JCAD deficiency attenuates activation of hepatic stellate cells and cholestatic fibrosis

Li Xie,Hui Chen,Li Zhang,Yue Ma,Yuan Zhou,Yong-Yu Yang,Chang Liu,Yu-Li Wang,Ya-Jun Yan,Jia Ding,Xiao Teng,Qiang Yang,Xiu-Ping Liu,Jian Wu 대한간학회 2024 Clinical and Molecular Hepatology(대한간학회지) Vol.30 No.2

Background/Aims: Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet. Methods: Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. In situ-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation. Results: In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated in situ HSC activation and reduced expression of fibrotic genes after BDL. Conclusions: JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.

A novel human KRAB-related zinc finger gene ZNF425 inhibits mitogen-activated protein kinase signaling pathway

( Yue Qun Wang ),( Xiang Li Ye ),( Jun Mei Zhou ),( Yong Qi Wan ),( Hua Ping Xie ),( Yun Deng ),( Yan Yan ),( Yong Qing Li ),( Xiong Wei Fan ),( Wu Zhou Yuan ),( Xiao Yang Mo ),( Xiu Shan Wu ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.1

Zinc finger (ZNF) proteins play a critical role in cell growth, proliferation, apoptosis, and intracellular signal transduction. In this paper, we cloned and characterized a novel human KRAB-related zinc finger gene, ZNF425, which encodes a protein of 752 amino acids. ZNF425 is strongly expressed in the three month old human embryos and then is almost undetectable in six month old embryos and in adult tissues. An EGFP-ZNF425 fusion protein can be found in both the nucleus and the cytoplasm. ZNF425 appears to act as a transcription repressor. Over-expression of ZNF425 inhibits the transcriptional activities of SRE, AP-1, and SRF. Deletion analysis indicates that the C2H2 domain is the main region responsible for the repression. Our results suggest that the ZNF425 gene is a new transcriptional inhibitor that functions in the MAPK signaling pathway. [BMB reports 2011; 44(1): 58-63]

Stem Cell-Derived Exosomes: A New Method for Reversing Skin Aging

Wu Jinyan,Wu Sai-Nan,Zhang Li-Ping,Zhao Xiansheng,Li Yue,Yang Quyang,Yuan Ruoyue,Liu Jian-Lan,Mao Hong-Ju,Zhu Ningwen 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.5

Senescence is an inevitable natural life process that involves structural and functional degeneration of tissues and organs. Recently, the process of skin aging has attracted much attention. Determining a means to delay or even reverse skin aging has become a research hotspot in medical cosmetology and anti-aging. Dysfunction in the epidermis and fibroblasts and changes in the composition and content of the extracellular matrix are common pathophysiological manifestations of skin aging. Reactive oxygen species and matrix metalloproteinases play essential roles in this process. Stem cells are pluripotent cells that possess self-replication abilities and can differentiate into multiple functional cells under certain conditions. These cells also possess a strong ability to facilitate tissue repair and regeneration. Stem cell transplantation has the potential for application in anti-aging therapy. Increasing studies have demonstrated that stem cells perform functions through paracrine processes, particularly those involving exosomes. Exosomes are nano-vesicular substances secreted by stem cells that participate in cell-to-cell communication by transporting their contents into target cells. In this chapter, the biological characteristics of exosomes were reviewed, including their effects on extracellular matrix formation, epidermal cell function, fibroblast function and antioxidation. Exosomes derived from stem cells may provide a new means to reverse skin aging.

Adipose-Derived Stem Cell Exosomes Promoted Hair Regeneration

Wu Jinyan,Yang Quyang,Wu Sainan,Yuan Ruoyue,Zhao Xiansheng,Li Yue,Wu Wenyu,Zhu Ningwen 한국조직공학과 재생의학회 2021 조직공학과 재생의학 Vol.18 No.4

Background: Some scholars have found that dermal papilla spheroid–derived exosomes could promote the development of hair follicles. However, whether adipose-derived stem cell exosomes (ADSC-Exos) have a similar effect on hair growth has not been determined yet. Thus, the purpose of this article was to detect whether ADSC-Exos could promote hair regeneration. Methods: Adipose-derived stem cells (ADSCs) were isolated from 6-week-old C57BL/6 mice. Then, ADSC-Exos were isolated from the ADSCs. Western blotting was used to detect specific exosome markers. The particle size and distribution of the exosomes were analyzed by NanoSight dynamic light scattering. A total of 12 nude mice were randomly divided into two groups (n = 6 each): the ADSC-Exos group and the control group. For the control group, a mixture of freshly isolated dermal cells (DCs) and epidermal cells (ECs) was grafted. For the ADSC-Exos group, a mixture of DCs, ECs, and 50 μg/ml of ADSC-Exos was grafted. Gross evaluation of the hair regeneration was carried out 2–3 weeks after the transplantation, and the graft site was harvested for histology at the third week. Results: The existence of exosomes derived from ADSCs was evidenced by CD63, ALX1, and CD9 expression. Two or three weeks after the grafting, the number of regenerated hairs in the ADSC-Exos group was higher than that in the control group (p < 0.001). Histologically, the terminal hairs were remarkable in the ADSC-Exos group, whereas the hair follicles observed in the control group were comparatively immature. The ADSC-Exos group had a higher number of regenerated follicles than the control group (p < 0.001). In addition, we found that the skin tissues in the ADSC-Exos group had higher PDGF and vascular endothelial growth factor expressions and lower transforming growth factor beta 1 levels than those in the control group. Conclusion: Our results indicated that ADSC-Exos could promote in vivo hair follicle regeneration. Background: Some scholars have found that dermal papilla spheroid–derived exosomes could promote the development of hair follicles. However, whether adipose-derived stem cell exosomes (ADSC-Exos) have a similar effect on hair growth has not been determined yet. Thus, the purpose of this article was to detect whether ADSC-Exos could promote hair regeneration. Methods: Adipose-derived stem cells (ADSCs) were isolated from 6-week-old C57BL/6 mice. Then, ADSC-Exos were isolated from the ADSCs. Western blotting was used to detect specific exosome markers. The particle size and distribution of the exosomes were analyzed by NanoSight dynamic light scattering. A total of 12 nude mice were randomly divided into two groups (n = 6 each): the ADSC-Exos group and the control group. For the control group, a mixture of freshly isolated dermal cells (DCs) and epidermal cells (ECs) was grafted. For the ADSC-Exos group, a mixture of DCs, ECs, and 50 μg/ml of ADSC-Exos was grafted. Gross evaluation of the hair regeneration was carried out 2–3 weeks after the transplantation, and the graft site was harvested for histology at the third week. Results: The existence of exosomes derived from ADSCs was evidenced by CD63, ALX1, and CD9 expression. Two or three weeks after the grafting, the number of regenerated hairs in the ADSC-Exos group was higher than that in the control group (p < 0.001). Histologically, the terminal hairs were remarkable in the ADSC-Exos group, whereas the hair follicles observed in the control group were comparatively immature. The ADSC-Exos group had a higher number of regenerated follicles than the control group (p < 0.001). In addition, we found that the skin tissues in the ADSC-Exos group had higher PDGF and vascular endothelial growth factor expressions and lower transforming growth factor beta 1 levels than those in the control group. Conclusion: Our results indicated that ADSC-Exos could promote in vivo hair follicle regeneration.

A sum of an alternating series involving central binomial numbers and its three proofs

Yue-Wu Li,Feng Qi 한국수학교육학회 2022 純粹 및 應用數學 Vol.29 No.1

In the note, by virtue of Abel's theorem and Abel's limit theorem in the theory of power series, the author provides three proofs for a sum of an alternating series involving central binomial numbers.

ZNF424, a novel human KRAB/C2H2 zinc finger protein, suppresses NFAT and p21 pathway

( Yue Qun Wang ),( Jun Mei Zhou ),( Xiang Li Ye ),( Yong Qi Wan ),( Yong Qing Li ),( Xiao Yan Mo ),( Wu Zhou Yuan ),( Yan Yan ),( Na Luo ),( Ze Qun Wang ),( Xiong Wei Fan ),( Yun Deng ),( Xiu Shan Wu 한국생화학분자생물학회 (구 한국생화학회) 2010 BMB Reports Vol.43 No.3

Zinc finger-containing transcription factors are the largest single family of transcriptional regulators in mammals, which play an essential role in cell differentiation, cell proliferation, apoptosis, and neoplastic transformation. Here we have cloned a novel KRAB-related zinc finger gene, ZNF424, encoding a protein of 555aa. ZNF424 gene consisted of 4 exons and 3 introns, and mapped to chromosome 19p13.3. ZNF424 gene was ubiquitously expressed in human embryo tissues by Northern blot analysis. ZNF424 is conserved across species in evolution. Using a GFP-labeled ZNF424 protein, we demonstrate that ZNF424 localizes mostly in the nucleus. Transcriptional activity assays shows ZNF424 suppresses transcriptional activity of L8G5-luciferase. Overexpression of ZNF424 in HEK- 293 cells inhibited the transcriptional activity of NFAT and p21, which may be silenced by siRNA. The results suggest that ZNF424 protein may act as a transcriptional repressor that suppresses NFAT and p21 pathway to mediate cellular functions. [BMB reports 2010; 43(3): 212-218]

High Levels of Malic Acid Production by the Bioconversion of Corn Straw Hydrolyte Using an Isolated Rhizopus Delemar Strain

Xingjiang Li,Ya Liu,Ying Yang,Hua Zhang,Hualin Wang,Yue Wu,Min Zhang,Ting Sun,Jieshun Cheng,Xuefeng Wu,Lijun Pan,Shaotong Jiang,Hongwei Wu 한국생물공학회 2014 Biotechnology and Bioprocess Engineering Vol.19 No.3

The microbial fermentation of malic acid,which is one of the most important organic acid platformsused widely in food and chemical engineering, hasattracted considerable interest. A malate production strainwas isolated, a mutation was induced, and regulation of themetabolic network was then conducted. The identificationresults showed that the malic acid production strain, HF-119, belonged to Rhizopus delemar. An analysis of themetabolic pathway showed that the malic acid flux of thisstrain occurred through three main pathways, and manybyproducts, such as succinic acid, fumaric acid andethanol, were produced. Although corn straw hydrolytewas used, the metabolism of xylose was not as rapid as thatof glucose. Subsequently, breeding of the strains andregulation of the metabolic network resulted in an increasein malate yield, and the strain HF-121 produced more than120 g/L malic acid within 60 h. The ability to producemalic acid from biomass hydrolyte highlights the industrialdevelopment potential of this strain.

Comparative Study of Bioactive Constituents in Crude and Processed Glycyrrhizae radix and Their Respective Metabolic Profiles in Gastrointestinal Tract In Vitro by HPLC-DAD and HPLC-ESI/MS Analyses

Wen-wu Huang,Xiaobo Li,Meng Yue Wang,Hai-ming Shi,Ying Peng,Chong-sheng Peng,Min Zhang,Yue Li,Jing Lu 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.11

Two HPLC methods with diode array detection (HPLC-DAD) and electrospray ionization-mass spectrometry (HPLC-ESI/MS), respectively, were developed to investigate the differences of chemical constituents and their metabolism in gastrointestinal tract in vitro between two decoctions of crude and processed Glycyrrhizae radix. Total of eleven constituents (liquiritin apioside, liquiritin, licuraside, isoliquiritin, ononin, glycyrrhizin, liquiritigenin-7,4'-diglucoside, licorice saponin A3, 22β-acetoxylglycyrrhizic acid, licorice saponin G2, and yunganoside E2) were identified in the two decoctions, whereas lower contents of these constituents were usually found in the decoction of processed G. radix. Furthermore, these constituents were metabolized into their respective aglycons in human intestinal bacteria juice, and the metabolism ratios were all higher in processed G. radix decoction. No change was found in artificial gastric or intestinal juice. This study revealed that the processing can alter the contents of main constituents in crude G. radix and their metabolism in gastrointestinal tract, in which intestinal bacteria play an important role in the metabolism of licorice constituents.

Effect of Trichostatin A on CNE2 Nasopharyngeal Carcinoma Cells - Genome-wide DNA Methylation Alteration

Yang, Xiao-Li,Zhang, Cheng-Dong,Wu, Hua-Yu,Wu, Yong-Hu,Zhang, Yue-Ning,Qin, Meng-Bin,Wu, Hua,Liu, Xiao-Chun,Lina, Xing,Lu, Shao-Ming Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor. We here investigated its effects on proliferation and apoptosis of the CNE2 carcinoma cell line, and attempted to establish genome-wide DNA methylation alteration due to differentially histone acetylation status. After cells were treated by TSA, the inhibitory rate of cell proliferation was examined with a CCK8 kit, and cell apoptosis was determined by flow cytometry. Compared to control, TSA inhibited CNE2 cell growth and induced apoptosis. Furthermore, TSA was found to induce genome-wide methylation alteration as assessed by genome-wide methylation array. Overall DNA methylation level of cells treated with TSA was higher than in controls. Function and pathway analysis revealed that many genes with methylation alteration were involved in key biological roles, such as apoptosis and cell proliferation. Three genes (DAP3, HSPB1 and CLDN) were independently confirmed by quantitative real-time PCR. Finally, we conclude that TSA inhibits CNE2 cell growth and induces apoptosis in vitro involving genome-wide DNA methylation alteration, so that it has promising application prospects in treatment of NPC in vivo. Although many unreported hypermethylated/hypomethylated genes should be further analyzed and validated, the pointers to new biomarkers and therapeutic strategies in the treatment of NPC should be stressed.

Macrophages Promote Coal Tar Pitch Extract-induced Tumorigenesis of BEAS-2B Cells and Tumor Metastasis in Nude Mice Mediated by AP-1

Zhang, Peng,Jin, Yue-Fei,Zhang, Qiao,Wu, Yi-Ming,Wu, Wei-Dong,Yao, Wu,Wu, Yong-Jun,Li, Zhi-Tao,Zhao, Yong,Liu, Yu,Feng, Fei-Fei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Background: We sought to evaluate the role of tumor associated macrophages (TAMs) on the promotion of coal tar pitch extract (CTPE)-induced tumorigenesis of human bronchial epithelial cells (BEAS-2B) and tumor metastasis in nude mice, and related mechanisms. Materials and Methods: BEAS-2B cells were first treated with 2.4 mg/mL CTPE for 72 hours. After removal of CTPE, the cells were continuously cultured and passaged using trypsin-EDTA. THP-1 cells were used as macrophage-like cells. BEAS-2B cells under different conditions (n=6/group) were injected into the back necks of nude mice, and alterations of tumor xenograft growth, indicative of tumorigenicity, and tumor metastasis were determined. Pathological changes (tumor nests and microvascular lesions) of HE-stained tumor tissues were also evaluated. The expression of AP-1(c-Jun) in xenografts and metastatic tumors was determined using immunohistochemistry. Results: Tumor size and weight in nude mice transplanted with the mixture of CTPE-induced passage 30 BEAS-2B and THP-1 cells (2:1) were increased compared to those from the CTPE-treated BEAS-2B cells at passage 30 alone at different observation time points. Tumor metastasis to lymph nodes and liver was only detected after transplantation of a mixture the two kinds of cells. The numbers of tumor nests and microvascular lesions, and the expression levels of AP-1 (c-Jun) in tumors from the mixture of two kinds of cells were increased apparently in contrast to those in tumor from the CTPE-treated BEAS-2B cells of passage 30 alone. In addition, there was positive correlation between AP-1 (c-Jun) expression level and the number of microvascular lesions, or between AP-1 (c-Jun) expression level and tumor metastasis in these two groups. Conclusions: TAMs not only facilitate tumorigenesis transformation of CTPE-induced BEAS-2B cells, but also promote tumor growth, angiogenesis and metastasis in nude mice in vivo, which may be mediated by AP-1.