No abstract

Various antibiotics have been used in the treatment of cancers, via their anti-proliferative, pro-apoptotic and anti-epithelial-mesenchymal-transition (EMT) capabilities. However, increasingly studies have indicated that antibiotics may also induce cancer generation by disrupting intestinal microbiota, which further promotes chronic inflammation, alters normal tissue metabolism, leads to genotoxicity and weakens the immune response to bacterial malnutrition, thereby adversely impacting cancer treatment. Despite the advent of high-throughput sequencing technology in recent years, the potential adverse effects of antibiotics on cancer treatments via causing microbial imbalance has been largely ignored. In this review, we discuss the double-edged sword of antibiotics in the field of cancer treatments, explore their potential mechanisms and provide solutions to reduce the potential negative effects of antibiotics.

Failing to repair DNA double-strand breaks by either nonhomologous end joining (NHEJ) or homologous recombination (HR) poses a threat to genome integrity, and may have roles in the onset of aging and age-related diseases. Recent work indicates an age-related decrease of NHEJ efficiency in mouse models, but whether NHEJ and HR change with age in humans and the underlying mechanisms of such a change remain uncharacterized. Here, using 50 eyelid fibroblast cell lines isolated from healthy donors at the age of 16-75 years, we demonstrate that the efficiency and fidelity of NHEJ, and the efficiency of HR decline with age, leading to increased IR sensitivity in cells isolated from old donors. Mechanistic analysis suggests that decreased expression of XRCC4, Lig4 and Lig3 drives the observed, age-associated decline of NHEJ efficiency and fidelity. Restoration of XRCC4 and Lig4 significantly promotes the fidelity and efficiency of NHEJ in aged fibroblasts. In contrast, essential HR-related factors, such as Rad51, do not change in expression level with age, but Rad51 exhibits a slow kinetics of recruitment to DNA damage sites in aged fibroblasts. Further rescue experiments indicate that restoration of XRCC4 and Lig4 may suppress the onset of stress-induced premature cellular senescence, suggesting that improving NHEJ efficiency and fidelity by targeting the NHEJ pathway holds great potential to delay aging and mitigate aging-related pathologies. Cell Death and Differentiation (2016) 23, 1765-1777; doi:10.1038/cdd.2016.65; published online 8 July 2016Aging in mammals is a complex biological process, characterized by several major hallmarks.1,2 Of all the features associated with aging, a gradual destabilization of genome integrity is perhaps the most fundamental as increased genomic instability may lead to other age-associated phenotypes such as cellular senescence and stem cell exhaustion. Indeed, for the past several decades, numerous studies have indicated that DNA mutations and chromosomal rearrangements gradually accumulate with age.3-6 Of all types of DNA lesions, which may contribute to the gradual loss of genetic information during aging, DNA double-strand breaks (DSBs) are the most hazardous to cells as unrepaired or inappropriately repaired DSBs can cause insertions, deletions and chromosomal rearrangements. Using different analysis approaches, several studies have demonstrated that aging is often associated with the accumulation of DNA DSBs in various organs and tissues in mammals such as mice and humans. [7][8][9][10][11] Moreover, a recent study provides direct evidence that an induction of DNA DSBs in genomes causes aging in mouse livers.12 However, why DNA DSBs accumulate with age remains an open question. A number of studies indicate that it may be a consequence of a progressing imbalance between DNA damage and the efficiency of the molecular machinery that catalyzes DNA repair. 7,9,11 Two major pathways, nonhomologous end joining (NHEJ) and homologous recombination (HR) evolved to repair DNA DSBs. NHEJ is...

ObjectiveDiabetic kidney disease (DKD) is the most common chronic kidney disease (CKD) and has the highest prevalence of end-stage kidney disease (ESKD) globally, owing mostly to the rise in Type 2 diabetes mellitus (T2DM) correlated with obesity. Current research suggested that the immune response and inflammation may play a role in the pathophysiology of T2DM. The systemic immune-inflammation index (SII) is a novel and integrated inflammatory biomarker that has not yet been linked to DKD. We aimed to identify the potential relationship between SII and DKD.MethodsIn the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018, the current cross-sectional study was conducted among adults with T2DM. SII was calculated as the platelet count × neutrophil count/lymphocyte count. DKD was diagnosed with impaired glomerular filtration rate (< 60 mL/min/1.73 m2 assessed by using the Chronic Kidney Disease Epidemiology Collaboration algorithm), albuminuria (urine albumin to creatinine ratio ≥ 30 mg/g), or both in T2DM patients. To investigate the independent association between SII and DKD, weighted univariate and multivariable logistic regression analyses and subgroup analyses were performed.ResultsThe study involved 3937 patients in total, of whom 1510 (38.4%) had DKD for the diagnosis. After adjustment for covariates, multivariable logistic regression revealed that a high SII level was associated with increased likelihood of DKD (OR = 1.42, 95% CI: 1.10-1.83, P = 0.01). Subgroup analyses and interaction tests revealed that age, gender, estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (ACR), body mass index (BMI), hypertension, hyperlipidemia, anti-inflammation therapy (yes or no), metformin use (yes or no), and insulin use (yes or no) had no significant dependence on this positive relationship (all p for interaction >0.05).ConclusionsOur results indicate that the higher SII level is associated with DKD in T2DM patients. The SII could be a cost-effective and straightforward approach to detecting DKD. This needs to be verified in further prospective investigations.

No abstract

No abstract

. (2017). Multi-walled carbon nanotubes-based magnetic solid-phase extraction for the determination of zearalenone and its derivatives in maize by ultra-high performance liquid chromatography-tandem mass spectrometry. Food Control, 79,[177][178][179][180][181][182][183][184] Publisher rights © 2017 Elsevier Ltd. This manuscript is distributed under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited. General rightsCopyright for the publications made accessible via the Queen's University Belfast Research Portal is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights.Take down policy The Research Portal is Queen's institutional repository that provides access to Queen's research output. Every effort has been made to ensure that content in the Research Portal does not infringe any person's rights, or applicable UK laws. If you discover content in the Research Portal that you believe breaches copyright or violates any law, please contact openaccess@qub.ac.uk.

No abstract