDs)with a color coordinate of(0.41,0.40).Importantly,the CA-based WLED device exhibits superior stability in operational conditions.展开更多
Insulin-like growth factors(IGFs)are key regulators of development and growth.Here,we characterized the igf2 gene from olive flounder(Paralichthys olivaceus)and determined its temporal and spatial expression.We set up...Insulin-like growth factors(IGFs)are key regulators of development and growth.Here,we characterized the igf2 gene from olive flounder(Paralichthys olivaceus)and determined its temporal and spatial expression.We set up an in-vitro protein expression system in eukaryotic human embryonic kidney(HEK293 T)cells and explored its effects on cell proliferation.The flounder igf2 cDNA contained a 648-bp open reading frame(ORF)encoding a protein of 215 amino acids(aa),which spanned the complete signal peptide(47 aa),mature peptide(70 aa),and E domain(98 aa).In adult flounder,igf2 mRNA was detected in all selected tissues.In early development,igf2 mRNA was detected throughout development from unfertilized eggs to hatching-stage embryos.In-situ hybridization analysis indicated that igf2 mRNA was specially expressed in the brain region,floor plate,hypochord,otic vesicle,and pectoral fin during embryogenesis.Western blotting analysis indicated that the soluble recombinant flounder IGF2 protein was successfully produced through eukaryotic expression in HEK293T cells.In addition,the recombinant IGF2 protein significantly promoted the proliferation of human cervical carcinoma(HeLa)and HEK293T cells.These results provide new information about the structural and functional conservation,expression patterns,and biological activity of the igf2 in teleosts.展开更多
Objective: To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis(AD).Methods: Sixty specific-pathog...Objective: To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis(AD).Methods: Sixty specific-pathogen free male BALB/c mice were randomly divided into the control group,model group, whole formula group(WF), exterior-releasing formula group(ERF), interior-clearing formula group(ICF), and positive control group(PC). A mouse model of AD was established using the semiantigen 2,4-dinitrofluorobenzene induction method. The lesion scores, transepidermal water loss and p H, and skin histopathology of mice in each group were observed. The expressions of filaggrin, loricrin,and involucrin were detected by the streptavidin peroxidase immunohistochemical method and western blotting, and their mRNA expressions were detected by quantitative polymerase chain reaction.Results: Mice in the WF, ERF, ICF, and PC groups showed reduced skin lesion performance, improved histopathology, decreased skin lesion score, transepidermal water loss and pH, and upregulated expressions of proteins including filaggrin, loricrin, and involucrin, and their mRNAs. The most obvious regulatory effect was observed in the WF group, followed by the ICF, ERF, and PC groups, accordingly.Conclusions: Mahuang Lianqiao Chixiaodou decoction and its disassembled formula can improve the skin barrier function in a mouse model of AD by upregulating filaggrin, loricrin, and involucrin, and their mRNA expressions, and the most optimal effect was noted in the WF group, followed by the ICF and ERF groups, which suggests that the effect of clearing heat and resolving dampness in improving the skin barrier function of AD is more obvious and is one of the key treatments for AD.展开更多
Objective:To establish an animal model consistent with the occurrence and development of non-alcoholic fatty liver disease(NAFLD)with which to assess the effects of a classical traditional Chinese medicine formula kno...Objective:To establish an animal model consistent with the occurrence and development of non-alcoholic fatty liver disease(NAFLD)with which to assess the effects of a classical traditional Chinese medicine formula known as Dachaihu Decoction(DD)on NAFLD.Methods:Sixty rats were randomized into four groups:control,model,pioglitazone hydrochloride(PH)and DD in equal.NAFLD was produced via administration of a high-fat high-sugar diet for 16 weeks in all but the control group.From the 13th week,a solution of PH or DD prepared with water was delivered via intragastric administration to the PH and DD groups;the remaining two groups received an equivalent volume of distilled water.Twelve hours from the last administration,we selected eight rats from each group in random.After anesthetization,the abdominal aorta blood and liver tissues were collected.The morphological changes were observed and the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),highdensity lipoprotein cholesterol(HDL-C),fasting plasma glucose(FBG),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),toll-like receptor-4(TLR4),and nuclear factor-kappa B(NF-κB)were tested.Results:Compared with the control group,the levels of serum ALT,AST,TC,TG,LDL-C and FBG,and TGF-β1,TNF-α,TLR4,NF-κB in the model group all showed significant increases(P<.01).Compared with the model group,these same indicators in the PH and DD groups all showed remarkable decreases(P<.05).Conclusion:The efficacy of DD in NAFLD rats was shown to be effectively equivalent to that of PH,with demonstrated effects of DD that included reductions in hepatic steatosis and serum and hepatic lipid levels,and lowered blood glucose levels.We deduce that DD has an inhibitory effect on NAFLD induced by a high-fat high-sugar diet in rats.展开更多
Objective:To identify the molecular mechanisms of the effects of the Buyin Qianzheng formula(BYQZF)on the mitochondrial dynamics in a Parkin overexpression Parkinson's disease(PD)cell model.Methods:First,a stable ...Objective:To identify the molecular mechanisms of the effects of the Buyin Qianzheng formula(BYQZF)on the mitochondrial dynamics in a Parkin overexpression Parkinson's disease(PD)cell model.Methods:First,a stable Parkin overexpression cell model was constructed using plasmid transfection.Then,we examined the protective effect of BYQZF on the mitochondrial dysfunction of the Parkin overexpression PD cell model induced by neurotoxin 1-methyl-4-phenylpyridinium ion(MPPþ).The mRNA expression level of Parkin was evaluated using real-time quantitative PCR.The cell survival rate was detected using the Cell Counting Kit-8 assay.We evaluated the cellular adenosine triphosphate(ATP)levels using luciferase assays.A laser scanning confocal microscope was used to observe the mitochondrial morphology,activity,and mitochondrial membrane potential(DJm).Western blot was conducted to evaluate the levels of the fusion proteins mitofusin1,mitofusin2,optic atrophy 1,dynaminrelated protein 1,and mitochondrial fission protein 1.Results:Parkin overexpression attenuated MPPþ-induced mitochondrial damage,increased mitochondrial activity and DJm.BYQZF increased the survival of MPPþ-induced cells that overexpressed Parkin and upregulated the mitochondrial form factor and activity.It also inhibited a decrease in the DJm and ATP levels.These findings suggested that BYQZF protected against MPPþ-induced mitochondrial dysfunction and enhanced the protective effect of Parkin overexpression.Furthermore,the formula upregulated the expression of the fusion proteins mitofusin1,mitofusin2,and optic atrophy 1(closely related to mitochondrial quality remodeling),and reduced the expression of the fission protein dynamicrelated protein 1,as well as mitochondrial fission protein 1.Conclusion:The mechanism by which BYQZF increased the mitochondrial protective effect of Parkin gene overexpression in MPPþ-induced cells may be related to improving mitochondrial function and regulating the balance of mitochondrial division and fusion proteins.展开更多
Objective:To explore the potential mechanism of intervention on the immune imbalance of atopic dermatitis(AD) by studying the effects of Mahuang Lianqiao Chixiaodou decoction(MLCD) on skin damage and inflammation fact...Objective:To explore the potential mechanism of intervention on the immune imbalance of atopic dermatitis(AD) by studying the effects of Mahuang Lianqiao Chixiaodou decoction(MLCD) on skin damage and inflammation factors in an AD-like mouse model.Methods:Ninety-six male BALB/c mice were divided into normal,model,positive control(mometasone furoate),and traditional Chinese medicine treatment(MLCD) groups by a random number table.2,4-dinitrofluorobenzene was used to induce AD-like mice in all groups except the normal group.The treatment or intervention was administered for seven consecutive days on days 4,18,32,and 39.The mRNA relative expressions of interleukin-4(IL-4),IL-10,interferon-γ(IFN-γ),thymic stromal lymphopoietin(TSLP),and the TSLP receptor(TSLPR) were measured using quantitative real-time polymerase chain reaction,and the serum immunoglobulin E,IL-4,IL-10,and IFN-γ levels were detected using enzyme-linked immunosorbent assay.Results:Compared with the normal group,the hematoxylin-eosin staining of the skin lesions of the mice in the model group was significantly thickened on days 11,25,and 39.Compared with the model group,the epidermal thickness of the positive control group was significantly alleviated on day 39(P <.001),and that of the MLCD group was significantly improved on days 25 and 39(P <.001).Compared with the four observation time points,MLCD had the best treatment effect on day 39 of the experiment and significantly improved the skin damage performance and relieved pathological lesions.On day 39,compared with the model group,MLCD downregulated the skin mRNA relative expressions of IL-4(P=.009),TSLP(P=.030),and TSLPR(P <.001),and reduced the mouse serum levels of IL-4(P=.003).For other serum indicators,no significant difference was observed between the model and MLCD groups.Conclusion:MLCD improved AD-like mice skin damage by regulating the Th1/Th2 immune imbalance.展开更多
Objective:It has been documented that ezrin/radixin/moesin(ERM)phosphorylation by the p38 mitogen-activated protein kinase(MAPK),Rho/ROCK,and protein kinase C(PKC)pathways leads to filamentous actin(F-actin)reorganiza...Objective:It has been documented that ezrin/radixin/moesin(ERM)phosphorylation by the p38 mitogen-activated protein kinase(MAPK),Rho/ROCK,and protein kinase C(PKC)pathways leads to filamentous actin(F-actin)reorganization and microvascular endothelial cell hyperpermeability.In this study,we investigated the effects of Xijiao Dihuang Decoction combined with Yinqiao Powder(XDY)on influenza virus(IV)-induced F-actin restructuring and ERM phosphorylation regulated by the Rho/Rho kinase 1(ROCK),p38 MAPK,and PKC signaling pathways in pulmonary microvascular endothelial cells(PMVECs).Methods:Serum containing XDY(XDY-CS;13.8 g/kg)was acquired using standard protocols for serum pharmacology.Primary PMVECs were obtained from male Wistar rats and cultured.After adsorption of IV A(multiplicity of infection,0.01)for 1 h,medium with 20%XDY-CS was added to the PMVECs.The distributions of F-actin and phosphorylated ERM were determined by confocal microscopy,and F-actin expression was measured by flow cytometry.The expression levels of ROCK1,phosphorylated myosin phosphatase target-subunit(p-MYPT),phosphorylated MAPK kinase,phosphorylated p38(p-p38),phosphorylated PKC(p-PKC),and phosphorylated ERM(p-ERM)were determined by western blotting.Results:F-actin reorganization in IV-infected PMVECs was reversed by XDY-CS treatment,which was accompanied by reduced p-ERM production.The p-ERM protein accumulated at plasma membrane of PMVECs infected with IV,which was also inhibited by XDY-CS treatment.展开更多
Objective:Ephedrine hydrochloride(EH)is a major component from Ephedra sinica STAPF,which is used as a traditional Chinese herbal medicine.This study was designed to investigate the effect of EH on water metabolism an...Objective:Ephedrine hydrochloride(EH)is a major component from Ephedra sinica STAPF,which is used as a traditional Chinese herbal medicine.This study was designed to investigate the effect of EH on water metabolism and further explore the relevant signaling pathway of body fluid regulation in“lung governing regulation of water passage”using a rabbit model of mechanical ventilation.The molecular mechanism of the EH effect in the kidney was also investigated.Methods:Rabbits were randomly divided into a control group,model group,EH group,and dexmedetomidine hydrochloride(DH)group.Urine volume was measured by the intubation method and pathologic changes in lung and renal tissue were measured by hematoxylin and eosin staining.Nitric oxide(NO)production in lung,serum,and kidney were analyzed using chemical methods.An ELISA was used to analyze angiotensin II(Ang II),antidiuretic hormone(ADH),prostaglandin E2(PGE2),atrial natriuretic peptide(ANP),and endothelin-1(ET-1)levels in the lung,serum,and kidney.Aquaporin-1(AQP1)and aquaporin-2(AQP2)mRNA and protein expression in the kidney was determined using qRT-PCR and immunohistochemistry.Results:EH significantly inhibited the decrease in the total urine volume in the third and fourth stages,and displayed significant regulatory effects on NO,Ang II,ADH,PGE2,ANP,and ET-1 in serum,lung,and renal tissues compared with the model group.In the kidney,AQP1 and AQP2 mRNA and protein expression in the EH group were remarkably downregulated compared with the model group.Conclusion:EH exerted a regulatory effect on water metabolism by diffusing the lung and increased urine volume in the rabbit model,which was consistent with the decrease in kidney AQP1 and AQP2 expression levels that led to an increase in urine volume.EH could assist with DH to exert a protective effect on the clinical application of mechanical ventilation.展开更多
Objective:To observe the effect of respiratory-function changes on urinary output and expression of aquaporin (AQP) in kidney tissue in bronchial asthma (BA) model mice.To explore the correlation between the lung cont...Objective:To observe the effect of respiratory-function changes on urinary output and expression of aquaporin (AQP) in kidney tissue in bronchial asthma (BA) model mice.To explore the correlation between the lung controlling breathing and the lung regulating the waterways,and observe regulation by the lung-diffusing herb platycodon root (Platycodon grandiflorus (JACQ.) A.DC.).Methods:Forty-five healthy female Balb/c mice were divided randomly into normal,model and platycodon root groups.The BA model was replicated by complex sensitization and stimulation with ovalbumin (OVA).Changes in airway resistance were detected using an AniRes2005 system,and 24-hour urine output collected by metabolic cages.Histopathologic changes in the lung and kidney were observed by H&rE staining.Expression of the mRNA of AQP1 and AQP2 was detected by reverse transcription-polymerase chain reaction,immunohistochemistry,and immunofluorescence.Results:Compared with the normal group,airway resistance in the inspiratory phase intensified in the model group (P <.01).Following the pathologic changes in lung tissue,but no significant change in kidney tissue,24-hour urinary output decreased significantly (P <.05),and levels of AQP1,AQP2 and their mRNA increased significantly in the model group (P <.01).Compared with the model group,airway resistance in the inspiratory phase was weakened(P <.01).The urinary output increased (P <.05),pathologic changes in lung tissues decreased,and renal expression of AQP1,AQP2 and their mRNA decreased significantly (P <.01) in the platycodon root group.Conclusion:Changes in respiratory function in BA model mice can affect how the lung regulates water pathways.Platycodon root diffusing the lung can ameliorate the respiratoryfunction and pathologic changes in the lung tissues of BA model mice,but also regulate urinary output and renal expression of AQP1 and AQP2.展开更多
Objective:To explore biological mechanisms underlying the traditional Chinese medicine theory of 'lung governing the regulation of water passage' by observing effects of mechanical ventilation on urine volume ...Objective:To explore biological mechanisms underlying the traditional Chinese medicine theory of 'lung governing the regulation of water passage' by observing effects of mechanical ventilation on urine volume and related bioactive substances.Methods:A total of 16 male rabbits were randomly divided into control and lung expansion model groups (n =8 per group),which were examined during the following four respiratory intervention stages (10 minutes each):(1) free breathing without any respiratory intervention;(2) lung expansion induced by mechanical ventilator;(3) free breathing without ventilator intervention;(4) cutting of bilateral sympathetic,vagus,and depressor nerves with mechanical ventilation.Data for breathing rate,blood pressure,and urine drops were recorded with a Medlab data acquisition system.Levels of nitric oxide (NO),antidiuretic hormone (ADH),endothelin 1 (ET-1),angiotensin Ⅱ (AngⅡ),prostaglandin E2 (PGE2),and atrial natriuretic peptide (ANP) were detected in lung tissue,kidney tissue,and serum by enzyme-linked immunosorbent assay.Protein expression of aquaporins 1 and 2 (AQP1 and AQP2) was detected in kidney tissue by immunohistochemistry,while Aqp1 mRNA and Aqp2 mRNA levels in kidney tissue were detected by real-time quantitative polymerase chain reaction.Histopathological changes in lung and kidney tissues were examined by hematoxylin and eosin staining.Results:Compared with the control group,number of urine drops during the second and fourth stages is significantly decreased in the model group (P <.05).In addition,NO and PGE2 content in lung and kidney tissues was significantly decreased in the model group (P <.05).ANP content in model group lung and kidney tissues was significantly increased (P <.05),while ET-1 content in these tissues was significantly decreased (P <.05).AngⅡ content in kidney tissue was significantly decreased in the model group (P <.05),while serum AngⅡ content of the animals was significantly increased (P <.05).Expression of AQP1 and AQP2 proteins in kidney tissue was significantly higher in the model group than in the control group (P <.05).No obvious histopathological changes were observed in lung or kidney tissues of animals in either group.Conclusions:Mechanical ventilation reduced urine volume,increased expression of AQP1 and AQP2 in kidney tissue,and altered levels of NO,ADH,ET-1,AngⅡ,PGE2,and ANP in lung tissue,kidney tissue,and serum.These results provide an experimental basis for preliminary studies of mechanisms under pinning the theory of 'lung governing the regulation of water passage'.展开更多
Crystallization of flexible polymer chains reveals distinct characters compared to small molecules, which provides a platform to study molecular self-assembly and morphogenesis. In this review, some examples,e.g., twi...Crystallization of flexible polymer chains reveals distinct characters compared to small molecules, which provides a platform to study molecular self-assembly and morphogenesis. In this review, some examples,e.g., twisting chirality of polymer lamellar crystals, recognition of different chain units and competitive nucleation of different polymorphs and different lamellar thicknesses are briefly discussed. It is shown that the polymer crystallization process far from equilibrium is in practically minimization of the system free energy in local space and finite time, leading to formation of twisted crystals, metastable polymorphism and lamellar crystals with finite thickness. Though each molecule is blind to others, the peculiar ordered configurations with stronger long-range interactions are chosen from the enormous random trials. At the end, we list some remaining questions and outlook the perspectives.展开更多
基金supported by the National Natural Science Foundation of China(82074036).
文摘Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.
文摘The build-up of misfoldedα-synuclein(α-syn)in the central nervous system is the pathological hallmark of a number of neurodegenerative diseases that are known asα-synucleinopathies.These include Parkinson’s disease(PD),Parkinson’s disease with dementia(PDD),dementia with Lewy body(LB),multiple system atrophy(MSA),and a subset of Alzheimer’s disease.Growing evidence underscores that the intercellular transmission and amplification of pathologicalα-syn are critical processes underlying the progression ofα-synucleinopathies(Peng et al.,2020),and as such,the study of these processes could lead to the identification of promising therapeutics to mitigate disease progression.Most previous studies have focused solely on pathological seeds in relation to disease progression.
基金supported by the National Natural Science Foundation of China(82374321)the Jie-Bang-Gua-Shuai Project of the Beijing University of Chinese Medicine(2023-JYB-JBZD-035).
文摘目的:探讨麻黄连翘赤小豆汤(Mahuang Lianqiao Chixiaodou decoction,MLCD)通过NOD样受体蛋白3(NOD-like receptor protein 3,NLRP3)角质形成细胞焦亡途径干预特应性皮炎样(atopic dermatitis-like,AD样)小鼠皮肤屏障功能障碍与免疫炎症“内外串扰”的疗效及机制。方法:用2,4-二硝基氟苯诱导AD样模型小鼠,分别用MLCD或糠酸莫米松凝胶(mometasone furoate,MF,阳性对照组)处理7天。采用马松染色法、甲苯胺蓝染色法检测皮肤组织的病理变化与肥大细胞浸润情况。采用智能皮肤分析仪、流式细胞术、荧光定量聚合酶链反应和免疫印迹法观察和评估AD样小鼠的皮肤屏障功能障碍、免疫炎症反应和皮肤细胞焦亡。结果:MLCD和MF均可不同程度地改善AD样小鼠的皮损状态,减少病理组织损伤和肥大细胞浸润。MLCD显著降低皮肤色素沉着和炎症状态(P=0.005,P=0.038),增加脾脏中CD4^(+)CD3^(+)T细胞的百分比(P=0.022),降低CD8^(+)CD3^(+)T细胞百分比(P=0.044),降低CD8^(+)CD3^(+)/CD3^(+)的比值(P=0.031),并增加CD4^(+)CD3^(+)/CD8^(+)CD3^(+)的比值(P=0.027)。MLCD还可显著降低角质形成细胞焦亡相关因子NLRP3、casp-1、白细胞介素(IL)-1β和IL-18得mRNA相对表达水平(P=0.027、P<0.001、P=0.012和P=0.039)以及NLRP3、casp-1、凋亡相关斑点蛋白和IL-1β的蛋白表达水平(P=0.002、P=0.006、P=0.004和P=0.035)。结论:MLCD通过干预NLRP3角质形成细胞焦亡介导的皮肤屏障功能障碍和免疫炎症的“内外串扰”机制,对AD样小鼠的治疗具有疗效。
基金financial from the National Natural Science Foundation of China(22279039 and 20181194)the Chinese National 1000-Talent-Plan program+2 种基金the Innovation Project of Optics Valley Laboratory(OVL2021BG008)the Frontier of the Application Foundation of Wuhan Science and Technology Plan Project(2020010601012202)the Foundation of State Key Laboratory of New Textile Materials and Advanced Processing Technologies(FZ2021011)。
文摘Perovskite nanocrystals(PNCs)have recently become promising optoelectronic materials due to their excellent photophysical properties.However,the highly dynamic binding state between ligands and the surface of PNCs has severely restricted their luminescent properties and stabilities.In this work,1,3-bisbenzyl-2-oxoimidazolidine-4,5-dicarboxylic acid(cycle acid,CA)is introduced as both an etchant and a ligand upon post-synthetic surface treatment of PNCs.By removing the imperfect octahedrons[Pb X_(6)]^(4-)and passivating the surface defects synergistically,this treatment improves photoluminescence quantum yields from 76%to 95%and enhances the stability of PNCs against polar solvent,moisture,heat,and illumination.Meanwhile,CA can effectively and instantly recover the luminescence emission for aged PNCs.As a result,the CA-Cs Pb Br_(3)PNCs and CA-Cs Pb IxBr_(3-x)PNCs are applied as color-converting layers on a blue LED chip for warm white light-emitting diodes(WLEDs)with a color coordinate of(0.41,0.40).Importantly,the CA-based WLED device exhibits superior stability in operational conditions.
基金Supported by the National Natural Science Foundation of China(No.31972774)the National Natural Science Foundation of China(No.31672636)the Key Research and Development Program of Shandong Province,China(No.2019GHY112007)。
文摘Insulin-like growth factors(IGFs)are key regulators of development and growth.Here,we characterized the igf2 gene from olive flounder(Paralichthys olivaceus)and determined its temporal and spatial expression.We set up an in-vitro protein expression system in eukaryotic human embryonic kidney(HEK293 T)cells and explored its effects on cell proliferation.The flounder igf2 cDNA contained a 648-bp open reading frame(ORF)encoding a protein of 215 amino acids(aa),which spanned the complete signal peptide(47 aa),mature peptide(70 aa),and E domain(98 aa).In adult flounder,igf2 mRNA was detected in all selected tissues.In early development,igf2 mRNA was detected throughout development from unfertilized eggs to hatching-stage embryos.In-situ hybridization analysis indicated that igf2 mRNA was specially expressed in the brain region,floor plate,hypochord,otic vesicle,and pectoral fin during embryogenesis.Western blotting analysis indicated that the soluble recombinant flounder IGF2 protein was successfully produced through eukaryotic expression in HEK293T cells.In addition,the recombinant IGF2 protein significantly promoted the proliferation of human cervical carcinoma(HeLa)and HEK293T cells.These results provide new information about the structural and functional conservation,expression patterns,and biological activity of the igf2 in teleosts.
基金supported by the Natural Science Foundation of Beijing Municipality Surface Project(7192114)。
文摘Objective: To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis(AD).Methods: Sixty specific-pathogen free male BALB/c mice were randomly divided into the control group,model group, whole formula group(WF), exterior-releasing formula group(ERF), interior-clearing formula group(ICF), and positive control group(PC). A mouse model of AD was established using the semiantigen 2,4-dinitrofluorobenzene induction method. The lesion scores, transepidermal water loss and p H, and skin histopathology of mice in each group were observed. The expressions of filaggrin, loricrin,and involucrin were detected by the streptavidin peroxidase immunohistochemical method and western blotting, and their mRNA expressions were detected by quantitative polymerase chain reaction.Results: Mice in the WF, ERF, ICF, and PC groups showed reduced skin lesion performance, improved histopathology, decreased skin lesion score, transepidermal water loss and pH, and upregulated expressions of proteins including filaggrin, loricrin, and involucrin, and their mRNAs. The most obvious regulatory effect was observed in the WF group, followed by the ICF, ERF, and PC groups, accordingly.Conclusions: Mahuang Lianqiao Chixiaodou decoction and its disassembled formula can improve the skin barrier function in a mouse model of AD by upregulating filaggrin, loricrin, and involucrin, and their mRNA expressions, and the most optimal effect was noted in the WF group, followed by the ICF and ERF groups, which suggests that the effect of clearing heat and resolving dampness in improving the skin barrier function of AD is more obvious and is one of the key treatments for AD.
基金supported by the National Natural Science Foundation of China(81673868).
文摘Objective:To establish an animal model consistent with the occurrence and development of non-alcoholic fatty liver disease(NAFLD)with which to assess the effects of a classical traditional Chinese medicine formula known as Dachaihu Decoction(DD)on NAFLD.Methods:Sixty rats were randomized into four groups:control,model,pioglitazone hydrochloride(PH)and DD in equal.NAFLD was produced via administration of a high-fat high-sugar diet for 16 weeks in all but the control group.From the 13th week,a solution of PH or DD prepared with water was delivered via intragastric administration to the PH and DD groups;the remaining two groups received an equivalent volume of distilled water.Twelve hours from the last administration,we selected eight rats from each group in random.After anesthetization,the abdominal aorta blood and liver tissues were collected.The morphological changes were observed and the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),highdensity lipoprotein cholesterol(HDL-C),fasting plasma glucose(FBG),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),toll-like receptor-4(TLR4),and nuclear factor-kappa B(NF-κB)were tested.Results:Compared with the control group,the levels of serum ALT,AST,TC,TG,LDL-C and FBG,and TGF-β1,TNF-α,TLR4,NF-κB in the model group all showed significant increases(P<.01).Compared with the model group,these same indicators in the PH and DD groups all showed remarkable decreases(P<.05).Conclusion:The efficacy of DD in NAFLD rats was shown to be effectively equivalent to that of PH,with demonstrated effects of DD that included reductions in hepatic steatosis and serum and hepatic lipid levels,and lowered blood glucose levels.We deduce that DD has an inhibitory effect on NAFLD induced by a high-fat high-sugar diet in rats.
基金This work is supported by the National Natural Science Foundation of China(81774110 and 81573773).
文摘Objective:To identify the molecular mechanisms of the effects of the Buyin Qianzheng formula(BYQZF)on the mitochondrial dynamics in a Parkin overexpression Parkinson's disease(PD)cell model.Methods:First,a stable Parkin overexpression cell model was constructed using plasmid transfection.Then,we examined the protective effect of BYQZF on the mitochondrial dysfunction of the Parkin overexpression PD cell model induced by neurotoxin 1-methyl-4-phenylpyridinium ion(MPPþ).The mRNA expression level of Parkin was evaluated using real-time quantitative PCR.The cell survival rate was detected using the Cell Counting Kit-8 assay.We evaluated the cellular adenosine triphosphate(ATP)levels using luciferase assays.A laser scanning confocal microscope was used to observe the mitochondrial morphology,activity,and mitochondrial membrane potential(DJm).Western blot was conducted to evaluate the levels of the fusion proteins mitofusin1,mitofusin2,optic atrophy 1,dynaminrelated protein 1,and mitochondrial fission protein 1.Results:Parkin overexpression attenuated MPPþ-induced mitochondrial damage,increased mitochondrial activity and DJm.BYQZF increased the survival of MPPþ-induced cells that overexpressed Parkin and upregulated the mitochondrial form factor and activity.It also inhibited a decrease in the DJm and ATP levels.These findings suggested that BYQZF protected against MPPþ-induced mitochondrial dysfunction and enhanced the protective effect of Parkin overexpression.Furthermore,the formula upregulated the expression of the fusion proteins mitofusin1,mitofusin2,and optic atrophy 1(closely related to mitochondrial quality remodeling),and reduced the expression of the fission protein dynamicrelated protein 1,as well as mitochondrial fission protein 1.Conclusion:The mechanism by which BYQZF increased the mitochondrial protective effect of Parkin gene overexpression in MPPþ-induced cells may be related to improving mitochondrial function and regulating the balance of mitochondrial division and fusion proteins.
基金This study was supported by the Beijing Natural Science Foundation(7192114).
文摘Objective:To explore the potential mechanism of intervention on the immune imbalance of atopic dermatitis(AD) by studying the effects of Mahuang Lianqiao Chixiaodou decoction(MLCD) on skin damage and inflammation factors in an AD-like mouse model.Methods:Ninety-six male BALB/c mice were divided into normal,model,positive control(mometasone furoate),and traditional Chinese medicine treatment(MLCD) groups by a random number table.2,4-dinitrofluorobenzene was used to induce AD-like mice in all groups except the normal group.The treatment or intervention was administered for seven consecutive days on days 4,18,32,and 39.The mRNA relative expressions of interleukin-4(IL-4),IL-10,interferon-γ(IFN-γ),thymic stromal lymphopoietin(TSLP),and the TSLP receptor(TSLPR) were measured using quantitative real-time polymerase chain reaction,and the serum immunoglobulin E,IL-4,IL-10,and IFN-γ levels were detected using enzyme-linked immunosorbent assay.Results:Compared with the normal group,the hematoxylin-eosin staining of the skin lesions of the mice in the model group was significantly thickened on days 11,25,and 39.Compared with the model group,the epidermal thickness of the positive control group was significantly alleviated on day 39(P <.001),and that of the MLCD group was significantly improved on days 25 and 39(P <.001).Compared with the four observation time points,MLCD had the best treatment effect on day 39 of the experiment and significantly improved the skin damage performance and relieved pathological lesions.On day 39,compared with the model group,MLCD downregulated the skin mRNA relative expressions of IL-4(P=.009),TSLP(P=.030),and TSLPR(P <.001),and reduced the mouse serum levels of IL-4(P=.003).For other serum indicators,no significant difference was observed between the model and MLCD groups.Conclusion:MLCD improved AD-like mice skin damage by regulating the Th1/Th2 immune imbalance.
基金This work was supported by funding from the National Natural Science Foundation of China(Grant Nos.81473520 and 81102697).
文摘Objective:It has been documented that ezrin/radixin/moesin(ERM)phosphorylation by the p38 mitogen-activated protein kinase(MAPK),Rho/ROCK,and protein kinase C(PKC)pathways leads to filamentous actin(F-actin)reorganization and microvascular endothelial cell hyperpermeability.In this study,we investigated the effects of Xijiao Dihuang Decoction combined with Yinqiao Powder(XDY)on influenza virus(IV)-induced F-actin restructuring and ERM phosphorylation regulated by the Rho/Rho kinase 1(ROCK),p38 MAPK,and PKC signaling pathways in pulmonary microvascular endothelial cells(PMVECs).Methods:Serum containing XDY(XDY-CS;13.8 g/kg)was acquired using standard protocols for serum pharmacology.Primary PMVECs were obtained from male Wistar rats and cultured.After adsorption of IV A(multiplicity of infection,0.01)for 1 h,medium with 20%XDY-CS was added to the PMVECs.The distributions of F-actin and phosphorylated ERM were determined by confocal microscopy,and F-actin expression was measured by flow cytometry.The expression levels of ROCK1,phosphorylated myosin phosphatase target-subunit(p-MYPT),phosphorylated MAPK kinase,phosphorylated p38(p-p38),phosphorylated PKC(p-PKC),and phosphorylated ERM(p-ERM)were determined by western blotting.Results:F-actin reorganization in IV-infected PMVECs was reversed by XDY-CS treatment,which was accompanied by reduced p-ERM production.The p-ERM protein accumulated at plasma membrane of PMVECs infected with IV,which was also inhibited by XDY-CS treatment.
基金the National Natural Science Foundation of China(No.81373503).
文摘Objective:Ephedrine hydrochloride(EH)is a major component from Ephedra sinica STAPF,which is used as a traditional Chinese herbal medicine.This study was designed to investigate the effect of EH on water metabolism and further explore the relevant signaling pathway of body fluid regulation in“lung governing regulation of water passage”using a rabbit model of mechanical ventilation.The molecular mechanism of the EH effect in the kidney was also investigated.Methods:Rabbits were randomly divided into a control group,model group,EH group,and dexmedetomidine hydrochloride(DH)group.Urine volume was measured by the intubation method and pathologic changes in lung and renal tissue were measured by hematoxylin and eosin staining.Nitric oxide(NO)production in lung,serum,and kidney were analyzed using chemical methods.An ELISA was used to analyze angiotensin II(Ang II),antidiuretic hormone(ADH),prostaglandin E2(PGE2),atrial natriuretic peptide(ANP),and endothelin-1(ET-1)levels in the lung,serum,and kidney.Aquaporin-1(AQP1)and aquaporin-2(AQP2)mRNA and protein expression in the kidney was determined using qRT-PCR and immunohistochemistry.Results:EH significantly inhibited the decrease in the total urine volume in the third and fourth stages,and displayed significant regulatory effects on NO,Ang II,ADH,PGE2,ANP,and ET-1 in serum,lung,and renal tissues compared with the model group.In the kidney,AQP1 and AQP2 mRNA and protein expression in the EH group were remarkably downregulated compared with the model group.Conclusion:EH exerted a regulatory effect on water metabolism by diffusing the lung and increased urine volume in the rabbit model,which was consistent with the decrease in kidney AQP1 and AQP2 expression levels that led to an increase in urine volume.EH could assist with DH to exert a protective effect on the clinical application of mechanical ventilation.
基金This study was supported by the National Natural Science Foundation of China(81373503).
文摘Objective:To observe the effect of respiratory-function changes on urinary output and expression of aquaporin (AQP) in kidney tissue in bronchial asthma (BA) model mice.To explore the correlation between the lung controlling breathing and the lung regulating the waterways,and observe regulation by the lung-diffusing herb platycodon root (Platycodon grandiflorus (JACQ.) A.DC.).Methods:Forty-five healthy female Balb/c mice were divided randomly into normal,model and platycodon root groups.The BA model was replicated by complex sensitization and stimulation with ovalbumin (OVA).Changes in airway resistance were detected using an AniRes2005 system,and 24-hour urine output collected by metabolic cages.Histopathologic changes in the lung and kidney were observed by H&rE staining.Expression of the mRNA of AQP1 and AQP2 was detected by reverse transcription-polymerase chain reaction,immunohistochemistry,and immunofluorescence.Results:Compared with the normal group,airway resistance in the inspiratory phase intensified in the model group (P <.01).Following the pathologic changes in lung tissue,but no significant change in kidney tissue,24-hour urinary output decreased significantly (P <.05),and levels of AQP1,AQP2 and their mRNA increased significantly in the model group (P <.01).Compared with the model group,airway resistance in the inspiratory phase was weakened(P <.01).The urinary output increased (P <.05),pathologic changes in lung tissues decreased,and renal expression of AQP1,AQP2 and their mRNA decreased significantly (P <.01) in the platycodon root group.Conclusion:Changes in respiratory function in BA model mice can affect how the lung regulates water pathways.Platycodon root diffusing the lung can ameliorate the respiratoryfunction and pathologic changes in the lung tissues of BA model mice,but also regulate urinary output and renal expression of AQP1 and AQP2.
基金This study was funded by the National Natural Science Foundation of China(81373503).
文摘Objective:To explore biological mechanisms underlying the traditional Chinese medicine theory of 'lung governing the regulation of water passage' by observing effects of mechanical ventilation on urine volume and related bioactive substances.Methods:A total of 16 male rabbits were randomly divided into control and lung expansion model groups (n =8 per group),which were examined during the following four respiratory intervention stages (10 minutes each):(1) free breathing without any respiratory intervention;(2) lung expansion induced by mechanical ventilator;(3) free breathing without ventilator intervention;(4) cutting of bilateral sympathetic,vagus,and depressor nerves with mechanical ventilation.Data for breathing rate,blood pressure,and urine drops were recorded with a Medlab data acquisition system.Levels of nitric oxide (NO),antidiuretic hormone (ADH),endothelin 1 (ET-1),angiotensin Ⅱ (AngⅡ),prostaglandin E2 (PGE2),and atrial natriuretic peptide (ANP) were detected in lung tissue,kidney tissue,and serum by enzyme-linked immunosorbent assay.Protein expression of aquaporins 1 and 2 (AQP1 and AQP2) was detected in kidney tissue by immunohistochemistry,while Aqp1 mRNA and Aqp2 mRNA levels in kidney tissue were detected by real-time quantitative polymerase chain reaction.Histopathological changes in lung and kidney tissues were examined by hematoxylin and eosin staining.Results:Compared with the control group,number of urine drops during the second and fourth stages is significantly decreased in the model group (P <.05).In addition,NO and PGE2 content in lung and kidney tissues was significantly decreased in the model group (P <.05).ANP content in model group lung and kidney tissues was significantly increased (P <.05),while ET-1 content in these tissues was significantly decreased (P <.05).AngⅡ content in kidney tissue was significantly decreased in the model group (P <.05),while serum AngⅡ content of the animals was significantly increased (P <.05).Expression of AQP1 and AQP2 proteins in kidney tissue was significantly higher in the model group than in the control group (P <.05).No obvious histopathological changes were observed in lung or kidney tissues of animals in either group.Conclusions:Mechanical ventilation reduced urine volume,increased expression of AQP1 and AQP2 in kidney tissue,and altered levels of NO,ADH,ET-1,AngⅡ,PGE2,and ANP in lung tissue,kidney tissue,and serum.These results provide an experimental basis for preliminary studies of mechanisms under pinning the theory of 'lung governing the regulation of water passage'.
基金the National Natural Science Foundation of China (No. 21374054)Fund of Key Laboratory of Advanced Materials of Ministry of Education (No. 2017AML07) for financial support
文摘Crystallization of flexible polymer chains reveals distinct characters compared to small molecules, which provides a platform to study molecular self-assembly and morphogenesis. In this review, some examples,e.g., twisting chirality of polymer lamellar crystals, recognition of different chain units and competitive nucleation of different polymorphs and different lamellar thicknesses are briefly discussed. It is shown that the polymer crystallization process far from equilibrium is in practically minimization of the system free energy in local space and finite time, leading to formation of twisted crystals, metastable polymorphism and lamellar crystals with finite thickness. Though each molecule is blind to others, the peculiar ordered configurations with stronger long-range interactions are chosen from the enormous random trials. At the end, we list some remaining questions and outlook the perspectives.
