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Project description:Pien Tze Huang (PZH) is a traditional Chinese medicinal formula that has been extensively used in Asia for the treatment of liver diseases. We created two groups of liver cancer mouse models induced by carbon tetrachloride (CCl4): one group received treatment with PZH and the other did not receive any treatment. In the non-PZH treated group, we observed a significant increase in liver function indices including albumin (ALB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological examination using hematoxylin and eosin (HE) staining revealed inflammation around the hepatic vein in the non-PZH treated group. Furthermore, Masson's trichrome staining demonstrated the presence of blue-stained collagen fibers around the hepatic vein in the non-PZH treated group. These findings suggest that PZH may have therapeutic effects on liver inflammation and cancer. To further explore the molecular mechanisms of PZH's action, we conducted mRNA, long non-coding RNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA) sequencing to identify potential drug targets at the transcriptome level. We identified 478 differentially expressed protein-coding transcripts and 68 differentially expressed lncRNA transcripts. Our study provides insights into potential transcriptional therapeutic targets for the clinical use of PZH in treating liver diseases.
2024-05-26 | GSE268337 | GEO
Project description:Pien Tze Huang (PZH) is a traditional Chinese medicine which was widely utilized in Asia for hepatic diseases. We construct two groups liver cancer mice model using CCl4, one group using PZH treatment and another group didn?t treatment. We found that the liver functional indices including ALB, ALT and AST were significantly increased in non-PZH treatment group. HE staining showed that inflammation was emerged surrounding the hepatic vein in the non-PZH treatment group, Masson staining revealed that there are blue collagenous fibre surrounding hepatic vein in the non-PZH treatment group, this result indicated that PZH cured the hepatic inflammation and cancer. We performed the mRNA,LncRNA,ciecRNA and miRNA sequencing aim to explore the drug target using PZH treatment on transcriptome level. 478 protein coding transcripts and 68 lncRNA transcripts were differentially expressed. Our research provided potential transcriptional therapeutic target for the clinical treatment using PZH.
2024-05-26 | GSE268335 | GEO
Project description:Pien Tze Huang (PZH) is a traditional Chinese medicinal formula that has been extensively used in Asia for the treatment of liver diseases. We created two groups of liver cancer mouse models induced by carbon tetrachloride (CCl4): one group received treatment with PZH and the other did not receive any treatment. In the non-PZH treated group, we observed a significant increase in liver function indices including albumin (ALB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological examination using hematoxylin and eosin (HE) staining revealed inflammation around the hepatic vein in the non-PZH treated group. Furthermore, Masson's trichrome staining demonstrated the presence of blue-stained collagen fibers around the hepatic vein in the non-PZH treated group. These findings suggest that PZH may have therapeutic effects on liver inflammation and cancer. To further explore the molecular mechanisms of PZH's action, we conducted mRNA, long non-coding RNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA) sequencing to identify potential drug targets at the transcriptome level. We identified 478 differentially expressed protein-coding transcripts and 68 differentially expressed lncRNA transcripts. Our study provides insights into potential transcriptional therapeutic targets for the clinical use of PZH in treating liver diseases.
2024-05-26 | GSE268336 | GEO
Project description:Pien Tze Huang (PZH), a common hepatoprotective Traditional Chinese Medicine that has been found to be an effective treatment for carbon tetrachloride‑induced hepatic damage, including liver fibrosis. Circular RNAs (circRNAs) serve a crucial role in regulating gene expression levels via circRNA/micro (mi)RNA/mRNA networks in several human diseases and biological processes. However, whether circRNAs are involved in the underlying mechanism of the therapeutic effects of PZH on liver fibrosis remains unclear. Therefore, the aim of the present study was to investigate these effects using circRNA expression profiles from PZH‑treated fibrotic livers in model mice. A case‑control study on >59,476 circRNAs from CCl4‑induced (control group, n=6) and PZH‑treated (case group, n=6) mice was performed using circRNA sequencing in liver tissues. PZH treatment resulted in the differential expression of 91 circRNAs, including 58 upregulated and 33 downregulated circRNAs. Furthermore, the construction of competing endogenous networks also indicated that differentially expressed circRNAs acted as miRNA sponges. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of miRNA targets demonstrated that PZH‑affected circRNAs were mainly involved in biological processes such as 'positive regulation of fibroblast proliferation', 'cellular response to interleukin‑1' and 'regulation of DNA‑templated transcription in response to stress' and in a number of important pathways, such as 'TNF signaling pathway', 'PI3K‑Akt signaling pathway', 'IL‑17 signaling pathway' and 'MAPK signaling pathway'. To further validate the bioinformatics data, reverse transcription‑-quantitative PCR was performed on seven miRNA targets in a human hepatic stellate LX‑2 cell model. The results suggested that seven of the miRNAs exhibited regulatory patterns that were consistent with those of the transcriptome sequencing results. Kaplan‑Meier survival analysis demonstrated that the expression levels of dihydrodiol dehydrogenase and solute carrier family 7, member 11 gene were significantly associated with patient survival, 269 patients with liver hepatocellular carcinoma from The Cancer Genome Atlas database. To the best of our knowledge, this was the first study to provide evidence that PZH affects circRNA expression levels, which may serve important roles in PZH‑treated fibrotic liver through the regulation of functional gene expression. In conclusion, the present study provided new insights into the mechanism underlying the pathogenesis of liver fibrosis and identified potential novel, efficient, therapeutic targets against liver injury.
| S-EPMC9437966 | biostudies-literature
Project description:BackgroundStroke caused by brain ischemia is the third leading cause of adult disability. Active prevention and early treatment of stroke targeting the causes and risk factors may decrease its incidence, mortality and subsequent disability. Pien Tze Huang (PZH), a Chinese medicine formula, was found to have anti-edema, anti-inflammatory and anti-thrombotic effects that can prevent brain damage. This study aims to investigate the potential mechanisms of the preventive effects of Pien Tze Huang on brain damage caused by chronic ischemia and hypertensive stroke in rats.MethodsThe effects of Pien Tze Huang on brain protein expression in spontaneously hypertensive rat (SHR) and stroke prone SHR (SHRsp) were studied with 2-D gel electrophoresis and mass spectrometric analysis with a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)/TOF tandem mass spectrometer and on brain cell death with enzyme link immunosorbent assay (ELISA) and immunostaining.ResultsPien Tze Huang decreased cell death in hippocampus and cerebellum caused by chronic ischemia and hypertensive stroke. Immunostaining of caspase-3 results indicated that Pien Tze Huang prevents brain cells from apoptosis caused by ischemia. Brain protein expression results suggested that Pien Tze Huang downregulated QCR2 in the electron transfer chain of mitochondria preventing reactive oxygen species (ROS) damage and possibly subsequent cell death (caspase 3 assay) as caused by chronic ischemia or hypertensive stroke to hippocampus and cerebellum.ConclusionPien Tze Huang showed preventive effects on limiting the damage or injury caused by chronic ischemia and hypertensive stroke in rats. The effect of Pien Tze Huang was possibly related to prevention of cell death from apoptosis or ROS/oxidative damage in mitochondria.
| S-EPMC2984508 | biostudies-literature
Project description:Cirrhosis has been one of the major causes of morbidity and mortality worldwide, but safe and effective therapy remains limited. A traditional Chinese medicine, Pien Tze Huang (PTH), has been reported to be effective in protecting the liver. Thus, in this study, we established a mouse cirrhosis model to investigate the effect of PTH on cirrhosis and the potential protective biomarkers using transcriptomic analysis. We identified 1689, 218, 61, and 145 differentially expressed mRNAs, lncRNAs, miRNAs, and circRNAs between the PTH treatment group and the cirrhosis group. Functional enrichment analysis demonstrated that biologically sensible GO terms, such as positive regulation of biological process and response to stimulus, and KEGG pathways, such as IL-17 signaling pathway and Steroid hormone biosynthesis, might be associated with PTH treatment. Similarity analysis based on the drug-induced gene expression profiles of Connectivity Map (version 2) suggested that PTH might have a similar effect to several drugs in clinical trials for cirrhosis. Finally, integration analysis of the competitive endogenous RNA network revealed that eight genes, i.e., P4ha1, Runx1, Inpp5d, Trp53inp1, Rrad, Pkm, Eva1a, and Jun, might be the potential protective biomarkers of PTH against cirrhosis.
2024-06-10 | GSE269013 | GEO
Project description:Cirrhosis has been one of the major causes of morbidity and mortality worldwide, but safe and effective therapy remains limited. A traditional Chinese medicine, Pien Tze Huang (PTH), has been reported to be effective in protecting the liver. Thus, in this study, we established a mouse cirrhosis model to investigate the effect of PTH on cirrhosis and the potential protective biomarkers using transcriptomic analysis. We identified 1689, 218, 61, and 145 differentially expressed mRNAs, lncRNAs, miRNAs, and circRNAs between the PTH treatment group and the cirrhosis group. Functional enrichment analysis demonstrated that biologically sensible GO terms, such as positive regulation of biological process and response to stimulus, and KEGG pathways, such as IL-17 signaling pathway and Steroid hormone biosynthesis, might be associated with PTH treatment. Similarity analysis based on the drug-induced gene expression profiles of Connectivity Map (version 2) suggested that PTH might have a similar effect to several drugs in clinical trials for cirrhosis. Finally, integration analysis of the competitive endogenous RNA network revealed that eight genes, i.e., P4ha1, Runx1, Inpp5d, Trp53inp1, Rrad, Pkm, Eva1a, and Jun, might be the potential protective biomarkers of PTH against cirrhosis.
2024-06-10 | GSE269012 | GEO
Project description:Cirrhosis has been one of the major causes of morbidity and mortality worldwide, but safe and effective therapy remains limited. A traditional Chinese medicine, Pien Tze Huang (PTH), has been reported to be effective in protecting the liver. Thus, in this study, we established a mouse cirrhosis model to investigate the effect of PTH on cirrhosis and the potential protective biomarkers using transcriptomic analysis. We identified 1689, 218, 61, and 145 differentially expressed mRNAs, lncRNAs, miRNAs, and circRNAs between the PTH treatment group and the cirrhosis group. Functional enrichment analysis demonstrated that biologically sensible GO terms, such as positive regulation of biological process and response to stimulus, and KEGG pathways, such as IL-17 signaling pathway and Steroid hormone biosynthesis, might be associated with PTH treatment. Similarity analysis based on the drug-induced gene expression profiles of Connectivity Map (version 2) suggested that PTH might have a similar effect to several drugs in clinical trials for cirrhosis. Finally, integration analysis of the competitive endogenous RNA network revealed that eight genes, i.e., P4ha1, Runx1, Inpp5d, Trp53inp1, Rrad, Pkm, Eva1a, and Jun, might be the potential protective biomarkers of PTH against cirrhosis.
2024-06-10 | GSE269011 | GEO
Project description:Ethnopharmacological relevance: Pien-Tze-Huang (PZH)—a traditional Chinese medicine (TCM) compound—has been employed to treat various liver inflammation and tumors for over 10 decades. Interestingly, most of the pharmacological effects had been validated and explored toward liver ailment along with pro-inflammatory conditions and cancer at the cellular and molecular level to date. Aim of the study: The present study aimed to investigate the therapeutic effect of PZH on autophagy and TGF-β1 signaling pathways in rats with liver fibrosis and hepatic stellate cell line (HSC). Materials and methods: Male SD rats with carbon tetrachloride (CCl4)-induced liver fibrosis were used as the animal model. Next, PZH treatment was given for 8 weeks. Afterward, the therapeutic effects of PZH were analyzed through a hepatic tissue structure by hematoxylin-eosin (H&E), Van Gieson (VG) staining, and transmission electron microscopy (TEM), activity of ALT and AST by enzyme-associated immunosorbent assay as well. Subsequently, mRNA and protein expression were examined by quantitative polymerase chain reaction (qPCR), Western blotting, and immunohistochemistry (IHC). Then, the cell vitality of PZH-treated HSC and the expression of key molecules prevailing to autophagy were studied in vitro. Meanwhile, SM16 (a novel small molecular inhibitor which inhibits TGFβ-induced Smad2 phosphorylation) was employed to confirm PZH’s effects on the proliferation and autophagy of HSC. Results: PZH pharmacologically exerted anti-hepatic fibrosis effects as demonstrated by protecting hepatocytes and improving hepatic function. The results revealed the reduced production of extracellular collagen by adjusting the balance of matrix metalloproteinase (MMP) 2, MMP9, and tissue inhibitor of matrix metalloproteinase 1 (TIMP1) in PZH-treated CCl4-induced liver fibrosis. Interestingly, PZH inhibited the activation of HSC by down-regulating TGF-β1 and phosphorylating Smad2. Furthermore, PZH down-regulated yeast Atg6 (Beclin-1) and microtubule-associated protein light chain 3 (LC3) toward suppressing HSC autophagy, and PZH exhibited similar effects to that of SM16. Conclusion: To conclude, PZH alleviated CCl4-induced liver fibrosis to reduce the production of extracellular collagen and inhibiting the activation of HSC. In addition, their pharmacological mechanisms related to autophagy and TGF-β1/Smad2 signaling pathways were revealed for the first time.
| S-EPMC9523731 | biostudies-literature
Project description:Transcriptome Analysis Reveals Potential Protective Effects and Biomarkers of Pien Tze Huang on CCl4-induced Liver Cancer
| PRJNA1116231 | ENA