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1.
Aging (Albany NY) ; 122021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33406500

RESUMO

Treatment of thoracic tumors with radiotherapy can lead to severe cardiac injury. We investigated the effects of dexrazoxane, a USFDA-approved cardioprotective drug administered with chemotherapy, on radiation-induced heart disease (RIHD) in a rat model. Male Sprague-Dawley rats were irradiated with a single dose of 20 Gy to the heart and treated with dexrazoxane at the time of irradiation and for 12 subsequent weeks. Dexrazoxane suppressed radiation-induced myocardial apoptosis and significantly reversed changes in serum cardiac troponin I levels and histopathological characteristics six months post-radiation. Treatment with dexrazoxane did not alter the radiosensitivity of thoracic tumors in a tumor formation experiment using male nude Balb/C mice with tumors generated by H292 cells. Dexrazoxane reduced the accumulation of reactive oxygen species in rat cardiac tissues, but not in tumors in nude mice. Transcriptome sequencing showed that IKBKE, MAP3K8, NFKBIA, and TLR5, which are involved in Toll-like receptor signaling, may be associated with the anti-RIHD effects of dexrazoxane. Immunohistochemistry revealed that dexrazoxane significantly decreased NF-κB p65 expression in cardiomyocytes. These findings suggest dexrazoxane may protect against RIHD by suppressing apoptosis and oxidative stress in cardiomyocytes.

2.
Soft Matter ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33416062

RESUMO

Adhesion of biological cells is mediated by the specific binding of receptors and ligands which are typically large proteins spanning through the plasma membranes of the contacting cells. The receptors and ligands can exhibit affinity for nanoscale lipid clusters that form within the plasma membrane. A central question is how these nanoscale lipid clusters physically affect and respond to the receptor-ligand binding during cell adhesion. Within the framework of classical statistical mechanics we find that the receptor-ligand binding reduces the threshold energy for lipid clusters to coalesce into mesoscale domains by up to ∼50%, and that the formation of these domains induces significant cooperativity of the receptor-ligand binding. The interplay between the receptor-ligand binding cooperativity and the lipid domain formation manifests acute sensitivity of the membrane system to changes in control parameters. This sensitivity can be crucial in cell signaling and immune responses.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33432591

RESUMO

This study aims to clarify the function of TRPM8 in colon cancer liver metastasis. Firstly, TRPM8 expression was determined by Western blotting in colon cancer patients with/without liver metastasis. Secondly, colon cancer cells were grouped into Mock, siCON and siTRPM8 groups. Then a series of in-vitro experiments were conducted. Lastly, CT26 cells were used to construct colon cancer liver metastasis models on mice in vivo, followed by comparison of liver metastasis and determination of AKT/GSK-3ß pathway. Consequently, TRPM8 was up-regulated in both colon cancer patients with/without liver metastasis, especially in those with metastasis. Compared to Mock and siCON groups, cells in siTRPM8 group demonstrated significant decreases in clone numbers, cell invasion and migration, and obvious down-regulations of p-AKT/AKT, p-GSK3ß/GSK3ß, Snail and Vimentin, with an up-regulation of E-cadherin. For in-vivo experiments, a sharp decrease was observed in metastatic liver of mice in siTRPM8 group, with significant down-regulations of p-AKT/AKT, p-GSK3ß/GSK3ß, Snail and Vimentin and an up-regulation of E-cadherin, as compared to Mock and siCON groups. Thus, TRPM8 was up-regulated in colon cancer patients with liver metastasis, and silencing TRPM8 may suppress the progression and EMT of colon cancer cells to block its liver metastasis possibly by inhibiting AKT/GSK-3ß pathway. This article is protected by copyright. All rights reserved.

4.
Hum Genet ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33433679

RESUMO

Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of enteric ganglia along variable lengths of the intestine. Genetic defects play a major role in HSCR pathogenesis with nearly 50% of patients having a structural or regulatory deficiency in the major susceptibility gene RET. However, complete molecular defects remain poorly characterized in most patients. Here, we performed detailed genetic, molecular, and populational investigations of rare null mutations and modifiers at the RET locus. We first verified the pathogenicity of three RET splice site mutants (c.1879 + 1G > A, c.2607 + 5G > A and c.2608-3C > G) at the RNA level. We also identified significantly higher risk allele (genotype) frequencies, and their over-transmission, from unaffected parents to affected offspring of three functionally independent enhancer variants (rs2506030, rs7069590 and rs2435357, with odd ratios (OR) of 2.09, 2.71 and 7.59, respectively, P < 0.001). These three common variants are in significant (P < 4.64 × 10-186) linkage disequilibrium in the Han Chinese population with ~ 60% of them carrying at least one copy and > 10% with two copies. We show that RET compound inheritance of rare and common variants prevails in 64% (seven out of 11) of Chinese HSCR families. This study supports the idea that common RET variants can modify the penetrance of rare null RET mutations in HSCR, and the combined high susceptibility allele dosage may constitute the unique raised "risk baseline" among the Chinese population.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33471497

RESUMO

3D monolithic reactor has shown great promise for varied heterogeneous catalysis reactions including water treatment, energy generation and storage, and clean fuel production. As a natural porous material, macroporous wood is regarded as an excellent support for inorganic catalyst due to its abundant polar functional groups and channels. On the other hand, a metal organic framework (MOF) has been widely used as heterogeneous catalyst due to its high specific surface area and large amount of microporosities. Combining macroporous wood and a microporous MOF is expected to produce a high-performance 3D reactor and is demonstrated here for Fischer-Tropsch synthesis. The carbonized MOF/wood reactor retains the original cellular structure with over 180 000 channels/cm2. When being decorated with hexagonal-shaped core-shell Co@C nanoparticles aggregates derived from Co-MOF, the MOF/wood reactor resembles a multi-cylinders reactor for Fischer-Tropsch synthesis. Because of the unique combination of macro- and microporous hierarchical structure, the 3D MOF/wood reactor demonstrates exceptional performance under high gas hourly space velocity (81.2% CO conversion and 48.5% C5+ selectivity at 50 L·h-1·gcat-1 GHSV). This validates that MOF/wood can serve as a multi-cylinders and high-power reactor for catalytic reactions, which is expected to be applicable for environmental and energy applications.

6.
Acta Pharmacol Sin ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33473182

RESUMO

Fingolimod has beneficial effects on multiple diseases, including type 1 diabetes (T1D) and numerous preclinical models of colitis. Intestinal dysbiosis and intestinal immune dysfunction contribute to disease pathogenesis of T1D. Thus, the beneficial effect of fingolimod on T1D may occur via the maintenance of intestinal homeostasis to some extent. Herein, we investigated the role of fingolimod in intestinal dysfunction in non-obese diabetic (NOD) mice and possible mechanisms. NOD mice were treated with fingolimod (1 mg · kg-1 per day, i.g.) from weaning (3-week-old) to 31 weeks of age. We found that fingolimod administration significantly enhanced the gut barrier (evidenced by enhanced expression of tight junction proteins and reduced intestinal permeability), attenuated intestinal microbial dysbiosis (evidenced by the reduction of enteric pathogenic Proteobacteria clusters), as well as intestinal immune dysfunction (evidenced by inhibition of CD4+ cells activation, reduction of T helper type 1 cells and macrophages, and the expansion of regulatory T cells). We further revealed that fingolimod administration suppressed the activation of CD4+ cells and the differentiation of T helper type 1 cells, promoted the expansion of regulatory T cells in the pancreas, which might contribute to the maintenance of pancreatic immune tolerance and the reduction of T1D incidence. The protection might be due to fingolimod inhibiting the toll-like receptor 2/4/nuclear factor-κB/NOD-like receptor protein 3 inflammasome pathway in the colon. Collectively, early-life fingolimod treatment attenuates intestinal microbial dysbiosis and intestinal immune dysfunction in the T1D setting, which might contribute to its anti-diabetic effect.

7.
Resuscitation ; 160: 16-17, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33450334

RESUMO

The World Health Organization declared the 2019 coronavirus (COVID-19) a global pandemic on March 12, 2020. However, inadequate attention seems to have been paid to the heart when managing COVID-19 in terms of detection, monitoring and treatment. We are of the opinion that these severe patients may have had myocardial injury or acute myocarditis. Signs that supports this opinion is the extremely high myocardial injury markers in severe patients, cardiac arrhythmia and suffer progressive heart failure or unexpected cardiac arrest in recent studies. Some suggestions involved of treatment need to be made. The use of an intra-aortic balloon pump (IABP) plus extracorporeal membrane oxygenation (ECMO) should be placed earlier if the pneumonia progresses rapidly, the ejection fraction decreases or there is heart failure. Besides, blood purification treatment including continuous kidney substitution treatment (CRRT) is recommended to clear inflammatory factors and block cytokine storm. In addition, the early usage of glucocorticoid and human immunoglobulin has been found to be preferable when acute myocarditis is accompanied by unstable hemodynamics.

9.
Diabetes Ther ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33481189

RESUMO

INTRODUCTION: The question of whether periodontal therapy is an effective strategy for achieving glycemic control in people with type 2 diabetes mellitus (T2DM) and periodontitis continues to be open to debate. To clarify this issue, we conducted a systematic review and meta-analysis. METHODS: A systematic literature search of randomized controlled trials (RCTs) was carried out by searching four electronic databases and four journals up to April 2020. RCTs that evaluated the effect of periodontal therapy on glycemic control in people with T2DM were included. RESULTS: A total of 23 RCTs were included in this systematic review and meta-analysis. We found that after 3 and 6 months, periodontal therapy could significantly reduce glycosylated hemoglobin (HbA1c) level (3-month: weighted mean difference [WMD] - 0.514, 95% confidence interval [CI] - 0.730, - 0.298, p = 0.000; 6-month: WMD - 0.548, 95% CI - 0.859, - 0.238, p = 0.000). However, huge heterogeneity existed. Further analyses on 11 potential sources of heterogeneity found that baseline HbA1c of the included studies was the most significant factor causing heterogeneity. The benefit of periodontal therapy on glycemic control was much more obvious in studies with a higher baseline HbA1c level than in those with a lower baseline HbA1c level. CONCLUSIONS: Periodontal therapy significantly contributed to glycemic control in T2DM patients, especially in patients with higher baseline HbA1c level.

10.
Nanotechnology ; 32(5): 055501, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33053519

RESUMO

A non-enzymatic sensor nanomaterial which is composed of ultra-thin scaly CoMn2O4 nanosheets grown on the surface of reduced graphene oxide sheets (CoMn2O4 NSs/rGO) has been successfully synthesized by a simple method for glucose sensing. The morphology and elemental composition of CoMn2O4 NSs/rGO are researched by means of x-ray diffraction, field emission scanning electron microscope, and transmission electron microscope. Cyclic voltammetry and amperometry are used to analyse the glucose oxidation characteristics of the material. The test results show that the non-enzymatic glucose sensor based on CoMn2O4 NSs/rGO has excellent glucose sensing performance, exhibiting a wide linear range of 0.1-30 mM with high sensitivity of 6830.5 µA mM-1 cm-2, which is better than other glucose sensors. In addition, the CoMn2O4 NSs/rGO sensor has superior anti-interference and stability. More importantly, the sensor can be applied to the measurement of real sample, which makes it have the potential to become a reliable clinical glucose sensor.

11.
ACS Sens ; 6(1): 245-251, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33373189

RESUMO

Four hydrogen bond-based macrocyclic and tripodal neutral receptors with increasing conformational complementarity with sulfate were used for the first time as ionophores to develop polymeric membrane sulfate-selective electrodes. Optimizing the membrane composition such as ionophores, lipophilic additives, and plasticizers yielded ISEs which showed Nernstian response to sulfate with the best selectivity so far and improved detection limits (a slope of -29.8 mV/dec in the linear range of 1 × 10-6-1 × 10-1 M with a detection limit of 5 × 10-7 M), which led to the success of the determination of sulfate in drinking water samples and neomycine tablets. The anion-ionophore complex constants in the membrane phase were determined and correlated with the selectivity sequence of the ISEs. Studies on the influence of pH of the sample solution demonstrated that the developed ISEs can be operated in a wide pH range of 3-8 with fast response and rapid (in 1 min) and long lifetime. The success of these ionophores represents a feasible strategy for overcoming the "Hofmeister series" by employing a combination of complementarity and hydrogen bonds.

12.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(6): 603-615, 2020 Dec 01.
Artigo em Chinês | MEDLINE | ID: mdl-33377335

RESUMO

Large general hospitals currently play an increasingly important role in the diagnosis and treatment for acute critical patients and difficult diseases because of the development of dual referral system and hierarchical diagnosis, as well as the formation of medical treatment alliance. Patients with oral cancers are often associated with systemic diseases, which increases the complexity of the condition. Thus, meeting the demand through the traditional single medical model is difficult. As such, a multidisciplinary team (MDT) model has been proposed and has achieved a good clinical effect. To standardize the application of this model, we organized an event in which relevant experts discussed and formulated a consensus to provide standardized suggestions on the MDT process and the diagnosis and treatment of common systemic diseases as reference for clinical practice.


Assuntos
Neoplasias Bucais , Equipe de Assistência ao Paciente , Consenso , Humanos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/terapia , Encaminhamento e Consulta
13.
Exp Biol Med (Maywood) ; : 1535370220977823, 2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33342284

RESUMO

Overdose of acetaminophen (APAP) is responsible for the most cases of acute liver failure worldwide. Hepatic mitochondrial damage mediated by neuronal nitric oxide synthase- (nNOS) induced liver protein tyrosine nitration plays a critical role in the pathophysiology of APAP hepatotoxicity. It has been reported that pre-treatment or co-treatment with glycyrrhizin can protect against hepatotoxicity through prevention of hepatocellular apoptosis. However, the majority of APAP-induced acute liver failure cases are people intentionally taking the drug to commit suicide. Any preventive treatment is of little value in practice. In addition, the hepatocellular damage induced by APAP is considered to be oncotic necrosis rather than apoptosis. In the present study, our aim is to investigate if glycyrrhizin can be used therapeutically and the underlying mechanisms of APAP hepatotoxicity protection. Hepatic damage was induced by 300 mg/kg APAP in balb/c mice, followed with administration of 40, 80, or 160 mg/kg glycyrrhizin 90 min later. Mice were euthanized and harvested at 6 h post-APAP. Compared with model controls, glycyrrhizin post-treatment attenuated hepatic mitochondrial and hepatocellular damages, as indicated by decreased serum glutamate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities as well as ameliorated mitochondrial swollen, distortion, and hepatocellular necrosis. Notably, 80 mg/kg glycyrrhizin inhibited hepatic nNOS activity and its mRNA and protein expression levels by 16.9, 14.9, and 28.3%, respectively. These results were consistent with the decreased liver nitric oxide content and liver protein tyrosine nitration indicated by 3-nitrotyrosine staining. Moreover, glycyrrhizin did not affect the APAP metabolic activation, and the survival rate of ALF mice was increased by glycyrrhizin. The present study indicates that post-treatment with glycyrrhizin can dose-dependently attenuate hepatic mitochondrial damage and inhibit the up-regulation of hepatic nNOS induced by APAP. Glycyrrhizin shows promise as drug for the treatment of APAP hepatotoxicity.

14.
Pharm Biol ; 58(1): 1244-1251, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33332205

RESUMO

CONTEXT: Oral submucous fibrosis (OSF) is a chronic and progressive disease. Arecoline, present in betel nuts, has been proposed as a vital aetiological factor. However, the underlying mechanism remains unclear. OBJECTIVES: This research elucidates the expression of tropomyosin-1 (TPM1) and its regulation mechanism in HaCaT cells treated with arecoline. MATERIALS AND METHODS: HaCaT cells were assigned into three groups: (1) Control; (2) Treated with arecoline (0.16 mM) for 48 h (3) Treated with arecoline (0.16 mM) and transfected with small interfering RNA (siRNA) for TPM1 (50 nM) for 48 h. CCK8, cell cycle, and apoptosis phenotypic analyses were performed. PCR and western blot analyses were performed to detect the expression level of TPM1 and examine the related signalling pathway. RESULTS: The IC50 of arecoline was approximately 50 µg/mL (0.21 mM). The arecoline dose (0.16 mM) and time (48 h) markedly increased TPM1 expression at the mRNA and protein levels in HaCaT cells. Arecoline suppressed the cell growth, caused cell cycle arrest at the G1 phase, and induced cell apoptosis in HaCaT cells. siRNA-mediated knockdown of TPM1 attenuated the effect of arecoline on cell proliferation, apoptosis, and cell cycle arrest at the G1 phase. Furthermore, blocking of the transforming growth factor (TGF)-ß receptor using SB431542 significantly suppressed TPM1 expression in the cells treated with arecoline. DISCUSSION AND CONCLUSIONS: Arecoline suppresses HaCaT cell viability by upregulating TPM1 through the TGF-ß/Smad signalling pathway. This research provides a scientific basis for further study of arecoline and TPM1 in OSF and can be generalised to broader pharmacological studies. TPM1 may be a promising molecular target for treating OSF.

15.
Tohoku J Exp Med ; 252(4): 365-372, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33342972

RESUMO

Biliary atresia (BA) is the most frequent hepatic cause of death in early childhood. Early referral and timely Kasai portoenterostomy are essential for the improvement of long-term native liver survival rate of BA patients. Screening with stool color card (SCC) has been implemented in Japan since 1994. Recently current digital edition of SCC consisted of seven digitally created images was introduced to China. Our study aimed to evaluate the repeatability and reliability of same edition of SCC used in Beijing, China and Sapporo, Japan. In Beijing from 2013 to 2014, SCCs were distributed to infants' guardians by trained nurses in maternal facilities during information sessions on neonatal screening programs. SCC was used at three checkpoints for each infant after birth for screening. The SCC data were collected from 27,561 infants (92.5%) in Beijing by 42-day health checkup, mobile phone and social network services. In Sapporo from 2012 to 2015, the SCCs with a postcard and guardian instructions were inserted into Maternal and Child Health Handbook and distributed to all pregnant women. The data were collected from a total of 37,478 (94.3%) infants in Sapporo via the postcard during the 1st month infant health checkup. We thus identified two BA patients in Sapporo and two BA patients in Beijing. High rates of sensitivity and specificity in both cities were observed. The frequency distribution of color images on SCC reported in both cities was similar. This study shows excellent repeatability and reliability of the current digital edition of SCC.

16.
Ying Yong Sheng Tai Xue Bao ; 31(9): 2875-2884, 2020 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-33345488

RESUMO

Forest soil-plant-atmosphere continuum (SPAC) is an important continuous process of water cycle. In this study, we analyzed hydrogen and oxygen stable isotope compositions of the precipitation, atmospheric water vapor, soil water, branch water, and leaf water to explain the characteristics of the continuous process and the associated controlling factors in a subtropical evergreen broadleaved forest. The results showed that the regression equations between hydrogen and oxygen stable isotopes were δDP=7.97δ18OP+12.68(R2=0.97) for precipitation, δDS=4.29δ18OS-18.62(R2=0.81) for soil water, δDB=3.31δ18OB-29.73(R2=0.49) for branch water and δDL=1.49δ18OL-10.09(R2=0.81) for leaf water of Podocarpus nagi, δDV=3.89δ18OV-51.29(R2=0.46) for atmospheric water vapor, respectively. In the process of water transport from precipitation to soil water to plant water, hydrogen and oxygen isotopes gradually enrich, while water vapor isotopes evaporated from soil and evaporated from plants were depleted. With the influence of precipitation and evaporation, soil water isotopes depleted with depth, and more enriched in the dry season than that in the rainy season. During the observation period, isotope content of branch water was slightly higher than that of soil water, indicating that water might be enriched by transpiration during the transportation process in plants. In the dry season, water isotope in branches of arbor plants was poorer than that of shrubs, indicating that arbor plants with deeper root distribution tended to use deep soil water. Because of the differences of leaf traits, transpiration rate and the response degree of environmental factors, the variation characteristics of water isotope composition in leaves of diffe-rent plants varied with the increases of leaf age. Environmental conditions in rainy season were more conducive to leaf transpiration, which made leaf water isotope enriched in rainy season than in dry season. The isotopic compositions in leaf water of Podocarpus nagi had a positive relationship with leaf water content (LWC), and a negative one with relative humidity, reflecting the water regulation function of plants in response to environmental changes.


Assuntos
Solo , Água , Atmosfera , Florestas , Hidrogênio , Oxigênio , Isótopos de Oxigênio , Folhas de Planta
17.
Plant Biotechnol J ; 2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33368973

RESUMO

Kernel number per spike determined by the spike or inflorescence development is one important agricultural trait for wheat yield that is critical for global food security. While a few important genes for wheat spike development were identified, the genetic regulatory mechanism underlying supernumerary spikelets (SSs) is still unclear. Here, we cloned the wheat FRIZZY PANICLE (WFZP) gene from one local wheat cultivar. WFZP is specifically expressed at the sites where the spikelet meristem and floral meristem are initiated, which differs from the expression patterns of its homologs FZP/BD1 in rice and maize, indicative of its functional divergence during species differentiation. Moreover, WFZP directly activates VERNALIZATION1 (VRN1) and wheat HOMEOBOX4 (TaHOX4) to regulate the initiation and development of spikelet. The haplotypes analysis showed that the favourable alleles of WFZP associated with spikelet number per spike (SNS) were preferentially selected during breeding. Our findings provide insights into the molecular and genetic mechanisms underlying wheat spike development and characterize the WFZP as elite resource for wheat molecular breeding with enhanced crop yield.

18.
Pediatr Investig ; 4(3): 178-185, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33150311

RESUMO

Importance: Cancer is the main cause of death by disease in children. Children experience the highest incidence of cancer in the first year of life. However, there is no comprehensive registration system for children with tumors in China. Objective: To summarize the diagnosis and treatment of infant cancer and analyze the status of standardized diagnosis and management among several treatment centers in Beijing, China, thereby providing evidence to guide further clinical research. Methods: From January 1, 2010 to December 31, 2019, patients with newly diagnosed infantile malignant solid tumors were admitted to six large tertiary pediatric solid tumor diagnosis and treatment centers in Beijing. The epidemiology, clinical features, and therapeutic effects of tumors in these patients were analyzed retrospectively. All patients were followed up until March 31, 2020. Results: In total, 938 patients were enrolled in this study. There were 530 boys (56.5%) and 408 girls (43.5%); the median age was 6.0 months (range, 0-12.0 months). The three most common tumors were retinoblastoma in 366 patients (39.0%), neuroblastoma in 266 patients (28.4%), hepatoblastoma in 133 patients (14.2%), and central nervous system tumors in 52 patients (5.5%). The estimated 5-year overall survival rate was 81.3% ± 1.8%, and the 5-year event-free survival rate was 71.8% ± 2.9%. The 5-year overall survival rates of non-rhabdomyosarcoma soft tissue sarcoma, neuroblastoma, and retinoblastoma were 100%, 88% ± 2.2%, and 86.9% ±2.1%, respectively. The 5-year event-free survival rates were 81.1% ± 2.7% for neuroblastoma, 81.6% ± 9.8% for non-rhabdomyosarcoma soft tissue sarcoma, and 72.7% ± 14.1% for extracranial malignant germ cell tumors. Interpretation: The three most common infantile malignant solid tumors were retinoblastoma, neuroblastoma, and hepatoblastoma. Multidisciplinary combined diagnosis and treatment is needed for infantile tumors.

19.
Adv Sci (Weinh) ; 7(22): 2002243, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33240772

RESUMO

It is very desirable to develop advanced sustainable biomedical materials with superior biosafety and bioactivity for clinical applications. Herein, biomass-derived multilayer-structured absorbable microparticles (MQ x T y ) composed of starches and plant polyphenols are readily constructed for the safe and effective treatment of bone defects with intractable bleeding by coating multiple layers of quaternized starch (Q+) and tannic acid onto microporous starch microparticles via facile layer-by-layer assembly. MQ x T y microparticles exhibit efficient degradability, low cytotoxicity, and good blood compatibility. Among various MQ x T y microparticles with distinct Q+/T- double layers, MQ2T2 with outmost polyphenol layer possess the unique properties of platelet adhesion/activation and red blood cell aggregation, resulting in the best hemostatic performance. In a mouse cancellous-bone-defect model, MQ2T2 exhibits the favorable hemostatic effect, low inflammation/immune responses, high biodegradability, and promoted bone repair. A proof-of-concept study of beagles further confirms the good performance of MQ2T2 in controlling intractable bleeding of bone defects. The present work demonstrates that such biomass-based multilayer-structured microparticles are very promising biomedical materials for clinical use.

20.
Front Oncol ; 10: 580513, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33251144

RESUMO

Hepatocellular carcinoma (HCC) is a highly malignant and aggressive cancer with high recurrence rates and mortality. Some studies have illustrated that RNA binding proteins (RBPs) were involved in the carcinogenesis and development of multiple cancers, but the roles in HCC were still unclear. We downloaded the RNA-seq and corresponding clinical information of HCC from The Cancer Genome Atlas (TCGA) database, and 330 differentially expressed RBPs were identified between normal and HCC tissues. Through series of the univariate, the least absolute shrinkage selection operator (LASSO), and the stepwise multivariate Cox regression analyses, six prognosis-related key RBPs (CNOT6, UPF3B, MRPL54, ZC3H13, IFIT5, and PPARGC1A) were screened out from DE RBPs, and a six-RBP gene risk score signature was constructed in training set. Survival analysis indicated that HCC patients with high-risk scores had significantly worse overall survival than low-risk patients, and furthermore, the signature can be used as an independent prognostic indicator. The good accuracy of this prognostic signature was confirmed by the ROC curve analysis and was further validated in the International Cancer Genome Consortium (ICGC) HCC cohort. Besides, a nomogram based on six RBP genes was established and internally validated in the TCGA cohort. Gene set enrichment analysis demonstrated some cancer-related phenotypes were significantly gathered in the high-risk group. Overall, our study first identified an RBP-related six-gene prognostic signature, which could serve as a promising prognostic biomarker and provide some potential therapeutic targets for HCC.

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