Neural Differentiation of Human-Induced Pluripotent Stem Cells (hiPSc) on Surface-Modified Nanofibrous Scaffolds Coated with Platelet-Rich Plasma

The field of tissue engineering exploits living cells in a variety of ways to restore, maintain, or enhance tissues and organs. Between stem cells, human induced pluripotent stem cells (hiPSCs), are very important due to their wide abilities. Growth factors can support proliferation, differentiation, and migration of hiPSCs. Platelet-rich plasma (PRP) could be used as the source of growth factors for hiPSCs. In the present study, proliferation and neural differentiation of hiPSCs on surface-modified nanofibrous Poly-l-lactic acid (PLLA) coated with platelet-rich plasma was investigated. The results of in vitro analysis showed that on the surface, which was modified nanofibrous scaffolds coated with platelet-rich plasma, significantly enhanced hiPSCs proliferation and neural differentiation were observed. Whereas the MTT ([3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide]) results showed biocompatibility of surface-modified nanofibrous scaffolds coated with platelet-rich plasma and the usage of these modified nanoscaffolds in neural tissue engineering in vivo is promising for the future.

     

Remote controlling of CAR-T cells and toxicity management: Molecular switches and next generation CARs

Cell-based immunotherapies have been selected for the front-line cancer treatment approaches. Among them, CAR-T cells have shown extraordinary effects in hematologic diseases including chemotherapy-resistant acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL). In this approach, autologous T cells isolated from the patient''s body genetically engineered to express a tumor specific synthetic receptor against a tumor antigen, then these cells expanded ex vivo and re-infusion back to the patient body. Recently, significant clinical response and high rates of complete remission of CAR T cell therapy in B-cell malignancies led to the approval of Kymriah and Yescarta (CD19-directed CAR-T cells) were by FDA for treatment of acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Despite promising therapeutic outcomes, CAR T cells also can elicit the immune-pathologic effects, such as Cytokine Release Syndrome (CRS), Tumor Lysis Syndrome (TLS), and on-target off-tumor toxicity, that hampered its application. Ineffective control of these highly potent synthetic cells causes discussed potentially life-threatening toxicities, so researchers have developed several mechanisms to remote control CAR T cells. In this paper, we briefly review the introduced toxicities of CAR-T cells, then describe currently existing control approaches and review their procedure, pros, and cons.     

Probiotics with ameliorating effects on the severity of skin inflammation in psoriasis: Evidence from experimental and clinical studies

Experimental and clinical studies have confirmed safety and the medical benefits of probiotics as immunomodulatory medications. Recent advances have emphasized the critical effect of gastrointestinal bacteria in the pathology of inflammatory disorders, even, outside the gut. Probiotics have shown promising results for curing skin-influencing inflammatory disorders through modulating the immune response by manipulating the gut microbiome. Psoriasis is a complex inflammatory skin disease, which exhibits a microbiome distinct from the normal skin. In the present review, we considered the impact of gastrointestinal microbiota on the psoriasis pathogenesis, and through literature survey, attempted to explore probiotic species utilized for psoriasis treatment.     

Expression levels of the tetratricopeptide repeat protein gene ttc39b covary with carotenoid-based skin colour in cichlid fish

Carotenoid pigments play a major role in animal body colouration, generating strong interest in the genes involved in the metabolic processes that lead from their dietary uptake to their storage in the integument. Here, we used RNA sequencing (RNA-Seq) to test for differentially expressed genes in a taxonomically replicated design using three pairs of related cichlid fish taxa from the genera Tropheus and Aulonocara. Within each pair, taxa differed in terms of red and yellow body colouration, and high‐performance liquid chromatography (HPLC) analyses of skin extracts revealed different carotenoid profiles and concentrations across the studied taxa. Five genes were differentially expressed in all three yellow–red skin contrasts (dhrsx, nlrc3, tcaf2, urah and ttc39b), but only the tetratricopeptide repeat protein-coding gene ttc39b, whose gene product is linked to mammalian lipid metabolism, was consistently expressed more highly in the red skin samples. The RNA-Seq results were confirmed by quantitative PCR. We propose ttc39b as a compelling candidate gene for variation in animal carotenoid colouration. Since differential expression of ttc39b was correlated with the presence/absence of yellow carotenoids in a previous study, we suggest that ttc39b is more likely associated with the concentration of total carotenoids than with the metabolic formation of red carotenoids.     

Scalable optimal Bayesian classification of single-cell trajectories under regulatory model uncertainty

Background

Biological networks describes the mechanisms which govern cellular functions. Temporal networks show how these networks evolve over time. Studying the temporal progression of network topologies is of utmost importance since it uncovers how a network evolves and how it resists to external stimuli and internal variations. Two temporal networks have co-evolving subnetworks if the evolving topologies of these subnetworks remain similar to each other as the network topology evolves over a period of time. In this paper, we consider the problem of identifying co-evolving subnetworks given a pair of temporal networks, which aim to capture the evolution of molecules and their interactions over time. Although this problem shares some characteristics of the well-known network alignment problems, it differs from existing network alignment formulations as it seeks a mapping of the two network topologies that is invariant to temporal evolution of the given networks. This is a computationally challenging problem as it requires capturing not only similar topologies between two networks but also their similar evolution patterns.

Results

We present an efficient algorithm, Tempo, for solving identifying co-evolving subnetworks with two given temporal networks. We formally prove the correctness of our method. We experimentally demonstrate that Tempo scales efficiently with the size of network as well as the number of time points, and generates statistically significant alignments—even when evolution rates of given networks are high. Our results on a human aging dataset demonstrate that Tempo identifies novel genes contributing to the progression of Alzheimer’s, Huntington’s and Type II diabetes, while existing methods fail to do so.

Conclusions

Studying temporal networks in general and human aging specifically using Tempo enables us to identify age related genes from non age related genes successfully. More importantly, Tempo takes the network alignment problem one huge step forward by moving beyond the classical static network models.