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1.
J Invest Surg ; : 1-6, 2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32036714

RESUMO

Background: The comparisons between open surgery and minimally invasive surgery for treatment of large adrenal tumor (LAT) are still lacking. In this study, we attempted to explore the safety and effectiveness of laparoscopic treatment of LAT by comparing the outcomes between open adrenalectomy (OA) and laparoscopic adrenalectomy (LA).Methods: From 2003 to 2018, 78 LAT patients underwent tumor resection by OA or LA method at a single academic institution. Data were retrospectively collected and analyzed.Results: The median largest diameter of LAT was 10.0 (IQR 9.0-13.4) cm. The median operation time in OA group was 215 (IQR 180-240) min versus 180 (IQR 135-245) min in LA group (P = 0.042). The median blood loss in OA group was 1000 (IQR 625-1500) ml versus 200 (IQR 100-700) ml in LA group (P < 0.001). The median Clavien-Dindo score in OA group was 2 (IQR 2-4) versus 0 (IQR 0-4) in LA group (P = 0.035). On univariate and multivariate analysis, the largest diameter of tumor was significantly associated with operation time, blood loss, and recovery time (P < 0.05).Conclusions: Laparoscopic treatment of LAT was found to be safe and feasible in experienced hands and can replace open surgeries in most cases.

2.
J Med Chem ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32039596

RESUMO

Photodynamic therapy (PDT) has emerged as a promising noninvasive treatment option for cancers and other diseases. The key factor that determines the effectiveness of PDT is the photosensitizers (PSs). Upon light irradiation, the PSs would be activated, produce reactive oxygen species (ROS), and induce cell death. One of the challenges is that traditional PSs adopt a large flat disc-like structure, which tend to interact with the adjacent molecules through strong π-π stacking that reduces their ROS generation ability. Aggregation-induced emission (AIE) molecules with a twisted configuration to suppress strong intermolecular interactions represent a new class of PSs for image-guided PDT. In this Miniperspective, we summarize the recent progress on the design rationale of AIE-PSs and the strategies to achieve desirable theranostic applications in cancers. Subsequently, approaches of combining AIE-PS with other imaging and treatment modalities, challenges, and future directions are addressed.

3.
Sci Rep ; 10(1): 253, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937849

RESUMO

Controlling the lasing mode, emission direction, threshold, and quality factor of whispering-gallery mode lasing is important for practical applications such as optical interconnections, on-chip communications, trace detection, high-density storage, etc. In order to simultaneously control the mode and emission direction and to achieve a high-quality factor in a low-threshold whisper-gallery mode laser, such as a GaN floating microdisk, a novel fabrication design of a microdisk with a vertical slit is proposed. To demonstrate proof of concept, we experimentally measure whispering-gallery mode lasing spectra of microdisks with and without a slit. Our findings suggest that the disks can indeed operate in whispering-gallery mode, and the slit is able to change the optical path in the microcavity without breaking lasing resonance. The slit in the microdisk can also influence the lasing mode, quality factor, and directional emission. Therefore, our study provides a feasible way to control whispering-gallery mode lasing properties.

4.
J Mater Chem B ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31951233

RESUMO

Reactive oxygen and nitrogen species (RONS) are an important class of oxidative stress mediators which are tightly associated with several diseases. Therefore, it is important to develop an accurate and reliable method for the in situ monitoring of biologically relevant RONS. Fluorescent bioprobes exhibit remarkable sensing properties such as easy operation, rapid response and good sensitivity, and thus have emerged as powerful tools in diverse biomedical applications. Benefiting from remarkable photophysical advantages like large Stokes' shifts, high signal-to-noise ratios and excellent photostability, aggregation-induced emission (AIE) luminogens (AIEgens) show unique superiority for RONS sensing and are widely applied in diverse biomedical applications. In this review, we first introduce the concept of RONS and the sensing principles of RONS by AIE bioprobes. Then we summarize the current state of AIEgens for RONS sensing with some representative examples. Finally, we present a perspective on the future development of RONS sensing based on AIEgens. We hope our review can inspire more endeavors in this fascinating area, further promoting the use of AIEgens in diagnostic analysis and therapy.

6.
J Bone Miner Res ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910305

RESUMO

Epigenetic regulation is highly correlated with osteoarthritis (OA) development, whereas its role and detailed mechanisms remain elusive. In this study, we explored the expression of EZH2, an H3K27me3 transferase, in human OA cartilages and its roles in regulating OA pathogenesis. Here, we found EZH2 was highly expressed in both mice and human OA cartilage samples by using histological analysis and RNA sequencing (RNA-Seq). The medial meniscectomy (MMx) OA model results indicated the conditional knockout of Ezh2 deteriorated OA pathological conditions. Furthermore, we showed the positive role of Ezh2 in cartilage wound healing and inhibition of hypertrophy through activating TNFSF13B, a member of the tumor necrosis factor superfamily. Further, we also indicated that the effect of TNFSF13B, increased by Ezh2, might boost the healing of chondrocytes through increasing the phosphorylation of Akt. Taken together, our results uncovered an EZH2-positive subpopulation existed in OA patients, and that EZH2-TNFSF13B signaling was responsible for regulating chondrocyte healing and hypertrophy. Thus, EZH2 might act as a new potential target for OA diagnosis and treatment. © 2020 American Society for Bone and Mineral Research.

7.
Nat Protoc ; 15(2): 316-337, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31915388

RESUMO

Current visual biosensing methods, including colorimetric-based, fluorescence-based and chemiluminescence-based methods, are inappropriate for the hundreds of millions of people affected by color blindness and color weakness. Compared with these available methods, a droplet motion-based strategy might be a promising protocol for extension to a wider user base. Here we report a protocol for manipulating the hydrophobicity of DNA, which offers a droplet motion-based biosensing platform for the visual detection of small molecules (ATP), nucleic acids (microRNA) and proteins (thrombin). The protocol starts with target-triggered rolling-circle amplification that can readily generate short single-stranded DNA (ssDNA) fragments or long ssDNA. By exploiting macroscopic wetting behavior and molecular interaction, one can tailor the conformation of ssDNA on the water-oil interface to control the relevant DNA hydrophobicity. The wettability of DNA can be translated into visual signals via reading the sliding speed or the critical sliding angle. The time range for the entire protocol is ∼1 d, and the detection process takes ∼1 min.

8.
Brain Behav ; 10(2): e01517, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31943892

RESUMO

OBJECTIVE: Delayed cerebral ischemia (DCI) greatly contributes to the high morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH) patients. Expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was substantially raised in the basilar arterial wall of SAH rabbits. We attempted to ascertain the relationship between serum soluble LOX-1 (sLOX-1) levels and the occurrence of DCI after aSAH. MATERIALS AND METHODS: We enrolled 125 aSAH patients and 125 healthy controls. Serum sLOX-1 levels were quantified using commercial enzyme-linked immunosorbent assay kit. The relationship between sLOX-1 levels and DCI was analyzed utilizing the multivariate logistic regression analysis. RESULTS: Serum sLOX-1 levels were significantly higher in stroke patients than in controls (median: 1,450.2 vs. 445.7 pg/ml, p < .001). Serum sLOX-1 levels were highly correlated with World Federation of Neurological Surgeons (WFNS) scores, Hunt-Hess scores, and modified Fisher scores (r = .574, .625, and .569, respectively). Forty-two patients (33.6%) experienced DCI. Serum sLOX-1 > 1,450.2 pg/ml, WFNS scores and modified Fisher scores were the independent predictors of DCI. Under receiver operating characteristic curve, serum sLOX-1 levels exhibited a significant discriminatory capability (area under curve 0.825, 95% confidence interval 0.747-0.887). The predictive power of serum sLOX-1 levels was similar to those of WFNS scores and modified Fisher grade (both p > .05). Moreover, serum sLOX-1 levels significantly improved their predictive capability (both p < .05). CONCLUSIONS: Serum soluble LOX-1, in positive association with hemorrhagic severity, appears to have the potential to become a promising predictor of DCI after aSAH.

9.
Mini Rev Med Chem ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31902359

RESUMO

Many berberine derivatives have been synthesized for their antibacterial activity in the past years. In order to elucidate their new structural activity relationship (SAR), the recently synthesized berberine derivatives are reviewed. The newly synthesized berberine derivatives are reported in this review with novel modifications on the berberine structure at various positions. It is hoped that this article would help scientists to design and synthesize new berberine derivatives with high potency and a broad spectrum of antimicrobial activities, more effectiveness and lower toxicity for improved antimicrobial therapy. These berberine derivatives could be developed as novel antibacterial agents to treat patients with infectious diseases, especially caused by resistant bacteria.

10.
Clin Chim Acta ; 500: 54-58, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31626762

RESUMO

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) and its receptor, lectin-like ox-LDL receptor-1 (LOX-1) are involved in the pathogenesis of atherosclerosis. Expression of LOX-1 was substantially raised in the basilar arterial wall of subarachnoid hemorrhage (SAH) rabbits. We ascertained the relationship between serum soluble LOX-1 concentrations and functional outcome after human aneurysmal SAH. METHODS: We enrolled 94 aneurysmal SAH patients and 94 healthy controls. Serum soluble TOX-1 concentrations were quantified using commercial enzyme-linked immunosorbent assay kit. A poor outcome was defined as Glasgow outcome scale score of 1-3. RESULTS: Median values of serum soluble LOX-1 in stroke patients were significantly higher than those in controls (1.5 vs. 0.4 ng/ml, P < 0.001). Thirty patients (31.9%) had a poor outcome at 6 months after stroke. Serum soluble LOX-1 was a strong predictor of poor outcome (OR 5.20, 95% CI 1.25-22.04). Serum soluble LOX-1 concentrations exhibited a significant discriminatory capability (area under curve 0.811, 95% confidence interval 0.717-0.884). The predictive powers of World Federation of Neurological Surgeons grade, Hunt-Hess grade, modified Fisher grade, and serum soluble LOX-1 concentrations were comparable (all P > 0.05). CONCLUSIONS: Serum soluble LOX-1 appears to have the potential to become a promising prognostic predictor after human aneurysmal SAH.

11.
Sci Total Environ ; 708: 134552, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31787280

RESUMO

Sulfonamide antibiotics are contaminants of emerging concern (CEC). These CECs raise considerable alarm because they are commonly present in water environments. Studies on the environmental existence of CECs in karst areas of Guilin (Southern China) have yet to be reported. Thus, this study aims to investigate the presence, temporal and spatial distributions of sulfonamides in surface water and groundwater of four major aquatic environments (i.e., aquafarm water, ditch water, wetland water, and groundwater) in the Huixian karst wetland system of Guilin. Furthermore, this study aims to determine the ecological and human health risks of individual sulfonamides and their mixtures. Ten sulfonamides (i.e., sulfadiazine, sulfapyridine, sulfamerazine, trimethoprim, sulfamethazine, sulfamethoxypyridazine, sulfachloropyridazine, sulfamethoxazole, sulfadimethoxine, and sulfaquinoxaline) were observed in the study area. The highest average concentrations of aquafarm water, ditch water, wetland water, and groundwater were those of sulfadiazine (48.24 µg/L), sulfamethoxypyridazine (1281.50 µg/L), sulfamethoxazole (51.14 µg/L), and sulfamethazine (20.06 µg/L), respectively. The potential ecological risks of the detected compounds were much higher in ditch water than in aquafarm water, wetland water, and groundwater. The most ecological risks were observed for sulfachloropyridazine with a risk quotient (RQ) reaching 335.5 to green algae and 152 to Daphnia magna in ditch water. Similarly, sulfachloropyridazine posed the highest ecological risks to green algae among the ten sulfonamides in aquafarm water (RQ = 3.39), wetland water (RQ = 2.98), and groundwater (RQ = 3.6). Human health risk for age groups<12 months was observed from sulfonamide in drinking groundwater. Ecological and human health risks caused by sulfonamide mixtures were larger than the individual risks. Overall, ecological and human health risks caused by sulfonamides were observed in the study area.

12.
J Cell Mol Med ; 24(1): 50-60, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31568643

RESUMO

Renal cell carcinoma (RCC) is a heterogeneous histological disease and it is one of the most common kidney cancer. The treatment of RCC has been improved for the past few years, but its mortality still remains high. Chelerythrine (CHE) is a natural benzo[c]phenanthridine alkaloid and a widely used broad-range protein kinase C inhibitor which has anti-cancer effect on various types of human cancer cells. However, its effect on RCC has not been fully elucidated. In this study, we evaluated the effect and mechanism of CHE on RCC cells. Our study showed that CHE induced colony formation inhibition and G2/M cell cycle arrest in a dose-dependent manner in RCC cells. In addition, CHE increased cellular ROS level, leading to endoplasmic reticulum (ER) stress, inactivating STAT3 activities and inducing apoptosis in RCC cells which were suppressed by NAC, a special ROS inhibitor. We further found that both knockdown of ATF4 protein and overexpression of STAT3 protein could reduce CHE-induced apoptosis in Caki cells. These results demonstrated that the apoptosis induced by CHE was mediated by ROS-caused ER stress and STAT3 inactivation. Collectively, our studies provided support for CHE as a potential new therapeutic agent for the management of RCC.

13.
Anal Chem ; 92(2): 2019-2026, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31854983

RESUMO

Donor-linker-acceptor (D-L-A)-based photoinduced electron transfer (PET) has been frequently used for the construction of versatile fluorescent chemo/biosensors. However, sophisticated and tedious processes are generally required for the synthesis of these probes, which leads to poor design flexibility. In this work, by exploiting a Schiff base as a linker unit, a covalently bound D-L-A system was established and subsequently utilized for the development of a PET sensor. Cysteamine (Cys) and N-acetyl-l-cysteine (NAC) costabilized gold nanoclusters (Cys/NAC-AuNCs) were synthesized and adopted as an electron acceptor, and pyridoxal phosphate (PLP) was selected as an electron donor. PLP can form a Schiff base (an aldimine) with the primary amino group of Cys/NAC-AuNC through its aldehyde group and thereby suppresses the fluorescence of Cys/NAC-AuNC. The Rehm-Weller formula results and a HOMO-LUMO orbital study revealed that a reductive PET mechanism is responsible for the observed fluorescence quenching. Since the pyridoxal (PL) produced by the acid phosphatase (ACP)-catalyzed cleavage of PLP has a weak interaction with Cys/NAC-AuNC, a novel turn-on fluorescent method for selective detection of ACP was successfully realized. To the best of our knowledge, this is the first example of the development of a covalently bound D-L-A system for fluorescent PET sensing of enzyme activity based on AuNC nanoprobes using a Schiff base.

14.
Biochim Biophys Acta Mol Basis Dis ; 1866(1): 165554, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31513833

RESUMO

Activation of interferon (IFN)-I signaling in B cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Recent studies have shown that myeloid-derived suppressor cells (MDSCs) significantly expand in SLE patients and lupus-prone MRL/lpr mice and contribute to the pathogenesis of SLE. However, the role of SLE-derived MDSCs in regulating IFN-I signaling activation of B cells remains unknown. Here, we demonstrate that expansions of MDSCs, including granulocyte (G)-MDSCs and monocytic (M)-MDSCs, during the progression of SLE were correlated with the IFN-I signature of B cells. Interestingly, G-MDSCs from MRL/lpr mice, but not M-MDSCs, could significantly promote IFN-I signaling activation of B cells and contribute to the pathogenesis of SLE. Mechanistically, we identified that the long non-coding RNA NEAT1 was over-expressed in G-MDSCs from MRL/lpr mice and could induce the promotion of G-MDSCs on IFN-I signaling activation of B cells through B cell-activating factor (BAFF) secretion. Importantly, NEAT1 deficiency significantly attenuated the lupus symptoms in pristane-induced lupus mice. In addition, there was a positive correlation between NEAT1 and BAFF with the IFN signature in SLE patients. In conclusion, G-MDSCs may contribute to the IFN signature in SLE B cells through the NEAT1-BAFF axis, highlighting G-MDSCs as a potential therapeutic target to treat SLE.

15.
ACS Nano ; 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31820925

RESUMO

Photodynamic therapy (PDT) strategy has been widely used in tumor treatment, and the reagents for reactive oxygen species (ROS) play a crucial role. Herein, we develop a fluorogen (TTB) containing an electron-accepting benzo[1,2-b:4,5-b']dithiophene 1,1,5,5-tetraoxide core and electron-donating 4,4'-(2,2-diphenylethene-1,1-diyl)bis(N,N-diphenylaniline) groups for image-guided targeting PDT application. TTB exhibits a prominent aggregation-induced emission (AIE) property with strong near-infrared (NIR) fluorescence in aggregates and is capable of efficiently generating ROS of O2•- and 1O2 under white light irradiation. The nanoparticles (RGD-4R-MPD/TTB NPs) with NIR emission (∼730 nm), high photostability, and low dark cytotoxicity are fabricated by encapsulating TTB within polymeric matrix and then modified with RGD-4R peptide. They show excellent performance in targeting PDT treatment of PC3, HeLa, and SKOV-3 cancer cells in vitro. The investigations on pharmacokinetics, biodistribution, and long-term tracing in vivo reveal that RGD-4R-MPD/TTB NPs can selectively accumulate in tumors for real-time, long-term image-guided PDT treatment. The RGD-4R-MPD/TTB NPs-mediated PDT in multiple xenograft tumor models disclose that the growth of cervical, prostate, and ovarian cancers in mice can be effectively inhibited. These results demonstrate that the reagents employing NIR fluorogen TTB as a photosensitizer could be promising candidates for in vivo image-guided PDT treatments of tumors.

16.
Oncol Lett ; 18(6): 6079-6089, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788082

RESUMO

Ependymomas (EPNs) are one of the most common types of malignant neuroepithelial tumors. In an effort to identify potential biomarkers involved in the pathogenesis of EPN, the mRNA expression profiles of the GSE25604, GSE50161, GSE66354, GSE74195 and GSE86574 datasets, in addition to the microRNA (miRNA/miR) expression profiles of GSE42657 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) between EPN and normal brain tissue samples were identified using the Limma package in R and GEO2R, respectively. Functional and pathway enrichment analyses were conducted using the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction network was constructed using the Search Tool for Retrieval of Interacting Genes database, which was visualized using Cytoscape. The targeted genes of DEMs were predicted using miRWalk2.0 and a miRNA-mRNA regulatory network was constructed. Following analysis, a total of 948 DEGs and 129 DEMs were identified. Functional enrichment analysis revealed that 609 upregulated DEGs were significantly enriched in 'PI3K-Akt signaling pathway', while 339 downregulated DEGs were primarily involved in 'cell junction' and 'retrograde endocannabinoid signaling'. In addition, 6 hub genes [cyclin dependent kinase 1, CD44 molecule (Indian blood group) (CD44), proliferating cell nuclear antigen (PCNA), MYC, synaptotagmin 1 (SYT1) and kinesin family member 4A] and 6 crucial miRNAs [homo sapiens (hsa)-miR-34a-5p, hsa-miR-449a, hsa-miR-106a-5p, hsa-miR-124-3p, hsa-miR-128-3p and hsa-miR-330-3p] were identified as biomarkers and potential therapeutic targets for EPN. Furthermore, a microRNA-mRNA regulatory network was constructed to highlight the interactions between DEMs and their target DEGs; this included the hsa-miR-449a-SYT1, hsa-miR-34a-5p-SYT1, hsa-miR-330-3p-CD44 and hsa-miR-124-3p-PCNA pairs, whose expression levels were confirmed using reverse transcription-quantitative polymerase chain reaction. In conclusion, the present study may provide important data for the investigation of the molecular mechanisms of EPN pathogenesis.

17.
ACS Biomater Sci Eng ; 5(4): 1661-1667, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-31788555

RESUMO

During aging, wear, and tear of intervertebral discs, human discs undergo a series of morphological and biochemical changes. Degradation of extracellular matrix proteins, e.g., collagen, arises as an important contributor and accelerator in this process. Existing methods to detect collagen degradation at the tissue level include histology and immunohistochemistry. Unfortunately, most of these methods only depict overall collagen content without the ability to specifically discern degraded collagen and to assess the severity of degeneration. To fill this technological gap, we developed a robust and simple approach to detect and assess early disc degeneration with a collagen hybridizing peptide (CHP) that hybridizes with the flawed triple helix structure in degraded collagen. Intriguingly, the CHP signal in mouse lumbar discs exhibited a linear incremental pattern with age. This finding was corroborated with histological analysis based on established methods. When comparing this analysis, a positive linear correlation was found between CHP fluorescence intensity and the histological score with a regression value of r 2 = 0.9478. In degenerative mouse discs elicited by pro-inflammatory stimuli (IL-1ß and LPS) ex vivo, the newly developed approach empowered prediction of the severity of disc degeneration. We further demonstrated higher CHP signals in a degenerative human disc tissue when compared to a normal sample. These findings also resonated with histological analysis. This approach lays a solid foundation for specific detection and assessment of intervertebral disc degeneration at the molecular level and will promote development of future disc regeneration strategies.

18.
J Asian Nat Prod Res ; : 1-10, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31791147

RESUMO

Various bioactive polyketides have been found in Aloe barbadensis. However, the polyketide synthases (PKSs), which participate in biosynthesis of polyketides in A. barbadensis remain unknown. In this study, two type III PKSs (AbPKS1 and AbPKS2) were identified from A. barbadensis. AbPKS1 and AbPKS2 were able to utilize malonyl-CoA to yield heptaketides (TW93a and aloesone) and octaketides (SEK4 and SEK4b), respectively. AbPKS1 also exhibited catalytic promiscuity in recognizing CoA thioesters of aromatics to produce unusual polyketides. What Is more, a whole cell biocatalysis system with the capability of producing 26.4 mg/L of SEK4/SEK4b and 2.1 mg/L of aloesone was successfully established.

19.
Am J Transl Res ; 11(11): 7049-7062, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814908

RESUMO

Non-gestational choriocarcinoma (NGC) is a rare subtype of choriocarcinoma differing in origin and phenotypic characteristics compared to gestational choriocarcinoma (GC). This study aimed to analyze the molecular biology of GC and NGC and evaluate genetic anomalies of choriocarcinoma subtypes. DNA was extracted and paired from tumor-normal tissue of one NGC and one GC (control) patient for whole-exome sequencing. To further understand the role of DNAJB9, a p53 regulator mutated in the NGC tumor, on p53 upregulation in choriocarcinoma, CRISPR/Cas9 was used to induce DNAJB9 site-specific mutations in choriocarcinoma cells JEG-3. We hypothesized that DNAJB9 dysfunction would result in p53 overexpression. Sequencing revealed the GC tumor contained > 7 times more somatic mutations than the NGC tumor. Missense (98.86% vs. 94.97%), stop-gain (0.57% vs. 0.93%), and frameshift mutations (0.57% vs. 4.10%) were observed in the GC and NGC samples, respectively (x 2 = 24.63, P < 0.00001). The transition substitution rate was 67.54% and 55.71% in the GC and NGC samples, while the transversion substitution rate was 32.46% and 44.29% in the GC and NGC samples, respectively (x 2 = 11.56, P < 0.000673). Pathway enrichment analysis revealed ECM-receptor interaction and graft-versus-host disease were most enriched in the GC and NGC tumors, respectively. In vitro investigations showed that DNAJB9 mRNA and protein levels were downregulated in Cas9-DNAJB9-sgRNA transfected cells compared to the control (P < 0.001), while p53 protein levels were upregulated. Our findings display the genetic distinctness of choriocarcinoma subtypes, especially NGC, and further highlight the relationship between p53 and DNAJB9 in choriocarcinoma cells, laying the foundation for further investigations.

20.
ACS Biomater Sci Eng ; 5(4): 2041-2051, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-31763444

RESUMO

Low back pain is the most common cause of disability worldwide, and intervertebral disc degeneration is a major cause of low back pain. Unfortunately, discogenic low back pain is often treated with symptomatic relief interventions, as no disease-modifying medications are yet available. Both to-be-deciphered disc biology/pathology and inadequate in vitro research platform are major hurdles limiting drug discovery progress for disc degeneration. Here, we developed a microfluidic disc-on-a-chip device tailored for mouse disc organ as an in vitro research platform. We hypothesize that continuous nutrients empowered by a microfluidic device would improve biological performance of cultured mouse discs compared to those in static condition. This device permitted continuous media flow to mimic in vivo disc microenvironment. Intriguingly, mouse discs cultured on the microfluidic device exhibited much higher cell viability, better preserved structure integrity and anabolic-catabolic metabolism in both nucleus pulposus and annulus fibrosus, for up to 21 days compared to those in static culture. This first "disc-on-a-chip" device lays groundwork for future preclinical studies in a relative long-term organ culture given the chronic nature of intervertebral disc degeneration. In addition, this platform is readily transformable into a streamlined in vitro research platform to recapitulate physiological and pathophysiological microenvironment to accelerate disc research.

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