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1.
Nature ; 626(8001): 984-989, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38326619

RESUMO

Controlled charge flows are fundamental to many areas of science and technology, serving as carriers of energy and information, as probes of material properties and dynamics1 and as a means of revealing2,3 or even inducing4,5 broken symmetries. Emerging methods for light-based current control5-16 offer particularly promising routes beyond the speed and adaptability limitations of conventional voltage-driven systems. However, optical generation and manipulation of currents at nanometre spatial scales remains a basic challenge and a crucial step towards scalable optoelectronic systems for microelectronics and information science. Here we introduce vectorial optoelectronic metasurfaces in which ultrafast light pulses induce local directional charge flows around symmetry-broken plasmonic nanostructures, with tunable responses and arbitrary patterning down to subdiffractive nanometre scales. Local symmetries and vectorial currents are revealed by polarization-dependent and wavelength-sensitive electrical readout and terahertz (THz) emission, whereas spatially tailored global currents are demonstrated in the direct generation of elusive broadband THz vector beams17. We show that, in graphene, a detailed interplay between electrodynamic, thermodynamic and hydrodynamic degrees of freedom gives rise to rapidly evolving nanoscale driving forces and charge flows under the extremely spatially and temporally localized excitation. These results set the stage for versatile patterning and optical control over nanoscale currents in materials diagnostics, THz spectroscopies, nanomagnetism and ultrafast information processing.

2.
Br J Cancer ; 130(12): 1990-2002, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38600326

RESUMO

BACKGROUND: Previous studies have suggested that patients with HER2-low breast cancers do not benefit from trastuzumab treatment although the reasons remain unclear. METHODS: We investigated the effect of trastuzumab monotherapy and its combination with different HER2 targeting treatments in a panel of breast cancer cell lines and patient-derived organoids (PDOs) using biochemical methods and cell viability assays. RESULTS: Compared to sensitive HER2 over-expressing (IHC3 + ) breast cancer cells, increasing doses of trastuzumab could not achieve IC50 in MDA-MB-361 (IHC 2 + FISH + ) and MDA-MB-453 (IHC 2 + FISH-) cells which showed an intermediate response to trastuzumab. Trastuzumab treatment induced upregulation of HER ligand release, resulting in the activation of HER receptors in these cells, which could account for their trastuzumab insensitivity. Adding a dual ADAM10/17 inhibitor to inhibit the shedding of HER ligands in combination with trastuzumab only showed a modest decrease in the cell viability of HER2-low breast cancer cells and PDOs. However, the panHER inhibitor neratinib was an effective monotherapy in HER2-low breast cancer cells and PDOs, and showed additive effects when combined with trastuzumab. CONCLUSION: This study demonstrates that neratinib in combination with trastuzumab may be effective in a subset of HER2-low breast cancers although further validation is required in a larger panel of PDOs and in future clinical studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Organoides , Quinolinas , Receptor ErbB-2 , Trastuzumab , Humanos , Trastuzumab/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Feminino , Organoides/efeitos dos fármacos , Quinolinas/farmacologia , Quinolinas/administração & dosagem , Linhagem Celular Tumoral , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos
3.
Opt Express ; 32(2): 2058-2066, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38297743

RESUMO

Lenses with a tunable focus are highly desirable but remain a challenge. Here, we demonstrate a microwave varifocal meta-lens based on the Alvarez lens principle, consisting of two mechanically movable tri-layer metasurface phase plates with reversed cubic spatial profiles. The manufactured multilayer Alvarez meta-lens enables microwave beam collimation/focusing at frequencies centered at 7.5 GHz, and shows one octave focal length tunability when transversely translating the phase plates by 8 cm. The measurements reveal a gain enhancement up to 15 dB, 3-dB beam width down to 3.5∘, and relatively broad 3-dB bandwidth of 3 GHz. These advantageous characteristics, along with its simplicity, compactness, and lightweightness, make the demonstrated flat Alvarez meta-lens suitable for deployment in many microwave systems.

4.
Chem Rec ; : e202300333, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39051717

RESUMO

Global agricultural by-products usually go to waste, especially in developing countries where agricultural products are usually exported as raw products. Such waste streams, once converted to "value-added" products could be an additional source of revenue while simultaneously having positive impacts on the socio-economic well-being of local people. We highlight the utilization of thermochemical techniques to activate and convert agricultural waste streams such as rice and straw husk, coconut fiber, coffee wastes, and okara power wastes commonly found in the world into porous activated carbons and biofuels. Such activated carbons are suitable for various applications in environmental remediation, climate mitigation, energy storage, and conversions such as batteries and supercapacitors, in improving crop productivity and producing useful biofuels.

5.
BMC Public Health ; 24(1): 1020, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609956

RESUMO

BACKGROUND: Consumption of sugar-sweetened beverages (SSB) is a major global public health problem. Increasing the price of SSBs through taxation is an effective tool to reduce SSB consumption. Price-elasticity estimates are useful in measuring the effect of taxation on consumption. We estimated the own price elasticities of demand for SSBs in Bangladesh, which will inform how SSB taxes could affect behaviour. METHODS: We used Household Income and Expenditure Survey (HIES) 2016 data, which is a nationally representative dataset at the household level across the country and is conducted using stratified random sampling method. Deaton's method was used to estimate the price elasticities for SSBs in Bangladesh. RESULTS: We found that the own price elasticity for SSBs varied between - 0.53% to -1.17% by types of SSBs in Bangladesh. The price elasticity for soft drinks was - 1.17, indicating that if the price of soft drinks increases by 10% via taxes, the quantity consumed of these beverages would reduce by 11.7%. CONCLUSION: This is the first study that estimates the own price elasticities of demand for SSBs in Bangladesh. Our results suggest to raise SSB prices through increased taxation in order to reduce SSB consumption and ensure public health gains in Bangladesh.


Assuntos
Bebidas Adoçadas com Açúcar , Humanos , Bangladesh , Bebidas , Impostos , Elasticidade
6.
BMC Public Health ; 24(1): 270, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263029

RESUMO

INTRODUCTION: To reduce the high prevalence of cervical cancers among the Bangladeshi women, the Government of Bangladesh established a national cervical cancer screening programme in 2005 for women aged 30 to 60 years. The District Health Information System Version 2 (DHIS2) based electronic aggregated data collection system is used since the year 2013. This study summarises data from the year 2014 to 2022 to assess the effectiveness of the electronic data collection system in understanding the outcome of the screening programme. METHODS: This is a descriptive study based on secondary data extracted in MS Excel from the DHIS2-based electronic repository of the national cervical cancer screening programme of Bangladesh. The respondents were women aged 30-60 years, screened for cervical cancer using VIA (Visual Inspection of cervix with Acetic acid) method in 465 government health facilities. The data were collected on the participants' residential location, month and year of screening, name and type of health facilities performing VIA, and VIA screening results. RESULTS: The national screening programme reported a total 3.36 million VIA tests from 465 government hospitals in 8 years (2014 to 2022). The national average VIA-positivity rate was 3.6%, which varied from 1.4 to 9.5% among the districts. This national screening programme witnessed an exponential growth, year after year, with 83.3% increase in VIA test from 2014 to 2022. The primary and the secondary care hospitals were the highest collective contributors of VIA tests (86.2%) and positive cases (77.8%). The VIA-positivity rates in different hospital types varied widely, 7.0% in the medical university hospital, 5.7% in the medical college hospitals, 3.9% in the district/general hospitals, and 3.0% in the upazila health complexes. CONCLUSIONS: A national cervical cancer screening programme using VIA method and a DHIS2-based electronic data collection backbone, is effective, sustainable, and useful to understand the screening coverage, VIA positivity rate and geographic distribution of the participants and case load to initiate policy recommendations and actions. Decentralization of the screening programme and more efforts at the primary and secondary care level is required to increase screening performances.


Assuntos
Detecção Precoce de Câncer , Neoplasias do Colo do Útero , Feminino , Humanos , Bangladesh , Coleta de Dados , Eletrônica , Hospitais de Distrito , Adulto , Pessoa de Meia-Idade
7.
Biomed Chromatogr ; 38(7): e5869, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38599336

RESUMO

The increasing demand for honey purification and authentication necessitates the global utilization of advanced processing tools. Common honey processing techniques, such as chromatography, are commonly used to assess the quality and quantity of valuable honey. In this study, 15 honey samples were authenticated using HPLC and GC-MS chromatographic methods to analyze their pollen spectrum. Various monofloral honey samples were collected, including Acacia, Hypoestes, Lavandula, Tamarix, Trifolium, and Ziziphus species, based on accurate identification by apiarists in 2023 from the Kingdom of Saudi Arabia. Honey analysis revealed the extraction of pollen from 20 different honeybee floral species. Pollen identified from honey samples using advanced chromatographic tools revealed dominant vegetation resources: Ziziphus species (23%), Acacia species (25%), Tamarix species (34%), Lavandula species (26%), Hypoestes species (34%), and Trifolium species (31%). This study uses HPLC to extract phenolic compounds, revealing dominant protocatechuic acid (4.71 mg g-1), and GC-MS to analyze organic compounds in honey pollen. Specifically, 2-dodecanone was detected with a retention time of 7.34 min. The utilization of chromatographic tools in assessing honey samples for pollen identification provides a reliable and efficient method for determining their botanical origins, thereby contributing to the quality control and authentication of honey products.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Mel , Pólen , Pólen/química , Mel/análise , Cromatografia Líquida de Alta Pressão/métodos , Arábia Saudita , Cromatografia Gasosa-Espectrometria de Massas/métodos , Abelhas , Animais , Fenóis/análise
8.
J Biol Chem ; 298(5): 101849, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35314194

RESUMO

The pathogen Mycobacterium tuberculosis (M.tb) resides in human macrophages, wherein it exploits host lipids for survival. However, little is known about the interaction between M.tb and macrophage plasmalogens, a subclass of glycerophospholipids with a vinyl ether bond at the sn-1 position of the glycerol backbone. Lysoplasmalogens, produced from plasmalogens by hydrolysis at the sn-2 carbon by phospholipase A2, are potentially toxic but can be broken down by host lysoplasmalogenase, an integral membrane protein of the YhhN family that hydrolyzes the vinyl ether bond to release a fatty aldehyde and glycerophospho-ethanolamine or glycerophospho-choline. Curiously, M.tb encodes its own YhhN protein (MtbYhhN), despite having no endogenous plasmalogens. To understand the purpose of this protein, the gene for MtbYhhN (Rv1401) was cloned and expressed in Mycobacterium smegmatis (M.smeg). We found the partially purified protein exhibited abundant lysoplasmalogenase activity specific for lysoplasmenylethanolamine or lysoplasmenylcholine (pLPC) (Vmax∼15.5 µmol/min/mg; Km∼83 µM). Based on cell density, we determined that lysoplasmenylethanolamine, pLPC, lysophosphatidylcholine, and lysophosphatidylethanolamine were not toxic to M.smeg cells, but pLPC and LPC were highly toxic to M.smeg spheroplasts, which are cell wall-deficient mycobacterial forms. Importantly, spheroplasts prepared from M.smeg cells overexpressing MtbYhhN were protected from membrane disruption/lysis by pLPC, which was rapidly depleted from the media. Finally, we found that overexpression of full-length MtbYhhN in M.smeg increased its survival within human macrophages by 2.6-fold compared to vector controls. These data support the hypothesis that MtbYhhN protein confers a growth advantage for mycobacteria in macrophages by cleaving toxic host pLPC into potentially energy-producing products.


Assuntos
Hidrolases , Proteínas de Membrana , Mycobacterium tuberculosis , Humanos , Hidrolases/genética , Hidrolases/metabolismo , Lisofosfatidilcolinas , Lisofosfolipídeos , Macrófagos/microbiologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mycobacterium smegmatis , Mycobacterium tuberculosis/enzimologia , Mycobacterium tuberculosis/genética , Plasmalogênios/metabolismo
9.
FASEB J ; 36(10): e22560, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36165236

RESUMO

Angiogenesis inhibitor drugs targeting vascular endothelial growth factor (VEGF) signaling to the endothelial cell (EC) are used to treat various cancer types. However, primary or secondary resistance to therapy is common. Clinical and pre-clinical studies suggest that alternative pro-angiogenic factors are upregulated after VEGF pathway inhibition. Therefore, identification of alternative pro-angiogenic pathway(s) is critical for the development of more effective anti-angiogenic therapy. Here we study the role of apelin as a pro-angiogenic G-protein-coupled receptor ligand in tumor growth and angiogenesis. We found that loss of apelin in mice delayed the primary tumor growth of Lewis lung carcinoma 1 and B16F10 melanoma when combined with the VEGF receptor tyrosine kinase inhibitor, sunitinib. Targeting apelin in combination with sunitinib markedly reduced the tumor vessel density, and decreased microvessel remodeling. Apelin loss reduced angiogenic sprouting and tip cell marker gene expression in comparison to the sunitinib-alone-treated mice. Single-cell RNA sequencing of tumor EC demonstrated that the loss of apelin prevented EC tip cell differentiation. Thus, apelin is a potent pro-angiogenic cue that supports initiation of tumor neovascularization. Together, our data suggest that targeting apelin may be useful as adjuvant therapy in combination with VEGF signaling inhibition to inhibit the growth of advanced tumors.


Assuntos
Neoplasias Experimentais , Neoplasias , Inibidores da Angiogênese/farmacologia , Animais , Apelina , Ligantes , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias Experimentais/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Receptores Acoplados a Proteínas G/fisiologia , Receptores de Fatores de Crescimento do Endotélio Vascular , Sunitinibe/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular/uso terapêutico
10.
FASEB J ; 36(1): e22080, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34882832

RESUMO

Angiogenesis is required in embryonic development and tissue repair in the adult. Vascular endothelial growth factor (VEGF) initiates angiogenesis, and VEGF or its receptor is targeted therapeutically to block pathological angiogenesis. Additional pro-angiogenic cues, such as CXCL12 acting via the CXCR4 receptor, co-operate with VEGF/VEGFR2 to cue vascular patterning. We studied the role of FGD5, an endothelial Rho GTP/GDP exchange factor (RhoGEF), to regulate CXCR4-dependent signals in the endothelial cell (EC). Patient-derived renal cell carcinomas produce a complex milieu of growth factors that stimulated sprouting angiogenesis and endothelial tip cell differentiation ex vivo that was blocked by EC FGD5 loss. In a simplified model, CXCL12 augmented sprouting and tip gene expression under conditions where VEGF was limiting. CXCL12-stimulated tip cell differentiation was dependent on PI3 kinase (PI3K)-ß activity. Knockdown of EC FGD5 abolished CXCR4 signaling to PI3K-ß and Akt. Further, inhibition of Rac1, a Rho GTPase required for PI3K-ß activity, recapitulated the signaling defects of FGD5 deficiency, suggesting that FGD5 may regulate PI3K-ß activity through Rac1. Overexpression of a RhoGEF deficient, Dbl domain-deleted FGD5 mutant reduced CXCL12-stimulated Akt phosphorylation and failed to rescue PI3K signaling in native FGD5-deficient EC, indicating that FGD5 RhoGEF activity is required for FDG5 function. Endothelial expression of mutant PI3K-ß with an inactivated Rho binding domain confirmed that CXCL12-stimulated PI3K activity in EC requires Rac1-GTP co-regulation. Together, this data identify the role of FGD5 to generate Rac1-GTP to regulate pro-angiogenic CXCR4-dependent PI3K-ß signaling in EC. Inhibition of FGD5 activity may complement current angiogenesis inhibitor drugs.


Assuntos
Carcinoma de Células Renais , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Neoplasias Renais , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proteínas de Neoplasias/genética , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Fosfatidilinositol 3-Quinases/genética
11.
Biotechnol Appl Biochem ; 70(3): 1057-1071, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36417773

RESUMO

Cellulases are used in textile, pulp and paper, brewery and wine, sugars, and ethanol industries. Four fungal isolates obtained from organic municipal solid wastes (OMSW) were selected based on their cellulolytic activity on carboxymethyl cellulose (CMC) agar medium. Based on the internal transcribed spacer (ITS) sequence of the ribosomal DNA, the four cellulolytic isolates were identified as Aspergillus fumigatus AKAL1, Aspergillus oryzae AKAL4, Aspergillus flavus AKAL8, and Aspergillus flavus AKAL9. After 9 days of fermentation at 30°C and pH 6.5 under 110 rpm agitation, these isolates produced the maximum amount of cellulase. The cellulase showed optimum activity at temperature 35-40°C and pH 6.0-7.0 and was stable for 1 h at 25-45°C and pH 5.0-7.0. The Mg2+ and Zn2+ significantly increased but Hg2+ , K+ , and Ca2+ severely repressed the cellulase activity. Degradation of filter papers and bio-stoning of denim was successfully done with the crude cellulase. An endo-ß-1,4-glucanase was isolated and characterized from Aspergillus isolates. Genome-wide analysis revealed that the genomes of A. oryzae, A. fumigatus, and A. flavus, the pertinent species of the fungal isolates, had 23, 25, and 22 cellulase genes, respectively. Phylogenetic analysis revealed that the cellulases in these fungal species were divided into three major groups, and the isolated endo-ß-1,4-glucanase clustered to Group II. Ten different motifs are present in cellulases of the three species. Results herein provide a valuable resource for understanding cellulase genes in Aspergillus species and potential application of cellulase in textile and fermentable sugars production industries.


Assuntos
Aspergillus oryzae , Celulase , Celulases , Celulase/genética , Celulase/metabolismo , Filogenia , Celulases/genética , Açúcares , Concentração de Íons de Hidrogênio
12.
BMC Public Health ; 23(1): 1411, 2023 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-37481536

RESUMO

BACKGROUND: Consumption of sugar-sweetened beverages (SSBs) or sugary drinks may reduce or even eliminate the household income allocation for other essential commodities. Reducing expenditure for consumption of other household commodities is known as the crowding-out effect of SSB. We aimed to determine the crowding-out effect of SSB expenditure on other household commodities. In addition, we also identified the factors influencing the household's decision to purchase of SSBs. METHODS: We used the logistic regression (logit and multinomial logit models) and the Seemingly Unrelated Regression (SUR) models. In order to find the probability of a given change in the socio-demographic variables, we also estimated the average marginal effects from the logistic regression. In addition, we regressed the SUR model by gender differences. We used Household Income and Expenditure Survey (HIES) 2016 data to estimate our chosen econometric models. HIES is nationally representative data on the household level across the country and is conducted using a multistage random sampling method by covering 46,075 households. RESULTS: The findings from the logit model describe that the greater proportion of male members, larger household size, household heads with higher education, profession, having a refrigerator, members living outside of the house, and households with higher income positively affect the decision of purchasing SSB. However, the determinants vary with the various types of SSB. The unadjusted crowding out effect shows that expenditure on SSB or sugar-added drinks crowds out the household expenditure on food, clothing, housing, and energy items. On the other hand, the adjusted crowding out effect crowds out the spending on housing, education, transportation, and social and state responsibilities. CONCLUSION: Although the household expenditure on beverages and sugar-added drinks is still moderate (around 2% of monthly household expenditure), the increased spending on beverages and sugar-added drinks is a concern due to the displacement of household expenditure for basic commodities such as food, clothing, housing, education, and energy. Therefore, evidence-based policies to regulate the sale and consumption of SSB are required for a healthy nation.


Assuntos
Bebidas Adoçadas com Açúcar , Humanos , Masculino , Bangladesh , Gastos em Saúde , Bebidas , Açúcares
13.
Opt Express ; 30(3): 4231-4248, 2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35209664

RESUMO

We propose the asynchronous control of anisotropic diffusion (AD) algorithm, and such asynchronous anisotropic diffusion (AAD) algorithm is demonstrated experimentally to reduce noise from the sensing signals obtained from Brillouin distributed optical fiber sensors. The performance of the proposed AAD algorithm is analyzed in detail for different experimental conditions and compared with that of block-matching and 3D filtering, two-dimensional wavelet denoising, AD, and non-local means algorithms. Some key factors of the proposed algorithm, such as the impact of convolution kernel size on the performance of AD algorithms, the influence of low sampling point number (SPN) on the quality of Brillouin frequency shift and the selection of diffusion thresholds are analyzed and discussed with experimental results. The experimental results validate that the AAD algorithm can provide better root-mean-square error (RMSE) and spatial resolution (SR) than the other four algorithms, especially for higher signal-to-noise ratio (SNR) improvement and higher SPNs. For lower SPNs, the performance of AAD is also not inferior to the RMSE performance of NLM and AD. The runtime of the AAD algorithm is also quite low. Moreover, the proposed algorithm offers the best SR performance as compared to other noise reduction algorithms investigated in this study. Thus, the proposed AAD algorithm can be an effective candidate to improve the measurement accuracy of Brillouin distributed optical fiber sensors.

14.
Molecules ; 27(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35011497

RESUMO

Genistein is a naturally occurring polyphenolic molecule in the isoflavones group which is well known for its neuroprotection. In this review, we summarize the efficacy of genistein in attenuating the effects of memory impairment (MI) in animals. Scopus, PubMed, and Web of Science databases were used to find the relevant articles and discuss the effects of genistein in the brain, including its pharmacokinetics, bioavailability, behavioral effects, and some of the potential mechanisms of action on memory in several animal models. The results of the preclinical studies highly suggested that genistein is highly effective in enhancing the cognitive performance of the MI animal models, specifically in the memory domain, including spatial, recognition, retention, and reference memories, through its ability to reduce oxidative stress and attenuate neuroinflammation. This review also highlighted challenges and opportunities to improve the drug delivery of genistein for treating MI. Along with that, the possible structural modifications and derivatives of genistein to improve its physicochemical and drug-likeness properties are also discussed. The outcomes of the review proved that genistein can enhance the cognitive performance and ameliorate MI in different preclinical studies, thus indicating its potential as a natural lead for the design and development of a novel neuroprotective drug.


Assuntos
Encéfalo/metabolismo , Genisteína/uso terapêutico , Transtornos da Memória/tratamento farmacológico , Doenças Neuroinflamatórias/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Animais , Desenho de Fármacos , Humanos , Transtornos da Memória/metabolismo , Doenças Neuroinflamatórias/metabolismo
15.
Molecules ; 27(3)2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35163934

RESUMO

Cardiovascular disorders (CVDs) are the leading risk factor for death worldwide, and research into the processes and treatment regimens has received a lot of attention. Tilianin is a flavonoid glycoside that can be found in a wide range of medicinal plants and is most commonly obtained from Dracocephalum moldavica. Due to its extensive range of biological actions, it has become a well-known molecule in recent years. In particular, numerous studies have shown that tilianin has cardioprotective properties against CVDs. Hence, this review summarises tilianin's preclinical research in CVDs, as well as its mechanism of action and opportunities in future drug development. The physicochemical and drug-likeness properties, as well as the toxicity profile, were also highlighted. Tilianin can be a natural lead molecule in the therapy of CVDs such as coronary heart disease, angina pectoris, hypertension, and myocardial ischemia, according to scientific evidence. Free radical scavenging, inflammation control, mitochondrial function regulation, and related signalling pathways are all thought to play a role in tilianin's cardioprotective actions. Finally, we discuss tilianin-derived compounds, as well as the limitations and opportunities of using tilianin as a lead molecule in drug development for CVDs. Overall, the scientific evidence presented in this review supports that tilianin and its derivatives could be used as a lead molecule in CVD drug development initiatives.


Assuntos
Produtos Biológicos/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Desenho de Fármacos , Desenvolvimento de Medicamentos , Flavonoides/farmacologia , Glicosídeos/farmacologia , Animais , Humanos
16.
Molecules ; 27(3)2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35163999

RESUMO

Kirenol, a potential natural diterpenoid molecule, is mainly found in Sigesbeckia species. Kirenol has received a lot of interest in recent years due to its wide range of pharmacological actions. In particular, it has a significant ability to interact with a wide range of molecular targets associated with inflammation. In this review, we summarise the efficacy and safety of kirenol in reducing inflammation, as well as its potential mechanisms of action and opportunities in future drug development. Based on the preclinical studies reported earlier, kirenol has a good therapeutic potential against inflammation involved in multiple sclerosis, inflammatory bowel disorders, diabetic wounds, arthritis, cardiovascular disease, bone damage, and joint disorders. We also address the physicochemical and drug-like features of kirenol, as well as the structurally modified kirenol-derived molecules. The inhibition of pro-inflammatory cytokines, reduction in the nuclear factor kappa-B (NF-κB), attenuation of antioxidant enzymes, stimulation of heme-oxygenase-1 (HO-1) expression, and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation are among the molecular mechanisms contributing to kirenol's anti-inflammatory actions. Furthermore, this review also highlights the challenges and opportunities to improve the drug delivery of kirenol for treating inflammation. According to the findings of this review, kirenol is an active molecule against inflammation in numerous preclinical models, indicating a path to using it for new drug discovery and development in the treatment of a wide range of inflammations.


Assuntos
Anti-Inflamatórios/farmacologia , Produtos Biológicos/farmacologia , Diterpenos/farmacologia , Desenho de Fármacos , Desenvolvimento de Medicamentos , Inflamação/tratamento farmacológico , Animais , Citocinas/metabolismo , Humanos
17.
Int J Environ Health Res ; 32(6): 1344-1358, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33504213

RESUMO

This study aims to identify blood biomarkers for rapidly predicting progression and severity assessment of COVID-19 in type 2 diabetic (DM) and non-DM (NDM) patients. Among 211 hospitalized patients suspected of COVID-19, 98 were confirmed COVID-19 by rRT-PCR. The COVID-19 positive group contained 58 DM and 40 NDM patients with total death 9 of which 7 were males and 6 were DM, indicating males and DM individuals as more susceptible to COVID-19. Blood biomarkers notably serum ferritin, CRP, D-dimer, ALT, troponin I, and Hb1Ac were significantly (p < 0.05) higher in COVID-19 patients. Ferritin and HbA1c levels were significantly (p < 0.05) higher in DM than NDM COVID-19 patients. The present study suggests that ferritin and HbA1c levels for DM patients, and ferritin, D-dimer, ALT for NDM patients could be routinely used as biomarkers for progression and severity assessment of COVID-19. CRP and Troponin-I could be the predictor only for poor prognosis of COVID-19.


Assuntos
COVID-19 , Diabetes Mellitus , Biomarcadores , COVID-19/diagnóstico , Estudos Transversais , Feminino , Ferritinas , Hemoglobinas Glicadas , Humanos , Masculino , SARS-CoV-2
18.
Medicina (Kaunas) ; 59(1)2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36676658

RESUMO

Background and Objectives: Nanomedicine is a constantly growing field for the diagnosis and treatment of various diseases as well as for regenerative therapy. Nanotechnology-based drug-delivery systems improve pharmacological and pharmacokinetic profiles of plants based biologically active molecules. Based on traditional claims, leaves of the Tamarix aphylla (TA) were investigated for their potential healing activity on burn wounds. Materials and Methods: In this study, TA-based nanoemulsion was prepared. The nanoemulsion was characterized for size, zeta potential, pH, viscosity, and stability. The nanoemulsion containing plant extract was converted into cream and evaluated for its efficacy against acid-burn wounds inflicted in the dorsum of rabbits. The animals were classified into four main groups: Group A as a normal control group, Group B as a positive control (treated with cream base + silver sulfadiazine), Group C as a standard drug (silver sulfadiazine), and Group D as a tested (treated with nanoemulsion cream containing TA extract). The prepared system could deliver TA to the target site and was able to produce pharmacological effects. On days 0, 7, 14, 21, 28, and 35, wound contraction rate was used to determine healing efficacy. The wound samples were collected from the skin for histological examination. Results: Based on statistical analysis using wound-healing time, Group D showed a shorter period (21.60 ± 0.5098) (p < 0.01) than the average healing time of Group C (27.40 ± 0.6002) (p < 0.05) and Group B (33.40 ± 0.8126) (p < 0.05). The histopathological assessment showed that burn healing was better in Group D compared with Group C and Group B. The nanoemulsion cream had a non-sticky texture, low viscosity, excellent skin sensations, and a porous structure. By forming a protective layer on the skin and improving moisture, it enhanced the condition of burnt skin. Conclusions: According to the findings of this study, nanoemulsion cream containing TA extract has great potential in healing acid-burn wounds


Assuntos
Queimaduras , Tamaricaceae , Animais , Coelhos , Sulfadiazina de Prata/farmacologia , Sulfadiazina de Prata/uso terapêutico , Cicatrização , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Queimaduras/tratamento farmacológico , Emolientes
19.
J Mol Cell Cardiol ; 157: 17-30, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33887328

RESUMO

BACKGROUND: PI3Kα (Phosphoinositide 3-kinase α) regulates multiple downstream signaling pathways controlling cell survival, growth, and proliferation and is an attractive therapeutic target in cancer and obesity. The clinically-approved PI3Kα inhibitor, BYL719, is in further clinical trials for cancer and overgrowth syndrome. However, the potential impact of PI3Kα inhibition on the heart and following myocardial infarction (MI) is unclear. We aim to determine whether PI3Kα inhibition affects cardiac physiology and post-MI remodeling and to elucidate the underlying molecular mechanisms. METHODS AND RESULTS: Wildtype (WT) 12-wk old male mice receiving BYL719 (daily, p.o.) for 10 days showed reduction in left ventricular longitudinal strain with normal ejection fraction, weight loss, mild cardiac atrophy, body composition alteration, and prolonged QTC interval. RNASeq analysis showed gene expression changes in multiple pathways including extracellular matrix remodeling and signaling complexes. After MI, both p110α and phospho-Akt protein levels were increased in human and mouse hearts. Pharmacological PI3Kα inhibition aggravated cardiac dysfunction and resulted in adverse post-MI remodeling, with increased apoptosis, elevated inflammation, suppressed hypertrophy, decreased coronary blood vessel density, and inhibited Akt/GSK3ß/eNOS signaling. Selective genetic ablation of PI3Kα in endothelial cells was associated with worsened post-MI cardiac function and reduced coronary blood vessel density. In vitro, BYL719 suppressed Akt/eNOS activation, cell viability, proliferation, and angiogenic sprouting in coronary and human umbilical vein endothelial cells. Cardiomyocyte-specific genetic PI3Kα ablation resulted in mild cardiac systolic dysfunction at baseline. After MI, cardiac function markedly deteriorated with increased mortality concordant with greater apoptosis and reduced hypertrophy. In isolated adult mouse cardiomyocytes, BYL719 decreased hypoxia-associated activation of Akt/GSK3ß signaling and cell survival. CONCLUSIONS: PI3Kα is required for cell survival (endothelial cells and cardiomyocytes) hypertrophic response, and angiogenesis to maintain cardiac function after MI. Therefore, PI3Kα inhibition that is used as anti-cancer treatment, can be cardiotoxic, especially after MI.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/genética , Inativação Gênica , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Biomarcadores , Modelos Animais de Doenças , Progressão da Doença , Suscetibilidade a Doenças , Ecocardiografia , Eletrocardiografia , Perfilação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Modelos Biológicos , Infarto do Miocárdio/diagnóstico , Neovascularização Fisiológica/genética , Especificidade de Órgãos/genética , Transdução de Sinais , Transcriptoma
20.
Phys Rev Lett ; 127(4): 043603, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34355970

RESUMO

Metasurfaces have recently entered the realm of quantum photonics, enabling manipulation of quantum light using a compact nanophotonic platform. Realizing the full potential of metasurfaces at the deepest quantum level requires the ability to tune coherent light-matter interactions continuously in space and time. Here, we introduce the concept of space-time quantum metasurfaces for arbitrary control of the spectral, spatial, and spin properties of nonclassical light using a compact photonic platform. We show that space-time quantum metasurfaces allow on-demand tailoring of entanglement among all degrees of freedom of a single photon. We also show that spatiotemporal modulation induces asymmetry at the fundamental level of quantum fluctuations, resulting in the generation of steered and vortex photon pairs out of vacuum. Space-time quantum metasurfaces have the potential to enable novel photonic functionalities, such as encoding quantum information into high-dimensional color qudits using designer modulation protocols, sculpting multispectral and multispatial modes in spontaneous emission, and generating reconfigurable hyperentanglement for high-capacity quantum communications.

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