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1.
J Chromatogr A ; 1681: 463474, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36088777

RESUMO

Owing to various health threats associated with phthalic acid esters (PAEs), this category of endocrine-disrupting compounds has attracted more and more public scrutiny. However, the efficient preconcentration of PAEs from complex food-contacted plastics still remains challenging. Herein, three covalent triazine-based frameworks (CTFs) were constructed by facile Friedel-Crafts reactions of cyanuric chloride (CC), with triptycene (TPC), fluorene (FL) and 1,3,5-triphenylbenzene (TPB), respectively. Three CTFs were then employed as solid-phase microextraction (SPME) coatings for the extraction of PAEs. Benefiting from the large surface area and high pore volume, the newly-synthesized CC-TPC based SPME method exhibited large enrichment factors (978-2210), low limits of detection (0.027-0.10 ng g - 1), satisfactory linear ranges (0.09-20 ng g - 1), acceptable repeatabilities (4.3-9.6%) and high relative recoveries (92.0-104.6%).


Assuntos
Ácidos Ftálicos , Microextração em Fase Sólida , Ésteres , Etilaminas , Fluorenos , Limite de Detecção , Plásticos , Microextração em Fase Sólida/métodos , Triazinas
2.
Ying Yong Sheng Tai Xue Bao ; 33(9): 2547-2556, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36131672

RESUMO

We screened and identified an endophytic bacterium that could efficiently degrade PAHs, which would expand the library of polycyclic aromatic hydrocarbons (PAHs) degrading microorganisms and reduce the pollution risk of crops. Its degradation mechanism and colonization performance were preliminarily examined. The results showed that strain PX1 belonged to Stenotrophomonas maltophilia. The strain had broad spectrum ability to remove PAHs. In PAH mineral salt (MS) media, almost 100% naphthalene was degraded by strain PX1 after 7-d incubation. In a cultivation system solely containing phenanthrene of 50.0 mg·L-1, pyrene of 20.0 mg·L-1, fluoranthene of 20.0 mg·L-1 or benzo[a]pyrene of 10.0 mg·L-1, the degradation efficiency of phenanthrene, pyrene, fluoranthene and benzo[a]pyrene by strain PX1 reached 72.6%, 50.7%, 31.9%, and 12.9%, respectively. Pyrene was selected as PAHs model to study the degradation characteristics of strain PX1. Enzyme activity tests showed that the activities of phthalate dioxygenase, catechol-1,2-dioxygenase, and catechol-2,3-dioxygenase in strain PX1 were induced by pyrene. Some metabolic intermediates such as 4,5-epoxypyrene, 4,5-dihydroxypyrene, gentilic acid/protocatechuic acid, salicylic acid, cis-hexadienedioic acid/2-hydroxymyxofuroic acid semialdehyde, cis-2'-carboxyphenylpyruvic acid, 1-hydroxy-2-naphthoic acid, and salicylaldehyde were detected during the degradation of pyrene by strain PX1. Results of the seed soaking experiment showed that strain PX1 could efficiently colonize in Ipomoea aquatic and Triticum aestivum. After inoculated with strain PX1, the growth of I. aquatic and T. aestivum was significantly increased, and the pyrene concentration in I. aquatic, T. aestivum and MS media was reduced by 29.8%-50.7%, 52.4%-67.1% and 8.0%-15.3%, respectively. Our results suggested that strain PX1 degraded pyrene mainly through 'salicylate pathway' and 'phthalate pathway', and could be colonized into plants and promote plant growth.


Assuntos
Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Stenotrophomonas maltophilia , Benzo(a)pireno/metabolismo , Biodegradação Ambiental , Catecol 2,3-Dioxigenase/metabolismo , Catecóis/metabolismo , Fluorenos , Minerais , Naftalenos/metabolismo , Fenantrenos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Pirenos/metabolismo , Ácido Salicílico , Stenotrophomonas maltophilia/metabolismo
3.
J Am Chem Soc ; 144(35): 16199-16205, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-35998350

RESUMO

We describe a stereocontrolled synthesis of 3, the fully glycosylated monomeric unit of the dimeric cytotoxic bacterial metabolite (-)-lomaiviticin A (2). A novel strategy involving convergent, site- and stereoselective coupling of the ß,γ-unsaturated ketone 6 and the naphthyl bromide 7 (92%, 15:1 diastereomeric ratio (dr)), followed by radical-based annulation and silyl ether cleavage, provided the tetracycle 5 (57% overall), which contains the carbon skeleton of the aglycon of 3. The ß-linked 2,4,6-trideoxy-4-aminoglycoside l-pyrrolosamine was installed in 73% yield and with 15:1 ß:α selectivity using a modified Koenigs-Knorr glycosylation. The diazo substituent was introduced via direct diazo transfer to an electron-rich benzoindene (4 → 27). The α-linked 2,6-dideoxyglycoside l-oleandrose was introduced by gold-catalyzed activation of an o-alkynyl glycosylbenzoate (75%, >20:1 α:ß selectivity). A carefully orchestrated endgame sequence then provided efficient access to 3. Cell viability studies indicated that monomer 3 is not cytotoxic at concentrations up to 1 µM, providing conclusive evidence that the dimeric structure of (-)-lomaiviticin A (2) is required for cytotoxic effects. The preparation of 3 provides a foundation to complete the synthesis of (-)-lomaiviticin A (2) itself.


Assuntos
Antineoplásicos , Fluorenos , Fluorenos/química , Glicosilação , Estrutura Molecular
4.
Int J Pharm ; 625: 122136, 2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-36029994

RESUMO

Although deferoxamine (DFO) has been approved for the treatment the iron overloaded diseases, its clinical application is impeded by very short circulation time and its relating toxicity. In this work, the fluorene methoxycarbonyl (FMOC) for "albumin hitchhiking" was used to prolong the plasma circulation time of DFO and reduce toxicity. The designed FMOC-PEG-DFO conjugates were found to reversible bind to albumin and gradually release DFO in vivo. Herein, the FMOC-PEG1000-DFO conjugates could increase 30 times the blood circulation time of DFO with the improvement of the iron elimination efficacy. Meanwhile, the conjugates markedly reduced the cytotoxicity of DFO. Taken together, the result demonstrated the FMOC-PEG1000-DFO conjugates could be a potential therapeutic choice for iron-overload-related diseases.


Assuntos
Desferroxamina , Sobrecarga de Ferro , Albuminas , Fluorenos/uso terapêutico , Humanos , Ferro , Quelantes de Ferro , Sobrecarga de Ferro/tratamento farmacológico , Polietilenoglicóis
5.
Soft Matter ; 18(34): 6360-6371, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35971808

RESUMO

Self-assembled peptide hydrogels have emerged as alternatives to the conventional approaches employed in controlled drug release, wound-healing, and drug delivery, and as anti-infective agents. However, peptide hydrogels possessing antibacterial properties are less explored. In this work, we have designed three ultrashort antibacterial peptide hydrogels: Fmoc-FFH-CONH2, Fmoc-FHF-CONH2, and Fmoc-HFF-CONH2. The rheological study showed the higher storage modulus of Fmoc-FFH-CONH2 (30.43 kPa) compared to Fmoc-FHF-CONH2 and Fmoc-HFF-CONH2, which may be attributed to the enhanced aromatic interaction in Fmoc-FFH-CONH2 compared to the other two variants, resulting in more mechanical rigidity. Further, the prepared hydrogels were evaluated for their inherent antibacterial potency against Gram-positive (Staphylococcus aureus, strain MTCC 96) and Gram-negative (Pseudomonas aeruginosa, strain PA01) bacteria. Antibacterial experiments demonstrated the potency of the hydrogels in the order of Fmoc-FFH-CONH2 > Fmoc-FHF-CONH2 > Fmoc-HFF-CONH2. The antibacterial effect of the hydrogels was predominantly due to the osmotic stress and membrane disruption, which was verified by reactive oxygen species (ROS) generation and outer membrane permeabilization assays. Our findings point to the scope of using the synthesized peptide hydrogels as agents for topical applications.


Assuntos
Fluorenos , Hidrogéis , Antibacterianos/química , Antibacterianos/farmacologia , Fluorenos/química , Hidrogéis/química , Peptídeos/química , Pseudomonas aeruginosa
6.
Antimicrob Agents Chemother ; 66(9): e0020722, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36036611

RESUMO

Antimalarial resistance threatens global malaria control efforts. The World Health Organization (WHO) recommends routine antimalarial efficacy monitoring through a standardized therapeutic efficacy study (TES) protocol. From June 2016 to March 2017, children with uncomplicated P. falciparum mono-infection in Siaya County, Kenya were enrolled into a standardized TES and randomized (1:1 ratio) to a 3-day course of artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP). Efficacy outcomes were measured at 28 and 42 days. A total of 340 children were enrolled. All but one child cleared parasites by day 3. PCR-corrected adequate clinical and parasitological response (ACPR) was 88.5% (95% CI: 80.9 to 93.3%) at day 28 for AL and 93.0% (95% CI: 86.9 to 96.4%) at day 42 for DP. There were 9.6 times (95% CI: 3.4 to 27.2) more reinfections in the AL arm compared to the DP arm at day 28, and 3.1 times (95% CI: 1.9 to 4.9) more reinfections at day 42. Both AL and DP were efficacious (per WHO 90% cutoff in the confidence interval) and well tolerated for the treatment of uncomplicated malaria in western Kenya, but AL efficacy appears to be waning. Further efficacy monitoring for AL, including pharmacokinetic studies, is recommended.


Assuntos
Antimaláricos , Artemisininas , Antagonistas do Ácido Fólico , Malária Falciparum , Malária , Quinolinas , Antimaláricos/efeitos adversos , Artemeter/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/efeitos adversos , Criança , Combinação de Medicamentos , Etanolaminas/efeitos adversos , Etanolaminas/uso terapêutico , Fluorenos/efeitos adversos , Fluorenos/uso terapêutico , Humanos , Lactente , Quênia , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Piperazinas , Plasmodium falciparum , Quinolinas/efeitos adversos , Reinfecção
7.
Antimicrob Agents Chemother ; 66(9): e0000222, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-35993723

RESUMO

The emergence of artemisinin-resistant parasites in Africa has had a devastating impact, causing most malaria cases and related deaths reported on the continent. In Ethiopia, artemether-lumefantrine (AL) is the first-line drug for the treatment of uncomplicated falciparum malaria. This study is one of the earliest evaluations of artemether-lumefantrine (AL) efficacy in western Ethiopia, 17 years after the introduction of this drug in the study area. This study aimed at assessing PCR- corrected clinical and parasitological responses at 28 days following AL treatment. Sixty uncomplicated falciparum malaria patients were enrolled, treated with standard doses of AL, and monitored for 28 days with clinical and parasitological assessments from September 15 to December 15, 2020. Microscopy was used for patient recruitment and molecular diagnosis of P. falciparum was performed by Var gene acidic terminal sequence (varATS) real-time PCR on dried blood spots collected from each patient from day 0 and on follow-up days 1, 2, 3, 7, 14, 21, and 28. MspI and msp2 genotyping was done to confirm occurrence of recrudescence. Data entry and analysis were done by using the WHO-designed Excel spreadsheet and SPSS version 20 for Windows. A P value of less or equal to 0.05 was considered significant. From a total of 60 patients enrolled in this efficacy study, 10 were lost to follow-up; the results were analyzed for 50 patients. All the patients were fever-free on day 3. The asexual parasite positivity rate on day 3 was zero. However; 60% of the patients were PCR positive on day 3. PCR positivity on day 3 was more common among patients <15 years old as compared with those ≥15 years old (AOR = 6.44, P = 0.027). Only two patients met the case definition of treatment failure. These patients were classified as a late clinical failure as they showed symptoms of malaria and asexual stages of the parasite detected by microscopy on day 14 of their follow-ups. Hence, the Kaplan-Meier analysis of PCR- corrected adequate clinical and parasitological response (ACPR) rate of AL among study participants was 96% (95% CI: 84.9-99). In seven patients, the residual submicroscopic parasitemia persists from day 0 to day 28 of the follow-up. In addition, 16% (8/50) of patients were PCR- and then turned PCR+ after day 7 of the follow-up. AL remains efficacious for the treatment of uncomplicated falciparum malaria in the study area. However, the persistence of PCR-detected residual submicroscopic parasitemia following AL might compromise this treatment and need careful monitoring.


Assuntos
Antimaláricos , Artemisininas , Malária Falciparum , Malária , Adolescente , Antimaláricos/uso terapêutico , Artemeter/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Progressão da Doença , Etanolaminas/uso terapêutico , Etiópia , Fluorenos/uso terapêutico , Humanos , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Parasitemia/tratamento farmacológico , Plasmodium falciparum/genética , Sudão , Resultado do Tratamento
8.
Ecotoxicol Environ Saf ; 243: 113982, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35987080

RESUMO

Fluorene-9-bisphenol (BHPF), which has been used as a substitute for bisphenol A (BPA) in consumer goods and industrial products, can be detected in environmental media and human urine. BHPF has been reported to have endocrine-disrupting effects, whereas deleterious effects on steroidogenesis in H295R cells and underlying mechanisms are still unclear. Here, we investigated effects of BHPF on steroidogenesis using human adrenocortical carcinoma cells (H295R). Cytotoxicity was initially assessed and half-maximal inhibitory concentration (IC50) was determined based on proliferation of cells. Responses of four steroid hormones, aldosterone, cortisol, testosterone and 17ß-estradiol (E2), and ten critical genes, StAR, HMGR, CYP11A1, CYP11B1, CYP11B1, HSD3B2, CYP21, CYP17, 17ß-HSD, and CYP19, involved in steroidogenesis after exposure to non-cytotoxic concentrations of BHPF were determined in the presence or absence of 100 µM dbcAMP. Adenylate cyclase (AC) activity, intracellular concentrations of cAMP, PKA activity and amounts of steroidogenic factor-1 (SF-1) gene and expressions of proteins were determined to elucidate underlying mechanisms of effects on steroidogenesis. BHPF was cytotoxic to H295R cells in a dose- and time-dependent manner. Effects on production of hormones results demonstrated that exposure to greater concentrations of BHPF inhibited productions of aldosterone, cortisol, testosterone and E2 by down-regulation of steroidogenic genes. Inhibition of AC activity, intercellular cAMP content and PKA activity after exposure to BHPF implied that the AC/cAMP/PKA signaling pathway was involved in BHPF-induced suppression of steroidogenesis in H295R cells. Additionally, BHPF inhibited steroidogenesis and expressions of steroidogenic genes via decreasing expression of SF-1 protein, both in basal and dbcAMP-induced treatment. These results contributed to understanding molecular mechanisms of BHPF-induced effects on steroidogenesis and advancing the comprehensive risk assessment of BPs.


Assuntos
Aldosterona , Hidrocortisona , Aldosterona/metabolismo , Compostos Benzidrílicos , Bucladesina , Linhagem Celular Tumoral , Fluorenos , Humanos , Hidrocortisona/metabolismo , Fenóis , Transdução de Sinais , Esteroide 11-beta-Hidroxilase/metabolismo , Testosterona/metabolismo
9.
Environ Health ; 21(1): 75, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35945606

RESUMO

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that may contribute to the etiology of obesity. However, it is unclear whether PAHs from environmental sources are associated with regional body fat distribution, and whether the association varies across racial/ethnic groups who may have differential PAH exposure patterns. OBJECTIVES: To examine correlations between PAHs and body fat distribution, and potential racial/ethnic differences among U.S. adults. METHODS: Ten PAHs were measured in spot urine samples from 2691 non-smoking adults (age ≥ 20 years) in the NHANES 2001-2016. Dual-energy X-ray absorptiometry was used to measure fat mass percent (FM%). Partial Pearson correlation coefficients (r) with multivariable adjustment were used to assess PAH-FM% associations. RESULTS: In the total population, 1-naphthalene, 3-fluorene, and 1-pyrene were inversely correlated with total FM% or trunk FM% (adjusted r ranged: - 0.06 to - 0.08), while 2-naphthalene, 9-fluorene, and 4-phenanthrene were positively correlated with the FM% measurements (r: 0.07-0.11). PAH levels are highest among non-Hispanic Blacks, followed by Hispanics and Whites and some of the correlations were different by these races/ethnicities. Among non-Hispanic Whites, no PAH was correlated with FM%. In contrast, 9-fluorene was positively correlated with total FM% (r = 0.20) and trunk FM% (r = 0.22) among Blacks, and 4-phenanthrene was positively correlated with total FM% (r = 0.23) and trunk FM% (r = 0.24) among Hispanics (P-interaction: 0.010-0.025). DISCUSSION: In this US adult population, certain PAHs are significantly associated with higher body fat contents among non-Hispanic Blacks and Hispanics but not non-Hispanic Whites, suggesting that minority groups might be particularly susceptible to PAH's obesogenic effects or the effects of other factors that determine the PAH exposure levels. Alternatively, differences in body composition may contribute to differential PAH metabolism in minority groups. Future studies are warranted to explore the racial/ethnic disparity in PAH exposures, drivers of these exposure differences, and mechanisms through which PAHs may influence body composition by races/ethnicities.


Assuntos
Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Adulto , Biomarcadores/urina , Distribuição da Gordura Corporal , Fluorenos/urina , Humanos , Naftalenos , Inquéritos Nutricionais , Fenantrenos/urina , Hidrocarbonetos Policíclicos Aromáticos/urina , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-35902060

RESUMO

Fluorene-9-bisphenol (BPFL) is used as an alternative compound for bisphenol A, an endocrine disruptor compound which is present in various materials including plastic bottles and packaging. Although it is used extensively in products that are labelled BPA-free, its effect on wildlife and humans have not been fully studied. Therefore, this study aimed to investigate the effects of BPFL in adult zebrafish. In the preliminary experiments of the study, the median lethal concentration value (LC50) of BPFL was 0.25 mg/L (95 % confidence interval 0.15-0.41) for 96 h. Following exposure to three different sublethal concentrations of BPFL after 96 h and 15 days, T4 hormone levels, expression levels of genes involved in thyroid metabolism and histopathological alterations were assessed. T4 hormone levels were found to be significantly higher in females at the lowest BPFL concentration following 96 h exposure (P < 0.05). Expression levels of trh, tshba and trhrb genes were upregulated following 96 h exposure at 0.025 mg/L concentration and crh was upregulated following 15 days exposure at 0.025 mg/L concentration in female zebrafish (P < 0.05). The most prominent histopathological findings in zebrafish exposed to 0.025 and 0.125 mg/L of BPFL were observed in the gill, liver, kidney and testis tissues. The gill tissues showed some hyperemia, lamellar fusion, hyperplasia, epithelial lifting, and telangiectasis, while passive hyperemia, hydropic degeneration, and necrosis were observed in the liver tissues. The BPFL is highly toxic to zebrafish even in sublethal concentrations according to the molecular and histopathological responses.


Assuntos
Disruptores Endócrinos , Poluentes Químicos da Água , Animais , Compostos Benzidrílicos/metabolismo , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/metabolismo , Feminino , Fluorenos , Hormônios/metabolismo , Humanos , Masculino , Fenóis , Plásticos/toxicidade , Glândula Tireoide , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/metabolismo
11.
Paediatr Drugs ; 24(5): 529-537, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35838919

RESUMO

BACKGROUND: Chronic hepatitis C virus (HCV) infection represents a crucial health problem in children that greatly influences their quality of life. Many efforts have been directed toward investing in effective drugs with a high safety profile and oral administration for better compliance. OBJECTIVES: This study aims to assess the safety of a fixed-dose combination of ledipasvir/sofosbuvir plus drug efficacy and sustained virologic response (SVR) at 12 weeks after treatment discontinuation. METHOD: One tablet (90 mg ledipasvir, 400 mg sofosbuvir) was administered to treatment-naïve children aged 12-18 years weighing at least 35 kg with chronic HCV infection for 6 months, genotype 4. Patients were divided into 2 groups, (1) without comorbidities (24 patients) and (2) with comorbidities (26 patients). RESULTS: At the end of the therapy, all patients (100%) had SVR and a significant reduction of liver enzymes with mild tolerable side effects. CONCLUSION: Ledipasvir/sofosbuvir fixed-dose combination is a safe and highly effective therapeutic option in Egyptian children aged ≥ 12 years, with chronic HCV infection, genotype 4, either without or with comorbidities.


Assuntos
Hepatite C Crônica , Sofosbuvir , Antivirais/efeitos adversos , Benzimidazóis , Criança , Quimioterapia Combinada , Fluorenos/efeitos adversos , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Humanos , Qualidade de Vida , Sofosbuvir/efeitos adversos , Resultado do Tratamento
12.
Ecotoxicol Environ Saf ; 242: 113906, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35878500

RESUMO

Identifying chemicals with endocrine disrupting properties linked to disease outcomes is a key concern, as stated in the WHO-UNEP 2012 report on endocrine-disrupting chemicals. The chemical 9,9-bis[4-(2-hydroxyethoxy)phenyl]fluorene (BPEF) is widely and increasingly applied in synthesizing fluorene-based cardo polymers with superior optical, thermal and mechanical properties for various uses. However, little toxicological information is available regarding its safety. Here, we studied the endocrine disrupting property of BPEF by multiple toxicological tools and investigated its effects on female development in adolescent mice. Using the yeast two-hybrid bioassay, BPEF showed strong antiestrogenicity which was similar to that of tamoxifen, an effective antiestrogenic drug. In adolescent CD-1 mice, BPEF significantly decreased the uterine weight at relatively low doses and induced marked endometrial atrophy. Immunohistochemical staining and transcriptome analyses of the mice uteri revealed that BPEF could repressed the expressions of estrogen-responsive genes. Molecular simulation indicated that BPEF could be docked into the antagonist pocket of human estrogen receptor α, and the formation of hydrogen bonds and hydrophobic interactions between BPEF and the active site of receptor maintained their strong binding. All of the data demonstrated that BPEF possessed strong antiestrogenic property and might disrupt female development, suggesting it should be avoided in making products that might directly expose to people, particularly immature women.


Assuntos
Disruptores Endócrinos , Antagonistas de Estrogênios , Adolescente , Animais , Disruptores Endócrinos/análise , Antagonistas de Estrogênios/toxicidade , Estrogênios , Feminino , Fluorenos/toxicidade , Humanos , Camundongos , Tamoxifeno
13.
J Am Chem Soc ; 144(30): 13499-13510, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35862745

RESUMO

The unique four-level photocycle characteristics of excited-state intramolecular proton transfer (ESIPT) materials enable population inversion and large spectral separation between absorption and emission through their respective enol and keto forms. This leads to minimal or no self-absorption losses, a favorable feature in acting as an optical gain medium. While conventional ESIPT materials with an enol-keto tautomerism process are widely known, zwitterionic ESIPT materials, particularly those with high photoluminescence, are scarce. Facilitated by the synthesis and characterization of a new family of 2-hydroxyphenyl benzothiazole (HBT) with fluorene substituents, HBT-Fl1 and HBT-Fl2, we herein report the first efficient zwitterionic ESIPT lasing material (HBT-Fl2). The zwitterionic ESIPT HBT-Fl2 not only shows a remarkably low solid-state amplified spontaneous emission (ASE) threshold of 5.3 µJ/cm2 with an ASE peak at 609 nm but also exhibits high ASE photostability. Coupled with its substantially large Stokes shift (≈236 nm ≈10,390 cm-1) and an extremely small overlap of excited-state absorption with ASE emission, comprehensive density functional theory (DFT) and time-dependent DFT studies reveal the zwitterionic characteristics of HBT-Fl2. In opposition to conventional ESIPT with π-delocalized tautomerism as observed in analogue HBT-Fl1 and parent HBT, HBT-Fl2 instead shows charge redistribution in the proton transfer through the fluorene conjugation. This structural motif provides a design tactic in the innovation of new zwitterionic ESIPT materials for efficient light amplification in red and longer-wavelength emission.


Assuntos
Fluorenos , Prótons
14.
Arab J Gastroenterol ; 23(3): 165-171, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35690556

RESUMO

BACKGROUND AND STUDY AIMS: Currently, there is no therapy approved for COVID-19. We evaluated the efficacy and safety of sofosbuvir/ledipasvir and nitazoxanide for the treatment of patients with COVID-19 infection. PATIENTS AND METHODS: A multicenter, open-label randomized controlled trial included one hundred and ninety patients with non-severe COVID-19 infection. Patients were randomized into three groups. All groups received standard care treatment (SCT). In addition, group 1 received sofosbuvir/ledipasvir, and group 2 received nitazoxanide. Follow-up by reverse-transcriptase polymerase chain reaction (RT-PCR) was done at intervals of 5, 8, 11, and 14 days. The primary endpoint was viral clearance. RESULTS: Viral clearance was significantly higher in the sofosbuvir/ledipasvir and nitazoxanide groups compared to the SCT group in all follow-up intervals (p < 0.001). In the sofosbuvir/ledipasvir arm, 36.9% showed early viral clearance by day 5. By day 14, 83.1% of the sofosbuvir/ledipasvir group, 39.7% of the nitazoxanide group, and 19.4% of the SCT group tested negative for SARS-CoV-2. Sofosbuvir/ledipasvir and nitazoxanide treatment were the only significant factors in Cox regression of negative RT-PCR with the highest OR (17.88, 95% CI: 6.66-47.98 and 2.59, 95% CI: 1.11-6.07, respectively). No mortality or serious adverse events were recorded. CONCLUSION: The addition of sofosbuvir/ledipasvir or nitazoxanide to the SCT results in an early and high viral clearance rate in mild and moderate patients with COVID-19. These drugs represent a safe and affordable treatment for COVID-19.


Assuntos
COVID-19 , Sofosbuvir , Antivirais/uso terapêutico , Benzimidazóis , COVID-19/tratamento farmacológico , Reposicionamento de Medicamentos , Quimioterapia Combinada , Fluorenos , Genótipo , Hepacivirus , Humanos , Nitrocompostos , SARS-CoV-2 , Sofosbuvir/uso terapêutico , Tiazóis , Resultado do Tratamento , Carga Viral
15.
Nanoscale ; 14(23): 8525-8533, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35660804

RESUMO

Over the last decade, three-dimensional (3D) printing technologies have attracted the interest of researchers due to the possibility of fabricating tissue- and organ-like structures with similarities to the organ of interest. One of the most widely used materials for the fabrication of bioinks is gelatin (Gel) due to its excellent biocompatibility properties. However, in order to fabricate stable scaffolds under physiological conditions, the most common approach is to use gelatin methacrylate (GelMA) that allows the crosslinking and therefore the stabilization of the hydrogel through UV crosslinking. The crosslinking process can be harmful to cells thus decreasing total cell viability. To overcome the need for post-printing crosslinking, a new approach of bioink formulation was studied, incorporating the Fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) peptide into the Gel bioink. However, although Fmoc-FF possesses excellent mechanical properties, the lack of elasticity and viscosity makes it unsuitable for 3D-printing. Here, we demonstrate that covalent conjugation of two different ethylene glycol (EG) motifs to the Fmoc-FF peptide increases the hydrophilicity and elasticity properties, which are essential for 3D-printing. This new approach for bioink formulation avoids the need for any post-printing manufacturing processes, such as chemical or UV crosslinking.


Assuntos
Etilenoglicol , Gelatina , Dipeptídeos , Etilenos , Fluorenos , Hidrogéis/química , Peptídeos , Fenilalanina , Impressão Tridimensional , Engenharia Tecidual/métodos , Tecidos Suporte/química
16.
Endocr Pract ; 28(9): 867-874, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35764250

RESUMO

OBJECTIVE: We aimed to analyze the association between certain types of urinary polycyclic aromatic hydrocarbons (PAHs) and bone mineral density (BMD) at specific sites of the body. METHODS: A total of 2978 eligible participants from the National Health and Nutrition Examination Survey 2001 to 2004 were included in this study. Data of 8 urinary PAHs and BMDs of 3 skeleton sites and the total body were analyzed. Univariate and multivariate linear regression analyses were performed to explore the association between urinary PAHs and BMDs. Subgroup analyses stratified by sex and body mass index were also performed. RESULTS: After adjustment for all confounders, elevated 3-fluorene (ß = 0.046; 95% confidence intervals [CIs], 0.007-0.084) and 2-fluorene (ß = 0.054; 95% CI, 0.007-0.100) levels were associated with greater left arm BMD, whereas no statistical differences were observed in the relationship between other PAHs and BMDs (all P > .05). Higher 3-fluorene and 2-fluorene levels were still associated with increased left arm BMD in men (P < .05), whereas the higher 2-phenanthrene level was related to decreased left arm BMD (ß = -0.062; 95% CI, -0.105 to -0.019), right arm BMD (ß = -0.059; 95% CI, -0.091 to -0.027), and total BMD (ß = -0.065; 95% CI, -0.119 to -0.012) in women. Similar results were also found in different body mass index populations (all P < .05). CONCLUSION: Certain urinary PAHs are associated with BMDs at specific body sites. Future studies are needed to illustrate the mechanisms behind the association to establish a causal relationship.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Adulto , Índice de Massa Corporal , Densidade Óssea , Feminino , Fluorenos , Humanos , Masculino , Inquéritos Nutricionais
17.
Drugs Today (Barc) ; 58(6): 299-309, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35670707

RESUMO

Epithelial ovarian cancers are gynecological malignancies with the poorest prognosis. Intensive research over the past few years has demonstrated ovarian cancer is a type of cancer in which new molecularly targeted drugs significantly affect patients' fate and prognosis. These drugs are poly [ADP-ribose] polymerase (PARP) inhibitors, which are used for maintenance treatment. These molecules continue to be intensively studied--their combination with other targeted therapies is carefully evaluated as more of them are discovered. Four PARP inhibitors have been approved by the U.S. Food and Drug Administration (FDA) so far. Olaparib, rucaparib and niraparib are approved for various indications in epithelial ovarian cancer, fallopian tube or primary peritoneal cancer, while the PARP inhibitors for the treatment of breast cancer are olaparib and talazoparib. Olaparib is also approved for the treatment of pancreatic cancer as well as prostate cancer, and rucaparib is also approved for prostate cancer. Pamiparib (Partruvix) is a new, selective inhibitor of PARP-1 and PARP-2 which was discovered by BeiGene Ltd. On April 30, 2021, pamiparib obtained its first registration worldwide--it was approved in China for the treatment of women with recurrent ovarian, fallopian tube or primary peritoneal cancer with confirmed germline BRCA mutation.


Assuntos
Neoplasias Ovarianas , Neoplasias da Próstata , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Tubas Uterinas/patologia , Feminino , Fluorenos , Células Germinativas/patologia , Humanos , Masculino , Mutação , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Proteínas Supressoras de Tumor/genética
18.
J Viral Hepat ; 29(9): 795-806, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35657133

RESUMO

The PRIORITIZE trial (clinicaltrials.gov: NCT02786537) was the first comparative effectiveness study to directly compare ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic hepatitis C virus (HCV). A secondary aim of this study was to compare LDV/SOF and EBR/GZR on sustainable changes in several HCV-associated symptoms and functional well-being in patients who achieved sustained virological response (SVR). PRIORITIZE, a randomized controlled trial conducted between 2016 and 2020, evaluated change in six PROMIS® symptom scores (fatigue, sleep disturbance, cognitive disturbance, nausea, diarrhoea, abdominal pain) and functional well-being using the disease-specific HCV-PRO instrument. Survey assessments were administered at baseline, early post-treatment (median = 6 months) and late post-treatment (median = 21 months). Constrained longitudinal linear mixed-effects models were used to evaluate within-treatment change and between-treatment differences. Data from 793 participants (average 55 years old, 57% male, 44% black, 17% with cirrhosis) were analysed. From baseline to early post-treatment, 5 out of 6 symptoms and functional well-being significantly improved (all p's < .05). In the LDV/SOF arm, mean changes ranged from -3.73 for nausea to -6.41 for fatigue and in the EBR/GZR, mean changes ranged from -2.19 for cognitive impairment to -4.67 for fatigue. Change of >3 points was consider clinically meaningful. Improvements in most symptoms slightly favoured LDV/SOF, although the magnitude of differences between the regimens were small. Both regimens demonstrated significant improvements in symptoms and functional well-being that were sustained during the late post-treatment phase. EBR/GZR and LDV/SOF regimens had clinically equivalent and durable improvements in HCV symptoms and functional well-being up to two years after SVR.


Assuntos
Hepatite C Crônica , Hepatite C , Amidas , Antivirais/uso terapêutico , Benzimidazóis , Benzofuranos , Carbamatos , Ciclopropanos , Quimioterapia Combinada , Fadiga , Feminino , Fluorenos/uso terapêutico , Genótipo , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Imidazóis , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológico , Quinoxalinas , Sofosbuvir/uso terapêutico , Sulfonamidas
19.
Org Biomol Chem ; 20(24): 4964-4969, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35660847

RESUMO

The base promoted domino reaction of bindone ([1,2'-biindenylidene]-1',3,3'-trione) with common 1,3-dipolarophiles showed interesting molecular diversities, from which the unique spiro and fused indeno[1,2-a]fluorine derivatives were conveniently synthesized in satisfactory yields. In the presence of a base, bindone underwent formal [3 + 3] cycloaddition with satylidene malononitriles to give dispiro[indene-2,4'-fluorene-1',3''-indoline]. It also underwent formal [4 + 2] cycloaddition with 4-arylidene-pyrazol-3-ones to give diastereoisomeric spiro[indeno[1,2-a]fluorene-5,4'-pyrazole]. On the other hand, a triethylamine promoted reaction of three molecules of 1,3-indanediones and isatins in toluene afforded spiro[diindeno[2,1-b:2',1'-d]anthracene-11,3'-indoline] derivatives through the domino [4 + 2] cycloaddition and ring-expansion process.


Assuntos
Compostos de Espiro , Reação de Cicloadição , Fluorenos
20.
Malar J ; 21(1): 194, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35725411

RESUMO

We read with interest the publication on malaria treatment by Obonyo et al. (Malaria J 21:30, 2022). This commentary questions the methodology, especially the chosen time points of treatment outcome measures.


Assuntos
Antimaláricos , Artemisininas , Malária Falciparum , Malária , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Combinação de Medicamentos , Etanolaminas/uso terapêutico , Fluorenos/uso terapêutico , Humanos , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Quinina/uso terapêutico , Resultado do Tratamento
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