The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy

Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. In this review, we will summarize the preclinical and clinical studies highlighting the critical role of the microbiome in the efficacy of cancer treatment, concerning mainly chemotherapy and immunotherapy with immune checkpoint inhibitors. In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies. Importantly, an emerging trend of using microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to overcome cancer treatment resistance will be also discussed.     

The Role of Exosomes in Cancer Progression

Early detection, characterization and monitoring of cancer are possible by using extracellular vesicles (EVs) isolated from non-invasively obtained liquid biopsy samples. They play a role in intercellular communication contributing to cell growth, differentiation and survival, thereby affecting the formation of tumor microenvironments and causing metastases. EVs were discovered more than seventy years ago. They have been tested recently as tools of drug delivery to treat cancer. Here we give a brief review on extracellular vesicles, exosomes, microvesicles and apoptotic bodies. Exosomes play an important role by carrying extracellular nucleic acids (DNA, RNA) in cell-to-cell communication causing tumor and metastasis development. We discuss the role of extracellular vesicles in the pathogenesis of cancer and their practical application in the early diagnosis, follow up, and next-generation treatment of cancer patients.     

Gangliosides as Biomarkers of Human Brain Diseases: Trends in Discovery and Characterization by High-Performance Mass Spectrometry

Gangliosides are effective biochemical markers of brain pathologies, being also in the focus of research as potential therapeutic targets. Accurate brain ganglioside mapping is an essential requirement for correlating the specificity of their composition with a certain pathological state and establishing a well-defined set of biomarkers. Among all bioanalytical methods conceived for this purpose, mass spectrometry (MS) has developed into one of the most valuable, due to the wealth and consistency of structural information provided. In this context, the present article reviews the achievements of MS in discovery and structural analysis of gangliosides associated with severe brain pathologies. The first part is dedicated to the contributions of MS in the assessment of ganglioside composition and role in the specific neurodegenerative disorders: Alzheimer’s and Parkinson’s diseases. A large subsequent section is devoted to cephalic disorders (CD), with an emphasis on the MS of gangliosides in anencephaly, the most common and severe disease in the CD spectrum. The last part is focused on the major accomplishments of MS-based methods in the discovery of ganglioside species, which are associated with primary and secondary brain tumors and may either facilitate an early diagnosis or represent target molecules for immunotherapy oriented against brain cancers.     

The Urinary Level of Injury Biomarkers Is Not Univocally Reflective of the Extent of Toxic Renal Tubular Injury in Rats

Nephrotoxicity is a major cause of intrinsic acute kidney injury (AKI). Because renal tissue damage may occur independently of a reduction in glomerular filtration rate and of elevations in plasma creatinine concentration, so-called injury biomarkers have been proposed to form part of diagnostic criteria as reflective of tubular damage independently of renal function status. We studied whether the urinary level of NGAL, KIM-1, GM2AP, t-gelsolin, and REGIIIb informed on the extent of tubular damage in rat models of nephrotoxicity, regardless of the etiology, moment of observation, and underlying pathophysiology. At a time of overt AKI, urinary biomarkers were measured by Western blot or ELISA, and tubular necrosis was scored from histological specimens stained with hematoxylin and eosin. Correlation and regression studies revealed that only weak relations existed between biomarkers and tubular damage. Due to high interindividual variability in the extent of damage for any given biomarker level, urinary injury biomarkers did not necessarily reflect the extent of the underlying tissue injury in individual rats. We contended, in this work, that further pathophysiological contextualization is necessary to understand the diagnostic significance of injury biomarkers before they can be used for renal tubular damage severity stratification in the context of nephrotoxic and, in general, intrinsic AKI.     

Mycotoxin Biomarkers of Exposure: A Comprehensive Review

To date, the use of biomarkers has become generally accepted. Biomarker‐driven research has been proposed as a successful method to assess the exposure to xenobiotics by using concentrations of the parent compounds and/or metabolites in biological matrices such as urine or blood. However, the identification and validation of biomarkers of exposure remain a challenge. Recent advances in high‐resolution mass spectrometry along with new analytical (post‐acquisition data‐mining) techniques will improve the quality and output of the biomarker identification process. Chronic or even acute exposure to mycotoxins remains a daily fact, and therefore it is crucial that the mycotoxins’ metabolism is unravelled so more knowledge on biomarkers in humans and animals is acquired. This review aims to provide the scientific community with a comprehensive overview of reported in vitro and in vivo mycotoxin metabolism studies in relation to biomarkers of exposure for deoxynivalenol, nivalenol, fusarenon‐X, T‐2 toxin, diacetoxyscirpenol, ochratoxin A, citrinin, fumonisins, zearalenone, aflatoxins, and sterigmatocystin.     

现场电解制次氯酸钠在污水处理厂出水消毒的应用研究

随着污水厂出水排放标准日益提高,对排水中粪大肠菌群的控制也越来越严格。现场电解制次氯酸钠发生系统是一种较为理想的环境友好型氯消毒技术,能够有效杀灭城镇污水处理厂出水中的粪大肠杆菌。因原水水质不同,次氯酸钠的杀菌效果会有差异。次氯酸钠对原水中的氨氮有一定的去除作用,但是有可能氧化原水中残留的有机氮,从而使得氨氮含量重新升高。现场连续投加试验中,反应池次氯酸钠浓度为1．2mg／L,出水中的粪大肠菌群始终稳定达到GB18918-2002一级A标准的要求,且其他水质指标（如氨氮、COD等）良好。     

粪便水对大坦沙污水厂生产运行的影响及控制措施

广州市大坦沙污水处理厂承担着全市粪便水的处理任务。生产实践表明，由粪便水造成的水质冲击负荷对生产运行不利，导致设备维护率提高、运行成本增加。通过建造粪便水调节池、调整工艺参数、加大设备维修和技术改造力度、对恶臭源进行加盖除臭等措施可以降低粪便水对生产运行的影响。