Saeedi, Mina Al

Poststenotic dilatation in renal artery stenosis, evaluated at abdominal CT, might be related to stenotic kidney damage and inflammation, particularly to monocyte chemoattractant protein-1 release.

Abstract Importance Mesenchymal stromal cells (MSCs) possess therapeutic properties that mediate repair. Obesity impairs MSC functionality and therapeutic efficacy, possibly by eliciting dynamic modifications of epigenetic markers, like 5-hydroxymethylcytosine (5hmC). Objective We hypothesized that human obesity alters the 5hmC landscape and anti-inflammatory capacity of adipose tissue-derived MSCs to activate the prominent inflammatory signaling mediator Interleukin (IL)-1β. Design, Setting, Participants, Intervention Adipose tissue samples were collected from obese and lean individuals (body mass index ≥30 or <30 kg/m2, respectively, n = 11 each) during weight-loss or kidney donation surgery. Main Outcomes and Measures MSCs were harvested and analyzed for 5hmC profiles (MeDIP-seq) and mRNA expression (RNA-seq) (n = 5 each). Subsequently, MSCs or a vehicle were injected into mice, (n = 6 each) and two-weeks later, kidneys were evaluated using in-vivo magnetic resonance imaging and ex vivo studies. The role of IL-1β was then studied in-vitro in MSC-induced immunomodulation using siRNA in macrophages. Results Compared to MSC from lean patients, obese-MSC genes showed 2087 differential 5hmC modifications and 175 differential mRNA expression. Among them, 14 genes with overlapping alterations were involved in regulation of cytokine production, prominently IL-1β. Injecting obese MSCs elevated renal expression of IL-1β and M1 macrophage count but lowered kidney perfusion. Silencing IL-1β in obese-MSCs in vitro reduced M1 phenotype switching in co-incubated macrophages. Conclusions and Relevance Obesity induces epigenetic and gene expression changes in MSCs, particularly in IL-1β, associated with impaired anti-inflammatory functionality of MSCs. Targeting IL-1β could be a useful therapeutic approach to modulate the decline in MSC functionality resulting from obesity.

Mesenchymal stromal cells (MSCs) possess therapeutic properties, which can be blunted by obesity. Autophagy, a cellular recycling process, is essential for MSC function. We investigated the mechanisms by which obesity affects the properties of MSCs, with a focus on autophagy. Adipose tissue was obtained from kidney donors [body mass index (BMI) <30 kg/m 2 , non-obese] or individuals undergoing weight loss surgery (BMI ≥30 kg/m 2 , obese) for MSC harvesting ( n = 11 each); samples were randomized to sequencing (seq; n = 5 each) or functional studies ( n = 6 each). MSCs were sequenced to determine their epigenetic (5-hydroxymethylcytosine) and transcriptomic profiles across autophagy-related genes using hydroxymethylated DNA immunoprecipitation sequencing and mRNA-seq, respectively. Genes with shared trends in both datasets underwent Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) validation. During functional studies, 2-h starvation was used to induce autophagy in vitro , enabling detection of changes in the protein expression of microtubule-associated protein 1A/1B-light chain-3 and in autophagic flux. Obesity amplified a starvation-induced reduction in autophagic flux in MSCs while promoting earlier generation of new autophagosomes during autophagy initiation. Integrated analysis of the two sequencing datasets revealed 124 differentially hydroxymethylated genes and 30 differentially expressed mRNAs. Among six overlapping autophagy-related genes, three exhibited same-direction trends. Of these, STX12 and SLC25A4 may be implicated in the impact of obesity on autophagic changes in MSCs. Therefore, human obesity may alter autophagy in adipose tissue–derived MSC, and thereby their metabolism and function.

Abstract Background and Aims The present study aims to shed light on the knowledge, attitude, and practice of breast self‐examination with breast cancer (BC) among female patients in the oncology department of Baghdad Medical City. Methods This cross‐sectional study involved 100 female participants at the Oncology Teaching Hospital in Baghdad Medical City between June 15 and October 15, 2022. Using convenient sampling, the study targeted females aged 30–75, recently or previously diagnosed with BC, admitted for treatment and follow‐ups. Results Regarding the assessment of knowledge, among the surveyed patients, 71 are aware of breast self‐examination (BSE), primarily through social media (42 patients). The study also explores the link between BSE and education levels. While Pearson's chi‐square shows no significance (0.107), the likelihood ratio suggests a significant association (0.041). Regarding the analysis of attitudes, the study assessment for the reasons for compliance showed that 19 patients cite medical reasons, and 48 patients attribute noncompliance to a lack of knowledge of how to perform BSE. Regarding the examination of practice, high statistical significance is evident in both Pearson's chi‐square (0.000) and likelihood ratio (0.000) tests, emphasizing the substantial relationship between the post‐diagnosis initiation timing of BSE and its correct execution. Additionally, a statistically significant association exists between performing BSE correctly and discovering BC ( p = 0.000). Conclusion Regarding the assessment of knowledge, our study found high awareness of BSE within the population, primarily through social media and health organizations. Regarding the analysis of attitudes, a notable proportion refrained from practicing BSE, primarily due to a perceived lack of knowledge about the methods. Regarding the examination of practice, the observed significant associations between performing BSE correctly, discovering BC, and the frequency of examinations underscore the pivotal role of consistent and accurate BSE in early detection.

Renal fibrosis is an important marker in the progression of chronic kidney disease, and renal biopsy is the current reference standard for detecting its presence. Currently, non-invasive methods have only been partially successful in detecting renal fibrosis. Magnetization transfer imaging (MTI) allows estimates of renal fibrosis but may vary with scanning conditions. We hypothesized that MTI-derived renal fibrosis would be reproducible at 1.5T and 3T MRI and over time in fibrotic kidneys. Fifteen pigs with unilateral renal artery stenosis (RAS, n = 9) or age-matched sham controls (n = 6) underwent MTI-MRI at both 1.5T and 3T 6 weeks post-surgery and again 4 weeks later. Magnetization transfer ratio (MTR) measurements of fibrosis in both kidneys were compared between 1.5T and 3T, and the reproducibility of MTI at the two timepoints was evaluated at 1.5T and 3T. MTR at 3T with 600 Hz offset frequency successfully distinguished between normal, stenotic, and contralateral kidneys. There was excellent reproducibility of MTI at 1.5T and 3T over the two timepoints and no significant differences between MTR measurements at 1.5T and 3T. Therefore, MTI is a highly reproducible technique which is sensitive to detect changes in fibrotic compared to normal kidneys in the RAS porcine model at 3T.