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Anti-cancer effect of ethylacetate fraction from Orostachys japonicus on HT-29 human colon cancer cells by induction of apoptosis through caspase-dependent signaling pathway

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Asian Pacific Journal of Tropical Medicine 2018年第5期11卷 330-335页

作者： Deok-Seon Ryu Hyun-Ji Lee Ji-Hye Kwon Dong-Seok Lee department of Biomedical Laboratory Science Soonchunhyang University department of smart foods and drugs Graduate School of Inje University

Objective: To investigate the anti-colon cancer effects of ethylacetate fraction from Orostachys japonicus(0. japonicus) on HT-29 cancer cells. Methods: The viability of HT-29 cells was assayed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium(MTS) method. Apoptosis induction and cell cycle inhibition were confirmed by fluorescein isothiocyanate and propidium iodide staining using flow *** changes in the nucleus were observed, using a fluorescence microscope with4',6-diamidino-2-phenylindole(DAPI) nuclear staining. The expression levels of the upstream and downstream proteins involved in the anti-cancer mechanism were confirmed by Western blotting. Results: After treating HT-29 cells with different concentrations of ethylacetate fraction from O. japonicus, the viability of cells decreased in a concentration-dependent manner,while apoptosis induction and apoptotic body formation increased. Cell cycle analysis showed that the arrest occurred at the sub-G_1 and S phase. Among the upstream and downstream proteins involved in anti-cancer activity, the level of B cell lymphoma-2 decreased, and the bcl-2-associated x protein increased. The level of pro-caspase-3, pro-caspase-8, and pro-caspase-9 decreased, while the level of cleaved-caspase-3, cleaved-caspase-8, and cleaved-caspase-9 increased. Moreover, the phosphorylation, that is, activation of extracellular signal regulated kinase 1/2, Jun-N-terminal kinase, and p38 increased. Conclusions: Combining the above results, it is thought that the survival of HT-29 cells is suppressed by ethylacetate fraction from0. japonicus through mitochondrial regulation-induced caspase cascade activation, induction of apoptosis and cell cycle arrest.

关键词： Orostachys japonicus HT-29 human colon cancer cells Anti-cancer activity Apoptosis Caspase cascade

Thrombolytic activity of cheonggukjang kinase in recovery from brain damage in a rat cerebral embolic stroke model

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Neural Regeneration Research 2010年第24期5卷 1875-1882页

作者： Angella M Anthony Jalin Chae Kwan Lee Chae Yeon Lee A Reum Kang Chung Mu Park Jae Ho Cha Jeong Hwan Kim Soo Woong Lee Young Sun Song Jong Tae Lee Sung Goo Kang School of Biological Sciences First Research GroupInje University Institute of Environmental and Occupational Medicine & department of Occupational and Environmental Medicine Pusan Paik HospitalInje University department of smart foods & drugs Inje University department of Microbiology Pusan National University Division of Applied Life Science Gyeongsang National University Advanced Research Center for Multiple Myeloma Department of MicrobiologyBio-Marker Research Center for Personalized TherapyCollege of MedicineInje University

Cheonggukjang is a soybean paste made by fermenting whole cooked soybeans with Bacillus subtilis. Cheonggukjang contains a fibrinolytic enzyme that could provide clinical applications for removing blood clots. In the present study, the term ＂cheonggukjang kinase＂（CGK） was used to refer to this fibrinolytic enzyme. The thrombolytic effects of CGK were analyzed in a rat model of cerebral embolic stroke produced by middle cerebral artery occlusion （MCAO）. Results from fibrin and platelet-rich clot lysis assays demonstrated that thrombolytic activity was greatest in CGKs, which were cultured for 40 hours. In addition, T50, the time needed to decompose 50% of the clot, did not change with plasminogen treatment, indicating that CGK was not a plasminogen activator, but was rather presumed to act as a plasmin-like protein. An intravenous infusion of CGK （1 U plasmin-like activity/100 μg CGK/kg） at 1 hour after MCAO resulted in removal of clots in a rat model of cerebral embolic stroke. CGK-treated groups exhibited a significant dose-dependent reduction in infarct volume. CGK treatment also improved functional recovery, as assessed by neurological deficit scores. Decreased infarct volume and improved functional recovery following CGK treatment was greater compared with recombinant tissue plasminogen activator （10 mg/kg）. These results suggested that CGK effectively reduced infarct volume and improved functional recovery following ischemic brain injury. CGK exhibits a number of potential clinical applications ir the treatment of cerebral embolic stroke.

关键词： brain damage cheonggukjang kinase fibrin clot lysis assay middle cerebral artery occlusion platelet rich clot lysis assay thrombolytic activity

Melatonin combined with exercise cannot alleviate cerebral injury in a rat model of focal cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2012年第13期7卷 993-999页

作者： Seunghoon Lee Jinhee Shin Minkyung Lee Yunkyung Hong Sang-Kil Lee Youngjeon Lee Tserentogtokh Lkhagvasuren Dong-Wook Kim Young-Ae Yang Kyu-Tae Chang Yonggeun Hong department of Rehabilitation Science in Interdisciplinary Ph.D.Program Inje UniversityGimhae 621-749Republic of Korea Cardiovascular & Metabolic Disease Center College of Biomedical Science & EngineeringGimhae 621-749Republic of Korea department of smart foods & drugs School of Food & Life SciencesInje UniversityGimhae 621-749Republic of Korea department of Pharmaceutical Engineering College of EngineeringInje UniversityGimhae 621-749Republic of Korea National Primate Research Center Korea Research Institute of BiotechnologyOchang 363-883Republic of Korea

Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also alleviate ischemic brain damage. In this study, adult rats were subjected to right middle cerebral artery occlusion after receiving 10 mg/kg melatonin or vehicle subcutaneously twice daily for 14 days. Forced exercise using an animal treadmill was performed at 20 m/min for 30 minutes per day for 6 days prior to middle cerebral artery occlusion. After middle cerebral artery occlusion, each rat received melatonin combined with exercise, melatonin or exercise alone equally for 7 days until sacrifice. Interestingly, rats receiving melatonin combined with exercise exhibited more severe neurological deficits than those receiving melatonin or exercise alone. Hypoxia-inducible factor la mRNA in the brain tissue was upregulated in rats receiving melatonin combined with exercise. Similarly, microtubule associated protein-2 mRNA expression was significantly upregulated in rats receiving melatonin alone. Chondroitin sulfate proteoglycan 4 （NG2） mRNA expression was significantly decreased in rats receiving melatonin combined with exercise as well as in rats receiving exercise alone. Furthermore, neural cell loss in the primary motor cortex was significantly reduced in rats receiving melatonin or exercise alone, but the change was not observed in rats receiving melatonin combined with exercise. These findings suggest that excessive intervention with melatonin, exercise or their combination may lead to negative effects on ischemia/reperfusion-induced brain damage.

关键词： wfocal cerebral ischemiaJreperfusion melatonin exercise neurological function brain tissue loss microtubule associated protein-2 chondroitin sulfate proteoglycan 4 NG2 hypoxia-inducible factor1 alpha neural regeneration

Research advancements in nanoparticles and cell-based drug delivery systems for the targeted killing of cancer cells

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Oncology Research 2025年第1期33卷 27-44页

作者： MERYEM A.ABDESSALEM SIRIN A.ADHAM department of Biology College of ScienceSultan Qaboos UniversityMuscat123Oman

Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized *** smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal *** nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs *** these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle ***-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer *** review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer *** covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer *** detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.

关键词： Drug delivery Cancer Nanoparticles Liposomes Micelles Combination therapies Targeted therapy Precision medicine Tumor microenvironment(TME)

In vivo retention of poloxamer-based in situhydrogels for vaginal application in mouse and rat models

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Acta Pharmaceutica Sinica B 2017年第4期7卷 502-509页

作者： Yu Liu Fujin Yang Linglin Feng Long Yang Lingyun Chen Gang Wei Weiyue Lu Key Laboratory of smart Drug Delivery Ministry of EducationFudan UniversityShanghai 201203China department of Pharmaceutics School of PharmacyFudan UniversityShanghai 201203China Yunnan University of Traditional Chinese Medicine Kunming 650500China Shanghai Institute of Planned Parenthood Research National Population and Family Planning Key Laboratory of Contraceptives Drugs and DevicesShanghai 200032China

The purpose of this study is to evaluate the in vivo retention capabilities of poloxamer-based in situ hydrogels for vaginal application with nonoxinol-9 as the model drug. Two in situ hydrogel formulations, which contained 18% poloxamer 407 plus 1% poloxamer 188 (GEL1, relative hydrophobic) or 6% poloxamer 188 (GEL2, relative hydrophilic), were compared with respect to the rheological properties, in vitro hydrogel erosion and drug release. The vaginal retention capabilities of these hydrogel formulations were further determined in two small animal models, including drug quantitation of vaginal rinsing fluid in mice and isotope tracing with 99mTc in rats. The two formulations exhibited similar phase transition temperatures ranging from 27 to 32 °C. Increasing the content of poloxamer 188 resulted in higher rheological moduli under body temperature, but slightly accelerated hydrogel erosion and drug release. When compared in vivo, GEL1 was eliminated significantly slower in rat vagina than GEL2, while the vaginal retention of these two hydrogel formulations behaved similarly in mice. In conclusion, increases in the hydrophilic content of formulations led to faster hydrogel erosion, drug release and intravaginal elimination. Rats appear to be a better animal model than mice to evaluate the in situ hydrogel for vaginal application.

关键词： Vaginal administration Poloxamer Thermosensitive hydrogel Retention Nonoxinol-9

Substance P-modified human serum albumin nanoparticles loaded with paclitaxel for targeted therapy of glioma

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Acta Pharmaceutica Sinica B 2018年第1期8卷 85-96页

作者： Chunhui Ruan Lisha Liu Yifei Lu Yu Zhang Xi He Xinli Chen Yujie Zhang Qinjun Chen Qin Guo Tao Sun Chen Jiang Key Laboratory of smart Drug Delivery Ministry of Education State Key Laboratory of Medical NeurobiologyDepartment of Pharmaceutics School of Pharmacy Fudan University

The blood–brain barrier(BBB) and the poor ability of many drugs to cross that barrier greatly limits the efficacy of chemotherapies for glioblastoma multiforme(GBM). The present study exploits albumin as drug delivery vehicle to promote the chemotherapeutic efficacy of paclitaxel(PTX) by improving the stability and targeting efficiency of PTX/albumin nanoparticles(NPs). Here we characterize PTX-loaded human serum albumin(HSA) NPs stabilized with intramolecular disulfide bonds and modified with substance P(SP) peptide as the targeting ligand. The fabricated SP-HSA-PTX NPs exhibited satisfactory drug-loading content(7.89%) and entrapment efficiency(85.7%) with a spherical structure(about 150 nm) and zeta potential of -12.0 mV. The in vitro drug release from SP-HSA-PTX NPs occurred in a redox-responsive manner. Due to the targeting effect of the SP peptide, cellular uptake of SP-HSA-PTX NPs into brain capillary endothelial cells(BCECs) and U87 cells was greatly *** low IC_(50), prolonged survival period and the obvious pro-apoptotic effect shown by TUNEL analysis all demonstrated that the fabricated SP-HSA-PTX NPs showed a satisfactory anti-tumor effect and could serve as a novel strategy for GBM treatment.

关键词： Human serum albumin Paclitaxel Drug delivery Substance P Blood–brain barrier Glioma

Silybin and the liver: From basic research to clinical practice

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World Journal of Gastroenterology 2011年第18期17卷 2288-2301页

作者： Carmela Loguercio Davide Festi Gastroenterology School-Interuniversity Research Centre on foods Nutrition and Gastrointestinal Tract (CIRANAD) 2nd University of Naples department of Clinical Medicine University of Bologna

Herbal products are increasingly used, mainly in chronic liver disease. Extracts of milk thistle, Silymarin and silybin, are the most prescribed natural compounds, with different indications, but with no definitive results in terms of clinical efficacy. This review analyzes the available studies on the effects of the purified product silybin, both as a free and a conjugated molecule, on liver cells or on experimentally induced liver damage, and in patients with liver disease. We searched PUBMED for articles pertaining to the in vitro and in vivo effects of silybin, its antifibrotic, anti-inflammatory, and antioxidant properties, as well as its metabolic effects, combined with the authors’ own knowledge of the literature. Results indicate that the bioavailability of silybin phytosome is higher than that of silymarin and is less influenced by liver damage; silybin does not show significant interactions with other drugs and at doses < 10 g/d has no significant side effects. Experimental studies have clearly demonstrated the antifibrotic, antioxidant and metabolic effects of silybin; previous human studies were insufficient for confirming the clinical efficacy in chronic liver disease, while ongoing clinical trials are promising. On the basis of literature data, silybin seems a promising drug for chronic liver disease.

关键词： Milk thistle Silymarin Liver disease Hepatic fibrosis Hepatic inflammation Radical species

Delivery strategies for macromolecular drugs in cancer therapy

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Acta Pharmaceutica Sinica B 2020年第6期10卷 979-986页

作者： Qin Guo Chen Jiang Key Laboratory of smart Drug Delivery Ministry of EducationState Key Laboratory of Medical NeurobiologyDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 201203China

With the development of biotherapy,biomacromolecular drugs have gained tremendous attention recently,especially in drug development field due to the sophisticated functions in *** the past few years,a motley variety of drug delivery strategies have been developed for biomacromolecular drugs to overcome the difficulties in the druggability,e.g.,the instability and easily restricted by physiologic *** application of novel delivery systems to deliver biomacromolecular drugs can usually prolong the half-life,increase the bioavailability,or improve patient compliance,which greatly improves the efficacy and potentiality for clinical use of biomacromolecular *** this review,recent studies regarding the drug delivery strategies for macromolecular drugs in cancer therapy are summarized,mainly drawing on the development over the last five years.

关键词： Macromolecular drugs Delivery strategies Cancer therapy Membrane-camouflage systems Exosomes

The association between the metabolites of intestinal flora and diabetes mellitus

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新疆医科大学学报 2010年第9期33卷 1063-1066页

作者： WANG Ye WANG Chang-hui YU Xin-lan LI Ge LIU Jing-bao GAO Bing MAO Xin-min LI Lin-lin department of Pharmacology Xinjiang Medical University Urumqi 830011 China Lanzhou General Military District Hospital Urumqi 830011 China） Xinjiang Laboratory for the Control of foods and drugs Urumqi 830011 China）

Objective To contrast and analyze the difference of metabolites of intestinal flora between patients with type 2diabetes and normal blood glucose human in Xinjiang Uygur and *** Uygur fecal samples and Kazak fecal samples were collected,and short-chain fatty acids(SCFA)were extracted by water from feces,then the content of SCFA in fecal samples was analyzed by gas-chromatography mass-spectrometry(GC-MS).Results Both Uygurs and Kazaks,in their feces,the content of SCFA in the feces showed significantly decreased in patients with type 2diabetes,and a significant negative linear correlation was shown between the fasting plasma glucose and the concentration of SCFA in the fecal ***,there was no statistical differences between uygurs and kazaks,in not only normal blood glucose group,but also type 2 diabetes *** The feces of patients with type 2diabetes has an decreased concentration of *** Uygurs and Kazaks,the metabolic changes of intestinal flora was similar in patients with type 2diabetes.

关键词： type 2diabetes intestinal flora SCFA GC-MS