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1.
Front Immunol ; 15: 1326370, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38566993

RESUMO

Background: While a few case-control studies indicated a possible correlation of IgG N-glycosylation patterns with pancreatitis, their restricted sample sizes and methodologies prevented conclusive insights into causality or distinguishing traits across pancreatitis types. Method: We conducted a two-sample Mendelian Randomization (MR) analysis to investigate the causal relationship between 77 IgG N-glycosylation traits and various types of pancreatitis, including acute pancreatitis (AP), chronic pancreatitis (CP), alcohol acute pancreatitis (AAP), and alcohol chronic pancreatitis (ACP). This analysis utilized summary-level data from genome-wide association studies (GWAS), employing methods such as IVW, MR-Egger, and weighted median. To ensure the robustness of our findings, several sensitivity analyses, including Cochran's Q statistic, leave-one-out, MR-Egger intercept, and MR-PRESSO global test were conducted. Result: Our study uncovered the causal relationship between specific IgG N-glycosylation traits and various types of pancreatitis. Notably, an increase in genetically predicted IGP7 levels was associated with a decreased risk of developing AP. For CP, our data suggested a protective effect associated with higher levels of both IGP7 and IGP31, contrasting with increased levels of IGP27 and IGP65, which were linked to a heightened risk. Moreover, in the case of AAP, elevated IGP31 levels were causatively associated with a lower incidence, while higher IGP26 levels correlated with an increased risk for ACP. Conclusion: This study establishes causal relationship between specific IgG N-glycosylation patterns and varying risks of different pancreatitis forms, underscoring their potential as predictive biomarkers. These findings necessitate further exploration into the underlying mechanisms, promising to inform more personalized diagnostic and therapeutic strategies in pancreatitis management.


Assuntos
Imunoglobulina G , Pancreatite Crônica , Humanos , Doença Aguda , Etanol , Estudo de Associação Genômica Ampla , Glicosilação , Pancreatite Crônica/genética , Análise da Randomização Mendeliana
2.
Environ Health Perspect ; 132(4): 47007, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38619879

RESUMO

BACKGROUND: Environmental pollutants, including polychlorinated biphenyls (PCBs) have been implicated in the pathogenesis of liver disease. Our group recently demonstrated that PCB126 promoted steatosis, hepatomegaly, and modulated intermediary metabolism in a rodent model of alcohol-associated liver disease (ALD). OBJECTIVE: To better understand how PCB126 promoted ALD in our previous model, the current study adopts multiple omics approaches to elucidate potential mechanistic hypotheses. METHODS: Briefly, male C57BL/6J mice were exposed to 0.2mg/kg polychlorinated biphenyl (PCB) 126 or corn oil vehicle prior to ethanol (EtOH) or control diet feeding in the chronic-binge alcohol feeding model. Liver tissues were collected and prepared for mRNA sequencing, phosphoproteomics, and inductively coupled plasma mass spectrometry for metals quantification. RESULTS: Principal component analysis showed that PCB126 uniquely modified the transcriptome in EtOH-fed mice. EtOH feeding alone resulted in >4,000 differentially expressed genes (DEGs), and PCB126 exposure resulted in more DEGs in the EtOH-fed group (907 DEGs) in comparison with the pair-fed group (503 DEGs). Top 20 significant gene ontology (GO) biological processes included "peptidyl tyrosine modifications," whereas top 25 significantly decreasing GO molecular functions included "metal/ion/zinc binding." Quantitative, label-free phosphoproteomics and western blot analysis revealed no major significant PCB126 effects on total phosphorylated tyrosine residues in EtOH-fed mice. Quantified hepatic essential metal levels were primarily significantly lower in EtOH-fed mice. PCB126-exposed mice had significantly lower magnesium, cobalt, and zinc levels in EtOH-fed mice. DISCUSSION: Previous work has demonstrated that PCB126 is a modifying factor in metabolic dysfunction-associated steatotic liver disease (MASLD), and our current work suggests that pollutants also modify ALD. PCB126 may, in part, be contributing to the malnutrition aspect of ALD, where metal deficiency is known to contribute and worsen prognosis. https://doi.org/10.1289/EHP14132.


Assuntos
Poluentes Ambientais , Fígado Gorduroso , Hepatopatias Alcoólicas , Bifenilos Policlorados , Masculino , Camundongos , Animais , Multiômica , Camundongos Endogâmicos C57BL , Etanol/toxicidade , Etanol/metabolismo , Fígado/metabolismo , Bifenilos Policlorados/toxicidade , Bifenilos Policlorados/metabolismo , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Poluentes Ambientais/toxicidade , Poluentes Ambientais/metabolismo , Zinco/metabolismo , Tirosina/metabolismo
3.
Zhongguo Zhong Yao Za Zhi ; 49(3): 735-743, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621877

RESUMO

Chemical constituents of 70% ethanol extract of Alangium chinense subsp. pauciflorum were investigated. The 70% ethanol extract of A. chinense subsp. pauciflorum was isolated and purified by D-101 macroporous resins, silica gel, Sephadex LH-20 and other methods. As a result, nineteen compounds were isolated and identified as 4-cyclohexene-1α,2α,3α-triol-1-O-ß-D-glucoside(1), 1ß,4α,6α,13-tetrahydroxy-eudesm-11(12)-ene(2), sucrose(3), 1'-O-benzyl-α-L-rhamnopyranosyl-(1″→6')-ß-D-glucopyranoside(4), bis(2-ethylhexyl)benzene-1,2-dicarboxylate(5),(Z)-10-heneicosenoic acid(6), di-O-methylcrenati(7), methyl-α-D-fructofuranoside(8), ß-daucosterol(9), syringic acid(10), vanillicacid(11), octacosanol(12), isoarborinol(13), 2,7-dihydroxy-6-methyl-4-(1-methylethyl)-1-naphthalenecarboxylate(14),vanillin(15), coniferyl aldehyde(16), 9(11)-dehydroergosterolperoxide(17), 5α,8α-epidioxy-(22E,24R)-ergosta-6,22-dien-3ß-ol(18), ß-sitosterol(19), respectively. Compounds 1 and 2 were new compounds, compounds 5-11, 13, 15-18 were isolated from Alangium for the first time.The anti-inflammatory activity of compourd 1 was determinded by the LPS-induced RAW264.7 macrophage inflammation model. The results showed that the new compound 1 has a certain inhibitory effect on LPS-induced NO production of RAW264.7 cells, and the inhibitory rate was 54.57%.


Assuntos
Alangiaceae , Lipopolissacarídeos , Anti-Inflamatórios/farmacologia , Etanol , Extratos Vegetais
4.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1217-1224, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621968

RESUMO

To investigate the quality differences between the seeds and husks of Amomum villosum and explore the rationality of using the seeds without husks, this study determined the content of protocatechuic acid, vanillic acid, epicatechin, quercitrin, volatile oil, water extract, and ethanol extract. The 2,2-diphenyl-1-picrylhydrazyl(DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), and hydroxyl radical scavenging activities were determined to evaluate the antioxidant activities of seeds and husks. The quality differences between the seeds and husks were assessed through orthogonal partial least squares-discriminant analysis(OPLS-DA) and analytic hierarchy process(AHP) combined with the entropy weight method(EWM). Significant differences(P<0.05) were observed in all 10 indicators between the seeds and husks. The levels of epicatechin, quercetin, and volatile oil were higher in the seeds, whereas those of protocatechuic acid, vanillic acid, water extract, and ethanol extract were higher in the husks. The seeds showed stronger scavenging ability against DPPH and ABTS radicals, while the husks showed a stronger scavenging effect on hydroxyl radicals. OPLS-DA significantly discriminated between the seeds and husks. Furthermore, volatile oil, water extract, DPPH radical scavenging rate, quercitrin, ABTS radical scavenging rate, hydroxyl radical scavenging rate, and vanillic acid were selected as the main differential indicators by variable importance in projection(VIP). Comprehensive scores calculated by AHP combined with EWM indicated that the seeds were superior to husks in terms of overall quality. However, there are still some dominant components and a certain antioxidant effect in the husks. Therefore, it is suggested to using Amomi Fructus with a certain amount of husks or utilizing the husks for other purposes.


Assuntos
Amomum , Benzotiazóis , Catequina , Hidroxibenzoatos , Óleos Voláteis , Ácidos Sulfônicos , Radical Hidroxila , Ácido Vanílico , Antioxidantes/química , Água , Etanol , Óleos Voláteis/química
5.
Sensors (Basel) ; 24(7)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38610464

RESUMO

Alcohol acts as a central nervous system depressant and falls under the category of psychoactive drugs. It has the potential to impair vital bodily functions, including cognitive alertness, muscle coordination, and induce fatigue. Taking the wheel after consuming alcohol can lead to delayed responses in emergency situations and increases the likelihood of collisions with obstacles or suddenly appearing objects. Statistically, drivers under the influence of alcohol are seven times more likely to cause accidents compared to sober individuals. Various techniques and methods for alcohol measurement have been developed. The widely used breathalyzer, which requires direct contact with the mouth, raises concerns about hygiene. Methods like chromatography require skilled examiners, while semiconductor sensors exhibit instability in sensitivity over measurement time and has a short lifespan, posing structural challenges. Non-dispersive infrared analyzers face structural limitations, and in-vehicle air detection methods are susceptible to external influences, necessitating periodic calibration. Despite existing research and technologies, there remain several limitations, including sensitivity to external factors such as temperature, humidity, hygiene consideration, and the requirement for periodic calibration. Hence, there is a demand for a novel technology that can address these shortcomings. This study delved into the near-infrared wavelength range to investigate optimal wavelengths for non-invasively measuring blood alcohol concentration. Furthermore, we conducted an analysis of the optical characteristics of biological substances, integrated these data into a mathematical model, and demonstrated that alcohol concentration can be accurately sensed using the first-order modeling equation at the optimal wavelength. The goal is to minimize user infection and hygiene issues through a non-destructive and non-invasive method, while applying a compact spectrometer sensor suitable for button-type ignition devices in vehicles. Anticipated applications of this study encompass diverse industrial sectors, including the development of non-invasive ignition button-based alcohol prevention systems, surgeon's alcohol consumption status in the operating room, screening heavy equipment operators for alcohol use, and detecting alcohol use in close proximity to hazardous machinery within factories.


Assuntos
Concentração Alcoólica no Sangue , Dirigir sob a Influência , Humanos , Etanol , Análise Espectral , Calibragem
6.
J Pak Med Assoc ; 74(3): 464-468, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38591279

RESUMO

Objectives: To evaluate the effectiveness of ethanol compared to citric acid in the removal of oil-based calcium hydroxide from the apical third of the root canal system using passive ultrasonic irrigation. METHODS: The in vitro study was conducted from September to October 2021 at the dental clinics of the Aga Khan University Hospital, Karachi, and comprised single-rooted teeth that were selected from institutional bank of extracted teeth. They were randomly divided into group A having 70% ethanol + passive ultrasonic irrigation, group B 10% citric acid + passive ultrasonic irrigation, group C positive controls and group D negative controls. The specimens were sectioned at 1mm and 3mm from the apex and examined under a dental operating microscope. A single examiner scored the specimens on two different occasions. Data was analysed using SPSS 25. RESULTS: Of the 90 teeth, there were 40(44.4%) in each of the 2 experimental groups and 5(5.5%) in each of the 2 control groups. At 3mm apical sections, ethanol was significantly more effective in the removal of oil-based calcium hydroxide (p=0.01). However, at 1mm from the apex, there was no significant difference between the experimental groups (p=0.064). Intragroup comparison showed that for groups A and B, residual medicament at 1mm sections was significantly greater than at 3mm sections (p<0.001, p=0.003). CONCLUSIONS: Neither irrigant showed complete removal at 1mm and 3mm from the apex. However, at 3mm apical sections, 70% ethanol was significantly more effective compared to 10% citric acid.


Assuntos
Hidróxido de Cálcio , Preparo de Canal Radicular , Humanos , Ácido Cítrico , Cavidade Pulpar , Etanol/farmacologia , Irrigantes do Canal Radicular/uso terapêutico
7.
Sci Rep ; 14(1): 8765, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627518

RESUMO

Green spectrophotometric and HPLC methods have been developed for the quantification of metoclopramide. In the spectrophotometric method, it was determined by direct absorbance measurement at 273 nm wavelength using ultrapure water as solvent. The Extend C18 column was used for the HPLC method. The mobile phase system consisted of a combination of ethanol and formic acid solution (pH 2.0; 30:70 v/v). Isocratic elution was applied and the flow rate was set at 1.0 mL min-1. Metoclopramide was detected at 273 nm. The methods performed were economical, rapid, environmentally friendly, and simple, providing metoclopramide analysis within 5 min. The methods have been successfully applied in pharmaceutical products without matrix interference. The results of the application of the developed methods to pharmaceutical products were statistically compared and no significant difference was observed between the methods. In addition, the greenness assessment of the developed methods was performed using AGREE software. Our developed methods, based on the use of solvents such as ethanol and water, are proposed as a more environmentally and analyst-friendly option for the quantification of metoclopramide in pharmaceutical products than other methods currently in use.


Assuntos
Etanol , Metoclopramida , Cromatografia Líquida de Alta Pressão/métodos , Metoclopramida/análise , Água , Preparações Farmacêuticas
8.
Antimicrob Resist Infect Control ; 13(1): 44, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627805

RESUMO

BACKGROUND: Antiseptics, disinfectants, and hand hygiene products can be contaminated with bacteria and cause healthcare-associated infections, which are underreported from low- and middle-income countries. To better understand the user-related risk factors, we conducted a knowledge, awareness, and practice survey among hospital staff in sub-Saharan Africa. METHODS: Self-administered questionnaire distributed among healthcare workers in three tertiary care hospitals (Burkina Faso, Benin, Democratic Republic of the Congo). RESULTS: 617 healthcare workers (85.3% (para)medical and 14.7% auxiliary staff) participated. Less than half (45.5%) had been trained in Infection Prevention & Control (IPC), and only 15.7% were trained < 1 year ago. Near two-thirds (64.2%) preferred liquid soap for hand hygiene, versus 33.1% for alcohol-based hand rub (ABHR). Most (58.3%) expressed confidence in the locally available products. Knowledge of product categories, storage conditions and shelf-life was inadequate: eosin was considered as an antiseptic (47.5% of (para)medical staff), the shelf life and storage conditions (non-transparent container) of freshly prepared chlorine 0.5% were known by only 42.6% and 34.8% of participants, respectively. Approximately one-third of participants approved using tap water for preparation of chlorine 0.5% and liquid soap. Most participants (> 80%) disapproved recycling soft-drink bottles as liquid soap containers. Nearly two-thirds (65.0%) declared that bacteria may be resistant to and survive in ABHR, versus 51.0% and 37.4% for povidone iodine and chlorine 0.5%, respectively. Depicted risk practices (n = 4) were ignored by 30 to 40% of participants: they included touching the rim or content of stock containers with compresses or small containers, storing of cotton balls soaked in an antiseptic, and hand-touching the spout of pump dispenser. Filling containers by topping-up was considered good practice by 18.3% of participants. Half (52.1%) of participants acknowledged indefinite reuse of containers. Besides small differences, the findings were similar across the study sites and professional groups. Among IPC-trained staff, proportions recognizing all 4 risk practices were higher compared to non-trained staff (35.9% versus 23.8%, p < 0.0001). CONCLUSIONS: The present findings can guide tailored training and IPC implementation at the healthcare facility and national levels, and sensitize stakeholders' and funders' interest.


Assuntos
Anti-Infecciosos Locais , Desinfetantes , Higiene das Mãos , Humanos , Estudos Transversais , Centros de Atenção Terciária , Benin , Burkina Faso , Cloro , República Democrática do Congo , Sabões , Etanol , Recursos Humanos em Hospital , Bactérias
9.
J Prim Care Community Health ; 15: 21501319241246992, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628054

RESUMO

OBJECTIVES: Study objectives were to: (1) better understand sleep experiences and unhealthy alcohol use among Veterans with long COVID and (2) explore providers' perceptions of barriers and facilitators to delivering evidence-based care for sleep problems and unhealthy alcohol use in patients with long COVID. METHODS: VA electronic health records were used to conduct chart reviews (n = 57) of patients evaluated in a VA COVID-19 Recovery Clinic during 1 calendar year; semi-structured interviews were completed with Veterans (n = 5) and clinicians (n = 7) recruited from the clinic. Veteran participants also completed quantitative, self-report measures assessing sleep- and alcohol-related experiences and behaviors. RESULTS: Data from chart reviews and interviews suggested that Veterans with long COVID often had pre-existing sleep problems that were exacerbated during long COVID. Patients and providers agreed that sleep interventions would be beneficial and acceptable in the COVID-19 Recovery clinic. Conversely, few Veterans with long COVID had a pre-existing alcohol use disorder (AUD) diagnosis; alcohol use occurred less frequently and was less often discussed between patients and providers. Providers had mixed viewpoints on delivering alcohol-related care in the clinic; some were highly amenable, others were unsure whether patients would be receptive. CONCLUSIONS: This study is among the first to take a mixed-method approach to understanding experiences of sleep-wake behaviors and unhealthy alcohol use in Veterans with long COVID. Characterizing sleep and alcohol-related experiences, examining associations with functioning, and exploring perspectives on treatment approaches is critical to support efforts to refine, personalize, and optimize evidence-based sleep and alcohol care for Veterans living with long COVID.


Assuntos
COVID-19 , Transtornos do Sono-Vigília , Veteranos , Estados Unidos/epidemiologia , Humanos , Síndrome Pós-COVID-19 Aguda , United States Department of Veterans Affairs , COVID-19/epidemiologia , Etanol , Transtornos do Sono-Vigília/epidemiologia , Pesquisa Qualitativa
10.
J Mol Neurosci ; 74(2): 44, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630337

RESUMO

Plants are a valuable source of information for pharmacological research and new drug discovery. The present study aimed to evaluate the neuroprotective potential of the leaves of the medicinal plant Sterculia setigera. In vitro, the effect of Sterculia setigera leaves dry hydroethanolic extract (SSE) was tested on cultured cerebellar granule neurons (CGN) survival when exposed to hydrogen peroxide (H2O2) or 6-hydroxydopamine (6-OHDA), using the viability probe fluorescein diacetate (FDA), a lactate dehydrogenase (LDH) activity assay, an immunocytochemical staining against Gap 43, and the quantification of the expression of genes involved in apoptosis, necrosis, or oxidative stress. In vivo, the effect of intraperitoneal (ip) injection of SSE was assessed on the developing brain of 8-day-old Wistar rats exposed to ethanol neurotoxicity by measuring caspase-3 activity on cerebellum homogenates, the expression of some genes in tissue extracts, the thickness of cerebellar cortical layers and motor coordination. In vitro, SSE protected CGN against H2O2 and 6-OHDA-induced cell death at a dose of 10 µg/mL, inhibited the expression of genes Casp3 and Bad, and upregulated the expression of Cat and Gpx7. In vivo, SSE significantly blocked the deleterious effect of ethanol by reducing the activity of caspase-3, inhibiting the expression of Bax and Tp53, preventing the reduction of the thickness of the internal granule cell layer of the cerebellar cortex, and restoring motor functions. Sterculia setigera exerts neuroactive functions as claimed by traditional medicine and should be a good candidate for the development of a neuroprotective treatment against neurodegenerative diseases.


Assuntos
Fármacos Neuroprotetores , Sterculia , Ratos , Animais , Ratos Wistar , Fármacos Neuroprotetores/farmacologia , Caspase 3 , Peróxido de Hidrogênio , Oxidopamina , Etanol/toxicidade
11.
Semin Liver Dis ; 44(1): 69-78, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38574752

RESUMO

Excessive alcohol consumption represents an important burden for health systems worldwide and is a major cause of liver- and cancer-related deaths. Alcohol consumption is mostly assessed by self-report that often underestimates the amount of drinking. While alcohol use disorders identification test - version C is the most widely used test for alcohol use screening, in patients with liver disease the use of alcohol biomarker could help an objective assessment. The amount of alcohol that leads to significant liver disease depends on gender, genetic background, and coexistence of comorbidities (i.e., metabolic syndrome factors). All patients with alcohol-associated liver disease are recommended to follow complete abstinence and they should be treated within multidisciplinary teams. Abstinence slows down and even reverses the progression of liver fibrosis and can help recompensate patients with complicated cirrhosis. Whether there is a safe amount of alcohol in the general population is a matter of intense debate. Large epidemiological studies showed that the safe amount of alcohol to avoid overall health-related risks is lower than expected even in the general population. Even one drink per day can increase cancer-related death. In patients with any kind of chronic liver disease, especially in those with metabolic-associated steatotic liver disease, no alcohol intake is recommended. This review article discusses the current evidence supporting the deleterious effects of small-to-moderate amounts of alcohol in the general population and in patients with underlying chronic liver disease.


Assuntos
Alcoolismo , Hepatopatias Alcoólicas , Neoplasias , Humanos , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Cirrose Hepática , Hepatopatias Alcoólicas/epidemiologia , Etanol/efeitos adversos
12.
J Agric Food Chem ; 72(15): 8476-8490, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38588403

RESUMO

Melosira nummuloides is a microalga with a nutritionally favorable polyunsaturated fatty acid profile. In the present study, M. nummuloides ethanol extract (MNE) was administered to chronic-binge alcohol-fed mice and alcohol-treated HepG2 cells, and its hepatoprotective effects and underlying mechanisms were investigated. MNE administration reduced triglyceride (TG), total cholesterol (T-CHO), and liver injury markers, including aspartate transaminase (AST) and alanine transaminase (ALT), in the serum of chronic-binge alcohol-fed mice. However, MNE administration increased the levels of phosphorylated adenosine monophosphate-activated protein kinase (P-AMPK/AMPK) and PPARα, which was accompanied by a decrease in SREBP-1; this indicates that MNE can inhibit adipogenesis and improve fatty acid oxidation. Moreover, MNE administration upregulated the expression of antioxidant enzymes, including SOD, NAD(P)H quinone dehydrogenase 1, and GPX, and ameliorated alcohol-induced inflammation by repressing the Akt/NFκB/COX-2 pathway. Metabolomic analysis revealed that MNE treatment modulated many lipid metabolites in alcohol-treated HepG2 cells. Our study findings provide evidence for the efficacy and mechanisms of MNE in ameliorating alcohol-induced liver injury.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Etanol , Camundongos , Animais , Etanol/efeitos adversos , Etanol/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Fígado/metabolismo , Metabolismo dos Lipídeos , Redes e Vias Metabólicas , Camundongos Endogâmicos C57BL
13.
J Nanobiotechnology ; 22(1): 156, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589867

RESUMO

Immunotherapy has revolutionized the treatment of cancer. However, its efficacy remains to be optimized. There are at least two major challenges in effectively eradicating cancer cells by immunotherapy. Firstly, cancer cells evade immune cell killing by down-regulating cell surface immune sensors. Secondly, immune cell dysfunction impairs their ability to execute anti-cancer functions. Radiotherapy, one of the cornerstones of cancer treatment, has the potential to enhance the immunogenicity of cancer cells and trigger an anti-tumor immune response. Inspired by this, we fabricate biofunctionalized liposome-like nanovesicles (BLNs) by exposing irradiated-cancer cells to ethanol, of which ethanol serves as a surfactant, inducing cancer cells pyroptosis-like cell death and facilitating nanovesicles shedding from cancer cell membrane. These BLNs are meticulously designed to disrupt both of the aforementioned mechanisms. On one hand, BLNs up-regulate the expression of calreticulin, an "eat me" signal on the surface of cancer cells, thus promoting macrophage phagocytosis of cancer cells. Additionally, BLNs are able to reprogram M2-like macrophages into an anti-cancer M1-like phenotype. Using a mouse model of malignant pleural effusion (MPE), an advanced-stage and immunotherapy-resistant cancer model, we demonstrate that BLNs significantly increase T cell infiltration and exhibit an ablative effect against MPE. When combined with PD-1 inhibitor (α-PD-1), we achieve a remarkable 63.6% cure rate (7 out of 11) among mice with MPE, while also inducing immunological memory effects. This work therefore introduces a unique strategy for overcoming immunotherapy resistance.


Assuntos
Lipossomos , Neoplasias , Humanos , Lipossomos/metabolismo , Neoplasias/radioterapia , Neoplasias/metabolismo , Macrófagos/metabolismo , Imunoterapia , Etanol/metabolismo , Linhagem Celular Tumoral
14.
Wiad Lek ; 77(2): 268-272, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38592988

RESUMO

OBJECTIVE: Aim: To find out the age remodeling of the structural components of the prostate gland at alcohol poisoning using quantitative morphological analysis. PATIENTS AND METHODS: Materials and Methods: The structure of the prostate gland of 4 white male rats groups were morphologically investigated. The 1 group included 30 control intact animals aged 8 months, the 2-nd group - 30 rats aged 24 months, the 3-rd group - 30 8-month-old animals with ethanol intoxication, and the 4-th group included 30 24-month-old rats with the specified simulated pathology. Ethanol intoxication was modeled by intragastric administration of 30% ethyl alcohol solution at a dose of 20 ml/kg once daily for 28 days. Rats were euthanized by bloodletting under general thiopental anesthesia 28 days after the beginning of the experiment. The area of glands, the height of glandular epithelial cells, the area of their nuclei and cytoplasm, the nuclear-cytoplasmic ratio in these cells and the stromal-parenchymal ratio in the organ were studied using light microscopy and were determined morphometrically. Morphometric parameters were processed statistically. RESULTS: Results: It was established that with age in the intact prostate of laboratory sexually mature white male rats, the area of glands, the height of glandular epitheliocytes, the area of their nuclei and cytoplasm, with the stability of nuclear-cytoplasmic ratios in the epithelial cells of the glands, significantly decreases, and the stromal-parenchymal ratio in the organ under study increases. Long-term ethanol poisoning leads to pronounced structural changes in the prostate, which is characterized by pronounced atrophy of the glandular epithelium, a decrease in the area of the glands, a decrease in the height of epithelial cells, a violation of nuclear-cytoplasmic relations in them, an increase in stromal-parenchymal ratio, and a prominent growth of the muscle-elastic stroma. The revealed structural changes of the studied components of the prostate dominated in 24-month-old experimental animals. CONCLUSION: Conclusions: Morphological analysis of the prostate gland established that morphometric and morphological changed significantly according to the age and were depend on the ethanol poisoning.


Assuntos
Intoxicação Alcoólica , Próstata , Ratos , Animais , Masculino , Intoxicação Alcoólica/patologia , Etanol , Animais de Laboratório , Células Epiteliais
15.
J Spec Pediatr Nurs ; 29(2): e12425, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38598084

RESUMO

PURPOSE: Substance use, that is of cigarettes, alcohol and chemical inhalants, is a major contributor to health-compromising behaviors and the related consequences among adolescents around the world. The purpose of this paper is to examine trends in this phenomenon in South Korea among sexually active adolescents who reported sexual minority behaviors as compared to their heterosexual (HS) peers. DESIGN AND METHODS: This study used data from the annual web-based survey called Korea Youth Risk Behavior Survey in 5-year intervals: 2006, 2011, and 2016. From 2017, the questions regarding the gender of sex partners were excluded from the survey, thus no data is available for sexual minorities after 2016. Selected data (Unweighted n = 10,029) was used to assess whether substance use increased, decreased, or remained unchanged among adolescents who reported same-sex (SS) behaviors and bisexual (BS) behaviors compared to their peers reporting HS behaviors. Demographic variables included age and assigned gender. Substances referred to are cigarettes, alcohol, and chemical inhalants. Logistic regression models were sex-stratified according to assigned gender. Trend analyses were carried out to examine disparities in substance use among sexually active adolescents across the three survey years. RESULTS: Across the three survey years, cigarette use, alcohol use, and problematic drinking declined among all sexually active youths, but there were some differences among the subgroups. In 2016, SS girls were more likely to use cigarettes than HS girls. The prevalence of alcohol use and problematic drinking among BS girls was relatively higher than among girls who exhibited either HS or SS behaviors. Inhalant use was very high among both boys and girls with SS and BS behaviors. PRACTICE IMPLICATIONS: The findings of the study reveal disparities in substance use between sexual minority and heterosexual adolescents in South Korea. This creates an alarm for collecting data separately for sexually diverse youth in future Korean national surveys with a goal of reducing substance use among all adolescents.


Assuntos
Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , Masculino , Feminino , Humanos , Adolescente , República da Coreia/epidemiologia , Etanol , Comportamentos Relacionados com a Saúde , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
16.
J Med Internet Res ; 26: e52118, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598286

RESUMO

BACKGROUND: Children whose parents have alcohol use problems are at an increased risk of several negative consequences, such as poor school performance, an earlier onset of substance use, and poor mental health. Many would benefit from support programs, but the figures reveal that only a small proportion is reached by existing support. Digital interventions can provide readily accessible support and potentially reach a large number of children. Research on digital interventions aimed at this target group is scarce. We have developed a novel digital therapist-assisted self-management intervention targeting adolescents whose parents had alcohol use problems. This program aims to strengthen coping behaviors, improve mental health, and decrease alcohol consumption in adolescents. OBJECTIVE: This study aims to examine the effectiveness of a novel web-based therapist-assisted self-management intervention for adolescents whose parents have alcohol use problems. METHODS: Participants were recruited on the internet from social media and websites containing health-related information about adolescents. Possible participants were screened using the short version of the Children of Alcoholics Screening Test-6. Eligible participants were randomly allocated to either the intervention group (n=101) or the waitlist control group (n=103), and they were unblinded to the condition. The assessments, all self-assessed, consisted of a baseline and 2 follow-ups after 2 and 6 months. The primary outcome was the Coping With Parents Abuse Questionnaire (CPAQ), and secondary outcomes were the Center for Epidemiological Studies Depression Scale, Alcohol Use Disorders Identification Test (AUDIT-C), and Ladder of Life (LoL). RESULTS: For the primary outcome, CPAQ, a small but inconclusive treatment effect was observed (Cohen d=-0.05 at both follow-up time points). The intervention group scored 38% and 46% lower than the control group on the continuous part of the AUDIT-C at the 2- and 6-month follow-up, respectively. All other between-group comparisons were inconclusive at either follow-up time point. Adherence was low, as only 24% (24/101) of the participants in the intervention group completed the intervention. CONCLUSIONS: The findings were inconclusive for the primary outcome but demonstrate that a digital therapist-assisted self-management intervention may contribute to a reduction in alcohol consumption. These results highlight the potential for digital interventions to reach a vulnerable, hard-to-reach group of adolescents but underscore the need to develop more engaging support interventions to increase adherence. TRIAL REGISTRATION: ISRCTN Registry ISRCTN41545712; https://www.isrctn.com/ISRCTN41545712?q=ISRCTN41545712. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/1471-2458-12-35.


Assuntos
Alcoolismo , Adolescente , Humanos , Criança , Etanol , Consumo de Bebidas Alcoólicas , 60670 , Internet , Pais
17.
World J Microbiol Biotechnol ; 40(5): 155, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581587

RESUMO

The study aims to enhance ethanol production by Wickerhamomyces subpelliculosus ZE75 isolated from marine sediment. In addition, analyzing the kinetic parameters of ethanol production and optimization of the fermentation conditions was performed. The marine yeast isolate ZE75 was selected as the front runner ethanol-producer, with an ethanol yield of 89.77 gL-1. ZE75 was identified relying on the phenotypic and genotypic characteristics of W. subpelliculosus. The genotypic characterization based on the Internal Transcribed Spacer (ITS) sequence was deposited in the GenBank database with the accession number OP715873. The maximum specific ethanol production rate (vmax) was 0.482 gg-1 h-1 at 175 gL-1 glucose concentration, with a high accuracy of R2 0.95. The maximum growth specific rates (µmax) were 0.141 h-1 obtained at 150 gL-1 glucose concentration with R2 0.91. Optimization of the fermentation parameters such as pH and salinity has been achieved. The highest ethanol yield 0.5637 gg-1 was achieved in a 100% natural seawater-based medium. The maximum ethanol production of 104.04 gL-1 was achieved at pH 4.5 with a specific ethanol rate of 0.1669 gg-1 h-1. The findings of the present study recommend the possibility of ethanol production from a seawater-based medium on a large scale using W. subpelliculosus ZE75.


Assuntos
Etanol , Saccharomycetales , Leveduras , Fermentação , Glucose
19.
Biol Res ; 57(1): 15, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576018

RESUMO

BACKGROUND: Alcohol, a widely abused drug, significantly diminishes life quality, causing chronic diseases and psychiatric issues, with severe health, societal, and economic repercussions. Previously, we demonstrated that non-voluntary alcohol consumption increases the opening of Cx43 hemichannels and Panx1 channels in astrocytes from adolescent rats. However, whether ethanol directly affects astroglial hemichannels and, if so, how this impacts the function and survival of astrocytes remains to be elucidated. RESULTS: Clinically relevant concentrations of ethanol boost the opening of Cx43 hemichannels and Panx1 channels in mouse cortical astrocytes, resulting in the release of ATP and glutamate. The activation of these large-pore channels is dependent on Toll-like receptor 4, P2X7 receptors, IL-1ß and TNF-α signaling, p38 mitogen-activated protein kinase, and inducible nitric oxide (NO) synthase. Notably, the ethanol-induced opening of Cx43 hemichannels and Panx1 channels leads to alterations in cytokine secretion, NO production, gliotransmitter release, and astrocyte reactivity, ultimately impacting survival. CONCLUSION: Our study reveals a new mechanism by which ethanol impairs astrocyte function, involving the sequential stimulation of inflammatory pathways that further increase the opening of Cx43 hemichannels and Panx1 channels. We hypothesize that targeting astroglial hemichannels could be a promising pharmacological approach to preserve astrocyte function and synaptic plasticity during the progression of various alcohol use disorders.


Assuntos
Alcoolismo , Conexina 43 , Camundongos , Ratos , Animais , Conexina 43/metabolismo , Astrócitos/metabolismo , Etanol/toxicidade , Etanol/metabolismo , Alcoolismo/metabolismo , Células Cultivadas , Conexinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo
20.
BMC Complement Med Ther ; 24(1): 148, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580956

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of stacked ß-amyloid peptides in the brain and associated with the generation of oxidative stress. So far, there is no cure for AD or a way to stop its progression. Although the neuroprotective effects of Ganoderma lucidum aqueous extract and G. lucidum-derived triterpenoids and polysaccharides have been reported, the influence of G. lucidum-fermented crops on AD still lacks clarity. METHODS: This study aimed to investigate the protective effect of G. lucidum-fermented crop extracts against hydrogen peroxide- or ß-amyloid peptide (Aß25-35)-induced damage in human neuroblastoma SH-SY5Y cells. RESULTS: Various extracts of G. lucidum-fermented crops, including extract A: 10% ethanol extraction using microwave, extract B: 70˚C water extraction, and extract C: 100˚C water extraction followed by ethanol precipitation, were prepared and analyzed. Extract B had the highest triterpenoid content. Extract C had the highest total glucan content, while extract A had the highest gamma-aminobutyric acid (GABA) content. The median inhibitory concentration (IC50, mg/g) for DPPH and ABTS scavenging activity of the fermented crop extracts was significantly lower than that of the unfermented extract. Pretreatment with these extracts significantly increased the cell viability of SH-SY5Y cells damaged by H2O2 or Aß25-35, possibly by reducing cellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Moreover, extract B markedly alleviated the activity of acetylcholinesterase (AChE), which is crucial in the pathogenesis of AD. CONCLUSION: These results clearly confirmed the effects of G. lucidum-fermented crop extracts on preventing against H2O2- or Aß25-35-induced neuronal cell death and inhibiting AChE activity, revealing their potential in management of AD.


Assuntos
Neuroblastoma , Reishi , Humanos , Peróxido de Hidrogênio/toxicidade , Acetilcolinesterase , Neuroblastoma/patologia , Antioxidantes/farmacologia , Peptídeos beta-Amiloides/toxicidade , Etanol , Água
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