Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we re...Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.展开更多
Pien Tze Huang(PTH)was documented as an imperial prescription composed of Notoginseng Radix,Calculus Bovis,Snake Gallbladder,and Musk.It is famous in China and Asian countries due to its excellent effects in heat clea...Pien Tze Huang(PTH)was documented as an imperial prescription composed of Notoginseng Radix,Calculus Bovis,Snake Gallbladder,and Musk.It is famous in China and Asian countries due to its excellent effects in heat clearing,detoxifying,swelling reduction,and pain relieving.Modern pharmacological studies demonstrate that PTH shows excellent effects against various inflammatory diseases,liver diseases,and cancers.This review summaries the pharmacological effects,clinical applications,and mainchemical components of PTH.More importantly,its potential quality markers(Q-markers)were then analyzed based on the“five principles”of Q-markers under the guidance of Traditional Chinese Medicine theory,including transfer and traceability,specificity,efficacy,compatibility,and measurability.As a result,ginsenosides Rb1,ginsenoside Rg1,ginsenoside Rd,ginsenoside Re,notoginsenoside R1,dencichine,bilirubin,biliverdin,taurocholic acid,and muscone are considered as the Q-markers of PTH.These findings will provide guidance and assistance for the construction of a quality control system for PTH.展开更多
BACKGROUND Traditional Chinese medicine has used the drug Pien Tze Huang(PTH),a classic prescription,to treat autoimmune hepatitis(AIH).However,the precise mode of action is still unknown.AIM To investigate the mechan...BACKGROUND Traditional Chinese medicine has used the drug Pien Tze Huang(PTH),a classic prescription,to treat autoimmune hepatitis(AIH).However,the precise mode of action is still unknown.AIM To investigate the mechanism of PTH in an AIH mouse model by determining the changes in gut microbiota structure and memory regulatory T(mTreg)cells functional levels.METHODS Following induction of the AIH mouse model induced by Concanavalin A(Con A),prophylactic administration of PTH was given for 10 d.The levels of mTreg cells were measured by flow cytometry,and intestinal microbiota was analyzed by 16S rRNA analysis,while western blotting was used to identify activation of the toll-like receptor(TLR)2,TLR4/nuclear factor-κB(NF-κB),and CXCL16/CXCR6 signaling pathways.RESULTS In the liver of mice with AIH,PTH relieved the pathological damage and reduced the numbers of T helper type 17 cells and interferon-γ,tumor necrosis factor-alpha,interleukin(IL)-1β,IL-2,IL-6,and IL-21 expression.Simultaneously,PTH stimulated the abundance of helpful bacteria,promoted activation of the TLR2 signal,which may enhance Treg/mTreg cells quantity to produce IL-10,and suppressed activation of the TLR4/NF-κB and CXCL16/CXCR6 signaling pathways.CONCLUSION PTH regulates intestinal microbiota balance and restores mTreg cells to alleviate experimental AIH,which is closely related to the TLR/CXCL16/CXCR6/NF-κB signaling pathway.展开更多
OBJECTIVE:To explore biomarkers of Pien Tze Huang(片仔癀)that ameliorated the symptoms of hepatic fibrosis.METHODS:Two groups of carbon tetrachloride-induced hepatic fibrosis(HF)mice model were constructed in our stud...OBJECTIVE:To explore biomarkers of Pien Tze Huang(片仔癀)that ameliorated the symptoms of hepatic fibrosis.METHODS:Two groups of carbon tetrachloride-induced hepatic fibrosis(HF)mice model were constructed in our study:one group received PZH treatment and another group received no treatment.We performed this study to investigate the role of PZH in the regulation process of hepatic fibrosis.RESULTS:We identified 31 down-regulated and 39 upregulated mi RNAs using small RNA-seq analysis.Combining RNA-Seq data analysis,our study revealed 7 significant target genes(Sp4,Slc2 a6,Tln2,Hmga2,Ank3,Pax9,Fgf9).The results of real-time quantitative polymerase chain reaction analysis suggested that the expression level of 6 genes(Sp4,Tln2,Hmga2,Ank3,Pax9,Fgf9)were down-regulated compared to control group.On the other hand,the expression level of Slc2 a6 appeared to be up-regulated.The protein mass spectrometry showed that PZH group had lower protein expression of Tln2 compared to control group.CONCLUSION:We identified 7 genes that were significantly related to PZH response in HF mice using multiple conjoint analysis methods.These genes could participate in underlying regulation mechanism of hepatic fibrosis during PZH treatment.展开更多
Epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)plays an important role in cancer therapy.However,EGFR is highly expressed in the skin and gives rise to one of the most concerning issues for the EG...Epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)plays an important role in cancer therapy.However,EGFR is highly expressed in the skin and gives rise to one of the most concerning issues for the EGFR-TKI treatment,namely skin toxicity.Antibiotics and corticosteroids are usually used to treat the EGFR inhibitor-associated skin rash,with prominent side effects over long-time use.Pien Tze Huang(PZH)Unguentum Compositum is a traditional product for external application which is made of traditional Chinese medicine and oil base.Herein,we reported the case of a 50-year-old man who presented with skin rash on the face,head,and back induced by an EGFR-TKI named erlotinib.By using PZH Unguentum Compositum,we observed that the skin rash was mitigated and eventually disappeared.This case report suggests that PZH Unguentum Compositum may be an effective therapy in treating skin rash caused by EGFR-TKI with fewer side effects.展开更多
DEUTSCHE YACHTEN集团旗下公司Otto Piening近日首次开发出可以用水基液压系统运行的可调螺距螺旋桨。该水基液压系统调距桨目前正在申请专利,将于今年9月6~9日在汉堡海事会展上展出。该系统是世界上第一台水基液压系统可调螺距螺旋桨,...DEUTSCHE YACHTEN集团旗下公司Otto Piening近日首次开发出可以用水基液压系统运行的可调螺距螺旋桨。该水基液压系统调距桨目前正在申请专利,将于今年9月6~9日在汉堡海事会展上展出。该系统是世界上第一台水基液压系统可调螺距螺旋桨,已经通过DNV、GL船级社认证,并且被巨型游艇市场认可,作为海军和海岸警卫队舰船使用也非常环保。展开更多
Objective:To investigate the effect of miR-483-5p on hepatocellular carcinoma(HCC)cells proliferation and stemness,as well as the attenuating effect of Pien Tze Huang(PZH).Methods:Differentially expressed miRNA betwee...Objective:To investigate the effect of miR-483-5p on hepatocellular carcinoma(HCC)cells proliferation and stemness,as well as the attenuating effect of Pien Tze Huang(PZH).Methods:Differentially expressed miRNA between HepG2 cells and hepatic cancer stem-like cells(HCSCs)were identified by a miRNA microarray assay.miR-483-5p mimics were transfected into HepG2 cells to explore the effects of miR-483-5p on cell proliferation and stemness.HepG2 cells and HCSCs were treated with PZH(0,0.25,0.50 and 0.75 mg/mL)to explore the effects of PzH on the proliferation and stemness,both in non-induced state and the state induced by miR-483-5p mimics.Results:miR-483-5p was significantly up-regulated in HCSCs and its overexpression increased cell proliferation and stemness in HepG2 cells(P<0.05).PZH not only significantly inhibited proliferation in HepG2 cells,but also significantly suppressed the cell proliferation and self-renewal of HCSCs(P<0.05).The effects of miR-483-5p mimics on proliferation and stemness of HepG2 cells were partially abolished by PZH.Conclusions:miR-483-5p promotes proliferation and enhances stemness of HepG2 cells,which were attenuated by PZH,demonstrating that miR-483-5p is a potential molecular target for the treatment of HCC and provide experimental evidence to support clinical use of PZH for patients with HCC.展开更多
Objective To investigate the anti-tumor effects of Pien Tze Huang(PZH)in mouse models of B16–F10 melanoma,MC38 colorectal cancer,Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model.M...Objective To investigate the anti-tumor effects of Pien Tze Huang(PZH)in mouse models of B16–F10 melanoma,MC38 colorectal cancer,Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model.Methods Various tumor models,including B16–F10,MC38 and Hep1-6 tumor hypodermic inoculation models,B16–F10 and Hep1-6 pulmonary metastasis models,Hep1-6 orthotopic implantation model,and chemically induced hepatocellular carcinoma model,were utilized to evaluate the anti-tumor function of PZH.Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice.For cell proliferation and death of tumor cells in vitro,as well as T cell activation markers,cytokine production and immune checkpoints analysis,single-cell suspensions were prepared from mouse spleen,lymph nodes,and tumors after PZH treatment.Results PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth(P<0.01).Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16–F10 melanoma models,and decreased pulmonary metastasis of B16–F10 melanoma and Hep1-6 hepatoma(P<0.01).However,in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells(P>0.05).Nevertheless,PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma,tumor necrosis factor alpha,and interleukin 2 in CD4^(+)T cells in vitro(P<0.01 or P<0.05).Importantly,PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8^(+)T cells(P<0.01 or P<0.05).Conclusion This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity,indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.展开更多
ObjectiveTo explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it’s down-stream mediators in colorectal cancer (CRC) cells.MethodsQuantitative polymerase chain reaction was ...ObjectiveTo explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it’s down-stream mediators in colorectal cancer (CRC) cells.MethodsQuantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues.ResultsPZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05).ConclusionThe mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.展开更多
Objective：To investigate the cellular effects of Pien Tze Huang（片仔癀,PZH） in the HT-29 human colon carcinoma cell line.Methods：The viability of HT-29 cells was determined by MTT assay.A fluorescence-activated ce...Objective：To investigate the cellular effects of Pien Tze Huang（片仔癀,PZH） in the HT-29 human colon carcinoma cell line.Methods：The viability of HT-29 cells was determined by MTT assay.A fluorescence-activated cell sorting（FACS） analysis with annexin-V/propidium iodide（PI） and JC-1 staining were performed to determine cell apoptosis and the loss of mitochondrial membrane potential,respectively.Activation of caspase 3 was evaluated by a colorimetric assay.The mRNA expression levels of Bcl-2 and Bax were measured by reverse transcription polymerase chain reaction（RT-PCR）.Results：PZH,in a dose- and time-dependent manner,reduced viability and induced apoptosis of HT-29 cells.Moreover,PZH treatment resulted in the collapse of the mitochondrial membrane potential,activation of caspase 3,and an increase in the Bax/Bcl-2 ratio.Conclusion：PZH inhibits the growth of HT-29 cells by inducing cancer cell apoptosis via regulation of the Bcl-2 family and activation of caspase 3,which may,in part,explain its anticancer activity.展开更多
Objective： TO investigate the anti-angiogenic effects of Pien Tze Huang （片仔癀, PZH） in vivo and in vitro. Me.otis： Human umbilical vein endothelial cells （HUVECs） were treated with 0 mg/mL, 0.25 mg/mL, 0.5 mg/...Objective： TO investigate the anti-angiogenic effects of Pien Tze Huang （片仔癀, PZH） in vivo and in vitro. Me.otis： Human umbilical vein endothelial cells （HUVECs） were treated with 0 mg/mL, 0.25 mg/mL, 0.5 mg/mL, and 1 mg/mL of PZH for 24 h, 48 h and 72 h, respectively. Chicken embryo chorioallantoic membrane （CAM） model was used to evaluate in vivo angiogenesis. An ECMatrix gel system was used to evaluate in vitro angiogenesis by examining the tube formation of HUVECs. 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay was performed to determine HUVEC viability. Cell density of HUVECs was observed by phase- contrast microscopy. HUVEC migration was determined by wound healing method. The mRNA and protein expression of vascular endothelial growth factor A （VEGF-A） and basic fibroblast growth factor （bFGF） in both HUVEC and human colon adenocaminoma cells （HT-29） was examined by reverse transcription polymerase chain reaction （RT-PCR） and enzyme linked immune sorbent assay （ELISA）, respectively. Results： PZH treatment significantly reduced the total number of blood vessels compared with the untreated control in the chicken embryos and resulted in a significant decrease in capillary tube formation and cell density of HUVECs （P〈0.05）. In addition, treatment with 0.25-1 mg/mL of PZH for 24 h, 48 h, and 72 h respectively reduced cell viability by 9%-52%, 24%-87% or 25%-87%, compared with the untreated control cells （P〈0.05）. Moreover, PZH treatment decreased the migration of HUVECs. Furthermore, PZH close-dependently suppressed the expression of VEGF-A and bFGF on both mRNA and protein levels （P〈0.05）. Conclusion： PZH could inhibit angiogenesis in vivo in CAM model and in vitro on HUVECs, suggesting that inhibiting tumor angiogenesis might be one of the mechanisms by which PZH treats cancer.展开更多
Objective: To evaluate the effect of Pien Tze Huang (片仔癀, PZH) on breast cancer chemo resistance and related epithelial-mesenchymal transition (EMT) and investigate the underlying mechanisms. Methods: 3-(4,5-Dimeth...Objective: To evaluate the effect of Pien Tze Huang (片仔癀, PZH) on breast cancer chemo resistance and related epithelial-mesenchymal transition (EMT) and investigate the underlying mechanisms. Methods: 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to determine the cell viability. Adriamycin (ADR) staining observed by fluorescence microscope was performed to detect the accumulation of ADR. Transwell assay was used to analyze the cell migration and invasion. Western-blot was performed to detect the protein expression of related genes. Results: MCF-7/ADR cells were resistant to ADR treatment, and PZH treatment inhibited the viability of MCF-7/ADR cells in a dose-dependent manner. PZH treatment also increased the intercellular accumulation of ADR and down-regulated the expression of ABCG2 and ABCB1 in MCF-7/ADR cells (P<0.05). In addition, PZH treatment inhibited EMT, migration and invasion of MCF-7/ADR cells (P<0.05). Moreover, PZH suppressed activation of transforming growth factor β 1 (TGF-β) signaling in MCF-7/ADR cells (P<0.05). Conclusion: PZH treatment can effectively overcome chemoresistance via down-regulating ABCG2, ABCB1 and inhibit EMT in ADR resistant human breast cancer cells via suppression of the TGF-β 1 pathway.展开更多
Non-alcoholic steatohepatitis(NASH)is a severe form of non-alcoholic fatty liver disease without effective treatment.The traditional Chinese medicine formulation Pien Tze Huang(PTH)can suppress inflammatory diseases.H...Non-alcoholic steatohepatitis(NASH)is a severe form of non-alcoholic fatty liver disease without effective treatment.The traditional Chinese medicine formulation Pien Tze Huang(PTH)can suppress inflammatory diseases.Here,we evaluate the effects of PTH on the evolution of NASH and its underlying mechanisms.We found that PTH prevented the development of steatohepatitis induced by various dietary models,including a high-fat high-cholesterol(HFHC)diet,choline-deficient high-fat diet(CD-HFD),and methionine-and choline-deficient(MCD)diet,along with significant suppression of liver injury,hepatic triglyceride,and lipid peroxidation.Moreover,ten days of PTH treatment after the onset of NASH significantly ameliorated MCD diet-induced steatosis and liver injury in mice.Through the metagenomic sequencing of stool samples,we found that PTH administration restored the gut microbiota with enrichment of probiotics including Lactobacillus acidophilus(L.acidophilus),Lactobacillus plantarum,Lactococcus lactis,and Bacillus subtilis.The enriched L.acidophilus prevented MCD diet-induced steatohepatitis.In addition,PTH restored the gut barrier function in mice with steatohepatitis,as evidenced by reduced intestinal permeability,decreased serum lipopolysaccharides(LPS)level,and increased epithelial tightjunction protein E-cadherin expression.Our metabolomic analysis via liquid chromatography-mass spectrometry profiling identified the alteration in the metabolism of bile acids in the portal vein of PTHtreated mice.We further confirmed that an intact gut microbiota is necessary for PTH to exhibit antisteatohepatitis effects.In conclusion,PTH protects against steatohepatitis development by modulating the gut microbiota and metabolites.PTH is a potential promising prophylactic and therapeutic option for patients with NASH.展开更多
基金supported by research funds from Zhangzhou Pien Tze Huang Pharmaceutical Co.Ltd(Grant Nos.:437b8f31,d6092dae,YHT-19064 to Chundong Yu)the National Natural Science Foundation of China(Grant Nos.:81970485,82173086 to Chundong Yu)the Natural Science Foundation of Fujian Province(Grant No.:2023J01249 to Shicong Wang).
文摘Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.
基金the Leading Technology Foundation Research Project of Jiangsu Province(No.BK20192005)the Sanming Project of Medicine in Shenzhen(No.SzSM201801060)+1 种基金the National Natural Science Foundation of China(No.82073928)CAMS Innovation Fund for Medical Sciences(No.021-I2M-5-011).
文摘Pien Tze Huang(PTH)was documented as an imperial prescription composed of Notoginseng Radix,Calculus Bovis,Snake Gallbladder,and Musk.It is famous in China and Asian countries due to its excellent effects in heat clearing,detoxifying,swelling reduction,and pain relieving.Modern pharmacological studies demonstrate that PTH shows excellent effects against various inflammatory diseases,liver diseases,and cancers.This review summaries the pharmacological effects,clinical applications,and mainchemical components of PTH.More importantly,its potential quality markers(Q-markers)were then analyzed based on the“five principles”of Q-markers under the guidance of Traditional Chinese Medicine theory,including transfer and traceability,specificity,efficacy,compatibility,and measurability.As a result,ginsenosides Rb1,ginsenoside Rg1,ginsenoside Rd,ginsenoside Re,notoginsenoside R1,dencichine,bilirubin,biliverdin,taurocholic acid,and muscone are considered as the Q-markers of PTH.These findings will provide guidance and assistance for the construction of a quality control system for PTH.
基金Supported by the National Natural Science Foundation of China,No.81603402,82060798,81860791the Special Fund Project for Graduate Innovation of Jiangxi University of Chinese Medicine,No.JZYC22S77+3 种基金a Special Fund Project for Graduate Innovation of Jiangxi Province,No.YC2022-s840,YC2022-B188Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program,No.CXTD22008the Young and Middle-aged Backbone Talent Project of Jiangxi Administration of Traditional Chinese Medicine,No.[2020]05Young Qhuang Scholars support Project of National Administration of Traditional Chinese Medicine,No.[2022]256.
文摘BACKGROUND Traditional Chinese medicine has used the drug Pien Tze Huang(PTH),a classic prescription,to treat autoimmune hepatitis(AIH).However,the precise mode of action is still unknown.AIM To investigate the mechanism of PTH in an AIH mouse model by determining the changes in gut microbiota structure and memory regulatory T(mTreg)cells functional levels.METHODS Following induction of the AIH mouse model induced by Concanavalin A(Con A),prophylactic administration of PTH was given for 10 d.The levels of mTreg cells were measured by flow cytometry,and intestinal microbiota was analyzed by 16S rRNA analysis,while western blotting was used to identify activation of the toll-like receptor(TLR)2,TLR4/nuclear factor-κB(NF-κB),and CXCL16/CXCR6 signaling pathways.RESULTS In the liver of mice with AIH,PTH relieved the pathological damage and reduced the numbers of T helper type 17 cells and interferon-γ,tumor necrosis factor-alpha,interleukin(IL)-1β,IL-2,IL-6,and IL-21 expression.Simultaneously,PTH stimulated the abundance of helpful bacteria,promoted activation of the TLR2 signal,which may enhance Treg/mTreg cells quantity to produce IL-10,and suppressed activation of the TLR4/NF-κB and CXCL16/CXCR6 signaling pathways.CONCLUSION PTH regulates intestinal microbiota balance and restores mTreg cells to alleviate experimental AIH,which is closely related to the TLR/CXCL16/CXCR6/NF-κB signaling pathway.
基金Supported by the 863 program(2012AA02A515,2012AA021802)the National Nature Science Foundation of China(81773818,81273596,30900799,81671326)+6 种基金National Key Research and Development Program(2017YFC0909303,2016YFC0905000,2016YFC0905002,2016YFC1200200,2016YFC0906400)the 4th Three-year Action Plan for Public Health of Shanghai(Project No.15GWZK0101)Shanghai Pujiang Program(17PJD020)Shanghai Key Laboratory of Psychotic Disorders(13dz2260500)Natural Science Foundation of Fujian Province(2016J05210)the Anhui Medical University for Scientific Research of BSKY(XJ201607)Anhui Medical University for Scientific Research(2017xkj006)
文摘OBJECTIVE:To explore biomarkers of Pien Tze Huang(片仔癀)that ameliorated the symptoms of hepatic fibrosis.METHODS:Two groups of carbon tetrachloride-induced hepatic fibrosis(HF)mice model were constructed in our study:one group received PZH treatment and another group received no treatment.We performed this study to investigate the role of PZH in the regulation process of hepatic fibrosis.RESULTS:We identified 31 down-regulated and 39 upregulated mi RNAs using small RNA-seq analysis.Combining RNA-Seq data analysis,our study revealed 7 significant target genes(Sp4,Slc2 a6,Tln2,Hmga2,Ank3,Pax9,Fgf9).The results of real-time quantitative polymerase chain reaction analysis suggested that the expression level of 6 genes(Sp4,Tln2,Hmga2,Ank3,Pax9,Fgf9)were down-regulated compared to control group.On the other hand,the expression level of Slc2 a6 appeared to be up-regulated.The protein mass spectrometry showed that PZH group had lower protein expression of Tln2 compared to control group.CONCLUSION:We identified 7 genes that were significantly related to PZH response in HF mice using multiple conjoint analysis methods.These genes could participate in underlying regulation mechanism of hepatic fibrosis during PZH treatment.
文摘Epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)plays an important role in cancer therapy.However,EGFR is highly expressed in the skin and gives rise to one of the most concerning issues for the EGFR-TKI treatment,namely skin toxicity.Antibiotics and corticosteroids are usually used to treat the EGFR inhibitor-associated skin rash,with prominent side effects over long-time use.Pien Tze Huang(PZH)Unguentum Compositum is a traditional product for external application which is made of traditional Chinese medicine and oil base.Herein,we reported the case of a 50-year-old man who presented with skin rash on the face,head,and back induced by an EGFR-TKI named erlotinib.By using PZH Unguentum Compositum,we observed that the skin rash was mitigated and eventually disappeared.This case report suggests that PZH Unguentum Compositum may be an effective therapy in treating skin rash caused by EGFR-TKI with fewer side effects.
基金Supported by the National Natural Science Foundation of China(No.81673721)Natural Science Foundation of Fujian Province(No.2018J01352)Natural Science Foundation of Fujian University of Traditional Chinese Medicine(No.X2023016)。
文摘Objective:To investigate the effect of miR-483-5p on hepatocellular carcinoma(HCC)cells proliferation and stemness,as well as the attenuating effect of Pien Tze Huang(PZH).Methods:Differentially expressed miRNA between HepG2 cells and hepatic cancer stem-like cells(HCSCs)were identified by a miRNA microarray assay.miR-483-5p mimics were transfected into HepG2 cells to explore the effects of miR-483-5p on cell proliferation and stemness.HepG2 cells and HCSCs were treated with PZH(0,0.25,0.50 and 0.75 mg/mL)to explore the effects of PzH on the proliferation and stemness,both in non-induced state and the state induced by miR-483-5p mimics.Results:miR-483-5p was significantly up-regulated in HCSCs and its overexpression increased cell proliferation and stemness in HepG2 cells(P<0.05).PZH not only significantly inhibited proliferation in HepG2 cells,but also significantly suppressed the cell proliferation and self-renewal of HCSCs(P<0.05).The effects of miR-483-5p mimics on proliferation and stemness of HepG2 cells were partially abolished by PZH.Conclusions:miR-483-5p promotes proliferation and enhances stemness of HepG2 cells,which were attenuated by PZH,demonstrating that miR-483-5p is a potential molecular target for the treatment of HCC and provide experimental evidence to support clinical use of PZH for patients with HCC.
文摘Objective To investigate the anti-tumor effects of Pien Tze Huang(PZH)in mouse models of B16–F10 melanoma,MC38 colorectal cancer,Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model.Methods Various tumor models,including B16–F10,MC38 and Hep1-6 tumor hypodermic inoculation models,B16–F10 and Hep1-6 pulmonary metastasis models,Hep1-6 orthotopic implantation model,and chemically induced hepatocellular carcinoma model,were utilized to evaluate the anti-tumor function of PZH.Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice.For cell proliferation and death of tumor cells in vitro,as well as T cell activation markers,cytokine production and immune checkpoints analysis,single-cell suspensions were prepared from mouse spleen,lymph nodes,and tumors after PZH treatment.Results PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth(P<0.01).Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16–F10 melanoma models,and decreased pulmonary metastasis of B16–F10 melanoma and Hep1-6 hepatoma(P<0.01).However,in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells(P>0.05).Nevertheless,PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma,tumor necrosis factor alpha,and interleukin 2 in CD4^(+)T cells in vitro(P<0.01 or P<0.05).Importantly,PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8^(+)T cells(P<0.01 or P<0.05).Conclusion This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity,indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.
基金Supported by National Natural Science Foundation of China(Nos.81803882,82274188 and 82274148)Natural Science Foundation of Fujian Province(No.2020J06026)。
文摘ObjectiveTo explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it’s down-stream mediators in colorectal cancer (CRC) cells.MethodsQuantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues.ResultsPZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05).ConclusionThe mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.
基金Supported by the National Natural Science Foundation of China(No.81073097)the Developmental Fund of CHEN Ke-ji Integrative Medicine(No.CKJ 2011001)the Natural Science Foundation of Fujian Province of China(No.2010J01195)
文摘Objective：To investigate the cellular effects of Pien Tze Huang（片仔癀,PZH） in the HT-29 human colon carcinoma cell line.Methods：The viability of HT-29 cells was determined by MTT assay.A fluorescence-activated cell sorting（FACS） analysis with annexin-V/propidium iodide（PI） and JC-1 staining were performed to determine cell apoptosis and the loss of mitochondrial membrane potential,respectively.Activation of caspase 3 was evaluated by a colorimetric assay.The mRNA expression levels of Bcl-2 and Bax were measured by reverse transcription polymerase chain reaction（RT-PCR）.Results：PZH,in a dose- and time-dependent manner,reduced viability and induced apoptosis of HT-29 cells.Moreover,PZH treatment resulted in the collapse of the mitochondrial membrane potential,activation of caspase 3,and an increase in the Bax/Bcl-2 ratio.Conclusion：PZH inhibits the growth of HT-29 cells by inducing cancer cell apoptosis via regulation of the Bcl-2 family and activation of caspase 3,which may,in part,explain its anticancer activity.
基金Surpported by the National Natural Science Foundation of China(No.81 073097)the Developmental Fund of Chen Ke-ji Integrative Medicine(No.CKJ 2011001)the Natural Science Foundation of Fujian Province of China(No.2010J01195)
文摘Objective： TO investigate the anti-angiogenic effects of Pien Tze Huang （片仔癀, PZH） in vivo and in vitro. Me.otis： Human umbilical vein endothelial cells （HUVECs） were treated with 0 mg/mL, 0.25 mg/mL, 0.5 mg/mL, and 1 mg/mL of PZH for 24 h, 48 h and 72 h, respectively. Chicken embryo chorioallantoic membrane （CAM） model was used to evaluate in vivo angiogenesis. An ECMatrix gel system was used to evaluate in vitro angiogenesis by examining the tube formation of HUVECs. 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay was performed to determine HUVEC viability. Cell density of HUVECs was observed by phase- contrast microscopy. HUVEC migration was determined by wound healing method. The mRNA and protein expression of vascular endothelial growth factor A （VEGF-A） and basic fibroblast growth factor （bFGF） in both HUVEC and human colon adenocaminoma cells （HT-29） was examined by reverse transcription polymerase chain reaction （RT-PCR） and enzyme linked immune sorbent assay （ELISA）, respectively. Results： PZH treatment significantly reduced the total number of blood vessels compared with the untreated control in the chicken embryos and resulted in a significant decrease in capillary tube formation and cell density of HUVECs （P〈0.05）. In addition, treatment with 0.25-1 mg/mL of PZH for 24 h, 48 h, and 72 h respectively reduced cell viability by 9%-52%, 24%-87% or 25%-87%, compared with the untreated control cells （P〈0.05）. Moreover, PZH treatment decreased the migration of HUVECs. Furthermore, PZH close-dependently suppressed the expression of VEGF-A and bFGF on both mRNA and protein levels （P〈0.05）. Conclusion： PZH could inhibit angiogenesis in vivo in CAM model and in vitro on HUVECs, suggesting that inhibiting tumor angiogenesis might be one of the mechanisms by which PZH treats cancer.
基金Supported by the National Natural Science Foundation of China(No.81673721)Natural Science Foundation of Fujian Province(No.2018j01352)the Developmental Fund of Chen Keji Integrative Medicine(No.CKJ2014004)
文摘Objective: To evaluate the effect of Pien Tze Huang (片仔癀, PZH) on breast cancer chemo resistance and related epithelial-mesenchymal transition (EMT) and investigate the underlying mechanisms. Methods: 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to determine the cell viability. Adriamycin (ADR) staining observed by fluorescence microscope was performed to detect the accumulation of ADR. Transwell assay was used to analyze the cell migration and invasion. Western-blot was performed to detect the protein expression of related genes. Results: MCF-7/ADR cells were resistant to ADR treatment, and PZH treatment inhibited the viability of MCF-7/ADR cells in a dose-dependent manner. PZH treatment also increased the intercellular accumulation of ADR and down-regulated the expression of ABCG2 and ABCB1 in MCF-7/ADR cells (P<0.05). In addition, PZH treatment inhibited EMT, migration and invasion of MCF-7/ADR cells (P<0.05). Moreover, PZH suppressed activation of transforming growth factor β 1 (TGF-β) signaling in MCF-7/ADR cells (P<0.05). Conclusion: PZH treatment can effectively overcome chemoresistance via down-regulating ABCG2, ABCB1 and inhibit EMT in ADR resistant human breast cancer cells via suppression of the TGF-β 1 pathway.
基金supported by the National Natural Science Foundation of China(82103355 and 82222901)Research Grants Council-General Research Fund(RGC-GRF+2 种基金14117422)Health and Medical Research Fund,Hong Kong(08191336)Vice-Chancellor’s Discretionary Fund CUHK.
文摘Non-alcoholic steatohepatitis(NASH)is a severe form of non-alcoholic fatty liver disease without effective treatment.The traditional Chinese medicine formulation Pien Tze Huang(PTH)can suppress inflammatory diseases.Here,we evaluate the effects of PTH on the evolution of NASH and its underlying mechanisms.We found that PTH prevented the development of steatohepatitis induced by various dietary models,including a high-fat high-cholesterol(HFHC)diet,choline-deficient high-fat diet(CD-HFD),and methionine-and choline-deficient(MCD)diet,along with significant suppression of liver injury,hepatic triglyceride,and lipid peroxidation.Moreover,ten days of PTH treatment after the onset of NASH significantly ameliorated MCD diet-induced steatosis and liver injury in mice.Through the metagenomic sequencing of stool samples,we found that PTH administration restored the gut microbiota with enrichment of probiotics including Lactobacillus acidophilus(L.acidophilus),Lactobacillus plantarum,Lactococcus lactis,and Bacillus subtilis.The enriched L.acidophilus prevented MCD diet-induced steatohepatitis.In addition,PTH restored the gut barrier function in mice with steatohepatitis,as evidenced by reduced intestinal permeability,decreased serum lipopolysaccharides(LPS)level,and increased epithelial tightjunction protein E-cadherin expression.Our metabolomic analysis via liquid chromatography-mass spectrometry profiling identified the alteration in the metabolism of bile acids in the portal vein of PTHtreated mice.We further confirmed that an intact gut microbiota is necessary for PTH to exhibit antisteatohepatitis effects.In conclusion,PTH protects against steatohepatitis development by modulating the gut microbiota and metabolites.PTH is a potential promising prophylactic and therapeutic option for patients with NASH.
