Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 450
Filtrar
1.
Clin Epigenetics ; 12(1): 25, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046777

RESUMO

BACKGROUND: Although massive studies have been conducted to investigate the mechanisms of esophageal squamous cell carcinoma (ESCC) carcinogenesis, the understanding of molecular alterations during the malignant transformation of epithelial dysplasia is still lacking, especially regarding epigenetic changes. RESULTS: To better characterize the methylation changes during the malignant transformation of epithelial dysplasia, a whole-genome bisulfite sequencing analysis was performed on a series of tumor, dysplastic, and non-neoplastic epithelial tissue samples from esophageal squamous cell carcinoma (ESCC) patients. Promoter hypermethylation in TGF-ß receptor type II (TGFBR2), an important mediator of TGF-ß signaling, was identified. Further, we evaluated the methylation and expression of TGFBR2 in tumor samples through The Cancer Genome Atlas multiplatform data as well as immunohistochemistry. Moreover, treatment of ESCC cell lines with5-Aza-2'-deoxycytidine, a DNA methyltransferase inhibitor, reactivated the expression of TGFBR2. The lentiviral mediating the overexpression of TGFBR2 inhibited the proliferation of ESCC cell line by inducing cell cycle G2/M arrest. Furthermore, the overexpression of TGFBR2 inhibited the tumor growth obviously in vivo. CONCLUSIONS: The characterization of methylation silencing of TGFBR2 in ESCC will enable us to further explore whether this epigenetic change could be considered as a predictor of malignant transformation in esophageal epithelial dysplasia and whether use of a TGFBR2 agonist may lead to a new therapeutic strategy in patients with ESCC.

3.
Chemosphere ; 244: 125568, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32050347

RESUMO

Persulfate (PS) is widely used for environmental remediation, but its organic contaminant removal performance strongly depends on its activation. In this study, we demonstrate that pyrite (FeS2) can more effectively activate PS than the commonly used FeSO4 for atrazine degradation. When 3.0 mM of PS and 4.2 mM of iron salts were used, the atrazine degradation efficiency of FeS2/PS was 1.4 times that of FeSO4/PS, while the amount of consumed PS in case of FeS2 was only 53% of that by FeSO4. The better PS activation performance of FeS2 could be attributed to its slow and sustainable release of dissolved Fe(II), inhibiting the quenching reaction between •SO4-/•OH and Fe(II) ions, and thus producing more reactive oxygen species for the atrazine degradation. More importantly, the surface bound Fe(II) of FeS2 could activate molecular oxygen to generate superoxide radical (•O2-), which could further promote the effective decomposition of PS by accelerating the Fe(III)/Fe(II) redox cycle. This study unravels the roles of dissolved Fe(II) and surface bound Fe(II) on the persulfate activation, and provides a promising heterogeneous persulfate activator for pollutant control and environmental remediation.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32027477

RESUMO

Burn infection is one of the commonest causes of death in severely burned patients. Developing multifunctional biological nanomaterials have a great significance for the comprehensive treatment of burn infection. In this paper, we developed a hydrogel-based nano-delivery system with antibacterial activity and skin regeneration function, which was used for photodynamic antimicrobial chemotherapy (PACT) in the treatment of burns. The treatment system is mainly composed of porphyrin photosensitizer DVDMS and PLGA-encapsulated bFGF nanospheres that embedded in carboxymethyl chitosan (CMCS)-sodium alginate to form CSDP hybrid hydrogel. We systematically evaluated the inherent antibacterial performance, rheological properties, fluorescence imaging and biocompatibility of the CSDP nanosystem. Under mild photo-irradiation (30 J/cm2, 5 min), 10 µg/ml CSDP showed excellent antibacterial and antibiofilm activities, which eradicated almost 99.99% of Staphylococcus aureus and multidrug-resistant (MDR) S. aureus in vitro. KEGG analysis identified multiple signaling pathways were changed in MDR S. aureus after PACT. In the burn-infection model, CSDP-PACT successfully inhibited bacteria growth and concurrently promoted wound healing. Moreover, several regenerative factors were increased and some pro-inflammatory factors were reduced in the burn wounds of CSDP hydrogel treatment. These results suggest that the multifunctional CSDP hydrogel is a portable, light-triggered, anti-bacterial theranostic-platform and CSDP-PACT provides a promising strategy or the mechanically-based synergistic treatment of burn infections.

5.
Ultrason Sonochem ; 63: 104968, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31972375

RESUMO

Titanium dioxide (TiO2) nanoparticle has good photo-/sono-catalytic features, the reunion of this particle in solution-phase generally limits the extensive biomedical application. In the present study, the aggregation of TiO2 nanoparticles was alleviated by facile fabrication under different pH conditions. A novel TiO2 nanocomposite was further synthesized by properly conjugation with trace amount of DVDMS sensitizer (named DFT). The characterization, sonoactivity, as well as the antibacterial efficiency were specially evaluated. The results showed that the sonochemical activity of DFT was greatly improved as compared with the simple surface modification of TiO2 (F-TiO2) and free DVDMS, regarding to the hydroxyl radicals and singlet oxygen yields using the same ultrasound exposure. Moreover, ultrasonic stimulation of DFT exhibited excellent bacterial eradication, with up to 92.41% of killing efficiency in S. aureus. The flow cytometry analysis indicated an increased intracellular ROS and membrane disturbance by combination of DFT and ultrasound. The findings suggest that the proper fabrication and DVDMS incorporation greatly improved the sonocatalytic process of TiO2, and the ultrasound based biomedical applications of DFT deserve future deep investigation.

6.
Sci Total Environ ; 714: 136550, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31981865

RESUMO

Cadmium (Cd) pollution in soils has received considerable research attention globally, and sulphur-modified biochar (SBC) could combine the advantages of biochar and the sulphur element for Cd remediation. Biochar from agricultural waste is feasible, which has a low preparation cost. However, there are few studies regarding the effects of the sulphur modification of biochar on the Cd immobilization mechanism. This study aimed to research the Cd immobilization mechanism of pristine wheat straw biochar (BC) and sulphur-modified biochar (SBC), and the Cd immobilization effects of BC and SBC in Cd-contaminated soils. Elemental and SEM analysis confirmed that sulphur was successfully loaded on the pristine biochar. XPS analysis confirmed that there was a considerable discrepancy between adsorption mechanisms of Cd on BC and SBC. In particular, cadmium sorption on BC was due to Cd(OH)2 and CdCO3 precipitation formation and interaction with carbonyl and carboxyl groups, whereas on SBC, sorption was mainly due to CdS and CdHS+ formation and interaction with organic sulphide. In the incubation experiment, SBC and BC additions increased pH value and also reduced the available Cd concentrations in the soil. Compared with the control, the contents of available Cd in soil were significantly decreased by 15.86% ~ 22.10% and 22.72% ~ 27.90%, following treatments with BC and SBC, respectively.

7.
Eur J Med Chem ; 187: 111961, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31865017

RESUMO

Accumulation of tau protein aggregation plays a crucial role in neurodegenerative diseases, such as Alzheimer's disease (AD). Uncontrollable neuroinflammation and tau pathology form a vicious circle that further aggravates AD progression. Herein, we reported the synthesis of usnic acid derivatives and evaluation of their inhibitory activities against tau-aggregation and neuroinflammation. The inhibitory activity of the derivatives against the self-fibrillation of the hexapeptide AcPHF6 was initially screened by ThT fluorescence assay. Using circular dichroism and transmission electron microscopy, compound 30 showed the most potent inhibitory activity against AcPHF6 self-fibrillation. Compound 30 was further confirmed to inhibit the aggregation of full-length 2N4R tau protein by a heparin-induced mechanism. In addition, we investigated the anti-inflammatory activity of compound 30, and showed that compared with sodium usnate, it reduced NO release in LPS-stimulated mouse microglia BV2 cells. More importantly, 30 showed significant protective effects against okadaic acid-induced memory impairment in rats. Thus, 30 was a novel tau-aggregation and neuroinflammation inhibitor that represented a potential therapeutic candidate for AD.

8.
Int J Mol Sci ; 20(23)2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31801204

RESUMO

The JASMONATE ZIM DOMAIN (JAZ) proteins act as negative regulators in the jasmonic acid (JA) signaling pathways of plants, and these proteins have been reported to play key roles in plant secondary metabolism mediated by JA. In this study, we firstly isolated one JAZ from P. cablin, PatJAZ6, which was characterized and revealed based on multiple alignments and a phylogenic tree analysis. The result of subcellular localization indicated that the PatJAZ6 protein was located in the nucleus of plant protoplasts. The expression level of PatJAZ6 was significantly induced by the methyl jasmonate (MeJA). Furthermore, by means of yeast two-hybrid screening, we identified two transcription factors that interact with the PatJAZ6, the PatMYC2b1 and PatMYC2b2. Virus-induced gene silencing (VIGS) of PatJAZ6 caused a decrease in expression abundance, resulting in a significant increase in the accumulation of patchouli alcohol. Moreover, we overexpressed PatJAZ6 in P. cablin, which down-regulated the patchoulol synthase expression, and then suppressed the biosynthesis of patchouli alcohol. The results demonstrate that PatJAZ6 probably acts as a repressor in the regulation of patchouli alcohol biosynthesis, contributed to a model proposed for the potential JA signaling pathway in P. cablin.

9.
Hortic Res ; 6: 133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814986

RESUMO

Lysine succinylation is a novel, naturally occurring posttranslational modification (PTM) in living organisms. Global lysine succinylation identification has been performed at the proteomic level in various species; however, the study of lysine succinylation in plant species is relatively limited. Patchouli plant (P. cablin (Blanco) Benth., Lamiaceae) is a globally important industrial plant and medicinal herb. In the present study, lysine succinylome analysis was carried out in patchouli plants to determine the potential regulatory role of lysine succinylation in patchouli growth, development, and physiology. The global succinylation sites and proteins in patchouli plants were screened with an immunoprecipitation affinity enrichment technique and advanced mass spectrometry-based proteomics. Several bioinformatic analyses, such as function classification and enrichment, subcellular location predication, metabolic pathway enrichment and protein-protein interaction networking, were conducted to characterize the functions of the identified sites and proteins. In total, 1097 succinylation sites in 493 proteins were detected in patchouli plants, among which 466 succinylation sites in 241 proteins were repeatedly identified within three independent experiments. The functional characterization of these proteins indicated that the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, photosynthesis processes, and amino acid biosynthesis may be regulated by lysine succinylation. In addition, these succinylated proteins showed a wide subcellular location distribution, although the chloroplast and cytoplasm were the top two preferred cellular components. Our study suggested the important role of lysine succinylation in patchouli plant physiology and biology and could serve as a useful reference for succinylation studies in other medicinal plants.

10.
Arthritis Rheumatol ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31876388

RESUMO

OBJECTIVE: Monocular cell infiltration and type I IFN system activation play an important role in primary Sjögren's syndrome (pSS). This study aimed to clarify the mechanism of Poly (ADP-Ribose) Polymerase Family Member 9 (PARP9) on monocular cell infiltration triggered by type I IFN. METHODS AND RESULTS: Differentially expressed proteins (DEPs) (p < 0.05 and fold change > 1.20) were identified by proteomic study in PBMCs from pSS patients (n=30) and healthy controls (n=30). The overexpression of PARP9 and CXCL10 as well as their co-localization was confirmed in pSS. PARP9 levels in labial salivary glands (LSGs) rose with the increase of Chisholm scores, indicating that PARP9 may be a crucial contributor to mononuclear cells infiltration in pSS progression. Either downregulation of PARP9 by AAV5-PARP9-siRNA or DTX3L by AAV5-DTX3L-siRNA alleviated the infiltration of mononuclear cells in the SGs in NOD/Ltj female mice models. Additionally, IPA networks of DEPs demonstrated that PARP9, STAT1 and IFIT1 participated in the IFN-related pathway. LV-PARP9 transfection experiment in B cells verified PARP9 could upregulate the expression of IFIT1 and CXCL10. LV-IFIT1 transfection experiment showed that IFIT1 could upregulate the expression of CXCL10. Moreover, IFN-α intervention experiment illustrated that PARP9 and CXCL10 could be induced by IFN-α in B cells. CONCLUSION: This study is the first to implicate PARP9 as a regulator of infiltration of mononuclear cells in pSS progression and reveal that PARP9 increased CXCL10 expression through upregulating IFIT1 which is mediated by phosphorylation of STAT1. PARP9 might therefore be a novel therapeutic target for pSS.

11.
Adv Mater ; : e1904347, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31880354

RESUMO

As one kind of promising next-generation photovoltaic devices, perovskite solar cells (PVSCs) have experienced unprecedented rapid growth in device performance over the past few years. However, the practical applications of PVSCs require much improved device long-term stability and performance, and internal defects and external humidity sensitivity are two key limitation need to be overcome. Here, gadolinium fluoride (GdF3 ) is added into perovskite precursor as a redox shuttle and growth-assist; meanwhile, aminobutanol vapor is used for Ostwald ripening in the formation of the perovskite layer. Consequently, a high-quality perovskite film with large grain size and few grain boundaries is obtained, resulting in the reduction of trap state density and carrier recombination. As a result, a power conversion efficiency of 21.21% is achieved with superior stability and negligible hysteresis.

12.
Autophagy ; : 1-23, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31674265

RESUMO

Limited penetration of chemotherapeutic drugs through the blood brain barrier (BBB), and the increased chemo-resistance of glioma cells due to macroautophagy/autophagy, result in high tumor recurrence and extremely limited survival of glioma patients. Ultrasound-targeted microbubble destruction (UTMD) is a technique of transient and reversible BBB disruption, which greatly facilitates intracerebral drug delivery. In addition, sonodynamic therapy (SDT) based on ultrasound stimulation and a sonosensitizer, can be a safe and noninvasive strategy for treating glioma. We innovatively designed a smart "all-in-one" nanosensitizer platform by incorporating the sonoactive chlorin e6 (Ce6) and an autophagy inhibitor-hydroxychloroquine (HCQ) into angiopep-2 peptide-modified liposomes (designated as ACHL), which integrates multiple diagnostic and therapeutic functions. ACHL selectively accumulated in the brain tumors during the optimal time-window of transient UTMD-mediated BBB opening. The nanosensitizer then responded to a second ultrasonic stimulation, and simultaneously unloaded HCQ and generated ROS in the glioma cells. The sonotherapy triggered apoptosis as well as MAPK/p38-PINK1-PRKN-dependent mitophagy, in which the antioxidant relieved the sonotoxicity and MAPK/p38 activation, while the inhibition of MAPK/p38 attenuated the progression toward mitophagy by compromising redistribution of PRKN. Moreover, HCQ blocking autophagosome degradation, augmented intracellular ROS production and resulted in an oxidative-damage regenerative loop. ACHL-SDT treatment using this construct significantly inhibited the xenograft-tumor growth and prolonged the survival time of tumor-bearing mice, exhibiting an improved therapeutic efficiency. All together, we demonstrated a precision sonotherapy with simultaneous apoptosis induction and mitophagy inhibition, which served as an intelligently strategic sense of working alongside, providing new insights into the theranostics of brain tumors.Abbreviations: ACHL: Angiopep-2-modified liposomes loaded with Ce6 and hydroxychloroquine; ACL: Angiopep-2-modified liposomes loaded with Ce6; BBB: blood brain barrier; Ce6: chlorin e6; CHL: liposomes loaded with Ce6 and hydroxychloroquine; CL: liposomes loaded with Ce6; CNS: central nervous system; DDS: drug delivery system; EB: Evans blue; FUS: focused ultrasound; HCQ: hydroxychloroquine; LRP1: low density lipoprotein receptor-related protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MBs: microbubbles; MTG: MitoTracker Green; MTR: MitoTracker Red; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PBS: phosphate-buffered saline; PDI: polydispersity index; PINK1: PTEN induced kinase 1; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; SDT: sonodynamic therapy; SQSTM1: sequestome 1; TA: terephthalic acid; TEM: transmission electron microscopy; TUNEL: terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling; US: ultrasound; UTMD: ultrasound-targeted microbubble destruction.

13.
Sci Rep ; 9(1): 17142, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729422

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

14.
Org Lett ; 21(21): 8558-8562, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31565948

RESUMO

The first examples of type B polycyclic polyprenylated acylphloroglucinols with a bicyclo[5.3.1]hendecane core, hyperberins A (1) and B (2), were isolated from Hypericum beanii, together with three biosynthetic congeners. Their structures were established by a combination of NMR, electric circular dichroism (ECD), and X-ray diffraction analyses. These isolates indicated divergent cationic cyclization as key steps in the biosynthesis of PPAPs with diverse architectures. Compounds 1 and 2 were moderately cytotoxic and exhibited significant anti-inflammatory activities.

15.
Nanoscale ; 11(41): 19520-19528, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31573595

RESUMO

The therapeutic efficacy of anti-cancer nanomedicines is generally constrained due to limited accumulation in the solid tumors. In this study, we developed a biomimetic nano-carrier to enhance the chemo-therapeutic efficacy of doxorubicin and icotinib in a chemo-resistant non-small cell lung cancer (NSCLC) cell line harboring a mutation in the epidermal growth factor receptor (EGFR). The unique nanomedicine was prepared by coating with targeting cancer cell membrane proteins as highly specific ligands. The resulting biomimetic nanoparticles were highly stable and exhibited superior homologous targeting ability in vitro compared with control groups. In a mouse EGFR-mutated NSCLC xenograft model, intravenous injection of the biomimetic nanomedicine led to a high tumour inhibition rate (87.56%). Histopathological analysis demonstrated that the biomimetic nanomedicine had minimal side effects. Taken together, a cancer cell membrane-based biomimetic drug carrier can significantly enhance drug accumulation and improve therapeutic efficacy in cancers.

16.
Med. clín (Ed. impr.) ; 153(8): 305-311, oct. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-185414

RESUMO

Objectives: The aim of this study is to identify the clinical characteristics of primary Sjögren's syndrome (PSS) patients with pulmonary involvement and the associated factors for pulmonary involvement in PSS. Methods: We retrospectively reviewed clinical features, laboratory examinations, imaging tests, pathological results and therapeutic strategy of 367 PSS patients. Comparisons were made between two subgroups: PSS with pulmonary involvement and those without. Correlation between the pathology of minor salivary gland biopsy (MSGB) and diverse features with pulmonary involvement were detected by Pearson correlation analysis and associated factors were selected by multivariate logistic regression analysis. Results: The lung involved PSS patients had significantly higher level of inflammatory associated indexes (p<0.05). There is no significant correlation between pathology of MSGB and lung involvements. Age, elevated neutrophils level and hypoproteinemia are significantly associated with lung disease with in PSS cohort (p<0.05). As for therapeutic strategy, moderate dose prednisone (15-40mg/d) and cyclophosphamide (CTX) are mainly different between two subgroups. Conclusions: PSS patients with pulmonary involvements show enhanced inflammation. Age, elevated neutrophils level and hypoproteinemia are independent associated with pulmonary involvements in PSS patients. For those PSS with pulmonary involvement moderate dose of prednisone and CTX were still the mainstream


Objetivos: El objetivo de este estudio es identificar las características clínicas de los pacientes con afectación pulmonar en el síndrome de Sjögren primario (SSp), y los factores relacionados con la afectación pulmonar en el SSp. Métodos: Hemos revisado retrospectivamente las características clínicas, los análisis de laboratorio, las pruebas de imagen, los resultados patológicos y la estrategia terapéutica de 367 pacientes con SSp. Se realizaron comparaciones entre 2 subgrupos: SSp con afectación pulmonar y SSp sin afectación pulmonar. La correlación entre la patología de la biopsia de la glándula salival menor (BGSM) y diversas características con afectación pulmonar se detectó mediante el análisis de correlación de Pearson, y los factores asociados se seleccionaron mediante un análisis de regresión logística multivariable. Resultados: Los pacientes con afectación pulmonar en el SSp tenían niveles significativamente más altos de índices inflamatorios asociados (p<0,05). No encontramos una correlación significativa entre la patología de la BGSM y la afectación pulmonar. La edad, el nivel elevado de neutrófilos y la hipoproteinemia se asociaron de manera independiente con la enfermedad pulmonar en la cohorte de SSp (p<0,05). En cuanto a la estrategia terapéutica: prednisona en dosis moderada (15-40mg/d) y ciclofosfamida (CTX) fueron los principales medicamentos entre los 2 subgrupos. Conclusiones: Los pacientes con afectación pulmonar en el SSp tenían una inflamación más elevada que el grupo de pacientes con SSp sin afectación pulmonar. La edad, el nivel elevado de neutrófilos y la hipoproteinemia se asocian de manera independiente con la afectación pulmonar en pacientes con el SSp. Para aquellos pacientes con afectación pulmonar en el SSp, el tratamiento más común fue una dosis moderada de prednisona y CTX


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/complicações , Estudos de Coortes , Pneumopatias/patologia , Estudos Retrospectivos , Modelos Logísticos , Glândulas Salivares Menores/patologia , Biópsia , Hipoproteinemia/complicações , Pneumopatias/diagnóstico , Pneumopatias/tratamento farmacológico , Prednisona/administração & dosagem , Análise Multivariada
17.
Small ; 15(44): e1902945, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31531961

RESUMO

Studies on distinctive performances and novel applications of amorphous inorganic nanomaterials are becoming attractive. Herein, Ag2 S amorphous and crystalline nanodots (ANDs and CNDs) are prepared via facile methods. In vitro and in vivo studies indicate that Ag2 S ANDs, rather than CNDs, can induce the self-destruction of tumors, which can be attributed to their distinctive chemical properties, e.g., the higher electrochemical active surface area and lower redox potential well matching with the redox reaction requirement in the tumor microenvironment. Ag2 S ANDs can be oxidized by intracellular reactive oxygen species (ROS) to release Ag+ , which further stimulates high generation of intracellular ROS. This mutual stimulation damages the mitochondria, induces apoptosis, and leads to the self-destruction of the tumor. Moreover, Ag2 S ANDs do not show observable in vitro and in vivo side effects. These findings provide a promising self-destructive strategy for cancer therapy by utilizing distinctive chemical properties of inorganic nanomaterials, while avoiding complicated external assistance.

18.
Theranostics ; 9(21): 6269-6283, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534550

RESUMO

Sepsis is a major cause of patient mortality and morbidity from bacterial infections. Although neutrophils are known to be important in the development of sepsis, how distinctive neutrophil subtypes regulate inflammatory processes involved in septicemia remains unclear. Preconditioning protects organisms against subsequent higher-dose exposures to the same, or even different, stimuli. Several studies have reported various effects of preconditioning on immune cells. However, the detailed mechanisms underlying neutrophil-mediated protection through preconditioning in sepsis remain unknown. Methods: Flow cytometry was conducted to sort the mice peritoneal lavage cells and the blood samples from patients with sepsis. Western blotting and ELISA were carried out to elucidate the expression of TLR9 signal transduction pathway proteins. Histological analysis was used to assess the effect of InP on intestine and liver structure in tlr9-/- and cav-1-/- mice. Fluorescence microscopy, Co-IP, and FRET were carried out to determine the association of TLR9 with Cav-1. Results: We show that membrane toll-like receptor-9 positive (mTLR9+) neutrophils exert a protective effect against fatal bacterial infections through the process of inflammatory preconditioning (InP). InP, which occurs in the setting of a low-dose bacterial challenge, active ingredient is Monophosphoryl lipid A (MPLA), triggers the membrane translocation of TLR9 from the neutrophil cytosol, where it binds to Cav-1. Our findings showed that InP enables TLR9 to facilitate MyD88-mediated TRAF3 and IRF3 signal transduction. Depletion of either TLR9 or Cav-1 largely eliminates the neutrophil-mediated InP effect in sepsis models in vitro and in vivo. Further, examination of clinical samples from patients with sepsis showed that clinical outcomes and likelihood of recovery are closely correlated with mTLR9 and Cav-1 expression in circulating neutrophils. Conclusion: These results demonstrate that the TLR9-Cav-1 axis is a critical signaling pathway involved in the regulation of neutrophil-dependent MPLA mediated InP, and the presence of mTLR9+ neutrophils could be an attractive indicator of clinical outcomes in bacterial sepsis that could be further explored as a potential therapeutic target.

19.
World J Clin Cases ; 7(17): 2611-2616, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31559300

RESUMO

BACKGROUND: Aplasia cutis congenita (ACC) in newborns is a condition in which congenital defects or hypoplasia is present in part of the epidermis, dermis and even subcutaneous tissue (including muscle and bones). First reported by Cordon in 1767, ACC is a rare disease with a low incidence of 1/100000 to 3/10000. Currently, there are 500 cases reported worldwide. ACC can be accompanied by other malformations. The onset mechanism of the disease remains unknown but is thought to be correlated to factors such as genetics, narrow uterus, foetal skin and amniotic membrane adhesion, use of teratogenic drugs in early pregnancy and viral infection. CASE SUMMARY: In August 2018, we treated a newborn with ACC on the left lower limbs using a combination of ionic silver dressing and moist exposed burn ointment (MEBO) and achieved a satisfactory treatment outcome. The skin defects were observed on the external genitals and on areas from the left foot to 3/4 of the upper left side. Subcutaneous tissue and blood vessels were observed in the regions with skin defects. The following treatments were provided. First, the wound was rinsed with 0.9% sodium chloride solution followed by disinfection with povidone-iodine twice. And then MEBO was applied to the wound at a thickness of approximately 1 mm. After applying ionic silver dressing, the wound was covered with sterile gauze. The wound dressing was replaced every 2-3 d. At the 4-mo follow-up, the treatment outcome was satisfactory. There was minimal scar tissue formation, and limb function was not impaired. CONCLUSION: The combination of ionic silver dressing and MEBO to ACC is helpful.

20.
Dig Liver Dis ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31495599

RESUMO

BACKGROUNDS AND AIMS: Microsatellite instability (MSI) is one of the promising biomarkers in human colorectal cancers (CRCs), and it is influenced by an intricate gene interaction network. Hence, we aimed to identify and validate hub genes associated with MSI CRC and to illustrate its underlying mechanisms. METHODS: Weighted gene co-expression network analysis (WGCNA) was used to investigate potential regulatory targets and relationships between key modules and hub genes associated with MSI CRC. RESULTS: In the red module (r = 0.83), SET nuclear proto-oncogene (SET) was selected due to its high intra-modular connectivity and module membership. In the test sets, SET expression was downregulated in MSI CRCs compared to that in microsatellite stability (MSS) CRCs. SET expression level had a good performance in stratifying patients into MSI or MSS CRCs (area under the curve = 0.953). Moreover, the BRAF V600E mutation was highly associated with SET expression, and MSI/HLA- samples showed lower levels of SET mRNA expression than MSS/HLA- samples. Finally, gene set enrichment analysis (GSEA) indicated that patients in the SET low expression group were enriched in base excision repair. CONCLUSION: SET was identified and validated as a novel potential biomarker in MSI CRCs, and SET probably acts through regulating the base excision repair pathway.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA