Safety, Virologic Efficacy, and Pharmacokinetics of CT-P59, a Neutralizing Monoclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Protein: Two Randomized, Placebo-Controlled, Phase I Studies in Healthy Individuals and Patients With Mild SARS-CoV-2 Infection.

Purpose: Neutralizing antibodies can reduce SARS-CoV-2 cellular entry, viral titers, and pathologic damage. CT-P59 (regdanvimab), a SARS-CoV-2 neutralizing monoclonal antibody, was examined in 2 randomized, double-blind, placebo-controlled, single ascending dose, Phase I studies.

Methods: In study 1.

Infliximab Biosimilar CT-P13 Observational Studies for Rheumatoid Arthritis, Inflammatory Bowel Diseases, and Ankylosing Spondylitis: Pooled Analysis of Long-Term Safety and Effectiveness.

Introduction: Long-term, real-world safety and effectiveness data are required to support biosimilar use. This analysis pooled 5-year findings from observational studies of infliximab biosimilar CT-P13 treatment in patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and ankylosing spondylitis (AS).

Methods: Patients enrolled in the CT-P13 4.

Comparative Analysis of Re-Annotated Genes Provides Insight into Evolutionary Divergence and Expressions of Aquaporin Family in Pepper.

Aquaporins (AQPs) are known to have a vital role in water transport in all living organisms including agriculturally important crops, but a comprehensive genomic study of AQPs in pepper has not been implemented. Here, we updated previous gene annotations and generated a total of 259 AQP genes from five plants, including pepper. Phylogenetic and motif analyses revealed that a large proportion of pepper AQP genes belong to the specific subgroup of tonoplast intrinsic protein (TIP) subfamily, TIP4.

Overexpression of Oct4 in porcine ovarian stem/stromal cells enhances differentiation of oocyte-like cells in vitro and ovarian follicular formation in vivo.

Background: Recent findings have revealed that the female gonad may have regenerative activity with having germ line stem cells in juveniles and adults. Application of these germ line stem cells could be an alternative therapy for reproductive disorders in regenerative medicine.

Methods: To enhance the potency of differentiation into oocyte-like cells (OLCs) and folliculogenesis, we overexpressed Oct4 in ovarian stem/stromal cell (OvSCs) and examined the cellular properties related to stemness and self-renewal ability and finally demonstrated the ability of in vitro differentiation and folliculogenesis.

Evaluation of phenotypic, functional and molecular characteristics of porcine mesenchymal stromal/stem cells depending on donor age, gender and tissue source.

The biological properties of mesenchymal stem cells (MSCs) are influenced by donor age, gender and/or tissue sources. The present study investigated the cellular and molecular properties of porcine mesenchymal stromal/stem cells (MSCs) isolated from different tissues (adipose & dermal skin) and sex at different ages (1 week & 8 months after birth) with similar genetic and environmental backgrounds. MSCs were analyzed for alkaline phosphatase (AP) activity, CD90 and Oct3/4 expression, in vitro differentiation ability, senescence-associated β-galactosidase (SA-β-Gal) activity, telomeric properties, cell cycle status and expression of senescence (IL6, c-myc, TGFβ, p53 and p21)- and apoptosis (Bak and Bcl2)-related proteins.

Comparison of Immunomodulation Properties of Porcine Mesenchymal Stromal/Stem Cells Derived from the Bone Marrow, Adipose Tissue, and Dermal Skin Tissue.

Mesenchymal stromal/stem cells (MSCs) demonstrate immunomodulation capacity that has been implicated in the reduction of graft-versus-host disease. Accordingly, we herein investigated the capacity of MSCs derived from several tissue sources to modulate both proinflammatory (interferon [IFN] γ and tumor necrosis factor [TNF] α) and immunosuppressive cytokines (transforming growth factor [TGF] β and interleukin [IL] 10) employing xenogeneic human MSC-mixed lymphocyte reaction (MLR) test. Bone marrow-derived MSCs showed higher self-renewal capacity with relatively slow proliferation rate in contrast to adipose-derived MSCs which displayed higher proliferation rate.

Development and gene expression of porcine cloned embryos derived from bone marrow stem cells with overexpressing Oct4 and Sox2.

The present study compared the potential of porcine bone marrow mesenchymal stem cells (pBMSCs) at different passages as nuclear transfer (NT) donors and the developmental efficiency of NT embryos from donor cells transfected with/without Oct4 and Sox2. Early-passage pBMSCs showed higher proliferation and expression of Oct4 and Sox2 and differentiation potential into mesenchymal lineages than middle- and late-passage pBMSCs. Cleavage rate did not differ among pBMSCs at different passages, but NT embryos with early-passage pBMSCs and middle-passage pBMSCs transfected with Oct4 (Oct4-pBMSCs) had significantly (p<0.

Ovarian-cell-like cells from skin stem cells restored estradiol production and estrus cycling in ovariectomized mice.

Reduction of estradiol production and high serum concentrations of follicular stimulating hormone (FSH) are endocrine disorders associated with premature ovarian failure. Here, we report that transplantation of ovarian-like cells differentiated from stem cells restored endogenous serum estradiol levels. Stem cells were isolated from postnatal mouse skin and differentiated into ovarian-cell-like cells that are consistent with female germ, and ovarian follicle somatic cells.

Characterisation and differentiation of porcine ovarian theca-derived multipotent stem cells.

In this study, the cellular properties and in vitro differentiation capacity of porcine ovarian theca-derived multipotent stem cells (TSCs) were examined. Isolated TSCs were expanded into a homogeneous population that had a typical fibroblast-shaped morphology and was positive for alkaline phosphatase activity. Cell cycle analysis indicated that TSCs had high proliferative potential.

NMR investigation on the DNA binding and B-Z transition pathway of the Zα domain of human ADAR1.

Human ADAR1, which has two left-handed Z-DNA binding domains, preferentially binds Z-DNA rather than B-DNA with a high binding affinity. Z-DNA can be induced in long genomic DNA by Z-DNA binding proteins through the formation of two B-Z junctions with the extrusion of one base pair from each junction. We performed NMR experiments on complexes of Zα(ADAR1) with three DNA duplexes at a variety of protein-to-DNA molar ratios.

Removal of cumulus cells before oocyte nuclear maturation enhances enucleation rates without affecting the developmental competence of porcine cloned embryos.

The present study compared the efficiency of somatic cell nuclear transfer (SCNT) using porcine oocytes that were denuded of their cumulus cells at different maturation time. In pre-denuded group, the cumulus cells from cumulus-oocyte complexes (COCs) were removed at 29 hr post in vitro maturation (hpm) and followed by further culture for 12 hr. In control group, as a commonly followed procedure, cumulus cells were removed from COCs at 41 hpm.

NMR dynamics study of the Z-DNA binding domain of human ADAR1 bound to various DNA duplexes.

The Z-DNA binding domain of human ADAR1 (Zα(ADAR1)) preferentially binds Z-DNA rather than B-DNA with high binding affinity. Here, we have carried out chemical shift perturbation and backbone dynamics studies of Zα(ADAR1) in the free form and in complex with three DNA duplexes, d(CGCGCG)(2), d(CACGTG)(2), and d(CGTACG)(2). This study reveals that Zα(ADAR1) initially binds to d(CGCGCG)(2) through the distinct conformation, especially in the unusually flexible β1-loop-α2 region, from the d(CGCGCG)(2)-(Zα(ADAR1))(2) complex.

Donor-matched functional and molecular characterization of canine mesenchymal stem cells derived from different origins.

Canine mesenchymal stem cells (cMSCs) have generated a great interest as a promising source for cell-based therapies. To understand the basic biological properties of cMSCs derived from bone marrow (cBM-MSCs), adipose tissue (cA-MSCs), and dermal skin (cDS-MSCs) from a single donor, the present study compared their alkaline phosphatase (AP) activity, expression of CD markers and stem cell transcription factors, differentiation ability into osteogenic, adipogenic, and chondrogenic lineages, in vivo ectopic bone formation, chromosomal stability, cell cycle status, telomere length, and telomerase activity. Expressions of AP activity and transcription factors (Oct3/4, Nanog, and Sox2) were either absent or extremely weak in all cMSCs.

Epigenetic modification of fetal fibroblasts improves developmental competency and gene expression in porcine cloned embryos.

Treatment of somatic cells with DNA methylation and histone deacetylation inhibitors has been hypothesized to improve the potential reprogramming after nuclear transfer (NT). The objective of this study was to investigate the developmental competence and gene expression during the porcine preimplantation development of in vitro fertilized (IVF) and embryos cloned with porcine fetal fibroblasts (pFF) (pFF-NT), and pFF treated by 0.5 μM 5-azacytidine (5-azaC) (pFF+5-azaC-NT) or 1.

Developmental expression of lineage specific genes in porcine embryos of different origins.

Purpose: This study compared the expression of genes involved in pluripotency, segregation of inner cell mass (ICM) and trophectoderm (TE), and primitive endoderm (PE) formation in porcine embryos produced by in vitro fertilization (IVF), parthenogenetic activation (PA), and nuclear transfer (NT) using either fetal fibroblasts (FF-NT) or mesenchymal stem cells (MSC-NT).

Methods: Blastocyst formation and total cell number were analyzed. The expression patterns of transcripts, including SRY-related HMG-box gene 2 (SOX2), reduced expression gene 1 (REX1/ZFP42), LIN28, caudal type homeobox 2 (CDX2), TEA domain family member 4 (TEAD4), integrin beta 1 (ITGB1) and GATA6 were assessed at the 4-8 cell and blastocyst stage embryos by real-time PCR.

NMR study on the B-Z junction formation of DNA duplexes induced by Z-DNA binding domain of human ADAR1.

Z-DNA is produced in a long genomic DNA by Z-DNA binding proteins, through formation of two B-Z junctions with the extrusion of one base pair from each junction. To answer the question of how Z-DNA binding proteins induce B-Z transitions in CG-rich segments while maintaining the B-conformation of surrounding segments, we investigated the kinetics and thermodynamics of base-pair openings of a 13-bp DNA in complex with the Z-DNA binding protein, Zα(ADAR1). We also studied perturbations in the backbone of Zα(ADAR1) upon binding to DNA.

Differential cytotoxic effects of sodium meta-arsenite on human cancer cells, dental papilla stem cells and somatic cells correlate with telomeric properties and gene expression.

We investigated the effects of sodium meta-arsenite (NaAsO(2)) on human cancer cells (MDA-MB-231, MCF-7 and U-87 MG), dental papilla tissue stem cells (DPSCs) and somatic cells [MRC-5 fetal fibroblasts and adult muscle cells (MCs)] by examining telomeric properties, endogenous reverse transcriptase (RT) activity and the expression of tumorigenesis-linked genes. Half maximal inhibitory concentration (IC(50)) values were higher in DPSCs and MCs, possessing longer telomere lengths when compared to cancer cells. Levels of telomerase and RT activity, and the expression of protein 53 (p53), B-cell lymphoma 2 (BCL2), nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB), transforming growth factor beta (TGFβ) and vascular endothelial growth factor (VEGF) were significantly lower in cancer cells following sodium meta-arsenite treatment, whereas the effect was absent or marginally detected in DPSCs and somatic cells.

Transplantation of porcine umbilical cord matrix mesenchymal stem cells in a mouse model of Parkinson's disease.

The present study compared mesenchymal stem cells derived from umbilical cord matrix (UCM-MSCs) with bone marrow (BM-MSCs) of miniature pigs on their phenotypic profiles and ability to differentiate in vitro into osteocytes, adipocytes and neuron-like cells. This study further evaluated the therapeutic potential of UCM-MSCs in a mouse Parkinson's disease (PD) model. Differences in expression of some cell surface and cytoplasm specific markers were evident between UCM-MSCs and BM-MSCs.

Neurogenic and cardiomyogenic differentiation of mesenchymal stem cells isolated from minipig bone marrow.

The present study investigated the potential of minipig bone marrow-mesenchymal stem cells (BM-MSCs) to differentiate in vitro into neuron- and cardiomyocyte-like cells. Isolated BM-MSCs exhibited a fibroblast-like morphology, expressed CD29, CD44 and CD90, and differentiated into osteocytes, adipocytes and chondrocytes. Upon induction in two different neuronal specific media, most of BM-MSCs acquired the distinctive morphological features and positively stained for nestin, neurofilament-M (NF-M), neuronal nuclei (NeuN), β-tubulin, galactocerebroside (Gal-C) and glial fibrillary acidic protein (GFAP).

Characterization of porcine multipotent stem/stromal cells derived from skin, adipose, and ovarian tissues and their differentiation in vitro into putative oocyte-like cells.

The present study evaluated the alkaline phosphatase activity, cell cycle stage, expression of markers and early transcriptional factors, and in vitro differentiation into selected cell lineages of porcine stem/stromal cells (SCs) isolated from skin (SSCs), adipose, and ovarian (OSCs) tissues. Skin and adipose SCs were isolated from a 6-month-old miniature pig, whereas OSCs were isolated from a newly born piglet. Isolated cells exhibited fibroblast-like cell population with significant renewal capacity and formed colonies by cells out-growth.

The Zβ domain of human DAI binds to Z-DNA via a novel B-Z transition pathway.

The human DNA-dependent activator of IFN-regulatory factor (DAI) protein, which activates the innate immune response in response to DNA, contains two tandem Z-DNA binding domains (Zα and Zβ) at the NH(2) terminus. The hZβ(DAI) structure is similar to other Z-DNA binding proteins, although it demonstrates an unusual Z-DNA recognition. We performed NMR experiments on complexes of hZβ(DAI) with DNA duplex, d(CGCGCG)(2), at a variety of protein-to-DNA molar ratios.

NMR study of hydrogen exchange during the B-Z transition of a DNA duplex induced by the Zα domains of yatapoxvirus E3L.

The Yaba-like disease viruses (YLDV) are members of the Yatapoxvirus family and have double-stranded DNA genomes. The E3L protein, which is essential for pathogenesis in the vaccinia virus, consists of two domains: an N-terminal Z-DNA binding domain and a C-terminal RNA binding domain. The crystal structure of the E3L orthologue of YLDV (yabZα(E3L)) bound to Z-DNA revealed that the overall structure of yabZα(E3L) and its interaction with Z-DNA are very similar to those of hZα(ADAR1).

Sequence discrimination of the Zα domain of human ADAR1 during B-Z transition of DNA duplexes.

The Zα domain of human ADAR1 (Zα(ADAR1)) preferentially binds Z-DNA rather than B-DNA with high binding affinity. Zα(ADAR1) binds to the Z-conformation of both non-CG-repeat DNA duplexes and a d(CGCGCG)(2) duplex similarly. We performed NMR experiments on complexes between the Zα(ADAR1) and non-CG-repeat DNA duplexes, d(CACGTG)(2) or d(CGTACG)(2), with a variety of protein-DNA molar ratios.