Biomedical applications of synthetic peptides derived from venom of animal origin: A systematic review.

Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases, infections, cardiovascular diseases, and respiratory diseases, are required. Recent studies have focused on identifying novel sources for pharmaceutical molecules to develop therapies against these diseases. Among the sources for potentially new therapies, animal venom-derived molecules have generated much interest. Various animal venom-derived proteins and peptides have been isolated, identified, synthesized, and tested to develop drugs. Venom-derived peptides have several biomedical properties, such as proapoptotic, cell migration, and autophagy regulation activities in cancer cell models; induction of vasodilation by nitric oxide and regulation of angiotensin II; modification of insulin response by controlling calcium and potassium channels; regulation of pain receptor activity; modulation of immune cell activity; alteration of motor neuron activity; degradation or inhibition of ß-amyloid plaque formation; antibacterial, antifungal, antiviral, and antiprotozoal activities; increase in sperm motility and potentiation of erectile function; reduction of intraocular pressure; anticoagulation, fibrinolytic, and antithrombotic activities; etc. This systematic review compiles these biomedical properties and potential biomedical applications of synthesized animal venom-derived peptides reported in the latest research. In addition, the limitations and areas of opportunity in this research field are discussed so that new studies can be developed based on the data presented.

Effects of canine adipose-derived mesenchymal stem cells on the epithelialization of rabbits' skin autograft (Oryctolagus cuniculus) / Efeitos das células-tronco mesenquimais derivadas do tecido adiposo de cães na epitelização de autoenxertos de pele em coelhos (Oryctolagus cuniculus)

The present study aimed to evaluate the effects of mesenchymal stem cells derived from canine adipose tissue in the healing process of full-thickness mesh skin grafts in rabbits. The stem cells were collected from young dogs; and, after characterization, remained in cryopreservation, in independent doses containing 2 x 106 cells. The mesh distal limb graft technique was performed in 60 rabbits, divided into three groups, CG (Control Group), GT1 (Intralesional Stem Cell Treated Group), and GT2 (Intravenous Stem Cell Treated Group), containing 20 animals each. After grafting, each group was randomly divided into four subgroups according to euthanasia time 3, 7, 14, and 30 days, containing five animals in each group. Animals of GT1_14, GT1_30, and GT2_14, GT2_30 subgroups received a second dose of xenogeneic cells on the seventh day. Meanwhile, animals from GT1_30 and GT2_30 received the third dose of xenogeneic cells on day 14. The groups treated with xenogeneic stem cells positively affected type III collagen re-epithelialization and deposition, and possibly GT1 had a controlled inflammatory response. However, no effect on angiogenesis. Thus, it was possible to demonstrate tolerance and therapeutic action of mesenchymal stem cells from canine adipose tissue in skin grafts in rabbits.(AU)

O presente estudo teve como principal objetivo avaliar os efeitos das células-tronco mesenquimais derivadas do tecido adiposo de cães no processo de cicatrização de autoenxertos de pele de espessura total em malha em coelhos. As células-tronco foram coletadas de cães jovens, após a caracterização estas permaneceram em criopreservação, em doses individuais contendo 2 x 106 células. A técnica de enxerto em malha na região distal do membro foi realizada em 60 coelhos, divididos em três grupos, GC (Grupo Controle), GT1 (Grupo tratado com células-tronco intralesional) e GT2 (Grupo tratado com células-tronco via endovenosa), contendo 20 animais cada. Imediatamente após a enxertia, cada grupo foi dividido aleatoriamente em quatro subgrupos, de acordo com o tempo de eutanásia 3, 7, 14 e 30 dias contendo cinco animais cada. Animais dos subgrupos GT1_14, GT1_30 e GT2_14, GT2_30 receberam uma segunda dose de células xenógenas no sétimo dia. Ademais, animais do GT1_30 e do GT2_30 receberam a terceira dose de células xenógenas no dia 14. Os grupos tratados com células-tronco xenógenas tiveram um efeito positivo na reepitelização e deposição de colágeno tipo III, e possivelmente, o GT1 teve uma resposta inflamatória controlada, entretanto o efeito na angiogênese não foi observado. Dessa forma, foi possível demonstrar que houve tolerância e ação terapêutica das células-tronco mesenquimais derivadas do tecido adiposo de cães em enxertos de pele em coelhos.(AU)

In Silico Analysis and In Vitro Characterization of the Bioactive Profile of Three Novel Peptides Identified from 19 kDa α-Zein Sequences of Maize.

In this study, we characterized three novel peptides derived from the 19 kDa α-zein, and determined their bioactive profile in vitro and developed a structural model in silico. The peptides, 19ZP1, 19ZP2 and 19ZP3, formed α-helical structures and had positive and negative electrostatic potential surfaces (range of -1 to +1). According to the in silico algorithms, the peptides displayed low probabilities for cytotoxicity (≤0.05%), cell penetration (10-33%) and antioxidant activities (9-12.5%). Instead, they displayed a 40% probability for angiotensin-converting enzyme (ACE) inhibitory activity. For in vitro characterization, peptides were synthesized by solid phase synthesis and tested accordingly. We assumed α-helical structures for 19ZP1 and 19ZP2 under hydrophobic conditions. The peptides displayed antioxidant activity and ACE-inhibitory activity, with 19ZP1 being the most active. Our results highlight that the 19 kDa α-zein sequences could be explored as a source of bioactive peptides, and indicate that in silico approaches are useful to predict peptide bioactivities, but more structural analysis is necessary to obtain more accurate data.

Antioxidant Activity of Zein Hydrolysates from Zea Species and Their Cytotoxic Effects in a Hepatic Cell Culture.

In recent years, food proteins with bioactivity have been studied for cancer treatment. Zein peptides have shown an important set of bioactivities. This work compares the cytotoxic activity of zein hydrolyzed, extracted from four Zea species: teosinte, native, hybrid, and transgenic (Teo, Nat, Hyb, and HT) in a hepatic cell culture. Zein fraction was extracted, quantified, and hydrolyzed. Antioxidant capacity and cytotoxicity assays were performed on HepG2 cells. The levels of expression of caspase 3, 8, and 9 were evaluated in zein-treated cell cultures. Zea parviglumis showed the highest zein content (46.0 mg/g) and antioxidant activity (673.40 TE/g) out of all native zeins. Peptides from Hyb and HT showed high antioxidant activity compared to their native counterparts (1055.45 and 724.32 TE/g, respectively). Cytotoxic activity was observed in the cell culture using peptides of the four Zea species; Teo and Nat (IC50: 1781.63 and 1546.23 ng/mL) had no significant difference between them but showed more cytotoxic activity than Hyb and HT (IC50: 1252.25 and 1155.56 ng/mL). Increased expression of caspase 3 was observed in the peptide-treated HepG2 cells (at least two-fold more with respect to the control sample). These data indicate the potential for zein peptides to prevent or treat cancer, possibly by apoptosis induction.

Anti-Cancer Activity of Maize Bioactive Peptides.

Cancer is one of the main chronic degenerative diseases worldwide. In recent years, consumption of whole-grain cereals and their derivative food products has been associated with a reduced risk of various types of cancer. The main biomolecules in cereals include proteins, peptides, and amino acids, all of which are present in different quantities within the grain. Some of these peptides possess nutraceutical properties and exert biological effects that promote health and prevent cancer. In this review, we report the current status and advances in knowledge regarding the bioactive properties of maize peptides, such as antioxidant, antihypertensive, hepatoprotective, and anti-tumor activities. We also highlight the potential biological mechanisms through which maize bioactive peptides exert anti-cancer activity. Finally, we analyze and emphasize the potential applications of maize peptides.

Extended Hildebrand Solubility Approach applied to Nimodipine in PEG 400 + ethanol mixtures / Método extendido de Hildebrand aplicado a la solubilidad de nimodipina en mezclas PEG 400 + etanol

La nimodipina (NMD) es un agente usado como vasodilatador cerebral y cuyas propiedades fisicoquímicas en solución aún no han sido totalmente estudiadas. En la presente investigación se aplicó el Método Extendido de Solubilidad de Hildebrand (MESH) al estudio de la solubilidad de NMD en algunas mezclas binarias PEG 400 + etanol a 298,15 K. Se obtuvo una capacidad predictiva aceptable del MESH (desviación general inferior al 1,3%) al utilizar un modelo polinómico regular de tercer orden, relacionando el parámetro de interacción W con el parámetro de solubilidad de las mezclas solventes. De esta forma, las desviaciones obtenidas en la solubilidad estimada fueron de magnitud inferior a las obtenidas al calcular esta propiedad directamente, utilizando una regresión empírica regular del mismo orden, de la solubilidad experimental del fármaco en función del parámetro de solubilidad de las mezclas disolventes, en la cual se obtuvo una desviación promedio del 1,7%.

Nimodipine (NMD) is a drug used as cerebral vasodilator whose physicochemical properties in solution have not been studied completely. In this work the Extended Hildebrand Solubility Approach (EHSA) was applied to evaluate the equilibrium solubility of NMD in some polyethylene glycol 400 + ethanol mixtures at 298.15 K. An acceptable correlative capacity of EHSA was found using a regular polynomial model in order three (overall deviation lower than 1.3%), when the W interaction parameter is related to the solubility parameter of the mixtures. Moreover, the mean deviation obtained in the estimated solubility with respect to experimental solubility was lower than the one obtained directly by means of an empiric regression in order three of the logarithm experimental solubility as a function of the mixtures' solubility parameters (1.7%).

A weighted risk index for antenatal prediction of perinatal outcome.

OBJECTIVE: The hypothesis is that a risk score derived from the risk index (RI) is correlated with perinatal outcomes. STUDY DESIGN: The RI is a weighted numerical score based on gestational risk factors applied to 782 gravidas antepartum. Management was independent of the score. Birth weight, Apgar scores, and cesarean birth were correlated with risk score. RESULTS: The break point score in this non-Gaussian cohort was 6. Using 6, 80.2% were low and 19.8% high risk. Birth weight < 2500 gm was inversely correlated (p < .001) and occurred in 13% of the high risk ((3)6) and 4.9% of the low risk (< 6) group, relative risk (RR) 2.7. C-section correlated (p < .001), and occurred in 51% of the high and 23% of the low risk group, RR 2.4. risk score inversely correlated with 5 minute Apgar (RR 4.7 p < .002) but not the 1 minute Apgar score. CONCLUSION: The RI identified gravidas at risk for low birth weight, low 5 minute Apgar score, and cesarean birth.