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1.
Int Wound J ; 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32755065

RESUMO

Perineal wound complications after APR have high morbidity in the colorectal surgical department. Although some approaches have been figured out to solve this clinical focus, the outcomes are still not satisfied. Herein, this prospective comparative clinical trial has been designed to evaluate a new surgical procedure of direct perineal wound full-thick closure (DPWC), compared with conventional perineal wound closure (CPWC), with hopes of making wound healing with less complications. In addition, an evaluation of an incision negative wound pressure therapy, as another focus in this field, was also analysed in the DPWC group. A total of 44 participants in our department were recruited from March 2018 to March 2020, divided into two groups randomly, CPWC group and DPWC group. The patients' characteristics, such as age, gender, BMI, smoking, alcohol consumption, comorbidities, CEA level, and high-risk of invasion, were recorded without statistical significance between the CPWC group and DPWC group. After the same standard abdominal phase, these two groups were performed in different perineal phases. And then, operative and postoperative outcomes were analysed with different statistical methods. Data on wound healing time and length of stay in the DPWC group were shorter than those in the CPWC group (P < .05). Furthermore, cases of wound infection within 30 days in the DPWC group were also less than that in the CPWC group (P < .05). However, no difference was found between the incisional negative pressure wound therapy assisted group (NPA group) and non- incisional negative pressure wound therapy assisted group (non-NPA group). During this study, hypoalbuminemia, as an independent high-risk factor, impacted perineal wound healing. (P = .0271) In conclusion, DPWC is a new surgical approach, which can lead to a better outcome than DPWC, and it can be another surgical procedure for clinicians. In addition, hypoalbuminemia should be interfered for avoiding perineal wound complications.

2.
Acta Pharmacol Sin ; 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32724174

RESUMO

We previously found that polydatin could attenuate renal oxidative stress in diabetic mice and improve renal fibrosis. Recent evidence shows that NADPH oxidase 4 (Nox4)-derived reactive oxygen species (ROS) contribute to inflammatory and fibrotic processes in diabetic kidneys. In this study we investigated whether polydatin attenuated renal fibrosis by regulating Nox4 in vitro and in vivo. In high glucose-treated rat glomerular mesangial cells, polydatin significantly decreased the protein levels of Nox4 by promoting its K48-linked polyubiquitination, thus inhibited the production of ROS, and eventually decreasing the expression of fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1), the main factors that exacerbate diabetic renal fibrosis. Overexpression of Nox4 abolished the inhibitory effects of polydatin on FN and ICAM-1 expression. In addition, the expression of Connexin32 (Cx32) was significantly decreased, which was restored by polydatin treatment. Cx32 interacted with Nox4 and reduced its protein levels. Knockdown of Cx32 abolished the inhibitory effects of polydatin on the expression of FN and ICAM-1. In the kidneys of streptozocin-induced diabetic mice, administration of polydatin (100 mg·kg-1·d-1, ig, 6 days a week for 12 weeks) increased Cx32 expression and reduced Nox4 expression, decreased renal oxidative stress levels and the expression of fibrotic factors, eventually attenuating renal injury and fibrosis. In conclusion, polydatin promotes K48-linked polyubiquitination and degradation of Nox4 by restoring Cx32 expression, thereby decreasing renal oxidative stress levels and ultimately ameliorating the pathological progress of diabetic renal fibrosis. Thus, polydatin reduces renal oxidative stress levels and attenuates diabetic renal fibrosis through regulating the Cx32-Nox4 signaling pathway.

3.
Genes Genomics ; 42(8): 927-935, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32623575

RESUMO

BACKGROUND: The main therapies for cancer often results in many side effects and drug resistance. Gamma linolenic acid (GLA) is a kind of natural reagent with negligible cytotoxicity. OBJECTIVE: This work aims at detecting whether GLA possesses anti-cancer activity in NSCLC cells and elucidating the potential molecular mechanism. METHODS: Cytotoxicity of GLA was evaluated by MTT assay and soft agar colony formation method. Immunoblotting analysis examined the effect of GLA on protein expressions of cell proliferation markers (e.g., PCNA, Ki-67 and MCM2), pro-survival protein bcl-2, apoptosis-associated proteins (e.g., bax and cleaved caspase 3), HIF1α and VEGF. Wound healing assay and transwell invasion assay were performed to test the effect of GLA on hypoxia-induced cell migration and invasion. Cell transfection was used to overexpress HIF1α followed by the treatment of GLA to test the effect of HIF1α overexpression on the tumoricidal activity of GLA in NSCLC cell lines. RESULTS: MTT and soft agar colony formation tests showed that GLA dose-dependently suppressed cell proliferation in both Calu-1 and SK-MES-1 cell lines. Immunoblotting analysis demonstrated that GLA suppressed protein expressions of PCNA, Ki-67, MCM2 and bcl-2, while GLA induced bax and cleaved caspase 3 expressions. Wound healing assay and transwell invasion assay revealed that GLA was very effective on the inhibition of NSCLC cell migration and invasion. Immunoblotting analysis and cell transfection method indicated that GLA inhibited hypoxia-induced cell proliferation and invasion by suppressing HIF1α-VEGF pathway. CONCLUSION: GLA suppresses hypoxia-induced proliferation and invasion of NSCLC cells by inhibition of HIF1α pathway in vitro.

4.
Int J Mol Sci ; 21(13)2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32640753

RESUMO

Photothermal therapy possesses great advantages for the treatment of drug-resistant tumors. Herein, Near Infrared (NIR)-triggered photothermal nanoparticles were developed through loading indocyanine green (ICG), a kind of NIR dye, into amino group-modified silica nanoparticles (SiO2-NH2 NPs). SiO2-NH2 NPs were prepared with immobilization of the amino groups into the framework of silica nanoparticles (SiO2 NPs) by employing (3-aminopropyl)-triethoxysilane (APTES). Before and after the modification of the amino group, the particle sizes of SiO2 NPs showed similar value, around 100 nm. ICG was further adsorbed into SiO2-NH2 NPs by electrostatic attraction to enable SiO2-NH2@ICG NPs as a kind of photothermal agent. The loading rate of ICG to SiO2-NH2 was greatly increased compared to unmodified SiO2, and the stability of ICG was also improved. Moreover, the SiO2-NH2@ICG NPs exhibited efficient photothermal effects due to ICG transforming laser power into local heat through the connected ICG, when NIR laser irradiation turned on for a couple of minutes. Finally, the in vitro antitumor efficacy of SiO2-NH2@ICG NPs was investigated by recording cell proliferation rate and further chronicled the apoptotic morphology evidence by a Calcein-AM/PI fluorescent staining assay, indicating the efficient photothermal targeted therapy for the HepG2 tumor cells.

5.
Dermatol Ther ; : e13993, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32648291

RESUMO

In-depth analysis on the rambling genes of psoriasis may help to identify the pathologic mechanism of this disease. However, this has seldom been performed. Using bioinformatic approaches, we analyzed four gene expression profiles in gene expression omnibus (GEO) database, identified the differentially expressed genes (DEGs), and found out the overlapping DEGs (common DEGs, CDEGs) in the above 4 profiles. The CDEGs were further subjected to Gene Ontology (GO) enrichment analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein-protein interaction (PPI) network analysis, and hub genes were ranked. We identified 139 CDEGs associated with a variety of GO processes including keratinization, immune and inflammatory responses, and type 1 interferon signaling pathway. These CDEGs were enriched in a variety of KEGG processes, including cytokine-cytokine receptor interaction and chemokine signaling. PPI analysis showed that seven genes (HERC6, ISG15, MX1, RSAD2, OAS2, OASL, OAS3) were likely the novel hub genes of psoriasis. RT-qPCR identified that five (ISG15, MX1, OAS2, OASL, and OAS3) of the seven predicted hub genes were overexpressed in TNF-α stimulated HaCaT cell lines, a result quite consistent with the predictions. The study provides new information in exploring the mechanisms and therapeutic targets of psoriasis. This article is protected by copyright. All rights reserved.

6.
Sci Rep ; 10(1): 11210, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641736

RESUMO

Cervical cancer is one of the most common tumors in women. Neutrophils (NEs) and platelets (PLTs) are components of cells in circulating blood. NEs are one of the components of white blood cells (WBCs), accounting for the vast majority of WBCs, recognized as one of the indicators of inflammation. PLTs are associated with thrombosis and inflammation. Both of them play an important role in tumor growth and metastasis. According to pre-radiotherapy PLT and NE media levels, we divided the patients into three groups: PLT and NE both high levels group, single high level group and both low group. By using COX regression models and nomogram, a prognostic model for patients was established. Both high levels of pre-radiotherapy PLT and NE group or high levels of post-radiotherapy PLT and NE group were correlated with worst overall survival (OS) compared with the other two groups. PLT and NE were correlated with outcomes of the patients with locally advanced cervical cancer.

7.
Biomed Res Int ; 2020: 4256301, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32685484

RESUMO

Coronaviruses are specific crown-shaped viruses that were first identified in the 1960s, and three typical examples of the most recent coronavirus disease outbreaks include severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19. Particularly, COVID-19 is currently causing a worldwide pandemic, threatening the health of human beings globally. The identification of viral pathogenic mechanisms is important for further developing effective drugs and targeted clinical treatment methods. The delayed revelation of viral infectious mechanisms is currently one of the technical obstacles in the prevention and treatment of infectious diseases. In this study, we proposed a random walk model to identify the potential pathological mechanisms of COVID-19 on a virus-human protein interaction network, and we effectively identified a group of proteins that have already been determined to be potentially important for COVID-19 infection and for similar SARS infections, which help further developing drugs and targeted therapeutic methods against COVID-19. Moreover, we constructed a standard computational workflow for predicting the pathological biomarkers and related pharmacological targets of infectious diseases.


Assuntos
Infecções por Coronavirus/genética , Pneumonia Viral/genética , Betacoronavirus/isolamento & purificação , Biomarcadores/análise , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Humanos , Modelos Genéticos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Mapas de Interação de Proteínas , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/virologia
8.
J Hazard Mater ; 401: 123281, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32629352

RESUMO

Developing economical and active materials is of great significance for VOC purification. Here, hierarchical porous Al2O3 and ZnO microspheres (Al2O3-pm and ZnO-pm) were synthesized by a facile hydrothermal strategy. The urchin-like Al2O3-pm and flower-like ZnO-pm possess high specific surface area (especially; external surface area) obviously boost the dispersion of Pd with 29.3 % and 30.1 % over Pd/Al2O3-pm and Pd/ZnO-pm, respectively, over 3.4 times higher than those of commercial Al2O3- and ZnO-supported counterparts. Pd/Al2O3-pm possesses excellent activity and CO2 yield in ethyl acetate (EA) degradation, with TOF reaches 7.76 × 10-3 s-1 at 160 °C under GHSV of 50,000 h-1. Moreover, Pd/Al2O3-pm exhibits satisfied performance in EA-contained binary VOCs oxidation and has high long-term stability under both dry and humid conditions. Both Pd sites and Brønsted acid sites participated in reaction process and initially react with EA to form ethylene and ethanol, respectively. Larger amount Brønsted acid sites over Pd/Al2O3-pm promote ethanol formation and C-C cleavage, resulting in different CO2 yields and EA activation mechanisms. The coating greatly enhances Pd dispersion over Pd supported monolithic catalyst, endowing its desired activity and stability even with a much lower Pd loading. This work promotes the potential application of noble-metal-based monolithic materials in VOC degradation.

9.
Virus Genes ; 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32676956

RESUMO

Outbreaks of short beak and dwarfism syndrome (SBDS), caused by a novel goose parvovirus (NGPV), have occurred in China since 2015. This rapidly spreading, infectious disease affects ducks in particular, with a high morbidity and low mortality rate, causing huge economic losses. This study analyzed the evolution of NGPV isolated from Jing-Xi partridge duck with SBDS in South China. Complete genome sequences of the NGPV strains GDQY1802 and GDSG1901 were homologous with other GPV/NGPV and Muscovy duck parvovirus (MDPV) strains. Phylogenetic analysis showed that the NGPV isolated from mainland China was related to the Taiwan 82-0321v strain of GPV. In contrast to 82-0321v and the SDLC01 strain, which was first isolated from China, the two isolates showed no deletions in the inverted terminal repeat (ITR) region. Further, in these isolates, 24 amino acid sites of the replication protein were different compared to that of GPV live vaccine strain 82-0321v, and 12 sites were unique across all NGPV isolates. These isolates also showed differences in 17 amino acid sites of the capsid protein from that of 82-0321v, two of which were the same as those in MDPV. Recombination analysis identified the major parents of GDSG1901 and GDQY1802 as the NGPV-GD and NGPV-Hun18 strains, and the minor parents as the classical GPV 06-0329 and GPV LH strains, respectively. GDQY1802 and GDSG1901 are recombinant GPV-related parvovirus isolated from domesticated partridge duck. Recombination is evident in the evolution of NGPV, and as such, the use of live attenuated vaccines for NGPV requires further study.

10.
Antiviral Res ; : 104868, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32659292

RESUMO

COVID-19, which is caused by the emerging human coronavirus SARS-CoV-2, has become a global pandemic that poses a serious threat to human health. To date, no vaccines or specific antiviral drugs have been approved for the treatment of this disease in clinic. Herein, therapeutic antibodies for SARS-CoV-2 were obtained from hyperimmune equine plasma. First, a recombinant SARS-CoV-2 spike protein receptor-binding domain (RBD) was obtained in gram-level quantities through high-cell density fermentation of Chinese hamster ovary cells. Then, the binding of the RBD to the SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, was verified by several biochemical methods. The efficacy of the RBD in triggering antibody response in vivo was subsequently tested in both mice and equines, and the results showed that the RBD triggered high-titer neutralizing antibody production in vivo. Immunoglobulin F(ab')2 fragments were prepared from equine antisera via removal of the Fc region from the immunoglobulins. Finally, a neutralization test with live virus demonstrated that RBD-specific F(ab')2 inhibited SARS-CoV-2 with an EC50 of 0.07 µg/ml and an EC80 of 0.18 µg/ml, showing a potent inhibitory effect on SARS-CoV-2. These results highlight RBD-specific equine immunoglobulin F(ab')2 fragment as a candidate for the treatment of SARS-CoV-2.

11.
Biochem Pharmacol ; 180: 114127, 2020 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-32603666

RESUMO

Gemcitabine is an intravenously administered anti-cancer nucleoside analogue. Systemic exposure following oral administration of gemcitabine is limited by extensive first-pass metabolism via cytidine deaminase (CDA) and potentially by saturation of nucleoside transporter-mediated intestinal uptake. An amino acid ester prodrug of gemcitabine, 5'-l-valyl-gemcitabine (V-Gem), was previously shown to be a substrate of the intestinally expressed peptide transporter 1 (PEPT1) and stable against CDA-mediated metabolism. However, preliminary studies did not evaluate the in vivo oral performance of V-Gem as compared to parent drug. In the present study, we evaluated the pharmacokinetics and in vivo oral absorption of gemcitabine and V-Gem following intravenous and oral administrations in mice. These studies revealed that V-Gem undergoes rapid systemic elimination (half-life < 1 min) and has a low oral bioavailability (<1%). Most importantly, the systemic exposure of gemcitabine was not different following oral administration of equimolar doses of gemcitabine (gemcitabine bioavailability of 18.3%) and V-Gem (gemcitabine bioavailability of 16.7%). Single-pass intestinal perfusions with portal blood sampling in mice revealed that V-Gem undergoes extensive activation in intestinal epithelial cells and that gemcitabine undergoes first-pass metabolism in intestinal epithelial cells. Thus, formulation of gemcitabine as the prodrug V-Gem does not increase systemic gemcitabine exposure following oral dosing, due, in part, to the instability of V-Gem in intestinal epithelial cells.

12.
Waste Manag ; 115: 1-7, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32707481

RESUMO

Separation and recovery of high-purity Si powder from kerf-loss Si slurry waste is a critical challenge for the photovoltaic industry. A green surfactant poly (propylene glycol) bis (2-aminopropyl ether) (PEA) was employed as a collector to facilitate the separation of Si and SiC from kerf-loss Si waste during flotation process. Single flotation tests of Si and SiC were conducted using 5 × 10-6 mol/L PEA, respectively. The separation efficiencies of Si and SiC in conjunction with PEA adsorption mechanism were investigated. It was found that the maximum recoveries rate of SiC and Si were 90.59% (pH 9.00) and 80.93% (pH 1.96), respectively. Furthermore, the maximum Si grade was determined as 92.31% at pH 8.95 for the sinking part of the mixture generating excellent floatability and selectivity. Zeta potential measurements, FT-IR spectra, and XPS analyses demonstrated that PEA was present on the surface of Si and SiC through electrostatic and hydrogen-bond interactions. The adsorption mechanism was explained based on the results. This research provides an efficient and environmentally friendly route for the separation and recovery of high purity silicon from kerf-loss Si waste.

13.
J Physiol ; 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32627185

RESUMO

KEY POINTS: In vascular smooth muscle cells (VSMCs), activation of Ca2+ -permeable store-operated channels (SOCs) composed of canonical transient receptor potential channel 1 (TRPC1) subunits mediate Ca2+ entry pathways which regulate contraction, proliferation and migration that are processes associated with vascular disease. Activation of TRPC1-based SOCs requires protein kinase C (PKC) activity, which is proposed to phosphorylate TRPC1 proteins to promote channel opening by phosphatidylinositol 4,5-bisphosphate (PIP2 ). We investigated the identity of the PKC isoform involved in activating TRPC1-based SOCs in rat mesenteric artery VSMCs. TRPC1-based SOCs were reduced by PKCδ inhibitors and knockdown of PKCδ expression. Store depletion induced interactions between TRPC1 and PKCδ and PKCδ-dependent phosphorylation of TRPC1. Furthermore, generation of store-operated interactions between PIP2 and TRPC1 and activation of TRPC1-based SOCs by PIP2 required PKCδ. These findings reveal that PKCδ activity has an obligatory role in activating TRPC1-based SOCs, through regulating PIP2 -mediated channel opening. ABSTRACT: In vascular smooth muscle cells (VMSCs), stimulation of Ca2+ -permeable canonical transient receptor potential channel 1 (TRPC1)-based store-operated channels (SOCs) mediate Ca2+ entry pathways which regulate cell contraction, proliferation and migration that are processes associated with vascular disease. It is therefore important to understand how TRPC1-based SOCs are activated. Stimulation of TRPC1-based SOCs requires protein kinase C (PKC) activity, with store-operated PKC-dependent phosphorylation of TRPC1 essential for channel opening by phosphatidylinositol 4,5-bisphosphate (PIP2 ). Experimental protocols used to activate TRPC1-based SOCs suggest that the PKC isoform involved requires diacylglycerol (DAG) but is Ca2+ -insensitive, which are characteristics of the novel group of PKC isoforms (δ, ε, η, θ). Hence the present study examines if a novel PKC isoform(s) is involved in activating TRPC1-based SOCs in contractile rat mesenteric artery VSMCs. Store-operated whole-cell cation currents were blocked by Pico145, a highly selective and potent TRPC1/4/5 channel blocker and T1E3, a TRPC1 blocking antibody. PKCδ was expressed in VSMCs, and selective PKCδ inhibitory peptides and knockdown of PKCδ expression with morpholinos oligomers inhibited TRPC1-based SOCs. TRPC1 and PKCδ interactions and phosphorylation of TRPC1 induced by store depletion were both reduced by pharmacological inhibition and PKCδ knockdown. In addition, store-operated PIP2 and TRPC1 interactions were blocked by PKCδ inhibition, and PKCδ was required for PIP2 -mediated activation of TRPC1 currents. These results identify involvement of PKCδ in stimulation of TRPC1-based SOCs and highlights that store-operated PKCδ activity is obligatory for channel opening by PIP2 , the likely activating ligand. This article is protected by copyright. All rights reserved.

14.
Folia Histochem Cytobiol ; 58(2): 117-126, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32608501

RESUMO

INTRODUCTION: Gastric cancer is one of the most common malignancies in China and the fifth most common cancer in the world. Gamma linolenic acid (GLA) was reported to have anti-inflammatory and anti-cancer effects. The purpose of this research was to investigate the effect and mechanism of GLA on gastric cancer cell growth under hypoxic conditions. MATERIAL AND METHODS: The hypoxia models of SGC-7901 and MGC-803 cells were established, and then were exposed to different concentrations of 50, 100 or 200 µM GLA. MTT assay, colony formation assay, wound healing assay and transwell assay were used to investigate the effects of GLA treatment on gastric cancer cell growth under hypoxia (1% O2). The expression of apoptosis- and epithelial-mesenchymal transition (EMT)-related proteins was detected by qPCR and western blot. RESULTS: GLA treatment significantly decreased viability and inhibited colony formation (p < 0.05, p < 0.01) of SGC-7901 and MGC-803 cells under hypoxia. Western blotting analysis showed that GLA treatment decreased the expression of proliferating cell nuclear antigen (PCNA), microchromosome maintenance complex component 2 (MCM-2) and anti-apoptotic protein Bcl-2, while increased the expression of pro-apoptotic proteins (Bax and Cleaved Caspase-3) (p < 0.05 and p < 0.01). In addition, Wound healing analysis and Transwell assays showed that GLA treatment inhibited the migration and invasion of SGC-7901 and MGC-803 cells in a dose-dependent manner (p < 0.01). Western blotting analysis showed that GLA treatment increased the expression of epithelial marker proteins (g-catenin and E-cadherin), while decreased the expression of stromal and extracellular matrix marker proteins (fibronectin, Snail and b-catenin) (p < 0.01). Further analyses showed that GLA treatment decreased the expression of b-catenin in Wnt/b-catenin pathway (p < 0.01). Moreover, exogenous Wnt3a reversed the inhibitory effect of GLA on b-catenin expression, and further reversed the inhibitory effect of GLA on gastric cancer cell growth and EMT markers (p < 0.05, p < 0.01). CONCLUSION: These findings suggest that GLA should be tested in animal models and in clinical studies as a potentially effective bioactive phytochemical substance for the treatment of gastric cancer.

15.
Aging (Albany NY) ; 12(14): 15077-15090, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32710731

RESUMO

PURPOSE: To determine the prognostication and treatment decision making of the American Joint Committee on Cancer (AJCC) 8th pathological staging system in elderly women (aged ≥65 years) with T1-2N0M0 breast cancer (BC). RESULTS: We included 67699 patients, and patients were restaged into stage IA (84.9%), IB (8.9%), and IIA (6.2%) using the 8th AJCC edition criteria. Overall, 69.4% and 30.6% of them underwent breast-conservation surgery (BCS) and mastectomy (MAST), respectively. In patients who received BCS, 30.3% of them underwent postoperative radiotherapy (RT). Patients with a higher pathological stage were more likely to receive MAST. The 5-year breast cancer-specific mortality rate was 2.2%, 6.5% and 13.7% in stage IA, IB, and IIA, respectively. Patients treated with BCS and RT had significantly lower risk of breast cancer-specific mortality compared to those treated with MAST or with BCS alone regardless of the pathological prognostic stages (P<0.001). CONCLUSIONS: The 8th AJCC pathological prognostic staging system provides accurate risk stratification and impacts the treatment decision making for elderly women with early-stage BC. METHODS: We identified stage T1-2N0M0 BC patients using the Surveillance, Epidemiology, and End Results database. Statistical analyses were used binomial logistic regression, and multivariable competing risk models in the Cox model framework.

16.
Mol Ther Nucleic Acids ; 21: 492-511, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32679544

RESUMO

Autophagy is associated with the cytoprotection of physiological processes against inflammation and oxidative stress. Salvia miltiorrhiza possesses cardiovascular protective actions and has powerful anti-oxidative and anti-inflammatory effects; however, whether and how Salvia miltiorrhiza-derived microRNAs (miRNAs) protect vascular smooth muscle cells (VSMCs) by inducing autophagy across species are unknown. We first screened and identified Sal-miR-58 from Salvia miltiorrhiza as a natural autophagy inducer. Synthetic Sal-miR-58 suppresses chronic angiotensin II (Ang II) infusion-induced abdominal aortic aneurysm (AAA) formation in mice, as well as induces autophagy in VSMCs and attenuates the inflammatory response elicited by Ang II in vivo and in vitro. Mechanistically, Sal-miR-58 downregulates Krüppel-like factor 3 (KLF3) expression through direct binding to the 3' UTR of KLF3, which in turn relieves KLF3 repression of E3 ubiquitin ligase neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L) expression, whereas NEDD4L upregulation increases the ubiquitination and degradation of the platelet isoform of phosphofructokinase (PFKP), subsequently leading to a decrease in the activation of Akt/mammalian target of rapamycin (mTOR) signaling and facilitating VSMC autophagy induced by Sal-miR-58 in the context of chronic Ang II stimulation and aneurysm formation. Our results provide the first evidence that plant-derived Sal-miR-58 induces autophagy and attenuates inflammation in VSMCs through cross-species modulation of the KLF3/NEDD4L/PFKP regulatory pathway.

17.
Vascul Pharmacol ; : 106776, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32707323

RESUMO

Phosphatidylinositol 4,5-bisphosphate (PIP2) acts as substrate and unmodified ligand for Gq-protein-coupled receptor signalling in vascular smooth muscle cells (VSMCs) that is central for initiating contractility. The present work investigated how PIP2 might perform these two potentially conflicting roles by studying the effect of myristoylated alanine-rich C kinase substrate (MARCKS), a PIP2-binding protein, on vascular contractility in rat and mouse mesenteric arteries. Using wire myography, MANS peptide (MANS), a MARCKS inhibitor, produced robust contractions with a pharmacological profile suggesting a predominantly role for L-type (CaV1.2) voltage-gated Ca2+ channels (VGCC). Knockdown of MARCKS using morpholino oligonucleotides reduced contractions induced by MANS and stimulation of α1-adrenoceptors and thromboxane receptors with methoxamine (MO) and U46619 respectively. Immunocytochemistry and proximity ligation assays demonstrated that MARCKS and CaV1.2 proteins co-localise at the plasma membrane in unstimulated tissue, and that MANS and MO reduced these interactions and induced translocation of MARCKS from the plasma membrane to the cytosol. Dot-blots revealed greater PIP2 binding to MARCKS than CaV1.2 in unstimulated tissue, with this binding profile reversed following stimulation by MANS and MO. MANS evoked an increase in peak amplitude and shifted the activation curve to more negative membrane potentials of whole-cell voltage-gated Ca2+ currents, which were prevented by depleting PIP2 levels with wortmannin. This present study indicates for the first time that MARCKS is important regulating vascular contractility and suggests that disinhibition of MARCKS by MANS or vasoconstrictors may induce contraction through releasing PIP2 into the local environment where it increases voltage-gated Ca2+ channel activity.

18.
Medicine (Baltimore) ; 99(26): e20985, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590811

RESUMO

RATIONALE: Among the various forms of colorectal carcinomas, primary signet ring cell carcinoma (SRCC) of rectum is infrequent. Primary SRCC with adenoma is even rarer. Due to its low morbidity and lack of obvious manifestations at early stages, it is difficult to make an early diagnosis and perform surgical intervention in time. Herein, we reported a case of primary SRCC with tubular adenoma of rectum and also performed a review of the literature of such cases, in hopes of expanding the general understanding regarding such cases. PATIENT CONCERNS: A 61-year-old male patient presented with rectal bleeding for 1 week. DIAGNOSES: A neoplasm could be palpated through a rectal examination, with a size of 4.0 cm by 3.0 cm, at a distance of 5 cm from the anal edge. Magnetic resonance imaging examination and colonoscopies were performed to confirm the finding, and 4 tissue specimens were obtained for histopathologic biopsy. The result of biopsy was high-grade intraepithelial neoplasia with an adenoma component. INTERVENTIONS: Surgical resection was performed, and histopathologic and immunohistochemical staining examination of the resection confirmed the diagnosis of SRCC with tubular adenoma. OUTCOMES: The patient was discharged from hospital 12 days postsurgery, without any complications. Further chemotherapy and supportive treatments were suggested to him and will be followed at a local hospital. LESSONS: Primary rectal SRCC has a rather low morbidity. Furthermore, a rectal SRCC with adenoma which was presenting in this case is even more rare. Besides lack of clinical characters, delay of diagnosis and treatment frequently occur. So far, a surgical procedure has still been one of the most effective treatments. Considering of metastasis and the poor prognosis, early diagnosis, in-time radical resection, and a comprehensive followed treatment are recommended for a higher 5-year overall survival.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma de Células em Anel de Sinete/diagnóstico , Neoplasias Retais/diagnóstico , Adenocarcinoma/patologia , Carcinoma de Células em Anel de Sinete/patologia , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Reto/patologia , Resultado do Tratamento
19.
Plant Dis ; 104(8): 2138-2143, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32539593

RESUMO

Members of Fusarium graminearum species complex (FGSC) are the major pathogens that cause Fusarium head blight (FHB) in cereals worldwide. Symptoms of FHB on rice, including dark staining or browning of rice glumes, were recently observed in Jiangsu Province, China. To improve our understanding of the pathogens involved, 201 FGSC isolates were obtained from freshly harvested rice samples and identified by phylogenetic analyses. Among the 201 FGSC isolates, 196 were F. asiaticum and the remaining 5 were F. graminearum. Trichothecene chemotype and chemical analyses showed that 68.4% of the F. asiaticum isolates were the 3-acetyldeoxynivalenol (3ADON) chemotype and the remainder were the nivalenol (NIV) chemotype. All of the F. graminearum isolates were the 15-acetyldeoxynivalenol chemotype. Pathogenicity assays showed that both the 3ADON and NIV chemotypes of F. asiaticum could infect wheat and rice spikes. FHB severity and trichothecene toxin analysis revealed that F. asiaticum with the NIV chemotype was less aggressive than that with the 3ADON chemotype in wheat, while the NIV-producing strains were more virulent than the 3ADON-producing strains in rice. F. asiaticum isolates with different chemotypes did not show significant differences in mycelial growth, sporulation, conidial dimensions, or perithecial production. These findings would provide useful information for developing management strategies for the control of FHB in China.


Assuntos
Fusarium , Oryza , China , Filogenia , Triticum
20.
Nat Commun ; 11(1): 3112, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561757

RESUMO

Previous flavivirus (dengue and Zika viruses) studies showed largely spherical particles either with smooth or bumpy surfaces. Here, we demonstrate flavivirus particles have high structural plasticity by the induction of a non-spherical morphology at elevated temperatures: the club-shaped particle (clubSP), which contains a cylindrical tail and a disc-like head. Complex formation of DENV and ZIKV with Fab C10 stabilize the viruses allowing cryoEM structural determination to ~10 Å resolution. The caterpillar-shaped (catSP) Fab C10:ZIKV complex shows Fabs locking the E protein raft structure containing three E dimers. However, compared to the original spherical structure, the rafts have rotated relative to each other. The helical tail structure of Fab C10:DENV3 clubSP showed although the Fab locked an E protein dimer, the dimers have shifted laterally. Morphological diversity, including clubSP and the previously identified bumpy and smooth-surfaced spherical particles, may help flavivirus survival and immune evasion.

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