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Phenylalanine deprivation inhibits multiple myeloma progression by perturbing endoplasmic reticulum homeostasis

Acta Pharmaceutica Sinica B 2024年第8期14卷 3493-3512页

作者： Longhao Cheng Xiaoxue Wang Aijun Liu Ying Zhu Hu Cheng Jiangling Yu Lili Gong Honglin Liu Guolin Shen Lihong Liu Institute of Clinical Medical Sciences ChinaeJapan Friendship HospitalCapital Medical UniversityBeijing 100029China Department of Pharmacy ChinaeJapan Friendship HospitalBeijing 100029China Beijing Chao-Yang Hospital Capital Medical UniversityBeijing 100020China Institute of Chemicals Safety Chinese Academy of Inspection and QuarantineBeijing 100020China

Amino acid metabolic remodeling is a hallmark of cancer,driving an increased nutritional demand for amino *** acids are pivotal for energetic regulation,biosynthetic support,and homeostatic maintenance to stimulate cancer ***,the role of phenylalanine in multiple myeloma(MM)remains ***,we demonstrate that phenylalanine levels in MM patients are decreased in plasma but elevated in bone marrow(BM)*** the treatment,phenylalanine levels increase in plasma and decrease in *** suggests that changes in phenylalanine have diagnostic value and that phenylalanine in the BM microenvironment is an essential source of nutrients for MM *** requirement for phenylalanine by MM cells exhibits a similar *** phenylalanine utilization suppresses MM cell growth and provides a synergistic effect with Bortezomib(BTZ)treatment in vitro and murine ***,phenylalanine deprivation induces excessive endoplasmic reticulum stress and leads to MM cell apoptosis through the ATF3eCHOPeDR5 *** with ATF3 significantly affects phenylalanine deprivation *** conclusion,we have identified phenylalanine metabolism as a characteristic feature of MM metabolic *** is necessary for MM proliferation,and its aberrant demand highlights the importance of lowphenylalanine diets as an adjuvant treatment for MM.

关键词： Multiple myeloma Phenylalanine Amino acid metabolism nutrient deprivation Cancer therapy Endoplasmic reticulum stress ATF3 Apoptosis

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How Growth Ability of Multidrug-Resistant Escherichia coli Is Affected by Abiotic Stress Factors

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Open Journal of Preventive Medicine 2014年第5期4卷 250-256页

作者： Lucinda Janete Bessa Vania Filipa Dias Angelo Mendes Paula Martins-Costa Helena Ramos Paulo Martins da Costa CIIMAR—Interdisciplinary Center for Marine and Environmental Research University of PortoPortoPortugal ICBAS—Institute Abel Salazar for the Biomedical Sciences University of PortoPortoPortugal FCUP—Faculty of Sciences University of PortoPortoPortugal Servico de Microbiologia Centro Hospitalar do PortoHospital Geral de Santo AntonioPortoPortugal

The ability of multidrug-resistant Escherichia coli to adapt and grow in a wide range of different environmental conditions may be crucial to the global spread of antimicrobial resistance. The aim of this study was to evaluate the survival ability of 54 multidrug-resistant E. coli strains, isolated from three different biotopes (clinical setting, gull intestine, river water) when subjected to variations in pH (from 3 to 11) and salinity (from 0.5% to 6% of NaCl) and to nutrient deprivation. The growth of each isolate as well as of a reference strain was assessed during 168 h in every varying condition. Slight variations in the growth ability under some abiotic stress factors were recorded among the isolates from the different biotopes. Multidrug-resistant isolates from gull feces were found to be the more tolerant to environmental abiotic changes, while isolates from river water were the less tolerant. In addition, it was notorious that the carriage of antimicrobial resistance has a clear fitness cost in comparison with the susceptible (reference) strain, highlighting the necessity of reducing the selective pressure exerted by antibiotics. This study underlines the ecological hardness of multidrug-resistant E. coli isolates with a consequent ability to reach and colonize new host and environments.

关键词： Escherichia coli Multidrug Resistance nutrient deprivation pH Salinity

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