Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
1.
Phytochemistry ; 223: 114132, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38714288

RESUMO

Honokiol (HK) and magnolol (MAG) are typical representatives of neolignans possessing a wide range of biological activities and are employed as traditional medicines in Asia. In the past few decades, HK and MAG have been proven to be promising chemical scaffolds for the development of novel neolignan drugs. This review focuses on recent advances in the medicinal chemistry of HK and MAG derivatives, especially their structure-activity relationships. In addition, it also presents a comprehensive summary of the pharmacology, biosynthetic pathways, and metabolic characteristics of HK and MAG. This review can provide pharmaceutical chemists deeper insights into medicinal research on HK and MAG, and a reference for the rational design of HK and MAG derivatives.


Assuntos
Compostos de Bifenilo , Lignanas , Lignanas/química , Lignanas/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/química , Relação Estrutura-Atividade , Humanos , Estrutura Molecular , Compostos Alílicos , Fenóis
2.
iScience ; 27(3): 109229, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38455977

RESUMO

Current studies on the immune microenvironment of colorectal cancer (CRC) were mostly limited to the tissue level, lacking relevant studies in the peripheral blood, and failed to describe its alterations in the whole process of adenocarcinoma formation, especially of adenoma carcinogenesis. Here, we constructed a large-scale population cohort and used the CyTOF to explore the changes of various immune cell subsets in peripheral blood of CRC. We found monocytes and basophils cells were significantly higher in adenocarcinoma patients. Compared with early-stage CRC, effector CD4+T cells and naive B cells were higher in patients with lymph node metastasis, whereas the basophils were lower. We also performed random forest algorithm and found monocytes play the key role in carcinogenesis. Our study draws a peripheral blood immune cell landscape of the occurrence and development of CRC at the single-cell level and provides a reference for other researchers.

3.
Chem Sci ; 15(6): 2221-2228, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38332839

RESUMO

Near-infrared (NIR) chromophores with analyte tunable emission and absorption properties are highly desirable for developing activatable fluorescence and photoacoustic (PA) probes for bioimaging and disease diagnosis. Here we engineer a class of new chromophores by extending the π-conjugation system of a xanthene scaffold at position 7 with different electron withdrawing groups. It is demonstrated that these chromophores exhibit pH-dependent transition from a spirocyclic "closed" form to a xanthene "open" form with remarkable changes in spectral properties. We further develop fluorescence and PA probes by caging the NIR xanthene chromophores with a dipeptidyl peptidase 4 (DPPIV) substrate. In vitro and live cell studies show that these probes allow activatable fluorescence and PA detection and imaging of DPPIV activity with high sensitivity, high specificity and fast response. Moreover, these two probes allow high-contrast and highly specific imaging of DPPIV activity in a tumour-bearing mouse model in vivo via systemic administration. This study highlights the potential of a xanthene scaffold as a versatile platform for developing high-contrast fluorescence and PA molecular probes.

4.
Int J Biol Macromol ; 260(Pt 1): 129312, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38216020

RESUMO

Flavin-dependent halogenases (FDHs) have tremendous applications in synthetic chemistry. A single-component FDH, AetF, exhibits both halogenase and reductase activities in a continuous polypeptide chain. AetF exhibits broad substrate promiscuity and catalyzes the two-step bromination of l-tryptophan (l-Trp) to produce 5-bromotryptophan (5-Br-Trp) and 5,7-dibromo-l-tryptophan (5,7-di-Br-Trp). To elucidate the mechanism of action of AetF, we solved its crystal structure in complex with FAD, FAD/NADP+, FAD/l-Trp, and FAD/5-Br-Trp at resolutions of 1.92-2.23 Å. The obtained crystal structures depict the unprecedented topology of single-component FDH. Structural analysis revealed that the substrate flexibility and dibromination capability of AetF could be attributed to its spacious substrate-binding pocket. In addition, highly-regulated interaction networks between the substrate-recognizing residues and 5-Br-Trp are crucial for the dibromination activity of AetF. Several Ala variants underwent monobromination with >98 % C5-regioselectivity toward l-Trp. These results reveal the catalytic mechanism of single-component FDH for the first time and contribute to efficient FDH protein engineering for biocatalytic halogenation.


Assuntos
Oxirredutases , Triptofano , Oxirredutases/metabolismo , Triptofano/metabolismo , Halogenação , Compostos Orgânicos , Flavinas/metabolismo
5.
Nat Commun ; 14(1): 8357, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102128

RESUMO

Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed 'subgenome dominance' remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.


Assuntos
Carpas , Evolução Molecular , Animais , Poliploidia , Genoma/genética , Epigênese Genética , Genoma de Planta
6.
Front Microbiol ; 14: 1276928, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849925

RESUMO

Cyclodepsipeptides are a large family of peptide-related natural products consisting of hydroxy and amino acids linked by amide and ester bonds. A number of cyclodepsipeptides have been isolated and characterized from fungi and bacteria. Most of them showed antitumor, antifungal, antiviral, antimalarial, and antitrypanosomal properties. Herein, this review summarizes the recent literatures (2010-2022) on the progress of cyclodepsipeptides from fungi and bacteria except for those of marine origin, in order to enrich our knowledge about their structural features and biological sources.

7.
BMC Public Health ; 23(1): 1254, 2023 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-37380948

RESUMO

AIMS: Neutrophils play a pivotal in immunity and inflammation. We aim to investigate the prevalence of neutropenia in the United States. METHODS: In this cross-sectional study, participants from the National Health and Nutrition Examination Survey (NHANES) (2011-2018) were enrolled. Demographic information, hematologic measurements, smoking status of all participants were collected for all participants. All statistical analyses were performed utilizing the NHANES survey weights. Covariate-adjusted linear regression was used to compare hematologic indices in different population grouped by age, sex, ethnicity, and smoking. We also employed multivariate-logistic regression to estimate the weighted odds ratio with a 95% confidence interval and predict the neutropenia risk among. RESULTS: 32,102 participants from NHANES survey were included, represented 286.6 million multiracial population in the United States. Black participants had lower mean leukocyte count (mean difference (MD): 0.71 × 109/L; P < 0.001) and lower neutrophil count (MD: 0.83 × 109/L; P < 0.001) compared with white participants after adjusting for age and sex. Furthermore, t a notable observation was the significant downward shift in the distribution curves of leukocyte count and neutrophil count among black participants. Smokers had a higher mean leukocyte count (MD: 1.10 × 109 cells/L; P < 0.001) and a higher mean neutrophil count (MD: 0.75 × 109 cells/L; P < 0.001) comparing with nonsmokers. The estimated prevalence of neutropenia was 1.24% (95% CI: 1.11 - 1.37%), which corresponds to approximately 35.5 million individuals in the United States. The prevalence of neutropenia in black participants was significantly higher than other races. Results of logistic regression analysis showed that black individuals, male individuals, and children younger than 5 years had a higher risk of neutropenia. CONCLUSIONS: Neutropenia is more common in the general population than we thought, especially in black individuals and children. More attention should be paid to neutropenia.


Assuntos
Neutropenia , Criança , Humanos , Masculino , Inquéritos Nutricionais , Estudos Transversais , Prevalência , Neutropenia/epidemiologia , Contagem de Leucócitos
8.
J Cancer Res Clin Oncol ; 149(11): 8335-8344, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37074453

RESUMO

BACKGROUND: In recent years, morbidity and mortality from colorectal cancer have increased. Colorectal adenoma is the main precancerous lesion. Understanding the pathogenesis of colorectal adenoma will help to improve the early diagnosis rate of colorectal cancer. METHODS: In this case-control study, we focused on three single nucleotide polymorphisms (SNPs) in genes SLC8A1 (rs4952490), KCNJ1 (rs2855798), and SLC12A1 (rs1531916). We analyzed 207 colorectal adenoma patients (112 high-risk cases and 95 low-risk cases) and 212 control subjects by Sanger sequencing. A food frequency questionnaire (FFQ) was used to survey demographic characteristics and dietary nutrition. RESULTS: In the overall analysis, the results suggested that the AA+AG and AG genotype carriers of rs4952490 had a 73.1% and 78% lower risk of colorectal adenoma compared to GG genotype carriers, respectively. However rs2855798 and rs1531916 were not associated with the incidence of colorectal adenoma. Additionally, stratified analysis showed that rs4952490 AA+AG and AG genotypes had a protective effect against low-risk colorectal adenoma in patients aged ≤ 60 years old who were non-smokers. We also observed that when calcium intake was higher than 616 mg/d and patients carried at least one gene with variant alleles there was a protective effect against low-risk colorectal adenoma. CONCLUSIONS: Interactions between dietary calcium intake and calcium reabsorption genes may affect the occurrence and development of colorectal adenoma.


Assuntos
Adenoma , Neoplasias Colorretais , Canais de Potássio Corretores do Fluxo de Internalização , Humanos , Pessoa de Meia-Idade , Cálcio , Cálcio da Dieta , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Genótipo , Neoplasias Colorretais/patologia , Adenoma/genética , Fatores de Risco , Canais de Potássio Corretores do Fluxo de Internalização/genética , Membro 1 da Família 12 de Carreador de Soluto/genética
9.
Int J Surg ; 109(4): 772-784, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36999800

RESUMO

BACKGROUND: With the elimination of schistosomiasis in China, its role in the pathogenesis of colorectal cancer (CRC) has decreased. However, the trends, clinicopathological features, surgical treatment patterns, and prognosis of schistosomiasis-associated CRC (SACRC) versus non-schistosomiasis-associated CRC (NSACRC) in China remain unclear. MATERIALS AND METHODS: The percentage trend of SACRC in CRC patients in China was analyzed using data retrieved from the Pathology Registry of Changhai Hospital (2001-2021). Clinicopathological characteristics, surgical treatment patterns, and prognosis-related parameters were compared between the two groups. Multivariate Cox regression analyses were performed for disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 31 153 CRC cases were included, with 823 (2.6%) cases of SACRC and 30 330 (97.4%) cases of NSACRC. The average percentage of SACRC cases has decreased continuously from 3.8 to 1.7% (from 2001 to 2021). Compared with the NSACRC group, the SACRC group had more men, older age at diagnosis, lower BMI, fewer symptoms; higher rates of rectal cancer, comorbidities, KRAS mutation, multiple primary CRC and concomitant polyps; less lymph node metastasis, distant metastasis, vascular invasion, and tumor budding; less preoperative radiotherapy and preoperative chemotherapy; and more positive resection margins and postoperative targeted therapy. There were no significant differences between the two groups regarding laparoscopic surgery, palliative resection, extended radical resection, or ostomy. Moreover, the SACRC group had adverse DFS and similar OS compared with the NSACRC group. In multivariate analyses, schistosomiasis was not an independent predictor of DFS or OS. CONCLUSION: The percentage of SACRC in CRC (2.6%) in our hospital was very low, and it decreased continuously over the last two decades, indicating that schistosomiasis is no longer an important risk factor for CRC in Shanghai, China. Patients with SACRC have distinct clinicopathological, molecular, and treatment-related features and survival rates similar to those with NSACRC.


Assuntos
Neoplasias Colorretais , Neoplasias Retais , Masculino , Humanos , Neoplasias Colorretais/patologia , Estudos Retrospectivos , China/epidemiologia , Prognóstico , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Estadiamento de Neoplasias
10.
Front Mol Neurosci ; 16: 1089871, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36818658

RESUMO

Introduction: Previous studies have suggested that the dysregulation of purine metabolism may be associated with autism spectrum disorder (ASD). Here, we adopted metabolomics and transcriptomics to verify and explore the underlying molecular mechanism of purine metabolism dysfunction in ASD and identify potential biomarkers within the purine metabolism pathway. Methods: Ultra-high-performance liquid chromatography-mass spectrometry was used to obtain the plasma metabolic profiles of 12 patients with ASD and 12 typically developing (TD) children. RNA sequencing was used to screen differentially expressed genes related to the purine metabolic pathway and purine receptor-coding genes in 24 children with ASD and 21 healthy controls. Finally, serum uric acid levels were compared in 80 patients with ASD and 174 TD children to validate the omics results. Results: A total of 66 identified metabolites showed significant between-group differences. Network analysis showed that purine metabolism was the most strongly enriched. Uric acid was one of the most highlighted nodes within the network. The transcriptomic study revealed significant differential expression of three purine metabolism-related genes (adenosine deaminase, adenylosuccinate lyase, and bifunctional enzyme neoformans 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/inosine monophosphate (IMP) cyclohydrolase) (p < 0.01) and five purinergic receptor genes (P2X7, P2Y2, P2Y6, P2Y8, and P2Y10) (p < 0.05). In the validation sample, there was a significant difference in serum uric acid levels between the two groups (p < 0.001), and the area under the curve for uric acid was 0.812 (sensitivity, 82.5%; specificity, 63.8%). Discussion: Patients with ASD had dysfunctional purine metabolic pathways, and blood uric acid may be a potential biomarker for ASD.

11.
J Nat Prod ; 85(11): 2592-2602, 2022 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-36288556

RESUMO

In this work, four new cyclodepsipeptides, fusarihexins C-E (1-3) and enniatin Q (4), four new cyclopentane derivatives, fusarilins A-D (5-8), together with eight known compounds (9-16), were isolated from cultures of the endophytic fungus Fusarium sp. The structures of the isolated compounds were elucidated by analysis of HRMS and NMR spectroscopic data. The absolute configurations were determined using Marfey's method, a modified Mosher's method, single-crystal X-ray diffraction analysis, and ECD analysis. The antitumor activities of the isolated compounds in vitro were evaluated. Cyclodepsipeptides displayed cytotoxicities against the Huh-7, MRMT-1, and HepG-2 cell lines. Compounds 4, 9, 10, and 12 with IC50 values of 1.0-9.1 µM exhibited the most potent cytotoxicities against the three cell lines as compared to the positive control-5-fluorouracil. Compounds 1-3 and 11 exhibited moderate cytotoxic activities (IC50 values of 10.7-20.1 µM).


Assuntos
Antineoplásicos , Ciclopentanos , Depsipeptídeos , Fusarium , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Cristalografia por Raios X , Ciclopentanos/química , Ciclopentanos/isolamento & purificação , Ciclopentanos/farmacologia , Depsipeptídeos/química , Fusarium/química , Estrutura Molecular , Células Hep G2 , Humanos
12.
Phytochemistry ; 203: 113397, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36029846

RESUMO

Oleanolic acid (OA), a ubiquitous pentacyclic oleanane-type triterpene isolated from edible and medicinal plants, exhibits a wide spectrum of pharmacological activities and tremendous therapeutic potential. However, the undesirable pharmacokinetic properties limit its application and development. Numerous researches on structural modifications of OA have been carried out to overcome this limitation and improve its pharmacokinetic and therapeutic properties. This review aims to compile and summarize the recent progresses in the medicinal chemistry of OA derivatives, especially on structure-activity relationship in the last few years (2010-2021). It gives insights into the rational design of bioactive derivatives from OA scaffold as promising therapeutic agents.


Assuntos
Ácido Oleanólico , Plantas Medicinais , Triterpenos , Química Farmacêutica , Ácido Oleanólico/química , Plantas Medicinais/química , Relação Estrutura-Atividade , Triterpenos/química
13.
Biomolecules ; 12(6)2022 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-35740903

RESUMO

The secondary metabolites of Fusarium sporotrichioides, an endophytic fungus with anti-tumor activity isolated from Rauvolfia yunnanensis Tsiang, were investigated. Five trichothecenes, including one previously undescribed metabolite, were isolated and identified. Their structures were elucidated by means of extensive spectroscopic methods; the absolute configuration of compound 1 was determined by the ECD method. Surprisingly, 8-n-butyrylneosolaniol (3) exhibited stronger anti-tumor activity than T-2 toxin against Huh-7 cell line, with an IC50 value of 265.9 nM. 8-n-butyrylneosolaniol (3) promoted apoptosis induction in Huh-7 cells. Moreover, cell cycle analysis showed that cell cycle arrest caused by 8-n-butyrylneosolaniol (3) at the G2/M phase resulted in cell proliferation inhibition and pro-apoptotic activity. Further studies showed a significant decrease in mitochondrial membrane permeabilization and a significant increase in ROS generation, which led to the activation of caspase cascades and subsequent cleavage of PARP fragments. In conclusion, 8-n-butyrylneosolaniol (3) induced cell apoptosis in Huh-7 cells via the mitochondria-mediated apoptotic signaling pathway, which could be a leading compound for anti-tumor agents.


Assuntos
Neoplasias , Tricotecenos , Apoptose , Caspases , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Fungos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tricotecenos/farmacologia
14.
Food Nutr Res ; 652021.
Artigo em Inglês | MEDLINE | ID: mdl-34984064

RESUMO

BACKGROUND: Pumpkin seed oil is widely used to treat benign prostatic hyperplasia (BPH), a common disease in elder men. However, its active components and mechanism have remained to be elucidated. OBJECTIVE: The objective of the present study was to investigate the active components of pumpkin seed oil and its mechanism against BPH. DESIGN: Total phytosterol (TPS) was isolated from hull-less pumpkin (Cucurbita pepo L. var. Styriaca) seed oil and analyzed by gas chromatography/mass spectrometry (GC/MS). Three phytosterols were purified by preparative HPLC (high performance liquid chromatography) and confirmed by NMR (nuclear magnetic resonance). TPS (3.3 mg/kg body weight, 1 mL/day/rat) was administered intragastrically to the testosterone propionate-induced BPH rats for 4 weeks. The structure changes of prostate tissues were assessed by hematoxylin & eosin (H&E) staining. The expression of androgen receptor (AR) and steroid receptor coactivator 1 (SRC-1) was analyzed by immunohistochemistry, while that of 5α-reductase (5AR), apoptosis, or proliferation-related growth factors/proteins was detected by real-time quantitative polymerase chain reaction or western blotting. RESULTS: The ∆7-phytosterols in TPS reached up to 87.64%. Among them, 24ß-ethylcholesta-7,22,25-trienol, 24ß-ethylcholesta-7,25(27)-dien-3-ol, and ∆7-avenasterol were confirmed by NMR. TPS treatment significantly ameliorated the pathological prostate enlargement and restored histopathological alterations of prostate in BPH rats. It effectively suppressed the expressions of 5AR, AR, and coactivator SRC-1. TPS inhibited the expression of proliferation-related growth factor epidermal growth factor, whereas it increased the expressions of apoptosis-related growth factor/gene transforming growth factor-ß1. The proliferation-inhibiting effect was achieved by decreasing the ERK (extracellular signal-regulated kinase) phosphorylation, while apoptosis was induced by Caspase 3 activation through JNK (c-Jun N-terminal kinase) and p38 phosphorylation. CONCLUSION: TPS from hull-less pumpkin seed oil, with ∆7-phytosterols as its main ingredients, is a potential nutraceutical for BPH prevention.

15.
Adv Parasitol ; 110: 1-62, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32563322

RESUMO

Being a zoonotic parasitic disease, schistosomiasis was widely spread in 12 provinces of Southern China in the 1950s, severly harming human health and hindering economic development. The National Institute of Parasitic Diseases at the Chinese Center for Diseases Control and Prevention, and Chinese Center for Tropical Diseases Research (NIPD-CTDR), as the only professional institution focussing on parasitic diseases at the national level, has played an important role in schistosomiasis control in the country. In this article, we look back at the changes of schistosomiasis endemicity and the contribution of NIPD-CTDR to the national schistosomiasis control programme. We review NIPD-CTDR's activities, including field investigations, design of control strategies and measures, development of diagnostics and drugs, surveillance-response of endemic situation, and monitoring & evaluation of the programme. The NIPD-CTDR has mastered the transmission status of schistosomiasis, mapped the snail distribution, and explored strategies and measures suitable for different types of endemic areas in China. With a good understanding of the life cycle of Schistosoma japonicum and transmission patterns of the disease, advanced research carried out in the NIPD-CTDR based on genomics and modern technology has made it possible to explore highly efficient and soft therapeutic drugs and molluscicides, making it possible to develop new diagnostic tools and produce vaccine candidates. In the field, epidemiological studies, updated strategies and targeted intervention measures developed by scientists from the NIPD-CTDR have contributed significantly to the national schistosomiasis control programme. This all adds up to a strong foundation for eliminating schistosomiasis in China in the near future, and recommendations have been put forward how to reach this goal.


Assuntos
Academias e Institutos , Doenças Endêmicas/prevenção & controle , Programas Governamentais , Programas Nacionais de Saúde , Esquistossomose Japônica , Animais , Bovinos , China/epidemiologia , Erradicação de Doenças , Desenvolvimento de Medicamentos , Humanos , Moluscocidas , Esquistossomose Japônica/tratamento farmacológico , Esquistossomose Japônica/epidemiologia , Esquistossomose Japônica/transmissão , Vacinação
16.
Photodiagnosis Photodyn Ther ; 31: 101881, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32562734

RESUMO

Infections with human papillomavirus in the anogenital area result in warty, papillary, and condylomatous lesions. The giant anogenital wart is relatively uncommon. Treatment of giant wart is challenging, especially in the immunosuppressive population. Here, a patient with systemic lupus erythematosis had extensive, fast-growing, recurrent anogenital condylomatosis shaped as giant cauliflowers. We reported this case and the successful treatment of photodynamic therapy combined with surgical management. It provided the feasibility for surgical ablation combined with ALA-PDT performed for these kinds of challenging cases.


Assuntos
Condiloma Acuminado , Lúpus Eritematoso Sistêmico , Fotoquimioterapia , Ácido Aminolevulínico/uso terapêutico , Condiloma Acuminado/complicações , Condiloma Acuminado/tratamento farmacológico , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico
17.
J Clin Med Res ; 10(10): 752-757, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30214646

RESUMO

Diabetes mellitus (DM) is a chronic, multifactorial metabolic disease whereby insulin deficiency or resistance results in hyperglycemia. Endothelial cells (ECs) form the innermost layer of the blood vessel and produce and release a variety of vasoactive substances and growth factors to regulate vascular homeostasis and angiogenesis. Hyperglycemia and insulin resistance can cause endothelial dysfunction, leading to vascular complications such as coronary artery disease, peripheral arterial disease, diabetic nephropathy, neuropathy and retinopathy. The detrimental effect exerted on ECs by hyperglycemia and insulin resistance underlines the importance of reparatory mechanisms in DM. Endothelial progenitor cells (EPCs), derived from bone marrow, have been recognized as endogenous cells involved in endothelial repair and new blood vessel formation. Initially isolated from a subset of circulating CD34+ mononuclear cells, EPCs were found to possess the ability to differentiate into ECs when cultured in vitro and incorporate into newly formed vessels upon transplantation in animal models of ischemia. Due to the low frequency of CD34+ cells in circulation, the vast majority of studies investigating EPC actions have used cells that are generated through the culture of peripheral blood mononuclear cells (PBMNCs) for 4 - 7 days in endothelial selective medium. These cells, mainly of myeloid hematopoietic cell origin, were termed "Early EPCs," of which, few expressed stem/progenitor-cell markers. Therefore, early EPCs were also termed "myeloid angiogenic cells" (MACs). When PBMNCs are cultured for over 2 weeks, early EPCs gradually diminish while so-called late EPCs appear. Late EPCs share phenotypic features with mature ECs and are therefore also termed blood-derived ECs; they will not be addressed in this review. MAC dysfunction has been observed in a variety of disease conditions including DM. In this article we review the activities and therapeutic potential of MACs in DM. We will interchangeably use "EPCs" and "MACs" to refer to the cells procured by culture of PBMNCs in EC selective medium for approximately 7 days.

18.
Can J Anaesth ; 65(8): 901-913, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29696581

RESUMO

PURPOSE: Hemodilutional anemia is associated with acute kidney injury (AKI) and mortality in patients undergoing cardiac surgery by mechanisms that may include tissue hypoxia. Our hypothesis was to assess if changes in the potential hypoxic biomarkers, including methemoglobin and erythropoietin, correlated with a decrease in hemoglobin (Hb) concentration following hemodilution on cardiopulmonary bypass (CPB). METHODS: Arterial blood samples were taken from patients (n = 64) undergoing heart surgery and CPB at baseline, during CPB, following CPB, and in the intensive care unit (ICU). Potential hypoxic biomarkers were measured, including methemoglobin, plasma Hb, and erythropoietin. Data were analyzed by repeated measures one-way analysis of variance on ranks and linear regression. RESULTS: Hemoglobin levels decreased following CPB and methemoglobin increased in the ICU (P < 0.001 for both). No correlation was observed between the change in Hb and methemoglobin (P = 0.23). By contrast, reduced Hb on CPB correlated with increased lactate, reduced pH, and increased erythropoietin levels following CPB (P ≤ 0.004 for all). Increased plasma Hb (P < 0.001) also correlated with plasma erythropoietin levels (P < 0.001). CONCLUSION: These data support the hypothesis that erythropoietin rather than methemoglobin is a potential biomarker of anemia-induced tissue hypoxia. The observed relationships between decreased Hb during CPB and the increase in lactate, reduced pH, and increase in erythropoietin levels suggest that early changes in plasma erythropoietin may be a pragmatic early biomarker of anemia-induced renal hypoxia. Further study is required to determine if anemia-induced increases in erythropoietin may predict AKI in patients undergoing cardiac surgery. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01883713). Registered 21 June 2013.


Assuntos
Injúria Renal Aguda/etiologia , Anemia/complicações , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Hemodiluição/efeitos adversos , Hipóxia/diagnóstico , Idoso , Biomarcadores/sangue , Ponte Cardiopulmonar/efeitos adversos , Eritropoetina/sangue , Feminino , Hemoglobinas/análise , Humanos , Masculino , Metemoglobina/análise , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Nanoscale ; 9(45): 17893-17901, 2017 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-29119988

RESUMO

Organic-inorganic perovskite solar cells have emerged as a promising photovoltaic technology because of their advantages such as low cost, high efficiency, and solution processability. The performance of perovskite solar cells is highly dependent on the crystallinity and morphology of the perovskite films. Herein, we report a simple, one-step anti-solvent deposition process using di-isopropyl ether as a dripping solvent to obtain extremely uniform and highly crystalline CH3NH3PbI3 perovskite films. Compared to toluene, chlorobenzene, chloroform, or diethyl ether, di-isopropyl ether has proven to be a more suitable solvent for an anti-solvent deposition process. The perovskite solar cells fabricated by the anti-solvent deposition process using di-isopropyl ether treatment exhibit an average power conversion efficiency (PCE) of 17.67 ± 0.54% and the highest PCE of 19.07%. Moreover, the higher boiling point of di-isopropyl ether makes the anti-solvent deposition process more tolerant to elevated ambient temperature, which can be carried out at ambient temperatures up to 40 °C. Our results demonstrate that di-isopropyl ether is an excellent dripping solvent in the anti-solvent deposition process for efficient and reproducible perovskite solar cells.

20.
Thorac Cardiovasc Surg ; 64(7): 555-560, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26366890

RESUMO

Background Acute kidney injury (AKI) is a common and serious complication of surgeries that include cardiopulmonary bypass (CPB). Currently, increases in serum creatinine levels are used to diagnose AKI, but this change may be slow to detect. Animal studies pertaining to renal hypoxia suggest a correlation between vasopressinase activity and AKI. The objective of this study is to determine if vasopressinase activity can be used as an early biomarker for renal hypoxia and CPB-associated AKI. This could potentially help improve the diagnosis and subsequent treatment of the condition. Materials and Methods We conducted a single-center, prospective observational study which analyzed serum vasopressinase activity and creatinine levels at seven time points from 31 patients undergoing CPB. We also measured urine vasopressinase activity in 19 of the 31 patients at five of the time points. Results Results show that serum and urine vasopressinase activity peak at the time of arrival to the ICU for patients undergoing CPB. This increase occurred earlier than the increase in creatinine, which generally occurred on postoperative day 2. In the five patients who were diagnosed with AKI, vasopressinase activity peaked 30 minutes into CPB while creatinine peaked on postoperative day 2. Conclusion Our findings suggest that vasopressinase might be a potential early biomarker for AKI. Further studies with other AKI biomarkers are required to determine if the vasopressinase response can be directly attributed to the presence of AKI.


Assuntos
Injúria Renal Aguda/diagnóstico , Ponte Cardiopulmonar/efeitos adversos , Ensaios Enzimáticos Clínicos , Cistinil Aminopeptidase/sangue , Cistinil Aminopeptidase/urina , Injúria Renal Aguda/sangue , Injúria Renal Aguda/urina , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Creatinina/sangue , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA