Objective:Buyinqianzheng Formula(BYQZF)is clinically employed in traditional Chinese medicine to treat Parkinson's disease(PD)by improving mitochondrial dysfunction.However,the underlying mechanisms by which BYQZF...Objective:Buyinqianzheng Formula(BYQZF)is clinically employed in traditional Chinese medicine to treat Parkinson's disease(PD)by improving mitochondrial dysfunction.However,the underlying mechanisms by which BYQZF affects mitochondrial morphology remain unknown.Therefore,we observed the effects of BYQZF on mitochondria from the perspective of the PINK1/Parkin pathway.Methods:Cell survival rates were assessed by Cell Counting Kit-8 assay.Expression levels of PINK1 and Parkin mRNA were examined by qRT-PCR.Protein expression levels of PINK1,PINK1-Ser228,Parkin,Parkin-Ser65,Drp1,and Drp1-Ser637 were examined by western blotting.PINK1,Parkin,and MitoTracker?Red CMXRos(MTR)were stained by triple-labeled immunofluorescence,and observed under laser confocal microscopy.Results:Cell survival rate,mitochondrial form factor,mean length and number of mitochondrial network branches,mitochondrial activity,m RNA expression levels of PINK1 and Parkin,and protein expression levels of PINK1,Parkin,and Drp1-Ser637 were reduced after 1-methyl-4-phenylpyridinium(MPP^(+))intervention.In contrast,Pearson's correlation coefficients between PINK1 and Parkin,and between Parkin and MTR,as well as protein expression levels of PINK1-Ser228,Parkin-Ser65,and Drp1 increased significantly after MPP^(+) intervention.Treatment with BYQZF increased cell survival rate,mitochondrial form factor,mean length and number of mitochondrial network branches,mitochondrial activity,m RNA expression levels of PINK1 and Parkin,and expression of PINK1,Parkin,and Drp1-Ser637 proteins.Pearson's correlation coefficients between PINK1 and Parkin,and between Parkin and MTR,as well as protein expression levels of PINK1-Ser228,Parkin-Ser65,and Drp1 decreased after BYQZF treatment.Conclusion:These results demonstrate that BYQZF has a protective effect on mitochondrial molecular mechanisms in the PD cell model,and the mechanism is related to the PINK1/Parkin pathway.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 observe the effect of electroacupuncture(EA) combined with oriented conductive bioprotein hydrogel(OCBH) on the recovery of nerve function in rats with complete spinal cord injury(SCI)and to explore its ...Objective: To observe the effect of electroacupuncture(EA) combined with oriented conductive bioprotein hydrogel(OCBH) on the recovery of nerve function in rats with complete spinal cord injury(SCI)and to explore its effect and mechanism on the formation and changes of glial scars.Methods: A total of 72 female Sprague-Dawley rats were randomly divided into groups according to the treatment received. A rat model of complete SCI was constructed using a spinal cord transection.Behavioral assessments, hematoxylin-eosin(H&E) staining, immunofluorescence staining, and Western blotting were performed at a fixed period after the operation.Results: The material group and the material + EA group obtained better results in the behavioral assessments(all P <.05) and the H&E staining. In the immunofluorescence staining and Western blotting,the GFAP protein was expressed more and denser in the material group and the material + EA group than in the model group, and the density of the GFAP expression in the material + EA group was lower at week 12 than in the material group(all P <.05). The expression of complement C3 in the model, material,and material + EA groups decreased in turn. Some inflammatory factors and the NF-κB signaling pathway showed similar results in the Western blotting(all P <.05). The expression of the GDNF protein in the material + EA group was significantly higher than that in the model group and the material group(both P <.01).Conclusion: EA combined with OCBH can promote the recovery of motor functions after SCI by facilitating the formation of glial scars in the early stage, preventing the further spread of an inflammatory response that would affect the activation of A1/A2 astrocytes and change the morphology of glial scars at the spinal cord-material interface in its late stage.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:To determine whether electro-acupuncture (EA) therapy could improve the cognitive functions of amyloid precursor protein Swedish mutation (APPswe)/presenilin 1 deleted in exon 9 (PS1dE9) mice and examine whe...Objective:To determine whether electro-acupuncture (EA) therapy could improve the cognitive functions of amyloid precursor protein Swedish mutation (APPswe)/presenilin 1 deleted in exon 9 (PS1dE9) mice and examine whether EA treatment could attenuate neuroinflammation by targeting the toll-like receptor 4 (TLR4)/myeloid differentiation primary response factor 88 (MyD88) signaling pathway.Methods:Twenty-seven double transgenic APPswe/PS1dE9 mice were randomly allocated into three groups:an Alzheimer's disease model group (AD group),a medication group (M group) and an EA treatment group (EA group).Each group contained nine mice,and nine wild-type mice were used in a normal group (N group).The animals in the M group were treated with oral administrations of 0.92 mg/kg donepezil hydrochloride for 15 days.For animals in the EA group,EA treatments were used on the Yintang (GV 29) and Baihui (GV 20) acupoints for 20 minutes,and the Shuigou (GV 26) acupoint was pricked without needle retention following EA treatments.Following treatments,the spatial learning and memory of the mice were measured using the Morris water maze test.The expression levels of TLR4,MyD88,nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) were analyzed by immunohistochemical staining and western blot.Results:The escape latencies of the M and EA groups were significantly lower than those of the AD group (vs M,P =.002;vs EA,P <.001).Moreover,compared with the AD group,the numbers of platform crossings was higher (vs M,P =.038;vs EA,P =.008) and the latency time for target quadrants was longer (vs M,P =.002;vs EA,P =.001) in the M and EA groups (P <.05).Furthermore,in the M and EA groups,the expression levels of TLR4,MyD88,NF-κB and iNOS decreased significantly compared with those of the AD group (all P <.01).Conclusion:EA treatment enhanced the memory and learning abilities of APPswe/PS1dE9 mice by regulating the TLR4/MyD88 inflammatory signaling pathway.展开更多
Objective:To determine the effect of Salvianolic acid B (Sal B) on glucose and lipid metabolism in mice with high-fat diet (HFD)-induced obesity,and to investigate the underlying mechanisms by measuring the expression...Objective:To determine the effect of Salvianolic acid B (Sal B) on glucose and lipid metabolism in mice with high-fat diet (HFD)-induced obesity,and to investigate the underlying mechanisms by measuring the expression levels of key adipogenic transcription factors.Methods:Six-week-old C57BL/6J male mice were fed for 12 weeks with a HFD to induce obesity or a standard diet to serve as normal controls.A mean body weight increase of more than 20% after these 12 weeks was used as the criteria for obesity.HFD-fed obese mice then received a supplement of Sal B (100 mg/kg body weight/day),metformin (75 mg/kg body weight/day) or water (an equivalent volume;served as model controls) by oral gavage for an additional 8 weeks,and the normal controls received water (an equivalent volume) by oral gavage for the same period.Results:Sal B significantly reduced body weight gain (P <.05) without influencing food intake in HFD-fed obese mice relative to model controls.Sal B also reduced the body fat mass of the obese mice relative to model controls in a time-dependent manner (P <.05).Sal B significantly decreased the serum concentrations of low-density lipoprotein cholesterol,total cholesterol,triglyceride and free fatty acids by 25.5%,20.2%,20.6% and 13.4%,respectively,and increased the concentration of high-density lipoprotein cholesterol by 50.1% relative to model controls.In addition,Sal B significantly lowered fasting glucose concentrations and improved insulin sensitivity relative to model controls (P <.05).Sal B acted by ameliorating the histopathological changes in both brown and white adipose tissues of obese mice.Moreover,in brown adipose tissue,Sal B up-regulated the mRNA and protein expression of PPARγ and c/EBPα,and the protein expression of PPARα and SREBP-1 (P <.05).In white adipose tissue,Sal B down-regulated the mRNA expression of PPARγ and c/EBPα,and decreased the protein expression of PPARγ and SREBP-1(P <.05).Conclusjons:The results suggest that Sal B can reduce body weight gain and regulate glucose and lipid metabolism in mice with diet-induced obesity by regulating adipogenic transcription factors in their adipose tissues.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: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
Organic electrochemical transistors(OECTs)have emerged as one type of promising building block for neuromorphic systems owing to their capability of mimicking the morphology and functions of biological neurons and syn...Organic electrochemical transistors(OECTs)have emerged as one type of promising building block for neuromorphic systems owing to their capability of mimicking the morphology and functions of biological neurons and synapses.Currently,numerous kinds of OECTs have been developed,while self-healing performance has been neglected in most reported OECTs.In this work,the OECTs using self-healing polymer electrolytes as dielectric layers are proposed.Several important synaptic behaviors are simulated in the OECTs by doping the channel layers with ions from the electrolytes.Benefitting from the dynamic hydrogen bonds in the self-healing polymer electrolytes,the OECTs can successfully maintain their electrical performance and the ability of emulating synaptic behaviors after self-healing compared with the initial state.More significantly,the sublinear spatial summation function is demonstrated in the OECTs and their potential in flexible electronics is also validated.These results suggest that our devices are expected to be a vital component in the development of future wearable and bioimplantable neuromorphic systems.展开更多
基金the National Natural Science Foundation of China(Grant Nos.81573773 and 81774110)。
文摘Objective:Buyinqianzheng Formula(BYQZF)is clinically employed in traditional Chinese medicine to treat Parkinson's disease(PD)by improving mitochondrial dysfunction.However,the underlying mechanisms by which BYQZF affects mitochondrial morphology remain unknown.Therefore,we observed the effects of BYQZF on mitochondria from the perspective of the PINK1/Parkin pathway.Methods:Cell survival rates were assessed by Cell Counting Kit-8 assay.Expression levels of PINK1 and Parkin mRNA were examined by qRT-PCR.Protein expression levels of PINK1,PINK1-Ser228,Parkin,Parkin-Ser65,Drp1,and Drp1-Ser637 were examined by western blotting.PINK1,Parkin,and MitoTracker?Red CMXRos(MTR)were stained by triple-labeled immunofluorescence,and observed under laser confocal microscopy.Results:Cell survival rate,mitochondrial form factor,mean length and number of mitochondrial network branches,mitochondrial activity,m RNA expression levels of PINK1 and Parkin,and protein expression levels of PINK1,Parkin,and Drp1-Ser637 were reduced after 1-methyl-4-phenylpyridinium(MPP^(+))intervention.In contrast,Pearson's correlation coefficients between PINK1 and Parkin,and between Parkin and MTR,as well as protein expression levels of PINK1-Ser228,Parkin-Ser65,and Drp1 increased significantly after MPP^(+) intervention.Treatment with BYQZF increased cell survival rate,mitochondrial form factor,mean length and number of mitochondrial network branches,mitochondrial activity,m RNA expression levels of PINK1 and Parkin,and expression of PINK1,Parkin,and Drp1-Ser637 proteins.Pearson's correlation coefficients between PINK1 and Parkin,and between Parkin and MTR,as well as protein expression levels of PINK1-Ser228,Parkin-Ser65,and Drp1 decreased after BYQZF treatment.Conclusion:These results demonstrate that BYQZF has a protective effect on mitochondrial molecular mechanisms in the PD cell model,and the mechanism is related to the PINK1/Parkin pathway.
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financially supported by the National Natural Science Foundation of China (81973882 and 81804119)
文摘Objective: To observe the effect of electroacupuncture(EA) combined with oriented conductive bioprotein hydrogel(OCBH) on the recovery of nerve function in rats with complete spinal cord injury(SCI)and to explore its effect and mechanism on the formation and changes of glial scars.Methods: A total of 72 female Sprague-Dawley rats were randomly divided into groups according to the treatment received. A rat model of complete SCI was constructed using a spinal cord transection.Behavioral assessments, hematoxylin-eosin(H&E) staining, immunofluorescence staining, and Western blotting were performed at a fixed period after the operation.Results: The material group and the material + EA group obtained better results in the behavioral assessments(all P <.05) and the H&E staining. In the immunofluorescence staining and Western blotting,the GFAP protein was expressed more and denser in the material group and the material + EA group than in the model group, and the density of the GFAP expression in the material + EA group was lower at week 12 than in the material group(all P <.05). The expression of complement C3 in the model, material,and material + EA groups decreased in turn. Some inflammatory factors and the NF-κB signaling pathway showed similar results in the Western blotting(all P <.05). The expression of the GDNF protein in the material + EA group was significantly higher than that in the model group and the material group(both P <.01).Conclusion: EA combined with OCBH can promote the recovery of motor functions after SCI by facilitating the formation of glial scars in the early stage, preventing the further spread of an inflammatory response that would affect the activation of A1/A2 astrocytes and change the morphology of glial scars at the spinal cord-material interface in its late stage.
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the National Natural Science Foundation of China(81473774).
文摘Objective:To determine whether electro-acupuncture (EA) therapy could improve the cognitive functions of amyloid precursor protein Swedish mutation (APPswe)/presenilin 1 deleted in exon 9 (PS1dE9) mice and examine whether EA treatment could attenuate neuroinflammation by targeting the toll-like receptor 4 (TLR4)/myeloid differentiation primary response factor 88 (MyD88) signaling pathway.Methods:Twenty-seven double transgenic APPswe/PS1dE9 mice were randomly allocated into three groups:an Alzheimer's disease model group (AD group),a medication group (M group) and an EA treatment group (EA group).Each group contained nine mice,and nine wild-type mice were used in a normal group (N group).The animals in the M group were treated with oral administrations of 0.92 mg/kg donepezil hydrochloride for 15 days.For animals in the EA group,EA treatments were used on the Yintang (GV 29) and Baihui (GV 20) acupoints for 20 minutes,and the Shuigou (GV 26) acupoint was pricked without needle retention following EA treatments.Following treatments,the spatial learning and memory of the mice were measured using the Morris water maze test.The expression levels of TLR4,MyD88,nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) were analyzed by immunohistochemical staining and western blot.Results:The escape latencies of the M and EA groups were significantly lower than those of the AD group (vs M,P =.002;vs EA,P <.001).Moreover,compared with the AD group,the numbers of platform crossings was higher (vs M,P =.038;vs EA,P =.008) and the latency time for target quadrants was longer (vs M,P =.002;vs EA,P =.001) in the M and EA groups (P <.05).Furthermore,in the M and EA groups,the expression levels of TLR4,MyD88,NF-κB and iNOS decreased significantly compared with those of the AD group (all P <.01).Conclusion:EA treatment enhanced the memory and learning abilities of APPswe/PS1dE9 mice by regulating the TLR4/MyD88 inflammatory signaling pathway.
基金This study is supported by grants from the National Natural Science Foundation of China(81274041 and 81503540)the International Cooperation Projects of MOE(2011DFA30920)+1 种基金a Co-construction Project of Beijing Board of Education(0101216-14)a Research Project of the Beijing University of Chinese Medicine(2014-X-003).
文摘Objective:To determine the effect of Salvianolic acid B (Sal B) on glucose and lipid metabolism in mice with high-fat diet (HFD)-induced obesity,and to investigate the underlying mechanisms by measuring the expression levels of key adipogenic transcription factors.Methods:Six-week-old C57BL/6J male mice were fed for 12 weeks with a HFD to induce obesity or a standard diet to serve as normal controls.A mean body weight increase of more than 20% after these 12 weeks was used as the criteria for obesity.HFD-fed obese mice then received a supplement of Sal B (100 mg/kg body weight/day),metformin (75 mg/kg body weight/day) or water (an equivalent volume;served as model controls) by oral gavage for an additional 8 weeks,and the normal controls received water (an equivalent volume) by oral gavage for the same period.Results:Sal B significantly reduced body weight gain (P <.05) without influencing food intake in HFD-fed obese mice relative to model controls.Sal B also reduced the body fat mass of the obese mice relative to model controls in a time-dependent manner (P <.05).Sal B significantly decreased the serum concentrations of low-density lipoprotein cholesterol,total cholesterol,triglyceride and free fatty acids by 25.5%,20.2%,20.6% and 13.4%,respectively,and increased the concentration of high-density lipoprotein cholesterol by 50.1% relative to model controls.In addition,Sal B significantly lowered fasting glucose concentrations and improved insulin sensitivity relative to model controls (P <.05).Sal B acted by ameliorating the histopathological changes in both brown and white adipose tissues of obese mice.Moreover,in brown adipose tissue,Sal B up-regulated the mRNA and protein expression of PPARγ and c/EBPα,and the protein expression of PPARα and SREBP-1 (P <.05).In white adipose tissue,Sal B down-regulated the mRNA expression of PPARγ and c/EBPα,and decreased the protein expression of PPARγ and SREBP-1(P <.05).Conclusjons:The results suggest that Sal B can reduce body weight gain and regulate glucose and lipid metabolism in mice with diet-induced obesity by regulating adipogenic transcription factors in their adipose tissues.
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supported by the National Key Research and Development Program of China(No.2021YFA1101303)the National Natural Science Foundation of China(Nos.62074111,62088101)+2 种基金the Science&Technology Foundation of Shanghai(No.20JC1415600)Shanghai Municipal Science and Technology Major Project(No.2021SHZDZX0100)the Innovation Program of Shanghai Municipal Education Commission(No.2021-01-07-0007-E00096)。
文摘Organic electrochemical transistors(OECTs)have emerged as one type of promising building block for neuromorphic systems owing to their capability of mimicking the morphology and functions of biological neurons and synapses.Currently,numerous kinds of OECTs have been developed,while self-healing performance has been neglected in most reported OECTs.In this work,the OECTs using self-healing polymer electrolytes as dielectric layers are proposed.Several important synaptic behaviors are simulated in the OECTs by doping the channel layers with ions from the electrolytes.Benefitting from the dynamic hydrogen bonds in the self-healing polymer electrolytes,the OECTs can successfully maintain their electrical performance and the ability of emulating synaptic behaviors after self-healing compared with the initial state.More significantly,the sublinear spatial summation function is demonstrated in the OECTs and their potential in flexible electronics is also validated.These results suggest that our devices are expected to be a vital component in the development of future wearable and bioimplantable neuromorphic systems.
基金supported by the National Natural Science Foundation of China(62074111 and 62374115)the Innovation Program of Shanghai Municipal Education Commission(2021-01-07-00-07-E00096)the National Key Research and Development Program of China(2022YFB3203502)。
文摘有机-无机卤化物钙钛矿因其可溶液加工和优异的光电特性而在光电探测器(PD)中得到了广泛应用.然而,基于钙钛矿的PD一般需要电荷传输层提供足够的分离和传输驱动力,这会增加钙钛矿PD的材料成本.本研究通过溶液法制备了基于苯基三甲基氯化铵(PTACl)处理的无电荷传输层钙钛矿自供电PD.以(CsFAMA)Pb(BrI)3作为光活性层,这种三元阳离子混合卤化物钙钛矿沉积后的垂直分布差异为电荷分离和传输提供了驱动力,PTACl处理能加强电荷分离和运输.这种PD在自供电模式下表现出优异的光电探测性能,其中光暗电流比为1.8×10^(5),响应度为198 mA W^(−1),探测率为1.48×10^(13)/1.24×10^(11) Jones(暗/噪声电流法计算).没有封装的PD在700 h的测试中也表现出良好的空气稳定性,且该PD对0.64 nW cm^(−2)的弱光仍有明显的响应,PD阵列也验证了这种弱光检测能力.本工作制备的钙钛矿自供电PD为弱光检测的发展提供了一种简单可行的途径.
