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Undescribed abietane-type diterpenoids and oleanane-type triterpenoids from the stem and branch of Tripterygium wilfordii

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PHYTOCHEMISTRY 2022年 201卷 113258页

作者： Hu, Ya-Lin Xu, Tian-Qi Cheng, Huai-Yu Liu, Ying Zhang, Xia Zhang, Yu-Bo Zhou, Guang-Xiong Jinan Univ Inst Tradit Chinese Med & Nat Prod Coll Pharm Guangdong Prov Key Lab Pharmacodynam Constituents Guangzhou Peoples R China

Six undescribed abietane-type diterpenoids (tripterydinoids A-f) and five undescribed oleanane-type triterpenoids (tripterytrinoids A-E) were obtained and determined from the stem and branch of Tripterygium wilfordii Hook. f. (Celastraceae). Tripterydinoids A-C possessed the abietane-type diterpenoid skeleton with rare 8, 9epoxy ring. The structures of undescribed compounds were established by extensive spectroscopic studies [HRESIMS, 1D/2D-NMR and electronic circular dichroism (ECD) calculation]. The absolute configurations of tripterydinoids A, B, E and tripterytrinoid A were defined by X-ray crystallographic analyses. Bioactivity screening indicated that tripterydinoids A-C exhibited potent inhibitory effects against NO release in LPSactivated RAW 264.7 macrophages with IC50 values of 6.93, 4.46 and 2.98 mu M, respectively. Meanwhile, tripterydinoids A-D and tripterytrinoids B, C showed moderate and selective cytotoxicities against five human tumor cell lines (A375, Huh7, MCf-7, HCT-116 and NCI-H460).

关键词： Tripterygium wilfordii Hook f Celastraceae Diterpenoid Triterpenoid Tripterydinoid Tripterytrinoid Bioactivity

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Chaotic emperor penguin optimised extreme learning machine for microarray cancer classification

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IET SYSTEMS BIOLOGY 2020年第2期14卷 85-95页

作者： Baliarsingh, Santos Kumar Vipsita, Swati Int Inst Informat Technol Dept Comp Sci & Engn DST FIST Bioinformat Lab Bhubaneswar Odisha India

Microarray technology plays a significant role in cancer classification, where a large number of genes and samples are simultaneously analysed. for the efficient analysis of the microarray data, there is a great demand for the development of intelligent techniques. In this article, the authors propose a novel hybrid technique employing fisher criterion, Relieff, and extreme learning machine (ELM) based on the principle of chaotic emperor penguin optimisation algorithm (CEPO). EPO is a recently developed metaheuristic method. In the proposed method, initially, fisher score and Relieff are independently used as filters for relevant gene selection. further, a novel population-based metaheuristic, namely, CEPO was proposed to pre-train the ELM by selecting the optimal input weights and hidden biases. The authors have successfully conducted experiments on seven well-known data sets. To evaluate the effectiveness, the proposed method is compared with original EPO, genetic algorithm, and particle swarm optimisation-based ELM along with other state-of-the-art techniques. The experimental results show that the proposed framework achieves better accuracy as compared to the state-of-the-art schemes. The efficacy of the proposed method is demonstrated in terms of accuracy, sensitivity, specificity, and f-measure.

关键词： genetic algorithms pattern classification biology computing cancer learning (artificial intelligence) search problems particle swarm optimisation optimal input weights data sets original EPO genetic algorithm particle swarm optimisation-based ELM microarray cancer classification microarray technology microarray data intelligent techniques fisher criterion Relieff chaotic emperor penguin optimisation algorithm CEPO recently developed metaheuristic method fisher score relevant gene selection population-based chaotic penguin optimised extreme learning machine f

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Quercetin and Luteolin may be the New Effective Drugs for Radiation Pneumonitis: Based on a Systems Pharmacology

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NATURAL PRODUCT COMMUNICATIONS 2022年第10期17卷

作者： Zhang, Mengmei Li, Guangcai Hu, Huaqing Yi, Mu Li, Yang Luo, Jihang Tang, Yan Xu, Guangmin Yang, Ze Liu, Xiao Zunyi Med & Pharmaceut Coll Zunyi Guizhou Peoples R China Gushi Cty Peoples Hosp Gu Shi Peoples R China Zunyi Med Univ Zunyi Guizhou Peoples R China Zunyi Med Univ Affiliated Hosp 2 Zunyi Guizhou Peoples R China Zunyi Med Univ Affiliated Hosp Zunyi Guizhou Peoples R China Jinan Univ Zhuhai Hosp Zhuhai Peoples R China

Background: The occurrence of radiation pneumonia not only affects the efficacy of radiotherapy, but also seriously threatens the health of patients undergoing radiotherapy for lung cancer. Studies have suggested that a feining granule is a potentially effective drug for the treatment of radiation pneumonitis, but its mechanism and main components are still unclear. Our study used bioinformatics methods to analyze the main drug Aster tataricus L. f. in feining granules and aims to gain the main mechanism in the treatment of radiation pneumonitis. Methods: Analyzed the effective drug components and targets of A tataricus through the Traditional Chinese Medicine Systems Pharmacology website. And obtained gene targets related to radiation pneumonia through the website of OMIM, Genecard, and Disgenet. Protein-protein interaction (PPI), gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the obtained drugs and gene-related targets were conducted. Verify the effects of small molecule drugs on corresponding targets by conducting molecular docking experiments. Results: In total, 193 targets were identified for 13 molecules of A tataricus, and 897 genes were identified to be related to radiation pneumonia. finally, we obtained 111 genes by crossing drug and disease-related target genes. Using PPI, GO, and KEGG analysis, we found TP53, HSP90AA1, RELA, JUN, AKT1, mitogen-activated protein kinase 1 (MAPK1), tumor necrosis factor (TNf), and interleukin-6 (IL-6) are the most critical genes, which were mainly focused on the GOs of DNA-binding transcription factor, RNA polymerase II-specific DNA-binding transcription factor and protein serine/threonine kinase activity, and the pathways of lipids and atherosclerosis, advanced glycation end products and their receptors, and IL-17. Conclusion: Through molecular docking experiments, it was found that the small molecules of quercetin and luteolin bind tightly to RELA and JUN proteins. We reveal the mechani

关键词： lung cancer radiation pneumonitis Aster tataricus L f network pharmacology traditional Chinese medicine

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Persistent Placoid Maculopathy: Lichen-like Lesions Growing between Retinal Pigment Epithelium and Bruch's Membrane

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OPHTHALMOLOGY RETINA 2024年第3期8卷 270-278页

作者： Li, Miaoling Zhang, Xiongze Wen, feng Ji, Yuying Mi, Lan Sun Yat Sen Univ Zhongshan Ophthalm Ctr Guangdong Prov Key Lab Ophthalmol & Visual Sci State Key Ophthalmol 54 South Xianlie Rd Guangzhou 510060 Peoples R China

Purpose: To report the novel imaging findings in persistent placoid maculopathy (PPM) from the first case series of Asian subjects. Design: Retrospective observational case series. Subjects: Patients with PPM from 2013 to 2023. Methods: Medical records and multimodal images from each visit were analyzed. Main Outcome Measures: Imaging and follow-up findings. Results: Twenty-one eyes of 16 patients were included. Mean age was 61 (range, 48-84) years old. five patients showed bilateral involvement. Persistent placoid maculopathy lesions were unremarkable on color fundus photography, autofluorescence, and fluorescein angiography. Hypofluorescent spots with a lichen-like appearance presented in all phases of indocyanine green angiography, which were most prominent in the late phase and presented in a fused (71%) or clustered (29%) pattern. The hypofluorescence correlated with the lesions between the retinal pigment epithelium (RPE) and Bruch's membrane (BM) with moderate reflectivity on OCT, and the thickness ranged from slit-like to mound-like. The intensity of hypofluorescence sometimes varied in the same eye and correlated with the thickness of sub-RPE lesions on OCT. No abnormal blood flow signals were detected in either the sub-RPE space or choriocapillaris slab of OCT angiography across the PPM lesions. Peripapillary (5 eyes, 24%) and extra posterior pole (2 eyes, 10%) involvements were seen, the former sparing the b zones of optic discs. Ten eyes of 7 patients were followed up (median, 26 months;range, 2-121 months). During follow-up, the lichen-like lesions spread and migrated slowly without changing the plane patterns of the first visit and were limited to sub-RPE growth. The fused lichen-like pattern sprawled around the enlarged base. The clustered lichen-like pattern gradually loosened. Ten eyes (48%, 9 eyes in the fused pattern, 1 eye in the clustered pattern) had secondary choroidal neovascularization (CNV) at the first visit, with type I (6 eyes, 5 of whic

关键词： follow-up Lichen-like lesion Multimodal imaging Persistent placoid maculopathy Sub-RPE space APMPPE acute posterior multifocal placoid pigment epitheliopathy BM Bruch’s membrane CNV choroidal neovascularization f A fluorescein angiography ICGA indocyanine green angiography OCTA OCT angiography PPM persistent placoid maculopathy RPE retinal pigment epithelium SC serpiginous choroidopathy

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Unexpected rare metastases of renal cell carcinoma

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World Journal of Nuclear Medicine 2022年第1期19卷 89-91页

作者： Alex Khoo Yew Cheong Department of Nuclear Medicine Penang Adventist Hospital Pulau Pinang Malaysia Department of Surgery Penang Adventist Hospital Pulau Pinang Malaysia

Renal cell carcinomas (RCCs) commonly metastasize to the lungs and bones and rarely to the parathyroid, maxillary sinus, and adrenals. It is indeed very rare to have these all these metastases occurring simultaneously in an individual. We share a case of 67-year-old woman provisionally treated for parathyroid carcinoma but subsequently found to actually have metastatic RCC to the left maxillary sinus, parathyroid, lungs, and adrenals on

关键词： f fluorodeoxyglucose maxillary sinus metastatic parathyroid positron emission tomography–computed tomography renal cell carcinoma

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Evaluating the utility of the Af Genital System test for pathogen diagnosis in acute male urethritis

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ANDROLOGIA 2022年第4期54卷 e14377-e14377页

作者： Sarier, Mehmet Sepin, Nevgun Emek, Mestan Germen, Aysegul Tezcan Hoscan, Mustafa Burak Konuk, Elcin Turgut, Hasan Istinye Univ Dept Urol Istanbul Turkey Med Pk Hosp Dept Urol Antalya Turkey Training & Res Hosp Antalya Dept Clin Microbiol & Infect Dis Antalya Turkey Akdeniz Univ Dept Publ Hlth Antalya Turkey Med Pk Hosp Dept Obstet & Gynaecol Antalya Turkey Bilim Univ Antalya Vocat Sch Hlth Serv Dept Dialysis Antalya Turkey Prov Directorate Hlth Publ Hlth Lab Antalya Turkey Avrasya Univ Fac Hlth Sci Trabzon Turkey

This study evaluated the effectiveness of the A.f. Genital System (Liofilchem(R), Italy) in detecting pathogens compared with multiplex real-time polymerase chain reaction (PCR) in men with acute urethritis. Men diagnosed as having acute urethritis between 1 April 2021 and 31 December 2021 were included. Urethral swab samples were obtained for A.f. Genital System and PCR testing in a randomly determined order. The efficacy of the A.f. Genital System was analysed by comparing the results of the two tests. The study included 83 patients (mean age 34.1 +/- 11.3 years). A urethritis pathogen was detected in 69 patients (83.1%) by PCR and only 15 patients (18.1%) with the A.f. Genital System. The sensitivity of the A.f. Genital System in detecting acute urethritis pathogens was 21.7% (95% confidence interval [CI]: 13.6-32.8), and the specificity was 100% (95% CI: 78.5-100). Its sensitivity was 20% (95% CI: 7.1-45.2) in the diagnosis of gonococcal urethritis and 19.1% (95% CI: 11.2-30.4) in the diagnosis of non-gonococcal urethritis. PCR detected two or more urethritis pathogens in 9 patients (13.0%), while no polymicrobial infection was detected with the A.f. Genital System. Based on the results of multiplex real-time PCR, the A.f. Genital System had very low sensitivity in the detection of pathogens in acute male urethritis. It should be kept in mind that using this test in patients with acute urethritis may result in a high missed diagnosis rate for urethritis pathogens.

关键词： A f genital Af genital system diagnosis non-gonococcal PCR urethritis

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Prostate-specific antigen cutoff value for ordering sodium fluoride positron emission tomography/computed tomography bone scan in patients with prostate cancer

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World Journal of Nuclear Medicine 2022年第4期17卷 281-285页

作者： Ismet Sarikaya Ali Sarikaya Abdelhamid Elgazzar Vuslat Caloglu Prem Sharma Ali Baqer Murat Caloglu Mahmoud Alfeeli Department of Nuclear Medicine Faculty of Medicine Kuwait University Kuwait City Department of Nuclear Medicine Faculty of Medicine Trakya University Edirne Department of Radiation Oncology Faculty of Medicine Trakya University Edirne Department of Statistics Faculty of Medicine Kuwait University Kuwait City Department of Nuclear Medicine Mubarak Al-Kabeer Hospital Kuwait City

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Discovery of (R)-(3-fluoropyrrolidin-1-yl)(6-((5-(trifluoromethyl) pyridin-2-yl)oxy)quinolin-2-yl)methanone (ABBV-318) and analogs as small molecule Nav1.7/Nav1.8 blockers for the treatment of pain

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BIOORGANIC & MEDICINAL CHEMISTRY 2022年 63卷 116743页

作者： Patel, Meena, V Peltier, Hillary M. Matulenko, Mark A. Koenig, John R. Scanio, Marc J. C. Gum, Rebecca J. El-Kouhen, Odile f. fricano, Meagan M. Lundgaard, Greta L. Neelands, Torben Zhang, Xu-feng Zhan, Cenchen Pai, Madhavi Ghoreishi-Haack, Nayereh Hudzik, Thomas Gintant, Gary Martin, Ruth McGaraughty, Steve Xu, Jun Bow, Daniel Kalvass, John C. Kym, Philip R. DeGoey, David A. Kort, Michael E. AbbVie Res & Dev Dept R467AP10-1081 North Waukegan Rd N Chicago IL 60064 USA

The voltage-gated sodium channel Na(v)1.7 is an attractive target for the treatment of pain based on the high level of target validation with genetic evidence linking Na(v)1.7 to pain in humans. Our effort to identify selective, CNS-penetrant Na(v)1.7 blockers with oral activity, improved selectivity, good drug-like properties, and safety led to the discovery of 2-substituted quinolines and quinolones as potent small molecule Na(v)1.7 blockers. The design of these molecules focused on maintaining potency at Na(v)1.7, improving selectivity over the hERG channel, and overcoming phospholipidosis observed with the initial leads. The structure-activity relationship (SAR) studies leading to the discovery of (R)-(3-fluoropyrrolidin-1-yl)(6-((5-(trifluoromethyl)pyridin-2-yl)oxy)quinolin-2-yl)methanone (ABBV-318) are described herein. ABBV-318 displayed robust in vivo efficacy in both inflammatory and neuropathic rodent models of pain. ABBV-318 also inhibited Na(v)1.8, another sodium channel isoform that is an active target for the development of new pain treatments.

关键词： Na v 1.7 voltage-gated sodium channel type 7 CIP congenital insensitivity to pain SCN9A sodium channel, voltage-gated, type IX, R subunit VGSC voltage-gated sodium channel SAR structure activity relationship hERG human Ether-à-go-go-Related Gene fRET fluorescence Resonance Energy Transfer MIA-OA mono-iodoacetate-induced osteoarthritis HEK human embryonic kidney CNS central nervous system PK pharmacokinetic Clint,u in- vitro intrinsic clearance, unbound f oral bioavailability TfA trifluoroacetic acid HATU (1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5– b ]pyridinium 3-oxid hexafluorophosphate) TBTU O-(benzotriazol-1-yl)- N,N,N′,N′- tetramethyluronium tetrafluoroborate DMSO dimethyl sulfoxide DRG Dorsal root ganglion LMA Locomotor assay SNL Spinal nerve ligation

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Evaluation of recurrent parathyroid carcinoma: A new imaging tool in uncommon entity

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World Journal of Nuclear Medicine 2022年第2期18卷 198-200页

作者： N. T. K. Thanseer Ashwin Singh Parihar Ashwani Sood Sanjay Kumar Bhadada Divya Dahiya Priyanka Singh Bhagwant Rai Mittal Department of Nuclear Medicine Postgraduate Institute of Medical Education and Research Chandigarh India

Parathyroid carcinoma (PTC) is a rare endocrine tumor and uncommon cause for primary hyperparathyroidism.

关键词： f fluorocholine f fluorodeoxyglucose positron emission tomography and computed tomography recurrent parathyroid carcinoma

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Lonicera rupicola *** Thoms flavonoids ameliorated dysregulated inflammatory responses, intestinal barrier, and gut microbiome in ulcerative colitis via PI3K/AKT pathway

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PHYTOMEDICINE 2022年第0期104卷 154284页

作者： Li, Congcong Zhao, Juebo Wei, Yucai Zhai, Shuo Tan, Min Guan, Kuikui Huang, Zhihong Chen, Chaoxi Southwest Minzu Univ Coll Anim & Vet Sci Chengdu 610041 Peoples R China Southwest Minzu Univ Key Lab Qinghai Tibetan Plateau Anim Genet Resourc Chengdu 610041 Peoples R China Southwest Minzu Univ Coll Anim & Vet Sci Key Lab Qinghai Tibetan Plateau Anim Genet Resourc Chengdu 610041 Peoples R China

Background: Lonicera rupicola *** Thoms (LRH) is used as a customary medicinal herb in Tibetans. And LRH flavonoids have excellent anti-inflammatory and antioxidant pharmacological activities. However, the specific effects of LRH and its mechanism remain unknown, and there is a deficiency of systematic research, leading to the waste of LRH as a medicinal ***: In this study, in an attempt to rationalize the development and utilization of Tibetan herbal resources, the therapeutic efficacy and the underlying molecular mechanisms of LRH flavonoids on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) were investigated, establishing the favorable basis for the pharmacodynamic material basis of LRH and providing a scientific basis for the discovery of new drugs for the treatment of UC. Methods: firstly, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used for identification and detection of the flavonoid components of LRH. Meanwhile, their potential targets, biological functions and signaling pathways were predicted with the assistance of network pharmacology analysis. Subsequently, pharmacological efficacy of LRH were evaluated by body weight loss, colon length, disease activity index (DAI), histology observation and the expression levels of inflammatory mediators, messenger RNA (mRNA) and tight junction proteins. Moreover, in the present investigation, we also profiled the gut microbiome via high-throughput sequencing of the V3 -V4 region of 16S ribosomal DNA (rDNA) for bacterial community composition and diversity by Illumina MiSeq platforms. finally, the key regulatory proteins in the PI3K/AKT pathways were measured to investigate their underlying molecular ***: A total of 37 LRH flavonoid components were identified and detected by UPLC-MS/MS, and 12 potential active components were obtained after screening. 137 of their common targets with UC were further predicted. GO and KEGG pathway enri

关键词： inflammation intestinal barrier gut microbiome ulcerative colitis PI3K AKT pathway Lonicera rupicola Hook f et Thoms

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