Osteoarthritis versus psoriasis arthritis: Physiopathology, cellular signaling, and therapeutic strategies.

Osteoarthritis and psoriasis arthritis are two degenerative forms of arthritis that share similar yet also different manifestations at the histological, cellular, and clinical levels. Rheumatologists have marked them as two entirely distinct arthropathies. Given recent discoveries in disease initiation and progression, potential mechanisms, cellular signaling pathways, and ongoing clinical therapeutics, there are now more opportunities for discovering osteoarthritis drugs. This review summarized the osteoarthritis and psoriasis arthritis signaling pathways, crosstalk between BMP, WNT, TGF-ß, VEGF, TLR, and FGF signaling pathways, biomarkers, and anatomical pathologies. Through bench research, we demonstrated that regenerative medicine is a promising alternative for treating osteoarthritis by highlighting significant scientific discoveries on entheses, multiple signaling blockers, and novel molecules such as immunoglobulin new antigen receptors targeted for potential drug evaluation. Furthermore, we offered valuable therapeutic approaches with a multidisciplinary strategy to treat patients with osteoarthritis or psoriasis arthritis in the coming future in the clinic.

Shark New Antigen Receptor (IgNAR): Structure, Characteristics and Potential Biomedical Applications.

Shark is a cartilaginous fish that produces new antigen receptor (IgNAR) antibodies. This antibody is identified with a similar human heavy chain but dissimilar sequences. The variable domain (VNAR) of IgNAR is stable and small in size, these features are desirable for drug discovery. Previous study results revealed the effectiveness of VNAR as a single molecule or a combination molecule to treat diseases both in vivo and in vitro with promising clinical applications. We showed the first evidence of IgNAR alternative splicing from spotted bamboo shark (Chiloscyllium plagiosum), broadening our understanding of the IgNARs characteristics. In this review, we summarize the discoveries on IgNAR with a focus on its advantages for therapeutic development based on its peculiar biochemistry and molecular structure. Proper applications of IgNAR will provide a novel avenue to understand its special presence in cartilaginous fishes as well as designing a number of drugs for undefeated diseases.

Sequence structure character of IgNAR Sec in whitespotted bamboo shark (Chiloscyllium plagiosum).

Whitespotted bamboo shark (Chiloscyllium plagiosum) is a demersal cartilaginous fish with an adaptive immune system founded upon immunoglobulins. In this manuscript, we characterize the IgNAR of the whitespotted bamboo shark. A newly discovered alternative splicing form of IgNAR Sec (IgNARshort (ΔC2-C3) Sec) was identified, in which the C1 domain was spliced directly to the C4 domain, the process resulted in a molecule containing three constant domains. However, a single unpaired cysteine remains in the highly flexible hinge region, contributing in the formation of an interchain disulfide bond. Two types of C1 domain were found, and the one lacking a short α-helix showed lower proportion. This finding suggests that short α-helices might be important to the stability of IgNAR. High-throughput sequencing revealed that the percentage of VNAR types significantly vary between the diverse species of sharks. The variable region of IgNAR (the VNAR) with small size and stabilization is a potential candidate for immunotherapeutic agents. The structure and stability analysis in this manuscript may be useful in future biomedical applications.

The Biological Activity of Natural Alkaloids against Herbivores, Cancerous Cells and Pathogens.

The growing incidence of microorganisms that resist antimicrobials is a constant concern for the scientific community, while the development of new antimicrobials from new chemical entities has become more and more expensive, time-consuming, and exacerbated by emerging drug-resistant strains. In this regard, many scientists are conducting research on plants aiming to discover possible antimicrobial compounds. The secondary metabolites contained in plants are a source of chemical entities having pharmacological activities and intended to be used for the treatment of different diseases. These chemical entities have the potential to be used as an effective antioxidant, antimutagenic, anticarcinogenic and antimicrobial agents. Among these pharmacologically active entities are the alkaloids which are classified into a number of classes, including pyrrolizidines, pyrrolidines, quinolizidines, indoles, tropanes, piperidines, purines, imidazoles, and isoquinolines. Alkaloids that have antioxidant properties are capable of preventing a variety of degenerative diseases through capturing free radicals, or through binding to catalysts involved indifferent oxidation processes occurring within the human body. Furthermore, these entities are capable of inhibiting the activity of bacteria, fungi, protozoan and etc. The unique properties of these secondary metabolites are the main reason for their utilization by the pharmaceutical companies for the treatment of different diseases. Generally, these alkaloids are extracted from plants, animals and fungi. Penicillin is the most famous natural drug discovery deriving from fungus. Similarly, marines have been used as a source for thousands of bioactive marine natural products. In this review, we cover the medical use of natural alkaloids isolated from a variety of plants and utilized by humans as antibacterial, antiviral, antifungal and anticancer agents. An example for such alkaloids is berberine, an isoquinoline alkaloid, found in roots and stem-bark of Berberis asculin P. Renault plant and used to kill a variety of microorganisms.