During bacterial and viral pathogen investigation of 30 specimens of bats captured in periurban forest areas in the city of Belém, Pará, Brazil, a case of cerebral filariasis was observed. In the ...course of histopathological examination, adult filariae were found in pseudocystic cavities brain of
Molossus barnesi
(Molossidae) and classified morphologically as
Litomosoides
by the shape of the spicules—left spicule with a handle longer than the blade; right spicule curved, with a sclerotized heel supporting a dorsal notch; the
area rugosa
constituted by a ventral band of small longitudinal crests; tail rounded in males; long esophagus with a slightly glandular distal portion; and a muscular bent vagina. All the specimens lack a stoma (buccal capsule). We compared our filarioids with the description of specimens of
Molossinema wimsatti
. Morphological characteristics of
M. wimsatti
resemble the genus
Litomosoides
. Thus, we believe that
M. wimsatti
is a synonym of
L. molossi
Esslinger, 1973, and filarioid specimens from material reported by Lichtenfels et al. (
Trans Am Micros Soc
100:216–219, 1981) and from de Souto et al. (
J. Helminthol
1195:e65, 2021) most probably correspond to
Litomosoides
. We suggest that the reduction of the buccal capsule may be attributable to the ectopic location. No evidence of tissue responses by the host was observed. This is the first record of
Litomosoides
infecting brain tissue of
Molossus barnesi
from Brazil, representing a record of a new host species. More specimens of bats should be examined in order to find filarioids in the brain and verify its taxonomic position using molecular techniques.
Obesity is associated with complex adipose tissue energy metabolism remodeling. Whether AT metabolic reprogramming differs according to body mass index (BMI) and across different obesity classes is ...unknown. This study’s purpose was to evaluate and compare bioenergetics and energy substrate preference of visceral adipose tissue (VAT) pertaining to individuals with obesity class 2 and class 3. VAT obtained from patients with obesity (n = 15) class 2 (n = 7; BMI 37.53 ± 0.58 kg/m2) or class 3 (n = 8; BMI 47.79 ± 1.52 kg/m2) was used to assess oxygen consumption rate (OCR) bioenergetics and mitochondrial substrate preferences. VAT of patients with obesity class 3 presented significantly higher non-mitochondrial oxygen consumption (p < 0.05). In VAT of patients with obesity class 2, inhibition of pyruvate and glutamine metabolism significantly decreased maximal respiration and spare respiratory capacity (p < 0.05), while pyruvate and fatty acid metabolism inhibition, which renders glutamine the only available substrate, increased the proton leak with a protective role against oxidative stress (p < 0.05). In conclusion, VAT bioenergetics of patients with obesity class 2 depicts a greater dependence on glucose/pyruvate and glutamine metabolism, suggesting that patients within this BMI range are more likely to be responsive to interventions based on energetic substrate modulation for obesity treatment.
(Cham.) Borhidi (
), an herbaceous plant distributed in tropical and subtropical regions is native of Brazil and widely used in folk medicine to treat respiratory and digestive diseases, ...inflammation, and some types of infections. Thus, this study aimed to investigate acute oral toxicity, antinociceptive, and anti-inflammatory activities of dry aqueous extract of
.
(AEVm) and to identify its compounds. Extract was obtained by lyophilized leaf infusion and its composition was analyzed by ultra-performance liquid chromatography-high resolution mass spectrometry (LC-MS). Acute oral toxicity was evaluated in female rats treated with AEVm (2,000 mg/kg) in a single oral dose. Mortality, body weight changes, feed and water intake, organ weights, histological and biochemical parameters were screened for 14 days. Antinociceptive activity was evaluated by writhing (WT), formalin (FT), and hot plate (HP) tests in male mice while anti-inflammatory activity was performed by carrageenan (CPE) and dextran (DPE)-induced paw edema tests and carrageenan-induced peritonitis (CP) test in male rats. Additionally, spontaneous open-field (OF) locomotion was evaluated. LC-MS analysis revealed the presence of flavonoids with biological activity. In toxicity evaluation, extract did not cause deaths in dose of 2,000 mg/kg, and there were no significant behavioral or biochemical alterations. Additionally, evidence of hepatoprotective and antioxidant activity was observed. In pharmacological evaluation AEVm showed dose-dependent antinociceptive activity in WT, with a median effective dose of 146.89 mg/kg, which showed selectivity by inflammatory base processes (FT first phase; p < 0.001), showing no activity in neuropathic nociception components (FT second phase and HP) or about consciousness and locomotion in OF. AEVm also showed significant anti-inflammatory activity, inhibiting CPE (p < 0.001) and cell migration (p < 0.05) and nitric oxide (NO) production (p < 0,01) in CP test. These data demonstrate that AEVm has low oral toxicity-with evidence of hepatoprotective and antioxidant properties-antinociceptive and anti-inflammatory activity, supporting
traditional use, possibly related to flavonoids present in its constitution.
Beneficial plant-microbe interactions lead to physiological and biochemical changes that may result in plant-growth promotion. This study evaluated the effect of the interaction between sugarcane and ...endophytic bacterial strains on plant physiological and biochemical responses under two levels of nitrogen (N) fertilization. Six strains of endophytic bacteria, previously selected as plant growth-promoting bacteria (PGPB), were used to inoculate sugarcane mini stalks, with and without N fertilization. After 45 days, biomass production; shoot nutrient concentrations; foliar polyamine and free amino acid profiles; activities of nitrate reductase and glutamine synthase; and the relative transcript levels of the
,
, and
genes in sugarcane leaves were determined. All six endophytic strains promoted sugarcane growth, increasing shoot and root biomass, plant nutritional status, and the use efficiency of most nutrients. The inoculation-induced changes at the biochemical level altered the foliar free amino acid and polyamine profiles, mainly regarding the relative concentrations of citrulline, putrescine, glycine, alanine, glutamate, glutamine, proline, and aspartate. The transcription of
,
, and
was higher in the N fertilized seedlings, and almost not altered by endophytic bacterial strains. The endophytic strains promoted sugarcane seedlings growth mainly by improving nutrient efficiency. This improvement could not be explained by their ability to induce the production of amino acid and polyamine composts, or
,
, and
, showing that complex interactions may be associated with enhancement of the sugarcane seedlings' performance by endophytic bacteria. The strains demonstrated biotechnological potential for sugarcane seedling production.
Obesity is a major risk factor for dysglycemic disorders, including type 2 diabetes (T2D). However, there is wide phenotypic variation in metabolic profiles. Tissue-specific epigenetic modifications ...could be partially accountable for the observed phenotypic variability.
The aim of this systematic review was to summarize the available data on epigenetic signatures in human adipose tissue (AT) that characterize overweight or obesity-related insulin resistance (IR) and dysglycemia states and to identify potential underlying mechanisms through the use of unbiased bioinformatics approaches.
Original data published in the last decade concerning the comparison of epigenetic marks in human AT of individuals with metabolically unhealthy overweight/obesity (MUHO) versus normal weight individuals or individuals with metabolically healthy overweight/obesity (MHO) was assessed. Furthermore, association of these epigenetic marks with IR/dysglycemic traits, including T2D, was compiled.
We catalogued more than two thousand differentially methylated regions (DMRs; above the cut-off of 5%) in the AT of individuals with MUHO compared to individuals with MHO. These DNA methylation changes were less likely to occur around the promoter regions and were enriched at loci implicated in intracellular signaling (signal transduction mediated by small GTPases, ERK1/2 signaling and intracellular trafficking). We also identified a network of seven transcription factors that may play an important role in targeting DNA methylation changes to specific genes in the AT of subjects with MUHO, contributing to the pathogeny of obesity-related IR/T2D. Furthermore, we found differentially methylated CpG sites at 8 genes that were present in AT and whole blood, suggesting that DMRs in whole blood could be potentially used as accessible biomarkers of MUHO.
The overall evidence linking epigenetic alterations in key tissues such AT to metabolic complications in human obesity is still very limited, highlighting the need for further studies, particularly those focusing on epigenetic marks other than DNA methylation. Our initial analysis suggests that DNA methylation patterns can potentially discriminate between MUHO from MHO and provide new clues into why some people with obesity are less susceptible to dysglycemia. Identifying AT-specific epigenetic targets could also lead to novel approaches to modify the progression of individuals with obesity towards metabolic disease.
PROSPERO, identifier CRD42021227237.
The aim is to examine the effect of metformin in human microvascular endothelial cells exposed to high glucose (HG) concentration and compare them with the effects of other 5' adenosine ...monophosphate-activated protein kinase (AMPK) modulators under the same condition.
In this experimental study, human microvascular endothelial cells (HMECs) were treated with 15 mM metformin, 1 mM 5-aminoimidazol-4-carboxamideribonucleotide (AICAR) and 10 mM compound C in the presence of 20 mM glucose (hyperglycemic condition). Migration, invasion and proliferation were evaluated as well as the capillary-like structures formation. Moreover, the expression of angiogenic genes was assessed.
Metformin significantly inhibited vessel formation and migration, although it did not change HMECs proliferation and invasion. In addition, metformin significantly reduced collagen formation as evidenced by histological staining. Concomitantly, expression of several genes implicated in angiogenesis and fibrosis, namely
and
, was slightly upregulated. Immunostaining for proteins involved in ALK5 receptor signaling, the alternative TGFß signaling pathway, revealed significant differences in SMAD2/3 expression.
Our data showed that metformin prevents vessel assembly in HMECs, probably through an AMPKindependent mechanism. Understanding the molecular mechanisms by which this pharmacological agent affects endothelial dysfunction is of paramount importance and paves the way to its particular use in preventing development of diabetic retinopathy and nephropathy, two processes where angiogenesis is exacerbated.
Grafting, a traditional agricultural technique, holds significant potential for increasing productivity by harnessing the plant microbiome. The microbiome provides adaptability and metabolic ...diversity, increasing plant capacity to cope with challenging conditions. Although grafting effects on the composition and structure of microbiome on the root endosphere and, consequently, on the aerial endosphere have been reported, the impact on potential functionalities for plant traits remains to be elucidated. Beneficial microbes assembled by plant grafting have significant biotechnological potential to increase plant performance against biotic and abiotic stressors. In view of the optimal use of rootstock-scion combinations, in this review, we focused on recent grafting studies with plant-microbiome underlying mechanisms related to growth promotion, nutrient accessibility, and protection against abiotic and biotic environmental stresses. We provide significant first-hand information to guide future directions and prospects in shaping plant and core microbiome interactions, which helps in sustainable agriculture.
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•Plant grafting can increase crop productivity, control pathogens, or alleviate abiotic stress.•Scions and rootstocks have an active impact on plant-associated microbiome assembly.•Configuring core microbiome through grafting can augment the sustainability of crops.•Plant breeding may include microbial-based approaches to improve agronomic traits.•Exploring grafting within economically important plants may boost crop resilience.
Intake of fructose-containing sugars is epidemiological and experimentally linked to metabolic syndrome (MS). We recently verified that the dietary polyphenol chrysin was able to abolish some of the ...metabolic changes induced by fructose-feeding in the rat. Because the role of the intestine upon fructose-induced MS is poorly understood, we decided to investigate the influence of fructose, in vivo, on the intestinal environment and the ability of chrysin to interfere with the putative observed changes. For this, adult male Sprague-Dawley rats were treated for 18 weeks as follows: (A) tap water (CONT), (B) tap water and chrysin (100 mg kg
day
) (CHRY), (C) 10% fructose in tap water (FRUCT), and (D) 10% fructose in tap water and chrysin (100 mg kg
day
) (FRUCT + CHRY). Our findings show that the relative expression of SGLT1 and GLUT2 mRNA were not affected by fructose-feeding and/or chrysin. In contrast, GLUT5 mRNA expression was markedly increased in fructose-fed animals, and this effect was reduced by chrysin. However, the apparent permeability to
C-FRUCT was markedly and similarly decreased in FRUCT, CHRY and FRUCT + CHRY rats. Jejunal villus width and crypt depth were significantly higher in FRUCT and FRUCT + CHRYS rats, respectively. Finally, chrysin did not alter gut microbiota composition, but fructose significantly increased Lactobacillus and E. coli. Moreover, FRUCT + CHRY rats had an increase on the Firmicutes to Bacteroidetes ratio. This is the first report showing that chrysin is able to interfere with the effects of fructose at the intestinal level, which may contribute to the fructose-induced MS features.
Background
Gastric cancer with lymphoid stroma (GCLS) is characterized by prominent stromal infiltration of T-lymphocytes. The aim of this study was to investigate GCLS biology through analysis of ...clinicopathological features, EBV infection, microsatellite instability (MSI), immune gene-expression profiling and PD-L1 status in neoplastic cells and tumor immune microenvironment.
Methods
Twenty-four GCLSs were analyzed by RNA in situ hybridization for EBV (EBER), PCR/fragment analysis for MSI, immunohistochemistry (PD-L1, cytokeratin, CD3, CD8), co-immunofluorescence (CK/PD-L1, CD68/PD-L1), NanoString gene-expression assay for immune-related genes and
PD-L1
copy number alterations. CD3+ and CD8+ T-cell densities were calculated by digital analysis. Fifty-four non-GCLSs were used as control group.
Results
GCLSs displayed distinctive clinicopathological features, such as lower pTNM stage (
p
= 0.02) and better overall survival (
p
= 0.01). EBV+ or MSI-high phenotype was found in 66.7 and 16.7% cases, respectively. GCLSs harbored a cytotoxic T-cell-inflamed profile, particularly at the invasive front of tumors (
p
< 0.01) and in EBV+ cases (
p
= 0.01). EBV+ GCLSs, when compared to EBV− GCLSs, showed higher mRNA expression of genes related to Th1/cytotoxic and immunosuppressive biomarkers. PD-L1 protein expression, observed in neoplastic and immune stromal cells (33.3 and 91.7%, respectively), and
PD-L1
amplification (18.8%) were restricted to EBV+/MSI-high tumors and correlated with high values of
PD-L1
mRNA expression.
Conclusions
This study shows that GCLS has a distinctive clinico-pathological and molecular profile. Furthermore, through an in-depth study of tumor immune microenvironment—by digital analysis and mRNA expression profiling—it highlights the role of EBV infection in promoting an inflamed tumor microenvironment, with putative therapeutic implications.
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