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Background: Islet cell transplantation is an emerging therapy in the treatment of diabetes mellitus. Differentiation of islet cells from mesenchymal stem cells (MSCs) is a potential solution to the challenge of insufficient donor sources. This study investigated whether human umbilical cord‐derived MSCs could effectively differentiate into insulin‐producing cells (IPCs) and evaluated the therapeutic efficacy of IPCs in treating diabetes. Methods: IPCs were induced from MSCs by a two‐step protocol. IPC expression products were evaluated by western blot and real‐time PCR. IPC insulin secretion was evaluated by ELISA. The viability of IPCs was measured by FDA/PI and dithizone staining. The non‐human primate tree shrew was used as a diabetes model. After a single STZ induction into a diabetes model, a single intraportal transplantation of IPCs, MSCs, or normal saline was performed (n = 6 per group). Blood glucose was monitored for 3 weeks, then the animals were euthanized and the distribution of IPCs in the liver was examined pathologically. Results: After about 3 weeks of in vitro induction, IPCs formed microspheres of 100–200 μm, with >95% viable cells that were dithizone stain positive. IPCs expressed islet‐related genes and proteins and secreted high levels of insulin whether stimulated by low or high levels of glucose. After transplantation of IPCs into diabetic tree shrews, blood glucose levels decreased rapidly to near normal and were significantly lower than the MSC or saline groups for 3 weeks thereafter. Conclusion: We present the novel discovery that IPCs derived from human umbilical cord MSCs exert a therapeutic effect in a non‐human primate model of diabetes. This study provides a preliminary experimental basis for the use of autologous MSC‐derived IPCs in the treatment of human diabetes. [ABSTRACT FROM AUTHOR]

Context: The association between visceral adipose tissue (VAT) and pre-eclampsia (PE) shows inconsistent results and the underlying mediator remains unknown. Objective: We aimed to explore the causal effect of VAT on PE risks and the mediation role of age at menarche (AAM) in explaining this relationship. Methods: Summary data for PE were obtained from the FinnGen genome-wide association study (3556 cases and 114 735 controls). For exposure data, 70 genetic variants associated with the predicted VAT in 161 149 European women from UK Biobank were used as instrumental variables. Inverse variance weighted and multiple sensitivity analyses were applied. We also conducted multivariable Mendelian randomization (MR) analyses to test the association between VAT-associated single-nucleotide variations and PE. Next, mediation analyses were performed to study whether the association between VAT and PE was mediated via AAM. Results: In univariable MR analysis, higher volume of VAT was associated with the advancement of AAM and increased PE risk (beta=−0.33; 95% CI, −0.49 to −0.16 for AAM; odds ratio 1.65, 95% CI, 1.23 to 2.20 for PE). After adjusting for waist circumference, waist to hip ratio, and hip circumference, the multivariable MR results presented the consistent positive causality of VAT on PE. Two-step MR analysis proved an estimated 14.3% of the positive effect of VAT on PE was mediated by AAM. Conclusion: Our findings provided evidence of the causal relationship between VAT and PE and proved VAT could accelerate AAM and then contribute to the risk of incident PE. [ABSTRACT FROM AUTHOR]

In thiswork, a methodology for characterizing reservoir pore pressure and permeability during underbalanced drilling of horizontal wells was presented. The methodology utilizes a transient multiphase wellbore flow model that is extended with a transient well influx analytical model during underbalanced drilling of horizontal wells. The effects of the density behavior of drilling fluid and wellbore heat transfer are considered in our wellbore flow model. Based on Kneissl's methodology, an improved method with a different testing procedure was used to estimate the reservoir pore pressure by introducing fluctuations in the bottomhole pressure. To acquire timely basic data for reservoir characterization, a dedicated fully automated control real-time data monitoring system was established. The methodology is applied to a realistic case, and the results indicate that the estimated reservoir pore pressure and permeability fit well to the truth values from well test after drilling. The results also show that the real-time data monitoring system is operational and can provide accurate and complete data set in real time for reservoir characterization. The methodology can handle reservoir characterization during underbalanced drilling of horizontal wells. [ABSTRACT FROM AUTHOR]