Positive correlation between the nuclear expression of GPER and pGLI3 in prostate cancer tissues from patients with different Gleason scores

Prostate cancer (PCa) is the most prevalent cause of death in the male population worldwide. The G Protein-Coupled Estrogen Receptor (GPER) has been gaining relevance in the development of PCa. Hedgehog (Hh) pathway activation is associated with aggressiveness, metastasis, and relapse in PCa patients. To date, no studies have evaluated the crosstalk between the GPER and the Hh pathway along different group grades in PCa. We conducted an analysis of paraffin-embedded tissues derived from patients with different prognostic grade of PCa using immunohistochemistry. Expression and correlation between GPER and glioma associated oncogene homologue (GLI) transcriptional factors in the parenchyma and stroma of PCa tumors were evaluated. Our results indicate that GPER is highly expressed in the nucleus and increases with higher grade groups. Additionally, GPER’s expression correlates with pGLI3 nuclear expression across different grade groups in PCa tissues; however, whether the receptor induces the activation of GLI transcriptional factors, or the latter modulate the expression of GPER is yet to be discovered, as well as the functional consequence of this correlation

Prenatal Alcohol Exposure in Rats Diminishes Postnatal Cxcl16 Chemokine Ligand Brain Expression

Maternal ethanol consumption during pregnancy is one of the main causes of Neurodevelopmental disorders (NDD). Prenatal alcohol exposure (PAE) produces several adverse manifestations. Even low or moderate intake has been associated with long-lasting behavioral and cognitive impairment in offspring. In this study we examined the gene expression profile in the rat nucleus accumbens using microarrays, comparing animals exposed prenatally to ethanol and controls. Microarray gene expression showed an overall downward regulatory effect of PAE. Gene cluster analysis reveals that the gene groups most affected are related to transcription regulation, transcription factors and homeobox genes. We focus on the expression of the C-X-C motif chemokine ligand 16 (Cxcl16) which was differentially expressed. There is a significant reduction in the expression of this chemokine throughout the brain under PAE conditions, evidenced here by quantitative polymerase chain reaction qPCR and immunohistochemistry. Chemokines are involved in neuroprotection and implicated in alcohol-induced brain damage and neuroinflammation in the developing central nervous system (CNS), therefore, the significance of the overall decrease in Cxcl16 expression in the brain as a consequence of PAE may reflect a reduced ability in neuroprotection against subsequent conditions, such as excitotoxic damage, inflammatory processes or even hypoxic-ischemic insult

C4d expression in focal segmental glomerulosclerosis

Background: There is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the expression of C4d in FSGS subtypes in percutaneous native renal biopsies in a second-level hospital and its correlation with clinical, biochemical and histological variables. Material and methods: A retrospective study in paraffin blocks of patients with biopsy with FSGS aged 16–65 years, indistinct sex, not diabetic or obese. Immunohistochemistry was performed for C4d and their expression was analyzing in non-sclerosed glomerular capillaries (GC) and sclerosis areas (SA). Clinical and biochemical variables were recorded. The cases were divided into C4d positive and C4d negative groups and compared. The correlation between C4d staining scores in CG and SA with clinical and biochemical variables were analyzed. Results: Twenty samples were analyzed, 4 for each subtype. At the time of biopsy average age 38.8 ± 18.6 years, 65% male, 8.7% were hypertension. The percentage of positivity for C4d was 40% in GC, 30% SA and 35% in mesangium. The highest expression was for cellular and collapsing subtypes. C4d positivity cases had increased proteinuria (p = 0.035). A significant correlation was found between percentage of C4d expression in CG with SA (p = 0.012) and SA with tubular atrophy and interstitial fibrosis (p < 0.05). Conclusions: C4d expression in FSGS predominated in the cellular and collapsing subtypes, which translates complement activation. C4d is a possible surrogate marker in GSFS. Resumen: Antecedentes: Existe poca información acerca de la expresión del C4d (fragmento del complemento) en la glomeruloesclerosis focal y segmentaria (GEFS) y sus variantes. El objetivo del estudio fue determinar la expresión de C4d en las variantes de GEFS en biopsia renal percutánea (BRP) de riñones nativos en un hospital de segundo nivel y su correlación con variables clínicas, bioquímicas e histológicas. Material y métodos: Estudio retrospectivo en bloques de parafina de pacientes con BRP con GEFS de 16–65 años, sexo indistinto, no diabéticos ni obesos. Se realizó inmunohistoquímica para C4d, analizando su expresión en capilares glomerulares (CG) no esclerosados y áreas de esclerosis (EC). Se registraron variables clínicas y bioquímicas. Los casos fueron clasificados en C4d positivo o negativos y se compararon entre ellos. Se analizó la correlación entre las puntuaciones de C4d en CG y EC con variables clínicas y bioquímicas. Resultados: Se analizaron 20 muestras, 4 para cada variante. Al momento de la BRP la edad fue de 38.8 ± 18.6 años, 65% sexo masculino, 8.7% hipertensos. El porcentaje de positividad para C4d fue 40% en CG, del 30% en EC y del 35% en mesangio. La mayor expresión de C4d fue para las variantes celular y colapsante. Los casos C4d positivos tenían mayor proteinuria (p = 0.035). Se encontró correlación entre el porcentaje de expresión de C4d en CG con EC (p = 0.012) y de EC con atrofia tubular y fibrosis intersticial (p < 0.05). Conclusiones: La expresión de C4d en GFS predominó en la variante celular y colapsante por probable activación del complemento. C4d es un posible marcador subrogado en GEFS

Alliin, An Allium sativum Nutraceutical, Reduces Metaflammation Markers in DIO Mice

Obesity generates a chronic low-grade inflammatory state which promotes oxidative stress and triggers comorbidities. Alliin is the main organosulfur compound in garlic and has been shown to induce a decrease in the expression of proinflammatory cytokines; its systemic effect on metabolic parameters and adipose tissue is not yet known, however. After nine weeks of HFD and with obesity established in C57BL/6 mice, we observed that a daily treatment with alliin for 3.5 weeks (15 mg/kg) did not affect body weight, but significantly improved insulin sensitivity and glucose tolerance, both evaluated through a blood glucose monitoring system. Once alliin treatment was completed, serum, adipose tissue, and organs of interest related to metabolism were removed for further analysis. We observed that alliin significantly decreased the size of adipocytes from epididymal adipose tissue, evaluated via microscopy. A decrease in gene expression and serum protein levels of the adipocytokines leptin and resistin, as well as decreased serum IL-6 concentration, were detected by qRT-PCR and ELISA, respectively. It did not, however, affect mRNA expression of antioxidant enzymes in the liver. Taken altogether, these results indicate that treatment with alliin reduces metaflammation markers in DIO mice and improves some metabolic parameters without affecting others