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1.
Gene ; 766: 145153, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32950633

RESUMO

AIM: Acute lung injury (ALI) is the mild form of acute respiratory distress syndrome (ARDS) which is a common lung disease with a high incidence and mortality rate. Recent studies manifested that some circular RNAs were associated with ALI. In this study, we aimed to uncover the effect of circular RNA circ_0054633 on ALI initiation and progression and proposed a new mechanism related to ALI. METHODS: The lipopolysaccharides (LPS)-induced acute lung injury model were build both in vivo of rat and in vitro of primary murine pulmonary microvascular endothelial cells (MPVECs). Hematoxylin and eosin (H&E) was employed to observe the tissue morphology and estimate the degree of lung damage. We used real-time quantitative polymerase chain reaction (RT-qPCR) to measure the expression level of circ_0054633. The expression levels of inflammatory cytokines IL-17A and tumor necrosis factor-α (TNF-α) were detected by ELISA. The effects of circ_0054633 on MPVECs proliferation and apoptosis were detected with the help of CCK-8 and apoptosis assay, separately. The expression level of NF-κB p65 protein was measured by Western blot. RESULTS: circ_0054633, IL-17A, TNF-α and NF-κB p65 were all overexpressed in LPS-treated rat and MPVECs, and LPS enhanced the proliferation and apoptosis of MPVECs. While circ_0054633 silencing reversed the above promotion effects of LPS on IL-17A, TNF-α expression and MPVECs proliferation and apoptosis. CONCLUSIONS: Quietness of circ_0054633 alleviated LPS-induced ALI via NF-κB signaling pathway, implicating circ_0054633 may be a potential biomarker for diagnose and therapy of ALI.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Proliferação de Células/fisiologia , Células Endoteliais/metabolismo , Inflamação/metabolismo , NF-kappa B/metabolismo , RNA Circular/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Inflamação/induzido quimicamente , Interleucina-17/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
2.
Br J Neurosurg ; : 1-5, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33136440

RESUMO

OBJECTIVE: To explore the changes of a series of cytokines before and after percutaneous balloon kyphoplasty (PKP) and prognostic markers for response to PKP. METHODS: From 1 January 2019 to 31 May 2019, all single-level lumbar osteoporotic vertebral compression fracture (OVCF) patients diagnosed by MRI who matched the inclusion and exclusion criteria were enrolled in this study. They were classified into the effective group and the ineffective group based on the outcome after PKP. The levels of a series of inflammatory factors and indices of spinal functions were obtained before and after PKP. RESULTS: A total of 72 patients were included in this study, 59 in the effective group and 13 in the ineffective group. The anterior height (AH) and posterior height (PH) were 77.3 ± 11.2% and 91.2 ± 9.3%, respectively, in the effective group after PKP, which were higher than that in the ineffective group (p<.001). While, the Kyphotic angle, visual analog scale (VAS), and Oswestry Disability Index (ODI) score were 9.1 ± 4.3°, 3.1 ± 1.9, and 19.2 ± 4.1 in the effective group, which was lower than that in ineffective group (p<.001). The serum levels of IL-1ß, IL-6, and TNF-α were found significantly decreased after treatment in the effective group (p<.05). The logistic regression showed that the levels of IL-6 TNF-α and AH were significant predictor of outcome. CONCLUSIONS: Our results demonstrated that PKP can reduce the serum levels of IL-6, IL-1ß, and TNF-α, moreover, the IL-6, TNF-α, and AH were significant predictors of outcome.

3.
Aging (Albany NY) ; 122020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154189

RESUMO

The present study aims to elucidate the potential therapeutic role of lncRNA XIST in gastric cancer through regulation of microRNA-132 (miR-132) and paxillin (PXN) expression. The study employed 65 gastric cancer tissue specimens and SGC7901 cell lines. Our results demonstrated that expression of lncRNA XIST and PXN was significantly elevated while the expression of miR-132 was significantly reduced in gastric cancer tissues. Dual-luciferase, RNA pull-down and RIP assays demonstrated that lncRNA XIST up-regulated the PXN expression by competitively binding to miR-132. Moreover, silencing of lncRNA XIST and up-regulation of miR-132 could suppress tumor formation ability, cell proliferation and migration, but enhanced apoptosis in gastric cancer. However, the overexpression of PXN achieved the opposite tumor-promotive effect. Meanwhile, rescue experiments suggested that silencing of lncRNA XIST could reverse the tumor-promotive effect exerted by either miR-132 inhibitor or PXN. Taken together, the present study demonstrates lncRNA XIST as a novel oncogenic lncRNA in gastric cancer, highlighting its therapeutic role in this disease.

4.
Life Sci ; : 118734, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33166590

RESUMO

AIMS: RNA regulatory genes were closely associated with tumorigenesis and prognosis in multiple tumors. Copy number variation (CNV) is a frequent characteristic in soft tissue sarcomas (STS). However, little is known regarding their possible roles in STS. MAIN METHODS: RNA sequence profiles and CNV data of 255 STS patients were downloaded from the Cancer Genome Atlas (TCGA). The correlation analysis involved CNVs of RNA regulatory genes, patient survival, immune infiltration, and DNA methylation. Drug sensitivity (IC50) was analyzed and validated by MTT assays in STS cell lines. KEY FINDINGS: CNV events were frequently observed in all kinds (m6A, m5C, ac4C, m1A, m3C, m6Am, m7G, and Ψ) of RNA regulatory genes. Diploid copy number (CN) of METTL4 was associated with better overall survival (OS) in STS and the subtypes (leiomyosarcoma, LMS; dedifferentiated liposarcoma, DDLPS). In STS and LMS, diploid CN of METTL4 was significantly associated with higher infiltration fraction of resting mast cells. In STS and DDLPS, diploid CN of METTL4 possessed lower methylation level in CpG site of cg12105018, which represented better OS. Besides, sensitive drugs for STS cell lines were analyzed according to lower IC50 for the loss CN of METTL4. Temozolomide and Olaparib were identified. Further validation by MTT assays demonstrated that GCT was the most sensitive cell line to both Temozolomide and Olaparib. SIGNIFICANCE: CNV of METTL4 could be a prognostic biomarker for STS by potentially influencing mast cell infiltration and DNA methylation. Besides, STS with loss CN of METTL4 would be sensitive to Temozolomide and Olaparib.

5.
Cancer Gene Ther ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33199830

RESUMO

Gastric cancer (GC) is a common cancer and a leading cause of cancer-related deaths worldwide. Recent studies have supported the important role of long non-coding RNAs (lncRNAs) in GC progression. This study identified functional significance of X inactive specific transcript (XIST) in GC. The expression of XIST and EPHA1 in GC tissues and cells was measured. Then, dual luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay and Chromatin Immunoprecipitation (ChIP) assay were performed to explore the interaction among XIST, EPHA1 and HNF4A. The effects of XIST on GG progression were evaluated by determining expression of proliferation- and invasion-related proteins (Ki67, PCNA, MMP-2, and MMP-9). Further, the functional role of XIST in GC with the involvement of NFκB pathway was also analyzed. Subsequently, the tumor growth in nude mice was evaluated. High expression of XIST and EPHA1 was observed in GC. XIST elevated EPHA1 expression by recruiting HNF4A. In addition, silencing of XIST inhibited GC progression in vitro and in vivo. Overexpressed XIST and EPHA1 yielded a reversed effect on cell proliferation and invasion. SN50 treatment (inhibitor of NFκB pathway) counteracted the promotive effect on GC cell proliferation and invasion mediated by XIST. The present study unveils that XIST increases the enrichment of HNF4A in the promoter region of EPHA1, thus promoting the deterioration of GC.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33210545

RESUMO

The primary aim was to identify potential risk factors for early conversion to total knee arthroplasty (TKA) in patients with high tibial osteotomy (HTO) surgery. A retrospective study was conducted and 240 patients received HTO surgery between January 2008 and January 2014 were included in this study. The associations between different clinical factors and HTO survivorship were analyzed. A logistic regression analysis was performed to detect independent risk factors for HTO survivorship. The cut-off value, sensitivity and specificity of these independent factors were calculated by receiver operating characteristic (ROC) curve. In this study, thirty-five (14.6%) patients were early conversion to TKA within a 5-year follow-up. These results indicated that age, body mass index (BMI), preoperative Kellgren-Lawrence (K-L) grade and preoperative visual analogue scale (VAS) score were potential risk factors for HTO survivorship. The cut-off values of those factors were 60 years, 25.35 kg/m2, 2 and 5, respectively. The combination of age, BMI, preoperative K-L grade and preoperative VAS score has the highest predictive value for HTO survivorship (AUC = 0.896, P < 0.001). Based on the present study, the five-year HTO survivorship for the treatment of medial compartment osteoarthritis of the knee was approximately 85.4%. We identified age >60 years, BMI >25.35 kg/m2, preoperative K-L grade >2 and preoperative VAS score >5 as independent risk factors for early conversion to TKA in patients with HTO surgery, and those factors combined had the highest predictive value for predicting early conversion to TKA.

7.
Ecotoxicol Environ Saf ; 206: 111406, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007542

RESUMO

Environmental air pollutants pose significant threats to public health, especially the toxicity and diseases caused by the atmospheric fine particulate matters (PM2.5). Since the health risks vary with both the concentrations and compositions of PM2.5 which are determined by aerosol sources, how are their toxic effects relevant to the pollution level becomes an important issue, such as the haze episodes covering clean and polluted days. With the transition from non-pollution to pollution stage, daily PM2.5 samples were collected from both the urban and industrial areas of Nanjing city, eastern China, covering a typical haze event in autumn-winter. Their unpropitious effects on human lung epithelial cells (A549) were compared by in vitro toxicity assays and chemical component analysis. Both air levels and cytotoxic effects of PM2.5 varied with the transition of haze event. Although the concentration of PM2.5 in air is of course the highest in pollution stage driven by local stable meteorological condition, unit mass of them posed higher toxicity (lower cell viability and higher IL-6) but induced lower cell oxidative (evidences of ROS and NQO1 mRNA expression) and inflammatory cytokine TNF-α responses than those particles during non-pollution stage. These patterns were explained by the metals and water-soluble components decreased with the haze development. Non-soluble particulate carbonaceous aerosol compositions might play a significant role in inducing cytotoxicity. Moreover, the regional pattern of episode pollution weakened the spatial variation within a city scale. Since the haze development intensified both the quantity and toxicity of PM2.5 in air, the health risks of overall aerosol exposure were synthetically amplified during haze weather, so the increased air particles with higher toxic components from fuel combustion sources should be key targets of pollution control.

8.
Phys Chem Chem Phys ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057555

RESUMO

Tuning the electrical transport behavior and reducing the Schottky barrier height of nanoelectronic devices remain a great challenge. To solve this issue, the electronic properties and Schottky barrier of the graphene/WSe2 heterostructure are investigated by the first-principles method under out-of-plane strain and an electric field. Our results show that the WSe2 monolayer and graphene could form a stable van der Waals heterostructure and the intrinsic electronic properties are well preserved. Furthermore, a transformation of a Schottky contact from the n-type to p-type occurs at d = 3.87 Å and E = +0.06 V Å-1. In addition, an ohmic contact is formed with E = -0.50, ±0.60 V Å-1. Lastly, the effective masses of electrons and holes are calculated to be 0.057m0 and -0.055m0 at the equilibrium state, respectively, indicating that the heterostructure has a high carrier mobility. Our research will provide promising approaches for the future design and development of graphene/WSe2 nano-field effect transistors.

9.
Nanotechnology ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33007765

RESUMO

The effect of gold and silver plasmonic films on InP/ZnSe/ZnSeS/ZnS nanocrystals (quantum dots) photoluminescence as well as on their photostability is reported. Colloidal gold films promote InP/ZnSe/ZnSeS/ZnS quantum dots photostability enhancement (more durable emission properties in presence of metal nanostructures) through reducing exciton lifetime. Silver, contrariwise, decreases InP/ZnSe/ZnSeS/ZnS quantum dots photostability without changing the photoluminescence intensity and kinetics. By adjusting the excitation wavelength closer to the extinction band of gold nanoparticles a 1.8-fold enhancement of luminescence intensity has been obtained using a polyelectrolyte spacer between the metal and InP/ZnSe/ZnSeS/ZnS nanoparticles. Thus plasmonics offers essential practical improvement of light emitters in terms of their durable luminescent properties upon prolonged optical excitation without losses in luminescence efficiency or even along with gain in efficiency.

10.
Anal Chem ; 92(22): 15145-15151, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33124411

RESUMO

MicroRNA (miRNA) has become a key indicator of cancer diagnosis based on its abnormal expression levels. However, high-performance monitoring of miRNA is still a difficult task because of its low concentration, small size, and similarity of sequences. Herein, an elegant and robust photoelectrochemical (PEC) biosensor for miRNA-122 has been flexibly designed based on the split mode between entropy-driven DNA signal amplification and photocurrent expression. The entropy-driven DNA circuit uses a multichain composite structure instead of a DNA hairpin structure, leading to decrease the reversibility of each step of the signal amplification system. Also, the unique increasing entropy mechanism, rather than the free energy release from the new base pairs forming, improves the reaction efficiency and enhances more thermal stability and strong specific identification ability. Particularly, the biologically functionalized superparamagnetic Fe3O4@SiO2 complex endows this split mode PEC biosensor with excellent specificity and enhanced efficiency of electrode fabrication. Additionally, this strategy of only the CdTe-signal DNA modified on the ITO electrode for photocurrent readout overcomes the shortcomings of tediously long layer-by-layer assembly process and multiple rinsing steps, leading to efficient improvement of the stability and reproducibility for the as-designed PEC biosensor. This elegant strategy opens a new path for miRNA measurements with superior performance.

11.
Cancer Med ; 9(16): 5719-5730, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32946170

RESUMO

Based on accumulating evidence, long noncoding RNAs (lncRNAs) are potential biomarkers and therapeutic targets for many diseases, including tumors. In this study, we consulted The Cancer Genome Atlas (TCGA) database to explore the functions and modulatory mechanisms of lncRNAs as competing endogenous RNAs (ceRNAs) in hepatocellular carcinoma (HCC) in Asian patients and constructed a risk scoring system composed of four lncRNAs (SNHG1, STEAP3-AS1, RUSC1-AS1, and SNHG3) to predict the outcomes of Asian patients with HCC. The prognostic value of this risk model was validated in the internal validation cohort (n = 157). The stratified survival analysis revealed good performance for the risk model in stratifying clinical features. According to the Cox proportional hazard regression analysis, the four-lncRNA risk model is an independent prognostic model for Asian patients with HCC. Finally, we developed a nomogram that integrates prognostic signals and other clinical information to predict 1-, 3-, and 5-year overall survival rates. In conclusion, the prognostic lncRNAs identified in our study exerted potential biological effects on the development of HCC. The risk scoring model based on four lncRNAs may be an effective classification tool for assessing the prognosis of Asian patients with HCC.

12.
Sensors (Basel) ; 20(17)2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32872634

RESUMO

Lipid content is an important indicator of the edible and breeding value of Pinus koraiensis seeds. Difference in origin will affect the lipid content of the inner kernel, and neither can be judged by appearance or morphology. Traditional chemical methods are small-scale, time-consuming, labor-intensive, costly, and laboratory-dependent. In this study, near-infrared (NIR) spectroscopy combined with chemometrics was used to identify the origin and lipid content of P. koraiensis seeds. Principal component analysis (PCA), wavelet transformation (WT), Monte Carlo (MC), and uninformative variable elimination (UVE) methods were used to process spectral data and the prediction models were established with partial least-squares (PLS). Models were evaluated by R2 for calibration and prediction sets, root mean standard error of cross-validation (RMSECV), and root mean square error of prediction (RMSEP). Two dimensions of input data produced a faster and more accurate PLS model. The accuracy of the calibration and prediction sets was 98.75% and 97.50%, respectively. When the Donoho Thresholding wavelet filter 'bior4.4' was selected, the WT-MC-UVE-PLS regression model had the best predictions. The R2 for the calibration and prediction sets was 0.9485 and 0.9369, and the RMSECV and RMSEP were 0.0098 and 0.0390, respectively. NIR technology combined with chemometric algorithms can be used to characterize P. koraiensis seeds.

13.
Inorg Chem ; 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32951430

RESUMO

Blue phosphorescent tetradentate pyridyl-carbolinyl Pt(II) complexes, Pt(ppzOclpy-Me), Pt(ppzOclpy-iPr), and Pt(ppzOclpy-mesi), were purposefully synthesized and investigated with their photophysical and luminescent properties. The complexes, incorporating with carbolinyl moieties, have twisted planar structure. X-ray crystallography revealed that the intraligand N···H-C hydrogen bond reversely turned the twisty pyridyl moiety back into the chelating plane. Computational analyses confirmed that the metal-to-ligand charge-transfer transition character appears in the singlet manifolds. However, the ligand-centered transitions rule in their triplet states, which accounts for the phosphorescent emission. The Pt(II) complexes emit blue light with peak wavelengths (λmax) of 461-481 nm and moderate photoluminescent quantum yields (Φ = 34-46% in dichloromethane and Φ = 44-52% in films). The electroluminescent devices were fabricated by solution processes, giving blue emissions peaking at around 470 nm.

14.
Biosens Bioelectron ; 169: 112588, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32956905

RESUMO

Electrophysiological study that records the action potential of cardiomyocyte served as excellent tool to explore cardiology and neuroscience, disease investigation and pharmacological screening. Advances of micro/nanotechnologies promote the development of three-dimensional (3D) nanodevices to record high-quality intracellular recordings by various perforation approaches of cells, however, the complicated fabrication processes limited their large-scale manufacture. In this work, a unique nanobranched microelectrode array (NBMEA) platform is developed to achieve high-quality intracellular recording of cultured cardiomyocytes in a minimally invasive manner. The NBMEA is consisting of high aspect ratio conductive nanobranches fabricated on patterned microelectrodes combining hydrothermal growth and standard microfabrication. The 3D structure of nanobranches enables the electrode to form tight coupling with cardiomyocytes to achieve the low voltage cell electroporation and high-quality intracellular recording. The recorded intracellular action potentials of cardiomyocytes by NBMEA exhibited significant enhancement on amplitude (~5 mV), signal-to-noise ratio (SNR) (~67.47 dB), recording duration (up to 105 min), and recording yield (69.5 ± 17.8%). This NBMEA platform is a promising and powerful tool for electrophysiology that opens up new opportunities for high-quality and stable intracellular recording of cardiomyocytes.

15.
Environ Int ; 145: 106130, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32971417

RESUMO

We conducted a cross-sectional study with 395 completely matched student samples enrolled from a public primary school in Nanjing of eastern China, including questionnaires, blood samples, growth indexes and school performances, all of which were used for the analysis of variance (ANOVA) and general linear model (GLM). The results showed that factors, such as gender, age, parents' education, residential passive smoking and picky eaters, had significant impacts on the blood lead levels (BPbs). As for the linear and non-linear dose-response relationship between BPbs and erythrocyte parameters, we found a positive association between BPbs and red blood cell count (RBC count) and mean corpuscular hemoglobin concentration (MCHC) but a negative association between BPbs and hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). When BPbs increased by 10 µg/L, the RBC count increased by 0.18 × 1012/L, while HGB and HCT decreased by 1.19 g/L and 0.41% for boys, respectively. As for girls, corresponding increases in RBC count was 0.05 × 1012/L, while HGB and HCT decreased by 0.82 g/L and 0.23%. Meanwhile, for both boys and girls, MCHC increased by 2.55 g/L, while MCV and MCH levels decreased by 0.41 fL and 0.12 pg each. Furthermore, a remarkable adverse effect (p < 0.05) was observed on children's school performances as a result of increased BPbs. As BPbs increased by 10 µg/L, children's scores for Chinese, Math and English decreased by 0.42 points, 0.39 points and 0.87 points, respectively. In summary, our study indicated that lead exposure can have adverse health effects on children's erythrocyte parameters, BMI, and school performances.

16.
J Opt Soc Am A Opt Image Sci Vis ; 37(9): 1404-1410, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32902427

RESUMO

We establish the propagation model of orbital angular momentum (OAM) modes carried by hollow vortex Gaussian (hvG) beams propagating in anisotropic atmospheric turbulence. Effects of light source parameters and atmospheric conditions on the OAM mode propagation performance are investigated in detail. The findings indicate the hvG beam with a smaller OAM quantum number, a larger beam order, or a longer source wavelength has more robust resistance to atmospheric turbulence interference. The waist width of the light source has different influences on the OAM mode propagation at different propagation distances. Atmospheric turbulences with larger values of anisotropy, inner-scale factor, non-Kolmogorov power spectrum index, and altitude are favorable for the OAM mode propagation. These research results are conducive to optimizing the design of light sources and space wireless communication systems with hvG beams.

17.
J Hazard Mater ; 399: 122895, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32937698

RESUMO

Arsenic-hyperaccumulator Pteris vittata is efficient in As absorption, reduction, and translocation. But the molecular mechanisms and locations of arsenate (AsV) reduction in P. vittata are still unclear. Here, we identified two new arsenate reductase genes from P. vittata, PvHAC1 and PvHAC2. Two PvHAC genes encoded a rhodanase-like protein, which were localized in the cytoplasm and nucleus. Both recombinant Escherichia coli strains and transgenic Arabidopsis thaliana lines showed arsenate reductase ability after expressing PvHAC genes. Further, expressing PvHAC2 enhanced As tolerance and reduced As accumulation in A. thaliana shoots under AsV exposure. Based on expression pattern analysis, PvHAC1 and PvHAC2 were predominantly expressed in the rhizomes and fronds of P. vittata. Different from those of HAC homologous genes in non-hyperaccumulators, little PvHAC was expressed in the roots. Besides, PvHAC1 expression was strongly upregulated under AsV exposure but not AsIII. The data suggest that arsenate reductase PvHAC1 in the rhizomes coupled with arsenate reductase PvHAC2 in the fronds of P. vittata played a critical role in As-hyperaccumulation by P. vittata, which helps to further improve its utility in phytoremediation of As-contaminated soils.

18.
Theranostics ; 10(21): 9477-9494, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32863940

RESUMO

Background: Patients with advanced soft tissue sarcomas (STS) have a dismal prognosis with few effective therapeutic options. A defect in the homologous recombination repair (HRR) pathway can accumulate DNA repair errors and gene mutations, which can lead to tumorigenesis. BRCAness describes tumors with an HRR deficiency (HRD) in the absence of a germline BRCA1/2 mutation. However, the characteristics of BRCAness in STS remain largely unknown. Thus, this study aimed to explore the genomic and molecular landscape of BRCAness using whole exome sequencing (WES) in STS, aiming to find a potential target for STS treatment. Methods: WES was performed in 22 STS samples from the First Affiliated Hospital of Sun Yat-sen University to reveal the possible genomic and molecular characteristics. The characteristics were then validated using data of 224 STS samples from The Cancer Genome Atlas (TCGA) database and in vitro data. The analysis of the potential biomarker for BRCAness was performed. Targeted drug susceptibility and combination therapy screening of chemotherapeutics for STS were evaluated in STS cell lines, cell-line-derived xenografts (CDX), and patient-derived xenografts (PDX). Results: Compared with 30 somatic mutation signatures of cancers, high cosine-similarity (0.75) was identified for HRD signatures in the 22 STS samples using nonnegative matrix factorization. Single nucleotide polymorphism indicated a low mutation rate of BRCA1/2 in the 22 STS samples (11.76% and 5.88%, respectively). However, copy number variation analyses demonstrated widespread chromosomal instability; furthermore, 54.55% of STS samples (12/22) carried BRCAness traits. Subsequently, similar genomic and molecular characteristics were also detected in the 224 STS samples from TCGA and in vitro. Poly (ADP-ribose) polymerases (PARP)-1 could be a promising reflection of HRD and therapeutic response. Furthermore, the level of PAR formation was found to be correlated with PARP-1. Subsequently, STS cell lines were determined to be sensitive to PARP inhibitor (PARPi), niraparib. Moreover, based on the screening test of the five common PARPis and combination test among doxorubicin, ifosfamide, dacarbazine, and temozolomide (TMZ), niraparib and TMZ were the most synergistic in STS cell lines. The synergistic effect and safety of niraparib and TMZ combination were also shown in CDX and PDX. Conclusions: BRCAness might be the common genomic and molecular characteristics of majority of STS cases. PARP-1 and PAR could be potential proper and feasible theranostic biomarkers for assessing HRD in patients. STSs were sensitive to PARPi. Moreover, the combination of niraparib and TMZ showed synergistic effect. Niraparib and TMZ could be a promising targeted therapeutic strategy for patients with STS.

19.
ANZ J Surg ; 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32808444

RESUMO

BACKGROUND: This study aimed to investigate the value of inflammatory markers for the prediction of small bowel obstruction (SBO) following appendectomy. METHODS: We included cases of acute appendicitis that underwent laparoscopic appendectomy (LA) in the Qingdao Municipal Hospital between January 2017 and January 2019. The cases were divided into an SBO group and a non-SBO group depending on whether patients had or did not have SBO, and patients were followed up for at least 1 year. The levels of interleukin (IL)-1ß, IL-6 and tumour necrosis factor-alpha (TNF-α) in abdominal exudate and venous blood were examined using enzyme-linked immunosorbent assay. RESULTS: After 1 year of follow-up, there were 985 cases in the non-SBO group and 16 cases in the SBO group. The levels of IL-1ß, IL-6 and TNF-α in abdominal exudate on post-operative day 1 in the SBO group were 172.5 ± 14.7, 2167.3 ± 372.1 and 253.9 ± 12.9 pg/mL, respectively, which were significantly higher than that in the non-SBO group. The serum levels of IL-1ß, IL-6, TNF-α and C-reactive protein (CRP) in the SBO group were significantly higher than that in the non-SBO group before surgery. Post-operatively, the inflammatory markers above decreased significantly and became similar with time in both groups. The logistic regression showed that the levels of peritoneal IL-6, preoperative serum CRP and perforated appendicitis were significant risk factors of SBO. The specificity and sensitivity of peritoneal IL-6 were 0.81 and 0.921, respectively. CONCLUSION: The IL-1ß, IL-6, TNF-α and CRP in serum and abdominal exudate played an important role in SBO after LA. The peritoneal IL-6 was the most reliable prediction marker for SBO.

20.
Exp Ther Med ; 20(3): 2828-2837, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32765779

RESUMO

The present study aimed to investigate the effect of carbachol on the intestinal tight-junction barrier in a rat model of severe acute pancreatitis (SAP) without aggravating pancreatic injury, and to determine whether cell division cycle 42 (Cdc42)/F-actin could have a regulatory role. Rats were separated into a sham-operation (SO) group (n=10), SO + carbachol group (n=10), SAP group (n=60) and SAP + carbachol group (n=60). Sodium taurocholate (5%) was retrogradely injected into the biliopancreatic duct of rats to induce SAP. Subsequently, 16S rRNA sequencing was used to detect bacterial translocation (BT) in the gut of surviving animals. Hematoxylin and eosin staining was used to detect morphological changes in the pancreas and intestine. The expression of F-actin and tight junction proteins was analyzed by western blotting and immunofluorescence, and Cdc42 expression was analyzed by immunohistochemistry and western blotting. The results demonstrated that the intestinal injury in SO and SO + carbachol groups was lower than that in the SAP + carbachol group (P<0.05); however, the intestinal injury was similar in the SO and SO + carbachol groups (P>0.05), and was significantly more severe in the SAP group compared with the SAP + carbachol group (P<0.05). Similarly, pancreatic injury in the SAP and SAP + carbachol groups was significantly higher compared with the SO and SO + carbachol groups (P<0.05); however, pancreatic injury was similar in the SAP and SAP + carbachol groups (P>0.05), and in the SO and SO + carbachol groups (P>0.05). Furthermore, the mortality rate and BT in the SAP group were significantly higher compared with the SAP + carbachol group (mortality rate, 50% vs. 30%, P<0.05; BT, 60% vs. 33.3%, P<0.05). In addition, the expression of Cdc42, F-actin and claudin-2 was significantly higher in the SAP and SAP + carbachol groups compared with the SO and SO + carbachol groups (P<0.05), and the expression of occludin and zonula occludens-1 were significantly higher in the SO and SO + carbachol groups compared with the SAP and SAP + carbachol groups (P<0.05). In conclusion, these findings demonstrated that carbachol may protect the intestinal barrier in the SAP rat model without aggravating pancreatic injury via regulation of Cdc42/F-actin expression.

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