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New era of electrochemotherapy in treatment of liver tumors in conjunction with immunotherapies

World Journal of Gastroenterology 2021年第48期27卷 8216-8226页

作者： BlažTrotovšek Mihajlo Djokić MajaČemažar Gregor Serša Department of Abdominal Surgery University Medical Centre LjubljanaLjubljana 1000Slovenia Medical Faculty Ljubljana University of LjubljanaLjubljana 1000Slovenia Department of experimental oncology Institute of OncologyLjubljana 1000Slovenia Faculty of Health Sciences University of PrimorskaIzola 6310Slovenia Faculty of Health Sciences University of LjubljanaLjubljana 1000Slovenia

Electrochemotherapy is a local ablative therapy that increases the cytotoxicity of either bleomycin or cisplatin by applying electric pulses(electroporation)to *** has already been widely used throughout Europe for the treatment of various types of human and veterinary cutaneous tumors,with an objective response rate ranging from 70%-90%,depending on the tumor ***,electrochemotherapy was introduced for the treatment of primary liver tumors,such as hepatocellular carcinoma(HCC).The complete response rate was 85%per treated lesion,with a durable ***,electrochemotherapy could become a treatment of choice for HCC,especially after achieving a transition from an open surgery approach to a percutaneous approach that uses dedicated *** elicits a local immune response and can be considered an in situ ***,among others,is a potentially immunogenic tumor;thus,electrochemotherapy could boost adjuvant immunotherapy to achieve a better and longer-lasting antitumor ***,therapeutic strategies that combine electrochemotherapy with immune checkpoint inhibitors or adjuvant treatment with cytokines are indicated for *** therapy using electroporation as a delivery system for plasmid DNA coding for interleukin-12 is a highly promising *** electroporation approach has shown efficacy in preclinical settings and veterinary oncology and is awaiting translation for the treatment of liver tumors,i.e.,HCC.

关键词： Electroporation Electrochemotherapy Gene therapy Gene electrotransfer Interleukin-12 Immune checkpoint inhibitors Hepatocellular carcinoma

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Water Soluble Propolis and Royal Jelly Enhance the Antimicrobial Activity of Honeys and Promote the Growth of Human Macrophage Cell Line

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Journal of Agricultural Science and Technology(B) 2016年第1期6卷 35-47页

作者： Bratko Filipic Lidija Gradisnik Eva Ruzic-Sabljic Brabara Trtnik Adriana Pereyra Domen Jaklic Rok Kopinc Jana Potokar Almin Puzic Hrvoje Mazija institute for Microbiology and Immunology Medical Faculty Ljubljana University of Ljubljana Zalogka 4 Ljubljana 1105 Slovenia institute for Biomedical Sciences Medical Faculty Maribor University of Maribor Taborska 8 Maribor 2000 Slovenia Research and Control Department MEDEX d o.o. Linhartova 49a Ljubljana 1000 Slovenia Veterinary Stations of Mostar Bigke Polje 106 Mostar 88000 Bosnia and Herzegovina croatian institute for experimental and translation oncology Koledinedka 3 Zagreb 10040 Croatia

Due to the overuse and misuse of antibiotic, an increase in antibiotic resistance of pathogenic bacteria is evolving. Attention should be focused on natural alternatives to antibiotics, like propolis, royal jelly （R J） and honeys. They all have strong antibacterial properties due to the active substances they contain. This study investigated the effect of combination of water soluble propolis （WSP） Greitl20 or fresh royal jelly （F-RJ）（MiZigoj） and Forest honeys as antibacterial against Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Acinetobacter baumanii, Staphylococcus aureus, methicillin resistant Staphylococcus aureus （MRSA）, Streptococcus pyogenes, Streptococcus agalactiae and Candida albicans. These substances are also cell growth promoters for human macrophage （TLT） cell line. WSP Greitl20, F-RJ （M） and different Forest honeys were prepared in saline as 10% solutions. The antimicrobial activity was expressed as the minimal inhibitory concentration （MIC） in mg/mL. The growth promotion activity was measured at optical density （OD） 595 nm. The combination ofWSP Greitl20 with different Forest honeys is better than F-RJ （M） in same combination with different Forest honeys. The best antibacterial/antifungal activity was found with the combination of 10% WSP Greit 120 in the Forest honey （1：10） from Italy or Spain. When measuring the growth promoting activity of TLT cell line, the best activity was detected at the combination of 10% WSP Greitl20 in the Forest honey from Italy （GI3 = 0.796 ± 0.014 and GI5 = 1.133± 0.022）. Antimicrobial and growth promoting activities are correlated and WSP-dependent.

关键词： Propolis royal jelly Forest honey antimicrobial activity human macrophage cell line cell growth promoting activity.

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The Polyphenol Content and Antimicrobial Activity of Selected Propolis’ Extracts

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Journal of Agricultural Science and Technology(B) 2020年第6期10卷 350-364页

作者： Bratko Filipič Lidija Gradišnik Dunja Gregorič Adriana Pereyra Eva Ružić-Sabljić Hrvoje Mazija croatian institute for experimental and translation oncology(CIETO) Koledinečka 03Zagreb 10040Croatia institutes of Biomedical Sciences Medical Faculty of MariborTaborska 8Maribor 2000Slovenia Retired Glavarjeva 19Ljubljana 1000Slovenia Research and Developement Medex D.o.o.Linhartova 049aLjubljana 1000Slovenia institutes of Microbiology and Immunology Medical FacultyZaloška 4Ljubljana 1105Slovenia

Propolis is a resinous natural product,produced by bees(Apis mellifera),from vegetable parts and plant ***’samples A,B,C and D were extracted with phosphate buffer saline(PBS)or with 70%EtOH at pH values 8.0,7.2 and 6.4 followed by:(1)reverse-phase high-performance liquid chromatography(RP-HPLC)on Purospher®Star RP-18 column,the quantity of caffeic acid,chrysin,pinocembrin and galangin was determined;(2)determination of total flavonoids in both extracts;(3)antimicrobial tests of both extracts against(a)Gram-positive bacteria:methicillin-resistant Staphylococcus aureus(MRSA),***,Streptococcus pyogenes,***,(b)Gram-negative bacteria:Escherichia coli,Pseudomonas aeruginosa,Proteus mirabilis,Acinetobacter baumanii and(c)yeast:Candida *** antimicrobial activity of propolis’PBS extracts against Gram-positive bacteria shows the lowest minimal inhibitory concentration(MIC,mg/mL)at pH 8.0 in sample C,followed by A,B and *** sample C,MICs at pH 8.0 were 0.007(***),0.015(MRSA),0.015(***)and 0.007(***).The polyphenol content of sample C is:flavonoid content 5.47±0.62 mg/mL,caffeic acid 1.33±0.92 mg/mL,chrysin 41.02±4.22μg/mL,pinocembrin 2.93±0.33 mg/mL and galangin 41.87±4.23 mg/*** extracts against Gram-negative bacteria show the lowest MIC(mg/mL)at pH 8.0 in sample D,followed by B,C and *** sample D,MICs at pH 8.0 were 0.003(***,***,***)and 0.007(***).Polyphenol content of sample D is:flavonoids 8.28±0.92 mg/mL,caffeic acid 3.56±0.32 mg/mL,chrysin 677.42±68.42μg/mL,pinocembrin 146.49±13.89 mg/mL and galangin 59.81±5.86 mg/*** strongest anti *** activity,with the lowest MIC(mg/mL),at pH 8.0 was in the sample C,followed by samples D,A and *** sample C,the MIC at pH 8.0 is 0.001(PBS extract).The antimicrobial activities of selected propolis samples correlate with their polyphenol content,more precisely,flavonoid,caffeic acid,chrysin,pinocembrin and galangin content.

关键词： Propolis pH phosphate buffer saline extract 70%EtOH extract antimicrobial activity

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Transplantation of stem cell-derived astrocytes for the treatment of amyotrophic lateral sclerosis and spinal cord injury

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World Journal of Stem Cells 2015年第2期7卷 380-398页

作者： Charles Nicaise Dinko Mitrecic Aditi Falnikar Angelo C Lepore Laboratory Neurodegeneration and Regeneration URPhy M-NARILISFaculty of MedicineUniversity of Namur Laboratory for Stem Cells Croatian Institute for Brain ResearchUniversity of Zagreb Department of Neuroscience Farber Institute for NeurosciencesSidney Kimmel Medical College at Thomas Jefferson University Medical College

Neglected for years, astrocytes are now recognized to fulfill and support many, if not all, homeostatic functionsof the healthy central nervous system(CNS). During neurodegenerative diseases such as amyotrophic lateral sclerosis(ALS) and spinal cord injury(SCI), astrocytes in the vicinity of degenerating areas undergo both morphological and functional changes that might compromise their intrinsic properties. Evidence from human and animal studies show that deficient astrocyte functions or loss-of-astrocytes largely contribute to increased susceptibility to cell death for neurons, oligodendrocytes and axons during ALS and SCI disease progression. Despite exciting advances in experimental CNS repair, most of current approaches that are translated into clinical trials focus on the replacement or support of spinal neurons through stem cell transplantation, while none focus on the specific replacement of astroglial populations. Knowing the important functions carried out by astrocytes in the CNS, astrocyte replacement-based therapies might be a promising approach to alleviate overall astrocyte dysfunction, deliver neurotrophic support to degenerating spinal tissue and stimulate endogenous CNS repair abilities. Enclosed in this review, we gathered experimental evidence that argue in favor of astrocyte transplantation during ALS and SCI. Based on their intrinsic properties and according to the cell type transplanted, astrocyte precursors or stem cell-derived astrocytes promote axonal growth, support mechanisms and cells involved in myelination, are able to modulate the host immune response, deliver neurotrophic factors and provide protective molecules against oxidative or excitotoxic insults, amongst many possible benefits. Embryonic or adult stem cells can even be genetically engineered in order to deliver missing gene products and therefore maximize the chance of neuroprotection and functional recovery. However, before broad clinical translation, further preclinical data

关键词： Neuroprotection Stem cell Cell therapy Astrocyte Transplantation Amyotrophic lateral sclerosis Spinal cord injury

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Additive Effects of Water-Soluble Propolis(Greit 120)and Human Interferon Alfa(HuIFN-αN3)against Influenza Viruses in Vitro

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Journal of Agricultural Science and Technology(A) 2018年第1期8卷 36-47页

作者： Bratko Filipic Lidija Gradisnik Adriana Pereyra Rok Kopino Klemen Rihar Eva Ruzic-Sabljic Snezana Kramar Damir Dermie Eugen Soos Nicola Volpi Alfredo Fachini and Hrvoje Mazija croatian institute of experimental and translation oncology Koledinecka 3Zagreb 10040Croatia institute of Biomedical Sciences Medical Faculty of MariborTaborska 8Maribor 2000Slovenia Medex D.o.o. Linhartova 49bLjubljana 1000Slovenia Chengdujska 4 Ljubljana 1000Slovenia institute of Microbiology and Immunology Medical FacultyZaloska 4Ljubljana 1105Slovenia Division of Molecular Biology Ruaer Boskovic InstituteBijenicka 54Zagreb 10000Croatia Trg Sv.Ivana 5 Klostar Ivanic 10312Croatia Department of Life Sciences University of Modena&Reggio EmiliaModena 41125Italy BNatural Via Gran Sasso 33Corbetta-MI 20011Italy

Influenza virus affects the respiratory tract in humans causing a range of distinct manifestations including fever, nasal secretions, cough, headaches, muscle pain and pneumonia, which could become violent and severe. It was found that influenza A viruses remain resistant to amantadine and rimantadin with high level of oseltamvir resistance. Therefore, there is a need for constant improvement of drugs active against resistant influenza viruses. Propolis has anti-influenza activity both in vitro and in vivo. Human leukocyte interferon （HuIFN-αN3） is a multi-subtype protein that displays an antiviral activity against influenza virus. In this study we elucidated the anti-influenza activity of the mixes of water-soluble propolis （WSP）（Greit 120） and HuIFN-αN3 at different ratios. Greit 120 polyphenols, total phenol acids and bioflavonoid were characterized by HPLC-UV-ESI-MS504971 and HuIFN-αN3 by reverse-phase high-performance liquid chromatography （RP-HPLC）. Influenza A and B viruses were separately added to the LLC-MK2 cells treated with WSP （Greit 120） and HuIFN-αN3 alone or in proportions 1：1, 1：2 and 2：1. Plates were incubated and cytopathic effect was determined. The best results （ID50） were obtained with the mix of 10% WSP and HuIFN-αN3 in proportion 1：2, showing ID50 at 12 ± 0.2 μg/mL and 19 ± 0.6 μg/mL for influenza A and B viruses, respectively. When comparing anti-influenza activity of WSP （Greit 120）/HuIFN-αN3 with that of ribavirin, it was found that 1：2 was the optimal ratio for WSP （Greit 120）/HuIFN-αN3 （0.5 and 0.6 for influenza A and B, respectively）. This new formulation of WSP （Greit 120） and HuIFN-αN3, showing better anti-Influenza activity, will definitely improve its application in flu infections.

关键词： Water-soluble propolis Greit 120 HuIFN-αN3 anti-influenza activity ribavirin ID_(50)

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Propolis Extracts Enhance the Antimicrobial Activity of Slovenian:Chestnut,Forest and Flower Honeys

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Journal of Agricultural Science and Technology(B) 2019年第3期9卷 203-219页

作者： Bratko Filipic Klemen Rihar Dunja Exel Gregoric Lidija Gradisnik Adriana Pereyra Eva Ruzic-Sabljic Fabio Galeotti Alfredo Fachini Hrvoje Mazija croatian institute for experimental and translational oncology(CIETO) Koledinecka 03Zagreb 10040Croatia Retired Chengdujska 4Ljubljana 1000Slovenia Retired Glavarjeva 19Ljubljana 1000Slovenia institute of Biomedical Sciences Medical Faculty of MariborTaborska 8Maribor 2000Slovenia Medex D.o.o. Linhartova 49aLjubljana 1000Slovenia institute for Microbiology and Immunology Medical Faculty of LjubljanaZloska 04Ljubljana 1105Slovenia Department of Life Sciences University of Modena&Regio EmiliaModena 41125Italy BNatural Via Gran SassoCorbettaMI 20011Italy

Because of the overuse and misuse of antibiotic, an increase in antibiotic resistance of pathogenic bacteria is evolving. Attention should be focused on natural alternatives to antibiotics, like propolis and honey. They all have strong antibacterial properties because of the active substances they contain. In the present study, the influence of P1 (water-soluble propolis (WSP) Greit 120) or P2 (phosphate buffer saline (PBS) propolis extract Lj. Center pH = 8.0) on antimicrobial activity of different Slovenian: chestnut honey (CH), forest honeys (FoH), and flower honey (FlH) against various Gram-positive or Gram-negative bacteria and yeast Candida albicans are shown. Gram-positive bacteria used in the experiments were: methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutans. The yeast was Candia albicans. Gram-negative bacteria used were: Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumanii. P1, P2, FoH, CH, FlH and their combinations were prepared in saline as 10% solutions. The composition of both propolis extracts and the three kinds of honey was determined by reverse-phase high-performance liquid chromatography (RP-HPLC). It expressed the antimicrobial activity as a minimal inhibitory concentration (MIC) in mg/mL. Each of the two propolis extracts showed antimicrobial activity when applied alone. Also, the application of each of honey yielded an antimicrobial activity in decreasing order: CH, FoH and FlH honey. The combination of any of the propolis extract with any of the honey showed the additive antimicrobial effect on either Gram-positive or Gram-negative bacteria and on yeast Candida albicans. The effectiveness of P1 or P2 depends on their nature and from the sort of honey and is the highest in the case of CH followed by FoH and FlH.

关键词： Honey propolis flavonoids antimicrobial activity enhancement

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抗SARS-CoV-2变异株的广谱mRNA疫苗RQ3013的临床前研究

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Science Bulletin 2023年第24期68卷 3192-3206,M0006页

作者：谭舒丹赵京华胡雪李玉凤武子涵逯国亮于朝丽杜彬荷刘燕李丽陈煜琛李晔姚艳丰张小宇饶具红高歌彭云刘航袁志明刘佳王倩然胡恒睿高小博周辉俞航徐颖洁余巍冯琳王曼丽单超卢静林金钟 State Key Laboratory of Genetic Engineering School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200438China Shanghai institute of Infectious Disease and Biosecurity Fudan UniversityShanghai 200438China Zhangjiang mRNA Innovation and translation Center Fudan UniversityShanghai 200438China State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Center for Biosafety Mega-Science Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Shanghai RNACure Biopharma Co. Ltd.Shanghai 200438China Shanghai Key Laboratory for Tumor Microenvironment and Inflammation Department of Biochemistry and Molecular Cell BiologyShanghai Jiao Tong University School of MedicineShanghai 200025China Department of experimental Research Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangzhou 510060China

全球SARS-CoV-2病毒的不同变异株导致已接种疫苗的人群中突破性感染的比例上升,迫切需要研发更为有效和广谱的COVID-19疫苗.本研究报告了一项mRNA疫苗RQ3013的临床前研究结果,旨在提供对SARS-CoV-2各种变异株(VOCs)的广谱保护.RQ3013疫... 详细信息

全球SARS-CoV-2病毒的不同变异株导致已接种疫苗的人群中突破性感染的比例上升,迫切需要研发更为有效和广谱的COVID-19疫苗.本研究报告了一项mRNA疫苗RQ3013的临床前研究结果,旨在提供对SARS-CoV-2各种变异株(VOCs)的广谱保护.RQ3013疫苗包含经过假尿苷修饰的mRNA,制备成脂质纳米颗粒的形式.该mRNA编码了SARS-CoV-2的刺突(S)蛋白嵌合体,包含与免疫逃逸有关的重要突变位点.我们在多种动物模型中对RQ3013的免疫原性、保护效果和安全性进行了评估.RQ3013在小鼠、仓鼠和非人灵长类动物(NHP)中引发了显著的免疫反应.它能够诱导高滴度的抗体产生,具备对野生型、B.1.1.7、B.1.351、B.1.617.2和奥密克戎系列变异株的广泛中和能力.在小鼠和NHP中,两剂RQ3013疫苗能够有效保护上呼吸道和下呼吸道免受SARS-CoV-2及其变异株的感染.此外,在NHP中对RQ3013的安全性进行了评估,未观察到不良反应.这些结果为在临床试验中评估RQ3013提供了有力的支持,表明它可能成为对抗COVID-19及其变种的广泛保护的有希望的候选疫苗.

关键词： RQ3013 COVID-19 mRNA vaccine SARS-CoV-2 Chimeric spike

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Gemcitabine pharmacogenomics:translation of the information from cell-based GWAS into clinical replication

Gemcitabine pharmacogenomics:translation of the information ...

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第八届中国肿瘤学术大会暨第十三届海峡两岸肿瘤学术会议

作者： Liang Li Brooke Fridley Gregory Jenkins Daniel Schaid Liewei Wang Department of oncology Institute of Medicinal Biotechnology Peking Union Medical College & Chinese Academy of Medical Science Departments of Molecular Pharmacology and experimental Therapeutics Mayo ClinicRochester MN 55905USA Departments of Health Sciences Research Mayo Clinic Rochester MN 55905USA

＜正＞Background Pancreatic cancer is a rapidly fatal disease with 5-year survival time less than 5%.Gemcitabine is still the first line therapy for patients with advanced pancreatic cancer till ***,response rate to g...

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