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Tumors affecting Bartholin’s gland are considered rare in human medicine; there are few reports in the veterinary literature, with descriptions occurring only in cows. This article described the clinical and pathological findings associated with Bartholin’s gland adenoma in a goat. Clinically, a 7-year-old pregnant Saanen goat presented bilateral enlargement of the vulva that did not regress spontaneously after parturition. Grossly, these vulvar masses were multilobulated, contained cystic areas from which oozed a whitish fluid. Histopathology revealed an adenoma characterized by the proliferation of irregularly shaped neoplastic epithelial cells that formed tubular to glandular-like structures. These neoplastic cells demonstrated moderate anisokaryosis and evident nucleoli. The intratumoral proliferation index (PI) was estimated by immunoreactivity with the protein ki-67. Further, the glandular-like structures produced a Periodic Acid-Schiff positive secretion. A diagnosis of Bartholin’s gland adenoma was established due to the anatomic location of the neoplastic growths, the histopathological features, and the PI of the tumor. RESUMO: Tumores que afetam a glândula de Bartholin são considerados raros em humanos e há poucos relatos na medicina veterinária, sendo descrito somente em vacas. Este artigo descreve os achados clínicos e patológicos associados ao adenoma na glândula de Bartholin em uma cabra. O animal da raça Saanen, com sete anos de idade e gestante apresentava aumento de volume bilateral na região da vulva, que não regrediu após o parto. Macroscopicamente, a massa era multilobulada, com presença de vários cistos preenchidos por uma secreção esbranquiçada. A histopatologia revelou um adenoma, caracterizado por proliferação de células epiteliais de formato irregular que formavam estruturas tubulares semelhantes à glândulas. Estas células neoplásicas apresentavam anisocariose moderada e nucléolos evidentes. O índice de proliferação celular intratumoral (PI) foi estimado por imunorreatividade à proteína ki-67. Além disso, a secreção produzida por essas estruturas do tipo glandular, foi positiva na coloração do Ácido Periódico-Schiff. O diagnóstico de adenoma da glândula de Bartholin foi estabelecido pela localização anatômica dos tumores neoplásicos, características histopatológicas e à PI do tumor.

Tumors affecting Bartholin's gland are considered rare in human medicine; there are few reports in the veterinary literature, with descriptions occurring only in cows. This article described the clinical and pathological findings associated with Bartholin's gland adenoma in a goat. Clinically, a 7-year-old pregnant Saanen goat presented bilateral enlargement of the vulva that did not regress spontaneously after parturition. Grossly, these vulvar masses were multilobulated, contained cystic areas from which oozed a whitish fluid. Histopathology revealed an adenoma characterized by the proliferation of irregularly shaped neoplastic epithelial cells that formed tubular to glandular-like structures. These neoplastic cells demonstrated moderate anisokaryosis and evident nucleoli. The intratumoral proliferation index (PI) was estimated by immunoreactivity with the protein ki-67. Further, the glandular-like structures produced a Periodic Acid- Schiff positive secretion. A diagnosis of Bartholin's gland adenoma was established due to the anatomic location of the neoplastic growths, the histopathological features, and the PI of the tumor. Key words: Histopathology, ki-67 protein, adenoma, major vestibular glands. Tumores que afetam a glandula de Bartholin sao considerados raros em humanos e ha poucos relatos na medicina veterinaria, sendo descrito somente em vacas. Este artigo descreve os achados clinicos e patologicos associados ao adenoma na glandula de Bartholin em uma cabra. O animal da raca Saanen, com sete anos de idade e gestante apresentava aumento de volume bilateral na regiao da vulva, que nao regrediu apos o parto. Macroscopicamente, a massa era multilobulada, com presenca de varios cistos preenchidos por uma secrecao esbranquicada. A histopatologia revelou um adenoma, caracterizado por proliferacao de celulas epiteliais de formato irregular que formavam estruturas tubulares semelhantes a glandulas. Estas celulas neoplasicas apresentavam anisocariose moderada e nucleolos evidentes. O indice de proliferacao celular intratumoral (PI) foi estimado por imunorreatividade a proteina ki-67. Alem disso, a secrecao produzida por essas estruturas do tipo glandular, foi positiva na coloracao do Acido Periodico-Schiff. O diagnostico de adenoma da glandula de Bartholin foi estabelecido pela localizacao anatomica dos tumores neoplasicos, caracteristicas histopatologicas e a PI do tumor. Palavras-chave: histopatologia, ki-67, adenoma, glandulas vestibulares maiores.

Hyperglycemia leads to microvascular lesions in various tissues. In diabetic nephropathy—DN, alterations in usual markers reflect an already installed disease. The study of new biomarkers for the early detection of diabetic complications can bring new prevention perspectives. Rats were divided into diabetic adult—DMA—or elderly—DME and control sham adult—CSA—or control sham elderly—CSE. Blood and urine samples were collected for biochemical analysis. Bulbar region, cardiac, hepatic and renal tissues were collected for target gene expression studies. As result, DMA showed decreased TNFR1 , MCT1 and CD147 expression in the bulbar region, TNFR1 in the heart, VEGFA and CD147 in the kidney and TNFR1 in blood. Positive correlations were found between TNFR1 and MCT1 in the bulbar region and HbA1c and plasma creatinine, respectively. DME showed positive correlation in the bulbar region between TNFR1 and glycemia, in addition to negative correlations between CD147 in the heart versus glycemia and urea. We concluded that the initial hyperglycemic stimulus already promotes changes in the expression of genes involved in the inflammatory and metabolic pathways, and aging alters this profile. These changes prior to the onset of diseases such as DN, show that they have potential for early biomarkers studies.

Ozonolysis is potentially an effective method for pretreating lignocellulosic biomass to improve the production of fermentable sugars via enzymatic hydrolysis. The eliminated branches from eucalyptus trees can represent a production of around 30 million m 3 of lignocellulosic material annually only in Brazil. Attempts of developing strategies for a rational use of this biomass are, thus, welcome. In this study, Eucalyptus grandis branches were pretreated with ozone in an attempt to increase enzymatic saccharification. Ozonolysis resulted in the degradation of lignin with negligible losses of cellulose and small losses of hemicellulose. Reduction in the lignin content from 26.63 to 9.53% already resulted in the maximal improvement of the saccharification yield (from 20 to 68%). The results indicate that ozone pretreatment can be a promising way of increasing the enzymatic digestibility of eucalyptus sawdust from eliminated branches of trees for its conversion into fermentable sugars.

Alzheimer’s disease (AD) is a progressive and complex neurodegenerative disease. Acetylcholinesterase inhibitors (AChEIs) are a major class of drugs used in AD therapy. ROCK2, another promising target for AD, has been associated with the induction of neurogenesis via PTEN/AKT. This study aimed to characterize the therapeutic potential of a novel donepezil–tacrine hybrid compound (TA8Amino) to inhibit AChE and ROCK2 protein, leading to the induction of neurogenesis in SH-SY5Y cells. Experiments were carried out with undifferentiated and neuron-differentiated SH-SY5Y cells submitted to treatments with AChEIs (TA8Amino, donepezil, and tacrine) for 24 h or 7 days. TA8Amino was capable of inhibiting AChE at non-cytotoxic concentrations after 24 h. Following neuronal differentiation for 7 days, TA8Amino and donepezil increased the percentage of neurodifferentiated cells and the length of neurites, as confirmed by β-III-tubulin and MAP2 protein expression. TA8Amino was found to participate in the activation of PTEN/AKT signaling. In silico analysis showed that TA8Amino can stably bind to the active site of ROCK2, and in vitro experiments in SH-SY5Y cells demonstrate that TA8Amino significantly reduced the expression of ROCK2 protein, contrasting with donepezil and tacrine. Therefore, these results provide important information on the mechanism underlying the action of TA8Amino with regard to multi-target activities.

In Brazil, the production and consumption of palm heart, especially from the Bactris gasipaes Kunth, generates a large number of lignocellulosic by-products. This study reports the obtainment of xylooligosaccharides (XOS) from xylans extracted from these residues. Xylans from peach palm waste (inner sheath and peel) were extracted using a mild alkali treatment with recovery yields of 82% and 80%, respectively. XOS were obtained through enzymatic hydrolysis employing a commercial xylanase with yields from xylan inner sheath and xylan peel of 50.1% and 48.8%, respectively. The antioxidant potential of XOS was measured employing five of the most commonly used procedures. In overall terms, the XOS from the xylans of peach palm wastes showed higher antioxidant capacity than the XOS obtained from the commercial xylans. The chemical structures of the XOS were determined by mass spectrometry (ESI–MS). The ESI–MS spectra suggest that XOS with grouped xylose or arabinose units ranging from 2 to 5 (differing by 132 Da) and as sodium adduct ions [M + Na] + in the range of 100–1000 m /z . These results indicate that peach palm wastes can be explored to XOS production, which could be applied as natural antioxidants in functional food and pharmaceutical preparations. Graphic Abstract

This article aims to describe the geographical distribution of hospital mortality from COVID-19 in children and adolescents during the 2020-2021 pandemic in Brazil. Ecological, census study (SIVEP GRIPE) with individuals up to 19 years of age, hospitalized with SARS due to COVID-19 or SARS not specified in Brazilian municipalities, stratified in two ways: 1) in the five macro-regions and 2) in three urban agglomerations: capital, municipalities of the metropolitan region and non-capital municipalities. There were 44 hospitalizations/100,000 inhabitants due to COVID-19 and 241/100,000 when including unspecified SARS (estimated underreporting of 81.8%). There were 1,888 deaths by COVID-19 and 4,471 deaths if added to unspecified SARS, estimating 57.8% of unreported deaths. Hospital mortality was 2.3 times higher in the macro-regions when considering only the cases of COVID-19, with the exception of the North and Center-West regions. Higher hospital mortality was also recorded in non-capital municipalities. The urban setting was associated with higher SARS hospital mortality during the COVID-19 pandemic in Brazil. Living in the North and Northeast macro-regions, and far from the capitals offered a higher risk of mortality for children and adolescents who required hospitalization.

This study investigated the chemical phenotypical variability of Piper lhotzkyanum Kunth (Piperaceae), a shrub found in Brazilian tropical forests, over time (different periods of the day and seasons) and under natural conditions. For this, essential oils (EOs) from the leaves were collected in different seasons and times of the day and analyzed by gas chromatography coupled with mass spectrometry, and gas chromatography coupled with a flame ionization detector. The indices were applied to evaluate the chemical diversity as well as the dynamics of redox of the mixtures. The results showed that the EOs were dominated by non-oxygenated sesquiterpenes, with β-elemene, E-caryophyllene, and α-zingiberene being the main compounds identified in all collections. Temporal and seasonal analyses revealed important fluctuations in the chemical composition, redox, and chemical diversity indices of the species. A correlation between climatic factors and the variation in redox and chemical diversity was observed, highlighting the chemical phenotypic plasticity P. lhotzkyanum. This study resolves a previously unanswered question by confirming that natural light does not produce interconversion of major compounds. The adaptation capacity of this species to the environmental changes suggests new cultivation strategies to maximize the quality of EO and promote a more sustainable future in partnership with nature.

Celtis iguanaea, widely used in Brazilian folk medicine, is known for its analgesic and anti-inflammatory properties. This study evaluated the in vitro antioxidant capacity and the in vivo antinociceptive and anti-inflammatory mechanisms of the standardized spray-dried Celtis iguanaea hydroethanolic leaf extract (SDCi). Phytochemical analysis showed that SDCi contains 21.78 ± 0.82 mg/g polyphenols, 49.69 ± 0.57 mg/g flavonoids, and 518.81 ± 18.02 mg/g phytosterols. UFLC-DAD-MS identified iridoid glycosides, p-coumaric acid glycosides, flavones, and unsaturated fatty acids. Antioxidant assays revealed an IC50 of 301.6 ± 38.8 µg/mL for DPPH scavenging and an electrochemical index of 6.1 μA/V. In vivo, SDCi (100–1000 mg/kg, p.o) did not impair locomotor function (rotarod test) but significantly reduced acetic acid-induced abdominal writhing and both phases of the formalin test at higher doses (300 and 1000 mg/kg). The antinociceptive effects were independent of α-2 adrenergic receptors. SDCi also increased latency in the hot-plate test and reduced paw edema in the carrageenan model, accompanied by decreased IL-1β and increased IL-10 levels. Histological analysis showed a 50% reduction in inflammatory cell infiltration. These findings support SDCi as an effective anti-inflammatory and antinociceptive phytopharmaceutical intermediate, with potential applications in managing pain and inflammation.

Cellular prion protein (PrP C ) is a glycoprotein of the plasma membrane that plays pleiotropic functions by interacting with multiple signaling complexes at the cell surface. Recently, a number of studies have reported the involvement of PrP C in dopamine metabolism and signaling, including its interactions with tyrosine hydroxylase (TH) and dopamine receptors. However, the outcomes reported by independent studies are still debatable. Therefore in this study, we investigated the effects of PrP C on the TH expression during the differentiation of N2a cells with dibutyryl-cAMP, a well-known cAMP analog that activates TH transcription. Upon differentiation, TH was induced with concomitant reduction of PrP C at protein level, but not at mRNA level. shRNA-mediated PrP C reduction increased the basal level of TH at both mRNA and protein levels without dibutyryl-cAMP treatment. This phenotype was reversed by re-expression of PrP C . PrP C knockdown also potentiated the effect of dibutyryl-cAMP on TH expression. Our findings suggest that PrP C has suppressive effects on TH expression. As a consequence, altered PrP C functions may affect the regulation of dopamine metabolism and related neurological disorders.