Biology of Glyphepomis dubia Campos & Souza, 2016 (Hemiptera: Pentatomidae) and the parasitoids Telenomus podisi Ashmead, 1893 and Trissolcus basalis (Wollaston, 1858) (Hymenoptera: Platygastridae) on rice / Biologia de Glyphepomis dubia Campos & Souza, 2016 (Hemiptera: Pentatomidae) e dos parasitoides Telenomus podisi Ashmead, 1893 e Trissolcus basalis (Wollaston, 1858 (Hymenoptera: Platygastridae) em arroz

Abstract The life cycle of stink bug, Glyphepomis dubia and the development of two egg parasitoids (Telenomus podisi and Trissolcus basalis) were studied at the Federal University of Maranhão, at 26 ± 2oC, relative humidity (RH) of 60 ± 10% and 12h photophase. Individuals used in the study were collected from seven rice fields located around the municipality of Arari, Maranhão, Brazil, and maintained in greenhouse and laboratory for the life cycle studies. From egg to adult, G. dubia took 35.2 days to complete the life cycle. The oviposition period was 37 days, with egg masses of about 12 eggs each and viability of 93.1%. Longevity was 53 and 65 days for females and males, respectively. The egg parasitoids Te. podisi and Tr. basalis parasitized and developed in G. dubia eggs; however, the biological characteristics of Tr. basalis were affected. Emergence of the parasitoids was higher for Te. podisi (83.5%) compared to the records for Tr. basalis (50.4%). Therefore, G. dubia may potentially achieve a pest status and Te. podisi is a promising biological control agent for G. dubia management in Brazil due to its higher longevity and better reproductive parameters.

Resumo O ciclo de vida do percevejo, Glyphepomis dubia e a biologia de dois parasitoides de ovos (Telenomus podisi e Trissolcus basalis) foram estudados na Universidade Federal do Maranhão, a 26 ± 2oC, umidade relativa (UR) de 60 ± 10% e fotofase de 12h. Sete indivíduos de G. dubia foram coletados em lavoura de arroz localizada no município de Arari, Maranhão, Brasil e mantidos em casa de vegetação e laboratório para estudos de ciclo de vida. Do ovo ao adulto, G. dubia levou 35.2 dias para completar o ciclo de vida. O período de oviposição foi de 37 dias com massas de ovos com cerca de 12 ovos/massa e viabilidade de 93.1%. A longevidade foi de 53 e 65 dias, respectivamente, para fêmeas e machos. Os parasitoides de ovos, Te. podisi e Tr. basalis parasitaram e se desenvolveram em ovos de G. dubia, no entanto as características biológicas de Tr. basalis foi afetada. A emergência dos parasitoides foi maior para Te. podisi (83.5%) em comparação com o registrado para Tr. basalis (50.4%). Portanto, G. dubia poderá apresentar potencial para atingir o status de praga e Te. podisi é um promissor agente de controle biológico para ser utilizado no manejo de G. dubia no Brasil, pois apresentou maior longevidade e os melhores parâmetros reprodutivos.

Biology of Glyphepomis dubia Campos & Souza, 2016 (Hemiptera: Pentatomidae) and the parasitoids Telenomus podisi Ashmead, 1893 and Trissolcus basalis (Wollaston, 1858) (Hymenoptera: Platygastridae) on rice / Biologia de Glyphepomis dubia Campos & Souza, 2016 (Hemiptera: Pentatomidae) e dos parasitoides Telenomus podisi Ashmead, 1893 e Trissolcus basalis (Wollaston, 1858) (Hymenoptera: Platygastridae) em arroz

The life cycle of stink bug, Glyphepomis dubia and the development of two egg parasitoids (Telenomus podisi and Trissolcus basalis) were studied at the Federal University of Maranhão, at 26 ± 2oC, relative humidity (RH) of 60 ± 10% and 12h photophase. Individuals used in the study were collected from seven rice fields located around the municipality of Arari, Maranhão, Brazil, and maintained in greenhouse and laboratory for the life cycle studies. From egg to adult, G. dubia took 35.2 days to complete the life cycle. The oviposition period was 37 days, with egg masses of about 12 eggs each and viability of 93.1%. Longevity was 53 and 65 days for females and males, respectively. The egg parasitoids Te. podisi and Tr. basalis parasitized and developed in G. dubia eggs; however, the biological characteristics of Tr. basalis were affected. Emergence of the parasitoids was higher for Te. podisi (83.5%) compared to the records for Tr. basalis (50.4%). Therefore, G. dubia may potentially achieve a pest status and Te. podisi is a promising biological control agent for G. dubia management in Brazil due to its higher longevity and better reproductive parameters.

O ciclo de vida do percevejo, Glyphepomis dubia e a biologia de dois parasitoides de ovos (Telenomus podisi e Trissolcus basalis) foram estudados na Universidade Federal do Maranhão, a 26 ± 2oC, umidade relativa (UR) de 60 ± 10% e fotofase de 12h. Sete indivíduos de G. dubia foram coletados em lavoura de arroz localizada no município de Arari, Maranhão, Brasil e mantidos em casa de vegetação e laboratório para estudos de ciclo de vida. Do ovo ao adulto, G. dubia levou 35.2 dias para completar o ciclo de vida. O período de oviposição foi de 37 dias com massas de ovos com cerca de 12 ovos/massa e viabilidade de 93.1%. A longevidade foi de 53 e 65 dias, respectivamente, para fêmeas e machos. Os parasitoides de ovos, Te. podisi e Tr. basalis parasitaram e se desenvolveram em ovos de G. dubia, no entanto as características biológicas de Tr. basalis foi afetada. A emergência dos parasitoides foi maior para Te. podisi (83.5%) em comparação com o registrado para Tr. basalis (50.4%). Portanto, G. dubia poderá apresentar potencial para atingir o status de praga e Te. podisi é um promissor agente de controle biológico para ser utilizado no manejo de G. dubia no Brasil, pois apresentou maior longevidade e os melhores parâmetros reprodutivos.

Biology of Glyphepomis dubia Campos & Souza, 2016 (Hemiptera: Pentatomidae) and the parasitoids Telenomus podisi Ashmead, 1893 and Trissolcus basalis (Wollaston, 1858) (Hymenoptera: Platygastridae) on rice

Abstract The life cycle of stink bug, Glyphepomis dubia and the development of two egg parasitoids (Telenomus podisi and Trissolcus basalis) were studied at the Federal University of Maranhão, at 26 ± 2oC, relative humidity (RH) of 60 ± 10% and 12h photophase. Individuals used in the study were collected from seven rice fields located around the municipality of Arari, Maranhão, Brazil, and maintained in greenhouse and laboratory for the life cycle studies. From egg to adult, G. dubia took 35.2 days to complete the life cycle. The oviposition period was 37 days, with egg masses of about 12 eggs each and viability of 93.1%. Longevity was 53 and 65 days for females and males, respectively. The egg parasitoids Te. podisi and Tr. basalis parasitized and developed in G. dubia eggs; however, the biological characteristics of Tr. basalis were affected. Emergence of the parasitoids was higher for Te. podisi (83.5%) compared to the records for Tr. basalis (50.4%). Therefore, G. dubia may potentially achieve a pest status and Te. podisi is a promising biological control agent for G. dubia management in Brazil due to its higher longevity and better reproductive parameters.

Resumo O ciclo de vida do percevejo, Glyphepomis dubia e a biologia de dois parasitoides de ovos (Telenomus podisi e Trissolcus basalis) foram estudados na Universidade Federal do Maranhão, a 26 ± 2oC, umidade relativa (UR) de 60 ± 10% e fotofase de 12h. Sete indivíduos de G. dubia foram coletados em lavoura de arroz localizada no município de Arari, Maranhão, Brasil e mantidos em casa de vegetação e laboratório para estudos de ciclo de vida. Do ovo ao adulto, G. dubia levou 35.2 dias para completar o ciclo de vida. O período de oviposição foi de 37 dias com massas de ovos com cerca de 12 ovos/massa e viabilidade de 93.1%. A longevidade foi de 53 e 65 dias, respectivamente, para fêmeas e machos. Os parasitoides de ovos, Te. podisi e Tr. basalis parasitaram e se desenvolveram em ovos de G. dubia, no entanto as características biológicas de Tr. basalis foi afetada. A emergência dos parasitoides foi maior para Te. podisi (83.5%) em comparação com o registrado para Tr. basalis (50.4%). Portanto, G. dubia poderá apresentar potencial para atingir o status de praga e Te. podisi é um promissor agente de controle biológico para ser utilizado no manejo de G. dubia no Brasil, pois apresentou maior longevidade e os melhores parâmetros reprodutivos.

Biology of Glyphepomis dubia Campos & Souza, 2016 (Hemiptera: Pentatomidae) and the parasitoids Telenomus podisi Ashmead, 1893 and Trissolcus basalis (Wollaston, 1858) (Hymenoptera: Platygastridae) on rice.

The life cycle of stink bug, Glyphepomis dubia and the development of two egg parasitoids (Telenomus podisi and Trissolcus basalis) were studied at the Federal University of Maranhão, at 26 ± 2oC, relative humidity (RH) of 60 ± 10% and 12h photophase. Individuals used in the study were collected from seven rice fields located around the municipality of Arari, Maranhão, Brazil, and maintained in greenhouse and laboratory for the life cycle studies. From egg to adult, G. dubia took 35.2 days to complete the life cycle. The oviposition period was 37 days, with egg masses of about 12 eggs each and viability of 93.1%. Longevity was 53 and 65 days for females and males, respectively. The egg parasitoids Te. podisi and Tr. basalis parasitized and developed in G. dubia eggs; however, the biological characteristics of Tr. basalis were affected. Emergence of the parasitoids was higher for Te. podisi (83.5%) compared to the records for Tr. basalis (50.4%). Therefore, G. dubia may potentially achieve a pest status and Te. podisi is a promising biological control agent for G. dubia management in Brazil due to its higher longevity and better reproductive parameters.

Degradation of diclofenac in water under LED irradiation using combined g-C3N4/NH2-MIL-125 photocatalysts.

This study reports the photocatalytic degradation of diclofenac by hybrid materials prepared by combination of graphitic carbon nitride (g-C3N4) and titanium-metal organic framework (NH2-MIL-125), in different mass proportions (MOF:C3N4 of 25:75, 50:50 and 75:25). The hybrid materials were fully characterized, and their properties compared to those of the individual components, whose presence was confirmed by XRD. The porous structure was the result of the highly microporous character of the MOF and the non-porous one of g-C3N4. The band gap values were very close to that of MOF component. Photoluminescence measurements suggested an increase on the recombination rate associated to the presence of g-C3N4. Photodegradation tests of diclofenac (10 mg·L-1) were performed under UV LED irradiation at 384 nm. The hybrid materials showed higher photocatalytic activity than the individual components, suggesting the occurrence of some synergistic effect. The photocatalyst with a MOF:g-C3N4 ratio of 50:50 yielded the highest conversion rate, allowing complete disappearance of diclofenac in 2 h. Experiments with scavengers showed that superoxide radicals and holes played a major role in the photocatalytic process photodegradation, being that of hydroxyl radicals less significant. From the identification of by-products species, a degradation pathway was proposed for the degradation of diclofenac under the experimental operating conditions.

Co-delivery of immunomodulators in biodegradable nanoparticles improves therapeutic efficacy of cancer vaccines.

To improve the efficacy of cancer vaccines we aimed to modulate the suppressive tumor microenvironment. In this study, the potential of intratumoral immune modulation with poly (I:C), Resiquimod (R848) and CCL20 (MIP3α) was explored. Biodegradable polymeric nanoparticles were used as delivery vehicles for slow and sustained release of these drugs in the tumor area and were combined with specific immunotherapy based on therapeutic peptide vaccination in two aggressive murine carcinoma and lymphoma tumor models. Whereas nanoparticle delivery of poly (I:C) or R848 improved therapeutic efficacy, the combination with MIP3α remarkably potentiated the cancer vaccine antitumor effects. The long-term survival increased to 75-100% and the progression free survival nearly doubled on mice with established large carcinoma tumors. The potent adjuvant effects were associated with lymphoid and myeloid population alterations in the tumor and tumor-draining lymph node. In addition to a significant influx of macrophages into the tumor, the phenotype of the suppressor tumor-associated macrophages shifted towards an acute inflammatory phenotype in the tumor-draining lymph node. Overall, these data show that therapeutic cancer vaccines can be potentiated by the combined nanoparticle mediated co-delivery of poly (I:C), R848 and MIP3α, which indicates that a more favorable milieu for cancer fighting immune cells is created for T cells induced by therapeutic cancer vaccines.

Phytoscreening of Vochysiaceae species: Molecular identification by HPLC-ESI-MS/MS and evaluating of their antioxidant activity and inhibitory potential against human α-amylase and protein glycation.

Scientific research based on medicinal plants has been highlighted as a complementary treatment to T2DM, stand out the Vochysiaceae family, which have been widely used in folk medicine by traditional South American communities to treat some diseases. Our study aimed to investigate the antioxidant and antiglycation activities of ethanol extracts of leaves (LF) and stem barks (SB) of Vochysiaceae species, evaluated their capacities to inhibit glycoside and lipid hydrolases related to T2DM and molecular identification by HPLC-ESI-MS/MS. Our main findings indicate that the ethanolic extract of four of eight analyzed plants such as LF and SB of Q. grandiflora, Q. parviflora, V. elliptica and Calisthene major exhibited, respectively, potential of α-amylase inhibition (IC50 of LF: 5.7 ±â€¯0.6, 4.1 ±â€¯0.5, 5.8 ±â€¯0.5, 3.2 ±â€¯0.6 and IC50 of SB: 3.3 ±â€¯0.7, 6.2 ±â€¯2.0, 121.0 ±â€¯8.6 and 11.2 ±â€¯2.8 µg/mL), capacities of antioxidant (ORAC of LF: 516.2 ±â€¯0.1, 547.6 ±â€¯4.9, 544.3 ±â€¯6.1, 442.6 ±â€¯2.4 and ORAC of SB: 593.6 ±â€¯22.3, 497.7 ±â€¯0.8, 578 ±â€¯12.3, 593.6 ±â€¯19.5 µmol trolox eq/g; FRAP of LF: 796.1 ±â€¯0.9, 427.7 ±â€¯22.0, 81.0 ±â€¯1.9, 685 ±â€¯37.9 and FRAP of SB: 947.4 ±â€¯24.9, 738.6 ±â€¯24.3, 98.8 ±â€¯7.9, 970.8 ±â€¯13.9 µmol trolox eq/g; DPPH IC50 of LF: 14.2 ±â€¯1.8, 36.3 ±â€¯6.9, 11.8 ±â€¯1.9, 13.3 ±â€¯1.2 and DPPH IC50 of SB: 16.0 ±â€¯3.0, 15.5 ±â€¯1.9, 126.1 ±â€¯23. 6, 5.3 ±â€¯0.3 µg/mL, respectively) and antiglycation (BSA/Frutose IC50 of LF: 43.1 ±â€¯3.4, 52.1 ±â€¯6.0, 175.5 ±â€¯32, 8, 111.8 ±â€¯14.7 and BSA/Frutose IC50 of SB:, 40.1 ±â€¯11.9, 51.2 ±â€¯16. 7, 46.6 ±â€¯5.7, 53.5 ±â€¯13.6 µg/mL) and presence of polyphenols, such as flavonoids and condensed tannins. The extracts presented low ability to inhibit α-glycosidase and lipase enzymes in the initial assays, with values below 40% of inhibition. In BSA/methylglyoxal, only Q. grandiflora SB, V. eliptica LF and V. tucanorum LF showed activity (IC50: 655.5 ±â€¯208.5, 401.9 ±â€¯135.2 and 617.1 ±â€¯80.6 µg/mL, respectively) and only C. major LF and SB, in Arg/methylglyoxal (IC50: 485.1 ±â€¯130.8 and 468.0 ±â€¯150.5 µg/ml, respectively). This study presented new findings about the biological and pharmacological potential of some species of Vochysiaceae family, contributing to the understanding of the action and efficacy in use of these plants, in their management of postprandial hyperglycemia and in glycation and oxidative processes that contribute to managing diabetes mellitus.

Renal developmental disturbances and their long-term consequences in female pups from vitamin D-deficient mothers: involved mechanisms.

The mechanisms involved in kidney disturbances during development, induced by vitamin D3 deficiency in female rats, that persist into adulthood were evaluated in this study. Female offspring from mothers fed normal (control group, n=8) or vitamin D-deficient (Vit.D-, n=10) diets were used. Three-month-old rats had their systolic blood pressure (SBP) measured and their blood and urine sampled to quantify vitamin D3 (Vit.D3), creatinine, Na+, Ca+2 and angiotensin II (ANGII) levels. The kidneys were then removed for nitric oxide (NO) quantification and immunohistochemical studies. Vit.D- pups showed higher SBP and plasma ANGII levels in adulthood (P<0.05) as well as decreased urine osmolality associated with increases in urinary volume (P<0.05). Decreased expression of JG12 (renal cortex and glomeruli) and synaptopodin (glomeruli) as well as reduced renal NO was also observed (P<0.05). These findings showed that renal disturbances in development in pups from Vit.D- mothers observed in adulthood may be related to the development of angiogenesis, NO and ANGII alterations.

Combinatory therapy adopting nanoparticle-based cancer vaccination with immune checkpoint blockade for treatment of post-surgical tumor recurrences.

Cancer immunotherapy is emerging as a candidate treatment modality for treating post-surgical metastasis and recurrences. Despite the great promises with therapeutic cancer vaccines and checkpoint blocking antibodies in pre-clinical studies, response rates in the clinic still remain unsatisfactory. The evaluation of immunotherapy after surgery in patients could confront significant unexpected hurdles. Surgery itself tends to cause immune suppression, while wound healing factors also stimulate tumor cell outgrowth and metastasis. Regarding the marked changes in the post-surgical tumor microenvironment, one can anticipate that better tumor growth control is attainable by combining cancer vaccines with immune checkpoint blockade. However, it is important that vaccines and checkpoint blocking antibodies are delivered efficiently to their target cells, are released sustained and locally and do not induce cytotoxic effects. The generation of effective anti-tumor immunity and durable response rates could largely depend on these parameters. In the last decade, researchers spend tremendous effort in optimizing the delivery of immunotherapeutic compounds with the use of nanomedicine. Biocompatible nanoparticle based delivery systems demonstrated intriguing results with regard to specific immune cell activation, improved drug delivery, cell targeting, limiting off target toxicity and improving treatment outcome. It therefore makes sense, to speculate on the promises of combined cancer vaccination and immune checkpoint blocking immunotherapy with the aid of nanomedicine. A powerful nanoparticle combination immunotherapy conferring durable therapeutic benefit whilst leaving healthy tissue untouched represents the base for more efficient post-surgical cancer treatment.

Influência da sanificação da água e das práticas de ordenha na qualidade do leite / Influence of water treatment and milking practices on milk quality

Objetivou-se avaliar a influência da cloração da água utilizada em salas de ordenha, assim como do manejo e da infraestrutura da ordenha, sobre a qualidade microbiológica da água e do leite. Foi instalado um equipamento para cloração de água, por duas semanas, na caixa de água de 20 propriedades leiteiras. Foram coletadas amostras de água e leite ao primeiro dia (sem cloro: controle), no sétimo e 14° dias (com cloro) e no 21º dia após a desinstalação dos cloradores (sem cloro: controle). Foram realizadas análises microbiológicas da água e do leite (contagem de células somáticas do leite, bactérias psicotróficas, mesófilas e coliformes totais), análises físico-químicas da água (pH, dureza e matéria orgânica), e aplicou-se um questionário estruturado aos produtores visando conhecer as técnicas de manejo de ordenha adotadas na propriedade. O uso de cloração na água melhorou (P<0,0001) a qualidade microbiológica da água, porém não afetou a qualidade microbiológica do leite (P>0,05). Práticas adequadas de manejo e higiene de ordenha e adequada estrutura para a ordenha estão relacionadas a baixas contagens de microrganismos no leite. Conclui-se que a cloração melhora a qualidade microbiológica da água, sem afetar a qualidade microbiológica do leite, a qual é melhorada pela adoção de boas práticas de ordenha e adequada infraestrutura.(AU)

The aim was to evaluate the influence of the use of sanitizing the water used on dairy farms, the management and the infrastructure on the dairy farm on the microbiological quality of water and milk. It was installed an equipment to chlorinate the water for a period of two weeks, in the water box of 20 dairy farms. In each dairy farm, water and milk samples were collected, being the first day (without chlorine: control), in the 7th and 14th day (chlorine), and 21 days after uninstalling the chlorinators (Chlorine-free: control). Microbiological analysis of water and milk (Somatic cell counts of milk, psychrotrophic bacteria, mesophilic and total coliforms) and physicochemical analysis of water were performed and a survey was applied to the farmers. The use of chlorine tablets in water improved (P<0.0001) the microbiological quality of water, but did not affect the microbiological quality of the milk (P>0.05). Management practices, hygiene and the structure of dairy farms are related to low microorganism counts in milk. In conclusion, chlorination of water improves the microbiological quality of water without affecting the microbiological quality of milk, which is improved by the adoption of good milking practices and adequate infrastructure.(AU)

Herpesvírus bovino tipo 1 (BoHV-1): método de diagnóstico e sua influência na qualidade espermática em touros infectados experimentalmente / Bovine Herpes virus type 1 (BoHV-1): Diagnosis method and its influence on spermatic quality in experimentally infected bulls

O herpesvírus bovino tipo-1 (BoHV-1) é um vírus amplamente distribuído no Brasil e no mundo, havendo um crescente número de estudos envolvendo métodos de diagnóstico e o seu impacto na reprodução animal. O objetivo deste trabalho foi identificar o material genético do BoHV-1 no sêmen de touros infectados experimentalmente por meio da técnica de PCR e avaliar a influência do vírus sobre a qualidade espermática desses animais. A técnica de PCR foi satisfatória, permitindo identificar a presença do material genético do vírus no sêmen de todos os animais a partir de sete dias pós-infecção, com persistência de 21 até 28 dias. Apesar da presença do vírus BoHV-1 por um longo período no sêmen dos animais experimentais, não foram observados efeitos deletérios na qualidade do sêmen fresco e nem após a criopreservação.(AU)

Bovine Herpesvirus type-1 (BoHV-1) is a virus widely distributed in Brazil and worldwide, with a growing number of studies involving diagnostic methods and their impact on animal reproduction. The objective of this work was to identify the genetic material of BoHV-1 in the semen of experimentally infected bulls through the PCR technique, and to evaluate the influence of the virus on the sperm quality of these animals. The PCR technique was satisfactory, allowing for the identification of the presence of the genetic material of the virus in the semen of all the animals from 7 days post infection, with persistence of 21 to 28 days. Despite the presence of the BoHV-1 virus over a long period in the semen of the experimental animals, no deleterious effects were observed on the quality of either fresh semen or semen after the cryopreservation.(AU)

The potential of multi-compound nanoparticles to bypass drug resistance in cancer.

PURPOSE: The therapeutic efficacy of conventional chemotherapy against several solid tumors is generally limited and this is often due to the development of resistance or poor delivery of the drugs to the tumor. Mechanisms of resistance may vary between cancer types. However, with current development of genetic analyses, imaging, and novel delivery systems, we may be able to characterize and bypass resistance, e.g., by inhibition of the right target at the tumor site. Therefore, combined drug treatments, where one drug will revert or obstruct the development of resistance and the other will concurrently kill the cancer cell, are rational solutions. However, drug exposure of one drug will defer greatly from the other due to their physicochemical properties. In this sense, multi-compound nanoparticles are an excellent modality to equalize drug exposure, i.e., one common physicochemical profile. In this review, we will discuss novel approaches that employ nanoparticle technology that addresses specific mechanisms of resistance in cancer. METHODS: The PubMed literature was consulted and reviewed. RESULTS: Nanoparticle technology is emerging as a dexterous solution that may address several forms of resistance in cancer. For instance, we discuss advances that address mechanisms of resistance with multi-compound nanoparticles which co-deliver chemotherapeutics with an anti-resistance agent. Promising anti-resistance agents are (1) targeted in vivo gene silencing methods aimed to disrupt key resistance gene expression or (2) protein kinase inhibitors to disrupt key resistance pathways or (3) efflux pumps inhibitors to limit drug cellular efflux.

The Potential of Nano-Vehicle Mediated Therapy in Vasculitis and Multiple Sclerosis.

The induction of immune tolerance towards self-antigens presents as a viable future strategy in the treatment of auto-immune diseases, including vasculitis and multiple sclerosis (MS). As specific targets are currently lacking for vasculitis due to incomplete understanding of the pathologies underlying this disease, current treatment options are based on modalities that induce general immune suppression. However, many immune suppressants used in the clinic are known to display wide biodistribution and are thus often accompanied by several adverse effects. Nano-vehicles (NVs) possess the ability to overcome such limitations by enabling more specific delivery of their content through modifications with targeting moieties. In this review, we describe the latest insights in the pathology of vasculitis that may function as potential targets for NV carrier systems, allowing more specific delivery of currently used immune suppressants. In addition, we describe the existing strategies to induce artificial immune tolerance and explore the feasibility of inducing regulatory T cell (Treg) mediated tolerance for MS, possibly mediated by NVs.

Combinatorial prospects of nano-targeted chemoimmunotherapy.

Despite the significant increase in our knowledge on cancer initiation and progression, and the development of novel cancer treatments, overall patient survival rates have thus far only marginally improved. However, it can be expected that lasting tumor control will be attainable for an increasing number of cancer patients in the foreseeable future, which is likely to be achieved by combining cancer chemotherapy with anticancer immunotherapy. A plethora of new cancer chemotherapy reagents are expected to become accessible to the clinic in the coming years which can then be used for efficient tumor debulking and aid in antigen exposure to the immune system. Durable remission and the eradication of micrometastases are likely to be achieved with specialized monoclonal antibodies and therapeutic cancer vaccines that modulate the immune system to overcome immunosuppression and kill distant cancer cells. Moreover, the method of drug delivery to tumors, stromal and immune cells is expected to shift largely from conventional 'free' drug molecules to encapsulated in targeted nano-vehicles, therapeutics often referred to or considered part of "nanomedicine". Several biocompatible nano-vehicles, such as metal-nanoparticles, biodegradable-nanoparticles, liposomes or dendrimers are potential candidates for targeted drug delivery but may also serve additional purposes. A dexterous combination of nanomedicine, cancer immunotherapy and chemotherapeutic engineering are likely to become the basis for new hope in the form of targeted cancer therapies that could attack tumors early in their development. One can envision nano-vehicles that would selectively deliver effective doses of chemotherapeutic agents to cancer cells while leaving healthy cells untouched. Furthermore, given that after chemotherapeutic treatment there often remains a limited number of chemo-resistant tumor cells, which go on to drive tumor progression, nano-vehicles could also be engineered to provoke an appropriate immune response to destroy these cells. Here, we discuss the potential of the combinatorial role of cancer chemotherapy, cancer immunotherapy and the prospective of nanotechnology for the targeted delivery of chemoimmunotherapeutic agents.

Toxicidade de espécies vegetais / Toxicity of plant species

RESUMO As plantas produzem uma grande variedade de metabólitos secundários que frequentemente são relacionados a mecanismos de proteção da planta contra predadores e patógenos. As espécies tóxicas são aquelas capazes de produzirem compostos que podem causar alterações metabólicas prejudiciais ao homem e aos animais. A toxicidade apresentada por uma espécie vegetal pode estar relacionada a fatores associados ao indivíduo, à planta, ao modo de exposição e a questões ambientais. A intoxicação, aguda ou crônica, causada por plantas é difícil de ser diagnosticada assim como a associação entre os sintomas e o consumo e/ou contato com algumas espécies é difícil de ser estabelecida. No âmbito da saúde pública, as intoxicações causadas por plantas possuem impacto expressivo. No Brasil foram registrados 1026 casos em 2012, sendo que a maior parte deles ocorreu com crianças de 0 a 4 anos, de acordo com os dados do SINITOX. O objetivo deste trabalho foi realizar um levantamento bibliográfico de espécies vegetais, brasileiras e exóticas aclimatadas, citadas como tóxicas apesar de serem utilizadas com fins ornamentais e medicinais.

ABSTRACT Plants produce a wide variety of secondary metabolites, which are frequently related to a plant’s protective mechanism against predators and pathogens. Toxic species are those capable of producing compounds that can cause metabolic changes harmful to humans and animals. The toxicity of plant species can be associated with aspects related to the individual, the plant, the manner of exposure, and to environmental issues. Acute or chronic intoxication caused by plants is difficult to diagnose and the association between the symptoms and the consumption of and/or contact with plants is hard to establish. In the public health sector, intoxications caused by plants have a wide impact. In Brazil, 1,026 cases were registered in 2012, most of which occurred with children between the ages of 0 to 4 years, according to data reported by SINITOX. The purpose of this study was to perform a bibliographic survey of Brazilian or acclimatized exotic plant species, which have been reported as toxic even though they are used for ornamental or medicinal purposes.

Morphological characterization and conservation of bovine spermatogenic cells by refrigeration at 4°C and freezing using different cryoprotective molecules.

The objectives of this study were study a practical method to characterize bovine spermatogenic cells and test the efficiency cells conservation by refrigeration at 4°C and cryopreservation in different solutions using two cooling curves. Cellular identification was performing by analysis of shape, size and morphology, associated with nucleus positioning and nuclear-cytoplasm ratio (NCR). Cellular samples were kept at 4°C for a period of 96 h in refrigeration solution and every 24h plasma membrane and DNA integrity were evaluated. Cryopreservation of cells was carried out using solutions containing 10% Dimethyl sulfoxide, 5% Dimethylformamide, 7% Glycerol and 7% Ethylene glycol, using a controlled and non-controlled cooling curve. Results of cellular characterization demonstrated that spermatocytes II presented a cylindrical shape, NCR of 1:1.5 and diameter ranging from 14.5 to 17.5 µm. Round spermatids presented diameter ranging from 7.6 to 13.4 µm, acrosomal cap and NCR of 1:2. Elongation and elongated spermatids showed to marked divergence in shape. There was a daily significant loss of viability of cooled cells until third day of storage, however they presented 72.77±5.16% viability after 4 days of storage at 4°C. There was no difference among the cryoprotectant solutions and cooling curves. In conclusion we demonstrated that association of microscopes and staining was a practical method to identify bovine spermatogenic cells. Furthermore, refrigeration at 4°C is an important strategy to preserve over 70% of viable cells after 4 days and cryopreservation, regardless of cryoprotectant solution or cooling curve used, can maintain over 50% of cells viable.

Significant lethality following liver resection in A20 heterozygous knockout mice uncovers a key role for A20 in liver regeneration.

Hepatic expression of A20, including in hepatocytes, increases in response to injury, inflammation and resection. This increase likely serves a hepatoprotective purpose. The characteristic unfettered liver inflammation and necrosis in A20 knockout mice established physiologic upregulation of A20 as integral to the anti-inflammatory and anti-apoptotic armamentarium of hepatocytes. However, the implication of physiologic upregulation of A20 in modulating hepatocytes' proliferative responses following liver resection remains controversial. To resolve the impact of A20 on hepatocyte proliferation and the liver's regenerative capacity, we examined whether decreased A20 expression, as in A20 heterozygous knockout mice, affects outcome following two-third partial hepatectomy. A20 heterozygous mice do not demonstrate a striking liver phenotype, indicating that their A20 expression levels are still sufficient to contain inflammation and cell death at baseline. However, usually benign partial hepatectomy provoked a staggering lethality (>40%) in these mice, uncovering an unsuspected phenotype. Heightened lethality in A20 heterozygous mice following partial hepatectomy resulted from impaired hepatocyte proliferation due to heightened levels of cyclin-dependent kinase inhibitor, p21, and deficient upregulation of cyclins D1, E and A, in the context of worsened liver steatosis. A20 heterozygous knockout minimally affected baseline liver transcriptome, mostly circadian rhythm genes. Nevertheless, this caused differential expression of >1000 genes post hepatectomy, hindering lipid metabolism, bile acid biosynthesis, insulin signaling and cell cycle, all critical cellular processes for liver regeneration. These results demonstrate that mere reduction of A20 levels causes worse outcome post hepatectomy than full knockout of bona fide liver pro-regenerative players such as IL-6, clearly ascertaining A20's primordial role in enabling liver regeneration. Clinical implications of these data are of utmost importance as they caution safety of extensive hepatectomy for donation or tumor in carriers of A20/TNFAIP3 single nucleotide polymorphisms alleles that decrease A20 expression or function, and prompt the development of A20-based liver pro-regenerative therapies.

Levantamento etnobotânico de plantas medicinais em área de Caatinga na comunidade do Sítio Nazaré, município de Milagres, Ceará, Brasil / Ethnobotanical survey of medicinal plants in the Caatinga area in the community of Sitio Nazaré, Milagres, Ceará, Brazil

O presente trabalho teve como objetivo realizar um levantamento das plantas medicinais nativas no bioma Caatinga na comunidade do Sítio Nazaré, no município de Milagres, Ceará. Foram utilizadas entrevistas semiestruturadas com 100 informantes entre 25 a 85 anos registrando informações de 62 espécies medicinais sobre o uso, parte utilizada, indicação terapêutica, e formas de preparo dos remédios caseiros, além de coleta do material botânico e produção de exsicatas. As famílias com maior representatividade na pesquisa foram Fabaceae (16 spp.), Euphorbiaceae (7 spp.), Cucurbitaceae e Malvaceae (3 spp.), e as demais com duas ou uma espécie cada. Nas preparações dos remédios caseiros verificou-se que todas as partes da planta são utilizadas, predominando as raízes (33,77%) e as cascas (29,87%). Observaram-se várias formas de preparo, sendo o chá a mais indicada (49,21%), seguida do lambedor (40,69%). Os dados encontrados revelaram que o conhecimento popular sobre as plantas medicinais é de extrema importância para o controle das afecções e contribui para a realização de estudos etnofarmacológicos.

The present study aimed to survey the native medicinal plants in the biome Caatinga in the community of Sítio Nazaré from Milagres, in Ceará, Brazil. Semi-structured interviews with 100 persons, from 25 to 85 years old, were recorded. Sixty-two species were pointed for medical information on use, used plant part, therapeutic indication and methods of preparation of home remedies. We also prepared the collection of botanical material and production of exsiccates. The most representative families reported in this study were: Fabaceae (15 spp.), Euphorbiaceae (7 spp.), Cucurbitaceae and Malvaceae (3 spp.). On the preparation of remedies, we found that all parts of the plants were used, predominantly the roots (33.77%) and the barks (29.87%). The most common way of preparation observed was tea (49.21%), followed by syrup (40.69%). These collected data revealed that popular knowledge on medicinal Caatinga plants were important for disease control in the local population and it has contributed to other ethnopharmacology studies.

Cryopreservation of boar sperm comparing different cryoprotectants associated in media based on powdered coconut water, lactose and trehalose.

In swine spermatozoa, the damage caused by cryopreservation is more severe than other species, provoking reduced potential for fertilization. Adjustments in the freezing extender composition may be an important alternative to increase its efficiency. The objective of this study was to test the efficiency of different cryoprotectant solutions during cryopreservation of swine semen with a controlled cooling curve. Three cryoprotectant solutions (5% dimethylformamide, 3% glycerol and the combination of these two cryoprotectants) were used in association with three base media (powdered coconut water, lactose and trehalose), constituting nine different treatments. The semen was frozen using a controlled-rate freezer (TK-3000). After thawing, semen was evaluated for total sperm motility, vigor, morphology, plasma membrane integrity and acrosome integrity. Cryopreservation with the controlled curve using an automated system showed satisfactory results, guaranteeing practicality and repeatability for the process of freezing swine sperm. With this curve, the solutions of lactose, trehalose and powdered coconut water associated with glycerol, as well as the solution of coconut water containing dimethylformamide, presented higher quality of sperm compared to the other solutions. Powdered coconut water associated with dimethylformamide appears as a new solution for swine sperm cryopreservation. The freezing controlled curve used in this study allowed standardization of the cryopreservation technique.

Effects of prolonged in vitro culture and cryopreservation on viability, DNA fragmentation, chromosome stability and ultrastructure of bovine cells from amniotic fluid and umbilical cord.

The objective of this work was to study cellular types that did not participated in the gastrulation process, amniotic fluid cells (AFCs) and umbilical cord cells (UCCs), in conditions of long-term culture and cryopreserved with different solutions. The AFCs and UCCs were used in a comparative study with ear fibroblast cells (EFCs) that were cultured in vitro until 20 cellular passages and cryopreserved in 10% dimethylsulphoxide (DMSO), 5% dimethyl formamide (DMF) and 7% glycerol (Gly) solutions. The cellular viability, ultrastructure, DNA fragmentation and chromosome stability were evaluated to determine the cellular type most resistant. In all cell types, it was possible to evaluate the AFCs until 15 passages and UCCs until 20 passages with different periods of cellular growth to reach the confluence phase. Solutions containing 10% DMSO ensured viability of 90.33 ± 5.58%, 90.56 ± 4.40% and 81.90 ± 3.31%, respectively for EFCs, AFCs and UCCs, being significantly more efficient and with less variation than other cryoprotectant solutions. The AFCs were more sensitive to cryopreservation and presented low viability rate at the passage 20 (17.2 ± 8.87%). There was no change in karyotype and nuclear fragmentation was low in all cellular passages studied. With the scanning electron analysis was possible the characterization of AFCs and UCCs in suspension. The three cellular types of cells presented different shapes and characteristics on the surface. The results demonstrate that bovine AFCs and UCCs can be isolated, cultured in vitro and cryopreserved in 10% DMSO, not causing damage to DNA and chromosomes. The UCCs were more resistant than AFCs in all aspects.