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ATP-binding cassette transporters in progression and clinical outcome of pancreatic cancer: what is the way forward?

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World Journal of Gastroenterology 2018年第29期24卷 3222-3238页

作者： Aleksandra Adamska Marco Falasca Metabolic signalling group School of Pharmacy and Biomedical Sciences Curtin Health Innovation Research Institute Curtin University

Pancreatic ductal adenocarcinoma(PDAC) is one of the most aggressive diseases and is characterized by high chemoresistance, leading to the lack of effective therapeutic approaches and grim prognosis. Despite increasing understanding of the mechanisms of chemoresistance in cancer and the role of ATPbinding cassette(ABC) transporters in this resistance, the therapeutic potential of their pharmacological inhibition has not been successfully exploited yet. In spite of the discovery of potent pharmacological modulators of ABC transporters, the results obtained in clinical trials have been so far disappointing, with high toxicity levels impairing their successful administration to the patients. Critically, although ABC transporters have been mostly studied for their involvement in development of multidrug resistance(MDR), in recent years the contribution of ABC transporters to cancer initiation and progression has emerged as an important area of research, the understanding of which could significantly influence the development of more specific and efficient therapies. In this review, we explore the role of ABC transporters in the development and progression of malignancies, with focus on PDAC. Their established involvement in development of MDR will be also presented. Moreover, an emerging role for ABC transporters as prognostic tools for patients' survival will be discussed, demonstrating the therapeutic potential of ABC transporters in cancer therapy.

关键词： Pancreatic ductal adenocarcinoma Multidrug resistance ATP-binding cassette transporters Targeted therapies Pancreatic ductal adenocarcinoma prognosis Predictive markers

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Emerging role of the KRAS-PDK1 axis in pancreatic cancer

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World Journal of Gastroenterology 2014年第31期20卷 10752-10757页

作者： Riccardo Ferro Marco Falasca Queen Mary University of London Barts and The London School of Medicine and Dentistry Blizard Institute Inositide Signalling GroupUnited Kingdom

Pancreatic cancer is a highly aggressive tumour that is very resistant to treatments and it is rarely diagnosed early because of absence of specific symptoms. Therefore, the prognosis for this disease is very poor and it has the grim supremacy in terms of unfavourable survival rates. There have been great advances in survival rates for many types of cancers over the past few decades but hardly any change for pancreatic cancer. Mutations of the Ras oncogene are the most frequent oncogenic alterations in human cancers. The frequency of KRAS mutations in pancreatic cancer is around 90%. Given the well-established role of KRAS in cancer it is not surprising that it is one of the most attractive targets for cancer therapy. Nevertheless, during the last thirty years all attempts to target directly KRAS protein have failed. Therefore, it is crucial to identify downstream KRAS effectors in order to develop specific drugs able to counteract activation of this pathway. Among the different signalling pathways activated by oncogenic KRAS, the phosphoinositide 3-Kinase(PI3K) pathway is emerging as one of the most critical KRAS effector. In turn, PI3 K activates several parallel pathways making the identification of the precise effectors activated by KRAS/PI3 K more difficult. Recent data identify 3-phosphoinositide-dependent protein kinase 1 as a key tumour-initiating event downstream KRAS interaction with PI3 K in pancreatic cancer.

关键词： Pancreatic cancer Signal transduction KRAS Phosphoinositide 3-kinase 3-phosphoinositide-dependent protein kinase 1

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calcium Carbonate and Ettringite Induced Efflorescence in CAC-Anhydrite Binary Systems

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Journal of Wuhan University of Technology(Materials Science) 2024年第5期39卷 1129-1137页

作者： SUN Zixuan CHEN Yuting XU Linglin LIU Siyu YU Long PAN Feng WANG Chaoqiang WU Kai YANG Zhenghong Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education School of Materials Science and EngineeringTongji UniversityShanghai 201804China Shanghai Construction No.5(group)Co. Ltd.Shanghai 200063China School of Material Science and Engineering Chongqing Jiaotong UniversityChongqing 400074China

We focused on the efflorescence induced microstructural evolution of ettringite-rich systems prepared with calcium aluminate cement(CAC)and *** effects of anhydrite on the visible efflorescence,and the corresponding capillary absorption of CAC-anhydrite mortars were *** composition and microstructure of efflorescence-causing substances were investigated by optical microscope,in-situ Raman spectroscopy,scanning electron microscope,energy dispersive spectrometer,thermogravimetric analysis,and differential scanning calorimetry,at *** indicate that,besides the calcium carbonate,ettringite is another main component of efflorescence-causing *** with the neat CAC mortars,the addition of anhydrite has a significant effect on the degree of efflorescence by acting on the composition of hydration products and pore *** addition,methods are proposed for the prevention of efflorescence of CAC-anhydrite binary system.

关键词： calcium aluminate cement anhydrite efflorescence ettringite phase assemblage pore structure

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Advanced nanomedicines and immunotherapeutics to treat respiratory diseases especially COVID-19 induced thrombosis

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World Journal of Clinical Cases 2024年第16期12卷 2704-2712页

作者： Jie Wu Ying Zheng Li-Na Zhang Cai-Li Gu Wang-Li Chen Min-Qiang Chang Department of Respiratory and Oncology 72nd Group Army Hospital of PLAHuzhou 313000Zhejiang ProvinceChina Department of Otorhinolaryngology 72^(nd)Group Army Hospital of PLAHuzhou 313000Zhejiang ProvinceChina

Immunotherapy and associated immune regulation strategies gained huge attraction in order to be utilized for treatment and prevention of respiratory *** specifically nanomedicines can be used to regulate host immunity in lungs in the case of respiratory diseases including coronavirus disease 2019(COVID-19)***-19 causes pulmonary embolisms,thus new therapeutic options are required to target thrombosis,as conventional treatment options are either not effective due to the complexity of the immunethrombosis *** this review,we discuss regulation of immune response in respiratory diseases especially *** further discuss thrombosis and provide an overview of some antithrombotic nanoparticles,which can be used to develop nanomedicine against thrombo-inflammation induced by COVID-19 and other respiratory infectious *** also elaborate the importance of immunomodulatory nanomedicines that can block pro-inflammatory signalling pathways,and thus can be recommended to treat respiratory infectious diseases.

关键词： Nanomedicines Immunotherapeutics Respiratory diseases COVID-19 Thrombosis

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Targeting pancreatic ductal adenocarcinoma:New therapeutic options for the ongoing battle

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Hepatobiliary & Pancreatic Diseases International 2022年第1期21卷 4-6页

作者： Pratibha Malhotra Ranjith Palanisamy Marco Falasca Metabolic signalling group Curtin Medical SchoolCurtin Health Innovation Research InstituteCurtin UniversityPerthWA6102Australia

Pancreatic ductal adenocarcinoma(PDAC),the most commonly reported form of pancreatic cancer,is a lethal malignancy that con-tributes to the global cancer burden with high morbidity and mor-tality[1].It has a poor 5-year survival mainly because PDAC poses a significant diagnostic challenge,has a high metastatic rate at di-agnosis and is stubbornly resistant to therapy[2].

关键词： adenocarcinoma ductal cancer

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Fermented calcium butyrate supplementation in post-peak laying hens improved ovarian function and tibia quality through the“gut-bone” axis

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Animal Nutrition 2024年第01期16卷 350-362页

作者： Huaiyong Zhang Yongshuai Wang Yilu Wang Bin Wei Leilei Wang Minh Tu Nguyen Xiangyun Lv Yanqun Huang Wen Chen College of Animal Science and Technology Key Laboratory of Animal Biochemistry and NutritionMinistry of AgricultureHenan Agricultural University Laboratory for Animal Nutrition and Animal Product Quality Department of Animal Sciences and Aquatic EcologyGhent University Department of Agriculture and Forestry Hue University Charoen Pokphand group Co. Ltd.

The compromised egg quality and leg abnormality during the end of the laying cycle(after 40 weeks)have been leading to poor animal welfare and substantial economic losses. Therefore, the effects of fermented calcium(Ca) butyrate, produced by fermentation by Clostridium butyricum, on production,eggshell quality, and tibial property of hens were explored. A total of 192 Hy-line brown laying hens at50-week-old were assigned to a basal diet or the basal diet with 300 mg/kg of the fermented Ca butyrate from 50 to 58 weeks of age. Each treatment had 6 replicates with 16 hens each. The diet supplemented with 300 mg/kg fermented Ca butyrate notably increased egg weight, ovarian follicle number, and eggshell strength(P = 0.072) as compared to the basal diet, which were associated with cytokine secretion, toll-like receptor signaling pathways, and intestinal immunity based on the RNA-seq data from the granulosa. Dietary Ca butyrate inclusion decreased the expression of ileal tumor necrosis factor-alpha and serum pro-inflammatory cytokine concentration, as well as increased the content of serum immunoglobulin A when compared to the basal diet(both P 0.05). In addition, the diet with fermented Ca butyrate reduced the number of osteoclasts in the proximal tibia and the level of C-terminal cross-linked telopeptide of type I collagen, a bone resorption marker(P < 0.05), whereas it tended to increase the concentration of the procollagen type I N-terminal propeptide that reflects bone formation marker in serum. Moreover, the layers fed fermented Ca butyrate diets possessed higher(P < 0.05) bone area and trabecular number of the proximal tibia, yield load, and ultimate load than those that consumed basal diets. Collectively, dietary fermented Ca butyrate supplementa

关键词： Fermented Ca butyrate Ovarian property Tibia metabolism Layer

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Evaluation of flue gas desulfurization gypsum as a low-cost precipitant for phosphorus removal from anaerobic digestion effluent filtrate

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International Journal of Agricultural and Biological Engineering 2024年第4期17卷 198-206页

作者： Yaping Guo Adam Khalaf Wenzhuo Kong Hongzhen Ma Jiawei Liang Dongxu Zhao Zhiguo Wang Yebo Li Fuqing Xu Technology Innovation Center for Land Engineering and Human Settlements Shaanxi Land Engineering Construction Group Co.Ltd and Xi’an Jiaotong UniversitySchool of Human Settlements and Civil EngineeringXi’an Jiaotong UniversityXi’an 710049China Department of Food Agriculturaland Biological Engineeringthe Ohio State UniversityColumbusOH 44691USA Shaanxi Environmental Survey and Assessment Center Xi’an 710054China

Land application of anaerobic digestion(AD)effluent as a fertilizer is desirable for nutrient recycling,but often supplies excess phosphorus(P),which contributes to surface water *** the P content in AD effluent filtrate using calcium(Ca)treatment prior to land application is a potential strategy for improving effluent disposal and meeting the discharge *** study took flue gas desulphurization(FGD)gypsum,a by-product of coal-fired power plants,as a low-cost Ca source,and combined with traditional phosphorus removal agents to achieve high phosphorus removal efficiency with less chemical *** the results showed,FGD gypsum dosages of 20 mmol/L Ca(3.44 g/L)and 40 mmol/L Ca(6.89 g/L)removed up to 97.1%of soluble P(initially 102.8 mg/L)within 60-90 *** FGD gypsum treatment with traditional chemical treatments using calcium hydroxide[Ca(OH)2]or ferric chloride(FeCl3)could achieve>99%P removal with reduced chemical *** study demonstrated that FGD gypsum is an efficient calcium-based precipitant for phosphorus removal,offering a cost-effective and sustainable approach to enhance wastewater treatment practices and meet discharge standards in wastewater management.

关键词： flue gas desulfurization gypsum anaerobic digestion effluent precipitation phosphorus removal eutrophication

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Phagocytosis of optically-trapped particles: delivery of the pure phagocytic signal

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Cell Research 2006年第11期16卷 8+853-854页

作者： Maurjce B Hallett UK Neutrophil signalling group School of Medicine CF14 4XN Cardiff University

Phagocytosis is a fundamental cell biological process exhibited by a wide variety of cell types from single cell organ-isms,which rely on this for feeding,to phagocytes in higher animals,which rely on specialised immune cells for com-bating infecting *** the immune system,both macrophages and neutrophils play roles as *** are often called"professional phagocytes"because of their remarkable capacity for phagocytosis,beingable to internalise microscopic particles(diam 0.5-3 μm)of virtually any surface *** efficiency and speedof phagocytosis is,however,increased by coating the surface of the particles with opsonins such as antibodies or thecomplement component C3bi(acting on β2 integrin receptors),and C3bi-accelerated phagocytosis by neutrophils is thefirst line of defence by the innate immune system in vivo,operating in advance of the slower production of *** the mechanism of phagocytosis is,therefore,clearly an important goal.

关键词： delivery of the pure phagocytic signal Phagocytosis of optically-trapped particles

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Protein synthesis,degradation,and energy metabolism in T cell immunity

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Cellular & Molecular Immunology 2022年第3期19卷 303-315页

作者： Julia M.Marchingo Doreen A.Cantrell Cell signalling and Immunology Division School of Life SciencesUniversity of DundeeDundeeDD15EHUK

T cell activation,proliferation,and differentiation into effector and memory states involve massive remodeling of T cell size and molecular content and create a massive increase in demand for energy and amino *** synthesis is an energy-and resource-demanding process;as such,changes in T cell energy production are intrinsically linked to proteome *** this review,we discuss how protein synthesis and degradation change over the course of a T cell immune response and the crosstalk between these processes and T cell energy *** highlight how the use of high-resolution mass spectrometry to analyze T cell proteomes can improve our understanding of how these processes are regulated.

关键词： T lymphocyte Protein Translation Proteomics Immunometabolism Protein degradation

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Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca^(2+) Signaling

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Chinese Journal of Integrative Medicine 2024年第6期30卷 525-533页

作者： Lucas dos Santos Zamarioli Michele Rosana Maia Santos Adolfo Garcia Erustes Vanessa Marques Meccatti Thais Cristine Pereira Soraya S Smaili Maria Cristina Marcucci Carlos Rocha Oliveira Gustavo JS Pereira Claudia Bincoletto Department of Pharmacology Paulista School of MedicineFederal University of São PauloSão PauloSP04044-020Brazil Research group on Phytocomplexes and Cell Signaling School of Health SciencesAnhembi Morumbi UniversitySão PauloSP03164-000Brazil Department of Biosciences and Oral Diagnosis Institute of Science and TechnologySão Paulo State University(ICT-UNESP)São PauloSP12231-280Brazil

Objective To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 *** Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass(HPLC)*** and cell death studies were performed using trypan blue and Annexin/FITC-7AAD,***-1(Fer-1)and necrostatin-1(Nec-1)were used to assess the mode of HEAV-induced cell death and acetoxymethylester(BAPTA-AM)was used to verify the involvement of cytosolic calcium in this *** calcium measurements were made using *** HEAV decreased the viability of MCF-7,SKBR-3 and K562 cells(P<0.05).The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts(P<0.05).Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD(P<0.05).The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone(P<0.01).HEAV-induced Ca^(2+)release mainly from lysosomes in K562 cells(P<0.01).Furthermore,BAPTA-AM,an intracellular Ca^(2+)chelator,decreased the number of non-viable cells treated with HEAV(P<0.05).Conclusions HEAV is cytotoxic and activates several modalities of cell death,which are partially dependent on lysosomal release of Ca^(2+).These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV.

关键词： Artemisia vulgaris necroptosis ferroptosis late apoptosis Ca^(2+)signaling

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