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1.
Comput Biol Med ; 174: 108436, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38643597

RESUMO

Great efforts have been made over the years to identify novel drug pairs with synergistic effects. Although numerous computational approaches have been proposed to analyze diverse types of biological big data, the pharmacogenomic profiles, presumably the most direct proxy of drug effects, have been rarely used due to the data sparsity problem. In this study, we developed a composite deep-learning-based model that predicts the drug synergy effect utilizing pharmacogenomic profiles as well as molecular properties. Graph convolutional network (GCN) was used to represent and integrate the chemical structure, genetic interactions, drug-target information, and gene expression profiles of cell lines. Insufficient amount of pharmacogenomic data, i.e., drug-induced expression profiles from the LINCS project, was resolved by augmenting the data with the predicted profiles. Our method learned and predicted the Loewe synergy score in the DrugComb database and achieved a better or comparable performance compared to other published methods in a benchmark test. We also investigated contribution of various input features, which highlighted the value of basal gene expression and pharmacogenomic profiles of each cell line. Importantly, DRSPRING (DRug Synergy PRediction by INtegrated GCN) can be applied to any drug pairs and any cell lines, greatly expanding its applicability compared to previous methods.


Assuntos
Sinergismo Farmacológico , Humanos , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética , Aprendizado Profundo , Perfilação da Expressão Gênica/métodos , Biologia Computacional/métodos , Redes Neurais de Computação
2.
ACS Appl Mater Interfaces ; 16(13): 16553-16562, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570940

RESUMO

In this study, two novel multiple resonance (MR) emitters, DtCzBN and Cy-DtCzBN, were designed based on the well-known BCzBN structure and synthesized for narrowband solution-processed organic light-emitting diodes (OLEDs). Cy-DtCzBN possesses a dimeric V-shaped structure formed by coupling two individual DtCzBN units via a nonconjugated cyclohexane linker. When compared with DtCzBN, Cy-DtCzBN, as a medium-sized molecule, was found to maintain the optical and photophysical properties of the corresponding monomeric unit, DtCzBN, but exhibits high thermal stability, excellent solubility, and good film-forming ability. Additionally, solution-processed OLEDs were fabricated by using two sets of molecules: one set of small molecular hosts and emitters (i.e., mCP and DtCzBN) and the other set of medium-sized molecular hosts and emitters (i.e., Cy-mCP and Cy-DtCzBN). Notably, devices using medium-sized molecular hosts and emitters exhibited similar optical and photophysical properties but showed significantly improved reproducibility and thermal stability compared with those based on small molecular hosts and emitters. Our current study provides some insights into molecular design strategies for thermally stable hosts and emitters, which are highly suitable for solution-processed OLEDs.

3.
Toxicol Lett ; 394: 57-65, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423481

RESUMO

Drug transporters are among the factors that determine the pharmacokinetic profiles after drug administration. In this study, we investigated the roles of drug transporters involved in transport of SN-38, which is an active metabolite of irinotecan, in the intestine under inflammatory conditions in vitro and determined their functional consequences. The expression alterations of breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 2B1 were determined at the mRNA and protein levels, and the subsequent functional alterations were evaluated via an accumulation study with the representative transporter substrates [prazosin and dibromofluorescein (DBF)] and SN-38. We also determined the cytotoxicity of SN-38 under inflammatory conditions. Decreased BCRP expression and increased OATP2B1 expression were observed under inflammatory conditions in vitro, which led to altered accumulation profiles of prazosin, DBF, and SN-38, and the subsequent cytotoxic profiles of SN-38. Treatment with rifampin or novobiocin supported the significant roles of BCRP and OATP2B1 in the transport and cytotoxic profile of SN-38. Collectively, these results suggest that BCRP and OATP2B1 are involved in the increased cytotoxicity of SN-38 under inflammatory conditions in vitro. Further comprehensive research is warranted to completely understand SN-38-induced gastrointestinal cytotoxicity and aid in the successful treatment of cancer with irinotecan.


Assuntos
Antineoplásicos , Neoplasias da Mama , Transportadores de Ânions Orgânicos , Humanos , Feminino , Irinotecano , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos/metabolismo , Proteínas de Membrana Transportadoras , Prazosina , Neoplasias da Mama/tratamento farmacológico
4.
Sensors (Basel) ; 24(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38339615

RESUMO

As cyber-attacks increase in unencrypted communication environments such as the traditional Internet, protected communication channels based on cryptographic protocols, such as transport layer security (TLS), have been introduced to the Internet. Accordingly, attackers have been carrying out cyber-attacks by hiding themselves in protected communication channels. However, the nature of channels protected by cryptographic protocols makes it difficult to distinguish between normal and malicious network traffic behaviors. This means that traditional anomaly detection models with features from packets extracted a deep packet inspection (DPI) have been neutralized. Recently, studies on anomaly detection using artificial intelligence (AI) and statistical characteristics of traffic have been proposed as an alternative. In this review, we provide a systematic review for AI-based anomaly detection techniques over encrypted traffic. We set several research questions on the review topic and collected research according to eligibility criteria. Through the screening process and quality assessment, 30 research articles were selected with high suitability to be included in the review from the collected literature. We reviewed the selected research in terms of dataset, feature extraction, feature selection, preprocessing, anomaly detection algorithm, and performance indicators. As a result of the literature review, it was confirmed that various techniques used for AI-based anomaly detection over encrypted traffic were used. Some techniques are similar to those used for AI-based anomaly detection over unencrypted traffic, but some technologies are different from those used for unencrypted traffic.

5.
Chem Biol Interact ; 390: 110886, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38280639

RESUMO

Niclosamide is an anthelmintic drug with a long history of use and is generally safe and well tolerated in humans. As the conventional dose of niclosamide results in a low but certain level in systemic circulation, drug interactions with concomitant drugs should be considered. We aimed to investigate the interaction between niclosamide and drug transporters, as such information is currently limited. Niclosamide inhibited the transport activity of OATP1B1, OATP1B3, OAT1, OAT3, and OCT2 in vitro. Among them, the inhibitory effects on OAT1, OAT3, and OCT2 were strong, with IC50 values of less than 1 µM. When 3 mg/kg of niclosamide was co-administered to rats, systemic exposure to furosemide (a substrate of OAT1/3) and metformin (a substrate of OCT2) increased, and the renal clearance (CLr) of the drugs significantly decreased. These results suggest that niclosamide inhibits renal transporters, OAT1/3 and OCT2, not only in vitro but also in vivo, resulting in increased systemic exposure to the substrates of the transporters by strongly blocking the urinary elimination pathway in rats. The findings of this study will support a meticulous understanding of the transporter-mediated drug interactions of niclosamide and consequently aid in effective and safe use of niclosamide.


Assuntos
Transportadores de Ânions Orgânicos Sódio-Independentes , Transportadores de Ânions Orgânicos , Humanos , Ratos , Animais , Transportador 2 de Cátion Orgânico , Proteínas de Transporte de Cátions Orgânicos , Niclosamida/farmacologia , Interações Medicamentosas , Transportadores de Ânions Orgânicos/metabolismo , Células HEK293
6.
Retina ; 44(3): 475-486, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37973043

RESUMO

PURPOSE: To investigate the prevalence and risk factors of age-related macular degeneration features among pilots of Republic of Korea Air Force. METHODS: This retrospective, cross-sectional study was performed with a total of 2781 Republic of Korea Air Force pilots who underwent regular medical examinations between 2020 and 2021. Age-related macular degeneration features were determined and graded by fundus photographs. Risk factors were identified with logistic regression analysis in odds ratio (OR) and 95% confidence interval (CI). RESULTS: The prevalence was 12.9% in the Republic of Korea Air Force pilots and 35.2% in those older than 50 years. Pilots with age-related macular degeneration features were positively associated with age (OR: 1.082, CI: 1.067-1.096, P < 0.001), male sex (OR: 0.229, CI: 0.056-0.939, P = 0.041), smoking (OR: 1.027, CI: 1.008-1.047, P = 0.006), flight time (OR: 1.004, CI: 1.003-1.005, P < 0.001), total cholesterol (OR: 1.004, CI: 1.000-1.007, P = 0.033), and low-density lipoprotein (OR: 1.005, CI: 1.001-1.008, P = 0.011). Aircraft type was also identified as a risk factor (OR: 0.617, CI: 0.460-0.827 for carrier, OR: 0.572, CI: 0.348-0.940 for helicopter, P = 0.002), with fighter pilots having a higher risk than carrier and helicopter pilots. The results were similar for pilots older than 50 years. CONCLUSION: The prevalence of age-related macular degeneration features in Republic of Korea Air Force pilots was higher than in other general populations studied. Identified risk factors such as flight time and aircraft type suggest potential occupational risk of age-related macular degeneration in aviators.


Assuntos
Degeneração Macular , Humanos , Masculino , Prevalência , Estudos Transversais , Estudos Retrospectivos , Degeneração Macular/diagnóstico , Degeneração Macular/epidemiologia , Degeneração Macular/etiologia , Fatores de Risco
7.
Medicina (Kaunas) ; 59(12)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38138276

RESUMO

Background and Objectives: Posterior capsular opacification (PCO) is the most common long-term complication of successful cataract surgery and can cause visual impairment. We aimed to investigate the effects of intraocular lens (IOL) characteristics on PCO by comparing the incidence of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy for different types of intraocular lenses. Materials and Methods: A retrospective analysis was performed on 2866 eyes that underwent cataract surgery between January 2010 and December 2017, with at least 5 years of follow-up. The IOLs used for surgery were the hydrophobic lenses SN60WF (Alcon, Fort Worth, TX, USA), ZCB00 (Johnson & Johnson Vision, Santa Ana, CA, USA), and MX60 (Bausch & Lomb, Rochester, NY, USA), and the hydrophilic lens MI60 (Bausch & Lomb, Rochester, NY, USA). We analyzed the incidence of Nd:YAG laser capsulotomy according to the type of IOL used. Results: The incidence of Nd:YAG laser capsulotomy was significantly higher with MI60 lenses (31.70%, 175/552 eyes) compared to SN60WF (7.90%, 113/1431 eyes), ZCB00 (10.06%, 64/636 eyes), and MX60 (10.57%, 13/123 eyes; p < 0.001) lenses. The incidence of Nd:YAG laser capsulotomy was significantly lower with the hydrophobic IOLs (8.68%, 190/2190 eyes) than with the hydrophilic IOL (31.70%, 175/552 eyes; p < 0.001). Over time, the rate of increase in the cumulative number of Nd:YAG laser capsulotomy cases was the highest with MI60. The cumulative rate of Nd:YAG laser capsulotomy during the first 3 years was 4.90% with SN60WF (70/1431 eyes), 6.76% with ZCB00 (43/636 eyes), 8.94% with MX60 (11/123 eyes), and 26.10% with MI60 (144/552 eyes) lenses. Conclusions: The incidence of PCO is influenced by the material of the IOLs. The hydrophilic IOL was associated with a higher rate of Nd:YAG laser capsulotomy than the hydrophobic IOLs, with a shorter time to Nd:YAG laser capsulotomy.


Assuntos
Opacificação da Cápsula , Catarata , Lasers de Estado Sólido , Lentes Intraoculares , Facoemulsificação , Humanos , Implante de Lente Intraocular/efeitos adversos , Lasers de Estado Sólido/efeitos adversos , Incidência , Estudos Retrospectivos , Lentes Intraoculares/efeitos adversos , Opacificação da Cápsula/epidemiologia , Opacificação da Cápsula/etiologia , Opacificação da Cápsula/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Catarata/etiologia , Facoemulsificação/efeitos adversos
8.
Nutrients ; 15(22)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38004168

RESUMO

Crocin, a glycoside of crocetin, has been known as the principal component responsible for saffron's antidiabetic, anticancer, and anti-inflammatory effects. Crocetin, originating from the hydrolytic cleavage of crocin in biological systems, was subjected to ligand-based virtual screening in this investigation. Subsequent biochemical analysis unveiled crocetin, not crocin, as a novel dual GPR40 and GPR120 agonist, demonstrating a marked preference for GPR40 and GPR120 over peroxisome proliferator-activated receptors (PPAR)γ. This compound notably enhanced insulin and GLP-1 secretion from pancreatic ß-cells and intestinal neuroendocrine cells, respectively, presenting a dual mechanism of action in glucose-lowering effects. Docking simulations showed that crocetin emulates the binding characteristics of natural ligands through hydrogen bonds and hydrophobic interactions, whereas crocin's hindered fit within the binding pocket is attributed to steric constraints. Collectively, for the first time, this study unveils crocetin as the true active component of saffron, functioning as a GPR40/120 agonist with potential implications in antidiabetic interventions.


Assuntos
Crocus , Hipoglicemiantes , Hipoglicemiantes/farmacologia , Crocus/química , Receptores Acoplados a Proteínas G/metabolismo
9.
ACS Appl Mater Interfaces ; 15(48): 56106-56115, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37994594

RESUMO

In solution-processed organic light-emitting diodes (OLEDs), achieving high color purity and efficiency is as important as that in vacuum processes. Emitters suitable for solution processing must have excellent solubility in organic solvents, high molecular weight, and compatibility with the host materials. In this study, we synthesized a deep-blue emitter that satisfies the above conditions by introducing a 1,4-bis(indolo[3,2,1-jk]carbazol-2-yl)benzene-based planar emitting core (DICz) structure and four 3,6-di-tert-butyl-9-phenyl-9H-carbazole (tCz) peripheral units, namely, 4tCz-DICz. A comparative compound, 4Hex-DICz, incorporating hexyl phenyl groups was synthesized. In contrast to 4Hex-DICz, 4tCz-DICz exhibited exceptional solubility in organic solvents and superior film-forming properties attributed to the presence of tCz units. Additionally, in the film state, the effective encapsulation of the emitting core (DICz) by the tCz units in 4tCz-DICz helps prevent undesirable molecular aggregation. The solution-processed OLEDs employing the CH-2D1 film, doped with 5 wt % 4tCz-DICz as the emitting layer, exhibited a deep-blue emission at 424 nm, characterized by a narrow bandwidth of 22 nm, and achieved a maximum external quantum efficiency (EQE) of approximately 4.0%. In contrast, the 4Hex-DICz-based device demonstrated an EQE of 2.91%. Consequently, we have successfully demonstrated that the introduction of four bulky tCz units into the DICz core is a promising molecular design strategy for the development of soluble indolocarbazole-based emitters, especially those used in high-performance deep-blue fluorescent OLEDs.

10.
Sci Rep ; 13(1): 19279, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37935760

RESUMO

We compared the efficacy and safety of autologous-serum (AS) and platelet-rich plasma (PRP) eye drops for dry eye (DE) treatment in primary Sjögren's syndrome (SS). This prospective, randomized, double-blinded clinical study included patients diagnosed with primary SS DE. Thirty-eight participants were randomly assigned to the AS or PRP groups. Corneal and conjunctival staining scores, Schirmer I test, tear film break-up time (TBUT), and ocular surface disease index (OSDI) scores were evaluated at 4 and 12 weeks. Conjunctival impression cytology (CIC) metaplasia grade and goblet cell density grade at 12 weeks were compared with those at baseline. Corneal and conjunctival staining scores and TBUT significantly improved at 4 and 12 weeks in both groups (all p < 0.005). No significant difference between the AS and PRP groups was observed at 4 and 12 weeks. The Schirmer I values, OSDI scores, CIC metaplasia grade, and goblet cell density grade did not significantly change at 4 and 12 weeks in either group. Both AS and PRP eye drops are effective for primary SS DE without a significant difference. Considering that the preparation time of PRP is shorter than that of AS, PRP can be a good alternative treatment for primary SS DE.


Assuntos
Síndromes do Olho Seco , Plasma Rico em Plaquetas , Síndrome de Sjogren , Humanos , Síndromes do Olho Seco/tratamento farmacológico , Metaplasia , Soluções Oftálmicas/efeitos adversos , Estudos Prospectivos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/terapia , Síndrome de Sjogren/diagnóstico , Lágrimas
12.
Biomed Mater ; 18(6)2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37769679

RESUMO

Stem cell therapy has shown great potential in treating various incurable diseases using conventional chemotherapy. Parkinson's disease (PD)-a neurodegenerative disease-has been reported to be caused by quantitative loss or abnormal functionality of dopaminergic neurons (DAnergic neurons). To date, stem cell therapies have shown some potential in treating PD throughex vivoengraftment of stem-cell-derived neurons. However, accurately identifying the differentiation and non-invasively evaluating the functionality and maturity of DAnergic neurons are formidable challenges in stem cell therapies. These strategies are important in enhancing the efficacy of stem cell therapies. In this study, we report a novel cell cultivation platform, that is, a nanocrater-like electrochemical nanoelectrode array (NCENA) for monitoring dopamine (DA) release from neurons to detect exocytotic DA release from DAnergic neurons. In particular, the developed NCENA has a nanostructure in which three-dimensional porous gold nanopillars are uniformly arranged on conductive electrodes. The developed NCENA exhibited great DA sensing capabilities with a linear range of 0.39-150µM and a limit of detection of 1.16µM. Furthermore, the nanotopographical cues provided by the NCENA are suitable for cell cultivation with enhanced cellular adhesion. Finally, we successfully analysed the functionality and maturity of differentiated neurons on the NCENA through its excellent sensing ability for exocytotic DA.

13.
Small ; 19(52): e2304271, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37649209

RESUMO

Stem-cell-based therapeutics have shown immense potential in treating various diseases that are currently incurable. In particular, partial recovery of Parkinson's disease, which occurs due to massive loss or abnormal functionality of dopaminergic (DAnergic) neurons, through the engraftment of stem-cell-derived neurons ex vivo is reported. However, precise assessment of the functionality and maturity of DAnergic neurons is still challenging for their enhanced clinical efficacy. Here, a novel conductive cell cultivation platform, a graphene oxide (GO)-incorporated metallic polymer nanopillar array (GOMPON), that can electrochemically detect dopamine (DA) exocytosis from living DAnergic neurons, is reported. In the cell-free configuration, the linear range is 0.5-100 µm, with a limit of detection of 33.4 nm. Owing to its excellent biocompatibility, a model DAnergic neuron (SH-SY5Y cell) can be cultivated and differentiated on the platform while their DA release can be quantitatively measured in a real-time and nondestructive manner. Finally, it is showed that the functionality of the DAnergic neurons derived from stem cells can be precisely assessed via electrochemical detection of their DA exocytosis. The developed GOMPON is highly promising for a wide range of applications, including real-time monitoring of stem cell differentiation into neuronal lineages, evaluating differentiation protocols, and finding practical stem cell therapies.


Assuntos
Grafite , Neuroblastoma , Humanos , Polímeros , Dopamina , Pirróis , Ouro , Neurônios , Técnicas Eletroquímicas
14.
Exp Mol Med ; 55(7): 1544-1555, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37464094

RESUMO

The endoplasmic reticulum (ER) is a subcellular organelle essential for cellular homeostasis. Perturbation of ER functions due to various conditions can induce apoptosis. Chronic ER stress has been implicated in a wide range of diseases, including autosomal dominant retinitis pigmentosa (ADRP), which is characterized by age-dependent retinal degeneration caused by mutant rhodopsin alleles. However, the signaling pathways that mediate apoptosis in response to ER stress remain poorly understood. In this study, we performed an unbiased in vivo RNAi screen with a Drosophila ADRP model and found that Wg/Wnt1 mediated apoptosis. Subsequent transcriptome analysis revealed that ER stress-associated serine protease (Erasp), which has been predicted to show serine-type endopeptidase activity, was a downstream target of Wg/Wnt1 during ER stress. Furthermore, knocking down Erasp via RNAi suppressed apoptosis induced by mutant rhodopsin-1 (Rh-1P37H) toxicity, alleviating retinal degeneration in the Drosophila ADRP model. In contrast, overexpression of Erasp resulted in enhanced caspase activity in Drosophila S2 cells treated with apoptotic inducers and the stabilization of the initiator caspase Dronc (Death regulator Nedd2-like caspase) by stimulating DIAP1 (Drosophila inhibitor of apoptosis protein 1) degradation. These findings helped identify a novel cell death signaling pathway involved in retinal degeneration in an autosomal dominant retinitis pigmentosa model.


Assuntos
Degeneração Retiniana , Retinose Pigmentar , Animais , Degeneração Retiniana/genética , Degeneração Retiniana/metabolismo , Rodopsina/genética , Rodopsina/metabolismo , Retinose Pigmentar/genética , Retinose Pigmentar/metabolismo , Transdução de Sinais , Drosophila/genética , Drosophila/metabolismo , Caspases/metabolismo
15.
Biosensors (Basel) ; 13(5)2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37232862

RESUMO

Non-invasive, non-destructive, and label-free sensing techniques are required to monitor real-time stem cell differentiation. However, conventional analysis methods, such as immunocytochemistry, polymerase chain reaction, and Western blot, involve invasive processes and are complicated and time-consuming. Unlike traditional cellular sensing methods, electrochemical and optical sensing techniques allow non-invasive qualitative identification of cellular phenotypes and quantitative analysis of stem cell differentiation. In addition, various nano- and micromaterials with cell-friendly properties can greatly improve the performance of existing sensors. This review focuses on nano- and micromaterials that have been reported to improve sensing capabilities, including sensitivity and selectivity, of biosensors towards target analytes associated with specific stem cell differentiation. The information presented aims to motivate further research into nano-and micromaterials with advantageous properties for developing or improving existing nano-biosensors to achieve the practical evaluation of stem cell differentiation and efficient stem cell-based therapies.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodos , Diferenciação Celular
16.
ACS Appl Mater Interfaces ; 15(23): 28277-28287, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37256769

RESUMO

Herein, a novel core molecule for V-shaped host molecules was synthesized, wherein two carbazoles were directly linked to cyclohexane. Cy-mCP and Cy-mCBP hosts were also successfully prepared for solution-processable thermally activated delayed fluorescence organic light-emitting diodes (TADF-OLEDs). The Cy-mCP and Cy-mCBP molecules contained a cyclohexane linker directly linked to two small molecular hosts (mCP and mCBP), exhibiting twice the molecular weight while maintaining the basic properties of a single host molecule with improved film-forming ability and solubility in organic solvents. These host materials showed superior thermal stability and high glass transition temperatures compared to lower molecular weight hosts. Green TADF-OLEDs were prepared using the two host materials and 2,4,5,6-tetra(3,6-di-tert-butylcarbazol-9-yl)-1,3-dicyanobenzene (t4CzIPN) emitter, achieving device efficiencies similar to that of a low-molecular-weight host. However, after the incorporation of a V-shaped host, superior characteristics were observed in terms of the thermal stability and operational stability of the device. The synthesis of V-shaped molecules by directly linking two carbazoles to a cyclohexane linker is promising for the development of different hosts for solution-processable OLEDs.

17.
Front Plant Sci ; 14: 1159625, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37180402

RESUMO

Introduction: Limonium (L.) tetragonum (Thunb.) A. A. Bullock, a halophyte that grows all over the southwest coast of Korea, is a medicinal plant with various pharmacological effects. The salt defense mechanism stimulates the biosynthesis of various secondary metabolites and improves functional substances. In this study, we investigated the optimal NaCl concentration for the growth and enhancement of secondary metabolites in hydroponically grown L. tetragonum. Methods: The seedlings grown for 3 weeks in a hydroponic cultivation system were treated with 0-, 25-, 50-, 75-, and 100-mM NaCl in Hoagland's nutrient solution for 8 weeks. No significant effect on the growth and chlorophyll fluorescence was observed for the NaCl concentrations below 100-mM. Results and discussions: The increase in the NaCl concentration resulted in the decrease in the water potential of the L. tetragonum leaves. The Na+ content accumulated in the aerial part increased rapidly and the content of K+, which acts as an antagonist, decreased with the increase in NaCl concentrations in hydroponics. The total amino acid content of L. tetragonum decreased compared to the 0-mM NaCl, and most of the amino acid content decreased as the NaCl concentration increased. In contrast, the content of urea, proline (Pro), ß-alanine, ornithine, and arginine was increased with an increase in NaCl concentration. The Pro content at 100-mM NaCl accounted for 60% of the total amino acids and was found to be a major osmoregulator as an important component of the salt defense mechanisms. The top five compounds identified in the L. tetragonum were classified as flavonoids while the flavanone compound was detected only in the NaCl treatments. A total of four myricetin glycosides were increased in comparison to the 0-mM NaCl. Among the differentially expressed genes, a significantly large change in Gene ontology was seen in the circadian rhythm. NaCl treatment enhanced the flavonoid-based substances of L. tetragonum. The optimum NaCl concentration for the enhancement of secondary metabolites of the L. tetragonum in the vertical farm-hydroponic cultivation system was 75-mM NaCl.

18.
Chem Biol Interact ; 379: 110504, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37084994

RESUMO

Organic cation transporter 2 (OCT2) is predominantly expressed in the basolateral membrane of renal proximal tubule cells and contributes to the renal excretion of various drugs such as metformin, cisplatin, oxaliplatin, cimetidine, and lamivudine. Cisplatin, an anticancer agent for various cancers, is a substrate of OCT2, and cisplatin-induced nephrotoxicity is in part attributed to OCT2 activity in the kidney, which increases the renal accumulation of cisplatin. In this study, we aimed to identify flavone derivatives with strong inhibitory effects on OCT2 transport. Among the 80 flavonoids tested, 24 showed moderate to strong inhibitory effects against OCT2 transport activity. The IC50 values were less than 5 µM for 10 flavonoids. All 10 compounds alleviated cisplatin-induced cytotoxicity in cells expressing OCT2, even though the magnitude of the effects varied depending on the functional moieties in each position. Multiple factor analysis revealed that the methyl group at the R1 position and methoxy group at the R6 position of the flavonol backbone are important for OCT2 inhibition. Information on the functional moieties in the flavonol backbone would help develop effective OCT2 inhibitors by providing a structural association with OCT2 inhibitory effects. In addition, the compounds with strong inhibitory effects on OCT2 identified in this study may be potential candidates for clinical use to mitigate cisplatin-induced nephrotoxicity.


Assuntos
Cisplatino , Proteínas de Transporte de Cátions Orgânicos , Cisplatino/farmacologia , Transportador 2 de Cátion Orgânico , Flavonoides/farmacologia , Flavonóis
19.
Case Rep Ophthalmol ; 14(1): 34-38, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36741294

RESUMO

Here, we report the case of a patient with multiple parallel-line endotheliitis with myopic shift, which has not been previously reported. A 36-year-old man visited our clinic with blurred vision in his left eye. A slit lamp examination revealed an interesting pattern of multiple parallel lines of keratic precipitates, along with subtle corneal edema. The spherical equivalents measured in the right and left eyes were -9.25 and -11.875 diopter, respectively, with the left eye showing more myopic progression. On specular microscopy, endothelial cell loss was found in the left eye. After administration of a weak topical steroid, keratic precipitates and corneal edema resolved completely within 2 days. The myopic shift in his left eye recovered to -10.0 diopters. Multiple parallel-line endotheliitis can be easily treated with a weak topical steroid in a short period. A temporary myopic shift may occur, which in this case resolved upon disease recovery. However, corneal endothelial cell loss is inevitable; therefore, careful monitoring is needed.

20.
Artigo em Inglês | MEDLINE | ID: mdl-36780202

RESUMO

To obtain high-efficiency solution-processed organic light-emitting diodes (OLEDs), a hole transport material (HTM) capable of solution processing with excellent charge transport properties is required. In this study, a new vinyl polymer (PmCP) containing hole-transporting 1,3-di(9H-carbazol-9-yl)benzene (mCP) in the side chain was successfully synthesized via radical polymerization. PmCP showed good film-forming ability and thermal stability. Moreover, PmCP has a higher triplet energy value and hole mobility than poly(N-vinylcarbazole) (PVK) used as a reference HTM, which can be applied as a hole transport layer (HTL) in thermally activated delayed fluorescence (TADF) OLEDs, providing green and blue emissions. PmCP-based solution-processable TADF-OLEDs containing green- and blue-emitting layers were easily fabricated without damaging the lower HTL while using ethyl acetate as an orthogonal solvent. The corresponding OLEDs possess high external quantum efficiencies of 29.60% and 11.00% for the green- and blue-emitting devices, respectively. They show superior performances compared to PVK-based devices used as a reference. It was confirmed that PmCP as a solution-processable HTM can replace PVK and is universally applicable to both green- and blue-emitting devices.

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