Effects of quercetin in preclinical models of Parkinson's disease: A systematic review.

Parkinson's disease (PD) is a neurodegenerative disease that affects dopaminergic neurons, thus impairing dopaminergic signalling. Quercetin (QUE) has antioxidant and neuroprotective properties that are promising for the treatment of PD. This systematic review aimed to investigate the therapeutic effects of QUE against PD in preclinical models. The systematic search was performed in PubMed, Scopus and Web of Science. At the final screening stage, 26 articles were selected according to pre-established criteria. Selected studies used different methods for PD induction, as well as animal models. Most studies used rats (73.08%) and mice (23.08%), with 6-OHDA as the main strategy for PD induction (38.6%), followed by rotenone (30.8%). QUE was tested immersed in oil, nanosystems or in free formulations, in varied routes of administration and doses, ranging from 10 to 400 mg/kg and from 5 to 200 mg/kg in oral and intraperitoneal administrations, respectively. Overall, evidence from published data suggests a potential use of QUE as a treatment for PD, mainly through the inhibition of oxidative stress, neuroinflammatory response and apoptotic pathways.

Experimental models of chemically induced Parkinson's disease in zebrafish at the embryonic larval stage: a systematic review.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra that results in a decrease in dopamine levels, resulting in motor-type disturbances. Different vertebrate models, such as rodents and fish, have been used to study PD. In recent decades, Danio rerio (zebrafish) has emerged as a potential model for the investigation of neurodegenerative diseases due to its homology to the nervous system of humans. In this context, this systematic review aimed to identify publications that reported the utilization of neurotoxins as an experimental model of parkinsonism in zebrafish embryos and larvae. Ultimately, 56 articles were identified by searching three databases (PubMed, Web of Science, and Google Scholar). Seventeen studies using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 4 1-methyl-4-phenylpyridinium (MPP+), 24 6-hydroxydopamine (6-OHDA), 6 paraquat/diquat, 2 rotenone, and 6 articles using other types of unusual neurotoxins to induce PD were selected. Neurobehavioral function, such as motor activity, dopaminergic neuron markers, oxidative stress biomarkers, and other relevant parameters in the zebrafish embryo-larval model were examined. In summary, this review provides information to help researchers determine which chemical model is suitable to study experimental parkinsonism, according to the effects induced by neurotoxins in zebrafish embryos and larvae.

Neuroprotective Effect of Vitamin D on Behavioral and Oxidative Parameters of Male and Female Adult Wistar Rats Exposed to Mancozeb (manganese/zinc ethylene bis-dithiocarbamate).

The constant exposure of rural workers to pesticides is a serious public health problem. Mancozeb (MZ) is a pesticide  linked to hormonal, behavioral, genetic, and neurodegenerative effects, mainly related to oxidative stress. Vitamin D is a promising molecule that acts as a protector against brain aging. This study aimed to evaluate the neuroprotective role of vitamin D in adult male and female Wistar rats exposed to MZ. Animals received 40 mg/kg of MZ i.p. and 12.5 µg/kg or 25 µg/kg vitamin D by gavage, twice a week, for 6 weeks. The concentration of manganese had a significant increase in the hippocampus of both sexes and in the striatum of females, unlike zinc, which did not show a significant increase. MZ poisoning led to mitochondrial changes in brain tissues and promoted anxiogenic effects, especially in females. Alterations in antioxidant enzymes, mainly in the catalase activity were observed in intoxicated rats. Taken together, our results showed that exposure to MZ leads to the accumulation of manganese in brain tissues, and the behavior and metabolic/oxidative impairment were different between the sexes. Furthermore, the administration of Vitamin D was effective in preventing the damage caused by the pesticide.

Snake venom, a potential treatment for melanoma. A systematic review.

Despite advances in treating patients with melanoma, there are still many treatment challenges to overcome. Studies with snake venom-derived proteins/peptides describe their binding potential, and inhibition of some proliferative mechanisms in melanoma. The combined use of these compounds with current therapies could be the strategic gap that will help us discover more effective treatments for melanoma. The present study aimed to carry out a systematic review identifying snake venom proteins and peptides described in the literature with antitumor, antimetastatic, or antiangiogenic effects on melanoma and determine the mechanisms of action that lead to these anti-tumor effects. Snake venoms contain proteins and peptides which are antiaggregant, antimetastatic, and antiangiogenic. The in vivo results are encouraging, considering the reduction of metastases and tumor size after treatment. In addition to these results, it was reported that these venom compounds could act in combination with chemotherapeutics (Acurhagin-C; Macrovipecetin), sensitizing and preparing tumor cells for treatment. There is a consensus that snake venom is a promising strategy for the improvement of antimelanoma therapies, but it has been little explored in the current context, combined with inhibitors, immunotherapy or tumor microenvironment, for example. We suggest Lebein as a candidate for combination therapy with BRAF inhibitors.

Effects of glyphosate on zebrafish: a systematic review and meta-analysis.

Glyphosate herbicide is widely used in worldwide crop production. Consequently, its active ingredient, surfactants, and adjuvants commonly reach the aquatic ecosystem, thereby harming the biota. An investigation into how this herbicide affects aquatic species is important, especially in fish, as they have the ability to absorb and concentrate toxins. We aimed to evaluate the effects of glyphosate on the embryonic, larval and adult stages of zebrafish (Danio rerio), an appreciable organismal model. In this sense, we performed a meta-analysis using published articles from online databases (PubMed and ScienceDirect), which covered studies published until 2022. From a massive compilation of studies evaluating the effects of active substance glyphosate and Glyphosate-Based Herbicides (GBH) on zebrafish, we selected 36 studies used in downstream analyses. Overall, we report that glyphosate affects developmental stages and demonstrates toxicity and damage in zebrafish. We observed that embryos exposed to glyphosate exhibit increased mortality. There was also an increase in the number of morphological abnormalities related to yolk sac oedema, pericardial oedema, spinal curvature and body malformations, and a decrease in body size was observed. Furthermore, there was a decrease in the number of beats. The biochemical results demonstrated an increase in reactive oxygen species and antioxidant capacity against peroxyl radicals in the gills. The literature shows that glyphosate decreased the distance covered and the mean speed of the animals and increased the number of rotations. We concluded that glyphosate causes damage in the embryonic, larval and adult stages of this species. These results are valid for zebrafish and can be applied to other freshwater fish species. Graphical abstract.

Combination of Curcumin and Photodynamic Therapy Based on the Use of Red Light or Near-Infrared Radiation in Cancer: A Systematic Review.

BACKGROUND: Photodynamic therapy (PDT) is a therapeutic intervention that can be applied to cancer treatment. The interaction between a photosensitizer (PS), ideal wavelength radiation, and tissue molecular oxygen triggers a series of photochemical reactions responsible for producing reactive oxygen species. These highly reactive species can decrease proliferation and induce tumor cell death. The search for PS of natural origin extracted from plants becomes relevant, as they have photoactivation capacity, preferentially targeting tumor cells and because they do not present any or little toxicity to healthy cells. OBJECTIVE: Our work aimed to carry out a qualitative systematic review to investigate the effects of curcumin (CUR), a molecule considered as PS of natural origin, on PDT, using red light or near-infrared radiation in tumor models. METHODS: A systematic search was performed in three databases (PubMed, Scopus, and Web of Science) using the PICOT method, retrieving a total of 1,373 occurrences. At the end of the peer screening, 25 eligible articles were included in this systematic review using inclusion, exclusion, and eligibility criteria. RESULTS: CUR, whether in its free state, associated with metal complexes or other PS and in a nanocarrier system, was considered a relevant PS for PDT using red light or near-infrared against tumoral models in vitro and in vivo, acting by increasing cytotoxicity, inhibiting proliferation, inducing cell death mainly by apoptosis, and changing oxidative parameters. CONCLUSION: The results found in this systematic review suggest the potential use of CUR as a PS of natural origin to be applied in PDT against many neoplasms, encouraging further search in PDT against cancer and serving as an investigative basis for upcoming pre-clinical and clinical applications.

Predictive Factors of Extubation Failure in COVID-19 Mechanically Ventilated Patients.

Purpose: We investigated whether COVID-19 patients on mechanical ventilation (MV) had a different extubation outcome compared to non-COVID-19 patients while identifying predictive factors of extubation failure in the former. Methods: A retrospective, single-center, and observational study was done on 216 COVID-19 patients admitted to an intensive care unit (ICU) between March 2020 and March 2021, aged ≥ 18 years, in use of invasive MV for more than 24 h, which progressed to weaning. The primary outcome that was evaluated was extubation failure during ICU stay. A statistical analysis was performed to evaluate the association of patient characteristics with extubation outcome, and a Poisson regression model determined the predictive value. Results: Seventy-seven patients were extubated; the mean age was 57.2 years, 52.5% were male, and their mean APACHE II score at admission was 17.8. On average, MV duration until extubation was 8.7 ± 3.7 days, with 14.9 ± 10.1 days of ICU stay and 24.6 ± 14.0 days with COVID-19 symptoms. The rate of extubation failure (ie, the patient had to be reintubated during their ICU stay) was 22.1% (n = 17), while extubation was successful in 77.9% (n = 60) of cases. Failure was observed in only 7.8% of cases when evaluated 48 hours after extubation. The mean reintubation time was 4.28 days. After adjusting the analysis for age, sex, during of symptoms, days under MV, dialysis, and PaO2/FiO2 ratio, some parameters independently predicted extubation failure: age ≥ 66 years (APR = 5.12 [1.35-19.46]; p = 0.016), ≥ 31 days of symptoms (APR = 5.45 [0.48-62.19]; p = 0.016), and need for dialysis (APR = 5.10 [2.00-13.00]; p = 0.001), while a PaO2/FiO2 ratio >300 decreased the probability of extubation failure (APR = 0.14 [0.04-0.55]; p = 0.005). The presence of three predictors (ie, age ≥ 66 years, time of symptoms ≥ 31 days, need of dialysis, and PaO2/FiO2 ratio < 200) increased the risk of extubation failure by a factor of 23.0 (95% CI, 3.34-158.5). Conclusion: COVID-19 patients had an extubation failure risk that was almost three times higher than non-COVID-19 patients, with the extubation of the former being delayed compared to the latter. Furthermore, an age ≥ 66 years, time of symptoms ≥ 31 days, need of dialysis, and PaO2/FiO2 ratio > 200 were independent predictors for extubation failure, and the presence of three of these characteristics increased the risk of failure by a factor of 23.0.

Trend and Inequality in Episiotomy in Southern Brazil, 2007-2016: Evidence of Reduced Abusive Practice.

OBJECTIVES: This study aimed to measure the prevalence, to describe the trend over time, and to evaluate socioeconomic inequalities in the occurrence of episiotomies in 2007, 2010, 2013, and 2016 in the municipality of Rio Grande, in Southern Brazil. METHODS: We included all women who had vaginal delivery in each of the studied years. All the information was obtained through a questionnaire applied at maternity wards within 48 h after delivery. The outcome consisted of episiotomy. A chi-square test was used to evaluate the linear trend. Absolute and relative inequalities were assessed from household income and schooling of the women through the Slope Index of Inequality and Relative Index of Inequality, respectively. RESULTS: This study included 4,521 parturients. The episiotomy rate in the period fell from 71.0% (95%CI: 68.4-73.5) in 2007 to 40.1% (95%CI: 37.3-42.8) in 2016, and it was more frequent among women with higher income and higher schooling. We observed a reduction in the rate of episiotomy in all income and schooling levels, and this was more evident among women in the lowest socioeconomic levels. Absolute inequality declined, while relative inequality remained unchanged. CONCLUSIONS FOR PRACTICE: Despite the significant reduction in the rate of episiotomy, its occurrence remains high. Women with higher income and education, therefore with lower risk for complications during childbirth, were the most frequently submitted to this procedure. Routine use of episiotomy must be reevaluated, especially among pregnant women with better socioeconomic status.

Environmental performance of commercial beef production systems utilizing conventional productivity-enhancing technologies.

The objective of this study was to evaluate the effects of using conventional productivity-enhancing technologies (PETs) with or without other natural PETs on the growth performance, carcass traits, and environmental impacts of feedlot cattle. A total of 768 cross-bred yearling steers (499 ±â€…28.6 kg; n = 384) and heifers (390 ±â€…34.9 kg; n = 384) were offered a barley grain-based basal diet and divided into implanted or non-implanted groups. Steers were then allocated to diets that contained either: (i) no additive (control); natural feed additives including (ii) fibrolytic enzymes (Enz), (iii) essential oil (Oleo), (iv) direct-fed microbial (DFM), (v) DFM + Enz + Oleo combination; conventional feed additives including (vi) Conv (monensin, tylosin, and beta-adrenergic agonists [ßAA]); or Conv with natural feed additives including (vii) Conv + DFM + Enz; (viii) Conv + DFM + Enz + Oleo. Heifers received one of the first three dietary treatments or the following: (iv) probiotic (Citr); (v) Oleo + Citr; (vi) Melengesterol acetate (MGA) + Oleo + ßAA; (vii) Conv (monensin, tylosin, ßAA, and MGA); or (viii) Conv + Oleo (ConvOleo). Data were used to estimate greenhouse gas (GHG) and ammonia (NH3) emissions, as well as land and water use. Implant and Conv-treated cattle exhibited improvements in growth and carcass traits as compared to the other treatments (P < 0.05). Improvements in the performance of Conv-cattle illustrated that replacing conventional feed additives with natural feed additives would increase both the land and water required to satisfy the feed demand of steers and heifers by 7.9% and 10.5%, respectively. Further, GHG emission intensity for steers and heifers increased by 5.8% and 6.7%, and NH3 emission intensity by 4.3% and 6.7%, respectively. Eliminating the use of implants in cattle increased both land and water use by 14.6% and 19.5%, GHG emission intensity by 10.5% and 15.8%, and NH3 emission intensity by 3.4% and 11.0% for heifers and steers, respectively. These results demonstrate that the use of conventional PETs increases animal performance while reducing the environmental impacts of beef production. Restricting use would increase the environmental footprint of beef produced for both domestic and international markets.

Carnivalizing health promotion in Samba Schools: a review of the literature / Carnavalizando a promoção de saúde nas Escolas de Samba: uma revisão bibliográfica

This is a systematic bibliographic review study to analyze articles published in the field of Health Sciences, especially in Public Health, whose theme was carnival and samba schools. The objective was to analyze how health research has portrayed the health-disease process in samba schools and in carnival. Eleven articles were analyzed. Thus, scientific productions were found related to the theme with issues related to STIs and HIV-AIDS, the hearing health of carnival workers, historical perspectives on the 1919 carnival and the 1918 Spanish flu, yet studies that make it possible to observe health promotion in health schools and carnival beyond an event, but rather as a process.The fundamental objective of the analysis was to shift the understanding of health as negative of the disease, to health as a life affirmation. As well as, demystifying prejudiced understandings about carnival and samba schools with regard to the health of those who produce and participate in the event.

Este trabalho trata-se de uma revisão bibliográfica sistemática que buscou analisar artigos produzidos no campo das Ciências da Saúde, em especial na Saúde Coletiva, que tiveram por temática o carnaval e as escolas de samba. Objetivou-se analisar como as pesquisas em saúde tem retratado o processo de saúde-doença nas escolas de samba e no carnaval. Foram analisados 11 artigos que se relacionavam com o escopo desta pesquisa. Assim, foram encontradas produções científicas relacionados a temática com questões ligadas às ISTs e HIV-AIDS, à saúde auditiva dos trabalhadores de escolas de samba, perspectivas históricas sobre o carnaval de 1919 e a gripe espanhola de 1918, ainda estudos que possibilitam observar a promoção de saúde nas escolas de saúde e o carnaval para além de um evento, mas sim como um processo. A análise teve por fundamental objetivo deslocar o entendimento de saúde enquanto negativo da doença, para saúde como afirmação da vida. Assim como, desmistificar entendimentos preconceituosos sobre o carnaval e as escolas de samba no que se refere a saúde daqueles que produzem e participam do evento.

Salivary cytokines as biomarkers of oral cancer: a systematic review and meta-analysis.

BACKGROUND: Oral cancer (OC) is usually diagnosed at advanced clinical stages due to its asymptomatic nature and absence of pathognomonic signs in its early development phase. Delayed diagnosis is one of the major causes of OC treatment failure and poor prognosis. Development of alternative diagnostic approaches are imperative for improving early detection and therapeutic success rates. Salivary cytokines (SC) have been studied as potential diagnostic biomarkers for OC and may represent a potential tool for improvement of its early detection. METHODS: In this systematic review and meta-analysis we identified SC studied as OC biomarkers by systematically reviewing the PubMed and Cochrane Library databases using the terms: "oral cancer", "cytokine", and "saliva", and also combined with "interleukin" or "interferon". Only case-control studies that measured SC by ELISA from treatment naïve patients were included in the qualitative review. For the meta-analysis were included all comparable studies that provided enough data (sample size, mean and standard deviation or standard error of the mean) for SC levels in OC patients, non-cancer controls and patients with oral potentially malignant disorders (OPMD), including leukoplakia. Comparisons with patients with oral lichen planus (OLP) and gingivitis were included in the qualitative analysis. RESULTS: A total of 28 articles (from 2004 to 2018) were included in the systematic review, describing 10 different SC, being IL-8 and IL-6 the most studied ones. SC levels were consistently higher among OC patients when compared to healthy controls and to patients with OPMD, OLP and gingivitis. Meta-analysis including 23 eligible studies showed that IL-8, IL-6, TNF-α, IL-1ß and IL-10 salivary levels were significantly higher in OC patients compared to controls; and that IL-8, IL-6, TNF-α and IL-1ß salivary levels were also higher in OC patients compared to individuals with OPMD. When compared to healthy controls, OPMD patients showed significantly higher IL-6 and TNF-α salivary levels. CONCLUSIONS: Our analyses showed that the salivary levels of some cytokines are consistently different among OC, OPMD and healthy patients, indicating that these SC may represent potential diagnostic biomarkers for OC and OPMD. Despite of that, SC levels were highly variable among studies, suggesting that further technical improvement and standardization for SC measurement by ELISA is needed in order to successfully translate these biomarkers to the clinical practice.

Multi-walled carbon nanotubes functionalized with pyrene-PEG via π-π interactions: toxicological assessment in zebrafish embryos.

Multi-walled carbon nanotubes (MWCNT) have many promising biological applications, even though functionalization is needed for better biocompatibility. Functionalization of MWCNT with polyethylene glycol (PEG) is a promising and widely studied approach, but the best PEGylation method is still under investigation. In this work, we have tested the biological implications of MWCNT functionalized via π-stacking with pyrene-PEG (MWCNT-Pyr-PEG) in zebrafish embryos. As Pyr toxicity is well documented and represents a major concern for the safety of the proposed approach, we have also tested the effects of the exposure to the isolated conjugate (Pyr-PEG). The resulting suspensions were stable in saline medium and well dispersed. Zebrafish embryos at 24 h post-fertilization (hpf) were dechorionated and randomly assigned to seven experimental groups (n = 50 per group): control, MWCNT-Pyr-PEG at 0.2, 2.0, and 20.0 mg l-1, and Pyr-PEG at the same concentrations, and exposures were performed in 96-well plates. Specimens were observed for heart rate, malformations, body length, mortality, traveled distance, and number of new movements. Heart rate was reduced in embryos exposed to any tested concentration of MWCNT-Pyr-PEG, while this effect was observed with Pyr-PEG from 2 mg l-1. The highest concentration of MWCNT-Pyr-PEG also led to increased occurrence of malformations, shortened body length and reduced traveled distance. The functionalization approach shows promise due to the stability in saline media, even though toxic effects were observed in the highest tested concentrations, being the MWCNT the main actors underlying these outcomes.

MASCULINITY IN PANDEMIC TIMES: WHERE POWER DECREASES, VIOLENCE INCREASES / MASCULINIDADE EM TEMPOS DE PANDEMIA: ONDE O PODER ENCOLHE, A VIOLÊNCIA SE INSTALA

The emergence of the pandemic caused by COVID-19 emphatically calls for thinking about the narrowing of the man-power-violence relationship and the resignification of the place of men in sustaining reproductive life, emotional ties and care. In this context of social isolation, as an important strategy against the spread of the disease, seeking to understand the increase in domestic violence against women, the objective of this essay is to reflect on the man-power-violence relations from the concepts of Hannah Arendt, problematizing the normalized concept of hegemonic masculinity. Throughout this essay, we seek to deconstruct the idea that there is a single model of hegemonic masculinity and that it proposes a global domination of men over women, since women also present aspects of masculinity, which is a historical-social construction that is transformed continuously. Thus, in the face of historical gender reforms, and the instability caused by the pandemic of COVID-19, there is an increase in domestic violence as an effect of the decrease in patriarchal power, in an attempt to stabilize the masculinity model defined by this patriarchal power, or the attempt to reconstitute it in new configurations. In view of this reality, it is necessary, within the scope of Collective Health, to reflect on the reformulation of the National Policy for Integral Attention to Men's Health.

A emergência da pandemia causada pela COVID-19 reclama enfaticamente pensar o estreitamento da relação homem-poder-violência e a ressignificação do lugar dos homens na sustentação da vida reprodutiva, dos laços emocionais e do cuidado. Nesse contexto de isolamento social, como importante estratégia contra a disseminação da doença, buscando compreender o aumento de violência doméstica contra a mulher, o objetivo deste ensaio é refletir sobre as relações homem-poder-violência a partir das concepções de Hannah Arendt, problematizando o conceito normalizado de masculinidade hegemônica. Ao longo deste ensaio, buscamos desconstruir a ideia de que existe um único modelo de masculinidade hegemônica e que propõe uma dominação global dos homens sobre as mulheres, uma vez que mulheres também apresentam aspectos de masculinidade, sendo uma construção histórico-social, que se transforma continuamente. Assim, diante das reformas históricas de gênero acrescidas da instabilidade provocada pela pandemia da COVID-19, observa-se o aumento da violência domiciliar como efeito da diminuição do poder patriarcal, na tentativa de estabilizar o modelo de masculinidade definido por esse poder patriarcal, ou tenta-se reconstituí-lo em novas configurações. Frente a essa realidade, faz-se necessário, no âmbito da Saúde Coletiva, refletir sobre a reformulação da Política Nacional de Atenção Integral à Saúde do Homem.

Water use intensity of Canadian beef production in 1981 as compared to 2011.

The amount of beef produced per animal in Canada increased significantly from 1981 to 2011, due to enhanced production efficiency and increased carcass weight. This study examined the impact of improvements in production efficiency on water use intensity over this period. Temporal and regional differences in cattle categories, water use for drinking, feed production and meat processing, feeding systems, average daily gains, and carcass weight were considered in the analysis. Potential evapotranspiration (PET) was estimated by the National Drought Model (NDM) from 679 weather stations across Canada using the Priestley and Taylor equation. To adjust PET estimates for each crop included in cattle diets, FAO crop coefficients were used to calculate total feed water demand. Estimates of drinking water consumed by a given class of cattle accounted for physiological status, body weight and dry matter intake as well as ambient temperature. In both years, drinking water accounted for less than 1% of total water use with precipitation (i.e., green water) included for feed and pasture production. With exclusion of green water, drinking water accounted for 24% and 21% of total water use for Canadian beef production in 1981 and 2011, respectively. The estimated intensity of blue water (surface and groundwater) use per kilogram of boneless beef was 577L in 1981 and 459 in 2011, a 20% decline. The observed reduction in water use intensity over the past three decades is attributed to an increase in average daily gain and slaughter weight, improved reproductive efficiency, reduced time to slaughter as well as improvements in crop yields and irrigation efficiency. Given that feed production accounts for the majority of water use in beef production, further advances may be achieved by improving feeding efficiencies and reducing water use per unit of feed crop and pasture production.

Toxicological assessment of PEGylated single-walled carbon nanotubes in early developing zebrafish.

Functionalization of single-walled carbon nanotubes (SWCNT) with polyethylene glycol (PEG) is among the most promising strategies to avoid SWCNT aggregation in aqueous media, improving its interactions with biological systems. However, the best molecular PEG weight and functionalization strategy remain under investigation. In this work we assessed the toxicological effects of SWCNT functionalized with PEG at 600 Da in zebrafish embryos. Embryos were exposed to SWCNT at 0.01, 0.1 and 1 mg/L from 3 to 96 h post-fertilization (hpf). At the highest concentration, SWCNT led to toxic effects at several endpoints, including mortality, delayed hatching, malformations, reduced body length, increased ROS production and DNA damage. Even with these effects, SWCNT could not be detected within the bodily tissues of the larvae. Our results give evidence that the tested PEGylation approach was unsuitable to avoid SWCNT aggregation in aqueous media, and that SWCNT can induce toxicity even without being absorbed by the organism by obstructing the chorion pores.

Enhanced cholinergic-tone during the stress induce a depressive-like state in mice.

Major depressive disorder has a heterogeneous etiology, since it arises from the interaction of multiple factors and different pathophysiological mechanisms are involved in the symptomatology. This study aimed to investigate the role of the cholinergic system in the susceptibility to stress and, consequently, in the depression-like behavior. C57BL/6 mice were treated with Physostigmine (PHYS), an acetylcholinesterase (AChE) inhibitor, and were submitted to the social defeat stress. For the behavioral evaluation of the locomotor activity, anxiety-like and depression-like behaviors the open field, elevated plus maze, sucrose preference, social interaction and forced swim were used. Hippocampus and prefrontal cortex samples were collected for evaluation of AChE activity, as well as blood samples for analysis of serum cortisol levels. Our results showed that 15 min after the injection of PHYS there was a significant inhibition of AChE activity in the hippocampus and in the prefrontal cortex. On the other hand, in the end of the experimental design, day 12, there was no difference in AChE activity levels. Inhibition of AChE and exposure to the stress led to an increase in cortisol levels. Animals that received PHYS and were exposed to stress showed less social interaction and greater learned helplessness, anhedonia and anxious-like behavior. Taken together, our findings suggest that increasing the cholinergic tone shortly before stress induction impacts on the ability to cope with upcoming stressful situations, leading to a depressive-like state.

Subcutaneous injection of multipotent mesenchymal stromal cells admixed with melanoma cells in mice favors tumor incidence and growth: a systematic review and meta-analysis.

Multipotent mesenchymal stem/stromal cells (MSCs) have strong tropism towards cancer cells, thus being tested as tools for the targeted delivery of therapeutic substances for the treatment of melanoma. However, different experimental approaches for melanoma induction and MSC treatment can have a direct impact on the outcomes. Systematic search was carried out in three databases (PubMed, Scopus, and Web of Science) to include all studies, where stem cells were used as intervention for animal models for melanoma. Selected articles were classified according to SYRCLE's risk of bias tool for animals' studies. Experimental variables and published data for tumor incidence and growth were extracted from the eligible articles and standardized using Hedge's G for random effects meta-analysis and meta-regression. From 627 entries, 11 articles were eligible for meta-analysis. All studies tested the effects of a single injection of mesenchymal stem/stromal cells (MSCs) (from bone marrow or adipose tissue) admixed with B16 mouse melanoma cells (B16-F0 or B16-F10) or with human melanoma cells (A375 or M4Beu) in mice. Mean SYRCLE score was 3.09 out of 10. Results from random effects meta-analysis indicate that MSCs favored both tumor incidence and tumor growth (p = 0.001) in melanoma. Our results show that MSCs are protumorigenic in co-injection mice models for melanoma, increasing both tumor incidence and growth.

Fullerene (C60) particle size implications in neurotoxicity following infusion into the hippocampi of Wistar rats.

The buckminsterfullerene (C60) is considered as a relevant candidate for drug and gene delivery to the brain, once it has the ability to cross the blood-brain barrier. However, the biological implications of this nanomaterial are not fully understood, and its safety for intracerebral delivery is still debatable. In this study, we investigated if C60 particle size could alter its biological effects. For this, two aqueous C60 suspensions were used with maximum particle size up to 200nm and 450nm. The suspensions were injected in the hippocampus, the main brain structure involved in memory processing and spatial localization. In order to assess spatial learning, male Wistar rats were tested in Morris water maze, and the hippocampal BDNF protein levels and gene expression were analyzed. Animals treated with C60 up to 450nm demonstrated impaired spatial memory with a significant decrease in BDNF protein levels and gene expression. However, an enhanced antioxidant capacity was observed in both C60 treatments. A decrease in reactive oxygen species levels was observed in the treatments with suspensions containing particles measuring with up to 450nm. Thiobarbituric acid reactive substances, glutamate cysteine ligase, and glutathione levels showed no alterations among the different treatments. In conclusion, different particle sizes of the same nanomaterial can lead to different behavioral outcomes and biochemical parameters in brain tissue.