Plant Therapeutic Proteases: Chemical Aspects, Applications and Pharmaceutical Formulations

Background: Plants are important sources of therapeutic proteases with expressive activity, stability, specificity, and efficiency. These proteases are employed at low concentrations and produce lesser side effects. They have complex tridimensional structures whose maintenance is a challenge, requiring specific conditions to guarantee the biological and pharmacological activities of these compounds. Aims: To conduct a literature review about plant therapeutic proteases, their principal biochemical aspects, potentials and clinical applications, and main pharmaceutical formulations. Materials and Methods: The present study consisted of a bibliographic survey of the major plant therapeutic proteases. An investigation was performed in the PUBMED, SciELO, ScienceDirect and Academic Google databases using the keywords plant enzymes, therapeutic protease, immobilization, formulation. Results: Some plant therapeutic proteases, such as papain and bromelain, are employed to treat many diseases and conditions, but the complexity of their structures is an important limitation of their uses. Thus, the structure and activities of their formulations need to be stabilized and protected against degradation, with improved pharmacokinetics, a prolonged time of action, reduced toxic effects, and proper direction towards their therapeutic target. Nanotechnology has made it possible to manufacture drug carriers such as polymeric nano- and microparticles, hydrogels, dendrimers and liposomes which are able to increase their efficacy and clinical applicability, as well as patient compliance. Sustainability initiatives that use Green Chemistry together with nanobiotechnology have managed to reduce the risks of toxicity to organisms and the environment. Green synthesis uses lower concentrations of metal ions, water-soluble, biocompatible and non-toxic compounds, as well as seeking energy efficiency and using renewable sources of raw materials. Conclusions: Investigations about new formulations of plant therapeutic proteases using biodegradable and biocompatible polymers is of great biomedical interest because they generate less toxic new biopharmaceuticals, in addition to protecting and stabilizing the enzymatic structure.

Comparison of the Scorpionism Caused by Centruroides margaritatus, Tityus pachyurus and Tityus n. sp. aff. metuendus Scorpion Venoms in Colombia

Among other scorpion species, Colombia has two genera of the Buthidae family Centruroides and Tityus, considered to be dangerous to humans. This research shares scientific knowledge aiming to a better understanding about the pathophysiological effects of such venoms. The venom of the three species: Centruroides margaritarus, Tityus pachyurus, and T. n. sp. aff. metuendus with biomedical interest were studied. An initial pre-glycemic sample was taken from ICR mice. They were later intraperitoneally inoculated with doses of 35% and 70% of LD50 of total venom. Poisoning signs were observed during a 6-h period to determine the level of scorpionism. After observation, a second glycemic sample was taken, and a histopathological evaluation of different organs was performed. This work revealed that all three venoms showed considerably notorious histopathological alterations in main organs such as heart and lungs; and inducing multiple organ failure, in relation to the glycemia values, only C. margaritatus and T. n. sp. aff. metuendus showed significant changes through manifestation of hyperglycemia. According to the Colombian scorpionism level; signs were mild to severe affecting the autonomous nervous system.

Short Overview of Some Assays for the Measurement of Antioxidant Activity of Natural Products and Their Relevance in Dermatology

Impaired systemic redox homeostasis is implicated in the onset and development of various diseases, including skin diseases. Therefore, continuous search for natural products with antioxidant bioactivities applicable in biomedicine is attractive topic of general interest. Research efforts aiming to validate antioxidant potentials of natural products has led to the development of several assays based on various test principles. Hence, understanding the advantages and limitations of various assays is important for selection of assays useful to study antioxidant and related bioactivities of natural products of biomedical interest. This review paper gives a short overview on some chemical and cellular bioassays used to estimate the antioxidant activity of chosen natural products together with a brief overview on the use of natural products with antioxidant activities as adjuvant medicinal remedies in dermatology.

Pluripotent Stem Cells for Livestock Health and Production

: Pluripotent stem cells (PSCs) have unlimited capacity of self-renewal and differentiation so that they can potentially produce any cell or tissue of animal’s body. The PSCs derived from livestock represents a more appropriate model than rodent for investigating human diseases due to their higher anatomical and physiological resemblance with human. Apart from that, livestock PSCs holds immense promises for the innovative therapies, transgenic animal production and their biomedical interest. The realization of the full potential of PSCs, however, depends on the elucidation of the molecular mechanisms which play a critical role in the maintenance of pluripotency and reprogramming procedure remains poorly understood in livestock which in turn impedes the generation of true PSCs and its usage for clinical research. An in-depth understanding of pluripotency is extremely essential for improving health and welfare of livestock animals. Therefore, present review focuses on the milestone achievements of PSCs in livestock animals and their potential application in health and production of livestock.

Extracellular vesicles in the host-helminth communication: biomedical applications

Extracellular vesicles participate in intercellular communications, altogether with classic mechanisms like direct contact between cells and the secretion of mediators. They have attracted considerable interest since their discovery in reticulocytes in 1983. The term includes different types of vesicles that vary in size and origin, with exosomes, microvesicles and apoptotic bodies as the major ones. These structures are sorrounded by a lipid membrane, where various types of receptors are located, and can carry different cargo molecules, including sugars, proteins, nucleic acids and metabolites. They have been described in all kingdoms in nature (participating in both intercellular and inter-specific communications), in all types of biological fluids (as part of liquid biopsy). In fact, their presence in samples from both physiological and pathological processes has suggested them as excellent biomarkers. Their role in health and disease is being widely investigated. In this context, the study of extracellular vesicles produced by parasites, and specifically by helminths, constitutes a growing field of research, with great biomedical interest, mainly in the control of infections caused by them. In fact, these vesicles can be used to generate rapid and specific diagnosis systems, to produce new tools for vaccination, and to identify targets for new treatments. The ability of extracellular vesicles to modulate the immune response also opens new possibilities for their use against autoimmune diseases.

Man-Specific, GalNAc/T/Tn-Specific and Neu5Ac-Specific Seaweed Lectins as Glycan Probes for the SARS-CoV-2 (COVID-19) Coronavirus

Seaweed lectins, especially high-mannose-specific lectins from red algae, have been identified as potential antiviral agents that are capable of blocking the replication of various enveloped viruses like influenza virus, herpes virus, and HIV-1 in vitro. Their antiviral activity depends on the recognition of glycoprotein receptors on the surface of sensitive host cells—in particular, hemagglutinin for influenza virus or gp120 for HIV-1, which in turn triggers fusion events, allowing the entry of the viral genome into the cells and its subsequent replication. The diversity of glycans present on the S-glycoproteins forming the spikes covering the SARS-CoV-2 envelope, essentially complex type N-glycans and high-mannose type N-glycans, suggests that high-mannose-specific seaweed lectins are particularly well adapted as glycan probes for coronaviruses. This review presents a detailed study of the carbohydrate-binding specificity of high-mannose-specific seaweed lectins, demonstrating their potential to be used as specific glycan probes for coronaviruses, as well as the biomedical interest for both the detection and immobilization of SARS-CoV-2 to avoid shedding of the virus into the environment. The use of these seaweed lectins as replication blockers for SARS-CoV-2 is also discussed.

Magnetoliposomes Incorporated in Peptide-Based Hydrogels: Towards Development of Magnetolipogels

A major problem with magnetogels is the encapsulation of hydrophobic drugs. Magnetoliposomes not only provide these domains but also improve drug stability and avert the aggregation of the magnetic nanoparticles. In this work, two magnetoliposome architectures, solid and aqueous, were combined with supramolecular peptide-based hydrogels, which are of biomedical interest owing to their biocompatibility, easy tunability, and wide array of applications. This proof-of-concept was carried out through combination of magnetoliposomes (loaded with the model drug curcumin and the lipid probe Nile Red) with the hydrogels prior to pH triggered gelation, and fluorescence spectroscopy was used to assess the dynamics of the encapsulated molecules. These systems allow for the encapsulation of a wider array of drugs. Further, the local environment of the encapsulated molecules after gelation is unaffected by the used magnetoliposome architecture. This system design is promising for future developments on drug delivery as it provides a means to independently modify the components and adapt and optimize the design according to the required conditions.

Direct Catalytic Fuel Cell Device Coupled to Chemometric Methods to Detect Organic Compounds of Pharmaceutical and Biomedical Interest

Making use of a small direct methanol fuel cell device (DMFC), used as an analytical sensor, chemometric methods, organic compounds very different from one another, can be determined qualitatively and quantitatively. In this research, the following seven different organic compounds of pharmaceutical and biomedical interest, having in common only one –OH group, were considered: chloramphenicol, imipenem, methanol, ethanol, propanol, atropine and cortisone. From a quantitative point of view, the traditional approach, involving the building of individual calibration curves, which allow the quantitative determination of the corresponding organic compounds, even if with different sensitivities, was followed. For the qualitative analysis of each compound, this approach has been much more innovative. In fact, by processing the data from each of the individual response curves, obtained through the fuel cell, using chemometric methods, it is possible to directly identify and recognize each of the seven organic compounds. Since the study is a proof of concept to show the potential of this innovative methodological approach, based on the combination of direct methanol fuel cell with advanced chemometric tools, at this stage, concentration ranges that may not be the ones found in some real situations were investigated. The three methods adopted are all explorative methods with very limited computation costs, which have different characteristics and, therefore, may provide complementary information on the analyzed data. Indeed, while PCA (principal components analysis) provides the most parsimonious summary of the variability observed in the current response matrix, the analysis of the current response behavior was performed by the “slicing” method, in order to transform the current response profiles into numerical matrices, while PARAFAC (Parallel Factor Analysis) allows to obtain a finer deconvolution of the exponential curves. On the other hand, the multiblock nature of “ComDim” (Common Components and Specific Weight Analysis) has been the basis to relate the variability observed in the current response behavior with the parameters of the linear calibrations.

Cytogenetic Mapping of 35 New Markers in the Alpaca (Vicugna pacos)

Alpaca is a camelid species of broad economic, biological and biomedical interest, and an essential part of the cultural and historical heritage of Peru. Recently, efforts have been made to improve knowledge of the alpaca genome, and its genetics and cytogenetics, to develop molecular tools for selection and breeding. Here, we report cytogenetic mapping of 35 new markers to 19 alpaca autosomes and the X chromosome. Twenty-eight markers represent alpaca SNPs, of which 17 are located inside or near protein-coding genes, two are in ncRNA genes and nine are intergenic. The remaining seven markers correspond to candidate genes for fiber characteristics (BMP4, COL1A2, GLI1, SFRP4), coat color (TYR) and development (CHD7, PAX7). The results take the tally of cytogenetically mapped markers in alpaca to 281, covering all 36 autosomes and the sex chromosomes. The new map assignments overall agree with human–camelid conserved synteny data, except for mapping BMP4 to VPA3, suggesting a hitherto unknown homology with HSA14. The findings validate, refine and correct the current alpaca assembly VicPac3.1 by anchoring unassigned sequence scaffolds, and ordering and orienting assigned scaffolds. The study contributes to the improvement in the alpaca reference genome and advances camelid molecular cytogenetics.