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1.
Biomed Khim ; 70(2): 83-88, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38711407

RESUMO

The toxic effect of ethanol on the cerebral cortex and protective effects of omega-3 fatty acids against this neurotoxicity were investigated. Twenty eight male Wistar-albino rats were divided into 4 groups. Rats of the ethanol and ethanol withdrawal groups were treated with ethanol (6 g/kg/day) for 15 days. Animals of the ethanol+omega-3 group received omega-3 fatty acids (400 mg/kg daily) and ethanol. In rats of the ethanol group SOD activity was lower than in animals of the control group. In rats treated with omega-3 fatty acids along with ethanol SOD, activity increased. GSH-Px activity and MDA levels in animals of all groups were similar. In ethanol treated rats NO levels significantly decreased as compared to the animals of the control group (6.45±0.24 nmol/g vs 11.05±0.53 nmol/g, p.


Assuntos
Córtex Cerebral , Etanol , Ácidos Graxos Ômega-3 , Óxido Nítrico , Ratos Wistar , Superóxido Dismutase , Animais , Masculino , Ratos , Ácidos Graxos Ômega-3/farmacologia , Córtex Cerebral/metabolismo , Córtex Cerebral/efeitos dos fármacos , Óxido Nítrico/metabolismo , Superóxido Dismutase/metabolismo , Glutationa Peroxidase/metabolismo , Antioxidantes/farmacologia , Malondialdeído/metabolismo
3.
J Toxicol Environ Health A ; 87(16): 662-673, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-38808737

RESUMO

Pseudobombax marginatum, popularly known as "embiratanha," is widely used by traditional communities as anti-inflammatory and analgesic agent. This study aimed to determine the phytochemical profile as well as cytotoxicity, acute oral toxicity, genotoxicity, and mutagenicity attributed to exposure to aqueous (AqEx) and ethanolic (EtEx) extracts of embiratanha bark. Phytochemical screening was conducted using thin-layer chromatography (TLC). Cell viability was analyzed using MTT assay with human mammary gland adenocarcinoma (MDA-MB-231) and macrophage (J774A.1) cell lines, exposed to concentrations of 12.5, 25, 50, or 100 µg/ml of either extract. For acute oral toxicity, comet assay and micronucleus (MN) tests, a single dose of 2,000 mg/kg of either extract was administered orally to Wistar rats. TLC analysis identified classes of metabolites in the extracts, including cinnamic acid derivatives, flavonoids, hydrolyzable tannins, condensed tannins, coumarins, and terpenes/steroids. In the cytotoxicity assay, the varying concentrations of extracts derived from embiratanha induced no significant alterations in the viability of MDA-MB-231 cells. The lowest concentration of EtEx significantly increased macrophage J774A.1 viability. However, the higher concentrations of AqEx markedly lowered macrophage J774A.1 viability. Animals exhibited no toxicity in the parameters analyzed in acute oral toxicity, comet assay, and MN tests. Further, EtEx promoted a significant reduction in DNA damage index and DNA damage frequency utilizing the comet assay, while the group treated with AqEx exhibited no marked differences. Thus, data demonstrated that AqEx or EtEx of embiratanha may be considered safe at a dose of 2,000 mg/kg orgally under our experimental conditions tested.


Assuntos
Extratos Vegetais , Ratos Wistar , Extratos Vegetais/toxicidade , Extratos Vegetais/química , Animais , Humanos , Ratos , Linhagem Celular Tumoral , Masculino , Ensaio Cometa , Testes para Micronúcleos , Feminino , Sobrevivência Celular/efeitos dos fármacos , Compostos Fitoquímicos/toxicidade , Compostos Fitoquímicos/análise , Camundongos , Casca de Planta/química , Mutagênicos/toxicidade , Testes de Mutagenicidade , Etanol/química
4.
Biomolecules ; 14(5)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38785934

RESUMO

Adverse experiences (e.g., acute stress) and alcohol misuse can both impair skeletal muscle homeostasis, resulting in reduced protein synthesis and greater protein breakdown. Exposure to acute stress is a significant risk factor for engaging in alcohol misuse. However, little is known about how these factors together might further affect skeletal muscle health. To that end, this study investigated the effects of acute stress exposure followed by a period of binge-patterned alcohol drinking on signaling factors along mouse skeletal muscle protein synthesis (MPS) and degradation (MPD) pathways. Young adult male C57BL/6J mice participated in the Drinking in the Dark paradigm, where they received 2-4 h of access to 20% ethanol (alcohol group) or water (control group) for four days to establish baseline drinking levels. Three days later, half of the mice in each group were either exposed to a single episode of uncontrollable tail shocks (acute stress) or remained undisturbed in their home cages (no stress). Three days after stress exposure, mice received 4 h of access to 20% ethanol (alcohol) to model binge-patterned alcohol drinking or water for ten consecutive days. Immediately following the final episode of alcohol access, mouse gastrocnemius muscle was extracted to measure changes in relative protein levels along the Akt-mTOR MPS, as well as the ubiquitin-proteasome pathway (UPP) and autophagy MPD pathways via Western blotting. A single exposure to acute stress impaired Akt singling and reduced rates of MPS, independent of alcohol access. This observation was concurrent with a potent increase in heat shock protein seventy expression in the muscle of stressed mice. Alcohol drinking did not exacerbate stress-induced alterations in the MPS and MPD signaling pathways. Instead, changes in the MPS and MPD signaling factors due to alcohol access were primarily observed in non-stressed mice. Taken together, these data suggest that exposure to a stressor of sufficient intensity may cause prolonged disruptions to signaling factors that impact skeletal muscle health and function beyond what could be further induced by periods of alcohol misuse.


Assuntos
Consumo Excessivo de Bebidas Alcoólicas , Camundongos Endogâmicos C57BL , Proteínas Musculares , Músculo Esquelético , Proteólise , Animais , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Camundongos , Proteínas Musculares/metabolismo , Proteínas Musculares/biossíntese , Consumo Excessivo de Bebidas Alcoólicas/metabolismo , Proteólise/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Etanol , Estresse Psicológico/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Consumo de Bebidas Alcoólicas/metabolismo
6.
Pak J Pharm Sci ; 37(2): 307-314, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38767097

RESUMO

Long-lasting hyperglycemia can potentially cause damage to organs such as the kidneys, liver and pancreas. Glimepiride (GLIM), as a drug of choice in the treatment of diabetes mellitus (DM), has the risk of decreasing the functioning of organs such as the kidneys, liver and pancreas. Black rice bran ethanol extract (EEBRB) with antioxidant content has been shown to protect the kidney, liver and pancreas organs. The aim of this study was to establish the effect of EEBRB on lowering fasting blood glucose (FBG) and protecting several organs after GLIM administration in alloxan (ALX)-induced hyperglycemic rats. A total of 20 rats were divided into 4 groups and treated for 21 days treatments using following preparations: normal control (NC), diabetic group (DC), GLIM 1 mg/ kgBW and combination of glimepiride 1mg/kgBW and EEBRB 50 mg/KgBW (GLBR). The results showed that the GLBR was able to lower blood glucose levels back to normal (<126 mg/dL) and protect kidney, liver and pancreas cells by increasing the amount in normal cells.


Assuntos
Glicemia , Diabetes Mellitus Experimental , Hipoglicemiantes , Rim , Fígado , Oryza , Pâncreas , Extratos Vegetais , Compostos de Sulfonilureia , Animais , Compostos de Sulfonilureia/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Rim/efeitos dos fármacos , Rim/metabolismo , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Oryza/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/isolamento & purificação , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Masculino , Ratos , Etanol/química , Ratos Wistar
7.
BMC Med ; 22(1): 205, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769537

RESUMO

BACKGROUND: It is unclear whether brief interventions using the combined classification of alcohol-metabolizing enzymes aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) together with behavioral changes in alcohol use can reduce excessive alcohol consumption. This study aimed to examine the effects of a brief intervention based on the screening of ALDH2 and ADH1B gene polymorphisms on alcohol consumption in Japanese young adults. METHODS: In this open-label randomized controlled trial, we enrolled adults aged 20-30 years who had excessive drinking behavior (average amount of alcohol consumed: men, ≥ 4 drinks/per day and women, ≥ 2 drinks/per day; 1 drink = 10 g of pure alcohol equivalent). Participants were randomized into intervention or control group using a simple random number table. The intervention group underwent saliva-based genotyping of alcohol-metabolizing enzymes (ALDH2 and ADH1B), which were classified into five types. A 30-min in-person or online educational counseling was conducted approximately 1 month later based on genotyping test results and their own drinking records. The control group received traditional alcohol education. Average daily alcohol consumption was calculated based on the drinking diary, which was recorded at baseline and at 3 and 6 months of follow-up. The primary endpoint was average daily alcohol consumption, and the secondary endpoints were the alcohol-use disorder identification test for consumption (AUDIT-C) score and behavioral modification stages assessed using a transtheoretical model. RESULTS: Participants were allocated to the intervention (n = 100) and control (n = 96) groups using simple randomization. Overall, 28 (29.2%) participants in the control group and 21 (21.0%) in the intervention group did not complete the follow-up. Average alcohol consumption decreased significantly from baseline to 3 and 6 months in the intervention group but not in the control group. The reduction from baseline alcohol consumption values and AUDIT-C score at 3 months were greater in the intervention group than in the control group (p < 0.001). In addition, the behavioral modification stages were significantly changed by the intervention (p < 0.001). CONCLUSIONS: Genetic testing for alcohol-metabolizing enzymes and health guidance on type-specific excessive drinking may be useful for reducing sustained average alcohol consumption associated with behavioral modification. TRIAL REGISTRATION: R000050379, UMIN000044148, Registered on June 1, 2021.


Assuntos
Álcool Desidrogenase , Consumo de Bebidas Alcoólicas , Aldeído-Desidrogenase Mitocondrial , Humanos , Masculino , Feminino , Álcool Desidrogenase/genética , Álcool Desidrogenase/metabolismo , Adulto , Aldeído-Desidrogenase Mitocondrial/genética , Consumo de Bebidas Alcoólicas/genética , Adulto Jovem , Genótipo , Etanol/metabolismo , Polimorfismo Genético , Resultado do Tratamento , Japão
9.
Alcohol Alcohol ; 59(4)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38783518

RESUMO

AIMS: Alcohol acutely impacts interoceptive processes, which in turn affect the perception of alcohol effects and the development of alcohol expectancies. However, previous research is limited by the tools used to measure cardiac interoception and subjective alcohol effects. This registered report proposes a re-examination of previous findings using a state-of-the-art measure of interoceptive capacity, the heart rate discrimination task, and measurements of subjective alcohol effects across both ascending and descending limbs. METHODS: In a double-blind, placebo-controlled experiment, n = 36 participants were given 0.4 g/kg of ethanol, and a baseline measure of alcohol expectancies was obtained. Changes in interoceptive capacity after beverage administration, along with measures of light-headedness, mood, and biphasic alcohol effects, were assessed over two sessions. HYPOTHESES: As registered in this secondary data analysis, alcohol was expected to acutely impact different indices of interoceptive capacity, and those changes were hypothesized to correlate with subjective alcohol effects and expectancies. Analyses were conducted only following in-principle acceptance. RESULTS: Alcohol-induced changes in interoceptive capacity predicted the development of light-headedness, stimulation, and negative mood. Changes in interoceptive capacity were also correlated with negative alcohol expectancies, as measured 2 weeks prior to the experiment. These effects were unique to the interoceptive condition, as null effects were observed in an exteroceptive control task. DISCUSSION: This report offers a replication of key previous findings that alcohol impacts interoceptive processes to shape the detection of subjective alcohol effects. We propose that, through repeated drinking occasions, bodily responses feed into the experience of intoxication, shaping future expectancies about alcohol effects.


Assuntos
Etanol , Frequência Cardíaca , Interocepção , Humanos , Masculino , Interocepção/fisiologia , Interocepção/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Método Duplo-Cego , Adulto Jovem , Adulto , Etanol/farmacologia , Afeto/efeitos dos fármacos , Afeto/fisiologia , Consumo de Bebidas Alcoólicas/psicologia , Publicação Pré-Registro
10.
Microb Cell Fact ; 23(1): 143, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38773442

RESUMO

BACKGROUND: Zymomonas mobilis is well known for its outstanding ability to produce ethanol with both high specific productivity and with high yield close to the theoretical maximum. The key enzyme in the ethanol production pathway is the pyruvate decarboxylase (PDC) which is converting pyruvate to acetaldehyde. Since it is widely considered that its gene pdc is essential, metabolic engineering strategies aiming to produce other compounds derived from pyruvate need to find ways to reduce PDC activity. RESULTS: Here, we present a new platform strain (sGB027) of Z. mobilis in which the native promoter of pdc was replaced with the IPTG-inducible PT7A1, allowing for a controllable expression of pdc. Expression of lactate dehydrogenase from E. coli in sGB027 allowed the production of D-lactate with, to the best of our knowledge, the highest reported specific productivity of any microbial lactate producer as well as with the highest reported lactate yield for Z. mobilis so far. Additionally, by expressing the L-alanine dehydrogenase of Geobacillus stearothermophilus in sGB027 we produced L-alanine, further demonstrating the potential of sGB027 as a base for the production of compounds other than ethanol. CONCLUSION: We demonstrated that our new platform strain can be an excellent starting point for the efficient production of various compounds derived from pyruvate with Z. mobilis and can thus enhance the establishment of this organism as a workhorse for biotechnological production processes.


Assuntos
Escherichia coli , Etanol , Ácido Láctico , Engenharia Metabólica , Piruvato Descarboxilase , Zymomonas , Zymomonas/metabolismo , Zymomonas/genética , Piruvato Descarboxilase/metabolismo , Piruvato Descarboxilase/genética , Engenharia Metabólica/métodos , Etanol/metabolismo , Ácido Láctico/metabolismo , Ácido Láctico/biossíntese , Escherichia coli/metabolismo , Escherichia coli/genética , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/genética , Alanina/metabolismo , Ácido Pirúvico/metabolismo , Fermentação
11.
Neuropharmacology ; 253: 109971, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38705568

RESUMO

The impact of environmental enrichment (EE) on natural rewards, including social and appetitive rewards, was investigated in male Swiss mice. EE, known for providing animals with various stimuli, was assessed for its effects on conditioned place preference (CPP) associated with ethanol and social stimuli. We previously demonstrated that EE increased the levels of the prosocial neuropeptide oxytocin (OT) in the hypothalamus and enhanced ethanol rewarding effects via an oxytocinergic mechanism. This study also investigated the impact of EE on social dominance and motivation for rewards, measured OT-mediated phospholipase C (PLC) activity in striatal membranes, and assessed OT expression in the hypothalamus. The role of dopamine in motivating rewards was considered, along with the interaction between OT and D1 receptors (DR) in the nucleus accumbens (NAc). Results showed that EE mice exhibited a preference for ethanol reward over social reward, a pattern replicated by the OT analogue Carbetocin. EE mice demonstrated increased social dominance and reduced motivation for appetitive taste stimuli. Higher OT mRNA levels in the hypothalamus were followed by diminished OT receptor (OTR) signaling activity in the striatum of EE mice. Additionally, EE mice displayed elevated D1R expression, which was attenuated by the OTR antagonist (L-368-889). The findings underscore the reinforcing effect of EE on ethanol and social rewards through an oxytocinergic mechanism. Nonetheless, they suggest that mechanisms other than the prosocial effect of EE may contribute to the ethanol pro-rewarding effect of EE and Carbetocin. They also point towards an OT-dopamine interaction potentially underlying some of these effects.


Assuntos
Dopamina , Etanol , Núcleo Accumbens , Ocitocina , Receptores de Dopamina D1 , Receptores de Ocitocina , Recompensa , Animais , Ocitocina/metabolismo , Ocitocina/análogos & derivados , Masculino , Etanol/farmacologia , Etanol/administração & dosagem , Camundongos , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D1/antagonistas & inibidores , Dopamina/metabolismo , Receptores de Ocitocina/metabolismo , Receptores de Ocitocina/antagonistas & inibidores , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Meio Ambiente , Hipotálamo/metabolismo , Hipotálamo/efeitos dos fármacos , Depressores do Sistema Nervoso Central/farmacologia , Predomínio Social , Comportamento Social , Motivação/fisiologia , Motivação/efeitos dos fármacos
12.
Orphanet J Rare Dis ; 19(1): 195, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741122

RESUMO

BACKGROUND: Clinically, arteriovenous malformations in the buttocks (bAVMs) are extremely rare. Our study aimed to evaluate the efficacy and safety of ethanol embolotherapy in managing bAVMs. RESULTS: A total of 32 patients with bAVMs (14 females and 18 males) from 2012 to 2021 were included in this study. All patients underwent complete clinical and imaging examinations. Further, the AVMs lesions were analyzed according to Schöbinger staging and Yakes classification. Each patient had undergone a multistage ethanol embolization. The amelioration of clinical symptoms and devascularization on angiography were evaluated at regular follow-ups. In the present cohort, the 11-20 age group had the most patients (15/32; 46.88%). A total of 124 embolization procedures were performed (average 3.88 procedures per patient), and the average dose of absolute ethanol was 18.96 mL per procedure. Thirteen patients with dominant draining veins underwent additional coil deployment before ethanol embolization (13/32; 40.63%). During follow-ups, clinical improvement was found in 23 of 27 who presented with a pulsating mass (85.19%), 17 of 20 with abnormal local skin temperature (85%), 5 of 6 with bleeding (83.33%), and 5 of 5 patients treated for pain (100%). More than 75% angiographic devascularization was achieved in 18 patients (18/32; 56.25%). Finally, 12 out of 13 patients (92.31%) reduced from Schöbinger Stage III to a lower grade, and ten patients exhibited a complete response (10/32; 31.23%). There was a single serious complication of local necrosis, while neither paranesthesia nor infection was observed postoperatively. CONCLUSIONS: Ethanol embolization assisted with coils can treat bAVMs effectively and safely. The Yakes classification contributed to the optimal ethanol embolotherapy of bAVMs.


Assuntos
Malformações Arteriovenosas , Embolização Terapêutica , Etanol , Humanos , Embolização Terapêutica/métodos , Feminino , Masculino , Etanol/uso terapêutico , Malformações Arteriovenosas/terapia , Nádegas/irrigação sanguínea , Adulto , Adulto Jovem , Adolescente , Criança , Pessoa de Meia-Idade , Resultado do Tratamento
13.
J Cancer Res Clin Oncol ; 150(5): 257, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753184

RESUMO

PURPOSE: Breast cancer metastasis relies on cellular invasion and angiogenesis facilitated by the downregulation of metastatic suppressor proteins like Cluster of Differentiation 82 (CD82). Currently, no medicines target multiple systems to prevent metastatic progression through CD82 upregulation. This study screened for plant extracts displaying effects on cell proliferation, invasion, and CD82 expression in breast cancer cells, and in vivo angiogenesis, and further correlated between the biological activities and effect on CD82 expression. METHODS: Seventeen ethanolic plant extracts were screened for their effect on cell proliferation (against MDA-MB-231 and MCF-7 breast cancer and Hek293 kidney cells), cell invasion and effect on CD82 expression in metastatic MDA-MB-231 cells. Selected extracts were further evaluated for in vivo anti-angiogenesis. RESULTS: Extracts displayed varying antiproliferative activity against the different cell lines, and those that showed selectivity indexes (SI) > 0.5 against MDA-MB-231 were selected for anti-invasion evaluation. Buddleja saligna Willd. (BS), Combretum apiculatum Sond. (CA), Foeniculum vulgare, Greyia radlkoferi, Gunnera perpensa and Persicaria senegalensis (Meisn.) Soják (PS) displayed 50% inhibitory concentration (IC50) values of 44.46 ± 3.46, 74.00 ± 4.48, 180.43 ± 4.51, 96.97 ± 2.29, 55.29 ± 9.88 and 243.60 ± 2.69 µg/mL, respectively against MDA-MB-231, and compared to Hek293 showed SI of 0.9, 0.7, 1.4, 1.1, 2.2 and 0.5. Significant invasion inhibition was observed at both 20 and 40 µg/mL for BS (94.10 ± 0.74 and 96.73 ± 0.95%) and CA (87.42 ± 6.54 and 98.24 ± 0.63%), whereas GR (14.91 ± 1.62 and 41 ± 1.78%) and PS (36.58 ± 0.54 and 51.51 ± 0.83%), only showed significant inhibition at 40 µg/mL, and FV (< 5% inhibition) and GP (10 ± 1.03 and 22 ± 1.31%) did not show significant inhibition at both concentrations. Due to the significant anti-invasive activity of BS, CA and PS at 40 µg/mL, these extracts were further evaluated for their potential to stimulate CD82. BS showed significant (p < 0.05) reduction in CD82 at 20 and 40 µg/mL (13.2 ± 2.2% and 20.3 ± 1.5% decrease, respectively), whereas both CA and PS at 20 µg/mL increased (p < 0.05) CD82 expression (16.4 ± 0.8% and 5.4 ± 0.6% increase, respectively), and at 40 µg/mL significantly reduced CD82 expression (23.4 ± 3.1% and 11.2 ± 2.9% decrease, respectively). Using the yolk sac membrane assay, BS (59.52 ± 4.12 and 56.72 ± 3.13% newly formed vessels) and CA (83.33 ± 3.17 and 74.00 ± 2.12%) at both 20 and 40 µg/egg showed significant (p < 0.001) angiogenesis inhibition, with BS showing statistical similar activity to the positive control, combretastatin A4 (10 nmol/egg), whereas PS only displayed significant (p < 0.001) angiogenesis stimulation at 40 µg/egg (120.81 ± 3.34% newly formed vessels). CONCLUSION: BS exhibits antiproliferative, anti-invasive, and anti-angiogenic activity despite inhibiting CD82, suggesting an alternative mode of action. CA at 20 µg/mL shows moderate anti-invasive and anti-angiogenic potential by stimulating CD82, while at 40 µg/mL it still displays these properties but inhibits CD82, suggesting an additional mode of action. PS, with the least antiproliferative activity, stimulates CD82 and inhibits angiogenesis at 20 µg/mL but inhibits CD82 and increases angiogenesis at 40 µg/mL, indicating CD82 targeting as a major mode of action. Future studies should explore breast cancer xenograft models to assess the extracts' impact on CD82 expression and angiogenesis in the tumor microenvironment, along with isolating bioactive compounds from the extracts.


Assuntos
Neoplasias da Mama , Proliferação de Células , Proteína Kangai-1 , Invasividade Neoplásica , Neovascularização Patológica , Extratos Vegetais , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Extratos Vegetais/farmacologia , Feminino , Animais , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Neovascularização Patológica/prevenção & controle , Proteína Kangai-1/metabolismo , Plantas Medicinais/química , Células HEK293 , Linhagem Celular Tumoral , Etanol/química , Etanol/farmacologia , Embrião de Galinha , Metástase Neoplásica , Membrana Corioalantoide/efeitos dos fármacos , Angiogênese
14.
Prog Neurobiol ; 237: 102616, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38723884

RESUMO

Alterations in cognitive and non-cognitive cerebral functions characterize Alzheimer's disease (AD). Cortical and hippocampal impairments related to extracellular accumulation of Aß in AD animal models have been extensively investigated. However, recent reports have also implicated intracellular Aß in limbic regions, such as the nucleus accumbens (nAc). Accumbal neurons express high levels of inhibitory glycine receptors (GlyRs) that are allosterically modulated by ethanol and have a role in controlling its intake. In the present study, we investigated how GlyRs in the 2xTg mice (AD model) affect nAc functions and ethanol intake behavior. Using transgenic and control aged-matched litter mates, we found that the GlyRα2 subunit was significantly decreased in AD mice (6-month-old). We also examined intracellular calcium dynamics using the fluorescent calcium protein reporter GCaMP in slice photometry. We also found that the calcium signal mediated by GlyRs, but not GABAAR, was also reduced in AD neurons. Additionally, ethanol potentiation was significantly decreased in accumbal neurons in the AD mice. Finally, we performed drinking in the dark (DID) experiments and found that 2xTg mice consumed less ethanol on the last day of DID, in agreement with a lower blood ethanol concentration. 2xTg mice also showed lower sucrose consumption, indicating that overall food reward was altered. In conclusion, the data support the role of GlyRs in nAc neuron excitability and a decreased glycinergic activity in the 2xTg mice that might lead to impairment in reward processing at an early stage of the disease.


Assuntos
Doença de Alzheimer , Modelos Animais de Doenças , Etanol , Camundongos Transgênicos , Núcleo Accumbens , Receptores de Glicina , Recompensa , Animais , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Receptores de Glicina/metabolismo , Etanol/administração & dosagem , Etanol/farmacologia , Camundongos , Masculino , Neurônios/metabolismo , Camundongos Endogâmicos C57BL , Consumo de Bebidas Alcoólicas/metabolismo
15.
Alcohol Alcohol ; 59(4)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742547

RESUMO

AIMS: Continued alcohol consumption despite negative consequences is a core symptom of alcohol use disorder. This is modeled in mice by pairing negative stimuli with alcohol, such as adulterating alcohol solution with quinine. Mice consuming alcohol under these conditions are considered to be engaging in aversion-resistant intake. Previously, we have observed sex differences in this behavior, with females more readily expressing aversion-resistant consumption. We also identified three brain regions that exhibited sex differences in neuronal activation during quinine-alcohol drinking: ventromedial prefrontal cortex (vmPFC), posterior insular cortex (PIC), and ventral tegmental area (VTA). Specifically, male mice showed increased activation in vmPFC and PIC, while females exhibited increased activation in VTA. In this study, we aimed to identify what specific type of neurons are activated in these regions during quinine-alcohol drinking. METHOD: We assessed quinine-adulterated alcohol intake using the two-bottle choice procedure. We also utilized RNAscope in situ hybridization in the three brain regions that previously exhibited a sex difference to examine colocalization of Fos, glutamate, GABA, and dopamine. RESULT: Females showed increased aversion-resistant alcohol consumption compared to males. We also found that males had higher colocalization of glutamate and Fos in vmPFC and PIC, while females had greater dopamine and Fos colocalization in the VTA. CONCLUSIONS: Collectively, these experiments suggest that glutamatergic output from the vmPFC and PIC may have a role in suppressing, and dopaminergic activity in the VTA may promote, aversion-resistant alcohol consumption. Future experiments will examine neuronal circuits that contribute to sex differences in aversion resistant consumption.


Assuntos
Consumo de Bebidas Alcoólicas , Neurônios , Quinina , Caracteres Sexuais , Animais , Quinina/farmacologia , Feminino , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Área Tegmentar Ventral/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/efeitos dos fármacos , Mesencéfalo/metabolismo , Mesencéfalo/efeitos dos fármacos , Córtex Insular/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Etanol/farmacologia , Ácido Glutâmico/metabolismo
16.
Microb Cell Fact ; 23(1): 123, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724968

RESUMO

BACKGROUND: Saccharomyces cerevisiae is an important microorganism in ethanol synthesis, and with sugarcane molasses as the feedstock, ethanol is being synthesized sustainably to meet growing demands. However, high-concentration ethanol fermentation based on high-concentration sugarcane molasses-which is needed for reduced energy consumption of ethanol distillation at industrial scale-is yet to be achieved. RESULTS: In the present study, to identify the main limiting factors of this process, adaptive laboratory evolution and high-throughput screening (Py-Fe3+) based on ARTP (atmospheric and room-temperature plasma) mutagenesis were applied. We identified high osmotic pressure, high temperature, high alcohol levels, and high concentrations of K+, Ca2+, K+ and Ca2+ (K+&Ca2+), and sugarcane molasses as the main limiting factors. The robust S. cerevisiae strains of NGT-F1, NGW-F1, NGC-F1, NGK+, NGCa2+ NGK+&Ca2+-F1, and NGTM-F1 exhibited high tolerance to the respective limiting factor and exhibited increased yield. Subsequently, ethanol synthesis, cell morphology, comparative genomics, and gene ontology (GO) enrichment analysis were performed in a molasses broth containing 250 g/L total fermentable sugars (TFS). Additionally, S. cerevisiae NGTM-F1 was used with 250 g/L (TFS) sugarcane molasses to synthesize ethanol in a 5-L fermenter, giving a yield of 111.65 g/L, the conversion of sugar to alcohol reached 95.53%. It is the highest level of physical mutagenesis yield at present. CONCLUSION: Our results showed that K+ and Ca2+ ions primarily limited the efficient production of ethanol. Then, subsequent comparative transcriptomic GO and pathway analyses showed that the co-presence of K+ and Ca2+ exerted the most prominent limitation on efficient ethanol production. The results of this study might prove useful by promoting the development and utilization of green fuel bio-manufactured from molasses.


Assuntos
Cálcio , Etanol , Fermentação , Melaço , Potássio , Saccharomyces cerevisiae , Saccharum , Etanol/metabolismo , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Saccharum/metabolismo , Cálcio/metabolismo , Potássio/metabolismo
17.
Curr Microbiol ; 81(6): 161, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700667

RESUMO

In the wake of rapid industrialization and burgeoning transportation networks, the escalating demand for fossil fuels has accelerated the depletion of finite energy reservoirs, necessitating urgent exploration of sustainable alternatives. To address this, current research is focusing on renewable fuels like second-generation bioethanol from agricultural waste such as sugarcane bagasse. This approach not only circumvents the contentious issue of food-fuel conflicts associated with biofuels but also tackles agricultural waste management. In the present study indigenous yeast strain, Clavispora lusitaniae QG1 (MN592676), was isolated from rotten grapes to ferment xylose sugars present in the hemicellulose content of sugarcane bagasse. To liberate the xylose sugars, dilute acid pretreatment was performed. The highest reducing sugars yield was 1.2% obtained at a temperature of 121 °C for 15 min, a solid-to-liquid ratio of 1:25 (% w/v), and an acid concentration of 1% dilute acid H2SO4 that was significantly higher (P < 0.001) yield obtained under similar conditions at 100 °C for 1 h. The isolated strain was statistically optimized for fermentation process by Plackett-Burman design to achieve the highest ethanol yield. Liberated xylose sugars were completely utilized by Clavispora lusitaniae QG1 (MN592676) and gave 100% ethanol yield. This study optimizes both fermentation process and pretreatment of sugarcane bagasse to maximize bioethanol yield and demonstrates the ability of isolated strain to effectively utilize xylose as a carbon source. The desirable characteristics depicted by strain Clavispora lusitaniae shows its promising utilization in management of industrial waste like sugarcane bagasse by its conversion into renewable biofuels like bioethanol.


Assuntos
Biocombustíveis , Celulose , Etanol , Fermentação , Saccharum , Saccharum/metabolismo , Etanol/metabolismo , Celulose/metabolismo , Gerenciamento de Resíduos/métodos , Agricultura , Xilose/metabolismo , Vitis/microbiologia , Hypocreales/metabolismo
18.
Int J Mol Sci ; 25(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38732196

RESUMO

The investigation of functional materials derived from sustainable and eco-friendly bioresources has generated significant attention. Herein, nanocomposite films based on chiral nematic cellulose crystals (CNCs) were developed by incorporating xylose and biocompatible ZnO nanoparticles (NPs) via evaporation-induced self-assembly (EISA). The nanocomposite films exhibited iridescent color changes that corresponded to the birefringence phenomenon under polarized light, which was attributed to the formation of cholesteric structures. ZnO nanoparticles were proved to successfully adjust the helical pitches of the chiral arrangements of the CNCs, resulting in tunable optical light with shifted wavelength bands. Furthermore, the nanocomposite films showed fast humidity and ethanol stimuli response properties, exhibiting the potential of stimuli sensors of the CNC-based sustainable materials.


Assuntos
Celulose , Etanol , Umidade , Nanopartículas , Óxido de Zinco , Celulose/química , Óxido de Zinco/química , Etanol/química , Nanopartículas/química , Nanocompostos/química
19.
Int J Mol Sci ; 25(9)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38732226

RESUMO

We previously reported that mice with low neuronal pH drink more alcohol, demonstrating the importance of pH for alcohol reward and motivation. In this study, we tested whether systemic pH affects alcohol consumption and if so, whether it occurs by changing the alcohol reward. C57BL/6J mice were given NaHCO3 to raise their blood pH, and the animals' alcohol consumption was measured in the drinking-in-the-dark and two-bottle free choice paradigms. Alcohol consumption was also assessed after suppressing the bitterness of NaHCO3 with sucrose. Alcohol reward was evaluated using a conditioned place preference. In addition, taste sensitivity was assessed by determining quinine and sucrose preference. The results revealed that a pH increase by NaHCO3 caused mice to decrease their alcohol consumption. The decrease in high alcohol contents (20%) was significant and observed at different ages, as well as in both males and females. Alcohol consumption was also decreased after suppressing NaHCO3 bitterness. Oral gavage of NaHCO3 did not alter quinine and sucrose preference. In the conditioned place preference, NaHCO3-treated mice spent less time in the alcohol-injected chamber. Conclusively, the results show that raising systemic pH with NaHCO3 decreases alcohol consumption, as it decreases the alcohol reward value.


Assuntos
Consumo de Bebidas Alcoólicas , Camundongos Endogâmicos C57BL , Recompensa , Bicarbonato de Sódio , Animais , Camundongos , Masculino , Feminino , Bicarbonato de Sódio/farmacologia , Concentração de Íons de Hidrogênio , Etanol , Sacarose/farmacologia , Quinina/farmacologia , Paladar/efeitos dos fármacos
20.
Nutrients ; 16(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38732511

RESUMO

Prenatal alcohol exposure (AE) affects cognitive development. However, it is unclear whether prenatal AE influences the metabolic health of offspring and whether postnatal AE exacerbates metabolic deterioration resulting from prenatal AE. Choline is a semi-essential nutrient that has been demonstrated to mitigate the cognitive impairment of prenatal AE. This study investigated how maternal choline supplementation (CS) may modify the metabolic health of offspring with prenatal and postnatal AE (AE/AE). C57BL/6J female mice were fed either a Lieber-DeCarli diet with 1.4% ethanol between embryonic day (E) 9.5 and E17.5 or a control diet. Choline was supplemented with 4 × concentrations versus the control throughout pregnancy. At postnatal week 7, offspring mice were exposed to 1.4% ethanol for females and 3.9% ethanol for males for 4 weeks. AE/AE increased hepatic triglyceride accumulation in male offspring only, which was normalized by prenatal CS. Prenatal CS also improved glucose tolerance compared to AE/AE animals. AE/AE suppressed hepatic gene expression of peroxisome proliferator activated receptor alpha (Ppara) and low-density lipoprotein receptor (Ldlr), which regulate fatty acid catabolism and cholesterol reuptake, respectively, in male offspring. However, these changes were not rectified by prenatal CS. In conclusion, AE/AE led to an increased risk of steatosis and was partially prevented by prenatal CS in male mice.


Assuntos
Colina , Suplementos Nutricionais , Etanol , Fígado , Camundongos Endogâmicos C57BL , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Gravidez , Colina/administração & dosagem , Masculino , Fígado/metabolismo , Fígado/efeitos dos fármacos , Camundongos , Fígado Gorduroso/prevenção & controle , Fígado Gorduroso/etiologia , Triglicerídeos/metabolismo , PPAR alfa/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , Intolerância à Glucose/prevenção & controle , Metabolismo dos Lipídeos/efeitos dos fármacos
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