The Arsenal of Bioactive Molecules in the Skin Secretion of Urodele Amphibians

Urodele amphibians (∼768 spp.), salamanders and newts, are a rich source of molecules with bioactive properties, especially those isolated from their skin secretions. These include pharmacological attributes, such as antimicrobial, antioxidant, vasoactive, immune system modulation, and dermal wound healing activities. Considering the high demand for new compounds to guide the discovery of new drugs to treat conventional and novel diseases, this review summarizes the characteristics of molecules identified in the skin of urodele amphibians. We describe urodele-derived peptides and alkaloids, with emphasis on their biological activities, which can be considered new scaffolds for the pharmaceutical industry. Although much more attention has been given to anurans, bioactive molecules produced by urodeles have the potential to be used for biotechnological purposes and stand as viable alternatives for the development of therapeutic agents.

Nanotechnology in Plant Metabolite Improvement and in Animal Welfare

Plant tissue culture plays an important role in plant biotechnology due to its potential for massive production of improved crop varieties and high yield of important secondary metabolites. Several efforts have been made to ameliorate the effectiveness and production of plant tissue culture, using biotic and abiotic factors. Nowadays, the addition of nanoparticles as elicitors has, for instance, gained worldwide interest because of its success in microbial decontamination and enhancement of secondary metabolites. Nanoparticles are entities in the nanometric dimension range: they possess unique physicochemical properties. Among all nanoparticles, silver-nanoparticles (AgNPs) are well-known for their antimicrobial and hormetic effects, which in appropriate doses, led to the improvement of plant biomass as well as secondary metabolite accumulation. This review is focused on the evaluation of the integration of nanotechnology with plant tissue culture. The highlight is especially conveyed on secondary metabolite enhancement, effects on plant growth and biomass accumulation as well as their possible mechanism of action. In addition, some perspectives of the use of nanomaterials as potential therapeutic agents are also discussed. Thus, the information provided will be a good tool for future research in plant improvement and the large-scale production of important secondary metabolites. Elicitation of silver-nanoparticles, as well as nanomaterials, function as therapeutic agents for animal well-being is expected to play a major role in the process. However, nanosized supramolecular aggregates have received an increased resonance also in other fields of application such as animal welfare. Therefore, the concluding section of this contribution is dedicated to the description and possible potential and usage of different nanoparticles that have been the object of work and expertise also in our laboratories.

An in silico method to assess antibody fragment polyreactivity

Antibodies are essential biological research tools and important therapeutic agents, but some exhibit non-specific binding to off-target proteins and other biomolecules. Such polyreactive antibodies compromise screening pipelines, lead to incorrect and irreproducible experimental results, and are generally intractable for clinical development. We designed a set of experiments using a diverse naive synthetic camelid antibody fragment ('nanobody') library to enable machine learning models to accurately assess polyreactivity from protein sequence (AUC > 0.8). Moreover, our models provide quantitative scoring metrics that predict the effect of amino acid substitutions on polyreactivity. We experimentally tested our model's performance on three independent nanobody scaffolds, where over 90% of predicted substitutions successfully reduced polyreactivity. Importantly, the model allowed us to diminish the polyreactivity of an angiotensin II type I receptor antagonist nanobody, without compromising its pharmacological properties. We provide a companion web-server that provides a straightforward means of predicting polyreactivity and polyreactivity-reducing mutations for any given nanobody sequence.

Jerveratrum-Type Steroidal Alkaloids Inhibit β-1,6-Glucan Biosynthesis in Fungal Cell Walls

Non- Candida albicans Candida species (NCAC) are on the rise as a cause of mycosis. Many antifungal drugs are less effective against NCAC, limiting the available therapeutic agents.

Synthesis and Biological Evaluation of N-Heterocyclic Substituted Fluoro-Benzothiazole Sulphonamido Analogs as a Potential Therapeutic Agents

The present investigation is aimed to synthesize fluorobenzothiazole comprising sulphonamido pyrazole analogs starting from fluoro-chloroaniline to get 2-amino-6-fluoro-7-chloro (1,3) benzothiazole (I), this was treated with anilino-s-methyl ethylene cyanoacetamide in the presence of ethanol to get desired molecules. The synthesized targeted molecules are characterized, docked and screened for their invitro antidiabetic properties. Keywords: Fluorobenzothiazole, Docking, antidiabetic

Nanomedicine Strategies for Management of Drug Resistance in Lung Cancer

Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer; presents novel nanomedicine therapeutics aimed to improve the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for clinical application of nanomedicine in management of LC resistance.