Alpha-synuclein (aSyn) is the major protein component of Lewy bodies and Lewy neurites, the typical pathological hallmarks in Parkinson's disease (PD) and Dementia with Lewy bodies. aSyn is capable ...of inducing transcriptional deregulation, but the precise effect of specific aSyn mutants associated with familial forms of PD, remains unclear. Here, we used transgenic mice overexpressing human wild-type (WT) or A30P aSyn to compare the transcriptional profiles of the two animal models. We found that A30P aSyn promotes strong transcriptional deregulation and increases DNA binding. Interestingly, COL4A2, a major component of basement membranes, was found to be upregulated in both A30P aSyn transgenic mice and in dopaminergic neurons expressing A30P aSyn, suggesting a crucial role for collagen related genes in aSyn-induced toxicity. Finally, we observed that A30P aSyn alters Golgi morphology and increases the susceptibility to endoplasmic reticulum (ER) stress in dopaminergic cells. In total, our findings provide novel insight into the putative role of aSyn on transcription and on the molecular mechanisms involved, thereby opening novel avenues for future therapeutic interventions in PD and other synucleinopathies.
•A30P aSyn exhibits robust transcriptional deregulation in transgenic mice.•ER-related pathways are found deregulated in A30P aSyn transgenic mice.•A30P aSyn binds to several regions of DNA and affects exon usage.•A30P aSyn upregulates COL4A2, a major component of basement membranes.•A30P aSyn alters Golgi morphology and increases the susceptibility to ER stress.
Background
Diarrhea associated with parvovirus infection is common in dogs. Supportive care is the mainstay of treatment, but recovery may be prolonged and mortality rate can be high. Modification of ...the intestinal bacterial microbiota has been promising in human and veterinary medicine as an adjunctive treatment of various enteric diseases.
Objectives
To investigate the safety and efficacy of fecal microbiota transplantation (FMT) on the clinical recovery of puppies with acute hemorrhagic diarrhea syndrome.
Animals
Sixty‐six puppies with parvovirus infection were evaluated at 2 veterinary hospitals.
Methods
Randomized clinical trial. Puppies were randomly distributed into 2 groups: standard treatment (STD) and standard treatment + FMT (STD + FMT). The STD puppies (n = 33) received only treatment with IV fluids and antimicrobials and the STD + FMT puppies (n = 33) received FMT in addition to standard treatment. For FMT, 10 g of feces from a healthy dog diluted in 10 mL of saline were administered rectally 6‐12 hours post‐admission.
Results
Among survivors, treatment with FMT was associated with faster resolution of diarrhea (P < .001) and shorter hospitalization time (P = .001; median, 3 days in STD + FMT; median, 6 days in STD) compared to standard treatment. Mortality in STD was 36.4% (12/33) as compared to 21.2% (7/33) in puppies treated with FMT, but there was no statistical difference between groups (P = .174). Polymerase chain reaction indicated that all animals carried canine parvovirus, strain CPV‐2b.
Conclusions
Fecal microbiota transplantation in parvovirus‐infected puppies was associated with faster resolution of diarrhea.
To investigate the SARS-CoV-2 Spike protein (Spk)-induced inflammatory response and its downmodulation by diminazene aceturate (DIZE).
Through inducing Spk inflammation in murine models, leukocyte ...migration to the peritoneum, levels of myeloperoxidase (MPO), malondialdehyde (MDA), rolling and adhesion of mesenteric leukocytes, and vascular permeability were investigated. Extracellular DNA traps (DETs) induced by Spk and the production of IL-6 and TNF-α were analyzed using human neutrophils, monocytes, and macrophages. In silico assays assessed the molecular interaction between DIZE and molecules related to leukocyte migration and DETs induction.
Spk triggered acute inflammation, demonstrated by increasing leukocyte migration. Oxidative stress was evidenced by elevated levels of MPO and MDA in the peritoneal liquid. DIZE attenuated cell migration, rolling, and leukocyte adhesion, improved vascular barrier function, mitigated DETs, and reduced the production of Spk-induced pro-inflammatory cytokines. Computational studies supported our findings, showing the molecular interaction of DIZE with targets such as β2 integrin, PI3K, and PAD2 due to its intermolecular coupling.
Our results outline a novel role of DIZE as a potential therapeutic agent for mitigating Spk-induced inflammation.
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•SARS-CoV-2 Spike protein (Spk) induces acute inflammatory responses in a murine model of peritonitis.•Diminazene aceturate (DIZE) exerts anti-inflammatory effects on Spk-induced inflammation in mice.•DIZE mitigates DNA extracellular traps (DETs) in human leukocytes: neutrophils, monocytes, and macrophages.
Global anthropogenic changes cause major impacts on species interactions, with cascading effects on ecosystem functioning. Animal-mediated pollination and seed dispersal are major mutualisms ...associated with distinct stages of plant reproduction. Nevertheless, we lack an integrated assessment on how multiple anthropogenic impacts affect these interrelated mutualisms. Here, we systematically reviewed the effect of the most important global anthropogenic factors (agrochemicals, climate change, fire, fragmentation, hunting, non-native species and urbanization) on pollination and seed dispersal. We evaluated which anthropogenic factors, mutualisms and their combinations have been more frequently investigated, the biogeographic and taxonomic tendencies and the most frequently recorded effects of anthropogenic factors. We show that pollination has been more broadly investigated, that the impacts of the anthropogenic factors on pollination and seed dispersal are biased towards the temperate region and forest biomes and lack representation from some relevant groups, such as mutualistic bats. Moreover, some anthropogenic factors have been more studied for one mutualism type in relation to the other, for instance, agrochemicals and urbanization on plant-pollinator interactions, even though these impacts could also generate direct and cascading effects on frugivores and seed dispersal. The predominance of negative effects observed, especially of climate change on plant-pollinator and non-native species on plant-frugivore interactions deserve special attention. Finally, we identify a gap in empirical studies that simultaneously consider pollination and seed dispersal as integrated components of plant reproduction, and combined anthropogenic factors in the same ecosystem. More integrative studies are needed to better understand the vulnerability of plant-animal mutualisms in a changing world.
•Plant-pollinator mutualism is more studied than plant-frugivore mutualism.•Studies with bats as mutualistic partners are scarce.•Negative effects of anthropogenic factors on both mutualisms are predominant.•Climate change impacts mostly on pollination and non-native species on seed dispersal.•More integrative studies considering multiple anthropogenic factors are recommended.
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•Preparation, optimization, and characterization of solid lipid nanoparticles (SLNs) co-encapsulated with doxorubicin and α-tocopheryl succinate (TS).•In situ formation of ion-pairing ...of TS with doxorubicin in nanoparticles.•SLN provide a controlled doxorubicin release.•TS Enhance encapsulation efficiency and anticancer activity of doxorubicin in solid lipid nanoparticles (SLNs).
This work aimed to develop solid lipid nanoparticles (SLN) co-loaded with doxorubicin and α-tocopheryl succinate (TS), a succinic acid ester of α-tocopherol that exhibits anticancer actions, evaluating the influence of TS on drug encapsulation efficiency. The SLN were characterized for size, zeta potential, entrapment efficiency (EE), and drug release. Studies of in vitro anticancer activity were also conducted. The EE was significantly improved from 30±1% to 96±2% for SLN without and with TS at 0.4%, respectively. In contrast, a reduction in particle size from 298±1 to 79±1nm was observed for SLN without and with TS respectively. The doxorubicin release data show that SLN provide a controlled drug release. The in vitro studies showed higher cytotoxicity for doxorubicin-TS-loaded SLN than for free doxorubicin in breast cancer cells. These findings suggest that TS-doxorubicin-loaded SLN is a promising alternative for the treatment of cancer.
We describe the use of bismuth(III) triflate as an efficient and environmentally friendly catalyst for the Nazarov reaction of aryl vinyl ketones, leading to the synthesis of ...3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones. By changing the temperature and reaction time, it was possible to modulate the reactivity, allowing the synthesis of two distinct product classes (3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones) in good to excellent yield. The reaction did not require additives and was insensitive to both air and moisture. Preliminary biological evaluation of some indanones showed a promising profile against some human cancer line cells.
Here, we have evaluated water-based paint formulations containing mineral binders, silver nanoparticles, and titanium dioxide. Scanning electron microscopy analysis of dried film samples showed that ...the paint base was highly porous, and that paint formulations containing 10% and 20% titanium dioxide had different surface morphology. CIELab measurements for methylene blue coloration decay showed that photocatalysis was more efficient for the samples with 20% titanium dioxide. Under ultraviolet radiation, silver nanoparticles contributed to photocatalysis performance. Contact angles proved that titanium dioxide concentration and type defined the wetting characteristics. The samples with 20% TiO
2
displayed porous surfaces with better adsorbance characteristics, higher wettability, and improved heterogeneous photocatalysis.
To present the essential guidelines for non-pharmacological management of patients with psychomotor agitation in Brazil.
These guidelines were developed based on a systematic review of articles ...published from 1997 to 2017, retrieved from MEDLINE (PubMed), Cochrane Database of Systematic Review, and SciELO. Other relevant articles identified by searching the reference lists of included studies were also used to develop these guidelines. The search strategy used structured questions formulated using the PICO model, as recommended by the Guidelines Project of the Brazilian Medical Association. Recommendations were summarized according to their level of evidence, which was determined using the Oxford Centre for Evidence-based Medicine system and critical appraisal tools.
We initially selected 1,731 abstracts among 5,362 articles. The final sample included 104 articles that fulfilled all the inclusion criteria. The management of agitated patients should always start with the least coercive approach. The initial non-pharmacological measures include a verbal strategy and referral of the patient to the appropriate setting, preferably a facility designed for the care of psychiatric patients with controlled noise, lighting, and safety aspects. Verbal de-escalation techniques have been shown to decrease agitation and reduce the potential for associated violence in the emergency setting. The possibility of underlying medical etiologies must be considered first and foremost. Particular attention should be paid to the patient's appearance and behavior, physical signs, and mental state. If agitation is severe, rapid tranquilization with medications is recommended. Finally, if verbal measures fail to contain the patient, physical restraint should be performed as the ultimate measure for patient protection, and always be accompanied by rapid tranquilization. Healthcare teams must be thoroughly trained to use these techniques and overcome difficulties if the verbal approach fails. It is important that healthcare professionals be trained in non-pharmacological management of patients with psychomotor agitation as part of the requirements for a degree and graduate degree.
The non-pharmacological management of agitated patients should follow the hierarchy of less invasive to more invasive and coercive measures, starting with referral of the patient to an appropriate environment, management by a trained team, use of verbal techniques, performance of physical and mental assessment, use of medications, and, if unavoidable, use of the mechanical restraint.
CRD42017054440.
To present the essential guidelines for pharmacological management of patients with psychomotor agitation in Brazil.
This is a systematic review of articles retrieved from the MEDLINE (PubMed), ...Cochrane Database of Systematic Reviews, and SciELO databases published from 1997 to 2017. Other relevant articles in the literature were also used to develop these guidelines. The search strategy used structured questions formulated using the PICO model, as recommended by the Guidelines Project of the Brazilian Medical Association. Recommendations were summarized according to their level of evidence, which was determined using the Oxford Centre for Evidence-based Medicine system and critical appraisal tools.
Of 5,362 articles retrieved, 1,731 abstracts were selected for further reading. The final sample included 74 articles that met all inclusion criteria. The evidence shows that pharmacologic treatment is indicated only after non-pharmacologic approaches have failed. The cause of the agitation, side effects of the medications, and contraindications must guide the medication choice. The oral route should be preferred for drug administration; IV administration must be avoided. All subjects must be monitored before and after medication administration.
If non-pharmacological strategies fail, medications are needed to control agitation and violent behavior. Once medicated, the patient should be monitored until a tranquil state is possible without excessive sedation.
CRD42017054440.
The post‐operative period can generate immunological stress and can be modulated through supplementation with the omega‐3 series of polyunsaturated fatty acids. This study aimed to evaluate the ...effects of diets enriched with high doses of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids and glutamine on inflammatory mediators in dogs before and after ovariohysterectomy (OVH). Twelve female dogs were divided into two groups: group A was fed a commercial diet without the addition of EPA and DHA, and group B was fed an experimental diet enriched with EPA and DHA (0.2 g/100 kcal). Experimental diet intake initiated 21 days before surgery and continued until 30 days after OVH. Parameters measured were serum cytokines (TNF‐α, IL‐6 and IL‐10), C‐reactive protein (CRP), IGF‐1, lymphoproliferation and body composition before and after surgery. Statistical analyses were performed with SAS software considering the effects of age and diet and their interactions, and means were compared by the Tukey test. There was no difference between groups in body weight (p = .682), lean mass (p = .101) and body fat (p = .103). There were no group differences in serum concentrations of TNF‐α, IL‐6, IL‐10, IGF‐1, CRP and the percentage of lymphocyte proliferation. However, a time effect for TNF‐α was observed (p < .001), in which T0P (10 days after the surgical procedure) presented lower values of this cytokine when compared to the other evaluation time points; and interaction effects between group and time were observed for serum concentrations of IL‐6 (p < .001) and IL‐10 (p = .002). OVH procedure was not considered invasive enough to increase inflammatory cytokines after 30 days of surgery, as well as the dosage of the EPA and DHA used before and after the surgery did not modulate the inflammatory markers.
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