Isthmin-1 (ISM1), a novel adipokine that reflects abdominal adipose tissue distribution in individuals with obesity.

BACKGROUND: The assessment of obesity-related health risks has traditionally relied on the Body Mass Index and waist circumference, but their limitations have propelled the need for a more comprehensive approach. The differentiation between visceral (VIS) and subcutaneous (SC) fat provides a finer-grained understanding of these risks, yet practical assessment methods are lacking. We hypothesized that combining the SC-VIS fat ratio with non-invasive biomarkers could create a valuable tool for obesity-related risk assessment. METHODS AND RESULTS: A clinical study of 125 individuals with obesity revealed significant differences in abdominal fat distribution measured by CT-scan among genders and distinct models of obesity, including visceral, subcutaneous, and the SC/VIS ratio. Stratification based on these models highlighted various metabolic changes. The SC/VIS ratio emerged as an excellent metric to differentiate metabolic status. Gene expression analysis identified candidate biomarkers, with ISM1 showing promise. Subsequent validation demonstrated a correlation between ISM1 levels in SC and plasma, reinforcing its potential as a non-invasive biomarker for fat distribution. Serum adipokine levels also correlated with the SC/VIS ratio. The Receiver Operating Characteristic analysis revealed ISM1's efficacy in discriminating individuals with favorable metabolic profiles based on adipose tissue distribution. Correlation analysis also suggested that ISM1 was involved in glucose regulation pathways. CONCLUSION: The study's results support the hypothesis that the SC-VIS fat ratio and its derived non-invasive biomarkers can comprehensively assess obesity-related health risks. ISM1 could predict abdominal fat partitioning and be a potential biomarker for evaluating obesity-related health risks.

Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression.

Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis.

In vivo dosimetry in low-voltage IORT breast treatments with XR-RV3 radiochromic film.

PURPOSE: The objectives of the study were to establish a procedure for in vivo film-based dosimetry for intraoperative radiotherapy (IORT), evaluate the typical doses delivered to organs at risk, and verify the dose prescription. MATERIALS AND METHODS: In vivo dose measurements were studied using XR-RV3 radiochromic films in 30 patients with breast cancer undergoing IORT using the Axxent® device (Xoft Inc.). The stability of the radiochromic films in the energy ranges used was verified by taking measurements at different depths. The stability of the scanner response was tested, and 5 different calibration curves were constructed for different beam qualities. Six pieces of film were placed in each of the 30 patients. All the pieces were correctly sterilized and checked to ensure that the process did not affect the outcome. All calibration and dose measurements were analyzed using the Radiochromic.com software application. RESULTS: The doses were measured for 30 patients. The doses in contact with the applicator (prescription zone) were 19.8 ± 0.9 Gy. In the skin areas, the doses were as follows: 1-2 cm from the applicator, 1.86 ± 0.77 Gy; 2-5 cm, 0.73 ± 0.14 Gy; and greater than 5 cm, 0.28 ± 0.17 Gy. The dose delivered to the pectoral muscle (tungsten shielding disc) was 0.51 ± 0.27 Gy. CONCLUSIONS: The study demonstrated the viability of XR-RV3 films for in vivo dose measurement in the dose and energy ranges applied in a complex procedure, such as breast IORT. The doses in organs at risk were far below the tolerances for cases such as those studied.

Carcinoma metaplásico de mama productor de matriz / Matrix-producing metaplastic carcinoma of the breast

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