RESUMO
Economic efficiency is affected by several traits, and as the unit of selection is the individual, in artificial selection, to promote the maximization of economic genetic gain, the traits to be improved must be weighted by their respective economic values. In Brazil, breeding goals are defined empirically, and not based on an economic evaluation, therefore, the aim of this study was to estimate economic values for traits of economic importance in dairy farming systems based on the use of purebred and crossbred Guzerat animals. The economic values for 305-days milk yield (MY), fat yield (FY), protein yield (PY), and somatic cell count (SCC) were calculated for different production systems based on the feed management: System 1, based on pasture grazing with Brachiaria brizantha or Panicum maximum cv. Mombaça during rainy season, and corn-silage supplementation during the dry season; System 2, based on pasture grazing with Brachiaria brizantha or Panicum maximum cv. Mombaça during rainy season, and the mixture of sugarcane including urea supplementation during the dry season. Bioeconomic models were applied to estimate economic values, and a sensitivity analysis was performed. Four selection indexes were defined, each one with different goals: milk (I1), milk + protein yield (I2), I2 + fat yield (I3) and I3 + somatic cell count (I4). The economic values for MY and PY were positive for both production systems. However, for FY, the values were positive for System 2 but negative for System 1. The economic value for SCC was negative (-7.33 per SCS per lactation). The selection responses for I1 were higher than those for I2, I3 and I4, for both production systems. I4 presented the highest expected genetic gain for each trait, except for fat yield, whose expected genetic gain was greater with the use of I2, in both production systems. The results indicates that the inclusion of milk quality traits in the selection index provides better economic return, and due to the small differences in expected genetic superiority, I1 is still the most suitable for crossbred Guzerat herds whose main activity is milk production in Brazil.
Assuntos
Cruzamento , Indústria de Laticínios , Leite , Animais , Brasil , Indústria de Laticínios/economia , Indústria de Laticínios/métodos , Leite/economia , Leite/química , Bovinos/genética , Bovinos/fisiologia , Cruzamento/economia , Feminino , Lactação , Seleção Genética , Ração Animal/análise , Ração Animal/economia , Brachiaria/genética , Contagem de Células/veterináriaRESUMO
We studied sows (Landrace × Yorkshire line, DanBred Hybrid) to evaluate the possible changes in progesterone receptor (PR) expression in the uterus and ovary caused by different non-hypophyseal gonadotropins treatments: equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG). Varying concentrations of eCG and hCG were evaluated (Groups 1, 2, 3, 4). PR expression was determined by immunohistochemistry, and labelling intensity was determined by the HScore method. In the ovary, PR expression in the granulosa cells of follicles did not differ significantly between Groups 1 and 2 (p < 0.05) but differed significantly from that in Groups 3 and 4 (p < 0.05), which in turn did not differ from each other. This PR expression pattern was similar across groups in the internal and external theca cells. Conversely, in the uterus, PR expression in the lining epithelium was lower in Group 4 than that in Group 1 (p < 0.05). Increased expression was observed in the endometrial lamina propria in all groups 2 and 4 compared to that in the control group (p < 0.05). Decreased expression was observed in the glandular epithelium and myometrium in Group 4 compared to that in Group 1 (p < 0.05). In the ovary, PR expression in the granulosa and outer and inner theca of the follicles was not significantly different (p < 0.05) between Groups 1 and 2 or Groups 3 and 4; however, the expression in these pairs of groups differed from each other. Thus, changes in PR expression may depend on the concentrations and proportions of exogenous hormones used in the treatments, indicating an alteration in the reproductive process.
Assuntos
Gonadotropina Coriônica , Ovário , Receptores de Progesterona , Útero , Animais , Feminino , Receptores de Progesterona/metabolismo , Gonadotropina Coriônica/farmacologia , Útero/metabolismo , Útero/efeitos dos fármacos , Ovário/metabolismo , Ovário/efeitos dos fármacos , Suínos , Cavalos , Humanos , Imuno-Histoquímica/veterinária , Gonadotropinas Equinas/farmacologia , Células da Granulosa/metabolismo , Células da Granulosa/efeitos dos fármacos , Endométrio/metabolismo , Endométrio/efeitos dos fármacosRESUMO
Over the past decade, research in the montane forests of the Mira River basin, spanning Ecuador and Colombia, has identified it as crucial for the adaptive radiation of flora and fauna, shaped by its complex geological and climatic history. This study focuses on the phylogenetic and systematic revision of a frog clade initially labeled as Pristimantis verecundus, revealing significant cryptic diversity. Through detailed analyses of type material and expanded molecular sampling, we found that the original description actually included specimens representing two additional species, which are described herein. In this work, we discovered and formally described four new species within montane forests at elevations from 1,600 to 2,300 meters. Genetic distances of 3.34% to 14% and clear morphological differences underscore the clade's hidden diversity. We propose renaming the group Pristimantis celator clade within Pristimantis myersi species group and subgenus Trachyphrynus, aligning with phylogenetic evidence and resolving taxonomic ambiguities using the oldest available name, Pristimantis celator (Lynch, 1976). This reclassification includes 14 species, seven formally described, and seven as candidates, distributed across northwestern Ecuador and southwestern Colombia, particularly in Mira and Esmeraldas River basins. The study highlights the Andean orogeny's role in species diversification within Pristimantis celator clade, with geographic barriers like Cerro Golondrinas influencing genetic isolation. Genetic divergences exceeding 3.34% indicate evolutionary isolation across these landscapes. Our findings provide insights into montane ecosystem speciation, emphasizing vicariance, niche adaptation, and altitudinal gradients in shaping biodiversity. A polytomy among three well-supported clades within Pristimantis myersi species group is noted due to incomplete genetic data, yet distinctiveness and evolutionary relationships are affirmed. Cryptic diversity within Pristimantis celator clade links to unique orogenic and climatic conditions, highlighting conservation needs. Lastly, we provide a redescription of Pristimantis verecundus and species identification key to aid future research and conservation in this biogeographically influential region.
Assuntos
Anuros , Filogenia , Rios , Equador , Animais , Anuros/genética , Colômbia , Especiação GenéticaRESUMO
We describe a new species of Leptophis (parrot snake) from the Cerrado ecoregion of Brazil. The new species, L. mystacinus sp. nov., differs from all other congeners in the following unique character combination: two Spectrum Green (129) to Light Parrot Green (133) dorsolateral stripes separated by a Buff (5) vertebral stripe, usually continuous onto the tail; loreal scale absent; postocular stripe Jet Black (300), wide and long (up 11 scales long onto nuchal region); maxillary teeth 21-25; ventrals 158-173; subcaudals 141-164; black spots on head absent; supracephalic plates of head not edged with black pigment; adult color pattern lacking dark oblique bands; keels absent on first dorsal scale rows; hemipenis unilobed, noncapitate, with undivided sulcus spermaticus, and first row of hemipenial body with four spines. Phylogenetic analysis of 16S mtDNA sequences indicate the new species is the sister taxon of L. dibernardoi, a species occurring in the neighboring Caatinga ecoregion.
Assuntos
Colubridae , Filogenia , Animais , Brasil , Colubridae/classificação , Colubridae/genética , Colubridae/anatomia & histologia , Masculino , DNA Mitocondrial/genética , RNA Ribossômico 16S/genética , FemininoRESUMO
Parkinson's disease (PD) is a progressive degenerative disease of the central nervous system associated with neuroinflammation and microglial cell activation. Chemokine signaling regulates neuron-glia communication and triggers a microglial inflammatory profile. Herein, we identified the neuronal chemokine CCL21 as a major cause of microglial cell imbalance through the CCR7 receptor pathway with therapeutic implications for PD. In humans, we found that CCL21 transcript expression was increased in dopaminergic neurons (DANs) of the substantia nigra in PD patients. CCL21 and CCR7 expressions were spatially associated with brain regional vulnerability to synucleinopathies, as well as with the expression of microglial activation, neuroinflammation, and degeneration-related genes. Also, in mouse models of PD, we showed that CCL21 was overexpressed in DANs in vivo and in vitro. Mechanistically, neuronal CCL21 was shown to regulate microglial cell migration, proliferation, and activation in a CCR7-dependent manner through both canonical (PI3K/AKT) and non-canonical (ERK1/2/JNK) signaling pathways. Finally, we demonstrated that navarixin, a clinically relevant chemokine inhibitor with high affinity for the CCR7 receptor, could block CCL21 effects on microglia and prevent neurodegeneration and behavioral deficits in two mouse models of PD induced with either α-synuclein oligomers (αSynO) or 3,4-dihydroxyphenylacetaldehyde (DOPAL). Altogether, our data indicate that navarixin blocks CCL21/CCR7-mediated neuron-microglia communication and could be used as a therapeutic strategy against PD.
Assuntos
Quimiocina CCL21 , Doenças Neuroinflamatórias , Doença de Parkinson , Receptores CCR7 , Animais , Camundongos , Receptores CCR7/metabolismo , Receptores CCR7/genética , Humanos , Quimiocina CCL21/metabolismo , Quimiocina CCL21/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Modelos Animais de Doenças , Microglia/efeitos dos fármacos , Microglia/metabolismo , Degeneração Neural/patologia , Degeneração Neural/tratamento farmacológico , Feminino , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/patologia , Camundongos TransgênicosRESUMO
Obesity, a global epidemic, is linked to adverse reproductive outcomes, including infertility and ovulation dysfunction. The cafeteria diet (CAF) serves as an animal model mirroring Western diet habit. Coenzyme Q10 (CoQ10), known for enhancing reproductive outcomes in various pathologies, is not fully understood for its effects on obesity treatment. Here, obesity was modeled using CAF-fed rats to assess CoQ10's impact on metabolic and ovarian disruptions caused by obesity. Wistar rats were divided into control (standard diet) and obese (CAF diet) groups. After 75 days, half of each group received oral CoQ10 (5 mg/kg) for 13 days, while the rest received a vehicle. Animals were euthanized during the estrus phase, and blood and ovaries were collected for analysis. CAF caused increased body weight gain (p < 0.01) associated with hyperglycemia, hypertriglyceridemia, and hypercholesterolemia (p < 0.05). Moreover, it caused a reduction in the number of AMH + follicles (p < 0.001), increasing follicular atresia (p < 0.05) and serum estradiol levels (p < 0.05). Obesity also altered the estrous cycle and reduced the ovulation rate (p < 0.05). CoQ10 administration showed beneficial effects on all ovarian disruptions but had no effect on the metabolic alterations induced by obesity. In summary, CoQ10 could be an additional treatment for obesity-related infertility in patients with normal metabolic profiles. While CoQ10 does not affect metabolic parameters influenced by obesity, crucial for reproductive issues and offspring health, it is recommended as part of a treatment plan that includes a balanced diet and increased physical activity for obese individuals with metabolic alterations seeking pregnancy.
Assuntos
Suplementos Nutricionais , Obesidade , Ratos Wistar , Reprodução , Ubiquinona , Animais , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico , Feminino , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Ratos , Reprodução/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovário/metabolismoRESUMO
Iguanas exhibit diverse colors and behaviors reflecting evolutionarily adaptation to various habitats; in particular, the Galápagos iguanas represent unique color morphologies with distinct ecological niches. While external coloration in iguanas has ecological implications, comprehensive studies on the histological and ultrastructural aspects of their skin can provide insight into their adaptation to extreme environments, such as high UV exposure. Starting from these considerations the present study investigates the histological, ultrastructural and immunohistochemical features to comprehensively characterize the skin in adults of three species of Galápagos iguanas (A. cristatus, C. subcristatus and C. marthae). Morphological analysis revealed significant differences among the species, with the black-colored skin of A. cristatus showing a melanin-rich but vessel-poor dermis, while C. subcristatus and C. marthae displayed varying distributions of melanosomes and melanocytes. Notably, the absence of iridophores was consistent across all samples due to the absence of birefringent material under the optical microscope. Morphometric evaluations highlighted interspecific differences in the stratum corneum thickness, particularly between black- and non-black-colored (irrespectively if yellowish or pink) skin. The ultrastructural investigation confirmed the absence of iridophores in all analyzed samples. The cytokeratin expression assessed by immunohistochemistry showed stratified epithelium in the epidermis of C. marthae non-black-colored (pink) skin. The presence of a thickened stratum corneum and the stratification of the epidermis in non-pigmented skin could help the pink iguana to cope with the extreme conditions of the Wolf volcano, especially in relation to UV exposure. These skin characteristics may reduce the penetration power of UV rays into the superficial loose dermis, thereby attenuating potential UV-related damage such as DNA breaks and ROS generation. These findings offer insights into the adaptive strategies of these iguanas.
Assuntos
Iguanas , Pigmentação da Pele , Pele , Animais , Masculino , Feminino , Especificidade da Espécie , EquadorRESUMO
Trypanosoma cruzi infection involves transmission of metacyclic trypomastigotes through injured skin or mucosa via contaminated feces from insect vectors like Triatoma dimidiata (Latreille, 1811). Currently, there is insufficient information describing the immune response to feces naturally contaminated with metacyclic trypomastigotes. Mice subcutaneously inoculated with tissue-culture derived trypomastigotes (TCT) or T. dimidiata feces containing metacyclic trypomastigotes (MT) or previously multi-exposed (ME) with feces without metacyclic trypomastigotes and then infected with feces containing metacyclic parasites or only T. dimidiata feces (F) was studied from 15 min to three months post-infection. PCR detection of parasite DNA at the inoculation site demonstrated persistence of T. cruzi DNA up to 20 days in MT and TCT but disappeared earlier in the ME test group. A rapid spread of T. cruzi DNA to regional lymph nodes was observed in all experimental groups. A lower amount of amastigote nests in the heart with concomitant intense inflammation was noticed in ME mice in comparison to the MT group. CD4 + T cell subtypes at popliteal lymph nodes shows early Th1 and Th17 responses at seven days in ME mice, whereas Th1, Th17 and Treg predominate in MT mice after three weeks, and feces induces Th1, Th17 and Treg at a later stage. Our study shows that previous exposure to feces prior to infection with T. cruzi helps control parasitism at the inoculation site and in heart tissue, and an early induction of Th1 and Th17 T cell subtypes.
Assuntos
Doença de Chagas , Modelos Animais de Doenças , Fezes , Triatoma , Trypanosoma cruzi , Animais , Triatoma/parasitologia , Triatoma/imunologia , Doença de Chagas/imunologia , Fezes/parasitologia , Trypanosoma cruzi/imunologia , Camundongos , Insetos Vetores/parasitologia , Reação em Cadeia da Polimerase , DNA de Protozoário/análise , FemininoRESUMO
Rhodococcus equi is an opportunistic soil-borne bacterium that is eliminated in feces of multi-host animals. An increase in multidrug-resistant R. equi isolates has been reported in humans and domestic animals, and it has been hypothesized that the treatment of R. equi in foals could increase the selective pressure on multidrug-resistant isolates and favor human infections by resistant isolates. We investigated the in vitro antimicrobial susceptibility/resistance of 41 R. equi strains from humans, which were isolated from patients with pulmonary signs, using 19 antimicrobials from 10 distinct classes, recommended exclusively to humans, recommended exclusively to domestic animals and used in both. All isolates were subjected to mass spectrometry and identified as R. equi. Among the antimicrobials used exclusively in humans, tigecycline and vancomycin showed 100% efficacy. Amikacin, amoxicillin/clavulanic acid, imipenem, levofloxacin, clarithromycin, rifampin, ciprofloxacin, and gentamicin, used in both humans and animals, revealed high efficacy (97-100%). Conversely, a higher frequency of isolates was resistant to penicillin (87.8%) and trimethoprim/sulfamethoxazole (43.9%), which are used in both humans and animals. Among the antimicrobials used only in animals, isolates were resistant to florfenicol (46.4%), ceftiofur (17.1%), and enrofloxacin (2.5%). Multidrug resistance was observed in 34% of isolates. The identification of drug-resistant R. equi isolated from humans used exclusively in animals is circumstantial evidence of the pathogen transmission from domestic animals to humans. This study contributes to the molecular identification of Rhodococcus species from humans and to the epidemiological vigilance of the multidrug-resistant isolates.
Assuntos
Infecções por Actinomycetales , Antibacterianos , Testes de Sensibilidade Microbiana , Rhodococcus equi , Rhodococcus equi/efeitos dos fármacos , Rhodococcus equi/isolamento & purificação , Animais , Antibacterianos/farmacologia , Humanos , Infecções por Actinomycetales/microbiologia , Infecções por Actinomycetales/tratamento farmacológico , Infecções por Actinomycetales/veterinária , Farmacorresistência Bacteriana Múltipla , Animais Domésticos/microbiologia , Cavalos/microbiologiaRESUMO
Malaria is a parasitic disease of great relevance in global public health. The development of new sensitive and specific diagnostic high-throughput methods remains a challenge in the eradication of this disease. In this study, we developed a flow cytometry test using latex microbeads and polyclonal antibodies obtained from rabbits and mice for the detection of the P. vivax lactate dehydrogenase (PvLDH) antigen. We processed 50 samples from Brazilian patients diagnosed with malaria caused by P. vivax and 40 samples from healthy individuals. The assay presented sensitivity of 64%, specificity of 97%, a positive predictive value of 97%, and a negative predictive value of 57% when analyzed using the fluorescent labeling method. Using the mean fluorescence intensity (MFI) analysis method, the sensitivity was 53%, specificity was 89%, the positive predictive value was 95%, and the negative predictive value was 33%. In both methods of analysis, we observed significant statistical differences between the analyzed groups (P-value <0.0001). A high correlation (0.60) between the two methods and a low correlation between PvLDH concentration and parasite density was found. The test was able to detect the PvLDH protein with high specificity, but its sensitivity should be improved. More promising results were observed when the samples were analyzed according to the percentage of fluorescent labeling. Improvement of this assay would enable its application as a serological test for the detection of asymptomatic patients and for the validation of rapid diagnostic tests.
Assuntos
Citometria de Fluxo , L-Lactato Desidrogenase , Malária Vivax , Microesferas , Plasmodium vivax , Sensibilidade e Especificidade , Citometria de Fluxo/métodos , Humanos , Plasmodium vivax/enzimologia , L-Lactato Desidrogenase/análise , Animais , Coelhos , Malária Vivax/diagnóstico , Camundongos , Látex , Estudos de Casos e Controles , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/análise , Valor Preditivo dos TestesRESUMO
Sirtuins (SIRTs) are key regulators of cellular metabolism, involved in a wide range of physiological and pathological processes. However, there is scarce knowledge about the effect of sugar consumption and physical activity on SIRTs in kidney disorders. Here, we evaluated the impact of prolonged consumption of an isocaloric high-sugar diet (HSD) and physical training on the modulation of renal Sirts and the link between these alterations and possible obesity-associated kidney damage. Newly weaned male Wistar rats were fed a standard chow diet (STD) or HSD ad libitum and then subjected or not to regular workload swimming training for 18 weeks. Morphometric and biochemical parameters were analyzed, and the kidneys were removed for lipid quantification, histological analysis, and for Sirts1-7 expression. HSD led to the development of obesity, increased serum triglyceride levels, and glucose intolerance, regardless of higher caloric consumption. However, training was able to partially inhibit the HSD-induced obesogenic effect. No changes were identified in kidney mass, lipid content, histology, and creatinine clearance among the groups; these results were associated with a decrease in the renal expression of Sirt2-3 and Sirt7; however, training was able to reverse this modulation. The interaction between HSD and training led to an increase in Sirt4-7. However, Sirt1 remained constant among experimental groups. In conclusion, our results indicated that the transcriptional modulation of Sirts precedes HSD-induced damage and loss of kidney function, as well as a possible protective adaptive response of physical exercise on long-term Sirts expression.
Assuntos
Condicionamento Físico Animal , Ratos Wistar , Sirtuínas , Natação , Animais , Masculino , Natação/fisiologia , Condicionamento Físico Animal/fisiologia , Sirtuínas/metabolismo , Ratos , Obesidade/metabolismo , Rim/metabolismoRESUMO
Hepatic ischemia reperfusion injury (HIRI) is a pathophysiological and complex systemic process involving multiple tissues and organs. Gastrodin (GSTD), a natural compound from Gastrodia elata, displays a variety of interesting pharmacological activities. Heme oxygenase-1 (HO-1), a stress-responsive protein, has a cytoprotective defense response against oxidative and inflammatory injuries. The aim of this investigation was to elucidate whether GSTD plays a protective role against HIRI by regulating HO-1 expression. GSTD (100 mg/kg) or zinc protoporphyrin (15 mg/kg; an HO-1 inhibitor) was administered to HIRI C57 male mice. GSTD decreased glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels in HIRI mice. Inflammatory (TNF-α and IL-6) and oxidative-stress (malondialdehyde, MDA) markers of HIRI mice were decreased by GSTD. GSTD up-regulated HO-1 protein and mRNA expression in HIRI mice but decreased caspase-3 and -9 protein expression. GSTD lowered mRNA expression of apoptosis-related genes (caspase-3, -9, -12, and Bax) in the liver of HIRI mice but enhanced mRNA level of the anti-apoptotic Bcl-2 gene. Consistent with in vivo results, GSTD displayed a similar regulatory effect on the expression of mRNA (HO-1, caspase-3, -9, -12, Bax, and Bcl-2) and protein (HO-1, caspase-3 and -9) as well as inflammatory (TNF-α and IL-6) and on oxidative stress factors (superoxide dismutase and MDA) in BRL-3A cells transfected with small interfering HO-1 RNA in a hypoxia-reperfusion model. In conclusion, GSTD up-regulated HO-1 expression to play a protective role in HIRI by anti-apoptotic, anti-inflammatory, and antioxidant effects. GSTD is a promising natural compound that alleviated HIRI in liver surgery.
Assuntos
Álcoois Benzílicos , Glucosídeos , Heme Oxigenase-1 , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Masculino , Glucosídeos/farmacologia , Álcoois Benzílicos/farmacologia , Heme Oxigenase-1/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Fígado/efeitos dos fármacosRESUMO
BACKGROUND: The nematode Angiostrongylus cantonensis, which is endemic to Southeast Asia and adjacent Pacific Islands, has already been recorded in more than 30 countries, including Brazil and other South American nations. It is one of the principal etiological agents of the zoonosis Eosinophilic Meningitis (EoM), which has a number of different species of terrestrial gastropods that act as its intermediate hosts. OBJECTIVE: The present study investigated the occurrence of the larvae of this nematode in specimens of terrestrial molluscs collected in half of the municipalities of the Brazilian State of Rio de Janeiro. METHODS: The study is based on the surveillance of this nematode in the Brazilian State of Rio de Janeiro, where terrestrial snails and slugs were collected in more than half of the state's municipalities (46 in all), and examined for parasitological infections. The nematode larvae retrieved from these specimens were identified based on their morphology and cytochrome oxidase I (COI) mitochondrial DNA sequences. FINDINGS: Angiostrongylid larvae were found in 230 (8.8%) of the 2,600 terrestrial molluscs examined, collected from 26 municipalities. Overall, 14 terrestrial gastropod species were identified, including both native and exotic taxa, and six were found to be infected naturally by A. cantonensis. The natural infection rates by Angiostrongylus in the different terrestrial molluscs species were 12.5% in Angustipes erinaceus, 9.7% in Achatina fulica, 6.8% in Bradybaena similaris, 6.3% in Sarasinula linguaeformis, 3.9% in Leptinaria unilamellata, and 4.6% in Subulina octona. A. fulica was the most frequent and extensively distributed species, with infected snails being found in 22 municipalities. MAIN CONCLUSIONS: The data from this first comprehensive survey of A. cantonensis in Rio de Janeiro highlights the potential epidemiological risk of human infection in this state. Mapping the spread of infected molluscs will also provide essential information for the evaluation of the risk of human infection, and should help local health authorities to provide a faster and more accurate diagnosis whenever neuroangiostrongyliasis is suspected.
Assuntos
Angiostrongylus cantonensis , Animais , Angiostrongylus cantonensis/isolamento & purificação , Angiostrongylus cantonensis/genética , Brasil/epidemiologia , Infecções por Strongylida/epidemiologia , Infecções por Strongylida/parasitologia , Zoonoses/parasitologia , Meningite/parasitologia , Meningite/epidemiologia , Humanos , Eosinofilia/parasitologia , Eosinofilia/epidemiologia , Moluscos/parasitologia , Caramujos/parasitologia , Larva , Gastrópodes/parasitologiaRESUMO
Alpinia zerumbet, a plant native to East Asia, is widely found on the Brazilian coast, where it is used in folk medicine as an antihypertensive, diuretic, and anxiolytic. This study investigated the effects of the hydroalcoholic extract obtained from Alpinia zerumbet leaves (AZE) on cardiovascular changes and oxidative status in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto male rats, 90 days old, treated or not with AZE (50 mg/kg/day in drinking water) for six weeks, were used in this study. Blood pressure (BP) was assessed weekly by tail plethysmography. At the end of treatment, the animals were anesthetized with thiopental (70 mg/kg, ip), blood was collected through abdominal aorta puncture, the thoracic aorta and left ventricle were isolated for morphometric analysis and immunostaining of NOX-4, SOD-2, 8-isoprostane, and angiotensin II AT1 receptors (AT1R), and the mesenteric arterial bed (MAB) was isolated for the assessment of vascular function. Oxidative damage in lipids and proteins and the enzymatic antioxidant activity were evaluated in plasma samples by spectrophotometry. AZE normalized BP in SHR. Although the treatment did not improve the MAB vascular dysfunction, it reversed the cardiovascular remodeling in the aorta and left ventricle. In addition, AZE improved antioxidant activity in plasma and SOD-2 immunostaining in the thoracic aorta and left ventricle, decreased protein carbonylation in plasma, and reduced 8-isoprostane, NOX-4, and AT1R immunostaining in the cardiovascular system. The results suggested that AZE reversed hypertension and cardiovascular remodeling in SHR, which was associated with lower oxidative stress and AT1R.
Assuntos
Alpinia , Anti-Hipertensivos , Hipertensão , Extratos Vegetais , Folhas de Planta , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Alpinia/química , Ratos , Folhas de Planta/química , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Remodelação Ventricular/efeitos dos fármacosRESUMO
Malaria, caused by Plasmodium spp., remains a major public health problem. Cerebral malaria is its deadliest form, with a 15-25% mortality rate, despite artemisinin-based treatments. In addition, the World Health Organization (WHO) strictly defines cerebral malaria as the presence of coma, 1 h after a seizure or the correction of hypoglycemia, in patients with P. falciparum parasitemia. Consequently, 25% of survivors experience neurocognitive and behavioral sequelae, particularly in children. However, more recently, neurocognitive and behavioral impairments were also reported in severe non-cerebral malaria, non-severe malaria, and even during asymptomatic Plasmodium infection. Such impairments have been observed in school-aged children, the elderly, and in animal models without classic cerebral malaria pathology. Additionally, mild vasogenic edema has been detected in neuroimaging of patients with severe non-cerebral and non-severe P. falciparum malaria. Therefore, given that approximately 98% of malaria cases in the world are non-severe, neurocognitive and behavioral sequelae may account for a significant proportion of global malaria morbidity. Taken together, these observations suggest that systemic inflammation from malaria, even without traditional cerebral malaria signs, can disrupt brain function and lead to long-term sequelae. We propose that the current definition of cerebral malaria may not fully capture the observed evidence and a new conceptualization is necessary to encompass these findings.
Assuntos
Malária Cerebral , Humanos , Malária Cerebral/complicações , Malária Falciparum/complicações , AnimaisRESUMO
Osteosarcoma (OS) remains the most common bone tumor and the prognosis for many patients remains stagnant due to the unsatisfactory therapeutic effect of conventional treatment regimens. This research explored the effect and mechanism of a novel natural product, Eriocalyxin B (EB), in pathogenesis and immunotherapy in OS. Cell Count Kit 8 assay, colony formation assay, and wound healing assay were employed to detect the proliferative, colony-forming, and migratory abilities of human OS cells following EB treatment. Moreover, xenograft growth assay was performed to assess the effect of EB on OS in vivo. Subcutaneous OS models constructed in immunocompetent mice were employed to evaluate the effect of EB treatment in combination with immune checkpoint blockades (ICBs) PD1ab and CTLA4ab. Immunohistochemistry (IHC) staining was utilized to detect the level of CD8+ T cells infiltration and Ki67 expression. TARGET database, RNA interference technology, and qPCR assay were employed to explore the mechanism of EB on OS. EB inhibited the proliferative, colony-forming, and migratory abilities of the human OS cells MG63 and U2OS both in vitro and in vivo. TARGET data analysis demonstrated that up-regulation of TCEA3 was significantly negatively correlated with overall survival in OS patients. EB exerted anti-tumor activity via downregulation of TCEA3. EB, in conjunction with ICBs, synergistically optimized anti-tumorigenic activity against OS in immunocompetent mice. EB may promote infiltration of CD8+ T cells and down-regulate Ki67 expression. These results signaled that EB may have a role as a candidate therapeutic or preventive agent for the treatment of OS.
Assuntos
Neoplasias Ósseas , Regulação para Baixo , Inibidores de Checkpoint Imunológico , Osteossarcoma , Osteossarcoma/tratamento farmacológico , Animais , Humanos , Regulação para Baixo/efeitos dos fármacos , Camundongos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Antígenos de Neoplasias , DiterpenosRESUMO
Necrotizing enterocolitis (NEC) is a severe intestinal disease of multifactorial origin that primarily affects premature infants. Approximately 27% of NEC babies develop short gut (SG) secondary to extensive intestinal resection, and 10% will have chronic dependence on total parenteral nutrition. We evaluated the Botox treatment in SG model rats. Twenty-day-old weanling male rats (weight range 38-70 g, n=72) were divided into four groups (n=18 each): 1) Control (fed a regular liquid diet); 2) Botox (Control submitted to laparotomy and intestinal injection of Botox®); 3) SG (short gut); and 4) SG and Botox (SG+Botox®). After seven post-operative days, samples were collected for biometrics [body weight (BW), intestine weight (IW) and IW/BW ratio (IBR), and intestine length (IL) and height (IH)], histometric analysis [villous height (VH), crypt depth (CD), muscular thickness (MT), and PCNA index)], and intestinal transit time (ITT). BW, IW, and IL decreased in SG (P<0.05). IH, VH, and PCNA index increased in Botox groups [Control = SG < Botox and SG+Botox (P<0.05)], CD increased in Botox, SG, and SG+Botox (P<0.005), and MT was higher in SG and SG+Botox. Botox groups had lower ITT (P<0.05). Botox provided dilatation and histological changes in SG. These findings suggested that Botox improved adaptation and might be applied in SG with promising results.
Assuntos
Adaptação Fisiológica , Síndrome do Intestino Curto , Animais , Masculino , Síndrome do Intestino Curto/tratamento farmacológico , Adaptação Fisiológica/efeitos dos fármacos , Ratos , Modelos Animais de Doenças , Ratos Wistar , Toxinas Botulínicas Tipo A/farmacologia , Toxinas Botulínicas Tipo A/administração & dosagem , Enterocolite Necrosante/tratamento farmacológico , Animais Recém-Nascidos , Desmame , Intestinos/efeitos dos fármacosRESUMO
Cancer is the second leading cause of death worldwide. Cancer cachexia is a multifactorial catabolic syndrome responsible for almost one third of cancer-related deaths. Drug repurposing has been used in oncological research and drugs like clenbuterol and metformin seem to be reasonable candidates in the context of cancer cachexia, because the former is a ß2-agonist that stimulates muscle gain and the latter has anti-inflammatory properties. The aim of this study was to assess the effects of a short-term treatment with metformin and clenbuterol, isolated or combined, on tumor growth and cancer cachexia parameters in Walker 256 tumor-bearing rats, a model of cancer cachexia. To this end, Wistar rats were separated into 8 groups and 4 of them were injected with Walker 256 tumor cells (W groups). Control (C) and W groups received the following treatments: metformin (M), clenbuterol (Cb), or metformin combined with clenbuterol (MCb). Body and tumor weight, metabolic parameters, and oxidative damage in the tumor were assessed. Compared to the C group, the W group showed body weight loss, hypoglycemia, hyperlactatemia, and hypertriacylglycerolemia. None of the treatments could reverse body weight loss, although they reversed the alterations of the assessed plasma metabolic parameters. Surprisingly, only clenbuterol alone reduced tumor weight. Hydrogen peroxide production and lipid peroxidation in tumor tissue was increased in this group. In conclusion, metformin and clenbuterol ameliorated metabolic cachexia parameters in Walker tumor-bearing rats, but only clenbuterol reduced the tumor weight, probably, through a lipid peroxidation-dependent cell death.
Assuntos
Caquexia , Carcinoma 256 de Walker , Clembuterol , Peroxidação de Lipídeos , Metformina , Ratos Wistar , Animais , Caquexia/tratamento farmacológico , Caquexia/etiologia , Metformina/farmacologia , Metformina/uso terapêutico , Clembuterol/farmacologia , Clembuterol/uso terapêutico , Carcinoma 256 de Walker/tratamento farmacológico , Carcinoma 256 de Walker/complicações , Masculino , Peroxidação de Lipídeos/efeitos dos fármacos , Ratos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Modelos Animais de Doenças , Agonistas Adrenérgicos beta/farmacologiaRESUMO
Lethal alleles are mutations in the genome that cause embryonic losses in affected homozygous embryos and, therefore, can negatively influence reproduction rates in commercial populations. Thus, this study aimed to identify genomic regions containing potential lethal haplotypes in Nellore breed; identify candidate genes located within these regions; and investigate the reproductive performance of heterozygous carriers of lethal haplotypes in Nellore cattle. Forty-five genomic regions harboring putative lethal haplotypes were identified, which overlap with 360 genes. Gene ontology analyses of these genes revealed biological processes associated with the development of sexual traits in males and females, key functions of the immune system, energy homeostasis, and embryonic development. The gene networks were involved in metabolic pathways including ovarian steroidogenesis, oocyte meiosis, and insulin secretion. Matings between carrier dam and carrier sire led to a reduction of up to -203.46% in pregnancy success probability, an increase of 275.15% in probability of pregnancy loss, 295.03% for stillbirth occurrence, and 301.40% for pre-weaning mortality when compared to non-carrier dam and sire matings. The results highlight the importance of identifying animals that are carriers of lethal haplotypes to avoid the propagation of these haplotypes in the population.
Assuntos
Haplótipos , Reprodução , Animais , Bovinos/genética , Feminino , Masculino , Reprodução/genética , Gravidez , Genes Letais , Genoma , CruzamentoRESUMO
Mytella strigata, a potentially invasive species native to South America, is rapidly spreading across various aquatic ecosystems around the globe, posing a threat to native mussels. This study presents the first comprehensive de novo transcriptome assembly of M. strigata. We generated 254 million reads, which were processed and assembled using the Trinity assembler, resulting in 60362 transcripts with an N50 of 1,578 bp and over 93-98% completeness, as confirmed by BUSCO analysis with multiple ortho-datasets. A number of databases were used for functional annotation, including UniProt, KEGG, Reactome, InterPro, and eggNOG. Gene Ontology and pathway analyses identified transcripts associated with key biological processes, including those associated with cell signalling, metabolism, stress responses, cancer pathways, and immune regulation. This dataset enriches the bivalve database by advancing the understanding of the adaptive success and evolutionary resilience of this invasive species. The present study provides a fundamental framework for future research on the ecological and evolutionary impacts of this invasive species.