1.Progress of metabolic studies on flavonoids of Radix Scutellariae
Liyu LUO ; Yang LIU ; Renbing SHI ; Yanyan JIANG ; Min FANG ; Yifang HAN
International Journal of Traditional Chinese Medicine 2010;32(4):359-361
We reviewed the metabolic studies on flavonoids of Radix Scutellariae, and found that intestinal flora has played a very important role in the metabolism on Radix Scutellariae. This provided the theoretical basis for studying the bioavailability and metabolic characteristics of Radix Scutellariae.
2.Analysis of Articles Cited by SCI about Metabolism of TCM
Yang LIU ; Jichun LIANG ; Renbing SHI ; Huaqiang ZHAI ; Yanyan JIANG ; Min FANG
International Journal of Traditional Chinese Medicine 2009;31(5):448-450
To analysis the articles cited by SCI about metabolism of Traditional Chinese Medicine (TCM) and help researchers studying metabolism of TCM.
3.Studies on metabolism of Chinese materia medica of radix from Paeonia lactiflora Pall
Yanli PAN ; Ling DONG ; Yang LIU ; Renbing SHI ; Tunhai XU ; Huaqiang ZHAI ; Baosheng ZHAO ; Min FANG ; Gruopeng WANG
International Journal of Traditional Chinese Medicine 2011;33(9):798-802
ObjectiveTo research the metabolism of components in the Radix of Paeonia lactiflora Pall. Methods(①) we established the HPLC fingerprint of water extract of Paeonia lactiflora Pall. and real-time monitored the chemical composition. (②) We established the HPLC fingerprint of rats' serum samples from hepatic portal vein, serum samples from aorta abdominalis and samples of intestinal absorption of Paeonia lactiflora Pall. (③) On this basis, using the established methods, I-IPLC fingerprint spectrum of serum samples,the sample of herb, the sample after intestinal metabolism, rats' serum samples from hepatic portal vein and rats'serum samples from aorta abdominalis were analyzed and compared in order to infer the metabolism of components in the Radix of Paeonia lactiflora Pall. Results24 compositions were detected, seven of which were metabolized by intestinal flora and could not be absorbed into blood; six of them could not be absorbed directedly into intestinal; eight new compounds were absorbed into blood after bowel metabolism while they were not detected in water extract in Paeonia lactiflora Pall. ConclusionWe could infer the metabolic processes of chemicals of Paeonia lactiflora Pall. in oral administration with this method.
4.Epigenetic drug library screening reveals targeting DOT1L abrogates NAD+synthesis by reprogramming H3K79 methylation in uveal melanoma
Xiang GU ; Yu HUA ; Jie YU ; Ludi YANG ; Shengfang GE ; Renbing JIA ; Peiwei CHAI ; Ai ZHUANG ; Xianqun FAN
Journal of Pharmaceutical Analysis 2023;13(1):24-38
Uveal melanoma(UM)is the most frequent and life-threatening ocular malignancy in adults.Aberrant histone methylation contributes to the abnormal transcriptome during oncogenesis.However,a comprehensive understanding of histone methylation patterns and their therapeutic potential in UM remains enigmatic.Herein,using a systematic epi-drug screening and a high-throughput transcriptome profiling of histone methylation modifiers,we observed that disruptor of telomeric silencing-1-like(DOT1L),a methyltransferase of histone H3 lysine 79(H3K79),was activated in UM,especially in the high-risk group.Concordantly,a systematic epi-drug library screening revealed that DOT1 L inhibitors exhibited salient tumor-selective inhibitory effects on UM cells,both in vitro and in vivo.Combining Cleavage Under Targets and Tagmentation(CUT&Tag),RNA sequencing(RNA-seq),and bioinformatics analysis,we identified that DOT1 L facilitated H3K79 methylation of nicotinate phosphoribosyltransferase(NAPRT)and epigenetically activated its expression.Importantly,NAPRT served as an oncogenic accel-erator by enhancing nicotinamide adenine dinucleotide(NAD+)synthesis.Therapeutically,DOT1L inhi-bition epigenetically silenced NAPRT expression through the diminishment of dimethylation of H3K79(H3K79me2)in the NAPRT promoter,thereby inhibiting the malignant behaviors of UM.Conclusively,our findings delineated an integrated picture of the histone methylation landscape in UM and unveiled a novel DOT1L/NAPRT oncogenic mechanism that bridges transcriptional addiction and metabolic reprogramming.
5.Novel insights into histone lysine methyltransferases in cancer therapy:From epigenetic regulation to selective drugs
Qili LIAO ; Jie YANG ; Shengfang GE ; Peiwei CHAI ; Jiayan FAN ; Renbing JIA
Journal of Pharmaceutical Analysis 2023;13(2):127-141
The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chemoresistance,invasiveness,and the immune microenvironment.Therapeutically,their promising effects are being evaluated in diversified preclinical and clinical trials,demonstrating encouraging outcomes in multiple malignancies.In this review,we have updated recent understandings of KMTs'functions and the development of their targeted inhibitors.First,we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis,tumor suppression,and im-mune regulation.In addition,we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors.In summary,we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.
6.Electronic cleaning of intestinal contents tagging by diatrizoate meglumine for single-source dual-energy CT colonography with sequential acquisitions and volume scanning
Dan LIANG ; Ling WANG ; Renbing ZHOU ; Xi ZHANG ; Yang LIU ; Junyan RONG ; Wenru LI ; Dongyun ZHU ; Wenli CAI ; Mingyue LUO
Chongqing Medicine 2018;47(10):1297-1300,1304
Objective To study the feasibility of applying electronic cleaning to intestinal contents tagging by diatrizoate meglumine for single-source dual-energy CT colonography with sequential acquisitions and volume scanning.Methods Twenty-four volunteers had fine effect of intestinal contents tagging by diatrizoate meglumine,good colorectal distension effect,fine image quality of dual-energy fusion colorectal images,and with informed consents were enrolled in this study.The single-source dual-energy CT colonography with sequential acquisitions and volume scanning was performed with an Acquilion ONE 320 row CT scanner,tube voltage 135 kVp/80 kVp.The intestinal contents conducted the dual-energy electronic cleaned based on decomposition of intestinal contents tagging by diatrizoate meglumine,soft tissue and air.The intestinal contents in one segment of intestinal lumen being 100% electronically cleaned served as the basic standard,the electronic cleaning effects were divided into the 5 grades:excellent,good,moderate,fair and poor;and grade 1-3 were effective fecal electronic cleaning.Results The grade 1,2,3,4,5 of electronic cleaning effect for solid as the main intestinal contents were 22.2%,53.3%,17.8%,6.7% and 0% respectively;and which of electronic cleaning effect for liquid as the main intestinal contents were 47.5%,47.5%,5.0%,0% and 0% respectively.The together total effective electronic cleaning of intestinal contents was 97.9% and the electronic cleaning effect was good.Conclusion Electronic cleaning could be used in the intestinal contents tagging by diatrizoate meglumine for single-source dual-energy CT colonography with sequential acquisitions and volume scanning.
7.Overlapping Cervical Cell Image Segmentation Based on Bottleneck Detection and Watershed Algorithm.
Peng DUAN ; Wenbo CHENG ; Qing QIAN ; Qiang ZHANG ; Renbing YANG ; Yujun PAN
Chinese Journal of Medical Instrumentation 2020;44(1):7-12
This study proposes an image segmentation method based on bottleneck detection and watershed algorithm to solve the problem of overlapping cervical cell image. First, we use polygon approximation to get all feature points on the cell contour and then use bottleneck detection and ellipse fitting to obtain the correct split point pairs. Therefore, the approximate range of the overlapping region was determined. The watershed algorithm was used to obtain the internal boundary information for the gradient image of the region. Finally, the segmentation results of the overlapped cells were obtained by superimposing with the outer contour. The experimental results show that this algorithm can segment the contour of a single cell from the overlapping cervical cell images with good accuracy and integrity. The segmentation result is close to that of doctors' manual marking, and the segmentation result is better than other existing algorithms.
Algorithms
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Cervix Uteri/cytology*
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Female
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Humans
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Image Processing, Computer-Assisted
8.Cucurbitacin B-induced G2/M cell cycle arrest of conjunctival melanoma cells mediated by GRP78-FOXM1-KIF20A pathway.
Jinlian WEI ; Xin CHEN ; Yongyun LI ; Ruoxi LI ; Keting BAO ; Liang LIAO ; Yuqing XIE ; Tiannuo YANG ; Jin ZHU ; Fei MAO ; Shuaishuai NI ; Renbing JIA ; Xiaofang XU ; Jian LI
Acta Pharmaceutica Sinica B 2022;12(10):3861-3876
Conjunctival melanoma (CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B (CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a K d value of 0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.