The Efficacy of Transplanting Human Umbilical Cord Mesenchymal Stem Cell Sheets in the Treatment of Myocardial Infarction in Mice.

The transplantation of mesenchymal stem cell (MSC) sheets derived from human umbilical cords (hUCs) was investigated in this study as a potential application in treating myocardial infarction (MI). Two groups of hUC-MSC sheets were formed by populating LunaGelTM, which are 3D scaffolds of photo-crosslinkable gelatin-based hydrogel with two different cell densities. An MI model was created by ligating the left anterior descending coronary artery of healthy BALB/c mice. After two weeks, the cell sheets were applied directly to the MI area and the efficacy of the treatment was evaluated over the next two weeks by monitoring the mice's weight, evaluating the left ventricle ejection fraction, and assessing the histology of the heart tissue at the end of the experiment. Higher cell density showed significantly greater efficiency in MI mice treatment in terms of weight gain and the recovery of ejection fraction. The heart tissue of the groups receiving cell sheets showed human-CD44-positive staining and reduced fibrosis and apoptosis. In conclusion, the hUC-MSC sheets ameliorated heart MI injury in mice and the efficacy of the cell sheets improved as the number of cells increased.

Encapsulation of Human Umbilical Cord Mesenchymal Stem Cells in LunaGel Photocrosslinkable Extracellular Matrix and Subcutaneous Transplantation in Mice.

Stem cells have significant potential in regenerative medicines. However, a major issue with implanting stem cells in the regeneration of new tissue is the methods to implant them and cell viability and functions before and after implantation. Here we developed a simple yet effective method that used photo-crosslinkable gelatin-based hydrogel (LunaGelTM) as a scaffold for the encapsulation, expansion, and eventually, transplantation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) into mice subcutaneously. We demonstrated the proliferation and maintenance of the original expression of mesenchymal stem cell markers as well as the ability to differentiate into mesoderm-derived cells. The hydrogel was highly stable with no signs of degradation after 20 days in PBS. The hUC-MSCs remained viable after transplantation into mice's subcutaneous pockets and migrated to integrate with the surrounding tissues. We showed a collagen-rich layer surrounding the transplanted cell-laden scaffold indicating the effects of growth factors secreted by the hUC-MSCs. A connective tissue layer was found between the implanted cell-laden scaffold and the collagen layer, and immunohistochemical staining results suggested that this tissue was derived from the MSCs which migrated from within the scaffold. The results, thus, also suggested a protective effect the scaffold has on the encapsulated cells from the antibodies and cytotoxic cells of the host immune system.

Stem cell sheet fabrication from human umbilical cord mesenchymal stem cell and Col-T scaffold.

Today, stem cell therapy has been shown to be a remarkable progress and an important application in the regeneration of defective tissues and organs. To deliver stem cells to the injured area, several methods have been proposed such as an intravenous infusion, direct damaged tissue injection, or stem cell sheet transplantation. In this study, we aimed to fabricate a stem cell sheet by culturing human umbilical cord mesenchymal stem cells (hUC-MSCs) on a Col-T scaffold to recover the structure and function of damaged tissues. The results showed that cells reach confluent on the scaffold surface 18 h after seeding. These stem cells were able to survive and proliferate on Col-T scaffold. The average tensile strength of the stem cell sheet was 2.65 MPa. The sheet reached the sterile standards when tested for total bacteria, Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus according to Circular number 06/2011/TT-BYT of Vietnam Ministry of Health. In addition, the stem cell sheet was non-toxic when evaluated for exposure toxicity and fluid toxicity according to iSO-10993. Importantly, 5 days after culturing on the Col-T scaffold, the seeded hUC-MSCs were still possessed all properties of MSC such as spindle-shaped, adhesive, could differentiate into mesoderm-derived cells, showed to be CD90, CD105, CD73 positive and CD45, CD34, CD11b, CD19, HLA-DR negative. In summary, our study was successful in creating a stem cell sheet from hUC-MSCs and Col-T scaffold for subsequent in vivo transplantation in the future.

Anti-Aging Effects of a Serum Based on Coconut Oil Combined with Deer Antler Stem Cell Extract on a Mouse Model of Skin Aging.

Anti-aging is one of the top goals in the field of health care and aesthetics. Anti-aging cosmetics derived from nature are oriented to long-term development, bringing safety to users and being environmentally friendly. The aim of this study was to develop an anti-aging cosmetic formulation process based on coconut oil in combination with deer antler stem cell extract. The results show that the presence of deer antler stem cell extract added to the foundation made the serum product highly stable and helped improve skin aging significantly after 2 weeks of use. The skin site where the serum product was applied showed a smooth and elastic skin surface, with very few fine lines and shallow wrinkles. Serum reduced the number of wrinkles (48.09% compared to commercial serum (ME) and 60.31% compared to positive control (PC)), reduced skin recovery time (39.31% compared to ME and 67.1% of PC) after two weeks of use. After 2 weeks of use, collagen density increased 10.18% compared to ME and 63.76% compared to control. Epidermal thickness increased by 106.1% compared to PC and 121.7% compared to ME.

Radiation Synthesis of Selenium Nanoparticles Capped with ß-Glucan and Its Immunostimulant Activity in Cytoxan-Induced Immunosuppressed Mice.

Selenium nanoparticles (SeNPs) with diameters from 64.8 to 110.1 nm were successfully synthesized by γ-irradiation of solutions containing Se4+ and water-soluble yeast ß-glucan. The size and size distribution of SeNPs were analyzed by dynamic light scattering (DLS). Analytical X-ray diffraction (XRD) pattern results confirmed the crystal structure of the Se nanoparticles and Fourier transform infrared (FTIR) spectroscopy revealed that ß-glucan could interact with SeNPs through steric (Se…O) linkages leading to a homogeneous and translucent solution state for 60 days without any precipitates. In vivo tests in cytoxan-induced immunosuppressed mice revealed that the daily supplementation of SeNPs/ß-glucan at concentrations of 6 mg per kg body weight of tested mice significantly stimulated the generation of cellular immune factors (white blood cells, neutrophil, lymphocyte, B cells, CD4+ cells, CD34+ cells and natural killer cells) and humoral immune indexes (IgM, IgG, TNF-α, IFN-γ and IL-2) in peripheral blood, bone marrow and spleen of the immunosuppressed mice. The obtained results indicated that radiation-synthesized SeNPs/ß-glucan may be a candidate for further evaluation as an agent for the prevention of immunosuppression in chemotherapy.

Recurrent BRCA1 Mutation, but no BRCA2 Mutation, in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing.

BACKGROUND: Identification of germline and somatic BRCA1/2 mutations in ovarian cancer is important for genetic counseling and treatment decision making with poly ADP ribose polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 mutations in Vietnamese patients are scare. METHODS: We aim to explore the occurrence of BRCA1/2 mutations in 101 Vietnamese patients with ovarian cancer including serous (n = 58), endometrioid (n = 14), mucinous (n = 24), and clear cell (n = 5) carcinomas. BRCA1/2 mutations were detected from formalin-fixed parafin-embedded tumor samples using the OncomineTM BRCA Research Assay on Personal Genome Machine Platform with Ion Reporter Software for sequencing data analysis. The presence of pathogenic mutations was confirmed by Sanger sequencing. RESULTS: We found no BRCA2 mutation in the entire cohort. Four types of pathogenic mutations in BRCA1 (Ser454Ter, Gln541Ter, Arg1751Ter, and Gln1779AsnfsTer14) were detected in 8 unrelated patients (7.9%) belonging to serous and endometrioid carcinoma groups. Except for the c.1360_1361delAG (Ser454Ter) mutation in BRCA1 exon 11 that was somatic, the other mutations in exons 11, 20, and 22 were germline.  Interestingly, the recurrent Arg1751Ter mutation in BRCA1 exon 20 appeared in 4 patients, suggesting that this is a founder mutation in Vietnamese patients. CONCLUSION: Mutational analysis of tumor tissue using next generation sequencing allowed the detection of both germline and somatic BRCA1/2 mutations.
.

Involvement of the N-terminal portion of influenza virus RNA polymerase subunit PB1 in nucleotide recognition.

The influenza virus PB1 protein functions as a catalytic subunit of the viral RNA-dependent RNA polymerase and contains the highly conserved motifs of RNA-dependent RNA polymerases together with putative nucleotide-binding sites. PB1 also binds to viral genomic RNAs and its replicative intermediates through the promoter regions. The detail function and interplay between functional domains are not clarified although a part of structures and functions of PB1 have been clarified. In this study, we analyzed the function of PB1 subunit in the sense of nucleotide recognition using ribavirin, which is a nucleoside analog and inhibits viral RNA synthesis of many RNA viruses including influenza virus. We screened ribavirin-resistant PB1 mutants from randomly mutated PB1 cDNA library using a mini-replicon assay, and we identified a single mutation at the amino acid position 27 of PB1 as an important residue for the nucleotide recognition.

The N-terminal region of influenza virus polymerase PB1 adjacent to the PA binding site is involved in replication but not transcription of the viral genome.

The influenza virus genome forms viral ribonucleoprotein (vRNP) complexes with nucleoprotein and viral RNA-dependent RNA polymerases (RdRp), PB1, PB2, and PA subunits. The vRNP complex catalyzes both genome replication and transcription reactions. PB1 contains the motifs highly conserved among RdRps and functions as a catalytic subunit of RdRp. The N-terminal region of PB1 between amino acid (a.a.) positions 1-83 contains both putative vRNA and cRNA promoter binding sites and a PA binding site. However, except for the PA binding site, the crystal structure and the function of the N-terminal region of PB1 are poorly understood. Here, we have examined the functional structure of the N-terminal region of PB1. The regions between a.a. positions 1-50 are highly conserved between influenza A and B viruses, but amino acids at positions 16, 27, and 44 are different between two viruses. To elucidate the functional importance of these amino acids in replication and transcription of the viral genome, we generated viruses containing mutations at these positions by reverse genetics and examined replication and transcription activities of these mutants. We found that a.a. positions 27 and 44 are responsible for the viral replication activity but not transcription activity.