Identification Strategy of Biological Half Sibling Relationship.

OBJECTIVES: To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and to provide a reference for the setting of relevant standards for identification of half sibling relationship. METHODS: (1) Based on the same genetic marker combinations, the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score (CIBS) and combined full sibling index in actual cases with the distributions in simulated cases. (2) In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters, were calculated. (3) The application value of LR method was compared with that of IBS method, by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. (4) According to the existing simulation data, the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting. RESULTS: (1) After the rank sum test, under the premise that the real relationship and the genetic marker combination tested were the same, there was no significant difference between the simulation method and the results obtained in the actual case. (2) In most cases, under the same conditions, the system effectiveness obtained by LR method was greater than that by IBS method. (3) According to the existing data, the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99. CONCLUSIONS: When distinguishing half sibling from full sibling pairs or unrelated pairs, it is recommended to give preference to the LR method, and estimate the required number of markers according to the identification types and the population data, to ensure the identification effect.

The relationship between serum miR-21 levels and left atrium dilation in elderly patients with essential hypertension.

BACKGROUND: MicroRNA-21 (miR-21) is related to hypertension and cardiac remodelling. Left atrium (LA) dilation is highly sensitive to small haemodynamic changes in the left ventricle (LV) that are induced by hypertension. This study aimed to elucidate the relationship between miR-21 expression and LA dilation in elderly patients with essential hypertension (EH). METHODS: In this cross-sectional study, one hundred elderly patients with EH were recruited for the study. According to their left atrium diameters (LADs), the patients were divided into the LA dilation group [42 patients (42%)] and the no-LA dilation group [58 patients (58%)]. The serum levels of miR-21 and chemical biomarkers used in the clinic, such as creatinine, blood urea nitrogen, uric acid, fasting blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol, Lp(a), apolipoprotein A1 (apoA1), and apolipoprotein B, were measured. All the patients underwent echocardiographic examination, and the LAD, interventricular septum (IVS), right atrium diameter (RAD), right ventricle diameter (RVD), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) were measured. RESULTS: The levels of miR-21 [8.02 (5.21, 14.39) vs. 6.05 (3.81, 8.95), P = 0.011] and LVEF (67.02 ± 3.82 vs. 64.14 ± 4.43, P = 0.001) were higher in the LA dilation group. The levels of creatinine [70.40 (64.45, 80.15) vs. 63.9(60.1, 73.43)], P = 0.020] were higher in the no-LA dilation group. The levels of HDLC (r = - 0.209, P = 0.037), apoA1 (r = -0.269, P = 0.007) and RAD (r = 0.203, P = 0.043) were significantly correlated with miR-21 expression. The LAD was significantly correlated with the RAD (r = 0.287, P = 0.004), RVD (r = 0.450, P < 0.001), LVEDD (r = 0.248, P = 0.013) and LVEF (r = 0.232, P = 0.020). Multivariate logistic regression revealed that miR-21 significantly influenced LA dilation in elderly patients with EH (P < 0.05). CONCLUSIONS: Circulating serum levels of miR-21 are increased in elderly patients with EH with LA dilation. miR-21 levels are significantly correlated with LA dilation in elderly patients with EH, and miR-21 may be a factor related to the clinical pathophysiological occurrence of and treatment for the progression of hypertension-related early heart damage in EH patients.

Protective effect of miRNA-containing extracellular vesicles derived from mesenchymal stromal cells of old rats on renal function in chronic kidney disease.

INTRODUCTION: Mesenchymal stromal cells (MSCs) play an important role in the prevention of cell and tissue fibrosis. Senescence may decrease the function of MSCs during recovery from tissue and organ damage. Extracellular vesicles (EVs) released from MSCs contribute to the repair of kidney injury. We explored the influence of senescence on EVs derived from MSCs (MSC-EVs) and detected the protective effects of MSC-EVs expressing low levels of miR-294/miR-133 derived from old rats against chronic kidney disease (CKD). METHODS: The effects of MSC-EVs derived from 3-month-old and 18-month-old male Fisher 344 rats on renal fibrosis were explored in a unilateral ureteral obstruction (UUO) model. pLV-miR-294/pLV-miR-133 mimic/inhibitor were injected into young and old rats before UUO to detect the effects of miR-294/miR-133, which were decreased in MSC-EVs and sera from old rats, on renal function in CKD. Transforming growth factor-ß1 (TGF-ß1)-induced human renal proximal tubular epithelial (HK2) cells were used to imitate the pathological process of renal fibrosis in vitro. Western blotting was used to assess the expression of epithelial/mesenchymal markers and phosphorylation of proteins in HK2 cells. RESULTS: The inhibition of UUO-induced CKD by MSC-EVs was weaker in old rats than in young rats. Downregulation of miRNAs (miR-294 and miR-133) in both MSC-EVs and sera from old rats obviously attenuated UUO-induced renal injury in old rats. miR-294 and miR-133 overexpression mitigated TGF-ß1-mediated epithelial-mesenchymal transition (EMT) in HK2 cells, and the obvious increase in the phosphorylation of both SMAD2/3 and ERK1/2 induced by TGF-ß1 was prevented in miR-294- and miR-133-overexpressing HK2 cells. CONCLUSIONS: The ability of MSC-EVs to inhibit renal fibrosis decreased with age. miR-294/miR-133 in MSC-EVs and sera had an important effect on renal fibrosis in old rats and on EMT in HK2 cells. Furthermore, miR-294/miR-133 overexpression prevented SMAD2/3 and ERK1/2 phosphorylation in HK2 cells during TGF-ß1-mediated EMT. These findings show that miR-294/miR-133 may be therapeutic in renal fibrosis and related renal dysfunction in elderly individuals.