Chemical and bioactive comparison of Panax notoginseng root and rhizome in raw and steamed forms

Yin Xiong,Lijuan Chen,Jinhui Man,Yupiao Hu,Xiuming Cui 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.3

Background: The root and rhizome are historically and officially utilized medicinal parts of Panaxnotoginseng (PN) (Burk.) F. H. Chen, which in raw and steamed forms are used differently in practice. Methods: To investigate the differences in chemical composition and bioactivities of PN root and rhizomebetween raw and steamed forms, high-performance liquid chromatography analyses and pharmacologiceffects evaluated by tests of anticoagulation, antioxidation, hemostasis, antiinflammation, and hematopoiesiswere combined. Results: With the duration of steaming time, the contents of ginsenosides Rg1, Re, Rb1, Rd, and notoginsenosideR1 in PN were decreased, while those of ginsenosides Rh1, 20(S)-Rg3, 20(R)-Rg3, Rh4, and Rk3were increased gradually. Raw PN samples steamed for 6 h at 120 C with stable levels of most constituentswere used for the subsequent study of bioeffects. Raw PN showed better hemostasis, anticoagulation,and antiinflammation effects, while steamed PN exhibited stronger antioxidation andhematopoiesis activities. For different parts of PN, contents of saponins in PN rhizome were generallyhigher than those in the root, which could be related to the stronger bioactivities of rhizome comparedwith the same form of PN root. Conclusion: This study provides basic information about the chemical and bioactive comparison of PNroot and rhizome in both raw and steamed forms, indicating that the change of saponins may have a keyrole in different properties of raw and steamed PN.

Chemical and bioactive comparison of Panax notoginseng root and rhizome in raw and steamed forms

Xiong, Yin,Chen, Lijuan,Man, Jinhui,Hu, Yupiao,Cui, Xiuming The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.3

Background: The root and rhizome are historically and officially utilized medicinal parts of Panax notoginseng (PN) (Burk.) F. H. Chen, which in raw and steamed forms are used differently in practice. Methods: To investigate the differences in chemical composition and bioactivities of PN root and rhizome between raw and steamed forms, high-performance liquid chromatography analyses and pharmacologic effects evaluated by tests of anticoagulation, antioxidation, hemostasis, antiinflammation, and hematopoiesis were combined. Results: With the duration of steaming time, the contents of ginsenosides $Rg_1$, Re, $Rb_1$, Rd, and notoginsenoside $R_1$ in PN were decreased, while those of ginsenosides $Rh_1$, $20(S)-Rg_3$, $20(R)-Rg_3$, $Rh_4$, and $Rk_3$ were increased gradually. Raw PN samples steamed for 6 h at $120^{\circ}C$ with stable levels of most constituents were used for the subsequent study of bioeffects. Raw PN showed better hemostasis, anticoagulation, and antiinflammation effects, while steamed PN exhibited stronger antioxidation and hematopoiesis activities. For different parts of PN, contents of saponins in PN rhizome were generally higher than those in the root, which could be related to the stronger bioactivities of rhizome compared with the same form of PN root. Conclusion: This study provides basic information about the chemical and bioactive comparison of PN root and rhizome in both raw and steamed forms, indicating that the change of saponins may have a key role in different properties of raw and steamed PN.

DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating miR-21 biogenesis

Yin, Jinlong,Park, Gunwoo,Lee, Jeong Eun,Choi, Eun Young,Park, Ju Young,Kim, Tae-Hoon,Park, Nayun,Jin, Xiong,Jung, Ji-Eun,Shin, Daye,Hong, Jun Hee,Kim, Hyunggee,Yoo, Heon,Lee, Seung-Hoon,Kim, Youn-Jae Oxford University Press 2015 Brain Vol.138 No.9

<P>Upregulation of microRNA-21 (miR-21) is strongly associated with glioma malignancy, but the regulatory mechanism that governs miR-21 biogenesis is unclear. Yin <I>et al.</I> demonstrate that the DEAD-box RNA helicase DDX23 promotes miR-21 biogenesis at the post-transcriptional level in glioma cells, and that DDX23 inhibition reduces glioma growth in mouse xenografts.</P><P> [Figure] </P><P>Upregulation of microRNA-21 (miR-21) is known to be strongly associated with the proliferation, invasion, and radio-resistance of glioma cells. However, the regulatory mechanism that governs the biogenesis of miR-21 in glioma is still unclear. Here, we demonstrate that the DEAD-box RNA helicase, DDX23, promotes miR-21 biogenesis at the post-transcriptional level. The expression of DDX23 was enhanced in glioma tissues compared to normal brain, and expression level of DDX23 was highly associated with poor survival of glioma patients. Specific knockdown of DDX23 expression suppressed glioma cell proliferation and invasion <I>in vitro</I> and <I>in vivo</I>, which is similar to the function of miR-21. We found that DDX23 increased the level of miR-21 by promoting primary-to-precursor processing of miR-21 through an interaction with the Drosha microprocessor. Mutagenesis experiments critically demonstrated that the helicase activity of DDX23 was essential for the processing (cropping) of miR-21, and we further found that ivermectin, a RNA helicase inhibitor, decreased miR-21 levels by potentially inhibiting DDX23 activity and blocked invasion and cell proliferation. Moreover, treatment of ivermectin decreased glioma growth in mouse xenografts. Taken together, these results suggest that DDX23 plays an essential role in glioma progression, and might thus be a potential novel target for the therapeutic treatment of glioma.</P>

Single-cell RNA sequencing reveals B cell–related molecular biomarkers for Alzheimer’s disease

Xiong Liu-Lin,Xue Lu-Lu,Du Ruo-Lan,Niu Rui-Ze,Chen Li,Chen Jie,Hu Qiao,Tan Ya-Xin,Shang Hui-Fang,Liu Jia,Yu Chang-Yin,Wang Ting-Hua 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

In recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression.

The inhibitory effect of pyrogallol on tyrosinase activity and structure: Integration study of inhibition kinetics with molecular dynamics simulation

Xiong, Shang-Ling,Lim, Gyu Tae,Yin, Shang-Jun,Lee, Jinhyuk,Si, Yue-Xiu,Yang, Jun-Mo,Park, Yong-Doo,Qian, Guo-Ying Elsevier 2019 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Vol.121 No.-

<P><B>Abstract</B></P> <P>Pyrogallol is naturally found in aquatic plant and has been proposed as a substrate of tyrosinase. In this study, we evaluated the dual effect of pyrogallol on tyrosinase as an inhibitor in the presence of L‑DOPA simultaneously via integrating methods of enzyme kinetics and computational molecular dynamics (MD) simulations. Pyrogallol was found to be a reversible inhibitor of tyrosinase in the presence of L‑DOPA and its induced mechanism was the parabolic non-competitive inhibition type (<I>IC</I> <SUB>50</SUB> = 0.772 ± 0.003 mM and <I>K</I> <SUB>i</SUB> = 0.529 ± 0.022 mM). Kinetic measurements by real-time interval assay showed that pyrogallol induced rapid inactivation process composing with slight activations at the low dose. Spectrofluorimetry studies showed that pyrogallol mainly induced regional changes in the active site of tyrosinase accompanying with hydrophobic disruption at high dose. The computational MD simulations further revealed that pyrogallol could interact with several residues near the tyrosinase active site pocket such as HIS61, HIS85, HIS259, ASN260, HIS263, VAL283, and ALA296. Our study provides insight into the mechanism by which hydroxyl group composing pyrogallol inhibit tyrosinase and pyrogallol is a potential natural anti-pigmentation agent.</P>

The Dual-frequency (20/40 kHz) Ultrasound Assisted Photocatalysis with the Active Carbon Fiber-loaded Fe³⁺-TiO₂ as Photocatalyst for Degradation of Organic Dye

Xiong, Shaofeng,Yin, Zhoulan,Zhou, Yuanjin,Peng, Xianzhong,Yan, Wenbin,Liu, Zhixiong,Zhang, Xiangyu Korean Chemical Society 2013 Bulletin of the Korean Chemical Society Vol.34 No.10

Dual-frequency ultrasound assisted photocatalysis (DUAP) method was proposed to degrade a stable organic model effluent, cresol red (CR), using the prepared $Fe^{3+}$-doped $TiO_2$ with active carbon fiber loading ($Fe^{3+}-TiO_2/ACF$) as photocatalyst. The influence of key factors, including Fe doping amount and power density of dual-frequency ultrasounds (20/40 kHz), on the degradation efficiency was investigated. The degradation efficiency rises to 98.7% in 60 min accompanied by the color removal of CR liquid samples from yellow to colorless transparent at optimal conditions. A synergy index of 1.40 was yielded by comparison with single ultrasound assisted photocatalysis (SUAP) and the photocatalysis without ultrasound assisted (UV/$TiO_2$), indicating that a clear synergistic effect exists for the DUAP process. Obvious enhancement of degradation efficiency for the DUAP process should be attributed to production of large amount of free radicals by strong cavitational effects of dual ultrasounds.

Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells

Yin, Jinlong,Park, Gunwoo,Kim, Tae Hoon,Hong, Jun Hee,Kim, Youn-Jae,Jin, Xiong,Kang, Sangjo,Jung, Ji-Eun,Kim, Jeong-Yub,Yun, Hyeongsun,Lee, Jeong Eun,Kim, Minkyung,Chung, Junho,Kim, Hyunggee,Nakano, I Public Library of Science 2015 PLoS biology Vol.13 No.5

<▼1><P>Epidermal growth factor receptor variant III (EGFRvIII) has been associated with glioma stemness, but the direct molecular mechanism linking the two is largely unknown. Here, we show that EGFRvIII induces the expression and secretion of pigment epithelium-derived factor (PEDF) via activation of signal transducer and activator of transcription 3 (STAT3), thereby promoting self-renewal and tumor progression of glioma stem cells (GSCs). Mechanistically, PEDF sustained GSC self-renewal by Notch1 cleavage, and the generated intracellular domain of Notch1 (NICD) induced the expression of Sox2 through interaction with its promoter region. Furthermore, a subpopulation with high levels of PEDF was capable of infiltration along corpus callosum. Inhibition of PEDF diminished GSC self-renewal and increased survival of orthotopic tumor-bearing mice. Together, these data indicate the novel role of PEDF as a key regulator of GSC and suggest clinical implications.</P></▼1><▼2><P>A permanently activated mutant form of the epidermal growth factor receptor found in glioblastoma promotes self-renewal and tumor progression by inducing autocrine signalling via pigment epithelium-derived factor (PEDF).</P></▼2><▼3><P><B>Author Summary</B></P><P>Malignant gliomas are among the most lethal types of cancer, due in part to the stem-cell-like characteristics and invasive properties of the brain tumor cells. However, little is known about the underlying molecular mechanisms that govern such processes. Here, we identify pigment epithelium-derived factor (PEDF) as a critical factor controlling stemness and tumor progression in glioma stem cells. We found that PEDF is secreted from glioblastoma expressing EGFRvIII, a frequently occurring mutation in primary glioblastoma that yields a permanently activated epidermal growth factor receptor. We delineate an EGFRvIII-STAT3-PEDF signaling axis as a signature profile of highly malignant gliomas, which promotes self-renewal of glioma stem cells. Our results demonstrate a previously unprecedented function of PEDF and implicate potential therapeutic approaches against malignant gliomas.</P></▼3>

Direct ethanol production from dextran industrial waste water by Zymomonas mobilis

Ming-xiong He,Han Qin,Xiao-bo Yin,Zhi-yong Ruan,Fu-rong Tan,Bo Wu,Zong-xia Shui,Li-chun Dai,Qi-chun Hu 한국화학공학회 2014 Korean Journal of Chemical Engineering Vol.31 No.11

The direct production of ethanol from dextran industrial waste water was investigated by using Zymomonasmobilis via batch and semi-continuous fermentation mode. In batch fermentation, pretreated waste water (unsterilizedand sterilized), pH value (3.8 and 6.0), and Mg2+(with and without) was compared with OD600, sugar and ethanol con-centration. After 24 h fermentation, sugar in the dextran waste water was almost exhausted, and the amount of ethanolaccumulated reached 24.33-29.92 g/l, which is nearly 99% of the theoretical yield of ethanol. Kinetic parameters ofZ. mobilis in batch fermentation were also investigated. The raw dextran waste water was also used in semi-continuousfermentation. After 48 h fermentation, the production of ethanol was 28.65 g/l. These results indicated that dextranwaste water may be used as a candidate substrate and Z. mobilis could convert the raw material into ethanol directly.

Prognostic value of preoperative neutrophil-to-lymphocyte ratio in histological variants of non-muscle-invasive bladder cancer

Deng-xiong Li,Xiao-ming Wang,Yin Tang,Yu-bo Yang,Dechao Feng,Ao Li,Fa-cai Zhang,Yun-jin Bai,Ping Han 대한비뇨의학회 2021 Investigative and Clinical Urology Vol.62 No.6

Purpose: Many studies identified that the preoperative neutrophil-to-lymphocyte ratio (PNLR) was associated with patient prognosis in non-muscle-invasive bladder cancer (NMIBC). We hypothesized that PNLR could be prognostic in patients with histological variants of NMIBC (VH-NMIBC). Materials and Methods: This retrospective study included patients with VH-NMIBC admitted at our center between January 2009 and May 2019. The best cut-off value of NLR was measured by the receiver operating characteristic curve and Youden index. The Kaplan-Meier method and Cox proportional hazard regression models were employed to evaluate the association between PNLR and disease prognosis, including recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results: A total of 243 patients with VH-NMIBC were enrolled in our study. According to the Kaplan-Meier method results, patients with PNLR ≥2.2 were associated with poor RFS (p<0.001), PFS (p<0.001), CSS (p<0.001), and OS (p<0.001). Multivariable analyses indicated that PNLR ≥ 2.2 was an independent prognostic factor of RFS (hazard ratio [HR], 2.11; 95% confidence interval [CI, 1.57–1.83; p<0.001), PFS (HR, 2.34; 95% CI, 1.70–3.21; p<0.001), CCS (HR, 2.87; 95% CI, 1.96–4.18; p< 0.001), and OS (HR, 2.83; 95% CI, 1.96–4.07; p<0.001). Conclusions: This study identified that PNLR ≥2.2 was usually associated with a poor prognosis for patients with VH-NMIBC.

Inhibition of ID1–BMPR2 Intrinsic Signaling Sensitizes Glioma Stem Cells to Differentiation Therapy

Jin, Xiong,Jin, Xun,Kim, Leo J.Y.,Dixit, Deobrat,Jeon, Hee-Young,Kim, Eun-Jung,Kim, Jun-Kyum,Lee, Seon Yong,Yin, Jinlong,Rich, Jeremy N.,Kim, Hyunggee American Association for Cancer Research 2018 Clinical Cancer Research Vol.24 No.2

<P><B>Purpose:</B> Normal stem cells tightly control self-renewal and differentiation during development, but their neoplastic counterparts, cancer stem cells (CSCs), sustain tumorigenicity both through aberrant activation of stemness and evasion of differentiation. Although regulation of CSC stemness has been extensively studied, the molecular mechanisms suppressing differentiation remain unclear.</P><P><B>Experimental Design:</B> We performed <I>in silico</I> screening and <I>in vitro</I> validation studies through Western blotting, qRT-PCR for treatment of WNT and SHH signaling inhibitors, and BMP signaling inducer with control and ID1-overexpressing cells. We also performed <I>in vivo</I> drug treatment assays with Balb/c nude mice.</P><P><B>Results:</B> Inhibitor of differentiation 1 (ID1) abrogated differentiation signals from bone morphogenetic protein receptor (BMPR) signaling in glioblastoma stem cells (GSCs) to promote self-renewal. ID1 inhibited BMPR2 expression through miRNAs, miR-17 and miR-20a, which are transcriptional targets of MYC. ID1 increases MYC expression by activating WNT and SHH signaling. Combined pharmacologic blockade of WNT and SHH signaling with BMP treatment significantly suppressed GSC self-renewal and extended survival of tumor-bearing mice.</P><P><B>Conclusions:</B> Collectively, our results suggested that ID1 simultaneously regulates stemness through WNT and SHH signaling and differentiation through BMPR-mediated differentiation signaling in GSCs, informing a novel therapeutic strategy of combinatorial targeting of stemness and differentiation. <I>Clin Cancer Res; 24(2); 383–94. ©2017 AACR</I>.</P>