Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 692
Filtrar
1.
Bioact Mater ; 22: 47-59, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36203955

RESUMO

Mild photothermal therapy combined with immune checkpoint blockade has received increasing attention for the treatment of advanced or metastatic cancers due to its good therapeutic efficacy. However, it remains a challenge to facilely integrate the two therapies and make it potential for clinical translation. This work designed a peptide-photosensitizer conjugate (PPC), which consisted of a PD-L1 antagonist peptide (CVRARTR), an MMP-2 specific cleavable sequence, a self-assembling motif, and the photosensitizer Purpurin 18. The single-component PPC can self-assemble into nanospheres which is suitable for intravenous injection. The PPC nanosphere is cleaved by MMP-2 when it accumulates in tumor sites, thereby initiating the cancer-specific release of the antagonist peptide. Simultaneously, the nanospheres gradually transform into co-assembled nanofibers, which promotes the retention of the remaining parts within the tumor. In vivo studies demonstrated that PPC nanospheres under laser irradiation promote the infiltration of cytotoxic T lymphocytes and maturation of DCs, which sensitize 4T1 tumor cells to immune checkpoint blockade therapy. Therefore, PPC nanospheres inhibit tumor growth efficiently both in situ and distally and blocked the formation of lung metastases. The present study provides a simple and efficient integrated strategy for breast cancer photoimmunotherapy.

2.
Asian J Pharm Sci ; 17(5): 697-712, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36382307

RESUMO

The combination regimen of trastuzumab (Tras) plus Nab-paclitaxel (Nab) is recommended to treat HER2-positive (HER2+) cancers. However, they exert effects in different mechanisms: Tras need to stay on cell membranes, while Nab need to be endocytosed, therefore the concurrent combination regimen may not be the best one in HER2+ tumors treatment. Caveolin-1 (Cav-1) is a key player in mediating their endocytosis and is associated with their efficacy, but few researches noticed the opposite effect of Cav-1 expression on the combination efficacy. Herein, we systematically studied the Cav-1 expression level on the combination efficacy and proposed an optimized and clinically feasible combination regimen for HER2+ Cav-1High tumor treatment. In the regimen, lovastatin (Lova) was introduced to modulate the Cav-1 expression and the results indicated that Lova could downregulate Cav-1 expression, increase Tras retention on cell membrane and enhance the in vitro cytotoxicity of Tras in HER2+ Cav-1High cells but not in HER2+ Cav-1Low cells. Therefore, by exchanging the dosing sequence of Nab and Tras, and by adding Lova at appropriate time points, the precise three-drug-sequential regimen (PTDS, Nab(D1)-Lova(D2)-Lova & Tras(D2+12 h)) was established. Compared with the concurrent regimen, the PTDS regimen exhibited a higher in vitro cytotoxicity and a stronger tumor growth inhibition in HER2+ Cav-1High tumors, which might be a promising combination regimen for these patients in clinics.

3.
Int J Pharm ; : 122414, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36403893

RESUMO

Infliximab (INF) is intravenously used for the clinical treatment of rheumatoid arthritis. However, it can cause serious side effects, which are mainly associated with systemic exposure and high doses. Here, we developed a modified hydrophobic ion-pairing complexes (INF HIPC) through the sequential introduction of bovine lactoferrin (BLF) and hyaluronic acid (HA) with opposite charges into the INF solution. INF and BLF were found to be not only integrally responsible for the structural integrity of HIPC but also were determined to have respective biological activities by binding human tumor necrosis factor-alpha (hTNF-α) or promoting the proliferation of osteoblasts. The INF HIPC had good stability, high drug-loading efficiency, and long-term retention effects. Whether via knee joint injection or intravenous injection, INF HIPC resulted in lower hTNF-α levels and less cartilage destruction than INFs in the transgenic mouse model. At the same time, INF HIPC could reduce toxicity based on body weight changes in transgenic mice. Our findings provide a simple and promising avenue to develop advanced delivery systems for other antibodies and macromolecules.

4.
Proteomics ; : e2200176, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36413357

RESUMO

It is challenging to study regulatory genetic variants as gene expression is affected by both genetic polymorphisms and non-genetic regulators. The mRNA allele-specific expression (ASE) assay has been increasingly used for the study of cis-acting regulatory variants because cis-acting variants affect gene expression in an allele-specific manner. However, poor correlations between mRNA and protein expressions were observed for many genes, highlighting the importance of studying gene expression regulation at the protein level. In the present study, we conducted a proof-of-concept study to utilize a recently developed allele-specific protein expression (ASPE) assay to identify the cis-acting regulatory variants of CES1 using a large set of human liver samples. The CES1 gene encodes for carboxylesterase 1 (CES1), the most abundant hepatic hydrolase in humans. Two cis-acting regulatory variants were found to be significantly associated with CES1 ASPE, CES1 protein expression, and its catalytic activity on enalapril hydrolysis in human livers. Compared to conventional gene expression-based approaches, ASPE demonstrated an improved statistical power to detect regulatory variants with small effect sizes since allelic protein expression ratios are less prone to the influence of non-genetic regulators (e.g., diseases and inducers). This study suggests that the ASPE approach is a powerful tool for identifying cis-regulatory variants. This article is protected by copyright. All rights reserved.

5.
Toxics ; 10(10)2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36287853

RESUMO

The intercropping of arsenic (As) hyperaccumulator Chinese brake fern (Pterisvittata L.) with maize (Zea mays L.) is being widely utilized to enhance phytoremediation without impeding agricultural production. Arbuscular mycorrhizal (AM) fungi can regulate the physiological and molecular responses of plants in tolerating heavy metal stress. We studied the effects of inoculation with AM fungi on As uptake by maize and P. vittata grown in soil contaminated with As. The results show that infection with the fungus Claroideoglomus etunicatum (Ce) increased the biomass of maize and P. vittata. Moreover, infection with Ce significantly reduced the accumulation of As and the coefficient for root-shoot transport of As in maize, whereas it enhanced the accumulation of As and coefficient for root-shoot transport of As in P. vittata. Infection with Ce led to a high content of available As in the soil planted with P. vittata, while there was a lower content of available As in the soil planted with maize. The different concentrations of available As in the soils suggest that inoculation with Ce may enhance the secretion of organic acids, particularly citric acid and tartaric acid, by maize roots and promote rhizosphere acidification, which then causes a decrease in As uptake by maize. Inoculation with Ce decreased the secretion of citric acid from P. vittata and promoted rhizosphere alkalization, which then caused an increase in As uptake by P. vittata and maize. Thus, co-combining AM fungi in the intercropping of the hyperaccumulator P. vittata with maize could be a promising approach to improving the efficiency of remediating As-contaminated soil.

6.
Artigo em Inglês | MEDLINE | ID: mdl-36310614

RESUMO

Objective: Inflammatory skin disorders are becoming major issues threatening public health with increasing prevalence. This study was to evaluate the anti-inflammatory, antioxidant, and antisenescent activities of traditional folk medicinal plant, Physalis alkekengi L. extracts to alleviate skin inflammation and its possible mechanisms. Methods: Lipopolysaccharides (LPS)-treated murine macrophages RAW264.7 and human skin keratinocytes HaCaT were incubated with the plant extracts, respectively. The production of nitric oxide (NO) was tested by using Griess reagents. The activity of nitric oxide synthase (NOS) was detected through a fluorescence microplate reader. Reactive oxygen species (ROS) production and cell apoptosis were quantified by flow cytometry. The proinflammatory cytokines were measured using ELISA and qRT-PCR. Human skin fibroblasts (HFF-1) were coincubated with D-galactose (D-gal) and the plant extracts. The senescence associated-galactosidase (SA-ß-gal) was stained to evaluate cellular senescence. The senescence-associated secretory phenotype (SASP), IL-1ß, was measured through ELISA. The mRNA of IL-1α in SLS-stimulated and PGE2 in UV-radiated 3D skin models were detected by qRT-PCR. In vivo ROS production and neutrophil recruitment in CuSO4-treated zebrafish models were observed by fluorescence microscopy. Inflammation-related factors were measured by qRT-PCR. Results. In vitro, Physalis alkekengi L. significantly reduced NO production, NOS activity, cell apoptosis, transcription of TNF-α, IL-6, IL-1ß and ROS production. These plant extracts markedly attenuated SA-ß-gal and IL-1ß and downregulated the production of IL-1α and PGE2. In vivo, the plant extracts dramatically dampened ROS production, the number of neutrophils, and proinflammatory cytokines. Conclusions: Cumulatively, this work systematically demonstrated the anti-inflammatory, antioxidant, and antisenescent properties of Physalis alkekengi L. and proposed the possible roles of Physalis alkekengi L. in inflammatory signaling pathways, providing an effective natural product for the treatment of inflammatory skin disorders.

7.
Front Cardiovasc Med ; 9: 1030618, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312268

RESUMO

Purpose: The study was designed to investigate the profile of plasma human growth cytokines in pediatric vasovagal syncope (VVS). Materials and methods: In the discovery set of the study, plasma human growth cytokines were measured using a Quantiboby Human Growth Factor Array in 24 VVS children and 12 healthy controls. Scatter and principal component analysis (PCA) diagrams were used to describe the samples, an unsupervised hierarchical clustering analysis was used to categorize the samples. Subsequently, the cytokines obtained from the screening assays were verified with a suspension cytokine array in the validation set of the study including 53 VVS children and 24 controls. Finally, the factors associated with pediatric VVS and the predictive value for the diagnosis of VVS were determined. Results: In the discovery study, the differential protein screening revealed that the plasma hepatocyte growth factor (HGF), transforming growth factor b1 (TGF-b1), insulin-like growth factor binding protein (IGFBP)-4, and IGFBP-1 in children suffering from VVS were higher than those of the controls (all adjust P- value < 0.05). However, the plasma IGFBP-6, epidermal growth factor (EGF), and IGFBP-3 in pediatric VVS were lower than those of the controls (all adjust P- value < 0.01). Meanwhile, the changes of 7 differential proteins were analyzed by volcano plot. Unsupervised hierarchical cluster analysis demonstrated that patients in the VVS group could be successfully distinguished from controls based on the plasma level of seven differential proteins. Further validation experiments showed that VVS patients had significantly higher plasma concentrations of HGF, IGFBP-1, and IGFBP-6, but lower plasma concentrations of EGF and IGFBP-3 than controls. The logistics regression model showed that increased plasma concentration of HGF and IGFBP-1 and decreased plasma concentration of EGF were correlated with the development of pediatric VVS. ROC curve analysis showed that the abovementioned 3 proteins were useful for assisting the diagnosis of VVS. Conclusion: Plasma human growth cytokine profiling changed in pediatric VVS. Elevated plasma concentrations of HGF and IGFBP-1, and decreased EGF were associated factors in the development of pediatric VVS. The abovementioned three proteins are helpful for the diagnosis of pediatric VVS.

8.
World J Clin Cases ; 10(29): 10614-10621, 2022 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-36312498

RESUMO

BACKGROUND: The Fontan operation is the only treatment option to change the anatomy of the heart and help improve patients' hemodynamics. After successful operation, patients typically recover the ability to engage in general physical activity. As a better ventilatory strategy, extracorporeal membrane oxygenation (ECMO) provides gas exchange via an extracorporeal circuit, and is increasingly being used to improve respiratory and circulatory function. After the modified Fontan operation, circulation is different from that of patients who are not subjected to the procedure. This paper describe a successful case using ECMO in curing influenza A infection in a young man, who was diagnosed with Tausing-Bing syndrome and underwent Fontan operation 13 years ago. The special cardiac structure and circulatory characteristics are explored in this case. CASE SUMMARY: We report a successful case using ECMO in curing influenza A infection in a 23-year-old man, who was diagnosed with Tausing-Bing syndrome and underwent Fontan operation 13 years ago. The man was admitted to the intensive care unit with severe acute respiratory distress syndrome as a result of influenza A infection. He was initially treated by veno-venous (VV) ECMO, which was switched to veno-venous-arterial ECMO (VVA ECMO) 5 d later. As circulation and respiratory function gradually improved, the VVA ECMO equipment was removed on May 1, 2018. The patient was successfully withdrawn from artificial ventilation on May 28, 2018 and then discharged from hospital on May 30, 2018. CONCLUSION: After the modified Fontan operation, circulation is different compared with that of patients who are not subjected to the procedure. There are certainly many differences between them when they receive the treatment of ECMO. Due to the special cardiac structure and circulatory characteristics, an individualized liquid management strategy is necessary and it might be better for them to choose an active circulation support earlier.

9.
Clin Transl Sci ; 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36259251

RESUMO

Several human host proteins play important roles in the lifecycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many drugs targeting these host proteins have been investigated as potential therapeutics for coronavirus disease 2019 (COVID-19). The tissue-specific expressions of selected host proteins were summarized using proteomics data retrieved from the Human Protein Atlas, ProteomicsDB, Human Proteome Map databases, and a clinical COVID-19 study. Protein expression features in different cell lines were summarized based on recent proteomics studies. The half-maximal effective concentration or half-maximal inhibitory concentration values were collected from in vitro studies. The pharmacokinetic data were mainly from studies in healthy subjects or non-COVID-19 patients. Considerable tissue-specific expression patterns were observed for several host proteins. ACE2 expression in the lungs was significantly lower than in many other tissues (e.g., the kidneys and intestines); TMPRSS2 expression in the lungs was significantly lower than in other tissues (e.g., the prostate and intestines). The expression levels of endocytosis-associated proteins CTSL, CLTC, NPC1, and PIKfyve in the lungs were comparable to or higher than most other tissues. TMPRSS2 expression was markedly different between cell lines, which could be associated with the cell-dependent antiviral activities of several drugs. Drug delivery receptor ICAM1 and CTSB were expressed at a higher level in the lungs than in other tissues. In conclusion, the cell- and tissue-specific proteomics data could help interpret the in vitro antiviral activities of host-directed drugs in various cells and aid the transition of the in vitro findings to clinical research to develop safe and effective therapeutics for COVID-19.

10.
Opt Express ; 30(10): 15858-15876, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-36221442

RESUMO

Ultra-high resolution mass sensing used to be realized by measuring the changed mechanical oscillation frequency by a small mass that should be detected. In this work we present a different approach of mass sensing without directly measuring such mechanical frequency change but relying on the modified light field due to a previously less explored nonlinear mechanism of optomechanical interaction. The concerned optomechanical setup used for the mass sensing is driven by a sufficiently strong two-tone field satisfying a condition that the difference of these two drive frequencies matches the frequency of the mechanical oscillation, so that a nonlinear effect will come into being and lock the mechanical motion under the radiation pressure into a series of fixed orbits. A small mass attached to the mechanical resonator slightly changes the mechanical frequency, thus violating the exact frequency match condition. Such small change can be detected by the amplitude modification on the higher order sidebands of the cavity field. Even given a moderate mechanical quality factor for the setup, the added mass can still be detected to the levels corresponding to a mechanical frequency shift from 5 to 7 order less than the mechanical damping rate. Because the output cavity field difference for very close values of mechanical frequency is not blurred by thermal noise, such mass sensing can be well performed at room temperature. The previous tough requirements for ultra-high resolution mass sensing can be significantly relaxed by the method.

11.
Front Plant Sci ; 13: 988845, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204077

RESUMO

Chenopodium quinoa is a crop with outstanding tolerance to saline soil, but long non-coding RNAs (LncRNAs) expression profile driven by salt stress in quinoa has rarely been observed yet. Based on the high-quality quinoa reference genome and high-throughput RNA sequencing (RNA-seq), genome-wide identification of LncRNAs was performed, and their dynamic response under salt stress was then investigated. In total, 153,751 high-confidence LncRNAs were discovered and dispersed intensively in chromosomes. Expression profile analysis demonstrated significant differences between LncRNAs and coding RNAs. Under salt stress conditions, 4,460 differentially expressed LncRNAs were discovered, of which only 54 were differentially expressed at all the stress time points. Besides, strongly significantly correlation was observed between salt-responsive LncRNAs and their closest neighboring genes (r = 0.346, p-value < 2.2e-16). Furthermore, a weighted co-expression network was then constructed to infer the potential biological functions of LncRNAs. Seven modules were significantly correlated with salt treatments, resulting in 210 hub genes, including 22 transcription factors and 70 LncRNAs. These results indicated that LncRNAs might interact with transcription factors to respond to salinity stress. Gene ontology enrichment of the coding genes of these modules showed that they were highly related to regulating metabolic processes, biological regulation and response to stress. This study is the genome-wide analysis of the LncRNAs responding to salt stress in quinoa. The findings will provide a solid framework for further functional research of salt responsive LncRNAs, contributing to quinoa genetic improvement.

12.
Adv Mater ; : e2206401, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36210733

RESUMO

Multienzyme-mimicking redox nanozymes, curated by defect engineering, in synergy with immunotherapy offer promising prospects for safe and efficient cancer therapy. However, the spatiotemporally precise immune response often gets challenged by off-target adverse effects and insufficient therapeutic response. Herein, a tumor cell membrane coated redox nanozyme (CMO-R@4T1) is reported for combinational second near-infrared window (NIR-II) photothermal immunotherapy. CMO-R@4T1 consists of a Cu-doped MoOx (CMO) nanozyme as the core, which is cloaked with tumor-cell-derived fused membranes with immunostimulants immobilized in the membrane shell. In addition to the enhanced tumor accumulation, the nanozyme can cause oxidative damage to tumor cells by the production of reactive oxygen species and attenuation of the antioxidant mechanism. CMO-R@4T1 also mediates a photothermal effect under NIR-II photoirradiation to trigger tumor eradication and immunogenic cell death, where the liberated agonist elicits the immune activation. Such a controlled therapeutic paradigm potentiates systemic primary tumor ablation, inhibits cancer metastasis to distant tumor, and procures long-term immunological memory. Thereby, this study takes advantage of defect engineering to illustrate a generic strategy to prepare cell-membrane-camouflaged nanozymes for targeted photo-immunotherapy of cancer.

13.
Nanoscale Horiz ; 7(12): 1501-1512, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36254659

RESUMO

Aqueous fibrous batteries with tiny volume, light weight and stretchability have furthered wearable smart textile systems like biocompatible electronics for a more efficient use of electricity. Challenges still faced by fibrous batteries include not only the deficient actual capacity but the cyclability on the cathode side. Herein, an in situ anodic oxidation strategy is reported to prepare 3D N-doped/defect-rich V2O5-x·nH2O nanosheets (DVOH@NC) as fibrous cathodes for aqueous zinc-ion batteries (AZIBs). Benefiting from the substantially abundant reaction sites, enhanced electrical conductivity, short electron/ion diffusion path and high mass loading, the newly designed DVOH@NC fibrous electrode delivers impressive capacity (711.9 mA h cm-3 at 0.3 A cm-3) and long-term durability (95.5% capacity retention after 3000 cycles), substantially outperforming previously reported fibrous vanadium-based cathodes. First-principles density functional theory (DFT) calculations further revealed that the oxygen vacancies can weaken the electrostatic interaction between Zn2+ and the host cathode accompanying the low Zn2+ diffusion energy barrier. To highlight the potential applications, a prototype wearable fiber-shaped AZIB (FAZIB) with remarkable flexibility and extraordinary weaving capability was demonstrated. More encouragingly, the resulting FAZIB could be charged with solar cells and power a pressure sensor. Thus, our work provides a promising strategy to rationally construct high-performance flexible vanadium-based cathodes for next-generation wearable AZIBs.


Assuntos
Carbono , Vanádio , Fontes de Energia Elétrica , Íons , Zinco
14.
Artigo em Inglês | MEDLINE | ID: mdl-36118096

RESUMO

Background: Acupoint application of herbal medicine (AAHM) has been widely used in China. At present, there is no systematic review of AAHM versus placebo in the treatment of asthma. This systematic review aims to assess the efficacy of AAHM for asthma. Methods: Searches were conducted in five English databases and four Chinese databases from their inceptions until December 2020. Randomized double-blind placebo-controlled trials were screened, and included studies evaluated routine pharmacotherapy (RP) plus AAHM versus RP plus placebo or AAHM versus placebo. The Cochrane risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were performed to evaluate the methodological quality and quality of evidence separately. Results: Sixteen studies involving 1,730 participants were included in this review. Compared with placebo plus RP, participants receiving long-term AAHM plus RP showed improvement in asthma quality of life questionnaire (AQLQ) with moderate-quality evidence (MD 6.53 points, 95% CI 2.70 to 10.36). Low-quality evidence indicated that AAHM plus RP was associated with improved FEV1 (%) compared with placebo plus RP, whether long- or short-term use (MD 11.80%, 95% CI 2.84 to 20.76; MD 10.57%, 95% CI 8.40 to 12.74; respectively). Moderate-quality evidence showed that participants receiving short-term AAHM were associated with a higher AQLQ score (MD 6.57 points, 95% CI 3.76 to 9.38) and a lower frequency of acute exacerbations (MD -1.84, 95% CI -2.32 to -1.36) compared with placebo. Low-quality evidence also indicated that AAHM was associated with improved FEV1 (L) compared with placebo, whether long- or short-term use (MD 0.35 litres, 95% CI 0.03 to 0.67; MD 0.66 litres, 95% CI 0.59 to 0.73; respectively). Conclusions: Moderate-quality evidence is promising that AAHM can improve the quality of life and reduce acute exacerbations in patients with asthma. AAHM also shows a positive role in improving lung function, but the evidence is so indefinite due to low quality.

15.
Plant Physiol Biochem ; 189: 115-125, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36084527

RESUMO

Epidermal waxes are part of the outermost hydrophobic structures of apples and play a significant role in enhancing apple resistance and improving fruit quality. The biosynthetic precursors of epidermal waxes are very long-chain fatty acids (VLCFAs), which are made into different wax components through various wax synthesis pathways. In Arabidopsis thaliana, the AtLACS1 protein can activate the alkane synthesis pathway to produce very long-chain acyl CoAs (VLC-acyl-CoAs), which provide substrates for wax synthesis, from VLCFAs. The apple protein MdLACS1, encoded by the MdLACS1 gene, belongs to the AMP-binding superfamily and has long-chain acyl coenzyme A synthase activity, but its function in apple remains unclear. Here, we identified MdLACS1 in apple (Malus × domestica) and analyzed its function. Our results suggest that MdLACS1 promotes wax synthesis and improves biotic and abiotic stress tolerance, which were directly or indirectly dependent on wax. Our study further refines the molecular mechanism of wax biosynthesis in apples and elucidates the physiological function of wax in resistance to external stresses. These findings provide candidate genes for the synergistic enhancement of apple fruit quality and stress tolerance.


Assuntos
Arabidopsis , Malus , Acil Coenzima A/metabolismo , Monofosfato de Adenosina/metabolismo , Alcanos/metabolismo , Arabidopsis/metabolismo , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica de Plantas , Malus/genética , Malus/metabolismo , Epiderme Vegetal/metabolismo , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Ceras/metabolismo
16.
Front Endocrinol (Lausanne) ; 13: 1003238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147577

RESUMO

Objectives: Canagliflozin (CANA), a kind of sodium-glucose cotransporter-2 (SGLT-2) inhibition, study in which the role of CANA monotherapy in polycystic ovary syndrome (PCOS) has been investigated, and it could become a novel option in the PCOS treatment. Nevertheless, trials focused on SGLT-2 combination therapy's efficacy, and safety in PCOS patients are limited. This randomized controlled trial compared the efficacy and safety of CANA and metformin (MET) combination therapy and MET monotherapy in endocrine and metabolic profiles of overweight and obese women with polycystic ovary syndrome (PCOS). Methods: Fifty-one overweight or obese non-diabetic PCOS women between 18 and 40 years old were enrolled. Patients were randomly allocated to receive either CANA/MET or MET treatment. The CANA/MET group received CANA 100 mg once daily plus MET 1000 mg twice daily, while the MET group received MET 1000 mg twice daily for three months. Changes in menstrual pattern, anthropometric parameters, gonadal parameters, glucose and lipid homeostasis, and adverse events (AEs) were evaluated. Results: Compared with the MET group, women have a significantly lower level of total testosterone (TT), area under the curve for glucose (AUCGlu), and area under the curve for insulin (AUCIns) to AUCGlu ratio in the combination group. There were no significant differences in menstrual frequency, body weight, body mass index, follicle-stimulating hormone, luteinizing hormone, free androgen index, sex hormone-binding globulin, androstenedione, fasting blood glucose, fasting insulin, AUCIns, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), and APO B/A1 ratio. AEs were seen in 57.70% (15/26) and 68.00% (17/25) of patients in the CANA/MET and MET groups, respectively. Conclusions: In overweight and obese women with PCOS, CANA and MET combination therapy may be similar to MET monotherapy in improving menstrual frequency, weight control, hyperandrogenemia, and relieving insulin resistance. CANA/MET may have more benefits in reducing TT, AUCGlu, and the AUCIns/AUCGlu ratio within three months than MET monotherapy. Trial registration: ClinicalTrials.gov, NCT04973891.


Assuntos
Canagliflozina , Resistência à Insulina , Metformina , Obesidade , Sobrepeso , Síndrome do Ovário Policístico , Adolescente , Adulto , Glicemia , Canagliflozina/uso terapêutico , Feminino , Humanos , Insulina , Metaboloma , Metformina/uso terapêutico , Obesidade/complicações , Obesidade/tratamento farmacológico , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/tratamento farmacológico , Estudos Prospectivos , Adulto Jovem
17.
Front Endocrinol (Lausanne) ; 13: 945609, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060969

RESUMO

Objective: To observe the effect of metformin (MET) monotherapy versus MET plus liraglutide (LIRA) on gonadal and metabolic profiles in overweight patients with polycystic ovary syndrome (PCOS). Methods: Sixty overweight patients with PCOS were recruited from January 2021 to January 2022 in Shengjing Hospital of China Medical University and were randomly assigned to the MET or combination (COM) group to receive 12 weeks of MET monotherapy or MET plus LIRA therapy. Anthropometric measurements, menstrual cycle changes, gonadal profiles, and oral glucose tolerance tests (OGTT) were conducted at baseline and after the 12-week treatment. Results: Fifty-two subjects completed the trial while eight were lost during the follow-up. Both MET and COM improved menstrual cycles, anthropometric parameters, and glucose metabolism after the 12-week treatment; however, there was no statistical difference between the two groups. MET plus LIRA therapy improved hyperandrogenemia, including TT (total testosterone), SHBG (sex hormone binding globulin) and FAI (free androgen index), whereas MET monotherapy only improved SHBG and FAI when compared with baseline. Furthermore, both MET monotherapy and MET plus LIRA therapy improved E2 (estradiol) while only MET plus LIRA therapy improved LH (luteinizing hormone), FSH (follicle stimulating hormone) and Prog (progesterone) more effectively than baseline. Additionally, MET plus LIRA therapy may improve TT, SHBG, FAI, LH and Prog more effectively than MET monotherapy; however, there were no significant differences on E2, FSH and LH/FSH between the two groups. Conclusions: In overweight patients with PCOS, both MET monotherapy and MET plus LIRA therapy improved glucose metabolism and relieved insulin resistance (IR). Additionally, MET plus LIRA therapy was more effective than MET monotherapy in improving reproductive abnormalities and hyperandrogenemia, potentially by modulating the hypothalamic-pituitary-ovarian axis.


Assuntos
Metformina , Síndrome do Ovário Policístico , Feminino , Hormônio Foliculoestimulante/metabolismo , Glucose , Humanos , Liraglutida/uso terapêutico , Metaboloma , Metformina/uso terapêutico , Obesidade/metabolismo , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo
18.
J Mol Model ; 28(10): 308, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36094544

RESUMO

A CCSD(T)//B3LYP method was employed to research the influence of monomolecular and bimolecular water molecules on the IO + CH2O reaction. H-abstraction and addition/elimination mechanisms have been located, and the H-abstraction mechanism occupied the whole reaction without water. The introduction of water complicates the reaction, but the final product remains unchanged. Water molecules influence each reaction pathway in six different pathways with monomolecular water and two different pathways with bimolecular water, respectively. The present calculations manifested that water has a positive influence on the IO + CH2O reaction with monomolecular water molecule, and plays negative catalytic influence on the IO + CH2O reaction with bimolecular water molecule. The effective rate constants are much lower than the IO + CH2O reaction without water.


Assuntos
Água , Catálise
19.
Phytochemistry ; 203: 113346, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35961408

RESUMO

1H-NMR guided fractionation led to the isolation of twenty-two coumarin monoterpenes from the whole plant of Gerbera piloselloides, among which fourteen were undescribed. All coumarin monoterpenes were initially found to be racemates without optical activity. Subsequently, eleven pairs of optically pure enantiomers were successfully separated by chiral phase HPLC. Their structures and absolute configurations were unambiguously determined based on their spectroscopic data, calculated/experimental electronic circular dichroism (ECD) data, and X-ray diffraction analysis. Bioassays in LPS-treated RAW 264.7 cells revealed that the four compounds possessed moderate anti-inflammatory activity. In addition, the correlations between the cotton effect (CE) from δ-lactone at approximately 210-220 nm in CD spectra and γ-C or the ring fused at γ-C of the skeleton were reported for the first time.


Assuntos
Asteraceae , Monoterpenos , Anti-Inflamatórios/farmacologia , Asteraceae/química , Cumarínicos/química , Cumarínicos/farmacologia , Lactonas , Lipopolissacarídeos/farmacologia , Estrutura Molecular , Monoterpenos/farmacologia , Espectroscopia de Prótons por Ressonância Magnética
20.
Cancer Chemother Pharmacol ; 90(4): 325-334, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36001108

RESUMO

PURPOSE: Fedratinib is an orally administered Janus kinase (JAK) 2-selective inhibitor for the treatment of adult patients with intermediate-2 or high-risk primary or secondary myelofibrosis. In vitro, fedratinib is predominantly metabolized by cytochrome P450 (CYP) 3A4 and to a lesser extent by CYP2C19. Coadministration of fedratinib with CYP3A4 inhibitors is predicted to increase systemic exposure to fedratinib. This study evaluated the effect of multiple doses of the dual CYP3A4 and CYP2C19 inhibitor, fluconazole, on the pharmacokinetics of a single dose of fedratinib. METHODS: In this non-randomized, fixed-sequence, open-label study, healthy adult participants first received a single oral dose of fedratinib 100 mg on day 1. Participants then received fluconazole 400 mg on day 10 and fluconazole 200 mg once daily on days 11-23, with a single oral dose of fedratinib 100 mg on day 18. Pharmacokinetic parameters were calculated for fedratinib administered with and without fluconazole. RESULTS: A total of 16 participants completed the study and were included in the pharmacokinetic population. Coadministration of fedratinib with fluconazole increased maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t) of fedratinib by 21% and 56%, respectively, compared with fedratinib alone. Single oral doses of fedratinib 100 mg administered with or without fluconazole were well tolerated. CONCLUSIONS: Systemic exposure after a single oral dose of fedratinib was increased by up to 56% when fedratinib was coadministered with fluconazole compared with fedratinib alone. TRIAL REGISTRY: CLINICALTRIALS.GOV: NCT04702464.


Assuntos
Fluconazol , Pirrolidinas , Adulto , Área Sob a Curva , Inibidores do Citocromo P-450 CYP3A/farmacologia , Interações Medicamentosas , Fluconazol/farmacocinética , Voluntários Saudáveis , Humanos , Pirrolidinas/farmacocinética , Sulfonamidas/farmacocinética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...