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1.
Nat Commun ; 12(1): 1215, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619266

RESUMO

The near-surface part of the crust, also called the skin of the earth, is the arena of human activity of which the stiffness is of great concern to engineers in infrastructure construction. The stiffness reduction of near-surface geomaterials also plays a vital role in geohazards triggering. However, the physical mechanism behind the material softening is still not fully understood. Here, we report a coseismic shear-wave velocity reduction in the near surface by up to a few tens of percent during the strongest shaking from the 11 March 2011 Tohoku-Oki Earthquake and a subsequent two-stage healing process including a rapid recovery within a few minutes and a slow recovery over many years. We also present a theoretical contact model between mineral grains in geomaterials containing multiple metastable contacts at small separations due to the oscillatory hydration interaction, which can explain the emergence of different stages in the healing process.

2.
Curr Microbiol ; 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33611618

RESUMO

Staphylococcus epidermidis is a common cause of nosocomial infections, and readily adheres to medical apparatus to form biofilms consisting of highly resistant persister cells. Owing to the refractory infections caused by S. epidermidis biofilms and persisters in immunosuppressed patients, it is crucial to develop new antimicrobials. In the present study, we analyzed the antimicrobial effects of the thrombopoietin receptor agonist eltrombopag (EP) against S. epidermidis planktonic cells, biofilms, and persister cells. EP was significantly toxic to S. epidermidis with the minimal inhibitory concentration of 8 µg/ml, and effectively inhibited the biofilms and persisters in a strain-dependent manner. In addition, EP was only mildly toxic to mammalian cells after 12 to 24 h treatment. It also partially synergized with vancomycin against S. epidermidis, which enhanced its antimicrobial effects and reduced its toxicity to mammalian cells. Taken together, EP is a potential antibiotic for treating refractory infections caused by S. epidermidis.

3.
Biomed Pharmacother ; 137: 111284, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33561641

RESUMO

BACKGROUND: Gelsemium elegans (G. elegans) is a flowering plant of the Loganiaceae family, which had been used in traditional Chinese herb medicine for many years for the treatment of rheumatoid pain, neuropathic pain, spasticity, skin ulcers, anxiety and cancer. Acute toxicity of the plant severely limits the application and development of G. elegans; however, long-term toxicity of exposure to G. elegans has not been illuminated. PURPOSE: This study is a comprehensive observation of the effects of long-term exposure (21 days at 70 mg/kg) to G. elegans in rats. METHODS AND RESULTS: The histopathological examination showed only a mild glial cell proliferation in the brain, and no lesions were observed in other organs. No abnormal changes in the biochemical parameters were observed that would have significant effects. The identification and analysis of absorbed natural ingredients showed that the active ingredients of the G. elegans could distribute to various tissues, and six compounds were identified in the brain, suggesting that they could cross the blood-brain barrier. Based on the intestinal content metabolomics, the tryptophan (Trp) biosynthesis, bile acid synthesis and bile secretion pathways have attracted our attention. Plasma metabolomic results showed that uric acid (UA) was significantly increased. The results of the brain metabolomic tests showed that the level of pyridoxal (PL) was decreased; considering the expression levels of the related enzymes, it was hypothesized that the level of pyridoxal 5'-phosphate (PLP) was decreased. PLP was important for the regulation of the neuronal γ-aminobutyric acid (GABA)/glutamate (Glu) interconversion and therefore neuronal excitability. The data of the study suggested that toxic reaction caused by G. elegans was due to a disruption of the balance of the neurotransmitter GABA/Glu transformation. CONCLUSIONS: Overall, G. elegans did not cause significant toxic reaction in the rats after long-term exposure. The results were significant for the future clinical applications of G. elegans and suggested that G. elegans could be potentially developed as a drug. The study provided a scientific basis for investigation of the mechanisms of toxicity and detoxification.

4.
Transl Oncol ; 14(4): 101039, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33618068

RESUMO

Neuron-specific enolase (NSE) has been used as a specific biomarker for small cell lung cancer (SCLC) patients. Nevertheless, the biological function and mechanism of NSE in SCLC are still unclear. In this study, we clarified the role of NSE in the progression of SCLC and found that NSE expression was positively correlated with distant metastasis. Functional analysis showed that overexpression of NSE promoted migration and invasion of SCLC cells. Mechanism analysis showed that NSE overexpression induced epithelial-mesenchymal transition (EMT) of SCLC cells. Moreover, overexpression of NSE increased the protein expression of ß-catenin and its downstream target genes, and silencing ß-catenin eliminated NSE-mediated cell migration, invasion and EMT process. Furthermore, NSE interacted with ß-catenin and inhibited the degradation of ß-catenin. Besides, the animal experiments also indicated that NSE could promote the EMT process and distant metastasis of SCLC cells in vivo. In summary, our results revealed that NSE could promote the EMT process of SCLC cells by activating the Wnt/ß-catenin signaling pathway, thereby promoting cell migration, invasion and distant metastasis, which might serve as a potential target for the therapy of SCLC patients.

5.
Pharmacol Res ; : 105497, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33609697

RESUMO

Osteoarthritis (OA) is a major cause of disability in the elderly population and represents a significant public health problem and socioeconomic burden worldwide. However, no disease-modifying therapeutics are currently available for OA due to an insufficient understanding of the pathogenesis of this disability. As a unique cell type in cartilage, chondrocytes are essential for cartilage homeostasis and play a critical role in OA pathogenesis. Mitochondria are important metabolic centers in chondrocytes and contribute to cell survival, and mitochondrial quality control (MQC) is an emerging mechanism for maintaining cell homeostasis. An increasing number of recent studies have demonstrated that dysregulation of the key processes of chondrocyte MQC, which involve mitochondrial redox, biogenesis, dynamics, and mitophagy, is associated with OA pathogenesis and can be regulated by the chondroprotective molecules 5' adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 3 (SIRT3). Moreover, AMPK and SIRT3 regulate each other, and their expression and activity are always consistent in chondrocytes, which suggest the existence of an AMPK-SIRT3 positive feedback loop (PFL). Although the precise mechanisms are not fully elucidated and need further validation, the current literature indicates that this AMPK-SIRT3 PFL regulates OA development and progression, at least partially by mediating chondrocyte MQC. Therefore, understanding the mechanisms of AMPK-SIRT3 PFL-mediated chondrocyte MQC in OA pathogenesis might yield new ideas and potential targets for subsequent research on the OA pathomechanism and therapeutics.

6.
Org Lett ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33606549

RESUMO

Inspired by the diversity created by nature, organic chemists have been using a divergent strategy to improve the synthetic efficiency of diverse molecules. Transition-metal-catalyzed C-H functionalization has become one of the most straightforward, powerful, and atom-economical methods to construct complex scaffolds. However, C-H activation initiated divergent transformation to prepare diverse molecules is still limited. To address this challenge, we herein developed Rh(III)-catalyzed C-H olefination/annulation reaction cascades to divergently construct diverse polyheterocycles by tuning manipulations of directing groups (DGs). Up to 9 distinct scaffolds were creatively synthesized under simple conditions with good functional group tolerance, chemo-, and regioselectivity. Such a versatile strategy and its extension may encourage researchers to discover more promising manipulations of DGs for transition-metal-catalyzed C-H bond activation, making diverse available targets and materials that would have been previously out of range.

7.
Int J Immunogenet ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33527680

RESUMO

Genetic polymorphisms of human leucocyte antigen (HLA)-DRB1, -DQA1 and -DQB1 among four main ethnic groups including Han (n = 70), Uyghur (n = 71), Kazakh (n = 52) and Hui (n = 40) subjects from Xinjiang Uyghur Autonomous Region were investigated using a polymerase chain reaction-sequence-based typing (PCR-SBT). In total, 32 HLA-DRB1 alleles, eight HLA-DQA1 alleles and 14 HLA-DQB1 alleles were identified. The most predominant HLA-DRB1, -DQA1 and -DQB1 alleles were DRB1*15:01 (12.50%), DQA1*01:02 (21.43%) and DQB1*03:01 (19.29%) in Han; DRB1*07:01 (18.48%), DQA1*05:01/03/05 (24.65%) and DQB1*02:01/02 (31.69%) in Uyghur; and DRB1*13:01 (13.64%), DQA1*05:01/03/05 (28.85%) and DQB1*02:01/02 (27.88%) in Kazakh, respectively. In Hui, DRB1*07:01, DRB1*11:01 and DRB1*14:01 were the most dominant alleles with the same frequency of 11.8%, while the predominant DQA1 and DQB1 alleles were DQA1*03:01/02/03 (23.75%) and DQB1*02:01/02 (16.25%), respectively. In addition, the most common two-locus haplotypes were DQA1*05:01/03/5-DQB1*03:01 (10.0%) in Han; DQA1*02:01-DQB1*02:01/02 (18.31%) in Uyghur; DQA1*05:01/03/05-DQB1*02:01/02 (15.38%) in Kazakh; and DQA1*03:01/02/03-DQB1*03:03 (11.25%) in Hui. The phylogenetic dendrograms constructed based on the allele frequencies of HLA-DRB1, -DQA1 and -DQB1 in 13 populations (e.g. Asian, Central Asian and European) revealed that the Han and Hui populations were clustered together and closest to Han population from China, while the Kazakh and Uyghur populations were closest to each other and two ethnic groups were clustered together with Central Asian and European populations.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33547949

RESUMO

OBJECTIVE: To investigate the efficacy and mechanism of ultrasound-targeted microbubble destruction (UTMD) combined with radiotherapy (XRT) on glioblastoma. METHODS: The enhanced radiosensitization by UTMD was assessed through colony formation and cell apoptosis in Human glioblastoma cells (U87MG). Subcutaneous transplantation tumors in 24 nude mice implanted with U87MG cells were randomly assigned to 4 different treatment groups (Control, UTMD, XRT, and UTMD + XRT) based on tumor sizes (100-300 mm3). Tumor growth was observed for 10 days after treatment, and then histopathology stains (HE, CD34, and γH2AX) were applied to the tumor samples. A TUNEL staining experiment was applied to detect the apoptosis rate of mice tumor samples. Meanwhile, tissue proteins were extracted from animal specimens, and the expressions of dsDNA break repair-related proteins from animal specimens were examined by the western blot. RESULTS: When the radiotherapy dose was 4 Gy, the colony formation rate of U87MG cells in the UTMD + XRT group was 32 ± 8%, lower than the XRT group (54 ± 14%, p < 0.01). The early apoptotic rate of the UTMD + XRT group was 21.1 ± 3% at 48 h, higher than that of the XRT group (15.2 ± 4%). The tumor growth curve indicated that the tumor growth was inhibited in the UTMD + XRT group compared with other groups during 10 days of observation. In TUNEL experiment, the apoptotic cells of the UTMD + XRT group were higher than that of the XRT group (p < 0.05). The UTMD + XRT group had the lowest MVD value, but was not significantly different from other groups (p > 0.05). In addition, γH2AX increased due to the addition of UTMD to radiotherapy compared to XRT in immunohistochemistry (p < 0.05). CONCLUSIONS: Our study clearly demonstrated the enhanced destructive effect of UTMD combined with 4 Gy radiotherapy on glioblastoma. This could be partly achieved by the increased ability of DNA damage of tumor cells.

9.
Xenobiotica ; : 1-24, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538636

RESUMO

The objective of this study was to investigate the single- and multiple-dose pharmacokinetics of chelerythrine (CHE) and its metabolite, dihydrochelerythrine (DHCHE), after oral and IM administrations in pigs. Six crossbreed (Landrace × Large White) female pigs (7 to 8 weeks old; 24.1 ± 2.6 kg bw) administered oral and IM CHE at a dose of 0.1 mg/kg orally and intramuscularly in a cross-over design. Multiple oral administration was performed at 0.1 mg/kg a time, three times a day at 8-h intervals for three consecutive days. Blood samples were collected from the anterior vena cava and placed into heparinized centrifuge tubes before dosing (time 0 h) and at different times after oral oral and IM administrations. Pretreatment plasma was analyzed by high-performance liquid chromatography tandem mass spectrometry. After IM administration, CHE and DHCHE rapidly reached peak concentrations (C max , 69.79 ± 15.41 and 3.47 ± 1.23 ng/ml) at 0.42 ± 0.13 and 0.33 ± 0.13 h, respectively. After single oral administration, CHE and DHCHE rapidly increased to reach C max of 5.04 ± 1.00 and 1.21 ± 0.35 ng/ml at 1.83 ± 0.26 and 1.67 ± 0.26 h, respectively. The half-life (T 1/2 ) was 2.03 ± 0.26 and 2.56 ± 1.00 h for CHE and DHCHE, respectively. After multiple oral administration, the average steady-state concentrations (C ss ) of CHE and DHCHE were 2.51 ± 0.40 and 0.6 ± 0.06 ng/ml, respectively. CHE is metabolized rapidly after a single oral administration, multiple daily doses and long-term use of CHE are recommended.

10.
Medicine (Baltimore) ; 100(4): e23866, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530180

RESUMO

INTRODUCTION: Metastasis of a papillary thyroid microcarcinoma (PTMC) in the lateral neck is characterized primarily by solid lymphadenopathy, although some cases may rarely present with a cervical cystic mass. We report a case of lateral cervical lymph node metastases of PTMC that appeared as a cystic lymphangioma of the lateral neck. PATIENT CONCERNS: A 55-year-old man with a painless egg-sized mass in the right side of the neck that had been present for 1 month underwent physical examination, ultrasonography, computed tomography (CT), fine needle aspiration biopsy (FNAB), and intraoperative fast-frozen pathological examination, which indicated that the cystic masses in the neck were benign. However, the final pathology report identified the lateral neck masses as lymph node metastases of thyroid carcinoma. DIAGNOSIS: The patient was diagnosed with PTMC of the right lobe of the thyroid gland with lateral neck metastases. INTERVENTIONS: The patient underwent right cervical neck dissection together with a right thyroidectomy, followed by levothyroxine therapy and routine follow-up. OUTCOMES: No postoperative complications were reported, and the thyroid-stimulating hormone inhibition target was <0.1 mmol/L; there was no detectable tumor recurrence on routine clinical follow-up for up to 16 months. CONCLUSIONS: This case report emphasizes the need to consider cervical lymph node metastases of thyroid carcinoma in the differential diagnosis for patients with large, multiple, simple cystic neck masses.


Assuntos
Carcinoma Papilar/patologia , Neoplasias de Cabeça e Pescoço/secundário , Linfangioma/patologia , Metástase Linfática , Neoplasias da Glândula Tireoide/patologia , Carcinoma Papilar/tratamento farmacológico , Carcinoma Papilar/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Terapia de Reposição Hormonal , Humanos , Linfangioma/cirurgia , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Tiroxina/uso terapêutico
11.
Qual Life Res ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595826

RESUMO

PURPOSE: To compare the anxiety, depression and explore their relationship to quality of life (QoL) among adult acute leukemia (AL) patients and family caregivers (FCs) in China. METHODS: A multicenter cross-sectional study was conducted from April 2017 to January 2018. The sample comprised 207 dyads of adult AL patients and FCs. The participants were required to complete socio-demographic information and the Hospital Anxiety and Depression Scale (HADS). The Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu, only for patients) and MOS 36-item Short-Form Health Survey (SF-36, only for FCs) were used to measure QoL. RESULTS: The mean scores of anxiety and depression for AL patients were 7.89 ± 3.85 and 7.18 ± 4.23, respectively. For FCs, the mean scores of anxiety and depression were 9.96 ± 3.73 and 8.64 ± 3.74. In this study, adult AL Patients' sex, patients' depression score, whether patients achieving a CR or not, education, FCs' depression score, patients' social/family well-being and emotional well-being were significantly associated with patients' anxiety or depression (p < 0.05). For FCs, depression was significantly related to the physical component summary (ß = 0.127, p = 0.008). There were significant differences in anxiety (t = - 5.92, p < 0.001) and depression (t = - 4.19, p < 0.001) between patients and FCs. CONCLUSIONS: AL patients' FCs showed higher score of anxiety and depression than that of patients. The psychological health may have a potential relationship between AL patients and their FCs. Healthcare professionals can conduct family-center interventions to improve mental health and QoL of AL patients and FCs.

12.
Int Heart J ; 62(1): 23-32, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33518662

RESUMO

The aim of this study was to explore potential predictive biomarkers and therapeutic targets of post-infarct heart failure (HF) using bioinformatics analyses.CEL raw data of GSE59867 and GSE62646 were downloaded from the GEO database. Differentially expressed genes (DEGs) between patients with ST-segment elevation myocardial infarction (STEMI) and those with stable coronary artery disease (CAD) at admission and DEGs between admission and 6 months after myocardial infarction (MI) in patients with STEMI were analyzed. A gene ontology (GO) analysis and a gene set enrichment analysis (GSEA) were performed, and a protein-protein interaction network was constructed. Critical genes were further analyzed.In total, 147 DEGs were screened between STEMI and CAD at admission, and 62 DEGs were identified in patients with STEMI between admission and 6 months after MI. The results of GO and GSEA indicate that neutrophils, neutrophil-related immunity responses, and monocytes/macrophages play important roles in MI pathogenesis. SLED1 expression was higher in patients with HF than in those without HF at admission and 1 month after MI. GSEA indicates that mTORC1 activation, E2F targets, G2M checkpoint, and MYC targets v1 inhibition may play key roles in the development of post-infarct HF. Furthermore, SLED1 may be involved in the development of post-infarct HF by activating mTORC1 and inhibiting E2F targets, G2M checkpoint, and MYC targets v1.SLED1 may be a novel biomarker of post-infarct HF and may serve as a potential therapeutic target in this disease.


Assuntos
Proteína Básica Maior de Eosinófilos/metabolismo , Insuficiência Cardíaca/metabolismo , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Biomarcadores/metabolismo , Proteína Básica Maior de Eosinófilos/genética , Perfilação da Expressão Gênica , Insuficiência Cardíaca/genética , Humanos , Mapas de Interação de Proteínas , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo
13.
Am J Hum Genet ; 108(2): 337-345, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33434492

RESUMO

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/genética , Anormalidades Congênitas/genética , Ductos Paramesonéfricos/anormalidades , Ductos Paramesonéfricos/crescimento & desenvolvimento , Mutação , Ductos Mesonéfricos/crescimento & desenvolvimento , Adulto , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 7/genética , Códon sem Sentido , Feminino , Estudos de Associação Genética , Pleiotropia Genética , Proteínas Homeobox A10/genética , Proteínas de Homeodomínio/genética , Humanos , Fator de Transcrição PAX8/genética , Herança Paterna , Penetrância , Proteínas com Domínio T/genética , Fatores de Transcrição/genética , Proteínas Wnt/genética , Ductos Mesonéfricos/anormalidades
14.
Artigo em Inglês | MEDLINE | ID: mdl-33420833

RESUMO

PURPOSE: Esophagojejunostomy is a challenging step in laparoscopic gastrectomy. Although the overlap method is a safe and feasible approach for esophagojejunostomy, it has several technical limitations. We developed novel modifications for the overlap method to overcome these disadvantages. METHODS: Forty-eight consecutive gastric cancer patients underwent totally laparoscopic total gastrectomy or laparoscopic proximal gastrectomy with double-tract reconstruction at our institution from January 2019 to April 2020 using the overlap method with the following modifications. The esophagus was initially rotated by 90° counterclockwise, followed by transection of two-thirds of the esophageal diameter. The unstapled esophagus was then transected with a harmonic ultrasonic scalpel to enable esophagostomy at the posterior side of the esophagus. A side-to-side esophagojejunostomy was then formed at the posterior side of the esophagus using an endoscopic linear stapler through the right lower trocar. The common entry hole was closed via hand sewing method using V-Loc suture. This procedure was termed "esophagus two-step-cut overlap method." RESULTS: Only one patient suffered from esophagojejunal anastomotic leakage but subsequently recovered after conservative treatment. Patients did not experience anastomotic bleeding or stricture. CONCLUSION: Our modified overlap method provides satisfactory surgical outcomes and overcomes several technical limitations, such as entering the false lumen of the esophagus, unnecessary pollution caused by nasogastric tube, and unintended left crus stapling during anastomosis.

15.
Ecotoxicol Environ Saf ; 211: 111940, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33476849

RESUMO

Desorption is one of the main factors causing groundwater and soil pollution. Therefore, the study of clay desorption characteristics is important for the prediction of groundwater and soil pollution. In previous studies, batch tests and column tests were used to study the desorption characteristics of pollutants on clay. However, the desorption parameters obtained via the two test methods were often quite different. To investigate differences in the desorption characteristics of different pollutants on clay particles and in compacted clay, batch and column desorption tests were conducted using cadmium chloride, fulvic acid, and sodium phosphate as the adsorbates and bentonite as the adsorbent. It was found that the unit particle surface area desorption distribution coefficients of pollutants on bentonite particles were approximately equal to the unit pore surface area distribution coefficients of pollutants in compacted bentonite. This indicates that the desorbed amount per unit of surface area is basically consistent, regardless of whether they are sorbed on particles or in compacted bentonite. A simple formula for determining the desorption retardation factor of pollutants in compacted bentonite is presented. The results of this study provide a reference for the prediction and evaluation of groundwater and soil pollution.


Assuntos
Bentonita/química , Poluentes Ambientais/química , Adsorção , Argila , Água Subterrânea , Modelos Químicos , Fosfatos
16.
Ren Fail ; 43(1): 141-148, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33427559

RESUMO

BACKGROUND: Long-term dietary phosphorus excess influences disturbances in mineral metabolism, but it is unclear how rapidly the mineral metabolism responds to short-term dietary change in dialysis populations. METHODS: This was a post hoc analysis of a randomized crossover trial that evaluated the short-term effects of low-phosphorus diets on mineral parameters in hemodialysis patients. Within a 9-day period, we obtained a total of 4 repeated measurements for each participant regarding dietary intake parameters, including calorie, phosphorus, and calcium intake, and markers of mineral metabolism, including phosphate, calcium, intact parathyroid hormone (iPTH), intact fibroblast growth factor 23 (iFGF23), and C-terminal fibroblast growth factor 23 (cFGF23). The correlations between dietary phosphorus intake and serum mineral parameters were assessed by using mixed-effects models. RESULTS: Thirty-four patients were analyzed. In the fully adjusted model, we found that an increase in dietary phosphorus intake of 100 mg was associated with an increase in serum phosphate of 0.3 mg/dL (95% confidence intervals [CI], 0.2-0.4, p < .001), a decrease in serum calcium of 0.06 mg/dL (95% CI, -0.11 to -0.01, p = .01), an increase in iPTH of 5.4% (95% CI, 1.4-9.3, p = .01), and an increase in iFGF23 of 5.0% (95% CI, 2.0-8.0, p = .001). Dietary phosphorus intake was not related to cFGF23. CONCLUSIONS: Increased dietary phosphorus intake acutely increases serum phosphate, iPTH, and iFGF23 levels and decreases serum calcium levels, highlighting the important role of daily fluctuations of dietary habits in disturbed mineral homeostasis in hemodialysis patients.

18.
Chemistry ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33443293

RESUMO

The [2+1] cycloaddition reaction of a metal carbene with an alkene can produce important cyclopropane products for synthesis intermediates, material and pharmaceutical applications. However, this reaction is often accompanied by side reactions such as coupling and self-coupling, so that the yield of cyclopropanation product of non-silver transition metal carbene and hindered alkene is generally lower than 50%. To solve this problem, addition of a low concentration of diazo compound (decomposition of sulfonyl hydrazones) to alkene catalyzed by either CuOAc or PdCl 2 was studied but side reactions still could not be avoided. Interestingly, however, the yield of cyclopropanation for such hindered alkenes was as high as 99% with AgOTf as catalyst. To explain this unexpected phenomenon, reaction pathways have been computed for four different catalysts using density functional theory (DFT). By combining the results of these calculations with the experimental ones, we concluded that the efficiency of the silver catalyst is due to the barrierless concerted cycloaddition step, and the kinetic inhibition of side reaction by a high concentration of alkene.

19.
Biomater Sci ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33464244

RESUMO

The satisfactory efficient tumor treatment and complete tumor ablation using a mono-therapeutic approach are limited owing to the tumor complexity, diversity, heterogeneity and the multiple pathways involved in tumor pathogenesis. Herein, novel, intelligent and tumor microenvironment (TME)-responsive biotin/R8 peptide co-modified nanocarriers (BRNC) loading paclitaxel (PTX)/glucose oxidase (GOx) were constructed. GOx could catalyze the oxidation of intracellular glucose to gluconic acid and poisonous H2O2 to cause the deterioration of the tumor survival microenvironment, simultaneously achieving starvation and oxidation therapy. The acidic amplification during the GOx-mediated oxidation progress could in turn accelerate the cleavage of the acid-degradable hydrazone bond, promoting the deep penetration of nanocarriers into tumors. Even better, the aforementioned two aspects further increased the tumors' sensitivity to chemotherapeutic agents. Both in vitro and in vivo investigations indicated that the co-administration of GOx-BRNC and PTX-BRNC can remarkably improve the therapeutic efficacy and reduce side effects through the high-specific tumor targeting multimodal synergistic starvation/oxidation/chemotherapy, which would be a promising strategy for the next generation cancer therapy.

20.
Chin J Integr Med ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33433847

RESUMO

OBJECTIVE: To explore the effectiveness of Danhong Injection () on improving microcirculatory injury after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). METHODS: A randomized controlled trial was conducted and 90 patients were enrolled. A random sequence was generated using statistical analysis software. Patients with microcirculatory injuries after PCI were randomly divided into 3 groups for treatment (30 subjects in each group): Danhong Injection group: after PCI, Danghong Injections were given with intravenous administration with 40 mL twice a day for a week; statins intensive group: after PCI, atorvastatin calcium tablets were given oral medication with 80 mg once, and then atorvastatin 40 mg daily for 1 week; the control group: after PCI, atorvastatin calcium tablets were given oral medication with 10-20 mg daily for 1 week. The index of microcirculation resistance (IMR) was used to assess microcirculatory injury during PCI. The IMR of the target vessel was reexamined after 1 week of drug treatment. RESULTS: After one week's drug treatment, IMR was significantly decreased in both statins intensive group and Danhong Injection group compared with the control group (P<0.01), but no difference was found between statins intensive group and Danhong injection group (14.03 ± 2.54 vs. 16.03 ± 5.72 U, P=0.080). CONCLUSIONS: The efficacy of Danhong Injection is non-inferior to statin. Early use of Danhong Injection after PCI can effectively improve coronary microcirculation injury after PCI.

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