Changes of drinking behavior in Korean pregnant women for the last 20 year.

BACKGROUND: The purpose of this study is to investigate the drinking behavior of Korean pregnant women in 2017 and to compare the changes of drinking status with the results of the research conducted in 1997 and 2008. METHODS: Pregnant women at one obstetrics and gynecology hospital and one university hospital were the subjects of the study. They were filled out questionnaire. RESULTS: The rate of positive responses to CAGE increased 16.0% in 2008 and 16.3% in 2017 compared to 11.8% in 1997 (P = 0.046). Blackout history rate was keep increasing from 1997 to 2017 (8.8% versus 27.7% versus 36.3%, P < 0.001). The rate of family history of alcohol was nearly doubled in 2017 (30.3%) compared to 1997 (17.6%) and 2008 (16.3) (P < 0.001). The rate of pregnant women who drink alcohol during pregnancy decreased from 57.5% in 1997 to 39.5% in 2008 and decreased to 25.6% in 2017 (P < 0.001). The rate of pregnant women who drink alcohol after knowing the pregnancy was decreased in 2017 (6.9%) compared to 2008 (23.5%) (P < 0.001). CONCLUSION: According to the results of the study in 2017, the rate of pregnant women who drink alcohol after pregnancy was decreased compared to 1997 and 2008. However drinking behavior severity has increased in 2017.

RIPK3 causes mitochondrial dysfunction and albuminuria in diabetic podocytopathy through PGAM5-Drp1 signaling.

BACKGROUND: Receptor-interacting protein kinase (RIPK)3 is an essential molecule for necroptosis and its role in kidney fibrosis has been investigated using various kidney injury models. However, the relevance and the underlying mechanisms of RIPK3 to podocyte injury in albuminuric diabetic kidney disease (DKD) remain unclear. Here, we investigated the role of RIPK3 in glomerular injury of DKD. METHODS: We analyzed RIPK3 expression levels in the kidneys of patients with biopsy-proven DKD and animal models of DKD. Additionally, to confirm the clinical significance of circulating RIPK3, RIPK3 was measured by ELISA in plasma obtained from a prospective observational cohort of patients with type 2 diabetes, and estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), which are indicators of renal function, were followed up during the observation period. To investigate the role of RIPK3 in glomerular damage in DKD, we induced a DKD model using a high-fat diet in Ripk3 knockout and wild-type mice. To assess whether mitochondrial dysfunction and albuminuria in DKD take a Ripk3-dependent pathway, we used single-cell RNA sequencing of kidney cortex and immortalized podocytes treated with high glucose or overexpressing RIPK3. RESULTS: RIPK3 expression was increased in podocytes of diabetic glomeruli with increased albuminuria and decreased podocyte numbers. Plasma RIPK3 levels were significantly elevated in albuminuric diabetic patients than in non-diabetic controls (p = 0.002) and non-albuminuric diabetic patients (p = 0.046). The participants in the highest tertile of plasma RIPK3 had a higher incidence of renal progression (hazard ratio [HR] 2.29 [1.05-4.98]) and incident chronic kidney disease (HR 4.08 [1.10-15.13]). Ripk3 knockout improved albuminuria, podocyte loss, and renal ultrastructure in DKD mice. Increased mitochondrial fragmentation, upregulated mitochondrial fission-related proteins such as phosphoglycerate mutase family member 5 (PGAM5) and dynamin-related protein 1 (Drp1), and mitochondrial ROS were decreased in podocytes of Ripk3 knockout DKD mice. In cultured podocytes, RIPK3 inhibition attenuated mitochondrial fission and mitochondrial dysfunction by decreasing p-mixed lineage kinase domain-like protein (MLKL), PGAM5, and p-Drp1 S616 and mitochondrial translocation of Drp1. CONCLUSIONS: The study demonstrates that RIPK3 reflects deterioration of renal function of DKD. In addition, RIPK3 induces diabetic podocytopathy by regulating mitochondrial fission via PGAM5-Drp1 signaling through MLKL. Inhibition of RIPK3 might be a promising therapeutic option for treating DKD.

Proteomics of Extracellular Vesicle in Glioblastoma.

Glioblastoma multiforme (GBM), a high-grade astrocytic brain tumor, has highly aggressive and heterogeneous phenotypes with active cellular invasion, angiogenesis, and immune system modulation in the tumor microenvironment driven by complex oncogenic mutations. This abnormal disease progression could be attributed to extracellular vesicles (EVs) containing diverse bioactive molecules, including proteins, genetic materials, lipids, and metabolites. Importantly, GBM-related EVs have emerged as key mediators in cancer progression, acting as carriers for the transfer of oncogenic proteins such as epidermal growth factor receptor variant III (EGFRvIII) and genetic materials (DNA and RNA). Remarkably, recent progress in EV analysis has enabled its purification with high confidence by estimating the purity level of isolated EVs. Thus, mass spectrometry-based proteomic analysis could generate highly reliable vesicular proteomes. Glioblastoma EV proteome studies have revealed the specific increase in vesicular protein cargo due to their oncogenic transformation, and these EV proteins are closely associated with cancer invasion. Moreover, their proteomic data reflects the molecular alterations that occur in parental GBM and provides potent diagnostic information in a minimally invasive manner in liquid biopsy. Thus, proteomic analysis of GBM EVs could provide an increased understanding of their biological properties and activity in the GBM microenvironment, and provide significant implications for advanced approaches in the diagnosis of these intractable tumors.