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An inulin-type fructan CP-A from Codonopsis pilosula attenuates experimental colitis in mice by promoting autophagy-mediated inactivation of NLRP3 inflammasome

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Chinese Journal of Natural Medicines 2024年第3期22卷 249-264页

作者： ZHOU Jiangtao WANG Jun WANG Jiajing LI Deyun HOU Jing LI Jiankuan BAI Yun’e GAO Jianping School of pharmaceutical science Shanxi Medical UniversityJinzhong 030600China

Inulin-type fructan CP-A,a predominant polysaccharide in Codonopsis pilosula,demonstrates regulatory effects on immune activity and *** efficacy of CP-A in treating ulcerative colitis(UC)is,however,not *** study employed an in vitro lipopolysaccharide(LPS)-induced colonic epithelial cell model(NCM460)and an in vivo dextran sulfate sodium(DSS)-induced colitis mouse model to explore CP-A’s protective effects against experimental colitis and its underlying *** monitored the clinical symptoms in mice using various parameters:body weight,disease activity index(DAI),colon length,spleen weight,and histopathological ***,molecular markers were assessed through enzyme-linked immunosorbent assay(ELISA),quantitative real-time polymerase chain reaction(qRT-PCR),immunofluorescence(IF),immunohistochemistry(IHC),and Western blotting *** showed that CP-A significantly reduced reactive oxygen species(ROS),tumor necrosis factor-alpha(TNF-α),and interleukins(IL-6,IL-1β,IL-18)in LPS-induced cells while increasing IL-4 and IL-10 levels and enhancing the expression of Claudin-1,ZO-1,and occludin proteins in NCM460 ***,in vivo findings revealed that CPA administration markedly improved DAI,reduced colon shortening,and decreased the production of myeloperoxidase(MPO),malondialdehyde(MDA),ROS,IL-1β,IL-18,and NOD-like receptor protein 3(NLRP3)inflammasome-associated genes/proteins in UC ***-A treatment also elevated glutathione(GSH)and superoxide dismutase(SOD)levels,stimulated autophagy(LC3B,P62,Beclin-1,and ATG5),and reinforced Claudin-1 and ZO-1 expression,thereby aiding in intestinal epithelial barrier repair in colitis ***,the inhibition of autophagy via chloroquine(CQ)diminished CP-A’s protective impact against colitis in *** findings elucidate that CP-A’s therapeutic effect on experimental colitis possibly involves mitigating intestinal inflammation through autophagymediated N

关键词： Inulin-type fructan CP-A Codonopsis pilosula Ulcerative colitis NLRP3 inflammasome Autophagy

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New phenylbutenoids and terpene glycosides from Ginkgo biloba leaves

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Chinese Journal of Natural Medicines 2024年第2期22卷 161-170页

作者： SUN Zeshi LIN Shan WU Zhi-Li DONG Hong-Yuan XU Xi-Ke LI Hui-Liang WANG Jinxin School of Pharmacy Second Military Medical UniversityShanghai 200433China State Key Laboratory of New Drug and pharmaceutical Process Shanghai Institute of Pharmaceutical IndustryChina State Institute of Pharmaceutical IndustryShanghai 201203China

Our continued works on the chemical constituents of Ginkgo biloba(***)leaves has led to the isolation of two novel phenylbutenoids(1,2),along with five previously unidentified terpene glycosides(3−7).Among them,compounds 1 and 2 represent unique(Z)-phenylbutenoids,3−6 are megastigmane glycosides,and 7 is identified as a rare bilobanone glycoside(Fig.1).This study marks the first reported isolation of phenylbutenoid and bilobanone glycoside from *** chemical structures of these compounds were elucidated through extensive spectroscopic analysis,including HR-ESI-MS and various 1D and 2D NMR ***,the absolute configurations of these molecules were determined using Mosher’s method,ECD experiments,and Cu-KαX-ray crystallographic analyses.

关键词： Ginkgo biloba Phenylbutenoid Megastigmane glycoside Bilobanone glycoside

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Real-time model correction using Kalman filter for Raman-controlled cell culture processes

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Chinese Journal of Chemical Engineering 2024年第6期70卷 251-260页

作者： Xiaoxiao Dong Zhuohong He Xu Yan Dong Gao Jingyu Jiao Yan Sun Haibin Wang Haibin Qu pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Hisun Biopharmaceutical Co.Ltd. Hangzhou 311404China

Raman spectroscopy has found extensive use in monitoring and controlling cell culture *** this context,the prediction accuracy of Raman-based models is of paramount ***,models established with data from manually fed-batch cultures often exhibit poor performance in Raman-controlled ***,there is a need for effective methods to rectify these *** objective of this paper is to investigate the efficacy of Kalman filter(KF)algorithm in correcting Raman-based models during cell ***,partial least squares(PLS)models for different components were constructed using data from manually fed-batch cultures,and the predictive performance of these models was ***,various correction methods including the PLS-KF-KF method proposed in this study were employed to refine the PLS ***,a case study involving the auto-control of glucose concentration demonstrated the application of optimal model correction *** results indicated that the original PLS models exhibited differential performance between manually fed-batch cultures and Raman-controlled *** glucose,the root mean square error of prediction(RMSEP)of manually fed-batch culture and Raman-controlled culture was 0.23 and 0.40 g·L^(-1).With the implementation of model correction methods,there was a significant improvement in model performance within Raman-controlled *** RMSEP for glucose from updating-PLS,KF-PLS,and PLS-KF-KF was 0.38,0.36 and 0.17 g·L^(-1),***,the proposed PLS-KF-KF model correction method was found to be more effective and stable,playing a vital role in the automated nutrient feeding of cell cultures.

关键词： Raman spectroscopy Model correction Algorithm Model-predictive control Bioprocess

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Overcoming neutrophil-induced immunosuppression in postoperative cancer therapy: Combined sialic acid-modified liposomes with scaffold-based vaccines

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Asian Journal of pharmaceutical sciences 2024年第2期19卷 153-169页

作者： Cong Li Lihong Wang Kexin Zhang Zeyu Wang Zhihang Li Zehao Li Lijiang Chen School of pharmaceutical science Liaoning UniversityShenyang 110036China

Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.

关键词： Postoperative tumor treatment Immunotherapy Scaffold-based cancer vaccine Inflammatory neutrophils Sialic acid-modied liposome

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The role of Piezo1 and Piezo2 proteins in tissue engineering:A Comprehensive review

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Engineered Regeneration 2024年第2期5卷 170-185页

作者： Tejaswini Tadge Ashwini Pattewar Namdev More Srivalliputtur Sarath Babu Ravichandiran Velyutham Govinda Kapusetti National institute of pharmaceutical Education and Research KolkataWest Bengal 700054India National institute of pharmaceutical Education and Research AhmedabadGujarat 382355India

Almost every life form,from the tiniest bacterium to humans,is mechanosensitive,implying it can use mechani-cal stresses to trigger certain physiological responses in the form of electric *** largely relies on ion channels that respond to mechanical forces,such as the epithelial sodium channels/degenerins,tran-sient receptor potential channel,and the two-pore domain potassium ***1 and Piezo2 proteins were discovered to be the biggest non-selective mechanosensitive cation channels in the cell membrane.A substantial amount of research has previously been published on the Piezo channel’s function in touch sensation,balance,and cardiovascular ***,the mechanistic perspective must be refined to fully understand the role of Piezo proteins in tissue *** review centers on the latest insights into the structure of Piezo chan-nels,activation mechanisms,and its interactions with cytoskeletal components,by emphasizing the physiological activities of Piezo channels in different *** study also places focus on the possibilities of targeting this cation channel family as a tissue regeneration aid.

关键词： Piezo1 Piezo2 Mechanotransduction Tissue regeneration Mechanoreceptors

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A naturally derived small molecule compound suppresses tumor growth and metastasis in mice by relieving p53-dependent repression of CDK2/Rb signaling and the Snail-driven EMT

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Chinese Journal of Natural Medicines 2024年第2期22卷 112-126页

作者： REN Boxue LI Yang DI Lei CHENG Ranran LIU Lijuan LI Hongmei LI Yi TANG Zhangrui YAN Yongming LU Tao FU Rong CHENG Yongxian WU Zhaoqiu State Key Laboratory of Natural Medicines Department of PharmacologySchool of PharmacyChina Pharmaceutical UniversityNanjing 211198China institute for Inheritance-Based Innovation of Chinese Medicine School of Pharmaceutical SciencesShenzhen University Health Science CenterShenzhen 518060China

The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in *** study introduced LZ22,a novel compound that selectively inhibits the growth,migration,and metastasis of tumor cells expressing wild-type p53,demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant ***22’s mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 *** interaction disrupted the MDM2-p53 binding,consequently stabilizing p53 by shielding it from proteasomal ***22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling ***,LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT,effectively reducing tumor cell migration and distal ***,LZ22 administration in tumor-bearing mice did not manifest notable side *** findings position LZ22 as a structurally unique reactivator of p53,offering therapeutic promise for the management of human cancers with wild-type TP53.

关键词： LZ22 Wild-type p53 p53 Reactivator Snail-driven EMT Tumor growth and metastasis

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Deep Guided Attention Network for Joint Denoising and Demosaicing in Real Image

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Chinese Journal of Electronics 2024年第1期33卷 303-312页

作者： Tao ZHANG Ying FU Jun ZHANG School of Computer science and Technology Beijing Institute of Technology Advanced Reasearch institute of Multidisciplinary science Beijing Institute of Technology

Denoising(DN) and demosaicing(DM) are the first crucial stages in the image signal processing pipeline. Recently, researches pay more attention to solve DN and DM in a joint manner, which is an extremely undetermined inverse problem. Existing deep learning methods learn the desired prior on synthetic dataset, which limits the generalization of learned network to the real world data. Moreover, existing methods mainly focus on the raw data property of high green information sampling rate for DM, but occasionally exploit the high intensity and signalto-noise(SNR) of green channel. In this work, a deep guided attention network(DGAN) is presented for real image joint DN and DM(JDD), which considers both high SNR and high sampling rate of green information for DN and DM, respectively. To ease the training and fully exploit the data property of green channel, we first train DN and DM sub-networks sequentially and then learn them jointly, which can alleviate the error accumulation. Besides, in order to support the real image JDD, we collect paired raw clean RGB and noisy mosaic images to conduct a realistic dataset. The experimental results on real JDD dataset show the presented approach performs better than the state-of-the-art methods, in terms of both quantitative metrics and qualitative visualization.

关键词： Training Visualization Inverse problems Green products Noise reduction Pipelines Signal processing

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Design and optimization of a greener sinomenine hydrochloride preparation process considering variations among different batches of the medicinal herb

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Chinese Journal of Chemical Engineering 2024年第7期71卷 77-90页

作者： Dandan Ren Jiale Xie Tianle Chen Haibin Qu Xingchu Gong pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China National Key Laboratory of Chinese Medicine Modernization Zhejiang UniversityHangzhou 310058China Jinhua institute of Zhejiang University Jinhua 321016China

The current methods used to industrially produce sinomenine hydrochloride involve several issues,including high solvent toxicity,long process flow,and low atomic utilization efficiency,and the greenness scores of the processes are below 65 *** solve these problems,a new process using anisole as the extractant was *** exhibits high selectivity for sinomenine and can be connected to the subsequent water-washing *** alkalization of the medicinal material,heating extraction,water washing,and acidification crystallization were carried *** process was modeled and *** design space was *** recommended operating ranges for the critical process parameters were 3.0–4.0 h for alkalization time,60.0–80.0℃ for extraction temperature,2.0–3.0(volume ratio)for washing solution amount,and 2.0–2.4 mol·L^(-1) for hydrochloric acid *** new process shows good robustness because different batches of medicinal materials did not greatly impact crystal purity or sinomenine transfer *** sinomenine transfer rate was about 20%higher than that of industrial *** greenness score increased to 90 points since the novel process proposed in this research solves the problems of long process flow,high solvent toxicity,and poor atomic economy,better aligning with the concept of green chemistry.

关键词： Sinomenine hydrochloride Process optimization Anisole

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Immunomodulatory potential of exopolysaccharides from Lactiplantibacillus plantarum YY-112

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Food science and Human Wellness 2024年

作者： Mengfan Luo Wanyi Zhou Wenyang Tao Jianrong Xing Jingrui Li Yuxing Guo Ying Yang institute of Food science Zhejiang Academy of Agricultural sciences School of Food science and pharmaceutical Engineering Nanjing Normal University

In vitro simulated colonic fermentation studies have shown the prebiotic potential of exopolysaccharides from Lactiplantibacillus plantarum YY-112 (YEPS). Its immunomodulatory effects and related mechanisms were systematically investigated in this study. We observed that YEPS intervene in immune responses and improve intestinal microbial structure in normal mice， including significantly increasing the relative abundance of Enterorhabdus and norank＿f＿＿norank＿o＿＿Clostridia UCG-014 as well as decreasing that of unclassified＿c＿＿Bacilli (P < 0.05). In the immunocompromised mouse model， YEPS decreased IL-6 levels (P < 0.05) and protected the spleen by regulating lymphocyte levels. YEPS preserved the intestinal barrier by improving Mucin 2， Zonula occludens protein 1， and Occludin expression. Moreover， YEPS significantly reduced the relative abundance of Bacillus， unclassified＿c＿＿Bacilli， Lachnoclostridium， Eubacterium＿xylanophilum＿group， and Desulfovibrio (P < 0.05)， potentially enhancing mice immunity by improving the intestinal microbiota associated with immune function. In conclusion， YEPS can be used as a natural functional extract with prebiotic effects that may improve host immunity. This provided the basis for the application of YEPS as a novel potential food additive.

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Caffeic acid 3,4-dihydroxyphenethyl ester prevents colorectal cancer through inhibition of multiple cancer-promoting signal pathways in 1,2-Dimethylhydrazine/dextran sodium sulphate mouse model

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Journal of Traditional Chinese Medicine 2024年第1期44卷 70-77页

作者： JIN Tao ZHOU Qian SHEN Jichen ZHANG Zhizhong LIAN Xiaoyuan College of pharmaceutical sciences Zhejiang UniversityHangzhou 310058China pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Ocean College Zhoushan Campus of Zhejiang UniversityZhoushan 316021China

OBJECTIVE:To elucidate the potential feature and mechanism of the caffeic acid 3,4-dihydroxyphenethyl ester(CADPE)molecule,which can prevent colorectal cancer(CRC)in the 1,2-Dimethylhydrazine(DMH)/dextran sodium sulphate(DSS)-induced mouse ***:institute of cancer research(ICR)male mice were injected with 20 mg/kg DMH for a *** that,2%DSS was administered in the drinking water for another 7 *** CADPE treatment was given to the DMH/DSS induced male mice at three different periods until their *** examination was used for observing the CRC development at colonic ***(IHC),blood cells smearing and crypt damage scoring methods were used for investigating the anti-inflammation feature of CADPE related to *** reversing targets searching method was applied with artificial intelligence(AI),computeraided drug designing(CADD)and Ingenuity Pathway Analysis(IPA)techniques for predicting the potential targets and mechanism of CADPE highly related to ***:The data indicated that CADPE inhibited CRC tumor development in the colitis-associated DMH/DSS induced mouse model after giving the early *** also impeded the acute inflammation by decreasing the infiltration of neutrophils significantly during the initial stage of CRC ***,our data showed that CADPE prevented CRC by blocking active sites of three pivotal protein targets including epidermal growth factor receptor(EGFR),extracellular signal-regulated kinase(ERK)and mammalian target of rapamycin(m TOR)in two major cancer development ***:CADPE effectively prevented CRC at early stage of tumor germination in the DMH/DSS mouse model highly likely due to its anti-acute inflammation characteristic and the ability of blocking EGFR,ERK and m TOR activities in two highly related CRC developing pathways.

关键词： caffeic acids colorectal neoplasms inflammation chemoprevention Sarcandra glabra

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