Bioactive peptides from scorpion venoms: therapeutic scaffolds and pharmacological tools / 中国天然药物

Evolution and natural selection have endowed animal venoms, including scorpion venoms, with a wide range of pharmacological properties. Consequently, scorpions, their venoms, and/or their body parts have been used since time immemorial in traditional medicines, especially in Africa and Asia. With respect to their pharmacological potential, bioactive peptides from scorpion venoms have become an important source of scientific research. With the rapid increase in the characterization of various components from scorpion venoms, a large number of peptides are identified with an aim of combating a myriad of emerging global health problems. Moreover, some scorpion venom-derived peptides have been established as potential scaffolds helpful for drug development. In this review, we summarize the promising scorpion venoms-derived peptides as drug candidates. Accordingly, we highlight the data and knowledge needed for continuous characterization and development of additional natural peptides from scorpion venoms, as potential drugs that can treat related diseases.

Identification of the target site of antimicrobial peptide AMP-17 against Candida albicans / 生物工程学报

Candida albicans is one of the major causes of invasive fungal infections and a serious opportunistic pathogen in immunocompromised individuals. The antimicrobial peptide AMP-17 has prominent anti-Candida activity, and proteomic analysis revealed significant differences in the expression of cell wall (XOG1) and oxidative stress (SRR1) genes upon the action of AMP-17 on C. albicans, suggesting that AMP-17 may exert anti-C. albicans effects by affecting the expression of XOG1 and SRR1 genes. To further investigate whether XOG1 and SRR1 genes were the targets of AMP-17, C. albicans xog1Δ/Δ and srr1Δ/Δ mutants were constructed using the clustered regulatory interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system. Phenotypic observations revealed that deletion of two genes had no significant effect on C. albicans growth and biofilm formation, whereas XOG1 gene deletion affected in vitro stress response and mycelium formation of C. albicans. Drug sensitivity assay showed that the MIC80 values of AMP-17 against xog1Δ/Δ and srr1Δ/Δ mutants increased from 8 μg/mL (for the wild type C. albicans SC5314) to 16 μg/mL, while the MIC80 values against srr1Δ/Δ: : srr1 revertants decreased to the level of the wild type SC5314. In addition, the ability of AMP-17 to inhibit biofilm formation of both deletion strains was significantly reduced compared to that of wild type SC5314, indicating that the susceptibility of the deletion mutants to AMP-17 was reduced in both the yeast state and during biofilm formation. These results suggest that XOG1 and SRR1 genes are likely two of the potential targets for AMP-17 to exert anti-C. albicans effects, which may facilitate further exploration of the antibacterial mechanism of novel peptide antifungal drugs.

Inhibition connexin 43 by mimetic peptide Gap27 mediates protective effects on 6-hydroxydopamine induced Parkinson's disease mouse model / 北京大学学报(医学版)

OBJECTIVE@#To explore whether the using of mimetic peptide Gap27, a selective inhibitor of connexin 43 (Cx43), could block the death of dopamine neurons and influence the expression of Cx43 in 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease mouse models.@*METHODS@#Eighteen C57BL/6 mice were randomly divided into control group, 6-OHDA group and 6-OHDA+Gap27 group, with 6 mice in each group. Bilateral substantia nigra stereotactic injection was performed. The control group was injected with ascorbate solution, 6-OHDA group was injected with 6-OHDA solution, and 6-OHDA+Gap27 group was injected with 6-OHDA and Gap27 mixed solution. Immuno-histochemical staining was used to detect the number of dopamine neurons, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of Cx43 messenger ribonucleic acid (mRNA), immuno-fluorescence staining was used to detect the distribution of Cx43 protein, the contents of Cx43 protein and Cx43 phosphorylation at serine 368 (Cx43-ps368) in mouse midbrain were detected by Western blot.@*RESULTS@#After injection of 6-OHDA, numerous dopamine neurons in substantia nigra died as Cx43 content increased, Cx43-ps368 content decreased. Mixing Gap27 while injecting 6-OHDA could reduce the number of death dopamine neurons and weaken the changes of Cx43 and Cx43-ps368 content caused by 6-OHDA. The number of tyrosine hydroxylase (TH) immunoreactive positive neurons in 6-OHDA group decreased to 27.7% ± 0.02% of the control group (P < 0.01); The number of TH immunoreactive positive neurons in 6-OHDA+Gap27 group was (1.64±0.16) times higher than that in 6-OHDA group (P < 0.05); The content of total Cx43 protein in 6-OHDA group was (1.44±0.07) times higher than that in 6-OHDA+Gap27 group (P < 0.05) while (1.68±0.07) times higher than that in control group (P < 0.01). In 6-OHDA group, the content of Cx43-ps368 protein and its proportion in total Cx43 protein were significantly lower than that in 6-OHDA+Gap27 group (P < 0.05).@*CONCLUSION@#In 6-OHDA mouse models, mimetic peptide Gap27 played a protective role in reducing the damage to substantia nigra dopamine neurons, which was induced by 6-OHDA. The overexpression of Cx43 protein might have neurotoxicity to dopamine neuron. Meanwhile, decreasing Cx43 protein level and keeping Cx43-ps368 protein level may be the protective mechanisms of Gap27.

Research progress of natural collagen peptides and its skincare efficacy / 生物医学工程学杂志

Natural collagen peptides are collagen hydrolysates. Because of their unique physicochemical properties and excellent biological activities, collagen peptides have been a research hotspot of cosmetic raw materials development and skincare efficacy improvement. Combined with the needs of the skincare efficacy and the development trends of cosmetics, the extraction methods and their structural characteristics of natural collagen peptides were summarized in detail. The applications and its research progress in skincare efficacy of collagen peptides, such as moisturizing and anti-wrinkle, trophism and anti-aging, filling and skin regeneration were expressed with emphasis. Finally, the development and practical applications in cosmetics of natural collagen peptides were adequately prospected.

Protective effect of Sika Deer bone polypeptide extract on dexamethasone-induced osteoporosis in rats

BACKGROUND: Osteoporosis attacks approximately 10% of the population worldwide. Sika Deer (Cervus nippon), one of China's precious traditional medicinal animals, has been widely recorded in ancient Chinese medical books and claimed for centuries to have numerous medical benefits including bone strengthening. This study aimed to find the use of Sika Deer bone in treating osteoporosis according to traditional records and to investigate the protective effect of Sika Deer bone polypeptide extract on glucocorticoidinduced osteoporosis (GIOP) in rats. RESULTS: Sika Deer bone polypeptide extract could increase serum Ca2+ and BGP, decrease serum P3+, ALP, PTH, and CT, but had no effect on serum NO in rats with GIOP. The immunohistochemical iNOS results of the rats' distal femur were negative in each group. Besides the model group, the eNOS color reaction in osteoblasts was strongly positive in the other three groups. CONCLUSIONS: Sika Deer bone polypeptide extract can improve pathological changes in the microstructure and stimulate the expression of eNOS in osteoblasts. The protective effect on bone might be mediated by eNOS-dependent NO generation.

Expression of antimicrobial peptide Cecropin P1 in Saccharomyces cerevisiae and its antibacterial and antiviral activity in vitro

BACKGROUND: Cecropin P1, acting as an antimicrobial, has a broad-spectrum antibacterial activity with some antiviral and antifungal properties. It is a promising natural alternative to antibiotics which is originally isolated from the pig intestinal parasitic nematode Ascaris suum. Many studies have shown that Cecropin P1 is helpful for the prevention or treatment of clinical diseases. Therefore, it is very necessary to establish a safe, nontoxic, and efficient expression method of Cecropin P1. RESULTS: The results indicated that the recombinant protein was about 5.5 kDa showed by Tricine­SDS­ PAGE and Western blot. And Cecropin P1 was efficiently secreted and expressed after 12 h of induction, with an increasing yield over the course of the induction. Its maximum concentration was 7.83 mg/L after concentration and purification. In addition, in vitro experiments demonstrated that Cecropin P1 not only exerted a strong inhibitory effect on Escherichia coli, Salmonella sp., Shigella sp., and Pasteurella sp., but also displayed an antiviral activity against PRRSV NADC30-Like strain. CONCLUSIONS: Collectively, the strategy of expressing Cecropin P1 in Saccharomyces cerevisiae is harmless, efficient, and safe for cells. In addition, the expressed Cecropin P1 has antiviral and antibacterial properties concurrently.

Oxidonitrergic and antioxidant effects of a low molecular weight peptide fraction from hardened bean (Phaseolus vulgaris) on endothelium

About 3000 tons of beans are not used in human food due to hardening. Several studies on bean-derived bioactive peptides have shown potential to treat some diseases, including those relying on oxidative dysfunctions. We assessed the effects of peptides extracted from hardened bean Phaseolus vulgaris (PV) on reactive oxygen species (ROS) and nitric oxide (NO) production, cytotoxic and cytoprotective effects in endothelial cells, and oxidonitrergic-dependent vasodilating effects. Extract was composed by peptide fraction <3 kDa (PV3) from hardened common bean residue. PV3 sequences were obtained and analyzed with bioinformatics. Human umbilical vein endothelial cells were treated with 10, 20, 30, and 250 µg/mL PV3. Oxidative stress was provoked by 3% H2O2. Cytotoxicity and cytoprotective effects were evaluated by MTT assay, whereas, ROS and NO were quantified using DHE and DAF-FM fluorescent probes by confocal microscopy. NO- and endothelium-dependent vasodilating effects of PV3 were assessed in isolated aortic rings. We found 35 peptides with an average mass of 1.14 kDa. There were no cell deaths with 10 and 20 μg/mL PV3. PV3 at 30 μg/mL increased cell viability, while cytotoxicity was observed only with 250 μg/mL PV3. PV3 at 10 μg/mL was able to protect cells from oxidative stress. PV3 also increased NO release without causing cell death. It also reduced relative ROS production induced by H2O2. PV3 vasodilating effects relied on endothelium-dependent NO release. PV3 obtained from low-commercial-value bean displays little cytotoxicity and exerts antioxidant effects, whereas it increases endothelial NO release.

Production of antimicrobial peptide (Oxysterlin 1) in Escherichia coli with ELP self-cleavage tag / 生物工程学报

Antimicrobial peptides are the most promising alternatives to antibiotics. However, the strategy of producing antimicrobial peptides by recombinant technology is complicated and expensive, which is not conducive to the large-scale production. Oxysterlin 1 is a novel type of cecropin antimicrobial peptide mainly targeting on Gram-negative bacteria and is of low cytotoxicity. In this study, a simple and cost-effective method was developed to produce Oxysterlin 1 in Escherichia coli. The Oxysterlin 1 gene was cloned into a plasmid containing elastin-like polypeptide (ELP) and protein splicing elements (intein) to construct the recombinant expression plasmid (pET-ELP-I-Oxysterlin 1). The recombinant protein was mainly expressed in soluble form in E. coli, and then the target peptide can be purified with a simple salting out method followed by pH changing. The final yield of Oxysterlin 1 was about 1.2 mg/L, and the subsequent antimicrobial experiment showed the expected antimicrobial activity. This study holds promise for large-scale production of antimicrobial peptides and the in-depth study of its antimicrobial mechanism.

Effects of Pigment Epithelium-derived Factor and Its Peptides on Proliferation, Apoptosis and Migration of Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#The anti-tumor effect of pigment epithelium-derived factor (PEDF) has been widely confirmed. However, the anti-tumor effect of its peptides is rarely reported. This study aims to investigate the effects of PEDF and its peptides on the apoptosis and migration of non-small cell lung cancer (NSCLC).@*METHODS@#In this study, A549 cells and H1299 cells were selected as the research object, and the cells were divided into normal group, PEDF treatment group, 34 peptide treatment group, 44 peptide treatment group and 34+44 peptide treatment group by administering different drugs at the same concentration to the cells. The proliferation activity of cells in each group was detected by CCK-8 method; the migration ability of cells was detected by scratch test; the expression levels of apoptosis related proteins such as protein kinase 3 (RIP3) and cleaved-caspase-3 were detected by Western blot; the expression levels of epithelial mesenchymal transition (EMT) markers in each group, such as cadherin (E-cadherin) and α-smooth muscle actin (α-SMA) were detected by Western blot; the apoptosis rate of each group was detected by flow cytometry.@*RESULTS@#The results of CCK-8 showed that PEDF and its peptides could inhibit cell proliferation, and the inhibitory effect of 34+44 peptide was the strongest (P<0.05); Observation under the microscope found that PEDF and its peptides can inhibit the proliferation and mesenchymal transformation of A549 cells and H1299 cells, and the inhibitory effect of the 34+44 peptide group is the most obvious; Western blot indicated that compared with other groups, the expressions of cleaved-caspase-3 and RIP3 in 34+44 peptide group were significantly higher (P<0.05), and the expressions of EMT protein E-cadherin were higher, the expression of α-SMA decreased (P<0.05); The results of flow cytometry showed that the apoptosis rate of 34+44 peptide group was significantly higher than those of other groups (P<0.05); The scratch test showed that compared with all the other groups, the healing rate of 34+44 peptide group was the lowest (P<0.05).@*CONCLUSIONS@#34+44 combination peptide can better promote the apoptosis of NSCLC, inhibit the migration of NSCLC, and thereby inhibit the growth of NSCLC.

Isolation and characterization of antihypertensive peptides from soy bean protein

Proteins and peptides are the most diverse biomolecules found in nature and make our interest due to their wide applications in food and pharmaceutical industry. Angiotensin Converting Enzyme (ACE) plays a major role in controlling blood pressure. The inhibition of ACE with peptides is a main target in the regulation of hypertension. The objective of the present study was to investigate the therapeutic potential of soy bean. This was accomplished by isolation of ACE inhibitory peptides using response surface methodology (RSM) and characterization of these bioactive peptides by mass spectrometry. 31 hydrolyzed fractions were isolated and evaluated for their ACE inhibition potential. Hydrolyzed fraction having highest ACE inhibitory activity was characterized by liquid chromatography-mass spectrometry (LC-MS) technique. RSM results showed maximum ACE inhibition potential (64%) by hydrolyzate was obtained at 45 ºC temperature, pH 8.0, E/S 0.2 in 2 hours hydrolysis time. Results of LC-MS analysis revealed Ser-Gly, Ser-Pro, Met-Ala, His-Ala, Lys-Pro, Phe-Thr, Met-Leu, Pro-Arg, Ala-Pro-Val, Pro-Ala-Leu, Val-Met-Gly, Pro-Leu-Val, Pro-Pro-Gln, His-Arg-Gly, Ser-Phe-Val-Leu, Ala-Val-His-Try, Arg-Thr-Val-Arg, His-His-Tyr-Leu-Val, Asp-Gly-Ala-Cys-Ser-Ala-Asn and MetVal-Thr-Gly-Pro-Gly-Cys-His bioactive peptides in hydrolyzed fraction of soy bean. Our data provide evidence that response surface methodology is a good approach for isolation of antihypertensive bioactive peptides with more potent activity as nutraceuticals or pharmaceuticals. Therefore soy bean can be use for industrial production of pharmaceutical grade natural medicines for handling high blood pressure.

Exenatide ameliorates hepatic steatosis and attenuates fat mass and FTO gene expression through PI3K signaling pathway in nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with metabolic syndrome and can lead to life-threatening complications like hepatic carcinoma and cirrhosis. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist antidiabetic drug, has the capacity to overcome insulin resistance and attenuate hepatic steatosis but the specific underlying mechanism is unclear. This study was designed to investigate the underlying molecular mechanisms of exenatide therapy on NAFLD. We used in vivo and in vitro techniques to investigate the protective effects of exenatide on fatty liver via fat mass and obesity associated gene (FTO) in a high-fat (HF) diet-induced NAFLD animal model and related cell culture model. Exenatide significantly decreased body weight, serum glucose, insulin, insulin resistance, serum free fatty acid, triglyceride, total cholesterol, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels in HF-induced obese rabbits. Histological analysis showed that exenatide significantly reversed HF-induced lipid accumulation and inflammatory changes accompanied by decreased FTO mRNA and protein expression, which were abrogated by PI3K inhibitor LY294002. This study indicated that pharmacological interventions with GLP-1 may represent a promising therapeutic strategy for NAFLD.

Intestinal inflammatory and redox responses to the perioperative administration of teduglutide in rats

Abstract Purpose: To investigate the inflammatory and redox responses to teduglutide on an animal model of laparotomy and intestinal anastomosis. Methods: Wistar rats (n=62) were allocated into four groups: "Ileal Resection and Anastomosis" vs. "Laparotomy", each one split into "Postoperative Teduglutide Administration" vs. "No Treatment"; and euthanized at the third or the seventh day. Ileal and blood samples were recovered at the baseline and at the euthanasia. Flow cytometry was used to study the inflammatory response (IL-1α, MCP-1, TNF-α, IFN-γ and IL-4 levels), oxidative stress (cytosolic peroxides, mitochondrial reactive species, intracellular glutathione and mitochondrial membrane potential) and cellular viability and death (annexin V/propidium iodide double staining). Results: Postoperative teduglutide treatment was associated with higher cellular viability index and lower early apoptosis ratio at the seventh day; higher cytosolic peroxides level at the third day and mitochondrial overgeneration of reactive species at the seventh day; higher tissue concentration of IL-4 and lower local pro-to-anti-inflammatory cytokines ratio at the seventh day. Conclusion: Those findings suggest an intestinal pro-oxidative and anti-inflammatory influence of teduglutide on the peri-operative context with a potential interference in the intestinal anastomotic healing.

Avaliação de biodisponibilidade e mecanismos de ação hipocolesterolemizante de peptídeos do amaranto (Amaranthus cruentus L. BRS-Alegria) / Evaluation of bioavailability and hypocholesterolemic mechanisms of peptides from Amaranth (Amaranthus cruentus L. BRS-Alegria)

Introdução: Doenças cardiovasculares constituem importante causa de morte em todo mundo e a hipercolesterolemia está diretamente relacionada a este problema de saúde pública. A dieta desempenha papel importante neste processo e alguns alimentos, como o amaranto (Amaranthus cruentus L. BRSAlegria), têm mostrado capacidade de redução do colesterol plasmático. Estudos sugerem que este efeito está relacionado a peptídeos liberados durante a digestão das proteínas, os quais atuam na modulação do metabolismo lipídico. Considerando-se que os efeitos da digestão gastrointestinal e da absorção destes peptídeos são claramente complexos torna-se importante a realização de estudos visando avaliar bioacessibilidade e mecanismos de ação destes peptídeos nos locais alvo do organismo. Objetivo: Analisar a biodisponibilidade de peptídeos em modelos animais após ingestão de isolado proteico de amaranto e relacioná-la com parâmetros ligados ao metabolismo do colesterol. Métodos: O amaranto teve sua proteína isolada. Os peptídeos da proteína do amaranto foram analisados após digestão in vitro. Dois experimentos in vivo foram conduzidos: um de fase aguda e outro de média duração. No primeiro, o isolado proteico de amaranto foi administrado a ratos e os peptídeos no sangue foram monitorados por 2 horas para verificação de fragmentos que resistissem à digestão gastrointestinal. O experimento in vivo 2 consistiu na alimentação de 3 grupos de hamster, um com dieta recomendada pela AIN93 (grupo N) e dois com dietas hipercolesterolêmicas por 21 dias, contendo a proteína de amaranto como única proteína da ração (grupo I), comparada ao controle de caseína (grupo H). Neste experimento foram analisados no plasma: peptídeos, colesterol total e frações; nas fezes: colesterol total e ácidos biliares; no fígado: colesterol, lipídeos totais, ácidos graxos, atividade enzimática da Hmgcr, expressão de Hmgcr, Srebf2, Lxr, Abca1, Abcg8 e Ampk. Resultados e discussão: Foram identificados fragmentos peptídicos provenientes da digestão in vitro do isolado proteico de amaranto, e outras dezenas de sequencias peptídicas em ratos após administração aguda de amaranto foram analisadas. Destaca-se a identificação do peptídeo ALGV, presente em proteína do amaranto de acordo com banco de dados, e similar a fragmentos com ação hipocolesterolemizante. No sangue de hamsters foram encontrados seis peptídeos com 100 por cento de cobertura e similaridade a base de dados de proteínas de amaranto, merecendo investigação sobre seus efeitos. Verificou-se que o isolado proteico de amaranto foi capaz de suprimir a hipercolesterolemia quando a dieta hipercolesterolemizante foi introduzida em paralelo a este ingrediente, com valores inferiores em 72 por cento (triglicerídeos), 64 por cento (colesterol total), 80 por cento (LDL-c) do grupo I em relação ao grupo H. Foi observada ainda menor concentração de colesterol e lipídeos totais no fígado dos animais do grupo I em relação ao grupo H (177 x 464 mg de colesterol/100 g de tecido; 2,06 x 2,86 g de lipídeos/100 g de tecido, respectivamente). Parâmetros lipídicos do sangue, das fezes e do fígado foram similares aos do grupo N, cuja dieta seguiu a preconização para roedores. Foi observada maior excreção de colesterol total no grupo I em relação ao grupo H, mas não houve maior excreção de ácidos biliares nas fezes. Não houve mudança na expressão dos genes analisados neste estudo, mas o amaranto reduziu a atividade da enzima Hmgcr. Postulase que parâmetros como expressão de Ldlr e atividade da Acat sejam alterados pela ingestão de amaranto. O perfil de ácidos graxos também foi modificado de forma a se assimilar ao grupo N, porém deve-se verificar parâmetros inflamatórios devido à maior proporção de ácido araquidônico em relação aos demais grupos estudados. Conclusão: Verifica-se biodisponibilidade dos peptídeos do amaranto e ação hipocolesterolemizante e hipolipemiante em diversas vias metabólicas, promovendo proteção cardiovascular

Introduction: Cardiovascular diseases are important causes of death worldwide, and hypercholesterolemia is directly related to this public health problem. Diet plays an important role in this process and some foods such as amaranth (Amaranthus cruentus L. BRS-Alegria) have been shown to reduce plasma cholesterol. Studies suggest that this effect is related to peptides released during the digestion of proteins, which would play an important role in the modulation of lipid metabolism. Considering that the effects of gastrointestinal digestion and the absorption of these peptides are clearly complex, it is important to carry out studies aiming to evaluate their bioaccessibility and evaluation of the mechanisms of action of these peptides in the target sites of the organism. Objective: To analyze the bioavailability of peptides in animal models after ingestion of amaranth protein isolate and to relate it to parameters associated to cholesterol metabolism. Methods: The amaranth was crushed, the flour was defatted and its protein isolated. Amaranth peptides were analysed after in vitro digestion. Two in vivo experiments were conducted: one of acute phase and one of medium duration. In the first, the amaranth protein isolate was administered to rats and the peptides in the blood were monitored for 2 hours to check for fragments that resisted gastrointestinal digestion. The in vivo experiment 2 consisted of feeding three groups of hamsters, one with a diet recommended by AIN93 (group N) and two with hypercholesterolemic diets for 21 days, containing amaranth protein as the only dietary protein (group I), compared to casein control (group H). In this experiment were analyzed in the plasma: peptides, total cholesterol and fractions; In feces: total cholesterol and bile acids; In the liver: cholesterol, total lipids, fatty acids, Hmgcr enzymatic activity, Hmgcr expression, Srebf-2, Lxr, Abca1, Abcg8 and Ampk. Results and discussion: Peptide fragments from the in vitro digestion of amaranth protein isolate were identified and other dozens of peptide sequences were found in rats after acute amaranth administration. A higher number of peptides were found in the serum in relation to the plasma of the animals. Remarkably, ALGV peptide was found in serum of rats. This peptide is present in amaranth protein, according to databases, and is similar to fragments that present hypocholesterolemic action. In the blood of hamsters it could be found six peptides with 100 per cent coverage and similarity to the database of amaranth proteins, deserving investigation about their effects. Amaranth protein was able to suppress hypercholesterolemia when the hypercholesterolemic diet was introduced in parallel with this ingredient, with values lower for group I in 72 per cent (triglycerides), 64 per cent (total cholesterol), 80 per cent (LDL-c) in relation to the H group. A lower concentration of cholesterol and total lipids were observed in the liver of the group I compared to the H group (177 x 464 mg cholesterol / 100 g of tissue, 2.06 x 2,86 g lipids / 100 g of tissue, respectively). Lipid parameters of blood, faeces and liver were similar to those of group N, whose diet followed the recommendation for rodents. There was greater excretion of total cholesterol in group I in relation to group H, but there was no greater excretion of bile acids in feces, indicating that the effect of amaranth protein may be due to increased transintestinal cholesterol excretion, decreased micellar solubilization of cholesterol and / or modification in the expression of cholesterol transport related proteins in the intestine. There was no change in the expression of the genes analyzed in this study, but amaranth reduced the activity of the Hmgcr enzyme. It is postulated that parameters such as Ldlr expression and Acat activity are altered by amaranth intake. The fatty acid profile was also modified in order to assimilate to the N group, but inflammatory parameters related to amaranth intake should be verified due to the higher proportion of arachidonic acid in relation to the higher proportion of arachidonic acid in relation to the other groups studied. Conclusion: The bioavailability of amaranth peptides and hypocholesterolemic and hypolipidemic activity in several metabolic pathways is verified, therefore promoting cardiovascular protection

Amyloid-beta immunotherapy: the hope for Alzheimer disease? / Inmunoterapia beta-amiloide: ¿la esperanza para la enfermedad de Alzheimer?

Abstract Alzheimer disease (AD) is the most prevalent form of dementia of adult-onset, characterized by progressive impairment in cognition and memory. There is no cure for the disease and the current treatments are only symptomatic. Drug discovery is an expensive and time-consuming process; in the last decade no new drugs have been found for AD despite the efforts of the scientific community and pharmaceutical companies. The Aβ immunotherapy is one of the most promising approaches to modify the course of AD. This therapeutic strategy uses synthetic peptides or monoclonal antibodies (mAb) to decrease the Aβ load in the brain and slow the progression of the disease. Therefore, this article will discuss the main aspects of AD neuropathogenesis, the classical pharmacologic treatment, as well as the active and passive immunization describing drug prototypes evaluated in different clinical trials.

Resumen La enfermedad de Alzheimer (EA) es la forma más frecuente de demencia de inicio en el adulto, caracterizada por un deterioro progresivo en la cognición y la memoria. No hay cura para la enfermedad y los tratamientos actuales son sólo sintomáticos. El descubrimiento de fármacos es un proceso costoso y que consume mucho tiempo; en la última década no se han encontrado nuevos fármacos para la EA a pesar de los esfuerzos de la comunidad científica y las compañías farmacéuticas. La inmunoterapia contra Aβ es uno de los enfoques más prometedores para modificar el curso de la EA. Esta estrategia terapéutica utiliza péptidos sintéticos o anticuerpos monoclonales (mAb) para disminuir la carga de Aβ en el cerebro y retardar la progresión de la enfermedad. Por lo tanto, este artículo discutirá los principales aspectos de la neuropatogénesis de la EA, el tratamiento farmacológico clásico, así como la inmunización activa y pasiva describiendo los prototipos de fármacos evaluados en diferentes ensayos clínicos.

Improvement of erectile dysfunction by the active pepide from urechis unicinctus by high temperature/pressure and ultra - wave assisted lysis in streptozotocin induced diabetic rats

ABSTRACT Introduction: We investigate the effect of active peptide from Urechis unicinctus (UU) by high temperature/pressure and ultra-wave assisted lysis on erectile dysfunction in streptozotocin-induced diabetic rats. Materials and Methods: Forty 12-week-old Sprague-Dawley rats were used in this study. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (50mg/kg). One week later, the diabetic rats were randomly divided into four groups: normal control, untreated diabetes control, and groups treated with 100 or 500mg/kg/d UU peptide. Rats were fed with UU peptide by intragastric administration for 8 weeks. After 8 weeks, penile hemodynamic function was evaluated in all groups by measuring the intracavernosal pressure after electrostimulating the cavernous nerve. Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) activities were measured and endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) protein expression was determined by Western blot. Results: Maximum intracavernosal pressure in diabetic control rats decreased significantly compared to normal control rats, and was increased significantly compared to untreated diabetic rats after UU peptide supplementation. Treatment with the higher dose of UU peptide significantly increased the NO and cGMP levels compared with the diabetic control group. Decreased activity and expression eNOS and nNOS were found in the diabetic rats compared with the normal control group. Decreased eNOS and nNOS in diabetic rats were improved by UU peptide administration. Conclusions: Active peptide from UU ameliorates erectile function in a streptozotocin induced diabetic rat model of erectile dysfunction.

Glucagon-like peptide 1 improves insulin resistance in vitro through anti-inflammation of macrophages

Glucagon-like peptide 1 (GLP-1), a kind of gut hormone, is used in the treatment of type 2 diabetes (T2D). Emerging evidence indicates that GLP-1 has anti-inflammatory activity. Chronic inflammation in the adipose tissue of obese individuals is a cause of insulin resistance and T2D. We hypothesized that GLP-1 analogue therapy in patients with T2D could suppress the inflammatory response of macrophages, and therefore inhibit insulin resistance. Our results showed that GLP-1 agonist (exendin-4) not only attenuated macrophage infiltration, but also inhibited the macrophage secretion of inflammatory cytokines including TNF-β, IL-6, and IL-1β. Furthermore, we observed that lipopolysaccharide (LPS)-induced macrophage conditioned media could impair insulin-stimulated glucose uptake. This effect was compensated by treatment with the conditioned media from macrophages treated with the combination of LPS and exendin-4. It was also observed that exendin-4 directly inhibited the activation of NF-κB in macrophages. In conclusion, our results indicated that GLP-1 improved inflammatory macrophage-derived insulin resistance by inhibiting NF-κB pathway and secretion of inflammatory cytokines in macrophages. Furthermore, our observations suggested that the anti-inflammatory effect of GLP-1 on macrophages can contribute to GLP-1 analogue therapy of T2D.

Prevalência de diagnóstico médico de asma em adultos brasileiros: Pesquisa Nacional de Saúde, 2013 / Prevalence of asthma medical diagnosis among Brazilian adults: National Health Survey, 2013

RESUMO: Objetivo: Estimar a prevalência de diagnóstico médico de asma na população adulta brasileira (≥ 18 anos). Métodos: Estudo transversal de base populacional com dados da Pesquisa Nacional de Saúde (PNS), de 2013; processo amostral por conglomerado com três estágios de seleção: setor censitário, domicílio e indivíduo. Calculou-se a prevalência e intervalo de confiança de 95% (IC95%) do desfecho "diagnóstico médico de asma" relatado pelo entrevistado e sua distribuição conforme variáveis demográficas, socioeconômicas, macrorregiões e zona urbana ou rural do país. Ainda foi investigado o manejo da asma naqueles que responderam afirmativamente sobre o diagnóstico médico; as análises foram ponderadas. Resultados: Foram entrevistados 60.202 adultos. A prevalência do diagnóstico médico de asma foi de 4,4% (IC95% 4,1 - 4,7), maior no sexo feminino, nos de cor branca, com maior escolaridade e moradores na região Sul; entre aqueles com diagnóstico médico, observou-se percentual elevado (38,2%) de crises de asma nos últimos 12 meses, com cerca de 80% usando medicação e 15% com limitação severa às atividades diárias. Conclusões: Apesar da estabilidade da prevalência da asma comparada a estudos anteriores no país, ainda são necessárias políticas para melhor manejo da doença.

ABSTRACT: Objective: To estimate the prevalence of asthma medical diagnosis among the adult Brazilian population (aged ≥ 18 years). Methods: This is a cross-sectional, population-based study from the 2013 National Health Survey (NHS); it is a sampling cluster process with three stages of selection: census tracts, households, and individuals. The prevalence and 95% confidence interval for the outcome "asthma medical diagnosis" reported by the interviewed subjects were calculated, besides its distribution according to demographic and socioeconomic variables, macroregions, and urban or rural area of the country. Management of the disease was also evaluated among those who reported asthma medical diagnosis and the analyses were weighted. Results: A total of 60,202 adults were interviewed. The prevalence of asthma medical diagnosis was 4.4% (95%CI 4.1 - 4.7), and it was higher among the female subjects, the white skin-colored subjects, those with higher educational level, and those who lived in the south of Brazil. Among those who reported asthma medical diagnosis, a high percentage of asthma attacks were seen in the last 12 months, with around 80% using medication and about 15% referring severe limitation to their daily activities. Conclusions: Although it seems there is asthma diagnosis stability in the country when compared with other researches, we still need public policies for improving the disease management.

Consumo de bebidas alcoólicas e direção de veículos nas capitais brasileiras e no Distrito Federal, segundo dois inquéritos nacionais de saúde / Alcohol consumption and driving in Brazilian capitals and Federal District according to two national health surveys

RESUMO: Objetivo Apresentar os resultados dos indicadores sobre consumo de álcool e direção para as capitais brasileiras obtidos em dois inquéritos populacionais realizados em 2013 no Brasil. Métodos: Estudo transversal realizado com dados da população adulta (≥ 18 anos) participante da Vigilância de Doenças Crônicas por Inquérito Telefônico (Vigitel) e da Pesquisa Nacional de Saúde (PNS). Foram calculadas as prevalências para os indicadores de consumo de bebida alcoólica e direção veicular. Resultados: A proporção de motoristas adultos de carro ou moto que dirigiram logo depois de beber foi significativamente maior no sexo masculino (29,3% - Vigitel; 24,4% - PNS), entre jovens de 18 a 29 anos (31,6% - Vigitel; 24,1% - PNS) e entre os residentes das capitais da Região Centro-Oeste (33,7% - Vigitel; 28,3% - PNS). A proporção de adultos que referiram beber e dirigir foi maior no sexo masculino (9,4% - Vigitel; 7,4% - PNS), no grupo de 18 a 29 anos (7,1% - Vigitel; 4,5% - PNS) e entre os residentes das capitais da Região Centro-Oeste (7,9% - Vigitel; 6,1% - PNS). Conclusão: O estudo permitiu estimar a prevalência do hábito de dirigir após ingestão de bebida alcoólica entre motoristas e na população em geral e mostrou coerência entre os resultados dos dois inquéritos epidemiológicos de abrangência nacional.

ABSTRACT: Objective: To present the results of indicators of alcohol consumption and driving for Brazilian capitals based on two population surveys performed in Brazil in 2013. Methods: Cross sectional study with data from adults (≥ 18 years) participants of the Telephone Survey on Risk and Protective Factors for Chronic Diseases (Vigitel) and the National Health Survey (NHS). Prevalence for indicators of alcohol consumption and driving was then calculated. Results: The proportion of adult drivers who drove soon after drinking was significantly higher among males (29.3% - Vigitel and 24.4% - NHS), the young aging 18 to 29 years (31.6% - Vigitel and 24.1% - NHS) and among residents of the capitals of the Midwest (33.7% - Vigitel and 28.3% - NHS). The proportion of adults who reported drinking and driving was higher among males (9.4% - Vigitel and 7.4% - NHS) in the 18 to 29 age group (7.1% - Vigitel; 4.5% - NHS), and among residents of the capitals of the Midwest (7.9% - Vigitel and 6.1% - NHS). Conclusion: The study estimated the prevalence of the habit of driving after alcohol consumption among drivers and in the general population. There was consistency between the results from two nationwide surveys.

Prevalência de doenças crônicas não transmissíveis e associação com autoavaliação de saúde: Pesquisa Nacional de Saúde, 2013 / Prevalence of chronic non-communicable diseases and association with self-rated health: National Health Survey, 2013

Resumo: Objetivo: Analisar o perfil de dez doenças crônicas não transmissíveis investigadas na Pesquisa Nacional de Saúde realizada no Brasil em 2013 e sua associação com a autoavaliação da saúde. Métodos: Estudo transversal de base populacional e abrangência nacional com 60.202 indivíduos com 18 anos ou mais. Foi utilizado processo amostral por conglomerado com três estágios de seleção: setor censitário, domicílio e indivíduo. Calculou-se a prevalência das doenças crônicas e os intervalos de confiança de 95% por idade, sexo e escolaridade, a idade média do primeiro diagnóstico e a proporção de limitação das atividades habituais. Para testar a associação com a autoavaliação de saúde, utilizou-se o procedimento de regressão logística ajustada por sexo e idade. Resultados: As doenças mais prevalentes foram hipertensão arterial (21,4%), depressão (7,6%), artrite (6,4%) e diabetes mellitus (6,2%). Indivíduos com diagnóstico de acidente vascular cerebral (AVC) referiram maior limitação das atividades habituais (38,6%). Observou-se um gradiente na prevalência segundo idade e escolaridade, e todas as doenças foram mais frequentes entre as mulheres. Pior autoavaliação de saúde foi encontrada entre aqueles com diagnóstico de AVC (OR = 3,60; valor de p < 0,001) e nos que referiram duas doenças (OR = 5,53; valor de p < 0,001) ou três ou mais doenças (OR = 10,86; valor de p < 0,001). Conclusões: Por se tratar de doenças associadas a fatores de risco modificáveis, a prevenção com foco populacional é a melhor estratégia para redução da carga dessas doenças.

ABSTRACT: Objective: To analyze the profile of 10 chronic noncommunicable diseases investigated in the National Health Survey carried out in Brazil in 2013 and their association with the self-rated health. Methods: A cross-sectional, population-based nationwide study with 60,202 individuals aged 18 years old or more. Sampling process by conglomerate was carried out in three stages of selection: census tract, household, and individual. The prevalence of chronic diseases by age, gender and educational status and the confidence intervals of 95% , the mean age at the first diagnosis and the proportion of limitation of the usual activities were calculated. To test the association with self-rated health, the logistic regression procedure adjusted for gender and age was used. Results: The more prevalent diseases were hypertension (21.4%), depression (7.6%), arthritis (6.4%), and diabetes mellitus (6.2%). Individuals diagnosed with stroke reported greater limitations in the daily activities (38.6%). There was a gradient in the prevalence by age and educational level, and all the diseases were more frequent among women. A worse self-rated health was observed among those with a diagnosis of stroke (OR = 3.60; p < 0.001) and those who referred two diseases (OR = 5.53; p < 0.001) or three or more diseases (OR = 10.86; p < 0.001). Conclusions: Because these diseases are associated with modifiable risk factors, the prevention with population focus is the best strategy to reduce the burden of these diseases.