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1.
J Cancer Educ ; 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35435621

RESUMO

To meet the rising demand for flexible learning in data-driven health research, we adapted an in-person undergraduate research program (Quantitative Sciences Undergraduate Research Experience (QSURE)) to an all-virtual framework in summer 2020 and 2021. We used Web-conferencing and remote computing to implement virtual hands-on research training within a comprehensive cancer center. We designed the program to achieve research and career development goals: students completed faculty-mentored quantitative research projects and received education in the responsible conduct of research and practical skills, such as oral and written presentation. We assessed virtual program efficacy using pre- and post-program quantitative and qualitative student feedback. Eighteen students participated (nine each year); they reported high satisfaction with the virtual format. Compared with baseline, students reported improved perceived competence in quantitative skills and research knowledge post-program; these improvements were comparable to the in-person program. Defined benchmarks and consistent communication (with mentors, program directors, other students) were crucial to students' success; however, students noted challenges in building camaraderie online. With adequate resources, Web-based technology can be leveraged as an effective format for hands-on quantitative research training. Our framework can be tailored to an institution's needs, particularly those for which available resources better align with a virtual research program.

2.
Cogn Neurodyn ; 16(2): 411-423, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35401866

RESUMO

Febrile seizure (FS) is a full-body convulsion caused by a high body temperature that affect young kids, however, how these most common of human seizures are generated by fever has not been known. One common observation is that cortical neurons become overexcited with abnormal running of sodium and potassium ions cross membrane in raised body temperature condition, Considering that astrocyte Kir4.1 channel play a critical role in maintaining extracellular homeostasis of ionic concentrations and electrochemical potentials of neurons by fast depletion of extracellular potassium ions, we examined here the potential role of temperature-dependent Kir4.1 channel in astrocytes in causing FS. We first built up a temperature-dependent computational model of the Kir4.1 channel in astrocytes and validated with experiments. We have then built up a neuron-astrocyte network and examine the role of the Kir4.1 channel in modulating neuronal firing dynamics as temperature increase. The numerical experiment demonstrated that the Kir4.1 channel function optimally in the body temperature around 37 °C in cleaning 'excessive' extracellular potassium ions during neuronal firing process, however, higher temperature deteriorates its cleaning function, while lower temperature slows down its cleaning efficiency. With the increase of temperature, neurons go through different stages of spiking dynamics from spontaneous slow oscillations, to tonic spiking, fast bursting oscillations, and eventually epileptic bursting. Thus, our study may provide a potential new mechanism that febrile seizures may be happened due to temperature-dependent functional disorders of Kir4.1 channel in astrocytes. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-021-09706-w.

5.
Ann Transl Med ; 10(2): 84, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35282076

RESUMO

Background: Transcatheter aortic valve implantation (TAVI) is an alternative method to treat patients with severe aortic valve disease. Accurate measurement of the aortic valve annulus and selection of the appropriate artificial valve are critical to the success of TAVI. Multilayer spiral computed tomography (MSCT) is recommended as the "gold standard" for assessing the aortic valve annulus before TAVI. However, MSCT scanning may not be possible for patients with iodine allergy, renal failure, or pregnancy. The purpose of this study is to evaluate the aortic valve annulus by three-dimensional transesophageal echocardiography (3D-TEE) and compare the results with MSCT, exploring the feasibility of 3D-TEE to guide the selection of artificial valve implantation in TAVI. Methods: We retrospectively analyzed 74 patients who successfully underwent TAVI in our hospital. Before the operation, 3D-TEE and MSCT were used to measure the maximum diameter, minimum diameter, area-derived diameter, and perimeter-derived diameter of the aortic valve annulus, and the results were analyzed for consistency. To predict the valve size based on 3D-TEE and the MSCT area-derived diameter, we compared the differences between the predicted valve size and the actual implanted valve size, and analyzed the differences between 3D-TEE and MSCT for guiding the selection of the prosthetic valve size. Results: There was no significant difference between 3D-TEE and MSCT in the measurement of the maximum diameter, minimum diameter, area, and perimeter of the aortic annulus and their derived diameter (P>0.05). The intraclass correlation coefficients for the maximum diameter, minimum diameter, area-derived diameter, and perimeter-derived diameter of the aortic annulus were 0.89, 0.83, 0.84, and 0.92, respectively. There was no statistical difference in the accuracy of both methods, 3D-TEE and MSCT, in predicting different prosthetic valve sizes for TAVI (P>0.05). Conclusions: 3D-TEE and MSCT have good agreement for measuring the values of various parameters of the aortic annulus. The accuracy of both methods was similar for predicting the aortic prosthetic valve size. 3D-TEE may provide guidance for selecting the prosthetic valve size for TAVI.

6.
Cancer Epidemiol ; 77: 102100, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35033923

RESUMO

BACKGROUND: Progressive telomere shortening may be related to genomic instability and carcinogenesis. Prospective evidence relating telomere length (TL) with colorectal cancer (CRC) risk has been limited and inconsistent. METHODS: We examined the association between pre-diagnostic peripheral blood leukocyte TL and CRC risk in two matched case-control studies nested within the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). Relative leukocyte TL was measured using qPCR among 356 incident CRC cases and 801 controls (NHS: 186/465, HPFS: 170/336). RESULTS: We did not find a significant association between pre-diagnostic TL and CRC risk [in all participants, multivariable-adjusted odds ratio (OR) (95% CI) for TL Quartile 1 (shortest) vs. Quartile 4 (longest) = 1.36 (0.85, 2.17), P-trend = 0.27; OR (95% CI) per 1 SD decrease in TL = 1.12 (0.92, 1.36)]. CONCLUSIONS: Our prospective analysis did not support a significant association between pre-diagnostic leukocyte TL and CRC risk.


Assuntos
Neoplasias Colorretais , Telômero , Estudos de Casos e Controles , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Seguimentos , Humanos , Leucócitos , Fatores de Risco , Telômero/genética
7.
J Natl Cancer Inst ; 114(4): 528-539, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35026030

RESUMO

BACKGROUND: The incidence of colorectal cancer (CRC) among individuals aged younger than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS) of 141 variants. METHODS: Relying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3486 cases and 3890 controls aged younger than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve. RESULTS: Increasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per SD of ERS = 1.14, 95% confidence interval [CI] = 1.08 to 1.20; odds ratio per SD of PRS = 1.59, 95% CI = 1.51 to 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615 to 0.647). Based on absolute risks, we can expect 26 excess cases per 10 000 men and 21 per 10 000 women among those scoring at the 90th percentile for both risk scores. CONCLUSIONS: Personal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco
8.
Cancer Epidemiol Biomarkers Prev ; 31(3): 647-653, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35027430

RESUMO

BACKGROUND: Use of the dietary supplement glucosamine has been associated with reduced risk of colorectal cancer; however, it remains unclear if the association varies by screening status, time, and other factors. METHODS: We therefore evaluated these questions in UK Biobank. Multivariable-adjusted HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression. RESULTS: No association was observed between use of glucosamine and risk of colorectal cancer overall (HR = 0.94; 95% CI, 0.85-1.04). However, the association varied by screening status (Pinteraction = 0.05), with an inverse association observed only among never-screened individuals (HR = 0.86; 95% CI, 0.76-0.98). When stratified by study time, an inverse association was observed in early follow-up among those entering the cohort in early years (2006-2008; HR = 0.80; 95% CI, 0.67-0.95). No heterogeneity was observed by age, sex, body mass index, smoking status, or use of nonsteroidal anti-inflammatory drugs. CONCLUSIONS: While there was no association between glucosamine use and colorectal cancer overall, the inverse association among never-screened individuals mirrors our observations in prior exploratory analyses of U.S. cohorts. The National Health Service Bowel Cancer Screening Program started in 2006 in England and was more widely implemented across the UK by 2009/2010. In line with this, we observed an inverse association limited to early follow-up in those surveyed from 2006 to 2008, before screening was widely implemented. IMPACT: These data suggest that unscreened individuals may benefit from use of glucosamine; however, further studies are needed to confirm the interplay of screening and timing.


Assuntos
Neoplasias Colorretais , Glucosamina , Bancos de Espécimes Biológicos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Humanos , Modelos de Riscos Proporcionais , Fatores de Risco , Medicina Estatal , Reino Unido/epidemiologia
10.
Int J Colorectal Dis ; 37(1): 231-238, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34698909

RESUMO

BACKGROUND AND AIMS: Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer and is associated with an increased lifetime risk of gastric and duodenal cancers of 8-16% and 7%, respectively; therefore, we aim to describe an esophagogastroduodenoscopy (EGD) surveillance program for upper gastrointestinal (GI) precursor lesions and cancer in LS patients. METHODS: Patients who either had positive genetic testing or met clinical criteria for LS who had a surveillance EGD at our institution from 1996 to 2017 were identified. Patients were included if they had at least two EGDs or an upper GI cancer detected on the first surveillance EGD. EGD and pathology reports were extracted manually. RESULTS: Our cohort included 247 patients with a mean age of 47.1 years (SD 12.6) at first EGD. Patients had a mean of 3.5 EGDs (range 1-16). Mean duration of follow-up was 5.7 years. Average interval between EGDs was 2.3 years. Surveillance EGD detected precursor lesions in 8 (3.2%) patients, two (0.8%) gastric cancers and two (0.8%) duodenal cancers. Two interval cancers were diagnosed: a duodenal adenocarcinoma was detected 2 years, 8 months after prior EGD and a jejunal adenocarcinoma was detected 1 year, 9 months after prior EGD. CONCLUSIONS: Our data suggest that surveillance EGD is a useful tool to help detect precancerous and cancerous upper GI lesions in LS patients. To our knowledge, this is the first study to examine a program of surveillance EGDs in LS patients. More data are needed to determine the appropriate surveillance interval.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Gastrointestinais , Neoplasias Gástricas , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Endoscopia do Sistema Digestório , Endoscopia Gastrointestinal , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/genética , Gastroscopia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética
11.
J Agric Food Chem ; 70(1): 229-237, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34955018

RESUMO

The study aims to enhance ß-amyrin production in Saccharomyces cerevisiae by peroxisome compartmentalization. First, overaccumulated squalene was determined as a key limiting factor for the production of ß-amyrin since it could inhibit the activity of ß-amyrin synthase GgbAs1. Second, to mitigate the inhibition effect, the enhanced squalene synthesis pathway was compartmentalized into peroxisomes to insulate overaccumulated squalene from GgbAs1, and thus the specific titer of ß-amyrin reached 57.8 mg/g dry cell weight (DCW), which was 2.6-fold higher than that of the cytosol engineering strain. Third, by combining peroxisome compartmentalization with the "push-pull-restrain" strategy (ERG1 and GgbAs1 overexpression and ERG7 weakening), the production of ß-amyrin was further increased to 81.0 mg/g DCW (347.0 mg/L). Finally, through fed-batch fermentation in a 5 L fermenter, the titer of ß-amyrin reached 2.6 g/L, which is the highest reported to date. The study provides a new perspective to engineering yeasts as a platform for triterpene production.


Assuntos
Engenharia Metabólica , Ácido Oleanólico/biossíntese , Saccharomyces cerevisiae , Esqualeno , Microbiologia Industrial , Transferases Intramoleculares , Ácido Oleanólico/análogos & derivados , Saccharomyces cerevisiae/genética
12.
JCO Precis Oncol ; 6: e2100401, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35108035

RESUMO

PURPOSE: The spectrum of somatic mutations among women with endometrial cancer (EC) younger than 50 years (early-onset EC) remains unknown. We investigated distinct somatic mutation patterns among early-onset and late-onset (age ≥ 50 years) EC patients. METHODS: This cohort study included individuals age 18+ years diagnosed with pathologically confirmed EC in the American Association of Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE, v9.1) consortium. We explored tumor mutational burden (TMB) and genomic patterns of EC by age at clinical sequencing using multivariable regression models adjusted for race, ethnicity, histology, sequencing assay, sample type, and TMB. RESULTS: Among 2,425 women with EC, 176 (7.3%) had early-onset EC and 1,923 (79.3%) had nonhypermutated (< 17.78 mutations/Mb) tumors. TMB significantly differed across age and histology groups. Among nonhypermutated ECs, early-onset patients had significantly lower odds of presenting with nonsilent FGFR2 and PIK3R1 somatic mutations compared with late-onset EC patients in adjusted models (FGFR2: odds ratio [OR] = 0.18, 95% CI, 0.04 to 0.76; PIK3R1: OR = 0.54, 95% CI, 0.31 to 0.92). By contrast, early-onset EC patients had increased odds of presenting with nonsilent CTNNB1 and BRCA2 mutations compared with late-onset patients (CTNNB1: OR = 3.32, 95% CI, 2.14 to 5.16; BRCA2: OR = 4.01, 95% CI, 1.55 to 10.38). Subsequent analyses stratified by race, ethnicity, and tumor histology identified distinct patterns of APC, KMT2D, KMT2C, and KRAS by race, ethnicity, and PTEN and APC patterns by histologic subtypes. CONCLUSION: Early-onset EC harbors a unique genomic landscape compared with late-onset disease. A distinct molecular phenotype of early-onset EC provides novel insights into a unique etiology and may yield clinical implications for developing targeted treatment modalities for younger patients.


Assuntos
Neoplasias do Endométrio , Genoma , Estudos de Coortes , Neoplasias do Endométrio/epidemiologia , Feminino , Genômica , Humanos , Mutação
13.
Nutr Cancer ; : 1-11, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34817305

RESUMO

Research suggests that high intake of supplemental vitamin B12 may be associated with increased risk of cancer, with some evidence that this association may vary by gender and smoking status. This investigation evaluates if similar patterns in association are observed for data for 11,757 adults from the National Health and Nutrition Examination Survey (1999-2006). Survey-weighted multivariable-adjusted linear regression was used to evaluate the association between regular B12 supplement use and log-transformed serum B12 levels. Persons taking vitamin B12 through a multivitamin/multimineral (MVMM) had a median supplemental intake of 12 mcg/day (Q1: 6, Q3: 25), compared to 100 mcg/day (Q1: 22, Q3: 500) for persons reporting supplemental B12 intake through a MVMM-exclusive source. MVMM users had a geometric mean serum B12 26% (95% CI: 23%-30%) higher than nonusers, whereas MVMM-exclusive users' geometric mean was 61% (95% CI: 53%-70%) higher than nonusers (p-trend < 0.001). Although a positive trend (p-trend < 0.001) was observed for both men and women, the association was stronger among women (p-interaction < 0.001). No interaction was observed for smoking status (p-interaction = 0.45). B12 supplementation is associated with higher levels of serum B12, with significant interaction by gender but not smoking. Further work is needed to better understand the interplay of B12 and gender.

14.
Metab Eng ; 68: 232-245, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34710614

RESUMO

Harnessing mitochondria is considered as a promising method for biosynthesis of terpenes due to the adequate supply of acetyl-CoA and redox equivalents in mitochondria. However, mitochondrial engineering often causes serious metabolic burden indicated by poor cell growth. Here, we systematically analyzed the metabolic burden caused by the compartmentalization of the MVA pathway in yeast mitochondria for squalene synthesis. The phosphorylated intermediates of the MVA pathway, especially mevalonate-5-P and mevalonate-5-PP, conferred serious toxicity within mitochondria, which significantly compromised its possible advantages for squalene synthesis and was difficult to be significantly improved by routine pathway optimization. These phosphorylated intermediates were converted into ATP analogues, which strongly inhibited ATP-related cell function, such as mitochondrial oxidative respiration. Fortunately, the introduction of a partial MVA pathway from acetyl-CoA to mevalonate in mitochondria as well as the augmentation of the synthesis of mevalonate in cytosol could significantly promote the growth of yeasts. Accordingly, a combinatorial strategy of cytoplasmic and mitochondrial engineering was proposed to alleviate the metabolic burden caused by the compartmentalized MVA pathway in mitochondria and improve cell growth. The strategy also displayed the superimposed effect of cytoplasmic engineering and mitochondrial engineering on squalene production. Through a two-stage fermentation process, the squalene titer reached 21.1 g/L with a specific squalene titer of 437.1 mg/g dcw, which was the highest at present. This provides new insight into the production of squalene and other terpenes in yeasts based on the advantages of mitochondrial engineering.


Assuntos
Saccharomyces cerevisiae , Esqualeno , Acetilcoenzima A , Engenharia Metabólica , Mitocôndrias/genética , Saccharomyces cerevisiae/genética
15.
Am J Hum Genet ; 108(10): 1852-1865, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34559995

RESUMO

Genome-wide association studies (GWASs) have discovered 20 risk loci in the human genome where germline variants associate with risk of pancreatic ductal adenocarcinoma (PDAC) in populations of European ancestry. Here, we fine-mapped one such locus on chr16q23.1 (rs72802365, p = 2.51 × 10-17, OR = 1.36, 95% CI = 1.31-1.40) and identified colocalization (PP = 0.87) with aberrant exon 5-7 CTRB2 splicing in pancreatic tissues (pGTEx = 1.40 × 10-69, ßGTEx = 1.99; pLTG = 1.02 × 10-30, ßLTG = 1.99). Imputation of a 584 bp structural variant overlapping exon 6 of CTRB2 into the GWAS datasets resulted in a highly significant association with pancreatic cancer risk (p = 2.83 × 10-16, OR = 1.36, 95% CI = 1.31-1.42), indicating that it may underlie this signal. Exon skipping attributable to the deletion (risk) allele introduces a premature stop codon in exon 7 of CTRB2, yielding a truncated chymotrypsinogen B2 protein that lacks chymotrypsin activity, is poorly secreted, and accumulates intracellularly in the endoplasmic reticulum (ER). We propose that intracellular accumulation of a nonfunctional chymotrypsinogen B2 protein leads to ER stress and pancreatic inflammation, which may explain the increased pancreatic cancer risk in carriers of CTRB2 exon 6 deletion alleles.


Assuntos
Quimotripsina/genética , Neoplasias Pancreáticas/patologia , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Deleção de Sequência , Estudos de Casos e Controles , Quimotripsina/antagonistas & inibidores , Quimotripsina/metabolismo , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/metabolismo
16.
Cancer Med ; 10(19): 6835-6844, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34510779

RESUMO

BACKGROUND: To evaluate the cost-effectiveness of prophylactic hysterectomy (PH) in women with Lynch syndrome (LS). METHODS: We developed a microsimulation model incorporating the natural history for the development of hyperplasia with and without atypia into endometrial cancer (EC) based on the MISCAN-framework. We simulated women identified as first-degree relatives (FDR) with LS of colorectal cancer patients after universal testing for LS. We estimated costs and benefits of offering this cohort PH, accounting for reduced quality of life after PH and for having EC. Three minimum ages (30/35/40) and three maximum ages (70/75/80) were compared to no PH. RESULTS: In the absence of PH, the estimated number of EC cases was 300 per 1,000 women with LS. Total associated costs for treatment of EC were $5.9 million. Offering PH to FDRs aged 40-80 years was considered optimal. This strategy reduced the number of endometrial cancer cases to 5.4 (-98%), resulting in 516 quality-adjusted life years (QALY) gained and increasing the costs (treatment of endometrial cancer and PH) to $15.0 million (+154%) per 1,000 women. PH from earlier ages was more costly and resulted in fewer QALYs, although this finding was sensitive to disutility for PH. CONCLUSIONS: Offering PH to 40- to 80-year-old women with LS is expected to add 0.5 QALY per person at acceptable costs. Women may decide to have PH at a younger age, depending on their individual disutility for PH and premature menopause.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/terapia , Análise Custo-Benefício/métodos , Histerectomia/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Histerectomia/métodos , Pessoa de Meia-Idade , Qualidade de Vida , Estados Unidos
17.
Int J Nanomedicine ; 16: 6383-6394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34556986

RESUMO

BACKGROUND: Satisfactory prognosis of breast cancer (BC) is limited by difficulty in early diagnosis and insufficient treatment. The combination of molecular imaging and photothermal therapy (PTT) may provide a solution. METHODS: Fe3O4-Aushell nanoparticles (NPs) were prepared by thermal decomposition, seeded growth and galvanic replacement and were comprehensively characterized. After conjugated to PEG, NPs were used as MRI and PTT agents in vitro and in vivo. RESULTS: Fe3O4-Aushell NPs which had uniform Janus-like morphology were successfully synthesized. The Fe3O4 had a size of 18 ± 2.2 nm, and the Aushell had an outer diameter of 25 ± 3.3 nm and an inner diameter of 20 ± 2.9 nm. The NPs showed superparamagnetism, a saturation magnetization of 36 emu/g, and an optical absorption plateau from 700 to 808 nm. The Fe3O4-Aushell NPs were determined to possess good biocompatibility. After PEG coating, the zeta potential of NPs was changed from -23.75 ± 1.37 mV to -13.93 ± 0.55 mV, and the FTIR showed the characteristic C-O stretching vibration at 1113 cm-1. The NPs' MR imaging implied that the T2 can be shortened by Fe3O4-Aushell NPs in a concentration-dependent manner, and the Fe3O4-Aushell NPs coated with PEG at the molar ratio of 160 (PEG: NPs) showed the highest transverse relaxivity (r 2) of 216 mM-1s-1. After irradiation at 0.65 W/cm2 for 5 min, all cells incubated with the Fe3O4-Aushell-PEG160 NPs (Fe: 30 ppm, Au: 70 ppm) died. After administrated intratumorally, Fe3O4-Aushell-PEG160 notably decreased the signal intensity of tumor in T2WI images. Under the same irradiation, the temperature of tumors injected with Fe3O4-Aushell-PEG160 quickly rose to 54.6°C, and the tumors shrank rapidly and were ablated in 6 days. CONCLUSION: Fe3O4-Aushell-PEG NPs show good r 2 and PTT performance and are promising synergistic theranostic agents of MRI and PTT for BC.


Assuntos
Neoplasias da Mama , Nanoestruturas , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Feminino , Humanos , Imageamento por Ressonância Magnética , Terapia Fototérmica , Medicina de Precisão , Nanomedicina Teranóstica
18.
Toxicol Appl Pharmacol ; 429: 115701, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34453990

RESUMO

Gut dysbiosis and dysregulation of gut-brain communication have been identified in hypertensive patients and animal models. Previous studies have shown that probiotic or prebiotic treatments exert positive effects on the pathophysiology of hypertension. This study aimed to examine the hypothesis that the microbiota-gut-brain axis is involved in the antihypertensive effects of curcumin, a potential prebiotic obtained from Curcuma longa. Male 8- to 10-week-old spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were divided into four groups: WKY rats and SHRs treated with vehicle and SHRs treated with curcumin in dosage of 100 or 300 mg/kg/day for 12 weeks. Our results show that the elevated blood pressure of SHRs was markedly decreased in both curcumin-treated groups. Curcumin treatment also altered the gut microbial composition and improved intestinal pathology and integrity. These factors were associated with reduced neuroinflammation and oxidative stress in the hypothalamus paraventricular nucleus (PVN). Moreover, curcumin treatment increased butyrate levels in the plasma, which may be the result of increased butyrate-producing gut microorganisms. In addition, curcumin treatment also activated G protein-coupled receptor 43 (GPR 43) in the PVN. These results indicate that curcumin reshapes the composition of the gut microbiota and ameliorates the dysregulation of the gut-brain communication to induce antihypertensive effects.


Assuntos
Anti-Hipertensivos/farmacologia , Bactérias/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Curcumina/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Butiratos/sangue , Cardiomegalia/metabolismo , Cardiomegalia/microbiologia , Cardiomegalia/fisiopatologia , Cardiomegalia/prevenção & controle , Modelos Animais de Doenças , Disbiose , Hipertensão/metabolismo , Hipertensão/microbiologia , Hipertensão/fisiopatologia , Mediadores da Inflamação/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptores Acoplados a Proteínas G/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-34325062

RESUMO

BACKGROUND & AIMS: Colorectal cancer (CRC) incidence has decreased overall in the last several decades, but it has increased among younger adults. Prior studies have characterized this phenomenon in the United States (U.S.) using only a small subset of cases. We describe CRC incidence trends using high-quality data from 92% of the U.S. population, with an emphasis on those younger than 50 years. METHODS: We obtained 2001 to 2016 data from the U.S. Cancer Statistics database and analyzed CRC incidence for all age groups, with a focus on individuals diagnosed at ages 20 to 49 years (early-onset CRC). We compared incidence trends stratified by age, as well as by race/ethnicity, sex, region, anatomic site, and stage at diagnosis. RESULTS: We observed 191,659 cases of early-onset and 1,097,765 cases of late-onset CRC during the study period. Overall, CRC incidence increased in every age group from 20 to 54 years. Whites were the only racial group with a consistent increase in incidence across all younger ages, with the steepest rise seen after 2012. Hispanics also experienced smaller increases in incidence in most of the younger age groups. Asians/Pacific Islanders and blacks saw no increase in incidence in any age group in 2016, but blacks continued to have the highest incidence of CRC for every age group. Greater increase in early-onset CRC incidence was observed for males, left-sided tumors, and regional and distant disease. CONCLUSIONS: Early-onset CRC incidence increased overall from 2001 to 2016, but the trends were markedly different for whites, blacks, Asians/Pacific Islanders, and Hispanics. These results may inform future research on the risk factors underlying early-onset CRC.

20.
Talanta ; 233: 122523, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215026

RESUMO

Deep eutectic solvents (DESs) have been considered to be one of the most promising green alternatives of conventional volatile solvents for liquid-liquid separation. However, acidic hydrophobic DESs have been less studied although they are of great importance for the extraction of compounds which are unstable in alkaline conditions. In this study, a novel family of acidic hydrophobic deep eutectic solvents was designed and prepared from methyl trioctyl ammonium chloride and a series of haloacetic acids. For the first time, the obtained DESs were used for extraction and determination of calcium dobesilate, which is an extensively used medicine for treating vascular diseases, but it can be easily oxidized under alkaline and neutral conditions. The factors influencing extraction process including pH, temperature, extract time, inorganic salts and organic coexistence were systematically investigated. It is found that these DESs exhibited outstanding extraction performance towards calcium dobesilate. The extraction equilibrium time was only 3 min in a wide range of pH (1.2-9.2) at room temperature and the extraction capacity was up to 504 mg/g. The detection limit of calcium dobesilate extracting from water samples was 0.05 µg/L and the limit of quantification was 0.5 µg/L. A variety of inorganic salts with the concentration up to 1.0 mol/L and common coexisting organic compounds, such as glucose and starch, with the concentration more than 1000 times higher than the target analyte had no obvious impact on the extraction efficiency. The relative recovery for real samples ranged from 93.2% to 108.6%. Furthermore, the DESs could be recycled and regenerated through back extraction. After fifteen cycles, the extraction efficiency was still up to 99%. Finally, the extraction and back extraction mechanism was discussed in detail.


Assuntos
Dobesilato de Cálcio , Poluentes Químicos da Água , Interações Hidrofóbicas e Hidrofílicas , Solventes , Água , Poluentes Químicos da Água/análise
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