Breast adiposity is correlated with body mass index, menopausal status and mammary density. We here wish to establish how these factors influence the cross-talk between breast adipocytes and normal or malignant breast cells. Adipocyte-derived stem cells (ASCs) were obtained from healthy women and classified into six distinct groups based on body mass index, menopausal status and mammary density. The ASCs were induced to differentiate, and the influence of their conditioned media (ACM) was determined. Unexpectedly, there were no detectable differences in adipogenic differentiation and secretion between the six ASC groups, while their corresponding ACMs had no detectable influence on normal breast cells. In clear contrast, all ACMs profoundly influenced the proliferation, migration and invasiveness of malignant breast cells and increased the number of lipid droplets in their cytoplasm via increased expression of the fatty acid receptor CD36, thereby increasing fatty acid uptake. Importantly, inhibition of CD36 reduced lipid droplet accumulation and attenuated the migration and invasion of the breast cancer cells. These findings suggest that breast-associated adipocytes potentiate the invasiveness of breast cancer cells which, at least in part, is mediated by metabolic reprogramming via CD36-mediated fatty acid uptake.

Focal segmental glomerulosclerosis (FSGS) is a major cause of end-stage renal disease and remains without specific treatment. To identify new events during FSGS progression, we used an experimental model of FSGS associated with nephroangiosclerosis in rats injected with L-NAME (N_ω-nitro-L-arginine methyl ester). After transcriptomic analysis we focused our study on the role of Isthmin-1 (ISM1, an anti-angiogenic protein involved in endothelial cell apoptosis. We studied the renal expression of ISM1 in L-NAME rats and other models of proteinuria, particularly at the glomerular level. In the L-NAME model, withdrawal of the stimulus partially restored basal ISM1 levels, along with an improvement in renal function. In other four animal models of proteinuria, ISM1 was overexpressed and localized in podocytes while the renal function was degraded. Together these facts suggest that the glomerular expression of ISM1 correlates directly with the progression-recovery of the disease. Further in vitro experiments demonstrated that ISM1 co-localized with its receptors GRP78 and integrin αvβ5 on podocytes. Treatment of human podocytes with low doses of recombinant ISM1 decreased cell viability and induced caspase activation. Stronger ISM1 stimuli in podocytes dropped mitochondrial membrane potential and induced nuclear translocation of apoptosis-inducing factor (AIF). Our results suggest that ISM1 participates in the progression of glomerular diseases and promotes podocyte apoptosis in two different complementary ways: one caspase-dependent and one caspase-independent associated with mitochondrial destabilization.

Purpose: Acute kidney injury (AKI) is common in patients with COVID-19, however, its mechanism is still controversial, particularly in ICU settings. Urinary proteinuria profile could be a non-invasive tool of interest to scrutinize the pathophysiological process underlying AKI in COVID-19 patients. Material and Methods: We conducted a retrospective study between March 2020 and April 2020. All patients with laboratory-confirmed COVID-19 and without end-stage kidney disease requiring renal replacement therapy before ICU admission were included. Our objectives were to assess the incidence and risk factors for AKI and to describe its clinical and biological characteristics, particularly its urinary protein profile. Results: Seventy patients were included; 87% needed mechanical ventilation and 61% needed vasopressor during their ICU stay; 64.3% of patients developed AKI and half of them needed dialysis. Total and tubular proteinuria on day 1 were higher in patients with AKI, whereas glomerular proteinuria was similar in both groups. The main risk factor for AKI was shock at admission (OR = 5.47 (1.74–17.2), p < 0.01). Mortality on day 28 was higher in AKI (23/45, 51.1%) than in no-AKI patients (1/25, 4%), p < 0.001. Risk factors for 28-days mortality were AKI with need for renal replacement therapy, non-renal SOFA score and history of congestive heart failure. Conclusions: AKI is common in COVID-19 patients hospitalized in ICU; it seems to be related to tubular lesions rather than glomerular injury and is related to shock at ICU admission.

Key Points: Autoimmune hypoglycemia belongs to the clinical spectrum of HHV8+ MCD and rituximab is an effective treatment of this condition. This rare complication is related to autoantibodies directed toward the insulin receptor and activating the insulin signaling pathway.

Background: People living with HIV (PLWH) are at risk of non-infectious comorbidities. It is important to individualize those at higher risk. Methods: In a single-center cohort of PLWH, we performed a cross-sectional analysis of comorbidities, diagnosed according to standard procedures. The primary endpoint was the prevalence of subclinical carotid/coronary atherosclerosis. Secondary endpoints were its association with selected inflammatory/immune activation biomarkers and with other comorbidities. Associations were examined using Chi-2 or Fisher’s exact test for categorical variables and Student or Wilcoxon tests for quantitative variables, and a stepwise multivariate logistical model was performed for further exploration. Results: Among 790 participants (median age : 49.8 years [IQR: 44.5-55.6], 77.1% males, median CD4: 536/mm3 [IQR: 390-754], 83.6% with undetectable viral load), asymptomatic atherosclerosis was found in 26% and was associated in multivariate analysis with older age, longer known duration of infection, higher sCD14 and lower adiponectin levels. Hypertension was found in 33.5% of participants, diabetes in 19.4%, renal impairment in 14.6%, elevated LDL-cholesterol in 13.3%, elevated triglyceride/HDL-cholesterol ratio in 6.6%, and osteoporosis in 7.9%. The presence of 2 or more comorbidities, was found in 42.1% of participants and was associated in multivariate analysis with older age, longer exposure to antiretrovirals, ever exposure to stavudine and higher sCD14 levels. Comorbidities were diversely associated with biomarkers: osteoporosis with higher IL-6, renal impairment with higher sCD14, hypertension with higher D-dimer, diabetes and elevated triglyceride/HDL-cholesterol ratio both with lower adiponectin and lower 25hydroxy-vitamin D. Conclusions: Asymptomatic atherosclerosis and multimorbidity were frequent in a cohort of middle-aged, well-controlled, PLWH and were associated with traditional and HIV-specific factors. Associations between morbidities and inflammatory/immune activation biomarkers were diverse.