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

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

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

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

A novel mutation in the ALS2 gene in an iranian kurdish family with juvenile amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a rare disorder that affects both upper and lower motor neurons. Mutations in Alsin Rho Guanine Nucleotide Exchange Factor (ALS2) correlates with three similar but distinctive syndromes, including the juvenile form of ALS. An Iranian Kurdish family was involved in this study and all members were evaluated with relevant clinical guidelines. Whole exome sequencing and sanger sequencing were applied to all family members to undermine the possible genetic factors. A substitution c. 2110 C>T (p. Arg704X) identified in the ALS2 gene. Bioinformatics analysis indicated the mutation is located in the well-conserved and functional domain of the protein. This study recognized a novel mutation in the ALS2 gene in a proband with the juvenile form of ALS. To our knowledge, this is the first identified ALS2 mutation among the Iranian population. © 2022 World Federation of Neurology on behalf of the Research Group on Motor Neuron Diseases

Pathogenic role of exosomes and microRNAs in HPV-mediated inflammation and cervical cancer: A review

Cervical cancer (CC) is the fourth most common cause of cancer death in women. The most important risk factor for the development of CC is cervical infection with human papilloma virus (HPV). Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response. Inflammation is beneficial if it is brief and well controlled; however, if the inflammation is excessive or it becomes of chronic duration, it can produce detrimental effects. HPV proteins are involved, both directly and indirectly, in the development of chronic inflammation, which is a causal factor in the development of CC. However, other factors may also have a potential role in stimulating chronic inflammation. MicroRNAs (miRNAs) (a class of noncoding RNAs) are strong regulators of gene expression. They have emerged as key players in several biological processes, including inflammatory pathways. Abnormal expression of miRNAs may be linked to the induction of inflammation that occurs in CC. Exosomes are a subset of extracellular vesicles shed by almost all types of cells, which can function as cargo transfer vehicles. Exosomes contain proteins and genetic material (including miRNAs) derived from their parent cells and can potentially affect recipient cells. Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response. In this review, we discuss the role of HPV proteins, miRNAs and exosomes in the inflammation associated with CC. © 2019 UIC

Pathogenic role of exosomes and microRNAs in HPV-mediated inflammation and cervical cancer: A review

Cervical cancer (CC) is the fourth most common cause of cancer death in women. The most important risk factor for the development of CC is cervical infection with human papilloma virus (HPV). Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response. Inflammation is beneficial if it is brief and well controlled; however, if the inflammation is excessive or it becomes of chronic duration, it can produce detrimental effects. HPV proteins are involved, both directly and indirectly, in the development of chronic inflammation, which is a causal factor in the development of CC. However, other factors may also have a potential role in stimulating chronic inflammation. MicroRNAs (miRNAs) (a class of noncoding RNAs) are strong regulators of gene expression. They have emerged as key players in several biological processes, including inflammatory pathways. Abnormal expression of miRNAs may be linked to the induction of inflammation that occurs in CC. Exosomes are a subset of extracellular vesicles shed by almost all types of cells, which can function as cargo transfer vehicles. Exosomes contain proteins and genetic material (including miRNAs) derived from their parent cells and can potentially affect recipient cells. Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response. In this review, we discuss the role of HPV proteins, miRNAs and exosomes in the inflammation associated with CC. © 2019 UIC

On-line monitoring of methanol and methyl formate in the exhaust gas of an industrial formaldehyde production plant by a mid-IR gas sensor based on tunable Fabry-Pérot filter technology

On-line monitoring of key chemicals in an industrial production plant ensures economic operation, guarantees the desired product quality, and provides additional in-depth information on the involved chemical processes. For that purpose, rapid, rugged, and flexible measurement systems at reasonable cost are required. Here, we present the application of a flexible mid-IR filtometer for industrial gas sensing. The developed prototype consists of a modulated thermal infrared source, a temperature-controlled gas cell for absorption measurement and an integrated device consisting of a Fabry-Pérot interferometer and a pyroelectric mid-IR detector. The prototype was calibrated in the research laboratory at TU Wien for measuring methanol and methyl formate in the concentration ranges from 660 to 4390 and 747 to 4610 ppmV. Subsequently, the prototype was transferred and installed at the project partner Metadynea Austria GmbH and linked to their Process Control System via a dedicated micro-controller and used for on-line monitoring of the process off-gas. Up to five process streams were sequentially monitored in a fully automated manner. The obtained readings for methanol and methyl formate concentrations provided useful information on the efficiency and correct functioning of the process plant. Of special interest for industry is the now added capability to monitor the start-up phase and process irregularities with high time resolution (5 s).Austrian research funding association (FFG) COMET753761