A review: Biological activities of novel cyanopyridine derivatives.

The discovery of new therapeutic drugs is heavily reliant on the structural diversity and pharmacological properties of heterocyclic compounds. Pyridine heterocyclic-related medicines, in particular, have garnered considerable attention due to their wide pharmacological activities and therapeutic effects. Among them, cyanopyridine derivatives have demonstrated diverse pharmacological effects. This review aims to systematically compile and discuss the diverse pharmacological effects of cyanopyridine derivatives. The review is divided into multiple sections, highlighting the biological activities of cyanide derivatives, with emphasis on anticancer, antimicrobial (i.e., antibacterial, insecticidal anticonvulsant, and antiviral activities), anticonvulsant, anti-Alzheimer's, and enzyme inhibitory activities. Furthermore, the review emphasizes the interesting therapeutic potential of cyanopyridine derivatives as kinase inhibitors and cytotoxic agents, which are promising candidates for anticancer drug development. The relationship between structure and activity is also discussed, with molecular docking used to provide insights into the mechanism of action of these compounds.

The impact of induced pluripotent stem cells in animal conservation.

It is widely acknowledged that we are currently facing a critical tipping point with regards to global extinction, with human activities driving us perilously close to the brink of a devastating sixth mass extinction. As a promising option for safeguarding endangered species, induced pluripotent stem cells (iPSCs) hold great potential to aid in the preservation of threatened animal populations. For endangered species, such as the northern white rhinoceros (Ceratotherium simum cottoni), supply of embryos is often limited. After the death of the last male in 2019, only two females remained in the world. IPSC technology offers novel approaches and techniques for obtaining pluripotent stem cells (PSCs) from rare and endangered animal species. Successful generation of iPSCs circumvents several bottlenecks that impede the development of PSCs, including the challenges associated with establishing embryonic stem cells, limited embryo sources and immune rejection following embryo transfer. To provide more opportunities and room for growth in our work on animal welfare, in this paper we will focus on the progress made with iPSC lines derived from endangered and extinct species, exploring their potential applications and limitations in animal welfare research.

Preclinical Research of Stem Cells: Challenges and Progress.

In recent years, great breakthroughs have been made in basic research and clinical applications of stem cells in regenerative medicine and other fields, which continue to inspire people to explore the field of stem cells. With nearly unlimited self-renewal ability, stem cells can generate at least one type of highly differentiated daughter cell, which provides broad development prospects for the treatment of human organ damage and other diseases. In the field of stem cell research, related technologies for inducing or isolating stem cells are relatively mature, and a variety of stable stem cell lines have been successfully constructed. To realize the full clinical application of stem cells as soon as possible, it is more and more important to further optimize each stage of stem cell research while conforming to Current Good Manufacture Practices (cGMP) standards. Here, we synthesized recent developments in stem cell research and focus on the introduction of xenogenicity in the preclinical research process and the remaining problems of various cell bioreactors. Our goal is to promote the development of technologies for xeno-free culture and clinical expansion of stem cells through in-depth discussion of current research. This review will provide new insight into stem cell research protocols and will contribute to the creation of efficient and stable stem cell expansion systems.

Cell Penetrating Peptide Derived from Human Eosinophil Cationic Protein Decreases Airway Allergic Inflammation.

Cell penetrating peptide derived from human eosinophil cationic protein (CPPecp) is a 10-amino-acid peptide containing a core heparan sulfate (HS)-binding motif of human eosinophil cationic protein (ECP). It binds and penetrates bronchial epithelial cells without cytotoxic effects. Here we investigated airway-protective effects of CPPecp in BEAS-2B cell line and mite-induced airway allergic inflammation in BALB/c mice. In BEAS-2B cell, CPPecp decreases ECP-induced eotaxin mRNA expression. CPPecp also decreases eotaxin secretion and p-STAT6 activation induced by ECP, as well as by IL-4. In vivo studies showed CPPecp decreased mite-induced airway inflammation in terms of eosinophil and neutrophil count in broncho-alveolar lavage fluid, peri-bronchiolar and alveolar pathology scores, cytokine production in lung protein extract including interleukin (IL)-5, IL-13, IL-17A/F, eotaxin; and pause enhancement from methacholine stimulation. CPPecp treated groups also showed lower serum mite-specific IgE level. In this study, we have demonstrated the in vitro and in vivo anti-asthma effects of CPPecp.

Low-molecular-weight heparin and unfractionated heparin decrease Th-1, 2, and 17 expressions.

BACKGROUND: We evaluated the effects of T helper cell differentiation in a mite-allergic animal model treated with inhaled heparins of different molecular weight. METHOD: BALB/c mice were divided into four groups: 1. Control, 2. Mite intratracheal (mIT), 3. Inhaled heparin (hIN), 4. Inhaled low-molecular-weight heparin (lmwhIN). Groups 2, 3, and 4 were sensitized twice with Der p allergen subcutaneously on day 1 and day 8. Der p allergen was administered intratracheally on day 15. Groups 3 and 4 were treated with heparin or low-molecular-weight (lmw) heparin intranasally from day 1 to 22. Splenocytes from sacrificed mice stimulated with 16 µg/ml of Der p were cultured for 72 hours. Supernatants of splenocyte were collected to analyze the effect of Interleukin (IL)17-A/F, Interferon(IFN)-γ, IL-4, IL-13, and IL-10. Serum was also collected for Der P-specific IgE level on day 23. Total RNA was extracted from spleen tissue for mRNA expression. Gene expression of Foxp3, IL-10 IFN-γ, GATA3, IL-5, and RORγt were analyzed. RESULTS: Both hIN and lmwhIN groups had lower serum IgE level than that of the mIT group (both p<0.0001). Both hIN and lmwhIN groups showed significantly decreased transcripts of GATA-3, IFN-γ, IL-5, and RORγt mRNA in their spleen. Regarding the supernatant of splenocyte culture stimulated with Der p, compared with the mIT group, there were significant decreases in IL-17A/F, IFN-γ, IL-4, IL-13, and IL-10 secretion in inhaled hIN and lmwhIN groups. CONCLUSIONS: From this balb/c mice study, the analyses of mRNA and cytokines revealed that both intranasal heparin and lmw heparin treatment decreased the expression of Th1, Th2, and Th17 in spleen. The underlying mechanism(s) warrant further studies.