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1.
Cell Metab ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38718791

RESUMO

The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) and its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen prevents NASH development as well as ameliorates established NASH and fibrosis without affecting total calorie intake. Furthermore, the IF 5:2 regimen blunted NASH-HCC transition when applied therapeutically. The timing, length, and number of fasting cycles as well as the type of NASH diet were critical parameters determining the benefits of fasting. Combined proteome, transcriptome, and metabolome analyses identified that peroxisome-proliferator-activated receptor alpha (PPARα) and glucocorticoid-signaling-induced PCK1 act co-operatively as hepatic executors of the fasting response. In line with this, PPARα targets and PCK1 were reduced in human NASH. Notably, only fasting initiated during the active phase of mice robustly induced glucocorticoid signaling and free-fatty-acid-induced PPARα signaling. However, hepatocyte-specific glucocorticoid receptor deletion only partially abrogated the hepatic fasting response. In contrast, the combined knockdown of Ppara and Pck1 in vivo abolished the beneficial outcomes of fasting against inflammation and fibrosis. Moreover, overexpression of Pck1 alone or together with Ppara in vivo lowered hepatic triglycerides and steatosis. Our data support the notion that the IF 5:2 regimen is a promising intervention against NASH and subsequent liver cancer.

2.
J Food Sci ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38660924

RESUMO

This study was conducted to evaluate the effect of two distances: close (0-10 m) and far (60 m) from the heavy traffic roadside, at three different cultivation sites (MS: Mevlanakapi-Silivrikapi, SB: Silivrikapi-Belgradkapi, and BY: Belgradkapi-Yedikule kapi) along the road line. First, the phenolic compounds, antioxidant activity, and physicochemical properties in kale and arugula vegetables were examined. Second, heavy metal concentrations in vegetables, soil, and irrigated water were investigated. In both vegetables, the highest total phenolic content was detected in samples obtained from far distance in SB site (3880.3 mg/kg) for kale and in BY site (1459.9 mg/kg) for arugula, whereas the lowest content was found at the close distance in MS site for both kale (448.5 mg/kg) and arugula (586.4 mg/kg). The antioxidant activity values [mg Trolox/kg (dw)] ranged from 366.74 to 586.10 and 2349.00 to 3757.4 for kale and from 520.00 to 945.60 and 3323.00 to 5814.70 for arugula in 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl methods, respectively. The levels of Cd and Hg in kale and arugula and Fe content in arugula exceeded FAO/WHO permissible limits, making them unsafe for human consumption. Meanwhile, the Pb content in kale and arugula and Fe content in kale were observed to be within acceptable limits set by FAO/WHO. In the irrigated water, the Pb value was below the permissible limit, whereas the Cd value was above it and no Hg and Fe were detected. In the soil samples, the Pb and Fe values were below the limit, whereas the Cd and Hg values were higher.

3.
Food Chem ; 448: 139185, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38574715

RESUMO

The impact of hydrogen (H2) producing magnesium (Mg) incorporation into minced beef meat (MBM) on the quality and safety of the product was investigated. The H2-producing Mg (H2-P-Mg)-incorporated MBMs were vacuumed (VP) and stored at 4 °C for 12 days. Other MBMs were vacuumed and gassed with H2 or N2. At the end of storage, the lowest browning index values were for H2 and H2-P-Mg samples. H2- PMg and VP methods generally decreased the counts of mesophilic and psychrotrophic bacteria and yeast molds and restricted the formation of thiobarbituric acid reactive substances and biogenic amines. Heat mapping, PCA, and multivariate analysis methods confirmed chemical analysis results. The volatile compounds were at their highest levels in the control samples at the end of storage, followed by H2, N2, H2-P-Mg, and VP samples. Using the H2-P-Mg method in MBM preparation could protect the quality characteristics and safety of the product during cold storage.


Assuntos
Conservação de Alimentos , Armazenamento de Alimentos , Hidrogênio , Magnésio , Animais , Bovinos , Hidrogênio/metabolismo , Hidrogênio/análise , Magnésio/análise , Magnésio/metabolismo , Conservação de Alimentos/métodos , Temperatura Baixa , Produtos da Carne/análise , Produtos da Carne/microbiologia , Bactérias/metabolismo , Bactérias/isolamento & purificação , Carne Vermelha/análise , Carne Vermelha/microbiologia
4.
Cell Mol Life Sci ; 81(1): 115, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436764

RESUMO

INTRODUCTION: The Hippo pathway and its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are targets for cancer therapy. It is important to determine if the activation of one factor compensates for the inhibition of the other. Moreover, it is unknown if YAP/TAZ-directed perturbation affects cell-cell communication of non-malignant liver cells. MATERIALS AND METHODS: To investigate liver-specific phenotypes caused by YAP and TAZ inactivation, we generated mice with hepatocyte (HC) and biliary epithelial cell (BEC)-specific deletions for both factors (YAPKO, TAZKO and double knock-out (DKO)). Immunohistochemistry, single-cell sequencing, and proteomics were used to analyze liver tissues and serum. RESULTS: The loss of BECs, liver fibrosis, and necrosis characterized livers from YAPKO and DKO mice. This phenotype was weakened in DKO tissues compared to specimens from YAPKO animals. After depletion of YAP in HCs and BECs, YAP expression was induced in non-parenchymal cells (NPCs) in a cholestasis-independent manner. YAP positivity was detected in subgroups of Kupffer cells (KCs) and endothelial cells (ECs). The secretion of pro-inflammatory chemokines and cytokines such as C-X-C motif chemokine ligand 11 (CXCL11), fms-related receptor tyrosine kinase 3 ligand (FLT3L), and soluble intercellular adhesion molecule-1 (ICAM1) was increased in the serum of YAPKO animals. YAP activation in NPCs could contribute to inflammation via TEA domain transcription factor (TEAD)-dependent transcriptional regulation of secreted factors. CONCLUSION: YAP inactivation in HCs and BECs causes liver damage, and concomitant TAZ deletion does not enhance but reduces this phenotype. Additionally, we present a new mechanism by which YAP contributes to cell-cell communication originating from NPCs.


Assuntos
Comunicação Celular , Fígado , Proteínas de Sinalização YAP , Animais , Camundongos , Comunicação Celular/genética , Células Endoteliais , Hepatócitos , Ligantes , Fígado/metabolismo , Proteínas de Sinalização YAP/genética , Proteínas de Sinalização YAP/metabolismo
5.
Sci Rep ; 14(1): 4806, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413692

RESUMO

The study aims to explore a novel approach for fabricating plasmonic nanostructures to enhance the optical properties and performance of various optoelectronic devices. The research begins by employing a piezo-inkjet printing technique to deposit drops containing Ag nanoparticles (NPs) onto a glass substrate at a predefined equidistance, with the goal of obtaining arrays of Ag microdots (Ag-µdots) on the glass substrate. This process is followed by a thermal annealing treatment. The printing parameters are first optimized to achieve uniform deposition of different sizes of Ag-µdots arrays by controlling the number of Ag ink drops. Subsequently, the printed arrays undergo thermal annealing at various temperatures in air for 60 min, enabling precise and uniform control over nanoparticle formation. The printed Ag nanoparticles are characterized using field emission scanning electron microscopy and atomic force microscopy to analyze their morphological features, ensuring their suitability for plasmonic applications. UV-Vis spectrophotometry is employed to investigate the enhanced surface-plasmonic-resonance properties of the printed AgNPs. Measurements confirm that the equidistant arrays of AgNPs obtained from annealing Ag microdots exhibit enhanced light-matter interaction, leading to a surface plasmon resonance response dependent on the Ag NPs' specific surface area. These enhanced surface plasmonic resonances open avenues for developing cutting-edge optoelectronic devices that leverage the benefits of plasmonic nanostructures, thereby enabling new opportunities for future technological developments across various fields.

6.
ACS Omega ; 9(6): 7053-7060, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38371798

RESUMO

Perovskite solar cells (PSCs) have garnered significant attention in the scientific community due to their rapid increase in performance. Inorganic perovskite devices have been noted for their high performance and long-term stability. This study introduces a device optimization process guided by modeling to produce high-efficiency PSCs using lead-free n-i-p methylammonium tin bromide (MASnBr3) materials. We have thoroughly examined the impact of both the absorber and interface layers on the optimized structure. Our approach utilized graphene as the interface layer between the hole transport and absorber layers. We employed zinc oxide (ZnO)/Al and 3C-SiC as interface layers between the absorber and electron transport layers. The optimization process involved adjusting the thicknesses of the absorber layer and interface layers and minimizing defect densities. Our proposed optimized device structure, ZnO/3C-SiC/MASnBr3/graphene/CuO/Au, demonstrates theoretical power conversion efficiencies of 31.97%, fill factors of 89.38%, a current density of 32.54 mA/cm2, a voltage of 1.112 V, and a quantum efficiency of 94%. This research underscores the ability of MASnBr3 as a nontoxic perovskite material for sustainable energy from renewable sources' applications.

7.
ACS Omega ; 9(1): 545-558, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38222644

RESUMO

The effect of Ga-substitution on bismuth ferrite BiGaxFe1-xO3 (x = 0, 0.05, 0.10, 0.15, 0.20, and 0.25) properties was investigated, which was fabricated using a microemulsion route. X-ray diffraction analysis confirmed that specimens had a single-phase rhombohedral structure with space group R3̅c. The concentration of Ga had an impact on various properties such as structural parameters, crystalline size, porosity, and unit cell volume. The samples exhibited notable values for the dielectric constant, tangent loss, and dielectric loss in the low-frequency range, which declined as the frequency increased due to different polarizations. The increment in the AC conductivity was associated with rise in frequency. The P-E loops demonstrated that the samples became more resistive as the Ga concentration increased. The retentivity (Mr) and saturation magnetization (Ms) values reduced as the Ga content increased, although all samples had Hc values within the range for electromagnetic materials. The Ga-substitution had a synergistic effect on the electrochemical characteristics of BiGaxFe1-xO3, resulting in greater conductivity than that of undoped BiFeO3. These enhanced properties contributed to their higher photocatalytic activity in the degradation of crystal violet under visible light irradiation. The doped BiGaxFe1-xO3 exhibited 79% dye degradation after 90 min of illumination compared to 54% for pure BiFeO3. Recycling experiments confirmed the stability and reusability of the synthesized nanoparticles. The antibacterial activity of the samples was certified against various microbes, and the doped BiGaxFe1-xO3 showed promising activity. Thus, doped materials are good candidates for memories, dielectric resonators, and photovoltaics because of their high dielectric constant and AC conductivity, while their higher photocatalytic activity under visible light makes them promising photocatalysts for removing noxious and harmful effluents from wastewaters.

8.
Chem Biol Drug Des ; 103(1): e14408, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38009559

RESUMO

The emergency of tyrosine kinase inhibitors has remarkably enhanced the clinical outcomes of cancer therapy, especially the use of EGFR inhibitors for non-small cell lung cancer (NSCLC). However, acquired resistance is inevitable after 8-12 months treatment. New agents or treatments are urgently required to resolve this problem. In this study, we identified that compound ZYZ384 can selectively inhibit the growth of gefitinib-resistant (G-R) lung cancer cells, without affecting that of normal lung epithelial cells. ZYZ384 induced G2 arrest in G-R NSCLC cells, decreasing the expression of Cyclin B1 and increasing the expression of P21. Meanwhile, ZYZ384 also induced apoptosis in NSCLC cells and correspondingly increased the expression of cleaved Caspase 3, 8, and 9 proteins. The expression of p-JNK, p-P38, and p-ERK were also increased in H1975 NSCLC cells treated with ZYZ384. Finally, we observed that the JNK inhibitor effectively reversed the pro-apoptotic effect of ZYZ384. In conclusion, ZYZ384 is a potential therapeutic agent to inhibit the growth of NSCLCs with EGFR mutations through activating JNK, which will help the development of related anticancer drugs.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Quinazolinas/farmacologia , Receptores ErbB/metabolismo , Linhagem Celular Tumoral , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transdução de Sinais , Apoptose , Resistencia a Medicamentos Antineoplásicos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
9.
Eur Radiol ; 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38133672

RESUMO

OBJECTIVES: Coronary artery calcifications (CACs) indicate the presence of coronary artery disease. CAC can be found on thoracic computed tomography (CT) conducted for non-cardiac reasons. This systematic review and meta-analysis of non-gated thoracic CT aims to assess the clinical impact and prevalence of CAC. METHODS: Online databases were searched for articles assessing prevalence, demographic characteristics, accuracy and prognosis of incidental CAC on non-gated thoracic CT. Meta-analysis was performed using a random effects model. RESULTS: A total of 108 studies (113,406 patients) were included (38% female). Prevalence of CAC ranged from 2.7 to 100% (pooled prevalence 52%, 95% confidence interval [CI] 46-58%). Patients with CAC were older (pooled standardised mean difference 0.88, 95% CI 0.65-1.11, p < 0.001), and more likely to be male (pooled odds ratio [OR] 1.95, 95% CI 1.55-2.45, p < 0.001), with diabetes (pooled OR 2.63, 95% CI 1.95-3.54, p < 0.001), hypercholesterolaemia (pooled OR 2.28, 95% CI 1.33-3.93, p < 0.01) and hypertension (pooled OR 3.89, 95% CI 2.26-6.70, p < 0.001), but not higher body mass index or smoking. Non-gated CT assessment of CAC had excellent agreement with electrocardiogram-gated CT (pooled correlation coefficient 0.96, 95% CI 0.92-0.98, p < 0.001). In 51,582 patients, followed-up for 51.6 ± 27.4 months, patients with CAC had increased all cause mortality (pooled relative risk [RR] 2.13, 95% CI 1.57-2.90, p = 0.004) and major adverse cardiovascular events (pooled RR 2.91, 95% CI 2.26-3.93, p < 0.001). When CAC was present on CT, it was reported in between 18.6% and 93% of reports. CONCLUSION: CAC is a common, but underreported, finding on non-gated CT with important prognostic implications. CLINICAL RELEVANCE STATEMENT: Coronary artery calcium is an important prognostic indicator of cardiovascular disease. It can be assessed on non-gated thoracic CT and is a commonly underreported finding. This represents a significant population where there is a potential missed opportunity for lifestyle modification recommendations and preventative therapies. This study aims to highlight the importance of reporting incidental coronary artery calcium on non-gated thoracic CT. KEY POINTS: • Coronary artery calcification is a common finding on non-gated thoracic CT and can be reliably identified compared to gated-CT. • Coronary artery calcification on thoracic CT is associated with an increased risk of all cause mortality and major adverse cardiovascsular events. • Coronary artery calcification is frequently not reported on non-gated thoracic CT.

10.
Inquiry ; 60: 469580231218421, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38140893

RESUMO

In Ethiopia, the WHO strategies to stop coronavirus transmission were implemented rapidly. As a result, there was a rapid change in hygiene behavior, which are basic for preventing COVID-19 and other contagious diseases. This research was designed to examine the sustainability of the COVID-19 imposed hygiene behaviors for future challenges. The study was conducted in 2 major nexus areas in Addis Ababa. The data were collected using a questionnaire and spot-check from 622 respondents selected by systematic random sampling. The questionnaire was given at every 15th interval in several spots of the site. Observational hygiene-check was done through observing key personal hygiene conditions. Proportion, χ2 test, and Poisson's regression were applied for the analysis. The χ2-test analyses showed that the hand washing frequency before, during, and post-COVID-19 was statistically significant (P < .005). Findings from the spot-check also show that the hands of 76.8%, the nails of 68.7%, and the hairs of 70.7% of the respondents were clean. The major driving factors for the rapid changes in hygiene behavior were the awareness developed (95%), the fear and panic (90%), and increased access to water and soap (63%). Nevertheless, the major reasons for failing to continue the COVID-19-imposed good hygiene practice in the post-COVID-19 times include the decline in infection and death rates (26%) and the decline in facility access (20%). Hand washing frequency significantly changed during the COVID-19 pandemic indicating that the practice as part of the preventive strategy was successful. However, as this was mainly due to the fear and panic in the community, the COVID-19 imposed hand washing practice did not bring real and sustainable behavioral changes. This indicates that for long-lasting changes in hygiene behavior, continuous and better approach need to be introduced.


Assuntos
COVID-19 , Humanos , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Etiópia , Higiene , Desinfecção das Mãos
12.
Hepatology ; 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37916976

RESUMO

BACKGROUND AND AIMS: HCC is the most common primary liver tumor, with an increasing incidence worldwide. HCC is a heterogeneous malignancy and usually develops in a chronically injured liver. The NF-κB signaling network consists of a canonical and a noncanonical branch. Activation of canonical NF-κB in HCC is documented. However, a functional and clinically relevant role of noncanonical NF-κB and its downstream effectors is not established. APPROACH AND RESULTS: Four human HCC cohorts (total n = 1462) and 4 mouse HCC models were assessed for expression and localization of NF-κB signaling components and activating ligands. In vitro , NF-κB signaling, proliferation, and cell death were measured, proving a pro-proliferative role of v-rel avian reticuloendotheliosis viral oncogene homolog B (RELB) activated by means of NF-κB-inducing kinase. In vivo , lymphotoxin beta was identified as the predominant inducer of RELB activation. Importantly, hepatocyte-specific RELB knockout in a murine HCC model led to a lower incidence compared to controls and lower maximal tumor diameters. In silico , RELB activity and RELB-directed transcriptomics were validated on the The Cancer Genome Atlas HCC cohort using inferred protein activity and Gene Set Enrichment Analysis. In RELB-active HCC, pathways mediating proliferation were significantly activated. In contrast to v-rel avian reticuloendotheliosis viral oncogene homolog A, nuclear enrichment of noncanonical RELB expression identified patients with a poor prognosis in an etiology-independent manner. Moreover, RELB activation was associated with malignant features metastasis and recurrence. CONCLUSIONS: This study demonstrates a prognostically relevant, etiology-independent, and cross-species consistent activation of a lymphotoxin beta/LTßR/RELB axis in hepatocarcinogenesis. These observations may harbor broad implications for HCC, including possible clinical exploitation.

13.
Front Vet Sci ; 10: 1238634, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37937155

RESUMO

Introduction: Brucella, a type of intracellular Gram-negative bacterium, has unique features and acts as a zoonotic pathogen. It can lead to abortion and infertility in animals. Eliminating brucellosis becomes very challenging once it spreads among both humans and animals, putting a heavy burden on livestock and people worldwide. Given the increasing spread of brucellosis, it is crucial to develop improved vaccines for susceptible animals to reduce the disease's impact. Methods: In this study, we effectively used an immunoinformatics approach with advanced computer software to carefully identify and analyze important antigenic parts of Brucella abortus. Subsequently, we skillfully designed chimeric peptides to enhance the vaccine's strength and effectiveness. We used computer programs to find four important parts of the Brucella bacteria that our immune system recognizes. Then, we carefully looked for eight parts that are recognized by a type of white blood cell called cytotoxic T cells, six parts recognized by T helper cells, and four parts recognized by B cells. We connected these parts together using a special link, creating a strong new vaccine. To make the vaccine even better, we added some extra parts called molecular adjuvants. These included something called human ß-defensins 3 (hBD-3) that we found in a database, and another part that helps the immune system called PADRE. We attached these extra parts to the beginning of the vaccine. In a new and clever way, we made the vaccine even stronger by attaching a part from a mouse's immune system to the end of it. This created a new kind of vaccine called MEV-Fc. We used advanced computer methods to study how well the MEV-Fc vaccine interacts with certain receptors in the body (TLR-2 and TLR-4). Results: In the end, Immunosimulation predictions showed that the MEV-Fc vaccine can make the immune system respond strongly, both in terms of cells and antibodies. Discussion: In summary, our results provide novel insights for the development of Brucella vaccines. Although further laboratory experiments are required to assess its protective effect.

14.
RSC Adv ; 13(45): 31426-31434, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37901272

RESUMO

We report on the fabrication of hybrid composite poly 4-vinlyphenol (PVPh)/graphene thin film via cost-effective electrospray atomization deposition technique. Thin films fabricated through manipulating deposition technique in two different ways which are blending and layer by layer (LBL). For investigation of PVPh/graphene hybrid composite dielectric behavior in comparison to PVPh; three asymmetric MIS thin film capacitors were fabricated, where dielectric thin films (i) PVPh and (ii & iii) hybrid composite thin films PVPh/graphene (blended and LBL) were sandwiched between electrodes i.e. indium tin oxide (ITO) and p-type semiconductor poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). The dielectric properties of the thin films were characterized for frequencies 1 to 100 kHz while utilizing the MIS thin film capacitors. The capacitance obtained at 1 kHz frequency for PVPh/graphene (LBL) dielectric layer at the voltage range ±10 volts was 8.5 mF cm-2 while for blended PVPh/graphene thin film the capacitance at the voltage range ±3 volts was 0.40 µF cm-2 and for pristine PVPh as dielectric layer the capacitance at voltage range ±1 volts was 1.45 µF cm-2. Similarly, even at higher frequencies up to 100 kHz, the PVPh/graphene (LBL) showed stable behavior. Thus, the composite PVPh/graphene (LBL) thin film has a better dielectric nature compared to the composite PVPh/graphene (blended) thin film, even at higher frequencies with larger operational voltage window. This distinguishing nature of the composite PVP/graphene (LBL) is attributed to increase in dielectric constant due to graphene flakes in between PVPh. For the thin films LBL and blended PVPh/graphene, the calculated dielectric constant at 10 kHz is 6.7 and 0.023 while at 100 kHz it is 2 and 0.0167, respectively.

15.
Pediatric Health Med Ther ; 14: 337-345, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901587

RESUMO

Food protein-induced enterocolitis syndrome (FPIES) is a form of non-IgE mediated food allergy that presents with delayed gastrointestinal symptoms after ingestion of the trigger food. The data regarding FPIES are sparse, despite being recognized as a distinct clinical entity. This narrative review presents the characteristics of this disorder in the pediatric population, as well-standard diagnostic and management protocols. FPIES can be classified into acute and chronic subtypes, and some cases may develop into an IgE-mediated allergy. Given that skin prick tests and specific IgE levels are negative in the majority of cases, diagnosis relies on clinical history and oral food challenges. Management involves elimination diets, assessment of tolerance through oral food challenges, and rehydration in the event of a reaction. Future research should focus on improving diagnostic methods, illustrating underlying pathogenesis and biomarkers, and assessing long-term natural history. Increased knowledge and awareness for FPIES are required.

16.
Molecules ; 28(18)2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37764279

RESUMO

A novel series of nitrostyrene-based spirooxindoles were synthesized via the reaction of substituted isatins 1a-b, a number of α-amino acids 2a-e and (E)-2-aryl-1-nitroethenes 3a-e in a chemo/regio-selective manner using [3+2] cycloaddition (Huisgen) reaction under microwave irradiation conditions. The structure elucidation of all the synthesized spirooxindoles were done using 1H and 13C NMR and HRMS spectral analysis. The single crystal X-ray crystallographic study of compound 4l was used to assign the stereochemical arrangements of the groups around the pyrrolidine ring in spiro[pyrrolidine-2,3'-oxindoles] skeleton. The in vitro anticancer activity of spiro[pyrrolidine-2,3'-oxindoles] analogs 4a-w against human lung (A549) and liver (HepG2) cancer cell lines along with immortalized normal lung (BEAS-2B) and liver (LO2) cell lines shows promising results. Out of the 23 synthesized spiro[pyrrolidine-2,3'-oxindoles], while five compounds (4c, 4f, 4m, 4q, 4t) (IC50 = 34.99-47.92 µM; SI = 0.96-2.43) displayed significant in vitro anticancer activity against human lung (A549) cancer cell lines, six compounds (4c, 4f, 4k, 4m, 4q, 4t) (IC50 = 41.56-86.53 µM; SI = 0.49-0.99) displayed promising in vitro anticancer activity against human liver (HepG2) cancer cell lines. In the case of lung (A549) cancer cell lines, these compounds were recognized to be more efficient and selective than standard reference artemisinin (IC50 = 100 µM) and chloroquine (IC50 = 100 µM; SI: 0.03). However, none of them were found to be active as compared to artesunic acid [IC50 = 9.85 µM; SI = 0.76 against lung (A549) cancer cell line and IC50 = 4.09 µM; SI = 2.01 against liver (HepG2) cancer cell line].


Assuntos
Antifibrinolíticos , Micro-Ondas , Humanos , Oxindóis , Fígado , Aminoácidos
18.
Ann Allergy Asthma Immunol ; 131(6): 752-758.e1, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37689113

RESUMO

BACKGROUND: Epinephrine is the first-line treatment for anaphylaxis but is often replaced with antihistamines or corticosteroids. Delayed epinephrine administration is a risk factor for fatal anaphylaxis. Convincing data on the role of antihistamines and corticosteroids in anaphylaxis management are sparse. OBJECTIVE: To establish the impact of prehospital treatment with epinephrine, antihistamines, and/or corticosteroids on anaphylaxis management. METHODS: Patients presenting with anaphylaxis were recruited prospectively and retrospectively in 10 Canadian and 1 Israeli emergency departments (EDs) between April 2011 and August 2022, as part of the Cross-Canada Anaphylaxis REgistry. Data on anaphylaxis cases were collected using a standardized form. Primary outcomes were uncontrolled reactions (>2 doses of epinephrine in ED), no prehospital epinephrine use, use of intravenous fluids in ED, and hospital admission. Multivariate regression was used to identify factors associated with primary outcomes. RESULTS: Among 5364 reactions recorded, median age was 8.8 years (IQR, 3.78-16.9); 54.9% of the patients were males, and 52.5% had a known food allergy. In the prehospital setting, 37.9% received epinephrine; 44.3% received antihistamines, and 3.15% received corticosteroids. Uncontrolled reactions happened in 250 reactions. Patients treated with prehospital epinephrine were less likely to have uncontrolled reactions (adjusted odds ratio [aOR], 0.955 [95% CI, 0.943-0.967]), receive intravenous fluids in ED (aOR, 0.976 [95% CI, 0.959-0.992]), and to be admitted after the reaction (aOR, 0.964 [95% CI, 0.949-0.980]). Patients treated with prehospital antihistamines were less likely to have uncontrolled reactions (aOR, 0.978 [95% CI, 0.967-0.989]) and to be admitted after the reaction (aOR, 0.963 [95% CI, 0.949-0.977]). Patients who received prehospital corticosteroids were more likely to require intravenous fluids in ED (aOR, 1.059 [95% CI, 1.013-1.107]) and be admitted (aOR, 1.232 [95% CI, 1.181-1.286]). CONCLUSION: Our findings in this predominantly pediatric population support the early use of epinephrine and suggest a beneficial effect of antihistamines. Corticosteroid use in anaphylaxis should be revisited.


Assuntos
Anafilaxia , Serviços Médicos de Emergência , Masculino , Humanos , Criança , Feminino , Anafilaxia/tratamento farmacológico , Anafilaxia/epidemiologia , Anafilaxia/etiologia , Estudos Retrospectivos , Dados de Saúde Coletados Rotineiramente , Canadá/epidemiologia , Epinefrina/uso terapêutico , Serviço Hospitalar de Emergência , Antagonistas dos Receptores Histamínicos/uso terapêutico , Corticosteroides/uso terapêutico
19.
Environ Sci Pollut Res Int ; 30(47): 103958-103971, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37691062

RESUMO

With the growing nature of the ecological footprint, research studies focus on exploring new determinants of environmental degradation. Moreover, the role of natural resources and energy consumption in environmental quality has gained much attention in the literature. However, tourism raises the demand for energy consumption and extraction of natural resources. This research study investigates the influence of natural resources, tourism, and renewable energy in MINT countries, using novel Cross-Sectional Auto Regressive Distributive Lag (CS-ARDL) methodological techniques and employing yearly data from 1995 to 2018. The study also applied recently developed Kónya (Econ Model 23:978-992, 2006) causality to identify the causal relationship between the variables of the heterogenous panel. The result shows that tourism, natural resources, and economic growth are positively associated with the ecological footprint in the long-run. However, renewable energy consumption negatively impacts ecological footprint in both in short-run and the long-run. Further, the study explored a bidirectional causality between economic growth and ecological footprint in MINT countries. Finally, based on the empirical results, the study recommends that the authorities in MINT countries revisit their tourism, natural resources, and economic activities policies to enhance the environmental quality and reduce the ecological footprint.


Assuntos
Dióxido de Carbono , Turismo , Estudos Transversais , Recursos Naturais , Desenvolvimento Econômico , Energia Renovável
20.
Environ Sci Pollut Res Int ; 30(46): 102750-102771, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37674067

RESUMO

Corporate social responsibility (CSR) is a vital strategy for promoting firms' sustainable development goals, encompassing social, environmental, and economic factors. In emerging economies, manufacturing firms face mounting challenges in ensuring their sustainability. This study aims to identify the key drivers of CSR and examine their impact on CSR adoption in the manufacturing industry of Pakistan. The study employs the survey method to collect data, utilizing a one-to-one interview approach with a matrix-style questionnaire administered to a panel of experts selected through purposive sampling technique. Interpretive structural modeling (ISM) combined with Matrices' Impacts Cruise's Multiplication Appliquée a UN Classement (MICMAC) and structural equation model (SEM) are used for data assessment, modeling, and analysis. The findings indicate that compliance with government regulations and stakeholders' pressure are the essential drivers of CSR adoption and positively influence CSR adoption. Consequently, firms should consider adopting CSR strategies to enhance their sustainability based on the outcomes of this analysis.

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