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1.
Bioinformatics ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636837

RESUMO

MOTIVATION: Immune cells are important components of the immune system and are crucial for disease initiation, progression, prognosis, and survival. Although several computational methods have been designed for predicting the abundance of immune cells, very few tools are applicable to mouse. Given that mouse is the most widely used animal model in biomedical research, there is an urgent need to develop a precise algorithm for predicting mouse immune cells. RESULTS: We developed a tool named ImmuCellAI-mouse (Immune Cell Abundance Identifier for mouse), for estimating the abundance of 36 immune cell (sub)types from gene expression data in a hierarchical strategy of three layers. Reference expression profile and robust marker gene sets of immune cell types were curated. The abundance of cells in three layers was predicted separately by calculating the ssGSEA enrichment score of the expression deviation profile per cell type. Benchmark results showed high accuracy of ImmuCellAI-mouse in predicting most immune cell types, with correlation coefficients between predicted value and real cell proportion of most cell types being larger than 0.8. We applied ImmuCellAI-mouse to a mouse breast tumor dataset and revealed the dynamic change of immune cell infiltration during treatment, which is consistent with the findings of the original study but with more details. We also constructed an online server for ImmuCellAI-mouse, on which users can upload expression matrices for analysis. ImmuCellAI-mouse will be a useful tool for studying the immune microenvironment, cancer immunology, and immunotherapy in mouse models, providing an indispensable supplement for human disease studies. AVAILABILITY: Software is available at http://bioinfo.life.hust.edu.cn/ImmuCellAI-mouse/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

2.
J Neurooncol ; 154(3): 275-283, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34476666

RESUMO

PURPOSE: Gliomas are the most common and aggressive malignant brain tumors and are associated with high mortality and incidence in humans. Despite rigorous multi-modal therapy, including surgery, chemotherapy and radiotherapy, patients with malignant glioma survive an average of 12-15 months following primary diagnosis. Therefore, new molecular biomarkers are urgently needed for diagnosis and targeted therapy. Here, we find that suppression of CKAP4 might inhibit glioma growth through regulation of Hippo signaling. METHODS: We examined the expression levels of CKAP4 through analysis of RNA sequencing data from GEPIA and CGGA databases. Then, Lentivirus was used to construct stable cell lines with knockout or overexpression of CKAP4. Next, the function of CKAP4 on glioma was investigated in vitro and in an orthotopic brain tumor model in mice. Lastly, luciferase reporter assay, immunofluorescence and immunoblotting were performed to explore the potential mechanism of how CKAP4 affects gliomas. RESULTS: CKAP4 is highly upregulated in glioma and high CKAP4 expressing tumors were associated with poor patient survival. And CKAP4 promotes malignant progression of gliomas via inhibiting Hippo signaling. CONCLUSION: CKAP4 has potential as a promising biomarker and can predict the prognosis of patients with gliomas. And targeting CKAP4 expression may be an effective therapeutic strategy for the treatment of human gliomas.

3.
Cell Signal ; 88: 110148, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34530056

RESUMO

Spi-B transcription factor (SPIB) is a member of the E-twenty-six (ETS) transcription factor family. Previous studies have shown that the expression of SPIB is downregulated in human colorectal cancer tissues. The purpose of our study was to explore the biological function and related mechanism of SPIB in colorectal cancer cells. Our study found that SPIB could inhibit the proliferation, migration and invasion of CRC cells; inhibit angiogenesis; and induce CRC cells cycle arrest in G2/M phase and promote the apoptosis of CRC cells. We also found that compared with the control group, the 50% inhibitory concentration (IC50) values of oxaliplatin and 5-FU in the SPIB overexpression group were significantly reduced. Western blot results showed that the overexpression of SPIB upregulated cleaved-PARP(c-PARP), nuclear factor kB p65 (NFkB p65), phospho-NFkB p65 (p-NFkB P65), JNK1, and C-Jun protein expression levels compared with the control group. The silence of SPIB downregulated c-PARP, NFκB p65, p-NFκB p65, JNK1, and C-Jun protein expression levels. A dual-luciferase reporter assay showed that SPIB could activate the promoter of MAP4K1 and enhance the expression of MAP4K1. After silencing MAP4K1, the protein expression levels of c-PARP, NFkB P65, p-NFkB P65, JNK1, and C-Jun were downregulated. In summary, we found that SPIB is a tumor suppressor in colorectal cancer cells and that SPIB sensitizes colorectal cancer cells to oxaliplatin and 5-FU, SPIB exerts its anti-colorectal cancer effect by activating the NFkB and JNK signaling pathways through MAP4K1. The above findings may provide a reference for new molecular markers and therapeutic targets for CRC.

4.
Nat Commun ; 12(1): 5311, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493724

RESUMO

Although some effective therapies have been available for cancer, it still poses a great threat to human health and life due to its drug resistance and low response in patients. Here, we develop a ferroptosis-based therapy by combining iron nanoparticles and cancer-specific gene interference. The expression of two iron metabolic genes (FPN and LCN2) was selectively knocked down in cancer cells by Cas13a or microRNA controlled by a NF-κB-specific promoter. Cells were simultaneously treated by iron nanoparticles. As a result, a significant ferroptosis was induced in a wide variety of cancer cells. However, the same treatment had little effect on normal cells. By transferring genes with adeno-associated virus and iron nanoparticles, the significant tumor growth inhibition and durable cure were obtained in mice with the therapy. In this work, we thus show a cancer therapy based on gene interference-enhanced ferroptosis.


Assuntos
Proteínas de Transporte de Cátions/antagonistas & inibidores , Ferroptose/genética , Ferro/metabolismo , Lipocalina-2/antagonistas & inibidores , Neoplasias/terapia , Interferência de RNA , Espécies Reativas de Oxigênio/agonistas , Animais , Proteínas Associadas a CRISPR/genética , Proteínas Associadas a CRISPR/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Linhagem Celular Tumoral , Dependovirus/genética , Dependovirus/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Lipocalina-2/genética , Lipocalina-2/metabolismo , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Nanopartículas/administração & dosagem , Nanopartículas/química , Neoplasias/genética , Neoplasias/mortalidade , Neoplasias/patologia , Regiões Promotoras Genéticas , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Baço/metabolismo , Baço/patologia , Análise de Sobrevida , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Water Res ; 204: 117601, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481286

RESUMO

The conversion of organic wastes/wastewater into medium chain fatty acids (MCFAs) such as caproate has attracted much attention, while the effects of toxic compounds on the process have rarely been studied. The present study investigated the effects of phenol (0-1.5 g/L), which is a toxicant and present in various organic wastes, on the caproate production in the chain elongation (CE) process with ethanol as electron donor via two-stage batch anaerobic fermentation of glucose. The results showed phenol ≤ 1 g/L did not affect short chain fatty acids (SCFAs) production, while 1 g/L phenol increased caproate production by 59.9% in the following CE process. The higher selectivity of caproate and higher consumption of ethanol contributed to the higher caproate production at 1 g/L phenol. It was also shown 1 g/L phenol had more positive effect on CE of butyrate than acetate. 1.5 g/L phenol inhibited both SCFAs production and CE processes. 16S rRNA genes analysis showed phenol had slight effect on the microbial communities for SCFAs production, while it obviously changed the dominant microbes in CE process. For CE process, metagenomic analysis was further conducted and phenol mainly affected fatty acid biosynthesis (FAB) pathway, but not reverse ß-oxidization (RBO) pathway. 1 g/L phenol increased the abundances of genes in FAB pathway, which could be related with the higher caproate production. Genome reconstruction identified the dominant microbial species in CE process, which were changed with different concentrations of phenol. Most of the dominant species were new microbial species potentially involved in CE. The syntrophic cooperation between Petrimonas mucosa FDU058 and Methanofollis sp. FDU007 might play important role in increased caproate production at 1 g/L phenol, and their adaption to phenol could be due to the presence of genes relating with active efflux system and refolding of proteins.


Assuntos
Etanol , Fenol , Anaerobiose , Bacteroidetes , Reatores Biológicos , Caproatos , Elétrons , Fermentação , Fenóis , RNA Ribossômico 16S/genética
6.
Lab Chip ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34549766

RESUMO

We 3D print micro-robotic swimmers with the size of animal cells using a Nanoscribe. The micro-swimmers are powered by the microstreaming flows induced by the oscillating air bubbles entrapped within the micro-robotic swimmers. Previously, micro-swimmers propelled by acoustic streaming require the use of a magnetic field or an additional ultrasound transducer to steer their direction. Here, we show a two-bubble based micro-swimmer that can be propelled and steered entirely using one ultrasound transducer. The swimmer displays boundary following traits similar to those biological swimmers that are known to be important for performing robust biological functions. The micro-robotic swimmer has the potential to advance the current technology in targeted drug delivery and remote microsurgery.

7.
J Interferon Cytokine Res ; 41(9): 347-354, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34543128

RESUMO

Sinapic acid (SA) was reported to protect against inflammation in various types of diseases. However, the role of SA in rheumatoid arthritis remains unclear. This study was designed to investigate the role of SA on rheumatoid arthritis. Rheumatoid arthritis mouse model was established by collagen immunization [collagen-induced arthritis (CIA)]. Histological analysis of articular cartilage tissue was carried out by hematoxylin and eosin (H&E) staining. Serum concentrations of tumor necrosis factor alpha and interleukin 6 were determined through enzyme-linked immunosorbent assay (ELISA). Oxidative damage indexes such as superoxide dismutase activity, malondialdehyde detection, glutathione detection, and catalase were determined by biochemical analysis. The protein levels of related genes were determined using Western blot. In CIA model, SA treatment attenuated paw swelling and clinical score of arthritis, attenuated articular cartilage tissues edema and infiltration of inflammatory cells, suppressed inflammatory cytokines release, and attenuated oxidative damage indexes. Mechanically, SA suppressed immune responses through inhibiting the IκB kinase (IKKs). SA attenuates rheumatoid arthritis through reducing inflammation and oxidative stress by downregulating IKKs.

8.
Molecules ; 26(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34577134

RESUMO

Solid waste silica fume was used to replace fly ash by different ratios to study the early-age hydration reaction and strength formation mechanism of concrete. The change pattern of moisture content in different phases and micro morphological characteristics of concrete at early age were analyzed by low field nuclear magnetic resonance (LF-NMR) and scanning electron microscope (SEM). The results showed that the compressive strength of concrete was enhanced optimally when the replacement ratio of solid waste silica fume was 50%. The results of LF-NMR analysis showed that the water content of modified concrete increased with the increase of solid waste silica fume content. The compressive strength of concrete grew faster within the curing age of 7 d, which means the hydration process of concrete was also faster. The micro morphological characteristics obtained by SEM revealed that the concrete was densest internally when 50% fly ash was replaced by the solid waste silica fume, which was better than the other contents.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34501855

RESUMO

Corporate environmental responsibility is an important component of corporate social responsibility. Based on data from Chinese listed companies from 2010-2018, the relationship between the two was explored using a fixed-effects model, with the supply chain net cash ratio being used as a proxy variable for supply chain power. This study found that supply chain power has a significant positive impact on the environmental responsibility of upstream suppliers and downstream customers. There is a vertical spillover effect of supply chain power on corporate environmental responsibility. A stepwise regression approach was used to investigate the mediating effect of business performance between the two, and the bootstrap method was used to test the existence of the mediating effect. Firms can use their power in the supply chain to reasonably allocate profits in the supply chain, which not only helps them to fulfil their environmental responsibility but also influences other firms in the supply chain to fulfil their environmental responsibility.

10.
Environ Sci Process Impacts ; 23(9): 1351-1361, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34350930

RESUMO

Despite the widespread presence of hydrogen peroxide (H2O2) in surface water and groundwater systems, little is known about the impact of environmental levels of H2O2 on the redox activity of minerals. Here we demonstrate that environmental concentrations of H2O2 can alter the reactivity of birnessite-type manganese oxide, an earth-abundant functional material, and decrease its oxidative activity in natural systems across a wide range of pH values (4-8). The H2O2-induced reductive dissolution generates Mn(II) that will re-bind to MnO2 surfaces, thereby affecting the surface charge of MnO2. Competition of Bisphenol A (BPA), used as a target compound here, and Mn(II) to interact with reactive surface sites may cause suppression of the oxidative ability of MnO2. This suppressive effect becomes more effective in the presence of oxyanions such as phosphate or silicate at concentrations comparable to those encountered in natural waters. Unlike nitrate, adsorption of phosphate or silicate onto birnessite increased in the presence of Mn(II) added or generated through H2O2-induced reduction of MnO2. This suggests that naturally occurring anions and H2O2 may have synergetic effects on the reactivity of birnessite-type manganese oxide at a range of environmentally relevant H2O2 amounts. As layered structure manganese oxides play a key role in the global carbon cycle as well as pollutant dynamics, the impact of environmental levels of hydrogen peroxide (H2O2/MnO2 molar ratio ≤ 0.3) should be considered in environmental fate and transport models.


Assuntos
Compostos de Manganês , Óxidos , Adsorção , Peróxido de Hidrogênio , Oxirredução
11.
Ann Palliat Med ; 10(8): 8584-8595, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34379984

RESUMO

BACKGROUND: The efficacy of early allograft dysfunction (EAD) definitions in predicting post-transplant graft survival in a Chinese population is still unclear. METHODS: A total of 607 orthotopic liver transplants (OLT) have been included in the current study. Model accuracy was evaluated using receiver operating characteristic (ROC) analysis. Risk factors for EAD was evaluated using univariable analysis and multivariable logistic regression model. RESULTS: The 3-, 6-, and 12-month patient/graft survival were 91.6%/91.4%, 91.1%/90%, and 87.5%/87.3%, respectively. MELDPOD5 had a superior discrimination of 3-month graft survival (C statistic, 0.83), compared with MEAF (C statistic, 0.77) and Olthoff criteria (C statistic, 0.72). Multivariate analysis of risk factors for EAD defined by MELDPOD5, showed that donor body mass index (P=0.001), donor risk index (P=0.006), intraoperative use of packed red blood cells (P=0.001), hypertension of recipient (P=0.004), and preoperative total bilirubin (P<0.001) were independent risk factors. CONCLUSIONS: The results suggest that MLEDPOD5 is a better criterion of EAD for the Chinese population, which might serve as a surrogate end-point for graft survival in clinical study.


Assuntos
Transplante de Fígado , Disfunção Primária do Enxerto , Aloenxertos , Sobrevivência de Enxerto , Humanos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
12.
Artigo em Inglês | MEDLINE | ID: mdl-34415520

RESUMO

Iron species that occur in natural surface water could affect the photochemical behavior of pollutants. Complexation between iron species and polycarboxylate or heavy metals has been widely reported, where the ligands could be oxidized via ligand-to-metal charge transfer (LMCT) by light inducement. Such complexation and photochemical reactions might also occur for low valance metal-containing organic compounds, which is worthy of investigation. This work studied the phototransformation of p-arsanilic acid (ASA), an organic arsenic compound that is widely used as a feed additive in the poultry industry, by colloidal ferric hydroxide (CFH) using black light lamps (λ = 365 nm) as the light source. The results revealed the contribution to ASA transformation at circumneutral conditions by CFH through an LMCT process, which is the same as that for As(III). The complexation between ASA and CFH was investigated using UV-vis spectroscopy. The estimated equilibrium constant for the CFH-ASA complex was log Kf271 = 4.22. The analysis of the photoproducts found the generation of both inorganic and organic arsenic. Our findings confirmed the similarities in the photochemical mechanisms of ASA and As(III) in the presence of CFH. The results help in further understanding the fate of organoarsenicals in the surface water environment.

13.
Adv Sci (Weinh) ; 8(19): e2101065, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34369112

RESUMO

In various reactive oxygen species (ROS)-based antitumor approaches (e.g., photodynamic therapy), increasing attentions are made to improve ROS level, but the short lifetime that is another decisive hurdle of ROS-based antitumor outcomes is not even explored yet. To address it, a photocleaved O2 -released nanoplatform is constructed to release and switch ROS into reactive nitrogen species (RNS) for repressing hypoxic breast tumor. Systematic explorations validate that the nanoplatforms can attain continuous photocontrolled O2 release, alleviate hypoxia, and elevate ROS level. More significantly, the entrapped PDE5 inhibitor (PDE5-i) in this nanoplatform can be enzymatically decomposed into nitric oxide that further combines with ROS to generate RNS, enabling the persistent antitumor effect since RNS features longer lifetime than ROS. Intriguingly, ROS conversion into RNS can help ROS to evade the hypoxia-induced resistance to ROS-based antitumor. Eventually, RNS production unlocks robust antitumor performances along with ROS elevation and hypoxia mitigation. Moreover, this extraordinary conversion from ROS into RNS also can act as a general method to solve the short lifetime of ROS.

14.
J Pathol ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34370292

RESUMO

Calcyphosine (CAPS) was initially identified from the canine thyroid. It also exists in many types of tumor, but its expression and function in glioma remain unknown. Here we explored the clinical significance and the functional mechanisms of CAPS in glioma. We found that CAPS was highly expressed in glioma and high expression of CAPS was correlated with poor survival, in glioma patients and public databases. Cox regression analysis showed that CAPS was an independent prognostic factor for glioma patients. Knockdown of CAPS suppressed the proliferation, whereas overexpression of CAPS promoted the proliferation of glioma both in vitro and in vivo. CAPS regulated the G2/M phase transition of the cell cycle, but had no obvious effect on apoptosis. CAPS affected PLK1 phosphorylation through interaction with MYPT1. CAPS knockdown decreased p-MYPT1 at S507 and p-PLK1 at S210. Expression of MYPT1 S507 phosphomimic rescued PLK1 phosphorylation and the phenotype caused by CAPS knockdown. The PLK1 inhibitor volasertib enhanced the therapeutic effect of temozolomide in glioma. Our data suggest that CAPS promotes the proliferation of glioma by regulating the cell cycle and the PLK1 inhibitor volasertib might be a chemosensitizer of glioma. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

15.
Planta Med ; 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34359084

RESUMO

The root Rhynchosia volubilis was widely used for contraception in folk medicine, although its molecular mechanism on antifertility has not yet been revealed. In human sperm, it was reported that the cation channel of sperm, an indispensable cation channel for the fertilization process, could be regulated by various steroid-like compounds in plants. Interestingly, these nonphysiological ligands would also disturb the activation of the cation channel of sperm induced by progesterone. Therefore, this study aimed to explore whether the compounds in R. volubilis affect the physiological regulation of the cation channel of sperm. The bioguided isolation of the whole herb of R. volubilis has resulted in the novel discovery of five new prenylated isoflavonoids, rhynchones A - E (1:  - 5: ), a new natural product, 5'-O-methylphaseolinisoflavan (6: ) (1H and 13C NMR data, Supporting Information), together with twelve known compounds (7:  - 18: ). Their structures were established by extensive spectroscopic analyses and drawing a comparison with literature data, while their absolute configurations were determined by electronic circular dichroism calculations. The experiments of intracellular Ca2+ signals and patch clamping recordings showed that rhynchone A (1: ) significantly reduced cation channel of sperm activation by competing with progesterone. In conclusion, our findings indicat that rhynchone A might act as a contraceptive compound by impairing the activation of the cation channel of sperm and thus prevent fertilization.

16.
Medicine (Baltimore) ; 100(30): e26762, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397721

RESUMO

ABSTRACT: Reliable biomarkers are of great significance for the treatment and diagnosis of hepatocellular carcinoma (HCC). This study identified potential prognostic epithelial-mesenchymal transition related lncRNAs (ERLs) by the cancer genome atlas (TCGA) database and bioinformatics.The differential expression of long noncoding RNA (lncRNA) was obtained by analyzing the lncRNA data of 370 HCC samples in TCGA. Then, Pearson correlation analysis was carried out with EMT related genes (ERGs) from molecular signatures database. Combined with the univariate Cox expression analysis of the total survival rate of hepatocellular carcinoma (HCC) patients, the prognostic ERLs were obtained. Then use "step" function to select the optimal combination of constructing multivariate Cox expression model. The expression levels of ERLs in HCC samples were verified by real-time quantitative polymerase chain reaction.Finally, we identified 5 prognostic ERLs (AC023157.3, AC099850.3, AL031985.3, AL365203.2, CYTOR). The model showed that these prognostic markers were reliable independent predictors of risk factors (P value <.0001, hazard ratio [HR] = 2.400, 95% confidence interval [CI] = 1.667-3.454 for OS). In the time-dependent receiver operating characteristic analysis, this prognostic marker is a good predictor of HCC survival (area under the curve of 1 year, 2 years, 3 years, and 5 years are 0.754, 0.720, 0.704, and 0.662 respectively). We analyzed the correlation of clinical characteristics of these prognostic markers, and the results show that this prognostic marker is an independent factor that can predict the prognosis of HCC more accurately. In addition, by matching with the Molecular Signatures Database, we obtained 18 ERLs, and then constructed the HCC prognosis model and clinical feature correlation analysis using 5 prognostic ERLs. The results show that these prognostic markers have reliable independent predictive value. Bioinformatics analysis showed that these prognostic markers were involved in the regulation of EMT and related functions of tumor occurrence and migration.Five prognostic types of ERLs identified in this study can be used as potential biomarkers to predict the prognosis of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/metabolismo , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Prognóstico
17.
Infect Dis Ther ; 10(3): 1677-1698, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34244956

RESUMO

INTRODUCTION: As the pandemic progresses, the pathophysiology of COVID-19 is becoming more apparent, and the potential for tocilizumab is increasing. However, the clinical efficacy and safety of tocilizumab in the treatment of COVID-19 patients remain unclear. METHODS: To assess the efficacy and safety of tocilizumab treatment in COVID-19 patients, we performed a retrospective case-control study. The study was conducted, including 95 patients treated with tocilizumab plus standard treatment and matched controls with 95 patients treated with standard treatment therapy by propensity score from February to April 2020. We searched some databases using the search terms for studies published from January 1, 2020, to June 1, 2021. RESULTS: Our case-control study found a lower mortality rate in the tocilizumab treatment group than in the standard treatment group (9.47% versus 16.84%, P = 0.134), but the results were not statistically significant. We also found that the mortality rate in tocilizumab treatment groups was significantly lower than in the standard treatment group in the stratified ICU analysis (OR 0.52, 95% CI 0.44-0.61, P = 0.048 and OR 0.31, 95% CI 0.10-0.99, P = 0.044). We selected 49 studies (including 6568 cases and 11,660 controls) that met the inclusion criteria in the meta-analysis. In the overall analysis, we performed a meta-analysis that showed significantly decreased mortality after patients received tocilizumab (OR 0.81, 95% CI 0.69-0.95, P = 0.008). We also revealed significant associations within some subgroups. The sequential trial analysis showed a true-positive result. No significant associations were observed between tocilizumab and elevated secondary infection risk, discharge, adverse events, and mechanical ventilation in the overall analysis. CONCLUSION: Tocilizumab significantly decreased mortality in COVID-19 patients with no increased discharge, secondary infection risk, adverse events, and mechanical ventilation in a meta-analysis. Our data suggest that clinicians should pay attention to tocilizumab therapy as an effective and safe treatment for COVID-19 patients.

18.
Reprod Biol ; 21(3): 100529, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34217103

RESUMO

Progestin and adipoQ receptor 7 (PAQR7) as an indispensable member of membrane progestin receptors in the Progestin and adipoQ receptor (PAQR) family that mediates nongenomic progesterone actions, initiated rapidly at the cell surface. Previous research demonstrated the distribution of PAQR7, which was mainly expressed in reproductive tissues, including ovary and testis. In the male reproductive system, PAQR7 is involved in progestin-induced sperm hypermotility. However, reports studying PAQR7 in female reproductive tissue mainly concentrate on oocyte maturation in fish, its expression in the ovary and gestational tissue, and regulation of uterine functions in mammals. Despite recent advances, many aspects of progestin signaling through PAQR7 are still unclear, especially in female reproductive tissue. Therefore, we reveal the structure and characteristics of PAQR7 and conclude the putative progestin-induced action mediated by PAQR7 in female reproductive tissue, such as the development of ovarian follicles, apoptosis of granulosa cells, oocyte maturation, and development of certain diseases, among others, to review the function of PAQR7 in the female reproductive system in detail.

19.
Mater Sci Eng C Mater Biol Appl ; 127: 112190, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225846

RESUMO

Multifunctional nanodrugs have emerged as an effective platform to integrate multiple imaging and therapeutic functions for tremendous biomedical applications. However, the development of a simple potent theranostic nanoplatform is still an intractable challenge. Herein, a novel theranostic nanoplatform was developed by coupling prepared Au nanobipyramids with Gd2O3, Au nanoclusters and denatured bovine serum albumin (AuNBP-Gd2O3/Au-dBSA) for FL/MR dual-modal imaging guided photothermal therapy. AS1411 aptamers were conjugated to enhance its targetability towards breast cancer. The AS1411-AuNBP-Gd2O3/Au-dBSA suspension could be readily heated above 40 °C at a low concentration (2 mg/L) and NIR density (1 W/cm2). The AS1411-AuNBP-Gd2O3/Au-dBSA revealed a fluorescence quantum yield of 4.2% and higher longitudinal relaxivity rate of 6.75 mM-1 s-1 compared to Gd-DTPA of 4.45 mM-1 s-1. As a result, the AS1411-AuNBP-Gd2O3/Au-dBSA functions as a multimodal nanoprobe of photothermal, fluorescence and MR imaging for specific tumor diagnosis and guidance of therapy, which was validated via in vitro and in vivo tests. Moreover, AS1411-AuNBP-Gd2O3/Au-dBSA nanoparticles indicated excellent photothermal anticancer effect more than 95% in both in vitro and in vivo tests. Besides, the low toxicity of AS1411-AuNBP-Gd2O3/Au-dBSA nanocomposites was further confirmed in vitro and in vivo. Thus, these results demonstrated the AS1411-AuNBP-Gd2O3/Au-dBSA nanocomposites as a rational design of multifunctional nanoplatform to enable multimodal imaging guided photothermal therapy.


Assuntos
Nanocompostos , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Humanos , Imageamento por Ressonância Magnética , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fototerapia , Terapia Fototérmica , Nanomedicina Teranóstica
20.
Stem Cell Res Ther ; 12(1): 421, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294156

RESUMO

BACKGROUND: Human dental pulp stem cells (hDPSCs) are the preferable choice of seed cells for craniomaxillofacial bone tissue regeneration. As a member of the miR-17-92 cluster, miR-20a-5p functions as an important regulator during bone remodeling. This study aimed to investigate the roles and mechanisms of miR-20a-5p during osteogenesis of hDPSCs. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to determine the expression of miR-20a-5p during osteogenesis of hDPSCs. We interfered with the expression of miR-20a-5p in hDPSCs to clarify the function of miR-20a-5p on osteogenesis both in vitro and vivo. Direct bind sites between miR-20a-5p and BAMBI were confirmed by dual-luciferase reporter assay, and the underlying mechanisms were investigated with cell co-transfections. RESULTS: The expression of miR-20a-5p was showed to be upregulated during osteogenesis of hDPSCs. Inhibition of miR-20a-5p could weaken the intensity of ALP/ARS staining and downregulate the expression of mRNAs and proteins of osteogenic markers, while overexpression of miR-20a-5p could enhance the intensity of ALP/ARS staining and the expression of osteogenic markers. Both micro-CT reconstruction images and histological results showed that miR-20a-5p could promote the regeneration of calvarial defects. miR-20a-5p directly targeted bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), and the latter one was an inhibitor of hDPSC osteogenesis. Silencing BAMBI partially reversed the suppression effect of miR-20a-5p knockdown on osteogenesis. Phosphorylation of Smad5 and p38 was decreased when miR-20a-5p was silenced, whereas p-Smad5 and p-p38 were upregulated when miR-20a-5p was overexpressed or BAMBI was silenced. CONCLUSIONS: It is demonstrated that miR-20a-5p functioned as a regulator of BAMBI to activate the phosphorylation of Smad5 and p38 during osteogenic differentiation of hDPSCs.


Assuntos
MicroRNAs , Osteogênese , Diferenciação Celular , Células Cultivadas , Polpa Dentária/metabolismo , Humanos , Proteínas de Membrana , MicroRNAs/genética , MicroRNAs/metabolismo , Osteogênese/genética , Fosforilação , Proteína Smad5/genética , Células-Tronco/metabolismo
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