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Presynaptic syntaxin binding protein 1 (STXBP1) is essential for neurotransmitter release. Heterozygous mutations in this protein cause STXBP1 encephalopathy (STXBP1-E), which is characterized by intellectual disabilities and epilepsies. Since nonhuman primates closely resemble humans, monkey models may advance studies on the pathogenesis and therapeutic treatments of STXBP1-E. We generated cynomolgus monkeys carrying STXBP1 (R292H) mutation through base editing of in vitro fertilized embryos to mimic a clinical condition. The newborn STXBP1-edited monkeys exhibited focal epilepsy, and the animal that survived beyond the first week postpartum presented typical EEG phenotypes. Biochemical analysis of brain biopsy samples showed reduced levels of STXBP1 (MUNC18-1) and SNARE complex proteins. Single-cell sequencing identified one specific cell cluster that may contribute to encephalopathy. Thus, our case report shows that base-edited STXBP1 mutant monkeys are a good animal model for STXBP1-E, and that a base-editing approach is useful for generating primate models of human genetic disorders.
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Encefalopatías , Epilepsia , Animales , Encéfalo/metabolismo , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Femenino , Macaca fascicularis/metabolismo , Proteínas Munc18/genética , Proteínas Munc18/metabolismo , MutaciónRESUMEN
Malignant pleural mesothelioma (MPM) is an aggressive malignancy with limited effective treatment options. Focal adhesion kinase (FAK) inhibitors have been shown to efficiently suppress MPM cell growth initially, with limited utility in the current clinical setting. In this study, we utilised a large collection of MPM cell lines and MPM tissue samples to study the role of E-cadherin (CDH1) and microRNA on the efficacy of FAK inhibitors in MPM. The immunohistochemistry (IHC) results showed that the majority of MPM FFPE samples exhibited either the absence of, or very low, E-cadherin protein expression in MPM tissue. We showed that MPM cells with high CDH1 mRNA levels exhibited resistance to the FAK inhibitor PND-1186. In summary, MPM cells that did not express CDH1 mRNA were sensitive to PND-1186, and MPM cells that retained CDH1 mRNA were resistant. A cell cycle analysis showed that PND-1186 induced cell cycle disruption by inducing the G2/M arrest of MPM cells. A protein-protein interaction study showed that EGFR is linked to the FAK pathway, and a target scan of the microRNAs revealed that microRNAs (miR-17, miR221, miR-222, miR137, and miR148) interact with EGFR 3'UTR. Transfection of MPM cells with these microRNAs sensitised the CHD1-expressing FAK-inhibitor-resistant MPM cells to the FAK inhibitor.
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Antígenos CD/genética , Antígenos CD/metabolismo , Cadherinas/genética , Cadherinas/metabolismo , Quinasa 1 de Adhesión Focal/antagonistas & inhibidores , Mesotelioma Maligno/tratamiento farmacológico , Mesotelioma Maligno/genética , MicroARNs/fisiología , Inhibidores de Proteínas Quinasas/farmacología , Aminopiridinas/farmacología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Receptores ErbB/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Mapas de Interacción de ProteínasRESUMEN
Through investigation,it was found that the main disease of leaves was grey mold on Dendrobium officinale in Hubei province,which has a great impact on the yield and quality of D. officinale. The identification of morphological and molecular biological was used to prove that the pathogen was Botrytis cinerea. Through test the effect of 5 plant source fungicides and 4 antibiotic fungicides on mycelial growth of strain HS1,which proved 0. 3% eugenol had the best inhibitory effect,EC50 was 0. 29 mg·L-1,the second was1% osthol and EC50 was 1. 12 mg·L-1,the EC50 of 0. 5% matrine was 9. 16 mg·L-1,the EC50 of the other six fungicides was higher than 10 mg·L-1. The field control effect test proved that 0. 3% eugenol had the best control effect,reaching 89. 44%,secondly for 1%osthole,which was 77. 17%,0. 5% matrine was in the third place with 62. 37% of effective rate. However,the control effect of the other fungicides was less than 60%. The three plant-derived fungicides were safe for the produce of D. officinale and showed no phytotoxicity. The effect of these fungicides on the growth of D. candidum was tested,and proved that all the fungicides were safe and harmless to D. candidum. This study provides a research basis for the safe and effective prevention and control gray mold of D. officinale.
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Botrytis/patogenicidad , Dendrobium/microbiología , Fungicidas Industriales , Enfermedades de las Plantas/microbiología , Alcaloides , Botrytis/efectos de los fármacos , Cumarinas , Eugenol , Enfermedades de las Plantas/prevención & control , Hojas de la Planta/microbiología , Quinolizinas , MatrinasRESUMEN
BACKGROUND: Endogenous circadian oscillators distributed across the mammalian body are synchronised among themselves and with external time via a variety of signalling molecules, some of which interact with G-protein-coupled receptors (GPCRs). GPCRs can regulate cell physiology via pathways originating with heterotrimeric G-proteins or ß-arrestins. We applied an optogenetic approach to determine the contribution of these two signalling modes on circadian phase. RESULTS: We employed a photopigment (JellyOp) that activates Gαs signalling with better selectivity and higher sensitivity than available alternatives, and a point mutant of this pigment (F112A) biased towards ß-arrestin signalling. When expressed in fibroblasts, both native JellyOp and the F112A arrestin-biased mutant drove light-dependent phase resetting in the circadian clock. Shifts induced by the two opsins differed in their circadian phase dependence and the degree to which they were associated with clock gene induction. CONCLUSIONS: Our data imply separable G-protein and arrestin inputs to the mammalian circadian clock and establish a pair of optogenetic tools suitable for manipulating Gαs- and ß-arrestin-biased signalling in live cells.
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Relojes Circadianos , Pigmentos Biológicos/metabolismo , Receptores Acoplados a Proteínas G/genética , Transducción de Señal , Animales , Relojes Circadianos/genética , Cubomedusas/química , Fibroblastos , Células HEK293 , Humanos , Optogenética , Ratas , Receptores Acoplados a Proteínas G/metabolismo , beta-Arrestinas/genéticaRESUMEN
BACKGROUND: Solid papillary carcinoma (SPC) is a rare variant of breast papillary carcinoma with unique pathological morphology and biological behavior. There is only one case report on T1-MRI of SPC. In this study, we report our findings on this new category of papillary carcinoma to fill the gap in MRI characterization of SPC. METHODS: This retrospective study included four pathology-confirmed in situ SPC patients. Conventional MRI, diffusion weighted imaging (DWI), and magnetic resonance spectroscopy (MRS) were performed with a 1.5 T whole-body MR scanner before surgical operation. The following characteristics of each lesion were recorded: signal intensity on T2WI/STIR and T1FSPGR, morphology, maximum lesion size, and time intensity curve (TIC) on dynamic contrast enhancement MRI (DCE-MRI), apparent diffusion coefficient (ADC) value from DWI, and Cho peak from MRS. RESULTS: Signal intensities of all lesions were heterogenous on T2WI/STIR and T1FSPGR. Mass enhancements were observed for all lesions with either oval or irregular shapes on DCE-MRI. The maximum lesion size ranged from 0.8 cm to 3.2 cm. All lesion margins were circumscribed, and internal enhancements were homogeneous or heterogeneous from DCE-MRI. TIC appeared with a rapid increase in initial contrast phases of all lesions. All lesions on DWI (b = 1000s/mm2) were slightly hyperintense with an ADC value range of 1.3 × 10-3 mm2/s to 1.9 × 10-3 mm2/s. Cho peak was absent at 3.2 ppm for all lesions. CONCLUSIONS: MRI characteristics of SPC include heterogeneous signal intensity within the lesion on T2WI/STIR and T1FSPGR, mass enhancement with circumscribed margins, either oval or irregular shapes, and a rapid initial enhancement of TIC on DCE-MRI. ADC values and the absence of Cho peak may provide valuable information to distinguish SPC from other invasive breast carcinomas.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Carcinoma Papilar/diagnóstico por imagen , Carcinoma Papilar/patología , Imagen por Resonancia Magnética , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Imagen por Resonancia Magnética/métodos , Proyectos PilotoRESUMEN
Five new diterpenoid alkaloids, ajacisines A-E (1-5), were isolated from Delphinium ajacis, along with seven known alkaloids (6-12). On the basis of their spectral data (IR, UV, HR-ESI-MS, 1D and 2D NMR) and chemical properties, the structures of compounds 1-12 were identified. All isolated compounds were evaluated for their in vitro antiviral activities against respiratory syncytial virus, and compounds 3-5 and 8 exhibited moderate to weak effects with IC50 values of 75.2 ± 1.1, 35.1 ± 0.6, 10.1 ± 0.3, and 50.2 ± 0.5 µM, respectively.
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Alcaloides/farmacología , Antivirales/farmacología , Delphinium/química , Diterpenos/farmacología , Estructura Molecular , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Alcaloides/química , Alcaloides/aislamiento & purificación , Antivirales/química , Antivirales/aislamiento & purificación , Línea Celular Tumoral , Diterpenos/química , Diterpenos/aislamiento & purificación , Humanos , Espectroscopía de Resonancia Magnética , Raíces de Plantas/química , Tallos de la Planta/químicaRESUMEN
As an emerging modality for whole breast imaging, ultrasound tomography (UST), has been adopted for diagnostic purposes. Efficient segmentation of an entire breast in UST images plays an important role in quantitative tissue analysis and cancer diagnosis, while major existing methods suffer from considerable time consumption and intensive user interaction. This paper explores three-dimensional GrabCut (GC3D) for breast isolation in thirty reflection (B-mode) UST volumetric images. The algorithm can be conveniently initialized by localizing points to form a polygon, which covers the potential breast region. Moreover, two other variations of GrabCut and an active contour method were compared. Algorithm performance was evaluated from volume overlap ratios ( T O , target overlap; M O , mean overlap; F P , false positive; F N , false negative) and time consumption. Experimental results indicate that GC3D considerably reduced the work load and achieved good performance ( T O = 0.84; M O = 0.91; F P = 0.006; F N = 0.16) within an average of 1.2 min per volume. Furthermore, GC3D is not only user friendly, but also robust to various inputs, suggesting its great potential to facilitate clinical applications during whole-breast UST imaging. In the near future, the implemented GC3D can be easily automated to tackle B-mode UST volumetric images acquired from the updated imaging system.
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The purpose of this study was to evaluate adaptive daily planning for cervi-cal cancer patients who underwent high-dose-rate intracavitary brachytherapy (HDR-BT) using comprehensive interfractional organ motion measurements. This study included 22 cervical cancer patients who underwent 5 fractions of HDR-BT. Regions of interest (ROIs) including high-risk clinical tumor volume (HR-CTV) and organs at risk (OARs) were manually contoured on daily CT images. All patients were clinically treated with adaptive daily plans (ADP), which involved ROI delineation and dose optimization at each treatment fraction. Single treatment plans (SP) were retrospectively generated by applying the first treatment fraction's dwell times adjusted for decay and dwell positions of the applicator to subsequent treatment fractions. Various existing similarity metrics were calculated for the ROIs to quantify interfractional organ variations. A novel similarity (JRARM) score was established, which combined both volumetric overlap metrics (DSC, JSC, and RVD) and distance metrics (ASD, MSD, and RMSD). Linear regression was performed to determine a relationship between interfractional organ varia-tions of various similarity metrics and D2cc variations from both plans. Wilcoxon signed-rank tests were used to assess ADP and SP by comparing EQD2 D2cc (α/ß = 3) for OARs. For interfractional organ variations, the sigmoid demonstrated the greatest variations based on the JRARM, DSC, and RMSD metrics. Comparisons between paired ROIs showed differences in metrics at each treatment fraction. RVD, MSD, and RMSD were found to be significantly correlated to D2cc varia-tions for bladder and sigmoid. The comparison between plans found ADP provided lower EQD2 D2cc of OARs than SP. Specifically, the sigmoid demonstrated sta-tistically significant dose variations (p = 0.015). Substantial interfractional organ motion occurs during HDR-BT based on comprehensive measurements and may significantly affect D2cc of OARs. Adaptive daily planning provides improved dose sparing for OARs compared to single planning with the extent of sparing being different among OARs.
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Braquiterapia , Procesamiento de Imagen Asistido por Computador/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/métodos , Radioterapia de Intensidad Modulada/métodos , Neoplasias del Cuello Uterino/radioterapia , Femenino , Humanos , Órganos en Riesgo/efectos de la radiación , Dosificación Radioterapéutica , Recto , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Vejiga Urinaria/efectos de la radiaciónRESUMEN
OBJECTIVE: To assess the antibiotic resistance and molecular characterization of cholera strains and to provide basis for clinical treatment and prevention of cholera. METHODS: 4 stains isolated from an outbreak of cholera epidemic in Huai'an City in Jiangsu province in September 2010 were characterized using antibiotic susceptibility, biotype analysis, virluence genes detection, ctxB gene sequencing, and PFGE analysis. RESULTS: The 4 strains were all resistant to sulphamethoxazole/trimethoprim, erythromycin, streptomycin. High drug susceptibility of the samples was found to 6 kinds of antibiotics such as amikacin, norfloxacin, ciprofloxacin, gentamicin, chloramphenicol, ampicillin. The isolates expressed phenotypic traits of both serogroup O1 ogawa and El Tor and carried 9 kinds of virulence genes, ctxA, ace, zot, toxR, tcpI, ompU, rtxC, tcpA, and hlyA gene. They were also identified as harboring the classical ctxB genotype based on amino acid residue substitutions. The PFGE profiles of NotI showed a single banding pattern, while SfiI's was 2 banding patterns. CONCLUSION: The bacterium type of Vibrio cholerae causing the epidemic outbreak of cholera belonged to the atypical EL Tor variant which was also identified as toxicogenic strain. The mapping of the strains prompted that there should be the common contamination source. Drug sensitivity test can guide the clinical drug use, in order to reduce the emergence of resistant strains.
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Farmacorresistencia Bacteriana , Epidemias , Genotipo , Vibrio cholerae O1 , Antibacterianos , Cólera , Toxina del Cólera , Brotes de Enfermedades , Farmacorresistencia Microbiana , Humanos , Vibrio cholerae , VirulenciaRESUMEN
OBJECTIVE: To evaluate the prognosis value of plasma cystatin C in predicting adverse cardiac events after percutaneous coronary intervention (PCI) for non-ST-elevation acute coronary syndrome (NSTEACS). METHODS: A total of 277 patients (212 male, mean age 59 ± 12 years) with NSTEACS underwent successful PCI. The patients were then divided into MACE group and non-MACE group. Patients were divided into 4 groups according to the level of cystatinC : Q1 (<0.78 mg/L), Q2 (0.78-0.93 mg/L), Q3 (0.94-1.11 mg/L), and Q4 ( ≥ 1.12 mg/L) . Risk factors for MACE were analyzed by Cox regression analysis. RESULTS: The plasma Cys-C level were higher in MACE group than in non-MACE group(P < 0.05). The areas under ROC curve of Cys-C, cTnI, hsCRP an CK-MB to predict cardiac event were 0.737,0.630,0.692 and 0.650 respectively. After a follow-up of 1 year, the MACE in the Q2, Q3, and Q4 groups was higher than in the Q1 group (Logrank = 23.751, P < 0.01). Multivariate Cox regression analysis showed that cystatin C elevation was an independent predictor of major adverse cardiac events (P < 0.01). CONCLUSION: High plasma cystatin C concentration is an independent predictor of major adverse cardiac events in patients with NSTEACS treated with PCI.
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Síndrome Coronario Agudo/sangre , Cistatina C/sangre , Intervención Coronaria Percutánea , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/terapia , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del TratamientoRESUMEN
Metarhizium anisopliae is an important class of entomopathogenic fungi used for the biocontrol of insects, but its virulence is affected by insect immunity. We identified a novel FK506 binding protein gene that was differentially expressed between control and Metarhizium-treated Locusta migratoria manilensis. We hypothesized that this protein played an important role in Metarhizium infection of L. migratoria and could provide new insights for developing highly efficient entomopathogenic fungi. We, therefore, cloned the specific gene and obtained its purified protein. The gene was then named FKBP52, and its dsRNA (dsFKBP52) was synthesized and used for gene interference. Bioassay results showed that the mortality of L. migratoria treated with dsFKBP52â +â Metarhizium was significantly lower than that of other treatments. Furthermore, immune-related genes (MyD88, Dorsal, Cactus, and Defensin) in L. migratoria treated with dsFKBP52â +â Metarhizium showed significant upregulation compared to that treated with Metarhizium only. However, the activities of peroxidase (POD), superoxide dismutase (SOD), and calcineurin (CaN) showed fluctuations. These results suggest that the FKBP52 gene may play a crucial role in the innate immunity of L. migratoria. The effect of its silencing indicated that this immunity-related protein might be a potential target for insect biocontrol.
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Proteínas de Insectos , Locusta migratoria , Metarhizium , Proteínas de Unión a Tacrolimus , Animales , Locusta migratoria/genética , Locusta migratoria/inmunología , Metarhizium/fisiología , Metarhizium/genética , Proteínas de Unión a Tacrolimus/genética , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Control Biológico de Vectores , Inmunidad Innata , Secuencia de AminoácidosRESUMEN
Background: The relationship between H. pylori infection and gastric cancer (GC) has been widely studied, and H. pylori is considered as the main factor. Utilizing bioinformatics analysis, this study examined gene signatures related to progressing H. pylori-associated GC. Materials and Methods: The dataset GSE13195 was chosen to search for abnormally expressed genes in H. pylori-associated GC and normal tissues. The TCGA-STAD database was chosen to verify the expression of key genes in GC and normal tissues. Results: In GSE13195, a total of 332 differential expression genes (DEGs) were screened. The results of weighted gene co-expression network analysis showed that the light cyan, plum2, black, and magenta4 modules were associated with stages (T3, T2, and T4), while the orangered4, salmon2, pink, and navajowhite2 modules were correlated with lymph node metastasis (N3, N2, and N0). Based on the results of DEGs and hub genes, a total of 7 key genes (ADAM28, FCER1G, MRPL14, SOSTDC1, TYROBP, C1QC, and C3) were screened out. These gene mRNA levels were able to distinguish between normal and H. pylori-associated GC tissue using receiver operating characteristic curves. After transcriptional level verification and survival analysis, ADAM28 and C1QC were excluded. An immune infiltration study revealed that key genes were involved in regulating the infiltration levels of cells associated with innate immune response, antigen presentation process, humoral immune response, or Tcell-mediated immune response. In addition, drugs targeting FCER1G and TYROBP have been approved and are under investigation. Conclusion: Our study identified five key genes involved in H. pylori-associated GC tumorigenesis. Patients with higher levels of C3 expression had a poorer prognosis than those with lower levels. In addition, these key genes may serve as biomarkers and therapeutic targets for H. pylori-associated GC diagnosis, targeted therapy, and immunotherapy in the future.
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To analyze the efficacy and influencing factors of Mifepristone combined with estrogen-progesterone sequential therapy (Femoston) in the treatment of incomplete abortion. This retrospective cohort study included 93 patients with incomplete abortion. All patients took 50 mg of Mifepristone 2 times a day for 5 days and then took Femoston once a day (starting with estradiol tablets/2 mg) for 28 days. Without any indication of intrauterine residue by ultrasonic examination was judged to be effective. According to statistical analysis, this study calculated the effective rate and analyzed its influencing factors. A 2-sided value of Pâ <â .05 was considered statistically significant. The total response rate of the treatment regimen was 86.67%. body mass index was a significant influencing factor for treatment outcome (OR 0.818, 95% confidence interval 0.668-0.991, Pâ =â .041). For patients with incomplete abortion, Mifepristone combined with estrogen-progesterone sequential therapy has a remarkable therapeutic effect. Patients with a lower body mass index may respond much more significantly to this treatment regimen.
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Abortivos , Aborto Incompleto , Aborto Inducido , Embarazo , Femenino , Humanos , Mifepristona/uso terapéutico , Progesterona , Aborto Incompleto/etiología , Estudios Retrospectivos , Aborto Inducido/efectos adversos , Estrógenos/uso terapéuticoRESUMEN
FK506 binding proteins (FKBPs) are a highly-conserved group of proteins known to bind to FK506, an immunosuppressive drug. They play different physiological roles, including transcription regulation, protein folding, signal transduction and immunosuppression. A number of FKBP genes have been identified in eukaryotes; however, very little information about these genes has been reported in Locusta migratoria. Here, we identified and characterized 10 FKBP genes from L. migratoria. Phylogenetic analysis and comparison of domain architectures indicated that the LmFKBP family can be divided into two subfamilies and five subclasses. Developmental and tissue expression pattern analysis revealed that all LmFKBPs transcripts, including LmFKBP46, LmFKBP12, LmFKBP47, LmFKBP79, LmFKBP16, LmFKBP24, LmFKBP44b, LmFKBP53, were periodically expressed during different developmental stages and mainly expressed in the fat body, hemolymph, testis, and ovary. In brief, our work depicts a outline but panoramic picture of LmFKBP family in L. migratoria, and provides a solid foundation to further investigate the molecular functions of LmFKBPs.
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Locusta migratoria , Proteínas de Unión a Tacrolimus , Masculino , Animales , Femenino , Proteínas de Unión a Tacrolimus/genética , Locusta migratoria/genética , Filogenia , Pliegue de Proteína , TacrolimusRESUMEN
Pleural mesothelioma (PM) is a highly aggressive, fast-growing asbestos-induced cancer with limited effective treatments. There has been interest in using naturally occurring anticancer agents derived from plant materials for the treatment of PM. However, it is unclear if an aqueous extract from Leptospermum polygalifolium (QV0) has activity against PM. Here we investigated the anti-cancer properties of QV0 and Defender® (QV0 dietary formula) in vitro and in vivo, respectively. QV0 suppressed the growth of eight PM cell lines in a dose-dependent manner, effective at concentrations as low as 0.02% w/v (equivalent to 0.2 mg/ml). This response was found to be associated with inhibited cell migration, proliferation, and colony formation but without evident cell cycle alteration. We observed mitochondrial dysfunction post-QV0 treatment, as evidenced by significantly decreased basal and maximal oxygen consumption rates. Ten SCID mice were treated with 0.25 mg/g Defender® daily and exhibited reduced tumor size over 30 days, which was associated with an average extension of seven days of mouse life. There was no evidence of liver toxicity or increased blood glucose post-treatment in animals treated with Defender®. Significantly enhanced tumor apoptosis was observed in the Defender®-treated animals, correlating to mitochondrial dysfunction. Lastly, the high levels of polyphenols and antioxidant properties of QV0 and Defender® were detected in HPLC analysis. To the best of our knowledge, this study constitutes the first demonstration of an improved host survival (without adverse effects) response in a QV0-treated PM mouse model, associated with evident inhibition of PM cell growth and mitochondrial dysfunction-related enhancement of tumor apoptosis.
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Purpose: Hepatocellular carcinoma (HCC) has poor prognosis and high mortality among gastrointestinal tumors because of its insidious onset and strong invasiveness. However, there was little understanding of their pathogenesis. The purpose of this study was to use bioinformatics analysis to identify genes associated with the immune microenvironment in HBV-related HCC and to develop new therapeutic targets to prevent and treat cancer. Methods: RNA-seq data of HBV-related HCC cases were downloaded from TCGA-LIHC database. ESTIMATE and Deseq2 algorithms were used to screen out differentially expressed genes (DEGs). WGCNA was used to construct gene coexpression networks. In key modules, functional enrichment analysis was performed. Protein-protein interaction (PPI) was used to screen hub genes, and survival analysis was conducted to assess their prognostic significance. Following, we search for key genes differentially expressed between cancerous and paracancerous tissues in GSE136247 and GSE121248 datasets. Reveal the potential links between key genes in immune infiltration by using TIMER. Finally, in TCGA-LIHC database, integration of key genes with clinical data were used to further validate their correlation with prognosis. Results: In the cohort of HBV-related HCC patients, immune/stromal/ESTIMATE scores were not significantly associated with patient prognosis. After bioinformatics analysis, screening out five key genes was significantly related to the prognosis of HBV-related HCC. Downregulation of SLAMF1 and TRAF3IP3 suggested poor prognosis and was related to a variety of immune cell infiltration. Furthermore, compared with adjacent nontumor tissues, TRAF3IP3 and SLAMF1 were highly expressed in tumor tissues and were linked to tumor recurrences. Conclusion: In conclusion, SLAMF1 and TRAF3IP3 were identified with higher expression in tumor tissues and associated with tumor recurrence. It will be a new research direction of tumor progress and treatment.
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Gastric cancer (GC) is one of the most common malignancies, and novel prognostic biomarkers for it are urgently required. This study is aimed at screening a group of immune-related lncRNAs (IRLs) in predicting the prognosis of GC patients. Genetic and clinical information from the 360 GC patients was included in this study. Eight IRLs in lncRNA-miRNA-mRNA network were screened out according to differential expression analysis. A novel risk score model with three IRLs (MIR4435-1HG, UCA1, and RP11-617F23.1) were identified, and patients were assigned to a high-risk group and a low-risk group. Patients in the low-risk group had a better prognosis. In addition, two nomograms were developed to predict the prognosis of GC. We evaluated the correlation between IRLs and the immune infiltration level of GC using TIMER. Furthermore, we verified that RP11-617F23.1 was significantly upregulated in human GC tissues compared with their adjacent tissues. And, patients with high RP11-617F23.1 expression in tumor tissues had poorer survival. In conclusion, we established a novel risk model based on IRLs for predicting the prognosis of GC. Meanwhile, a novel IRL, RP11-617F23.1, could serve as a predictor of prognosis for patients with GC.
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Malignant pleural mesothelioma (MPM) is a deadly thoracic malignancy and existing treatment options are limited. Chemotherapy remains the most widely used first-line treatment regimen for patients with unresectable MPM, but is hampered by drug resistance issues. The current study demonstrated a modest enhancement of MPM cell sensitivity to chemotherapy drug treatment following microRNA (miRNA) transfection in MPM cell lines, albeit not for all tested miRNAs. This effect was more pronounced for FAK (PND-1186) small molecule inhibitor treatment; consistent with previously published data. We previously established that MPM response to survivin (YM155) small molecule inhibitor treatment is unrelated to basal survivin expression. Here, we showed that MPM response to YM155 treatment is enhanced following miRNA transfection of YM155-resistant MPM cells. We determined that YM155-resistant MPM cells secrete a higher level of exosomes in comparison to YM155-sensitive MPM cells. Despite this, an exosome inhibitor (GW4896) did not enhance MPM cell sensitivity to YM155. Additionally, our study showed no evidence of a correlation between the mRNA expression of inhibitor of apoptosis (IAP) gene family members and MPM cell sensitivity to YM155. However, two drug transporter genes, ABCA6 and ABCA10, were upregulated in the MPM cell lines and correlated with poor sensitivity to YM155.
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The title compound, C(15)H(20)N(2)O(2) (2+)·2PF(6) (-), was prepared by anion exchange of two bromide ions in the ionic liquid 2,2'-bis-(pyridinium-1-ylmeth-yl)-propane-1,3-diol dibromide with potassium hexa-fluoro-phosphate. The two pyridine rings are planar (r.m.s. deviations = 0.008 and 0.00440â Å) and make a dihedral angle of 44.0â (2)°. Intermolecular O-Hâ¯F and C-Hâ¯F interactions occur. The four F atoms in each anion were refined as disordered over two sets of sites with an occupancy ration of 0.700â (19):0.300â (19).