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1.
Clin Ophthalmol ; 18: 1217-1224, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737597

RESUMO

Aim: To determine the prevalence of dry eye (DE) and some related factors in patients with type 2 diabetic nephropathy (T2DN). Methods: We performed a cross-sectional study on 338 people, who were divided into 2 groups: 169 T2DN patients and 169 patients diagnosed with type 2 diabetic mellitus (T2DM) without renal complications as a control group. The Ocular Surface Disease Index (OSDI) and test fluorescein tear-film break-up time (TBUT) were done in all 338 subjects. Patients with OSDI scores < 13 and TBUT values equal to or under 10 seconds were diagnosed with dry eye. Results: The prevalence of DE in T2DN patients was significantly higher than T2DM group (55.6% versus 37.3%). The T2DN groups with dry eye had a median duration of DM, the proportion of hypertension, peripheral nerve complications, anemia, proportion of using insulin, and concentration of plasma glucose, HbA1C, urea, creatinine, CRP-hs significantly higher than those of T2DN without dry eye. Advanced age, high HbA1C level, and decreased eGFR were independent factors associated with dry eye in T2DN patients. Conclusion: Dry eye was a common condition associated with advanced age, high HbA1C levels, and decreased GFR in T2DN patients.

2.
Heliyon ; 10(4): e26048, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38370184

RESUMO

For enhanced applications of solar cells, organic luminescence materials like long persistent luminescence (LPL) present one of the promising avenues for light enhancement. Currently, most existing luminescent materials are based on an inorganic system that requires rare elements such as europium and dysprosium, with a very high processing temperature. Adopting organic luminescence materials that are free from rare elements is necessary, considering the low-temperature fabrication and low material cost. In this work, we investigate the optical properties of an organic luminescence blend consisting of 2,8-bis(diphenylphosphoryl)dibenzo [b,d]thiophene (PPT) and N,N,N',N'-tetramethylbenzidine (TMB) through computational studies and experimental validations. Optical characteristics of the luminescence materials like optical absorption, photoluminescence, and time-resolved photoluminescence spectroscopy are characterized. To validate the functionality of the organic luminescence blend, the material is incorporated into the perovskite solar cell structure. Unfortunately, the blend is unable to emit sufficient illumination over extended periods due to its low intersystem crossing efficiency and weak spin-orbit coupling. Although the power conversion efficiency of the Luminescence/FTO/TiO2/Perovskite/Carbon structure is observed to be small under dark conditions, the application of organic luminescence materials can be further enhanced and explored.

3.
Int J Gen Med ; 17: 553-557, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38371519

RESUMO

Objective: To evaluate the effectiveness of ultrasound-guided needle aspiration in treating lactating breast abscesses. Methods: This study was conducted in Bach Mai Hospital, from 6/2020 to 7/2021. Lactating patients with breast abscesses underwent ultrasound-guided aspiration followed by antibiotics therapy. Results: There were 59 lactating patients with 82 breast abscesses. Most of the abscesses had heterogeneous echogenicity, no capsule, and a size smaller than 5cm. Bacterial culture results showed that 85.4% of cases were Methicillin-resistant Staphylococcus aureus. The number of aspirations was from 1 to 5. The cure rate was 91.5%, and 5.3% of these cases had a complication associated with galactocele after treatment. Conclusion: Ultrasound-guided needle aspiration is a minimally invasive treatment option for lactating breast abscesses with a high complete cure rate and good cosmetic results.

4.
Int J Gen Med ; 17: 105-113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38229881

RESUMO

Aim: To determine all-cause mortality rate and the predictive value of plasma ferritin and total iron-binding capacity (TIBC) concentrations for mortality during the first 3 years of hemodialysis in patients with end-stage chronic renal disease (ESRD). Methods: We conducted a study on 174 ESRD patients (estimated Glomerular Filtration Rate < 15 mL/min/1.73m2). The plasma TIBC level was quantified by the ELISA method in all patients at the time before hemodialysis. Based on TIBC concentration, patients were divided equally into 2 groups. Each group had 87 patients. Patients were initiated on hemodialysis, and patients who died from any cause during the first 3 years of hemodialysis were recorded. Results: The all-cause mortality rate of ESRD patients in the first 3 years of maintenance hemodialysis was 22.9%. Plasma high hs-CRP, high ferritin, and low TIBC concentrations were independent factors associated with all-cause mortality in the patients. Plasma ferritin (cut-off value = 454.2 ng/L) and TIBC (cut-off value = 39.84 µmol/L) were predictors of all-cause mortality, AUC is: 0.772; 0.723, p < 0.001. Conclusion: Plasma ferritin and TIBC were good predictors of all-cause mortality in ESRD patients during the first 3 years of hemodialysis.

5.
Mol Ecol ; : e17244, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38108560

RESUMO

Natural variation can provide important insights into the genetic and environmental factors that shape social behaviour and its evolution. The sweat bee, Lasioglossum baleicum, is a socially flexible bee capable of producing both solitary and eusocial nests. We demonstrate that within a single nesting aggregation, soil temperatures are a strong predictor of the social structure of nests. Sites with warmer temperatures in the spring have a higher frequency of social nests than cooler sites, perhaps because warmer temperatures provide a longer reproductive window for those nests. To identify the molecular correlates of this behavioural variation, we generated a de novo genome assembly for L. baleicum, and we used transcriptomic profiling to compare adults and developing offspring from eusocial and solitary nests. We find that adult, reproductive females have similar expression profiles regardless of social structure in the nest, but that there are strong differences between reproductive females and workers from social nests. We also find substantial differences in the transcriptomic profiles of stage-matched pupae from warmer, social-biased sites compared to cooler, solitary-biased sites. These transcriptional differences are strongly predictive of adult reproductive state, suggesting that the developmental environment may set the stage for adult behaviours in L. baleicum. Together, our results help to characterize the molecular mechanisms shaping variation in social behaviour and highlight a potential role of environmental tuning during development as a factor shaping adult behaviour and physiology in this socially flexible bee.

6.
Biomedicines ; 11(10)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37893216

RESUMO

Osteoarthritis (OA) is the most common joint disease that causes local inflammation and pain, significantly reducing the quality of life and normal social activities of patients. Currently, there are no disease-modifying OA drugs (DMOADs) available, and treatment relies on pain relief agents or arthroplasty. To address this significant unmet medical need, we aimed to develop monoclonal antibodies that can block the osteoclast-associated receptor (OSCAR). Our recent study has revealed the importance of OSCAR in OA pathogenesis as a novel catabolic regulator that induces chondrocyte apoptosis and accelerates articular cartilage destruction. It was also shown that blocking OSCAR with a soluble OSCAR decoy receptor ameliorated OA in animal models. In this study, OSCAR-neutralizing monoclonal antibodies were isolated and optimized by phage display. These antibodies bind to and directly neutralize OSCAR, unlike the decoy receptor, which binds to the ubiquitously expressed collagen and may result in reduced efficacy or deleterious off-target effects. The DMOAD potential of the anti-OSCAR antibodies was assessed with in vitro cell-based assays and an in vivo OA model. The results demonstrated that the anti-OSCAR antibodies significantly reduced cartilage destruction and other OA signs, such as subchondral bone plate sclerosis and loss of hyaline cartilage. Hence, blocking OSCAR with a monoclonal antibody could be a promising treatment strategy for OA.

7.
Methods Mol Biol ; 2702: 93-106, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37679617

RESUMO

Rabbits have distinct advantages over mice as a source of target-specific antibodies. They produce higher affinity antibodies than mice and may elicit strong immune response against antigens or epitopes that are poorly immunogenic or tolerated in mice. However, a great majority of currently available monoclonal antibodies are of murine origin because of the wider availability of murine fusion partner cell lines and well-established tools and protocols for fusion and cloning of mouse hybridoma. Phage display selection of antibody libraries is an alternative method to hybridoma technology for the generation of target-specific monoclonal antibodies. High-affinity monoclonal antibodies from non-murine species can readily be obtained by constructing immune antibody libraries from B cells of the immunized animal and screening the library by phage display. In this article, we describe the construction of a rabbit immune Fab library for the facile isolation of rabbit monoclonal antibodies. After immunization, B-cell cDNA is obtained from the spleen of the animal, from which antibody variable domain repertoires are amplified and assembled into a Fab repertoire by PCR. The Fab genes are then cloned into a phagemid vector and transformed to E. coli, from which a phage-displayed immune Fab library is rescued. Such a library can be biopanned against the immunization antigen for rapid identification of high-affinity, target-specific rabbit monoclonal antibodies.


Assuntos
Anticorpos Monoclonais , Escherichia coli , Animais , Camundongos , Anticorpos Monoclonais/genética , Linfócitos B , Linhagem Celular , Técnicas de Visualização da Superfície Celular
8.
bioRxiv ; 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37645955

RESUMO

Natural variation can provide important insights into the genetic and environmental factors that shape social behavior and its evolution. The sweat bee, Lasioglossum baleicum , is a socially flexible bee capable of producing both solitary and eusocial nests. We demonstrate that within a single nesting aggregation, soil temperatures are a strong predictor of the social structure of nests. Sites with warmer temperatures in the spring have a higher frequency of social nests than cooler sites, perhaps because warmer temperatures provide a longer reproductive window for those nests. To identify the molecular correlates of this behavioral variation, we generated a de novo genome assembly for L. baleicum , and we used transcriptomic profiling to compare adults and developing offspring from eusocial and solitary nests. We find that adult, reproductive females have similar expression profiles regardless of social structure in the nest, but that there are strong differences between reproductive females and workers from social nests. We also find substantial differences in the transcriptomic profiles of stage-matched pupae from warmer, social-biased sites compared to cooler, solitary-biased sites. These transcriptional differences are strongly predictive of adult reproductive state, suggesting that the developmental environment may set the stage for adult behaviors in L. baleicum . Together, our results help to characterize the molecular mechanisms shaping variation in social behavior and highlight a potential role of environmental tuning during development as a factor shaping adult behavior and physiology in this socially flexible bee.

9.
Biol Lett ; 19(6): 20230149, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37311547

RESUMO

The evolution of group living is associated with increased pressure from parasites and pathogens. This can be offset by greater investment in personal immune defences and/or the development of cooperative immune defences (social immunity). An enduring question in evolutionary biology is whether social-immune benefits arose in response to an increased need in more complex societies, or arose early in group living and helped facilitate the evolution of more complex societies. In this study, we shed light on this question through investigating how immunity varies intraspecifically in a socially polymorphic bee. Using a novel immune assay, we show that personal antibacterial efficacy in individuals from social nests is higher than that of solitary individuals, but that this can be explained by higher densities in social nests. We conclude that personal immune effects are likely to play a role in the social/solitary transition in this species. These patterns are consistent with the idea that social immunity evolved secondarily, following the evolution of group living. The flexibility of the individual immune system may have favoured a reliance on its use during the facultative phase early in social evolution.


Assuntos
Antibacterianos , Status Social , Animais , Abelhas
10.
Mov Disord ; 38(5): 854-865, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36788159

RESUMO

BACKGROUND: Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose-response relations based on time-varying exposures. OBJECTIVES: We examined whether statin use is associated with PD incidence while attempting to overcome the limitations described previously, especially reverse causation. METHOD: We used data from the E3N cohort study of French women (follow-up, 2004-2018). Incident PD was ascertained using multiple sources and validated by experts. New statin users were identified through linked drug claims. We set up a nested case-control study to describe trajectories of statin prescriptions and medical consultations before diagnosis. We used time-varying multivariable Cox proportional hazards regression models to examine the statins-PD association. Exposure indexes included ever use, cumulative duration/dose, and mean daily dose and were lagged by 5 years to address reverse causation. RESULTS: The case-control study (693 cases, 13,784 controls) showed differences in case-control trajectories, with changes in the 5 years before diagnosis in cases. Of 73,925 women (aged 54-79 years), 524 developed PD and 11,552 started using statins in lagged analyses. Ever use of any statin was not associated with PD (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.67-1.11). Alternatively, ever use of lipophilic statins was significantly associated with lower PD incidence (HR = 0.70, 95% CI = 0.51-0.98), with a dose-response relation for the mean daily dose (P-linear trend = 0.02). There was no association for hydrophilic statins. CONCLUSION: Use of lipophilic statins at least 5 years earlier was associated with reduced PD incidence in women, with a dose-response relation for the mean daily dose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Doença de Parkinson , Humanos , Feminino , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos de Coortes , Estudos de Casos e Controles , Incidência
11.
Brain ; 146(6): 2535-2546, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36415953

RESUMO

Despite experimental studies suggesting a disease-modifying role of oestrogens, results from epidemiological studies on the relation of reproductive characteristics and hormonal exposures with Parkinson disease in women are conflicting. We used the data from the E3N cohort study including 98 068 women aged 40-65 years in 1990 followed until 2018. Parkinson disease was ascertained using a validation process based on drug claim databases and medical records. Reproductive characteristics and hormonal exposures were self-reported (11 questionnaires). Associations of exposures with Parkinson disease incidence were investigated using time-varying Cox proportional hazards regression with a 5-year exposure lag and age as the timescale adjusted for confounders. We identified 1165 incident Parkinson disease cases during a mean follow-up of 22.0 years (incidence rate = 54.7 per 100 000 person-years). Parkinson disease incidence was higher in women with early (<12 years, HR = 1.21, 95% CI = 1.04-1.40) or late age at menarche (≥14 years, HR = 1.18, 95% CI = 1.03-1.35) than in women with menarche at 12-13 years. Nulliparity was not associated with Parkinson disease, but Parkinson disease incidence increased with the number of children in parous women (P-trend = 0.009). Women with artificial (surgical, iatrogenic) menopause were at greater risk than women with natural menopause (HR = 1.28, 95% CI = 1.09-1.47), especially when artificial menopause occurred at an early age (≤45.0 years). Postmenopausal hormone therapy tended to mitigate greater risk associated with artificial or early menopause (≤45.0 years). While fertility treatments were not associated with Parkinson disease overall, ever users of clomiphene were at greater Parkinson disease risk than never users (HR = 1.81, 95% CI = 1.14-2.88). Other exposures (breastfeeding, oral contraceptives) were not associated with Parkinson disease. Our findings suggest that early and late age at menarche, higher parity, and artificial menopause, in particular at an early age, are associated with increased Parkinson disease incidence in women. In addition, there was some evidence that use of exogenous hormones may increase (fertility treatments) or decrease (postmenopausal hormone therapy) Parkinson disease incidence. These findings support the hypothesis that hormonal exposures play a role in the susceptibility to neurodegenerative diseases. If confirmed, they could help to identify subgroups at high risk for Parkinson disease.


Assuntos
Doença de Parkinson , Criança , Feminino , Humanos , Doença de Parkinson/epidemiologia , Doença de Parkinson/tratamento farmacológico , Estudos de Coortes , Menopausa , Estrogênios/uso terapêutico , Incidência , Fatores de Risco
12.
Sci Total Environ ; 854: 158589, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36087676

RESUMO

Drought may lead to severe and diverse impacts on agriculture, economy, and society across different regions and periods, posing predictive and adaptive challenges. In recent years, severe droughts have affected >60 million people in the Mekong River Basin (MRB). Additionally, El Niño Southern Oscillation (ENSO) episodes had distinct influences on the occurrence and intensity of drought variability in the regions. Understanding the spatiotemporal characteristics of droughts across the MRB is critical to improving management and mitigation actions. This study aims to investigate spatiotemporal drought characteristics in the MRB and their teleconnection with the ENSO. Three multiple drought indices, including the Standardized Precipitation Index (SPI) for meteorological drought, Standardized Soil Water Index (SSWI) for agricultural drought, and Standardized Runoff Index (SRI) for hydrological drought were calculated to quantify drought events, drought frequency, and drought severity. The overall patterns showed more events and larger intensity were identified by the SPI than those by the SRI or the SSWI, while the higher frequency was observed by the SRI. The Middle Mekong basins seem to experience more drought events, while higher levels of frequency and intensity of droughts were observed in the Upper Mekong Basin. The correlation analysis between ENSO index and precipitation suggested that the strongest ENSO events in Dec-Jan-Feb may result in developments of meteorological drought in Mar-Apr-May, and further led to hydrological and agricultural drought in Apr-May-Jun. Such ENSO effects had significant influences on drought variabilities in southern MRB and were insignificant in the north. The multiple drought indices show skills in identifying spatial and temporal drought characteristics from meteorological, agricultural, and hydrological perspectives, and potential for drought outlook further considering their ENSO teleconnections. The results can be applied to the development of drought monitoring methods and adaptive strategies to mitigate drought impacts through scientific and quantitative assessments.

13.
Mov Disord ; 37(12): 2376-2385, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36054665

RESUMO

BACKGROUND: Available treatments for Parkinson's disease (PD) are only partially or transiently effective. Identifying existing molecules that may present a therapeutic or preventive benefit for PD (drug repositioning) is thus of utmost interest. OBJECTIVE: We aimed at detecting potentially protective associations between marketed drugs and PD through a large-scale automated screening strategy. METHODS: We implemented a machine learning (ML) algorithm combining subsampling and lasso logistic regression in a case-control study nested in the French national health data system. Our study population comprised 40,760 incident PD patients identified by a validated algorithm during 2016 to 2018 and 176,395 controls of similar age, sex, and region of residence, all followed since 2006. Drug exposure was defined at the chemical subgroup level, then at the substance level of the Anatomical Therapeutic Chemical (ATC) classification considering the frequency of prescriptions over a 2-year period starting 10 years before the index date to limit reverse causation bias. Sensitivity analyses were conducted using a more specific definition of PD status. RESULTS: Six drug subgroups were detected by our algorithm among the 374 screened. Sulfonamide diuretics (ATC-C03CA), in particular furosemide (C03CA01), showed the most robust signal. Other signals included adrenergics in combination with anticholinergics (R03AL) and insulins and analogues (A10AD). CONCLUSIONS: We identified several signals that deserve to be confirmed in large studies with appropriate consideration of the potential for reverse causation. Our results illustrate the value of ML-based signal detection algorithms for identifying drugs inversely associated with PD risk in health-care databases. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Doença de Parkinson/diagnóstico , Estudos de Casos e Controles , Aprendizado de Máquina , Algoritmos , Substâncias Protetoras
14.
RSC Adv ; 12(34): 22004-22019, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-36043070

RESUMO

A new approach for the synthesis of podophyllotoxin-naphthoquinone compounds using microwave-assisted three-component reactions is reported in this study. Novel podophyllotoxin-naphthoquinone derivatives with modification on ring E were synthesized. All the synthetic compounds were assessed in terms of their cytotoxicity profile against four cancer cell lines (KB, HepG2, A549, and MCF7), and noncancerous Hek-293 cell lines. Notably, treatment of SK-LU-1 cells with compounds 5a and 5b resulted in G2/M phase arrest of the cell cycle, caspase-3/7 activation, and apoptosis. Additionally, molecular docking studies were performed and showed important interaction of two compounds against residues in the colchicine-binding-site of tubulin as well. Taken together, compounds 5a and 5b were identified as potent anticancer agents.

15.
Int J Mol Sci ; 23(11)2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35682935

RESUMO

Antibody discovery by phage display consists of two phases, i.e., the binding phase and the amplification phase. Ideally, the selection process is dominated by the former, and all the retrieved clones are amplified equally during the latter. In reality, the amplification efficiency of antibody fragments varies widely among different sequences and, after a few rounds of phage display panning, the output repertoire often includes rapidly amplified sequences with low or no binding activity, significantly diminishing the efficiency of antibody isolation. In this work, a novel synthetic single-chain variable fragment (scFv) library with complementarity-determining region (CDR) diversities aimed at improved amplification efficiency was designed and constructed. A previously reported synthetic scFv library with low, non-combinatorial CDR diversities was panned against protein A superantigen, and the library repertoires before and after the panning were analyzed by next generation sequencing. The enrichment or depletion patterns of CDR sequences after panning served as the basis for the design of the new library. Especially for CDR-H3 with a higher and more random diversity, a machine learning method was applied to predict potential fast-amplified sequences among a simulated sequence repertoire. In a direct comparison with the previous generation library, the new library performed better against a panel of antigens in terms of the number of binders isolated, the number of unique sequences, and/or the speed of binder enrichment. Our results suggest that the amplification-centric design of sequence diversity is a valid strategy for the construction of highly functional phage display antibody libraries.


Assuntos
Regiões Determinantes de Complementaridade , Anticorpos de Cadeia Única , Regiões Determinantes de Complementaridade/genética , Sequenciamento de Nucleotídeos em Larga Escala , Biblioteca de Peptídeos , Anticorpos de Cadeia Única/genética
16.
Eur J Epidemiol ; 37(5): 513-523, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35286513

RESUMO

Parkinson's disease (PD) is an uncommon disease with a long prodromal period and higher incidence in men than women. Large cohort studies of women with a long follow-up are needed. Within the E3N French cohort study (98,995 women, 40-65 years at baseline), we identified 3,584 participants who self-reported PD or used anti-parkinsonian drugs over 27 years (1992-2018). We obtained medical records to validate PD diagnosis (definite, probable, possible, no). When medical records were not available, we used a validated algorithm based on drug claims to predict PD status. We retained a PD diagnosis for 1,294 women (medical records, 62%; algorithm, 38%). After exclusion of prevalent/possible cases, cases without age at diagnosis, and women lost to follow-up, our analyses included 98,069 women, of whom 1,200 had incident PD (mean age at diagnosis = 71.8 years; incidence rate = 0.494/1,000 person-years). Age-adjusted incidence rates increased over the six first years of follow-up, possibly due to healthy volunteer bias, and remained stable thereafter, similar to incidence rates in women from Western Europe. Forty three percent of PD cases occurred after 20 years of follow-up (2012-2018). The cumulative incidence of PD from 50 to 90 years was 2.41% (95% confidence interval [CI] = 2.27-2.65). PD incidence was lower in ever than never smokers (hazard ratio = 0.86, 95% CI = 0.76-0.96). In conclusion, we estimated PD incidence rates in French women over a 27-year follow-up, and showed stable incidence between 2002 and 2018. The long follow-up and large sample size make this study a valuable resource to improve our knowledge on PD etiology in women.


Assuntos
Doença de Parkinson , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Masculino , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Risco
17.
Planta Med ; 88(13): 1141-1151, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34963183

RESUMO

Three prenylated xanthones, garcinone E (1: ), bannaxanthone D (2: ) and bannanxanthone E (3: ) were isolated from the leaves of Garcinia mckeaniana Graib. Their structures were elucidated by spectral methods and compared with literature data. To evaluate their anti-proliferative effects in tumor cells, firstly, cisplatin was used as a positive control and the effects of compound 1:  - 3: were determined by performing MTT assay in MDA-MB-231, CNE-2 and A549 cancer cells. The results showed compound 1:  - 3: exhibited stronger inhibitory effect than cisplatin in MDA-MB-231. Further effects of compound 1:  - 3: in TNBC MDA-MB-231 and MDA-MB-468 cells were examined by performing cell cycle and apoptosis assays. The results indicated that compound 1:  - 3: had ability to arrest cell cycle at G2/M phase and induce apoptosis. Furthermore, compound 2: significantly down-regulated PI3K, Akt and mTOR levels in both total proteins and phosphorylated form, which is its potential anti-cancer mechanism. These findings indicated that those prenylated xanthones might serve as promising leading compounds for the development of anticancer drug for TNBC.


Assuntos
Antineoplásicos , Neoplasias de Mama Triplo Negativas , Xantonas , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Xantonas/farmacologia , Xantonas/uso terapêutico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células , Linhagem Celular Tumoral
18.
Nat Prod Res ; 36(19): 5074-5080, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33939580

RESUMO

From the ethyl acetate extract (EtOAc) of the Vietnamese Garcinia mckeaniana leaves, a new flavone 8-C-glycoside 2'',6''-di-O-acetylvitexin (1), together with six known analogs 2-7 were isolated. Their structures were determined by spectral methods and compared with literature data. In α-glucosidase inhibitory assay, the EtOAc extract and its flavone and biflavone derivatives possessed the significant IC50 range of 9.17-97.53 µM, as compared with that of the positive control acarbose (249 µM). Flavones and biflavones showed are better than flavone glycosides in both α-glucosidase and acetylcholinesterase inhibitory activities[Formula: see text].


Assuntos
Flavonas , Garcinia , Acarbose , Acetilcolinesterase , Flavonas/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Garcinia/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , alfa-Glucosidases
19.
Molecules ; 26(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34361559

RESUMO

The aim of this research is to obtain new data about the complexation between ß-cyclodextrin (ß-CD) and benzoic acid (BA) as a model reaction of the complex formation of hydrophobic molecules with cyclodextrins (CDs) in various media. This research may help developing cyclodextrin-based pharmaceutical formulations through the choice of the appropriate solvent mixture that may be employed in the industrial application aiming to control the reactions/processes in liquid phase. In this paper, NMR results for the molecular complex formation between BA and ß-CD ([BA⊂ß-CD]) in D2O-DMSO-d6 and in D2O-EtOH have shown that the stability of the complex in the H2O-DMSO-d6 varies within the experimental error, while decreases in H2O-EtOH. Changes in the Gibbs energy of BA resolvation in water and water-dimethylsulfoxide mixtures have been obtained and have been used in the analysis of the reagent solvation contributions into the Gibbs energy changes of the [BA⊂ß-CD] molecular complex formation. Quantum chemical calculations of the interaction energy between ß-CD and BA as well as the structure of the [BA⊂ß-CD] complex and the energy of ß-CD and BA interaction in vacuum and in the medium of water, methanol and dimethylsulfoxide solvents are carried out. The stability of [BA⊂ß-CD] complex in H2O-EtOH and H2O-DMSO solvents, obtained by different methods, are compared. The thermodynamic parameters of the [BA⊂ß-CD] molecular complexation as well as the reagent solvation contributions in H2O-EtOH and H2O-DMSO mixtures were analyzed by the solvation-thermodynamic approach.

20.
Transpl Immunol ; 66: 101392, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33838297

RESUMO

BACKGROUND: To assess the incidence of new-onset diabetes after transplantation (NODAT) for the first year post-transplantation and the predictive value of high-sensitivity C-reactive Protein (hs-CRP) before transplantation for NODAT prediction in kidney transplantation patients. MATERIAL AND METHODS: A study of 251 consecutive adult end-stage kidney disease patients transplanted kidneys from living donors, follow-up during the first year to find NODAT. We diagnosed NODAT based on blood glucose or HbA1c following to the criteria of the American Diabetes Association. RESULTS: The ratio of NODAT was 12.4%. The mean age, mean BMI, the proportion of arteriosclerosis, and the median hs-CRP level in NODAT group were significantly higher than those of non-NODAT group with p < 0.05. Age, BMI and serum hs-CRP had a predictive value for NODAT (Age: AUC = 0.62, p < 0.05, BMI: AUC = 0.626, hs-CRP: AUC = 0.748, p < 0.001). CONCLUSION: Serum hs-CRP level measured prior transplantation is a good predictor for NODAT in renal transplant recipients.


Assuntos
Proteína C-Reativa , Diabetes Mellitus , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias , Adulto , Fatores Etários , Proteína C-Reativa/imunologia , Proteína C-Reativa/metabolismo , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/imunologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/imunologia , Fatores de Risco
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