The protective effect of coenzyme Q10 and berberine on sperm parameters, with and without varicocelectomy in rats with surgically induced varicoceles

The current study aimed to investigate the protective effects of coenzyme Q10 (Co Q10) and berberine (BB) with and without varicocelectomy on sperm parameters in postoperative varicocele rats. For the current purpose, a total of 60 mature male Wistar rats were randomly divided into control (n = 6 rats), control-sham (n = 6 rats), and experimental (n = 6 rats) groups. The animals in the experimental groups were undergone experimental varicocele, and simple laparotomy was performed in control-sham group. The experimental group was subdivided into the following groups 60 days after varicocele (VCL) induction: non-treated VCL-induced rats (n = 6 rats), VCL-induced rats administered 100 mg (kg per day) BB (n = 6 rats), VCL-induced rats administered Co Q10 75 mg (kg per day) (n = 6 rats), VCL-induced rats administered 100 mg (kg per day) BB + Co Q10 75 mg (kg per day) (n = 6 rats), varicocelectomy rats (n = 6 rats), varicocelectomy rats administered 100 mg (kg per day) BB (n = 6 rats), varicocelectomy rats administered Co Q10 75 mg (kg per day) (n = 6 rats), varicocelectomy rats administered 100 mg (kg per day) BB + Co Q10 75 mg (kg per day) (n = 6 rats). Following 60 days, the animals were euthanized and sperm parameters were evaluated. Non-treated VCL-induced animals indicated a significant (P < 0.05) decrease in sperm parameters and a significant (P < 0.05) increase in sperm DNA damage compared to control and control-sham groups. Insignificant changes were found between control and control-sham groups. Meanwhile, each treatment group showed a remarkable (P < 0.05) increase in sperm parameters as well as a significant (P < 0.05) decrease in sperm DNA damage. Based on current results, BB and Co Q10 alone and/or together could improve sperm parameters and reduce sperm DNA damage in varicocele-induced rats compared to control and control-sham groups. Varicocelectomy alone will improve sperm parameters, but this recovery will be greater when combined with Co Q10 and BB. © 2018, Springer-Verlag London Ltd., part of Springer Nature

MicroRNAs-mediated regulation pathways in rheumatic diseases

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are two common rheumatic disorders marked by persistent inflammatory joint disease. Patients with RA have osteodestructive symptoms, but those with AS have osteoproliferative manifestations. Ligaments, joints, tendons, bones, and muscles are all affected by rheumatic disorders. In recent years, many epigenetic factors contributing to the pathogenesis of rheumatoid disorders have been studied. MicroRNAs (miRNAs) are small, non-coding RNA molecules implicated as potential therapeutic targets or biomarkers in rheumatic diseases. MiRNAs play a critical role in the modulation of bone homeostasis and joint remodeling by controlling fibroblast-like synoviocytes (FLSs), chondrocytes, and osteocytes. Several miRNAs have been shown to be dysregulated in rheumatic diseases, including miR-10a, 16, 17, 18a, 19, 20a, 21, 27a, 29a, 34a, 103a, 125b, 132, 137, 143, 145, 146a, 155, 192, 203, 221, 222, 301a, 346, and 548a.The major molecular pathways governed by miRNAs in these cells are Wnt, bone-morphogenic protein (BMP), nuclear factor (NF)-kappa B, receptor activator of NF-kappa B (RANK)-RANK ligand (RANKL), and macrophage colony-stimulating factor (M-CSF) receptor pathway. This review aimed to provide an overview of the most important signaling pathways controlled by miRNAs in rheumatic diseases

MicroRNAs-mediated regulation pathways in rheumatic diseases

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are two common rheumatic disorders marked by persistent inflammatory joint disease. Patients with RA have osteodestructive symptoms, but those with AS have osteoproliferative manifestations. Ligaments, joints, tendons, bones, and muscles are all affected by rheumatic disorders. In recent years, many epigenetic factors contributing to the pathogenesis of rheumatoid disorders have been studied. MicroRNAs (miRNAs) are small, non-coding RNA molecules implicated as potential therapeutic targets or biomarkers in rheumatic diseases. MiRNAs play a critical role in the modulation of bone homeostasis and joint remodeling by controlling fibroblast-like synoviocytes (FLSs), chondrocytes, and osteocytes. Several miRNAs have been shown to be dysregulated in rheumatic diseases, including miR-10a, 16, 17, 18a, 19, 20a, 21, 27a, 29a, 34a, 103a, 125b, 132, 137, 143, 145, 146a, 155, 192, 203, 221, 222, 301a, 346, and 548a.The major molecular pathways governed by miRNAs in these cells are Wnt, bone-morphogenic protein (BMP), nuclear factor (NF)-kappa B, receptor activator of NF-kappa B (RANK)-RANK ligand (RANKL), and macrophage colony-stimulating factor (M-CSF) receptor pathway. This review aimed to provide an overview of the most important signaling pathways controlled by miRNAs in rheumatic diseases

Decellularized amniotic membrane Scaffolds improve differentiation of iPSCs to functional hepatocyte-like cells

Human-induced pluripotent stem cells-derived hepatocyte-like cells (hiPSCs-HLCs) holds considerable promise for future clinical personalized therapy of liver disease. However, the low engraftment of these cells in the damaged liver microenvironment is still an obstacle for potential application. In this study, we explored the effectiveness of decellularized amniotic membrane (dAM) matrices for culturing of iPSCs and promoting their differentiation into HLCs. The DNA content assay and histological evaluation indicated that cellular and nuclear residues were efficiently eliminated and the AM extracellular matrix component was maintained during decelluarization. DAM matrices were developed as three-dimensional scaffolds and hiPSCs were seeded into these scaffolds in defined induction media. In dAM scaffolds, hiPSCs-HLCs gradually took a typical shape of hepatocytes (polygonal morphology). HiPSCs-HLCs that were cultured into dAM scaffolds showed a higher level of hepatic markers than those cultured in tissue culture plates (TCPs). Moreover, functional activities in term of albumin and urea synthesis and CYP3A activity were significantly higher in dAM scaffolds than TCPs over the same differentiation period. Thus, based on our results, dAM scaffold might have a considerable potential in liver tissue engineering, because it can improve hepatic differentiation of hiPSCs which exhibited higher level of the hepatic marker and more stable metabolic functions. © 2019 Wiley Periodicals, Inc

Micro-RNA-incorporated electrospun nanofibers improve osteogenic differentiation of human-induced pluripotent stem cells

Smart scaffolds have a great role in the damaged tissue reconstruction. The aim of this study was developing a scaffold that in addition to its fiber's topography has also content of micro-RNAs (miRNAs), which play a regulatory role during osteogenesis. In this study, we inserted two important miRNAs, including miR-22 and miR-126 in the electrospun polycaprolactone (PCL) nanofibers and after scaffold characterization, osteoinductivity of the fabricated nanofibers was investigated by evaluating of the osteogenic differentiation potential of induced pluripotent stem cells (iPSCs) when grown on miRNAs-incorporated PCL nanofibers (PCL-miR) and empty PCL. MiRNAs incorporation had no effect on the fibers size and morphology, cell attachment, and protein adsorption, although viability and proliferation rate of the human iPSCs were increased after a week in PCL-miR compared to the empty PCL. The results obtained from alkaline phosphatase activity, calcium content, bone-related genes, and proteins expression assays demonstrated that the highest osteogenic markers were observed in iPSCs grown on the PCL-miR compared to the cells cultured on PCL and culture plate. According to the results, miR-incorporated PCL nanofibers could be considered as a promising potential tissue-engineered construct for the treatment of patients with bone lesions and defects. © 2019 Wiley Periodicals, Inc

PCL/PVA nanofibrous scaffold improve insulin-producing cells generation from human induced pluripotent stem cells

Pancreatic differentiation of stem cells will aid treatment of patients with type I diabetes mellitus (T1DM). Synthetic biopolymers utilization provided extracellular matrix (ECM) and desired attributes in vitro to enhance conditions for stem cells proliferation, attachment and differentiation. A mixture of polycaprolactone and polyvinyl alcohol (PCL/PVA)-based scaffold, could establish an in vitro three-dimensional (3D) culture model. The objective of this study was investigation of the human induced pluripotent stem cells (hiPSCs) differentiation capacity to insulin-producing cells (IPCs) in 3D culture were compared with conventional culture (2D) groups evaluated at the mRNA and protein levels by quantitative PCR and immunofluorescence assay, respectively. The functionality of differentiated IPCs was assessed by C-peptide and insulin release in response to glucose stimulation test. Real-Time PCR results showed that iPSCs-IPCs expressed pancreas-specific transcription factors (Insulin, Pdx1, Glucagon, Glut2 and Ngn3). The expressions of these transcription factors in PCL/PVA scaffold were higher than 2D groups. In addition to IPCs specific markers were detected by immunochemistry. These cells in both groups secreted insulin and C-peptide in a glucose challenge test by ELISA showing in vitro maturation. The results of current study demonstrated that enhanced differentiation of IPCs from hiPSCs could be result of PCL/PVA nanofibrous scaffolds. In conclusion, this research could provide a new approach to beta-like cells replacement therapies and pancreatic tissue engineering for T1DM in the futur

Improved osteogenic differentiation of human induced pluripotent stem cells cultured on polyvinylidene fluoride/collagen/platelet-rich plasma composite nanofibers

Blood transfusion or blood products, such as plasma, have a long history in improving health, but today, platelet-rich plasma (PRP) is used in various medical areas such as surgery, orthopedics, and rheumatology in many ways. Considering the high efficiency of tissue engineering in repairing bone defects, in this study, we investigated the combined effect of nanofibrous scaffolds in combination with PRP on the osteogenic differentiation potential of human induced pluripotent stem cells (iPSCs). Electrospinning was used for fabricating nanofibrous scaffolds by polyvinylidene fluoride/collagen (PVDF/col) with and without PRP. After scaffold characterization, the osteoinductivity of the fabricated scaffolds was studied by culturing human iPSCs under osteogenic medium. The results showed that PRP has a considerable positive effect on the biocompatibility of the PVDF/col nanofibrous scaffold when examined by protein adsorption, cell attachment, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. In addition, the results obtained from alkaline phosphatase activity and calcium content assays demonstrated that nanofibers have higher osteoinductivity while grown on PRP-incorporated PVDF/col nanofibers. These results were also confirmed while the osteogenic differentiation of the iPSCs was more investigated by evaluating the most important bone-related genes expression level. According to the results, it can be concluded that PVDF/col/PRP has much more osteoinductivity while compared with the PVDF/col, and it can be introduced as a promising bone bio-implant for use in bone tissue engineering applications. © 2019 Wiley Periodicals, Inc