Role of collagen and immunostaining for TGF-ß in the clinical and microscopic findings of pyogenic granuloma and peripheral ossifying fibroma.

BACKGROUND: Collagen is a component of Pyogenic Granuloma (PG) and Peripheral Ossifying Fibroma (POF) and performs different functions in these lesions. The objective of this study is to evaluate the role of collagen and immunostaining for Transforming Growth Factor beta (TGF-ß) in the clinical and microscopic findings of PG and POF. MATERIAL AND METHODS: PG (n=20) and POF (n=20) were selected for clinical evaluation (sex, age, localization, size and evolution time) and microscopic analysis (picrosirius red staining for collagen analysis and immunohistochemistry for TGF-ß) performed in the superficial and deep areas of the two lesions. ANOVA/Bonferroni and t-test, Pearson correlation and χ2 were used to compare the sites and parameters analyzed (p<0.05, GraphPad Prism 5.0). RESULTS: The depth of PG presented the highest amount of collagen (p<0.001), and its surface showed the lowest amount of type 1 collagen (yellow-red strong birefringence). Type 1 collagen gradually increased in depth of PG, surface and depth of POF (p<0.001). The number of TGF-ß+ cells was lower on the surface of PG compared with the depth of PG and the two areas of POF (p<0.001). Sex and localization did not affect these parameters, but the profile of collagen and immunostaining for TGF-ß suffered from modifications by the time of evolution and the size of the lesion. CONCLUSIONS: Although PG and POF are reactive gingival lesions, the expression of TGF-ß and its role in collagen showed different biological behaviors in these lesions, suggesting different biological origins for its components.

Insecticidal activity of essential oils on Spodoptera frugiperda and selectivity to Euborellia annulipes / Atividade inseticida de óleos essenciais sobre Spodoptera frugiperda e seletividade para Euborellia annulipes

Fall armyworm (Spodoptera frugiperda) is the main species that causes damage to the maize crop in Brazil. In the perspective of studying alternatives of control of this pest that preserve the natural enemies, the aim of this research was to evaluate the insecticidal efficiency of the essential oils of Vanillosmopsis arborea and Lippia microphylla on S. frugiperda and verify the selectivity to the predator Euborellia annulipes. The bioassays were carried out in the Agricultural Entomology Laboratory of the Federal University of Paraiba, using insects, from 3rd instar of S. frugiperda and E. annulipes, originating from mass rearing in the laboratory itself. Dilutions of the oils were performed in Tween® 80 at concentrations of 0, 100, 150 and 200 mg mL-1. 1.0 µL from each dilution was applied to the prothoracic region of the insects. The S. frugiperda mortality was verified by topical contact of V. arborea oil with LC10 = 74.3 mg mL-1 and LC50 = 172.86 mg mL-1, for L. microphyla, LC10 = 51.26 mg mL-1 and LC50 = 104.52 mg mL-1. The observed lethal concentrations for E. annulipes were V. arborea LC10 = 71.3 mg mL-1 and LC50 = 160.2 mg mL-1. While L. microphyla, were LC10 = 50.3 mg mL-1 and LC50 = 134.67 mg mL-1. The essential oils of V. arborea and L. microphylla are efficient in the control of S. frugiperda, but are not selective to the predator E. Annulipes.

A lagarta-do-cartucho (Spodoptera frugiperda) é a principal espécie que causa danos à cultura do milho no Brasil. Na perspectiva de estudar alternativas de controle desta praga que preservem os inimigos naturais, o objetivo desta pesquisa foi avaliar a eficiência inseticida dos óleos essenciais de Vanillosmopsis arborea e Lippia microphylla sobre S. frugiperda e verificar a seletividade ao predador Euborellia annulipes. Os bioensaios foram realizados no Laboratório de Entomologia Agropecuária da Universidade Federal da Paraíba, utilizando insetos, de 3º instar de S. frugiperda e E. annulipes, oriundos de criação massal no próprio laboratório. As diluições dos óleos foram realizadas em Tween® 80 nas concentrações de 0, 100, 150 e 200 mg mL-1. 1,0 µL de cada diluição foi aplicado na região protorácica dos insetos. A mortalidade de S. frugiperda foi verificada pelo contato tópico do óleo de V. arborea com LC10 = 74,3 mg mL-1 e LC50 = 172,86 mg mL-1, para L. microphyla, LC10 = 51,26 mg mL-1 e LC50 = 104,52 mg mL-1. As concentrações letais observadas para E. annulipes foram V. arborea LC10 = 71,3 mg mL-1 e LC50 = 160,2 mg mL-1. Enquanto L. microphyla, foram LC10 = 50,3 mg mL-1 e LC50 = 134,67 mg mL-1. Os óleos essenciais de V. arborea e L. microphylla são eficientes no controle de S. frugiperda, mas não são seletivos ao predador E. Annulipes.

Clinical manifestations of tooth eruption in the first year of life and related risk factors in three regions of Brazil: multicenter birth cohort study.

PURPOSE: Estimate the incidence of teething symptoms and investigate risk factors at three centers in different regions of Brazil. METHODS: A prospective cohort study enrolled children at birth in the cities of Manaus (northern region), Porto Alegre (southern region) and Salvador (northeast region). Sociodemographic and anthropometric variables were collected at baseline and 6 months. At 12 months, data were collected on the child's health through structured interviews and dental examinations, including the primary outcome: occurrence of signs and symptoms of tooth eruption reported by parents. Statistical analysis involved Poisson regression with robust variance, with calculation of relative risks (RR). RESULTS: The incidence of teething symptoms was 82.4% (238/289). The multivariate analysis revealed a higher occurrence of the outcome in the city of Salvador (RR = 1.39; 95% CI 1.23-1.58), when mother's education was more than 11 years (RR = 1.31; 95% CI 1.04-1.65), when a larger number of individuals resided in the home (RR = 1.15; 95% CI 1.02-1.29), when a smoker resided in the home (RR = 1.16; 95% CI 1.03-1.31) and when the child presented flu or cold in the first year of life (RR = 1.23; 95% CI 1.09-1.38). The most reported symptoms were fever (50.5%), irritability (42.6%), itching (40.8%) and diarrhea (35.3%). Most parents (82%) took some action to alleviate symptoms, including unprescribed systemic medication, such as analgesic, anti-inflammatory and anti-diarrheic agents. CONCLUSION: Reports of teething symptoms were associated with the city investigated, socioeconomic factors of the families and characteristics of the child's health. A high rate of administering unprescribed medication was also found.

Complete bladder eversion in periparturient Nellore cow: case report / Eversão completa de bexiga no pré-parto em vaca Nelore: relato de caso

Partial or complete bladder eversion is a rare condition of poor prognosis in cows, commonly associated with intense tenesmus observed in the peripartum period. A 14-year-old obese Nellore cow at 280 days of gestation was referred with 24-hour bladder prolapse. The bladder was complete eversion through the vulvar vestibule showing a thick congested wall and small residual urine volume. After clinical examination, the cow received scopolamine butylbromide and intercoccygeal epidural anesthesia, and the externalized bladder segment was partially reduced, remaining only 10 cm externalized. The cow was maintained with an intravesical human gastric tube number 16 and constant monitoring. The eversion was fully reduced after 12 hours of local treatment, and as the cow presented subclinical ketosis, hypocalcemia and cystitis, antibiotic, glucose, calcium and propylene glycol therapy were performed. We opted for induction of parturition, and after 24 hours, a healthy 52kg calf was born and the placenta was delivered 16 hours after calving. The cow and calf were discharged on the sixth day of hospitalization, with no recurrences or secondary complications after treatment.

A eversão vesical parcial ou completa é uma condição rara de mau prognóstico em vacas, comumente associada a tenesmo intenso observado no período periparto. Uma vaca Nelore obesa de 14 anos de idade, com 280 dias de gestação, foi encaminhada com prolapso de bexiga de 24 horas. A bexiga apresentava eversão completa por meio do vestíbulo vulvar apresentando parede espessa e congestionada e pequeno volume residual de urina. Após exame clínico, a vaca recebeu butilbrometo de escopolamina e anestesia peridural intercoccígea, e o segmento vesical exteriorizado foi parcialmente reduzido, permanecendo apenas 10cm exteriorizado. A vaca foi mantida com sonda gástrica humana número 16 por via intravesical e monitorada constantemente. A eversão foi totalmente reduzida após 12 horas de tratamento local, e, como a vaca apresentava cetose subclínica, hipocalcemia e cistite, foi realizada antibioticoterapia, glicose, cálcio e propilenoglicol. Optou-se pela indução do parto. Após 24 horas, nasceu um bezerro saudável de 52kg e a placenta foi expelida 16 horas após o parto. A vaca e o bezerro receberam alta no sexto dia de internação, sem recidivas ou complicações secundárias após o tratamento.

Chronic progressive lymphoedema in a Friesian horse: clinical aspects and diagnostic approach - case report / [Linfedema progressivo crônico em um cavalo Friesian: aspectos clínicos e abordagem diagnóstica - relato de caso]

Chronic Progressive Lymphoedema (CPL) is a disabling disease of draft horses that affects lymphatic system function typically in the distal limbs. Deformities of distal limbs, especially of the pastern, with fibrosis and skin nodular lesions are consequences of disease progression. A 15-year-old Friesian stallion presented for evaluation with history of forelimb enlargement and nodule formations distal to the carpus for four years. Simple radiographs showed soft tissue nodular lesions and venous contrasted radiography showed intense enlargement of II common digital palmar vein of both forelimbs. Tissue culture tests revealed Streptococcus equi and Proteus mirabilis isolation and skin scraping test identified Chorioptes bovis mites. Histological examination revealed perivasculitis and lymph vessels distention. History, clinical and histological findings, and complementary exams suggested CPL diagnosis. We were unable to find previously published cases describing this disease in Brazil, where the increasing number of draft horses requires attention to this problem. The correct and early diagnosis substantially delays disease progression. Therefore, we highlight the need for nationwide propagation of these data to ensure better diagnosis and early treatment of future CPL cases.

O linfedema crônico progressivo (LCP) é uma enfermidade incapacitante de cavalos de tração que afeta o sistema linfático e se manifesta especialmente na região distal dos membros. A progressão da doença resulta em deformações na região distal dos membros, especialmente na quartela, com fibrose e lesões nodulares na pele. Foi atendido um garanhão da raça Friesian, de 15 anos de idade, com histórico de aumento de volume, nodulações e deformações na região distal dos membros torácicos, com início há aproximadamente quatro anos. Ao exame radiográfico simples, foram identificadas nodulações na pele e no subcutâneo e, ao exame venoso contrastado, identificou-se marcante dilatação II veia digital palmar comum em ambos os membros torácicos. Foi isolado Streptococcus equi e Proteus mirabilis ao cultivo tecidual e identificou-se sarna do tipo corióptica ao raspado de pele. No exame histopatológico, foram identificadas perivasculite e dilatação de vasos linfáticos. Os achados clínicos, histórico, de raça do animal e os exames complementares direcionaram o diagnóstico para o LCP. A pesquisa da literatura nacional não revelou descrições clínicas dessa enfermidade, mas, devido ao aumento do número de animais de tração no país nos últimos anos, a descrição dessa enfermidade se torna importante. O diagnóstico correto e precoce é necessário para retardar a progressão da doença. Nesse sentido, ressalta-se a relevância da divulgação nacional desses achados, a fim de contribuir para o diagnóstico precoce e permitir o retardo da evolução da doença.

Paclobutrazol reduces growth and increases chlorophyll indices and gas exchanges of basil (Ocimum basilicum).

Basil (Ocimum basilicum) is a medicinal, ornamental and aromatic plant, however, its size can be an obstacle to its commercialization as a potted ornamental plant. Paclobutrazol (PBZ) is a substance that can retard plant growth by inhibiting the synthesis of gibberellins. The objective of this work was to evaluate the effect of paclobutrazol on growth regulation and gas exchange of basil (var. Cinnamon). The experiment was carried out in a completely randomized design with five treatments (PBZ doses: 0, 2.5, 5, 7.5 and 10 mg L-1), with eight replicates. Growth (plant height, number of leaves, stem diameter, leaf dry mass, stem dry mass, inflorescence dry mass, and total), growth rates (leaf mass ratio, stem mass ratio, inflorescence mass ratio, and robustness quotient), chlorophyll indices, gas exchange (gs, A, E, Ci, WUE, iWUE and iCE) were evaluated. Paclobutrazol reduced the growth of basil plants and increased the chlorophyll indices, A, gs, and WUE. Paclobutrazol can be used to regulate plant growth of basil plants var. Cinnamon, without altering its physiological and ornamental characteristics.

Is immunohistochemistry more sensitive than hematoxylin-eosin staining for identifying perineural or lymphovascular invasion in oral squamous cell carcinoma? A systematic review and meta-analysis.

BACKGROUND: This study aimed to analyze whether immunohistochemistry (IHC) is more sensitive than hematoxylin-eosin (H&E) staining for identifying perineural invasion (PNI) or lymphovascular invasion (LVI) in oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: In this systematic review and meta-analysis (Prospective Register of Systematic Reviews - CRD 42021256515), data were obtained from six databases (PubMed, Scopus, LILACS, Web of Science, EBSCO, LIVIVO, Embase) and the grey literature. Cross-sectional observational studies of the diagnostic sensitivity of IHC for PNI and LVI were included. Studies were selected in two phases: first collection and reference retrieval. The Quality Assessment of Diagnostic Accuracy Studies-2 tool assessed study quality, while the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach assessed evidence quality. The meta-analysis (random effects model) was performed using MedCalc 18.2.1 software (MedCalc®) (p<0.05). RESULTS: Four studies (560 patients with 295 biopsies) were analyzed. The combined sensitivity was 76% (95% confidence interval [CI], 44.30-97.19%) and specificity was 42% (95% CI, 23.40-62.02%). The positive predictive value (PPV) and negative predictive value (NPV) were 61% (95% CI, 49.78-71.53%) and 70% (95% CI, 37.63-94.43%). The overall accuracy was 58% (95% CI, 45.17-70.65%). The risk of bias was low, and GRADE analysis showed a very low certainty of evidence. CONCLUSIONS: Our data suggest that IHC staining to highlight PNI/LVI may be useful in cases in which H&E analysis results in a negative decrease in the prevalence of false-negative cases and underestimated treatment.

Insecticidal activity of essential oils on Spodoptera frugiperda and selectivity to Euborellia annulipes.

Fall armyworm (Spodoptera frugiperda) is the main species that causes damage to the maize crop in Brazil. In the perspective of studying alternatives of control of this pest that preserve the natural enemies, the aim of this research was to evaluate the insecticidal efficiency of the essential oils of Vanillosmopsis arborea and Lippia microphylla on S. frugiperda and verify the selectivity to the predator Euborellia annulipes. The bioassays were carried out in the Agricultural Entomology Laboratory of the Federal University of Paraiba, using insects, from 3rd instar of S. frugiperda and E. annulipes, originating from mass rearing in the laboratory itself. Dilutions of the oils were performed in Tween® 80 at concentrations of 0, 100, 150 and 200 mg mL-1. 1.0 µL from each dilution was applied to the prothoracic region of the insects. The S. frugiperda mortality was verified by topical contact of V. arborea oil with LC10 = 74.3 mg mL-1 and LC50 = 172.86 mg mL-1, for L. microphyla, LC10 = 51.26 mg mL-1 and LC50 = 104.52 mg mL-1. The observed lethal concentrations for E. annulipes were V. arborea LC10 = 71.3 mg mL-1 and LC50 = 160.2 mg mL-1. While L. microphyla, were LC10 = 50.3 mg mL-1 and LC50 = 134.67 mg mL-1. The essential oils of V. arborea and L. microphylla are efficient in the control of S. frugiperda, but are not selective to the predator E. Annulipes.

Dynamics of the orphan myosin MyoF over Trypanosoma cruzi life cycle and along the endocytic pathway.

Trypanosoma cruzi proliferative forms perform endocytosis through a specialized structure named the cytostome-cytopharynx complex (SPC). The SPC is a specialized invagination of the cell membrane that extends through the cell body towards the posterior regions, with its aperture close to the flagellar pocket. Recently, diverse proteins were found along the cytopharynx, including two myosin motors. One of these is the orphan myosin MyoF, that was proved to be essential for endocytosis in epimastigotes. However, the dynamics of MyoF localization along the endocytic pathway and through the T. cruzi life cycle remain unclear. Using CRISPR-Cas9 genome editing, we generated epimastigotes expressing MyoF fused to mNeonGreen from its endogenous locus. Using these cells, we observed that during the epimastigote cell cycle MyoF signal disappeared during G2, reappearing at early cytokinesis. Additionally, we show that MyoF localization during metacyclogenesis is compatible with the progressive disappearance of the SPC, being absent in metacyclic trypomastigotes. Detergent fractionation showed that MyoF was predominantly present in the insoluble fraction and immunolocalized at the SPC microtubules in whole-mount cytoskeleton preparations. Moreover, during tracer uptake through the SPC, MyoF followed the tracer along the endocytic pathway and was found in posterior compartments after 30 min. Taken together, the data suggest that MyoF may play a role not only at the cargo entry site but also along the endocytic pathway.

Paclobutrazol reduces growth and increases chlorophyll indices and gas exchanges of basil (Ocimum basilicum) / Paclobutrazol reduz o crescimento e aumenta os índices de clorofila e trocas gasosas de manjericão (Ocimum basilicum)

Basil (Ocimum basilicum) is a medicinal, ornamental and aromatic plant, however, its size can be an obstacle to its commercialization as a potted ornamental plant. Paclobutrazol (PBZ) is a substance that can retard plant growth by inhibiting the synthesis of gibberellins. The objective of this work was to evaluate the effect of paclobutrazol on growth regulation and gas exchange of basil (var. Cinnamon). The experiment was carried out in a completely randomized design with five treatments (PBZ doses: 0, 2.5, 5, 7.5 and 10 mg L-1), with eight replicates. Growth (plant height, number of leaves, stem diameter, leaf dry mass, stem dry mass, inflorescence dry mass, and total), growth rates (leaf mass ratio, stem mass ratio, inflorescence mass ratio, and robustness quotient), chlorophyll indices, gas exchange (gs, A, E, Ci, WUE, iWUE and iCE) were evaluated. Paclobutrazol reduced the growth of basil plants and increased the chlorophyll indices, A, gs, and WUE. Paclobutrazol can be used to regulate plant growth of basil plants var. Cinnamon, without altering its physiological and ornamental characteristics.(AU)

Manjericão (Ocimum basilicum) é uma planta medicinal, ornamental e aromática, contudo, seu porte pode ser um entrave para a sua comercialização como planta ornamental de vaso. O paclobutrazol (PBZ) é uma substância que pode retardar o crescimento de plantas, através da inibição da síntese de giberelinas. O objetivo deste trabalho foi avaliar o efeito do paclobutrazol na regulação do crescimento e trocas gasosas no manjericão (Ocimum basilicum var. Cinnamon). O experimento foi realizado em delineamento inteiramente casualizado com 5 tratamentos (doses de PBZ: 0; 2,5; 5; 7,5 e 10 mg L-1), com oito repetições. O crescimento (altura de planta, número de folhas, diâmetro de caule, massa seca da folha, do caule, da inflorescência e total), taxas de crescimento (razão de massa da folha, do caule e da inflorescência e quociente de robustez), índices de clorofilas a e b, trocas gasosas (gs, A, E, Ci, WUE, iWUE e iCE) foram avaliados. Paclobutrazol reduziu o crescimento de plantas de manjericão e aumentou o índice de clorofilas, A, gs e WUE. Paclobutrazol pode ser usado para regular o crescimento de plantas de manjericão var. Cinnamon, sem alterar suas características fisiológicas e ornamentais.(AU)

Resilience and Stress during Pregnancy: A Comprehensive Multidimensional Approach in Maternal and Perinatal Health.

This narrative review addresses resilience and stress during pregnancy, which is part of a broader concept of maternal health. Pregnancy and postpartum are opportune periods for health promotion interventions, especially because the close contact of the women with health professionals. In this way, it can be considered a useful window of opportunity to identify women at higher risk for adverse outcomes. Integrated health is a concept that aims at providing comprehensive care related to the promotion of individuals' physical, mental, and social well-being. In this context, stress during pregnancy has been targeted as a remarkable condition to be addressed whether due to individual issues, social issues, or specific pregnancy issues, since it is directly and indirectly associated with pregnancy complications. Stress is associated with preterm birth, postpartum depression, anxiety, child neurodevelopment, and fetal distress. The way that an individual faces a stressful and adverse situation is called resilience; this reaction is individual, dynamic, and contextual, and it can affect maternal and fetal outcomes. Low resilience has been associated with poorer pregnancy outcomes. The social context of pregnancy can act as a protective or contributory (risk) factor, indicating that environments of high social vulnerability play a negative role in resilience and, consequently, in perceived stress. A given stressor can be enhanced or mitigated depending on the social context that was imposed, as well as it can be interpreted as different degrees of perceived stress and faced with a higher or lower degree of resilience. Understanding these complex mechanisms may be valuable for tackling this matter. Therefore, in the pregnancy-puerperal period, the analysis of the stress-resilience relationship is essential, especially in contexts of greater social vulnerability, and is a health-promoting factor for both the mother and baby.

α,ß-Amyrin prevents steatosis and insulin resistance in a high-fat diet-induced mouse model of NAFLD via the AMPK-mTORC1-SREBP1 signaling mechanism.

Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,ß-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.

A proline derivative-enriched methanol fraction from Sideroxylon obtusifolium leaves (MFSOL) stimulates human keratinocyte cells and exerts a healing effect in a burn wound model.

It was previously demonstrated that the methanol fraction of Sideroxylon obtusifolium (MFSOL) promoted anti-inflammatory and healing activity in excisional wounds. Thus, the present work investigated the healing effects of MFSOL on human keratinocyte cells (HaCaT) and experimental burn model injuries. HaCaT cells were used to study MFSOL's effect on cell migration and proliferation rates. Female Swiss mice were subjected to a second-degree superficial burn protocol and divided into four treatment groups: Vehicle, 1.0% silver sulfadiazine, and 0.5 or 1.0% MFSOL Cream (CrMFSOL). Samples were collected to quantify the inflammatory mediators, and histological analyses were performed after 3, 7, and 14 days. The results showed that MFSOL (50 µg/mL) stimulated HaCaT cells by increasing proliferation and migration rates. Moreover, 0.5% CrMFSOL attenuated myeloperoxidase (MPO) activity and also stimulated the release of interleukin (IL)-1ß and IL-10 after 3 days of treatment. CrMFSOL (0.5%) also enhanced wound contraction, promoted improvement of tissue remodeling, and increased collagen production after 7 days and VEGF release after 14 days. Therefore, MFSOL stimulated human keratinocyte (HaCaT) cells and improved wound healing via modulation of inflammatory mediators of burn injuries.

Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder.

Evaluation of expression profile in autism spectrum disorder (ASD) patients is an important approach to understand possible similar functional consequences that may underlie disease pathophysiology regardless of its genetic heterogeneity. Induced pluripotent stem cell (iPSC)-derived neuronal models have been useful to explore this question, but larger cohorts and different ASD endophenotypes still need to be investigated. Moreover, whether changes seen in this in vitro model reflect previous findings in ASD postmortem brains and how consistent they are across the studies remain underexplored questions. We examined the transcriptome of iPSC-derived neuronal cells from a normocephalic ASD cohort composed mostly of high-functioning individuals and from non-ASD individuals. ASD patients presented expression dysregulation of a module of co-expressed genes involved in protein synthesis in neuronal progenitor cells (NPC), and a module of genes related to synapse/neurotransmission and a module related to translation in neurons. Proteomic analysis in NPC revealed potential molecular links between the modules dysregulated in NPC and in neurons. Remarkably, the comparison of our results to a series of transcriptome studies revealed that the module related to synapse has been consistently found as upregulated in iPSC-derived neurons-which has an expression profile more closely related to fetal brain-while downregulated in postmortem brain tissue, indicating a reliable association of this network to the disease and suggesting that its dysregulation might occur in different directions across development in ASD individuals. Therefore, the expression pattern of this network might be used as biomarker for ASD and should be experimentally explored as a therapeutic target.

Photobiomodulation modulates the expression of inflammatory cytokines during the compensatory hypertrophy process in skeletal muscle.

Compensatory hypertrophy (CH) occurs due to excessive mechanical load on a muscle, promoting an increase in the size of muscle fibers. In clinical practice, situations such as partial nerve injuries, denervation, and muscle imbalance caused by trauma to muscles and nerves or diseases that promote the loss of nerve conduction can induce CH in muscle fibers. Photobiomodulation (PBM) has demonstrated beneficial effects on muscle tissue during CH. The aim of the present study was to evaluate the effect of PBM on the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) as well as type 2 metalloproteinases (MMP-2) during the process of CH due to excessive load on the plantaris muscle in rats. Forty-five Wistar rats weighing 250 g were divided into three groups: control group (n = 10), hypertrophy (H) group (n = 40), and H + PBM group (n = 40). CH was induced through the ablation of synergist muscles of the plantaris muscle. The tendons of the gastrocnemius and soleus muscles were isolated and sectioned to enable the partial removal of each of muscle. The preserved plantaris muscle below the removed muscles was submitted to excessive functional load. PBM was performed with low-level laser (AsGaAl, λ = 780 nm; 40 mW; energy density: 10 J/cm2; 10 s on each point, 8 points; 3.2 J). Animals from each group were euthanized after 7 and 14 days. The plantaris muscles were carefully removed and sent for analysis of the gene and protein expression of IL-6 and TNF-α using qPCR and ELISA, respectively. MMP-2 activity was analyzed using zymography. The results were submitted to statistical analysis (ANOVA + Tukey's test, p < 0.05). The protein expression analysis revealed an increase in IL-6 levels in the H + PBM group compared to the H group and a reduction in the H group compared to the control group. A reduction in TNF-α was found in the H and H + PBM groups compared to the control group at 7 days. The gene expression analysis revealed an increase in IL-6 in the H + PBM group compared to the H group at 14 days as well as an increase in TNF-α in the H + PBM group compared to the H group at 7 days. Increases in MMP-2 were found in the H and H + PBM groups compared to the control group at both 7 and 14 days. Based on findings in the present study, it is concluded that PBM was able to modulate pro-inflammatory cytokines that are essential for the compensatory hypertrophy process. However, it has not shown a modulation effect directly in MMP-2 activity during the same period evaluated.

Genome-enabled prediction of reproductive traits in Nellore cattle using parametric models and machine learning methods.

This study aimed to assess the predictive ability of different machine learning (ML) methods for genomic prediction of reproductive traits in Nellore cattle. The studied traits were age at first calving (AFC), scrotal circumference (SC), early pregnancy (EP) and stayability (STAY). The numbers of genotyped animals and SNP markers available were 2342 and 321 419 (AFC), 4671 and 309 486 (SC), 2681 and 319 619 (STAY) and 3356 and 319 108 (EP). Predictive ability of support vector regression (SVR), Bayesian regularized artificial neural network (BRANN) and random forest (RF) were compared with results obtained using parametric models (genomic best linear unbiased predictor, GBLUP, and Bayesian least absolute shrinkage and selection operator, BLASSO). A 5-fold cross-validation strategy was performed and the average prediction accuracy (ACC) and mean squared errors (MSE) were computed. The ACC was defined as the linear correlation between predicted and observed breeding values for categorical traits (EP and STAY) and as the correlation between predicted and observed adjusted phenotypes divided by the square root of the estimated heritability for continuous traits (AFC and SC). The average ACC varied from low to moderate depending on the trait and model under consideration, ranging between 0.56 and 0.63 (AFC), 0.27 and 0.36 (SC), 0.57 and 0.67 (EP), and 0.52 and 0.62 (STAY). SVR provided slightly better accuracies than the parametric models for all traits, increasing the prediction accuracy for AFC to around 6.3 and 4.8% compared with GBLUP and BLASSO respectively. Likewise, there was an increase of 8.3% for SC, 4.5% for EP and 4.8% for STAY, comparing SVR with both GBLUP and BLASSO. In contrast, the RF and BRANN did not present competitive predictive ability compared with the parametric models. The results indicate that SVR is a suitable method for genome-enabled prediction of reproductive traits in Nellore cattle. Further, the optimal kernel bandwidth parameter in the SVR model was trait-dependent, thus, a fine-tuning for this hyper-parameter in the training phase is crucial.

α, ß-Amyrin prevents steatosis and insulin resistance in a high-fat diet-induced mouse model of NAFLD via the AMPK-mTORC1-SREBP1 signaling mechanism

Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,β-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.