Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling

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.

Pien Tze Huang alleviates Concanavalin A-induced autoimmune hepatitis by regulating intestinal microbiota and memory regulatory T cells

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.

Skin rash caused by EGFR-TKI could be treated successfully by Pien Tze Huang Unguentum Compositum: a case report

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.

CHEONG FATT TZE 宅第的适时重建,槟榔屿,马来西亚

场地面积:5 888m2项目造价:200万美元(人民币 1660万元)业主:Cheong Fatt Tze 宅第公司机电工程师:Penkonsult 股份有限公司主承包商:萨里卡特兴发工程公司(重建工程)

Elliptische Identifikationsstze als bildungselement ■gyptischer eulogien und hymnen

Bei seinen Bemuhungen um die Stilistik agyptischer Texte ging H. Grapow an verschiedenen Stellen auf die ,,Hymnenform in pw-Satzen' ein. Als ein wichtiges Kriterium stellte er dabei heraus, daβ es sich hierbei nicht um Hymnen an, sondern um Hymnen auf den Konig handelt.2 Mit ihrem deskriptiven Charakter, durch den sie Aussagen uber den Konig machen (NN pw - ,,Ein NN ist er'), entfaltet diese Form der Hymnen Wesenszuge des Konigs (besser: dogmatische Charakteristika des Konigtums) und setzt sich damit gegen

Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10,MC38 and Hep1-6 Tumor Models

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.

Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway

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.

Research progress on the pharmacological effects and chemical constituents of Pien Tze Huang and its potential Q-markers

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.

片仔癀通过调节小鼠的肠道菌群和代谢物抑制非酒精性脂肪性肝炎

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.

非遗医药企业数字营销的实践探索与路径优化——以片仔癀为例

数字营销具有覆盖面广、交互性强、形式多样、投放精准、性价比高等优点,逐渐成为企业营销战略的重要组成部分。非遗医药企业拥有悠久的历史和深厚的文化底蕴,但是部分企业营销策略滞后于数字时代,营业状况不容乐观。基于非遗医药企业片仔癀数字营销实践的典型案例,针对片仔癀数字营销存在问题,企业应运用数字媒体塑造品牌,加强数字营销平台产品联动,利用数字技术拓展营销方式,强化线上线下渠道协同营销等优化策略。片仔癀数字营销案例的剖析能为同类型非遗医药企业开展数字营销实践提供借鉴。

片仔癀对情志内热诱导流感病毒易感性的作用研究

目的本研究在中医情志致病理论指导下,基于课题组前期利用小鼠拘束应激附加H1N1感染构建情志内热诱导流感病毒易感模型,评价了名优清热中成药片仔癀对流感病毒易感性的作用。方法小鼠拘束应激18 h后滴鼻感染H1N1流感病毒,记录小鼠的体征和体质量变化,统计各组小鼠的发病率。在病毒感染后的第4日取肺脏组织采用HE染色、免疫组化、Western blot、ELISA等方法检测病理情况和炎症水平;分别通过Western blot和试剂盒检测脂质过氧化终产物水平;利用氧化磷脂组学检测肺组织中各类氧化磷脂的含量。结果片仔癀能够显著降低情志应激小鼠感染流感病毒的发病率,抑制肺组织流感病毒复制与炎症因子释放,改善肺部炎症,缓解脂质过氧化终产物堆积。氧化磷脂组学结果显示,情志应激附加流感感染小鼠肺组织中氧化磷脂酰胆碱和氧化磷脂酰乙醇胺水平均明显增加,片仔癀给药能显著降低磷脂过氧化水平。结论清热中药片仔癀对情志内热诱导的流感病毒易感有良好的改善作用,作用机制可能与调节磷脂过氧化有关。

片仔癀通过BCL-2及Caspase途径参与急性淋巴白血病耐药细胞株MOLT-4/ADM耐药逆转机制的研究

目的探讨片仔癀对耐阿霉素的急性淋巴细胞白血病细胞株MOLT-4/ADM药物耐受逆转的机制。方法在不同浓度片仔癀作用MOLT-4/ADM细胞48 h后,用MTS法检测MOLT-4/ADM增殖的影响;利用流式细胞术检测MOLT-4/ADM细胞凋亡率;实时荧光PCR检测耐药基因MDR1以及BCL-2 mRNA、Caspase-3/8/9 mRNA表达;蛋白免疫印迹法(western blotting)检测凋亡蛋白BCL-2、Caspase-3/8/9以及多药耐药蛋白(P-gp)表达。结果0.4 mg/ml片仔癀组对MOLT-4/ADM耐阿霉素的IC50逆转倍数为4.02倍。0.2 mg/ml片仔癀组凋亡率为(9.87±0.47)%,0.4 mg/ml片仔癀组凋亡率为(15.17±0.69)%,0.8 mg/ml片仔癀组凋亡率为(20.32±0.87)%,均高于阴性对照组(6.06±0.35)%。随着片仔癀用药浓度的增大,BCL-2 mRNA表达下降,而Caspase-3/8/9 mRNA升高。BCL-2蛋白表达下降,而Caspase-3/9蛋白表达量升高,Caspase-8蛋白相对变化不大。结论片仔癀可以通过BCL-2以及Caspase途径诱导凋亡,增加MOLT-4/ADM对阿霉素的敏感性。

Pien Tze Huang(片仔癀)-Induced Apoptosis in Human Colon Cancer HT-29 Cells Is Associated with Regulation of the Bcl-2 Family and Activation of Caspase 3

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.

Effects of Pien Tze Huang(片仔癀) on Angiogenesis in vivo and in vitro

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.

Pien Tze Huang(片仔癀) Overcomes Doxorubicin Resistance and Inhibits Epithelial-Mesenchymal Transition in MCF-7/ADR Cells

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.

“不言之教”的哲学意义

自柏拉图以来,知识不仅被定义为有证成的真信念,而且被看作教育的认知目标。然而,知识的定义遭遇了盖梯尔问题的挑战,这使得知识不再被看作教育的认知目标或唯一认知目标。教育领域的盖梯尔问题是指,虽然学生给出了正确答案,但是,他并没有掌握正确答案背后的科学原理,他仅仅是碰巧给出了正确答案。这个问题也被称为教育的认知运气。从教育认知运气的角度可以重新发现《老子》“不言之教”的哲学意义。所谓“不言之教”并不像陈汉生认为的那样是反对语言或者放弃语言,而是反对自以为是、故步自封的学习方式和教学方式。对“不言之教”的解释不仅借鉴了威廉姆森的认知主义,而且得到《老子》文本证据的支持。

片仔癀研粉外敷在小儿肛肠疾病术后肛周皮肤护理中的应用

目的探讨片仔癀研粉外敷在小儿肛肠疾病术后肛周皮肤护理中的应用效果。方法选取2022年1月至2023年11月福建医科大学附属漳州市医院小儿外科收治的82例外科手术治疗的肛肠疾病患儿为研究对象,基于随机数字表法分为研究组和对照组,均为41例。术后对照组采取常规肛周皮肤护理,研究组同时应用片仔癀研粉外敷,对比分析两组患儿肛周皮损的发生率、皮损严重程度、儿童疼痛行为量表(FLACC)评分及愈合时间,以及家长对护理的满意度。结果研究组肛周皮损发生率为9.76%,低于对照组的26.83%(P<0.05)。研究组肛周皮损严重度评分、FLACC评分及愈合时间均低于对照组(均P<0.05)。研究组干预总有效率、护理满意度分别是95.12%、95.12%,均高于对照组的75.61%、76.92%(均P<0.05)。结论在小儿肛肠疾病术后肛周皮肤护理中应用片仔癀研粉外敷,可有效提高护理效果,减少肛周皮损发生,并减轻皮损严重度和疼痛度,促进皮损愈合。

Drug response biomarkers of Pien Tze Huang(片仔癀) treatment for hepatic fibrosis induced by carbon tetrachloride

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.

片仔癀抑制胰腺癌细胞上皮间质转化机制研究

目的探讨片仔癀(PZH)对AsPC-1、PANC-1细胞增殖、迁移及上皮间质转化(EMT)的调控作用。方法采用MTT实验筛选出PZH溶液干预AsPC-1、PANC-1细胞的最佳浓度为0、0.5、1 mg/mL。转录组测序检测0、1 mg/mL PZH干预AsPC-1细胞的基因表达变化;划痕愈合实验检测AsPC-1、PANC-1细胞的迁移能力;Transwell迁移实验检测AsPC-1、PANC-1细胞的迁移能力;Western blot检测AsPC-1、PANC-1细胞E-钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)、N-钙黏蛋白(N-cadherin)和E盒结合锌指蛋白1(ZEB1)的蛋白表达。结果①转录组测序:0、1 mg/mL组在与EMT相关的重要指标中基因表达量具有明显差异(P<0.05)。②划痕愈合实验:与0 mg/mL组比较,1 mg/mL组PANC-1细胞12 h划痕损伤率明显降低(P<0.05),1 mg/mL组AsPC-1细胞24 h划痕损伤率明显降低(P<0.05),0.5、1 mg/mL组AsPC-1和PANC-1细胞48 h划痕损伤率明显降低(P<0.05)。③Transwell迁移实验:与0 mg/mL组比较,1 mg/mL组AsPC-1和PANC-1细胞相对迁移比值明显降低(P<0.05)。④Western blot实验:与0 mg/mL组比较,1 mg/mL组AsPC-1细胞E-cadherin蛋白表达量明显升高(P<0.05),0.5、1 mg/mL组AsPC-1细胞Vimentin蛋白表达量均明显降低(P<0.05);与0 mg/mL组比较,1 mg/mL组PANC-1细胞N-cadherin、ZEB1蛋白表达量均明显降低(P<0.05)。结论PZH明显抑制人胰腺癌细胞的增殖、迁移及EMT,具有抗胰腺癌转移的潜在功效。

片仔癀对酒精诱导的急性肝损伤小鼠自噬和NLRP3炎症小体活化的影响

目的研究片仔癀(PTH)对酒精诱导小鼠急性肝损伤的保护作用及可能机制。方法将C57BL/6小鼠随机分为空白组、酒精组、PTH低(75 mg·kg^(-1))、中(150 mg·kg^(-1))、高(300 mg·kg^(-1))剂量组,连续灌胃给药3 d(2次/天)。除空白组外,其余各组小鼠于末次给药2 h后灌胃酒精(0.12 mg/10 g)进行造模;24 h后各组小鼠摘眼球取血以测定ALT、AST和TG水平;并取肝组织进行HE检查;qRT-PCR检测肝组织中IL-6、IL^(-1)β和TNF-αmRNA表达水平;Western blot检测NLRP3、Caspase-1 p20、IL^(-1)8、Beclin1、LC3蛋白表达水平。结果与模型组相比,PTH可明显减轻酒精诱导的小鼠急性肝损伤病理情况,降低血清中ALT、AST和TG的含量(P<0.05或P<0.01);PTH可明显降低酒精诱导的急性肝损伤小鼠肝组织中IL-6、IL^(-1)β和TNF-αmRNA的表达水平(P<0.05或P<0.01);PTH可明显上调酒精诱导急性肝损伤小鼠肝组织中LC3-Ⅱ/LC3-Ⅰ比值以及Beclin1的蛋白表达水平(P<0.05或P<0.01),下调NLRP3、Caspase-1 p20、IL^(-1)8蛋白表达水平(P<0.05或P<0.01)。结论片仔癀可能通过调控自噬和NLRP3炎症小体活化而减少炎症介质释放,进而改善酒精诱导的小鼠急性肝损伤。