Improved Differentiation of Mesenchymal Stem Cells into Hepatocyte-like Cells using FGF4 and IGF-1 in 3D Culture

Human Umbilical Cord Mesenchymal Stem Cells (UCMSCs) are considered as an excellent candidate for cell therapy to treat end-stage liver disease. Fibroblast Growth Factor-4 (FGF4), Hepatocyte Growth Factor, and Insulin-like Growth Factor-1 are some of the critical cytokines involved in liver development and regeneration. To evaluate the differentiation potency of cells into hepatocyte-like cells we used these cytokines. UCMSCs were isolated from Wharton's jelly of fullterm infants. The cells were characterized as MSCs by flow-cytometry and their multilineage differentiation capacity. Then, UCMSCs were cultured in 3D collagen scaffold and hepatogenic media with or without FGF4 for 21 days and the data were compared to control. The expression of liver specific genes was evaluated by real-time quantitative RT-PCR and immunocytochemistry. These cells expressed MSC markers and could differentiate into adipocytes and osteocytes. A non–significant higher level of liver specific genes, such as cytokeratin-18 and 19, alpha-fetoprotein and albumin, and also a significant higher level of CYP2B6 expressed by UCMSCs in hepatogenic medium containing FGF4 compared with control. In some specimens, cytokeratin-19-positive cells surrounded a luminal space within collagen scaffolds. Liver-specific marker expression was increased by pre-exposing the cells to FGF4 before treating with IGF-1 and HGF in 3D collagen scaffold. Abbreviations: UCMSCs: Human Umbilical Cord Mesenchymal Stem Cells; FGF4: Fibroblast Growth Factor 4; HGF: Hepatocyte Growth Factor; IGF-1: Insulin-like Growth Factor-1; MSCs: Mesenchymal Stem Cells; ICG: Indocyanine green; PAS: periodic acid Schiff; CK-18: cytokeratin-18; CK-19: Cytokeratin-19; AFP: alpha-fetoprotein; G6P: glucose 6 phosphatase; PEPCK: phosphoenolpyruvate carboxykinase; TAT: tyrosine amino transferase; FBS: Fetal Bovine Serum; OSM: oncostatin M; RT-PCR: Reverse Transcription Polymerase Chain Reaction; PBS: Phosphate-Buffered Saline; Hep- Par1: Hepatocyte paraffin 1; DAB: Diaminobenzidine; CYP2B6: Cytochrome P450 2B6

Determination of maternal risk factors of preterm delivery: Adjusted for sparse data bias; results from a population-based case-control study in Iran

Objective To determine the maternal risk factors associated with preterm delivery in Iran. Methods A population-based case-control study was conducted including 48 women having preterm delivery (case group) and 100 women having term delivery (control group) between March 2007 and March 2012 in the maternity hospitals of the Selseleh County, Lorestan province, Iran. Information regarding maternal risk factors was collected by structured interview and reviewing the medical records. The maternal risk factors associated with preterm delivery were identified using univariate and multivariable logistic regression analysis after adjusting the sparse data bias. The area under the receiver operating characteristic (ROC) curves was estimated to evaluate the discrimination power of the statistical models. Results Multivariable analysis demonstrated that multiparty (odds ratio OR, 14.23; 95% confidence interval CI, 1.60-127.05), history of gestational diabetes (OR, 0.10; 95% CI, 0.01-0.99), thyroid dysfunction (OR, 97.32; 95% CI, 5.78-1,637.80), urinary tract infection (OR, 16.60; 95% CI, 3.20-85.92), and taking care during pregnancy (OR, 0.12; 95% CI, 0.03-0.50) had significant impact on preterm delivery after adjusting the potential confounders. The area under the ROC curve for the aforementioned maternal risk factors was 0.86 (95% CI, 0.80-0.92). Conclusion Our study provides evidence for the associations between multiparty, history of gestational diabetes, thyroid dysfunction, urinary tract infection, as well as taking care during pregnancy, and preterm delivery. © 2020 Korean Society of Obstetrics and Gynecology

Apigenin as Tumor Suppressor in Cancers: Biotherapeutic Activity, Nanodelivery, and Mechanisms With Emphasis on Pancreatic Cancer

Pancreatic cancer is the most lethal malignancy of the gastrointestinal tract. Due to its propensity for early local and distant spread, affected patients possess extremely poor prognosis. Currently applied treatments are not effective enough to eradicate all cancer cells, and minimize their migration. Besides, these treatments are associated with adverse effects on normal cells and organs. These therapies are not able to increase the overall survival rate of patients; hence, finding novel adjuvants or alternatives is so essential. Up to now, medicinal herbs were utilized for therapeutic goals. Herbal-based medicine, as traditional biotherapeutics, were employed for cancer treatment. Of them, apigenin, as a bioactive flavonoid that possesses numerous biological properties (e.g., anti-inflammatory and anti-oxidant effects), has shown substantial anticancer activity. It seems that apigenin is capable of suppressing the proliferation of cancer cells via the induction of cell cycle arrest and apoptosis. Besides, apigenin inhibits metastasis via down-regulation of matrix metalloproteinases and the Akt signaling pathway. In pancreatic cancer cells, apigenin sensitizes cells in chemotherapy, and affects molecular pathways such as the hypoxia inducible factor (HIF), vascular endothelial growth factor (VEGF), and glucose transporter-1 (GLUT-1). Herein, the biotherapeutic activity of apigenin and its mechanisms toward cancer cells are presented in the current review to shed some light on anti-tumor activity of apigenin in different cancers, with an emphasis on pancreatic cancer. © Copyright © 2020 Ashrafizadeh, Bakhoda, Bahmanpour, Ilkhani, Zarrabi, Makvandi, Khan, Mazaheri, Darvish and Mirzaei

Synthesis and characterization of thermosensitive hydrogel based on quaternized chitosan for intranasal delivery of insulin

Nasal administration is a form of systemic administration in which drugs are insufflated through the nasal cavity. Steroids, nicotine replacement, antimigraine drugs, and peptide drugs are examples of the available systematically active drugs as nasal sprays. For diabetic patients who need to use insulin daily, the nasal pathway can be used as an alternative to subcutaneous injection. In this regard, intranasal insulin delivery as a user-friendly and systemic administration has recently attracted more attention. In this study, a novel formulation consists of chitosan, chitosan quaternary ammonium salt (HTCC), and gelatin (Gel) was proposed and examined as a feasible carrier for intranasal insulin administration. First, the optimization of the chitosan�HTCC hydrogel combination has done. Afterward, Gel with various amounts blended with the chitosan�HTCC optimized samples. In the next step, swelling rate, gelation time, degradation, adhesion, and other mechanical, chemical, and biological properties of the hydrogels were studied. Finally, insulin in clinical formulation and dosage was blended with optimized thermosensitive hydrogel and the release procedure of insulin was studied with electrochemiluminescence technique. The optimal formulation (consisted of 2 wt chitosan, 1 wt HTCC, and 0.5 wt Gel) showed low gelation time, uniform pore structure, and the desirable swelling rate, which were resulted in the adequate encapsulation and prolonged release of insulin in 24 H. The optimal samples released 65 of the total amount of insulin in the first 24 H, which is favorable for this study. © 2020 International Union of Biochemistry and Molecular Biology, Inc

Modelling corrosion rate of biodegradable magnesium-based alloys: the case study of Mg-Zn-RE-xCa (x = 0, 0.5, 1.5, 3 and 6 wt%) alloys

The ternary Mg-Zn-RE and the quaternary Mg-Zn-RE-xCa (x = 0.5, 1.5, 3 and 6 wt%) alloys are evaluated in term of their corrosion rate both experimentally and theoretically. According to the electrochemical tests, the quaternary Mg-Zn-RE-0.5Ca alloy possess a lower corrosion current density (icorr) and higher charge transfer resistance (Rt) compared to the ternary Mg-Zn-RE alloy. However, as the Ca increases, icorr and Rt tend toward the higher and lower values, respectively. Immersion tests also show that the addition of 0.5 wt% Ca decreases the corrosion rate of the Mg-Zn-RE alloy. This despite the fact that with increasing the Ca content to 6 wt% a significant increase occurs in the corrosion rate as a result of the galvanic coupling effect. The study also defines a new reliability simulation framework to predict the corrosion behavior of the Mg-based alloys using gene expression programming (GEP) tool. For this purpose a colossal database is collected from the literature and all of the parameters affecting the corrosion rate are introduced to the GEP model. Two case study on the ternary Mg-Zn-RE and the quaternary Mg-Zn-RE-xCa (x = 0.5, 1.5, 3 and 6 wt%) alloys are also conducted to evaluate the accuracy of the presented GEP model. according to the results obtained, the maximum error of the presented model in the predicting corrosion rate was close to 0.5 mm/yr which is promising result

Non-coding RNAs underlying chemoresistance in gastric cancer.

BackgroundGastric cancer (GC) is a major health issue in the Western world. Current clinical imperatives for this disease include the identification of more effective biomarkers to detect GC at early stages and enhance the prevention and treatment of metastatic and chemoresistant GC. The advent of non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long-non coding RNAs (lncRNAs), has led to a better understanding of the mechanisms by which GC cells acquire features of therapy resistance. ncRNAs play critical roles in normal physiology, but their dysregulation has been detected in a variety of cancers, including GC. A subset of ncRNAs is GC-specific, implying their potential application as biomarkers and/or therapeutic targets. Hence, evaluating the specific functions of ncRNAs will help to expand novel treatment options for GC.ConclusionsIn this review, we summarize some of the well-known ncRNAs that play a role in the development and progression of GC. We also review the application of such ncRNAs in clinical diagnostics and trials as potential biomarkers. Obviously, a deeper understanding of the biology and function of ncRNAs underlying chemoresistance can broaden horizons toward the development of personalized therapy against GC