1.Treatment Effect on Structure and Function of Submandibular Gland in Sjögren's Syndrome Model Mice by Artemisinin
Ziwei HUANG ; Qian HE ; Jiahe LIAO ; Xinbo YU ; Jing LUO ; Weijiang SONG ; Qingwen TAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):158-165
ObjectiveTo investigate the effects of artemisinin (ART) on histopathological damage and salivary secretion in the submandibular gland (SMG) of mice with Sjögren's syndrome (SS) model,and on the expression of aquaporin 5 (AQP5) in SMG cells. MethodsThe NOD/Ltj mice were used as a model of SS and randomly divided into the SS model group,the ART group,and the hydroxychloroquine sulfate (HCQ) group,with six mice per group. Another 6 female BALB/c mice at the same week were selected as the control group. Mice in the ART group was fed with the ART solution daily in the dosage of 50 mg·kg-1,and mice in the HCQ group was given with the HCQ solution (1 300 mg·kg-1). Mice in the SS model and control groups were given saline daily. The treatment lasted for 8 weeks. The 24-hour average water intake,salivary flow rate,SMG pathology scores of mice in each group were measured,as well as the expression levels of AQP5 protein and gene in the SMG tissues. ResultsCompared with the control group,the 24-hour average water intake of mice in the model group was significantly increased (P<0.01),and the saliva flow rate was significantly decreased (P<0.01). Compared to the SS model group,the 24-hour average water intake of mice in the ART and HCQ groups was significantly reduced (P<0.01),and the salivary flow rate was significantly increased in the ART group(P<0.01),comparisons between groups showed that the ART was superior to the HCQ in reducing water intake and improving saliva flow rate in SS model mice (P<0.05). The HE staining results showed that,compared with the normal group,the number of lymphocyte infiltration foci in SMG tissue in the model group increased,and the pathological score increased (P<0.01). Compared to the SS model group,after the intervention of the ART and HCQ,the number of lymphocytic infiltration foci in the SMG tissue decreased,the area of the lymphocytic infiltration foci was reduced,and the pathology score of the SMG tissues was lowered in the ART group(P<0.01). However,there was no difference in pathological scores between the ART and HCQ groups . The results of IHC,Western blot,and Real-time PCR showed that,compared with the normal group,the expression levels of AQP5 protein and gene in SMG tissue in the model group significantly decreased (P<0.05). Comparing with the SS model group,the ART and HCQ groups could significantly up-regulated the expression levels of AQP5 protein and mRNA in the SMG tissue,and the treatment effect was better than that of HCQ. ConclusionART was able to ameliorate SMG structural damage and salivary secretion function in SS model mice,and its mechanism of action may be related to the up-regulation of AQP5 protein and gene expression levels in SMG cells.
2.From Physiology to Pathology of Astrocytes: Highlighting Their Potential as Therapeutic Targets for CNS Injury.
Yimin YUAN ; Hong LIU ; Ziwei DAI ; Cheng HE ; Shangyao QIN ; Zhida SU
Neuroscience Bulletin 2025;41(1):131-154
In the mammalian central nervous system (CNS), astrocytes are the ubiquitous glial cells that have complex morphological and molecular characteristics. These fascinating cells play essential neurosupportive and homeostatic roles in the healthy CNS and undergo morphological, molecular, and functional changes to adopt so-called 'reactive' states in response to CNS injury or disease. In recent years, interest in astrocyte research has increased dramatically and some new biological features and roles of astrocytes in physiological and pathological conditions have been discovered thanks to technological advances. Here, we will review and discuss the well-established and emerging astroglial biology and functions, with emphasis on their potential as therapeutic targets for CNS injury, including traumatic and ischemic injury. This review article will highlight the importance of astrocytes in the neuropathological process and repair of CNS injury.
Astrocytes/drug effects*
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Humans
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Animals
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Central Nervous System/pathology*
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Central Nervous System Diseases/physiopathology*
3.Molecular Mechanism Study of Compound Dihuang Granule in Treating PD Rats with Yin-Deficiency and Dynamic Wind Syndrome by Ubiquitin-Proteasome System
Ziwei LYU ; Jianqing LIANG ; Xingling WANG ; Guangjie SUN ; Jiancheng HE ; Yongqiang KANG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(6):608-617
OBJECTIVE To explore the molecular mechanism of Compound Dihuang Granule in treating Parkinson's disease(PD)with yin-deficiency and dynamic wind syndrome by regulating the changes of ubiquitin-proteasome system-related proteins.METHODS SPF male SD rats were randomly selected as normal control group and sham operation group,13 rats in each group.The remaining rats were treated with 6-hydroxydopamine lateral brain injection to damage the substantia nigra to establish PD yin-deficien-cy and dynamic wind syndrome rat model.The established rats were randomly divided into model group,madopar group(150 mg·kg-1),low,medium and high dose groups of Compound Dihuang Granule(1.75,3.5,7 g·kg-1),13 rats in each group.Each group was given drugs by intragastric gavage for 28 d.The general conditions and neurobehavioral manifestations of the rats were observed;the expression of ubiquitin(UB),ubiquitin activating enzyme(UBE1),ubiquitin conjugating enzyme(UBE2A)and ubiquitin carboxyl terminal hydrolase(UCH-L1)positive cells,protein and mRNA expression levels in the damaged lateral stria-tum of the brain of rats were detected by immunohistochemistry,Western blot and qPCR methods;changes of dopamine(DA)content in the damaged lateral striatum of the brain of rats were detected by ELISA.RESULTS There was no significant difference in general conditions between the normal control group and the sham operation group,and there was no significant difference in the number of ro-tations,suspension time and number of moving grids.Compared to the sham-op group,the model group rats showed poor spirit,irrita-bility,limb tremor,slow movement,dark yellow fur,less food intake,reduced body weight;the modeling increased number of rota-tions,decreased hanging time and number of moving grids(P<0.01),significantly decreased expression of UB,UBE1,UBE2A,and UCH-L1 positive cells,mRNA and protein expression levels in the damaged lateral striatum(P<0.01),and significantly decreased DA content(P<0.01).Compared with the model group,the general condition of the rats in the madopar group and Compound Di-huang Granule groups was improved,the number of rotations was reduced,the hanging time and number of moving grids were increased(P<0.05,P<0.01),the expression of UB,UBE1,UBE2A,and UCH-L1 positive cells,mRNA and protein expression levels were increased(P<0.05,P<0.01),and the DA content was increased(P<0.01);behavioral tests and the expression levels of various in-dicators were most significantly improved in the madopar group and the high-dose Compound Dihuang Granule group(P<0.05,P<0.01),and there was no statistical significance between the two groups.CONCLUSION Compound Dihuang Granule may play a role in treating PD yin-deficiency and dynamic wind syndrome by regulating the expression of ubiquitin-proteasome system-related proteins,reducing abnormal protein aggregation,and thus alleviating DA content deficiency,and the high-dose Compound Dihuang Granule has the best effect.
4.Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sj?gren's syndrome model mice by regulating Hippo-YAP/TAZ expression
Ziwei HUANG ; Qingwen TAO ; Jiahe LIAO ; Xinbo YU ; Qian HE ; Bojie TANG ; Jing LUO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1527-1540
Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.
5.Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sj?gren's syndrome model mice by regulating Hippo-YAP/TAZ expression
Ziwei HUANG ; Qingwen TAO ; Jiahe LIAO ; Xinbo YU ; Qian HE ; Bojie TANG ; Jing LUO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1527-1540
Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.
6.Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sj?gren's syndrome model mice by regulating Hippo-YAP/TAZ expression
Ziwei HUANG ; Qingwen TAO ; Jiahe LIAO ; Xinbo YU ; Qian HE ; Bojie TANG ; Jing LUO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1527-1540
Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.
7.Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sj?gren's syndrome model mice by regulating Hippo-YAP/TAZ expression
Ziwei HUANG ; Qingwen TAO ; Jiahe LIAO ; Xinbo YU ; Qian HE ; Bojie TANG ; Jing LUO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1527-1540
Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.
8.Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sj?gren's syndrome model mice by regulating Hippo-YAP/TAZ expression
Ziwei HUANG ; Qingwen TAO ; Jiahe LIAO ; Xinbo YU ; Qian HE ; Bojie TANG ; Jing LUO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1527-1540
Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.
9.Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sj?gren's syndrome model mice by regulating Hippo-YAP/TAZ expression
Ziwei HUANG ; Qingwen TAO ; Jiahe LIAO ; Xinbo YU ; Qian HE ; Bojie TANG ; Jing LUO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1527-1540
Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.
10.Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sj?gren's syndrome model mice by regulating Hippo-YAP/TAZ expression
Ziwei HUANG ; Qingwen TAO ; Jiahe LIAO ; Xinbo YU ; Qian HE ; Bojie TANG ; Jing LUO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1527-1540
Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.

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