Schizophrenia (SZ) is a complex neuropsychiatric disorder, affecting 1% of the world population. Long-standing clinical observations and molecular data have pointed to a possible vascular deficiency ...that could be acting synergistically with neuronal dysfunction in SZ. As SZ is a neurodevelopmental disease, the use of human-induced pluripotent stem cells (hiPSC) allows disease biology modeling while retaining the patient's unique genetic signature. Previously, we reported a VEGFA signaling impairment in SZ-hiPSC-derived neural lineages leading to decreased angiogenesis. Here, we present a functional characterization of SZ-derived brain microvascular endothelial-like cells (BEC), the counterpart of the neurovascular crosstalk, revealing an intrinsically defective blood-brain barrier (BBB) phenotype. Transcriptomic assessment of genes related to endothelial function among three control (Ctrl BEC) and five schizophrenia patients derived BEC (SZP BEC), revealed that SZP BEC have a distinctive expression pattern of angiogenic and BBB-associated genes. Functionally, SZP BEC showed a decreased angiogenic response in vitro and higher transpermeability than Ctrl BEC. Immunofluorescence staining revealed less expression and altered distribution of tight junction proteins in SZP BEC. Moreover, SZP BEC's conditioned media reduced barrier capacities in the brain microvascular endothelial cell line HCMEC/D3 and in an in vivo permeability assay in mice. Overall, our results describe an intrinsic failure of SZP BEC for proper barrier function. These findings are consistent with the hypothesis tracing schizophrenia origins to brain development and BBB dysfunction.
Abstract
In grazing systems, cattle produce a high molar ratio of acetate, resulting in greater methane production and greater energy loss via gas production. Thus, the objective of this study was to ...evaluate in vitro gas production and methane concentration using a mineral mixture containing 0.4% HMTBa in a Tifton hay-based substrate. The experiment was carried out under anaerobic conditions using ANKOM Gas Pressure Monitor bottles kept at 39 ºC containing artificial saliva, ruminal fluid, and two grams of a substrate from each treatment: (FE) Control, 1.75 g of Tifton hay and 0.25 g of mineral mixture; and (FM) 1.75 g of Tifton hay and 0.25 g of Suplemax mineral mixture (Suplemento Nutrição Animal) containing 0.4% of HMTBa. Duplicate substrates and duplicate blanks were fermented for each treatment in two runs, with a total of four repetitions per treatment. The accumulated pressure resulting from the fermentation was measured automatically over 48 hours using the Gas Monitor software connected to the ANKOM modules of each bottle. The conversion of pressure to gas volume was calculated as follows: Volume (mL) = 2.3932 + 3.4053 × pressure (R2 = 0.9146; n = 1.151). At the end of each run, a gas sample was collected from each bottle to measure methane concentration using gas chromatography. To obtain the methane production for every 100 mL of gas produced, the total volume of methane produced was multiplied by 100 and divided by the total gas production. Data were analyzed in a completely randomized design using analysis of variance (ANOVA) at α = 0.05. Gas production was not affected by the inclusion of HMTBa (P = 0.3938), with an average of 54.14 mL (Table 1). There was a reduction in methane production from 25.41 to 20.05 mL with the addition of HMTBa (P = 0.0034), representing a decrease of 21.09%. There was a tendency to reduce methane production for each 100 mL of gas produced from 46.01 to 37.86 mL (P = 0.0889). Although HMTBa reduces the molar proportion of propionate, it is considered to be one of the main hydrogen users. In environments with a high concentration of H2 (above 1 mmol) and the presence of an anti-methanogen, the most favored path for using hydrogen is acetogenesis, which reduces methane production. Thus, the use of a mineral mixture containing 0.4% HMTBa in a Tifton-hay-based substrate reduced methane production in an in vitro assay.
Abstract
The reduction in enteric methane production in cattle can have a rapid impact on global warming. Therefore, changes in the population of microorganisms in the rumen can significantly reduce ...the production of this greenhouse gas. This in vitro study aimed to evaluate the production of gases and methane with the inclusion of Suplemax mineral mixture containing methionine. The experiment was carried out under anaerobic conditions using ANKOM Gas Pressure Monitor bottles kept at 39 ºC containing artificial saliva, ruminal fluid, and two grams of a substrate from each treatment: (FE) Control, 1.75 g of Tifton hay 85 and 0.25 g of a mineral mix; and (FM) 1.75 g of hay and 0.25 g of Suplemax mineral mixture (Suplemento Nutrição Animal) containing 0.3% of methionine. Duplicate substrates and duplicate blanks were fermented for each treatment in two runs, with a total of four repetitions per treatment. The accumulated pressure resulting from the fermentation was measured automatically over 48 h using the Gas Monitor software connected to the ANKOM modules of each bottle. The conversion of pressure to gas volume was calculated as follows: Volume (mL) = 2.3932 + 3.4053 × pressure (R2 = 0.9146; n = 1.151). At the end of each run, a gas sample was collected from each bottle to measure methane concentration using gas chromatography. To obtain the methane production for every 100 mL of gas produced, the total volume of methane produced was multiplied by 100 and divided by the total gas production. Data were analyzed in a completely randomized design using analysis of variance (ANOVA) at α = 0.05. There was no significant effect on gas production with the inclusion of 0,3% of methionine (FE 37.77 mL vs FM 42.54 mL, P = 0.3175; Table 1). Methane production decreased from 22.74 to 18.15 mL (P = 0.0121) in the FM treatment compared with the FE treatment, representing a 20.18% decrease. Methane production for every 100 mL of gas decreased by 31.08% with the inclusion of methionine (FE 61.62 vs FM 42.47 mL, P = 0.0248). The inclusion of methionine in the mineral supplement contributes to a change in the molar proportion of short-chain fatty acids, increasing propiogenesis, that is considered a sink of hydrogen ions in the ruminal environment, which in turn inhibits methane production. Thus, the inclusion of Suplemax with hay reduced gas and methane production in vitro.
Abstract
The objective of this study was to evaluate the effect of the inclusion of hay and Suplemento Total concentrate as a substitute for corn on gas production and methane concentration in vitro. ...The experiment was conducted under anaerobic conditions using bottles that simulate the ruminal environment (ANKOM Gas Pressure Monitor) containing artificial saliva, rumen liquid, and two g of substrates from each treatment: (MI) Control, 1.62 g of corn containing 9% of crude protein and 0.38 g of mineral mix and; (FMM) 1.02 g of Tifton 85 hay and 0.98 g of Suplemento Total concentrate (Suplemento Nutrição Animal) containing 13.5% of crude protein, 0.32% of monensin and 0.63% of methionine. Duplicate substrates and duplicate blanks were fermented for each treatment in two runs, with a total of four repetitions per treatment. The accumulated pressure resulting from the fermentation was measured automatically over 48 h using the Gas Monitor software connected to the ANKOM modules of each bottle. The conversion of the pressure to gas volume was calculated as follows: Volume (mL) = 2.3932 + 3.4053 × pressure (R2 = 0.9146; n = 1.151). At the end of each run, a gas sample was collected from each bottle to measure methane concentration using gas chromatography. To obtain the methane production for every 100 mL of gas produced, the total volume of methane produced was multiplied by 100 and divided by the total gas production. Data were analyzed in a completely randomized design using analysis of variance (ANOVA) at α = 0.05. Was observed 23.86% of increase in gas production (64.79 vs 80.25 mL, P = 0.0072), 45.53% reduction in total methane production (46.50 vs 25.33 mL, P < 0.001), and 56.07% reduction in methane production for every 100 mL of gas produced (71.96 vs 31.61 mL, P < 0.001) in the FMM treatment compared with the MM, respectively (Table 1). Improvement in the quality of the diet, as well as the use of monensin and methionine, increases the fermentation rate, which explains the increase in gas production. Linked to this, there is also a reduction in methane production by reducing the population of gram-positive bacteria, which are precursors of methanogenesis. Therefore, the inclusion of hay and Suplemento Total concentrate containing 0.32 percent of monensin and 0.63 percent of methionine in place of corn with mineral mixture increased gas production and reduced methane production in vitro.
Abstract
The mitigation of greenhouse gases is a strong trend in promoting the intensification of ruminant production through greater efficiency in the use of dietary energy. The objective of this ...study was to evaluate the effects of the inclusion of the NC Conf Engorda Greentech mineral mixture containing feed additives to replace the regular mineral mixture in corn-based substrates on the production of gases and methane. The experiment was carried out under anaerobic conditions using ANKOM Gas Pressure Monitor bottles at 39 ºC containing artificial saliva, ruminal fluid, and two grams of substrates from each treatment: (MI) Control, 1.62 g of corn and 0.38 g of mixture mineral; and (MM) 1.28 g of corn and 0.72 g of NC Conf Engorda Greentech (Suplemento Nutrição Animal) containing 0.326% of glucomannans, 0.253% of mannans, 0.200% monensin and 1x106· kg-1 UFC of Saccharomyces cerevisiae. Duplicate substrates and duplicate blanks were fermented for each treatment in two runs, with a total of four repetitions per treatment. The accumulated pressure resulting from the fermentation was measured automatically over 48 h using the Gas Monitor software connected to the ANKOM modules of each bottle. The conversion of pressure to gas volume was calculated as follows: Volume (mL) = 2.3932 + 3.4053 × pressure (R2 = 0.9146; n = 1.151). At the end of each run, a gas sample was collected from each bottle to measure methane concentration using gas chromatography. To obtain the methane production for every 100 mL of gas produced, the total volume of methane produced was multiplied by 100 and divided by the total gas production. Data were analyzed in a completely randomized design using analysis of variance (ANOVA) at α = 0.05. There was a 24.53% decrease in the total gas production in the MM treatment (64.79 mL) compared with the MI substrate (48.90 mL; P = 0.0084; Table 1). Methane production decreased from 46.5 to 14.91 mL in the presence of MM (P < 0.001). A reduction from 71.96 to 30.59 mL of methane was observed for every 100 mL of gas produced when feed additives were included (P < 0.001). The Saccharomyces cerevisiae strain is a precursor of mannans, which, like glucomannans, acts as a prebiotic, and together with monensin, influences the selection of the ruminal microbiota and modifies the volatile fatty acid profile, increasing the molar proportion of propionate, and consequently reducing methane production. The addition of the NC Conf Engorda Greentech mineral mixture with glucomannans, mannans, monensin, and Saccharomyces cerevisiae decreased the production of gases and methane in a corn-based substrate.
Objective
To compare the oral health status and oral health-related quality of life (OHRQoL) in symptomatic and asymptomatic patients with human T-cell leukemia virus-1 (HTLV-1).
Material and methods
...This cross-sectional study included 204 seropositive patients, classified into two groups, symptomatic and asymptomatic. The first group included patients with neurological symptoms associated with HTLV-1 (
n
= 69), and the second group, asymptomatic HTLV-1 carriers (
n
= 135). We evaluated the total unstimulated saliva flow, oral mucosa, the Decayed, Missing, Filled Teeth (
DMFT
)
index
, and Periodontal Screening and Recording (PSR). The Oral Health Impact Profile (OHIP14) measured the oral health-related quality of life. General health-related quality of life was measured by the 36-Item Short-Form Health Survey (SF-36). Variables with a value of
p
< 0.25 in bivariate analysis were selected, together with SF-36 summaries’ scores and total OHIP-14, for composing a logistic regression model that had symptomatology as the dependent variable.
Results
The OHIP-14 total score was poor in symptomatic and asymptomatic groups, but with no marked difference between them. Symptomatic patients showed significantly lower SF-36 scores (
P
≤ 0.05
)
compared to asymptomatic ones, except for mental component summary (MCS). Family income (1–2.99 minimal wages), reduced salivary flow, flossing, and lower physical component summary (PCS) were associated (
P
≤ 0.05) with symptomatology.
Conclusions
Symptomatic individuals living with HTLV-1 showed lower HRQoL and poorer OHRQoL compared to asymptomatic ones. Family income, flossing, reduced salivary flow, and lower PCS were associated with symptomatic HTLV-1 individuals.
Clinical relevance
In the present study, symptomatic individuals with HTLV-1 showed higher family income, poorer oral health status, lower salivary flow, poorer OHRQoL, and lower HRQoL compared to asymptomatic ones.
Schizophrenia is a neurodevelopmental disease characterized by cerebral connectivity impairment and loss of gray matter. It was described in adult schizophrenia patients (SZP) that concentration of ...VEGFA, a master angiogenic factor, is decreased. Recent evidence suggests cerebral hypoperfusion related to a dysfunctional Blood Brain Barrier (BBB) in SZP. Since neurogenesis and blood-vessel formation occur in a coincident and coordinated fashion, a defect in neurovascular development could result in increased vascular permeability and, therefore, in poor functionality of the SZP's neurons. Here, we characterized the conditioned media (CM) of human induced Pluripotent Stem Cells (hiPSC)-derived Neural Stem Cells of SZP (SZP NSC) versus healthy subjects (Ctrl NSC), and its impact on angiogenesis. Our results reveal that SZP NSC have an imbalance in the secretion and expression of several angiogenic factors, among them non-canonical neuro-angiogenic guidance factors. SZP NSC migrated less and their CM was less effective in inducing migration and angiogenesis both in vitro and in vivo. Since SZP originates during embryonic brain development, our findings suggest a defective crosstalk between NSC and endothelial cells (EC) during the formation of the neuro-angiogenic niche.
Photodynamic therapy (PDT) utilizes the potential of photosensitizing substances to absorb light energy and produce reactive oxygen species. Tetra-cationic porphyrins, which have organic or ...coordination compounds attached to their periphery, are heterocyclic derivatives with well-described antimicrobial and antitumoral properties. This is due to their ability to produce reactive oxygen species and their photobiological properties in solution. Consequently, these molecules are promising candidates as new and more effective photosensitizers with biomedical, environmental, and other biomedical applications. Prior to human exposure, it is essential to establish the toxicological profile of these molecules using in vivo models. In this study, we used Caenorhabditis elegans, a small free-living nematode, as a model for assessing toxic effects and predicting toxicity in preclinical research. We evaluated the toxic effects of porphyrins (neutral and tetra-cationic) on nematodes under dark/light conditions. Our findings demonstrate that tetra-methylated porphyrins (3TMeP and 4TMeP) at a concentration of 3.3 µg/mL (1.36 and 0.93 µM) exhibit high toxicity (as evidenced by reduced survival, development, and locomotion) under dark conditions. Moreover, photoactivated tetra-methylated porphyrins induce higher ROS levels compared to neutral (3TPyP and 4TPyP), tetra-palladated (3PdTPyP and 4PdTPyP), and tetra-platinated (3PtTPyP and 4PtTPyP) porphyrins, which may be responsible for the observed toxic effects.
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Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we ...describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it.
Copper (Cu) and Zinc (Zn) are required in small concentrations for metabolic functions, but are also toxic. There is a great concern about soil pollution by heavy metals, which may exposure the ...population to these toxicants, either by inhalation of dust or exposure to toxicants through ingestion of food derived from contaminated soils. In addition, the toxicity of metals in combination is questionable, as soil quality guidelines only assess them separately. It is well known that metal accumulation is often found in the pathologically affected regions of many neurodegenerative diseases, including Huntington's disease (HD). HD is caused by an autosomal dominantly inherited CAG trinucleotide repeat expansion in the huntingtin (HTT) gene. This results in the formation of a mutant huntingtin (mHTT) protein with an abnormally long polyglutamine (polyQ) repeat. The pathology of HD results in loss of neuronal cells, motor changes, and dementia. Rutin is a flavonoid found in various food sources, and previous studies indicate it has protective effects in HD models and acts as a metal chelator. However, further studies are needed to unravel its effects on metal dyshomeostasis and to discern the underlying mechanisms. In the present study, we investigated the toxic effects of long-term exposure to copper, zinc, and their mixture, and the relationship with the progression of neurotoxicity and neurodegeneration in a C. elegans-based HD model. Furthermore, we investigated the effects of rutin post metal exposure. Overall, we demonstrate that chronic exposure to the metals and their mixture altered body parameters, locomotion, and developmental delay, in addition to increasing polyQ protein aggregates in muscles and neurons causing neurodegeneration. We also propose that rutin has protective effects acting through mechanisms involving antioxidant and chelating properties. Altogether, our data provides new indications about the higher toxicity of metals in combination, the chelating potential of rutin in the C. elegans model of HD and possible strategies for future treatments of neurodegenerative diseases caused by the aggregation of proteins related to metals.
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•Copper, zinc and mixture concentrations for Brazilian soils.•Exposure to metals versus the relationship with the progression of Huntington's disease.•Natural antioxidant rutin exerted protection against metal toxicity.
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