Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 285
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Int J Biol Sci ; 15(11): 2308-2319, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31595149

RESUMO

Acute lung injury (ALI) is a common clinical disease with high incidence and mortality rate, which is characterized by severe inflammatory response and tissues damage. MicroRNAs (miRNAs) have been regarded as novel regulators of inflammation, and play an important role in various inflammatory diseases. However, it remains unknown whether the regulatory mechanisms mediated by miR-106a is involved in LPS-induced ALI. In this study, we found that expression of miR-106a was significantly decreased in lung tissues of ALI mice and LPS-stimulated macrophages. We also revealed that over-expression of miR-106a significantly decreased the production of pro-inflammatory cytokines, including IL-1ß, IL-6 and TNF-α, whereas this effect was reversed by the inhibition of miR-106a. Moreover, miR-106a inhibits NF-κB activation by targeting TLR4 expression. We further demonstrated that miR-106a inhibited TLR4 expression via binding directly to the 3'-UTR of TLR4. Taken together, the results of the present study illuminated that miR-106a is a negative feedback regulator in LPS-stimulated inflammation through TLR4/NF-κB signaling pathway.

2.
Mol Genet Genomic Med ; : e973, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31568715

RESUMO

BACKGROUND: The nuclear encoded gene RMND1 (Required for Meiotic Nuclear Division 1 homolog) has recently been linked to RMND1-related mitochondrial disease (RRMD). This autosomal recessive condition characteristically presents with an infantile-onset multisystem disease characterized by severe hypotonia, global developmental delay, failure to thrive, sensorineural hearing loss, and lactic acidosis. Renal disease, however, appears to be one of the more prominent features of RRMD, affecting patients at significantly higher numbers compared to other mitochondrial diseases. We report the clinical, histological, and molecular findings of four RRMD patients across three academic institutions with a focus on the renal manifestations. METHODS: Four patients were identified for the purpose of this study, all of whom had molecular confirmation at the time of inclusion, which included the common pathogenic variant c.713A>G (p.N238S) as well as the three rare variants: c.485delC (p.P162fs), c.533C>T (p.T178M), and c.1317 + 1G>C splice donor variant. Medical history and laboratory findings were collected from the medical records and medical providers. RESULTS: In this study, all four patients developed renal disease characterized as tubulopathy (3/4), renal tubular acidosis (2/4), interstitial nephritis (1/4), and/or end-stage renal disease (4/4) necessitating renal transplantation (2/4). Histological evaluation of renal biopsy specimens revealed generalized tubular atrophy and on electron microscopy, abundant mitochondria with pleomorphism and abnormal cristae. CONCLUSION: Our experience with RRMD demonstrates a specific pattern of renal disease manifestations and clinical course. Patients are unlikely to respond to traditional chronic kidney disease (CKD) treatments, making early diagnosis and consideration of renal transplantation paramount to the management of RRMD.

3.
J Cell Physiol ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541458

RESUMO

Breast cancer is a common malignancy that is highly lethal with poor survival rates and immature therapeutics that urgently needs more effective and efficient therapies. MicroRNAs are intrinsically involved in different cancer remedies, but their mechanism in breast cancer has not been elucidated for prospective treatment. The function and mechanism of microRNA-188-5p (miR-188) have not been thoroughly investigated in breast cancer. In our study, we found that the expression of miR-188 in breast cancer tissues was obviously reduced. Our findings also revealed the abnormal overexpression of miR-188 in 4T1 and MCF-7 cells significantly suppressed cell proliferation and migration and also enhanced apoptosis. miR-188 induced cell cycle arrest in the G1 phase. To illuminate the molecular mechanism of miR-188, Rap2c was screened as a single target gene by bioinformatics database analysis and was further confirmed by dual-luciferase assay. Moreover, Rap2c was found to be a vital molecular switch for the mitogen-activated protein kinase signaling pathway in tumor progression by decreasing apoptosis and promoting proliferation and migration. In conclusion, our results revealed that miR-188 is a cancer progression suppressor and a promising future target for breast cancer therapy.

4.
Microb Pathog ; 136: 103721, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31494298

RESUMO

Acute lung Injury (ALI) is the clinical syndrome of parenchymal lung disease, leading to an extremely high mortality. The pathogenesis of ALI is suggested to be a consequence of uncontrolled inflammation. Lipopolysaccharide (LPS)-induced ALI mice model is often used for the mechanism. Studies show that TGF-beta activated kinase 1 (MAP3K7) binding protein 1/2 (TAB2) plays a crucial role in LPS-induced inflammation response. Furthermore, microRNA-142a-3p (miR-142a-3p) has been observed to be involved in inflammation-induced disease. Thus, we investigated the role of miR-142a-3p and TAB2 on LPS-induced ALI, which involved the TLR4/TAB2/NF-κB signaling. ALI and normal lung tissues were collected to access the relative expression of pro-inflammatory cytokines and miR-142a-3p. Histopathological examination and Wet to Dry weight ratios of lung tissues were used to access the establishment of ALI models. Raw264.7 cells were transfected with si-TAB2 or miR-142a-3p mimics to elucidate the role of TAB2 or miR-142a-3p in the inflammatory cascade in ALI. Additionally, the relationship between miR-142a-3p and TAB2 was validated by dual-luciferase report system. Our study discovered that miR-142-3p was up-regulated both in LPS-induced ALI mice model and RAW264.7 cells model. MiR-142a-3p mimics group experienced significant decrease in the secretion of pro-inflammatory cytokines as a result of the inhibition of NF-κB signaling pathway. Bioinformatics database showed that the adaptor protein, TAB2, was critical in this pathway and it is the target gene of miR-142a-3p. Their relation was first confirmed by us via dual-luciferase report system. Results of our study demonstrated that miR-142a-3p exerts as a protective role in LPS-induced ALI through down-regulation of NF-κB signaling pathway.

5.
J Genet Couns ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31478310

RESUMO

BACKGROUND: Despite growing evidence of diagnostic yield and clinical utility of whole exome sequencing (WES) in patients with undiagnosed diseases, there remain significant cost and reimbursement barriers limiting access to such testing. The diagnostic yield and resulting clinical actions of WES for patients who previously faced insurance coverage barriers have not yet been explored. METHODS: We performed a retrospective descriptive analysis of clinical WES outcomes for patients facing insurance coverage barriers prior to clinical WES and who subsequently enrolled in the Undiagnosed Diseases Network (UDN). Clinical WES was completed as a result of participation in the UDN. Payer type, molecular diagnostic yield, and resulting clinical actions were evaluated. RESULTS: Sixty-six patients in the UDN faced insurance coverage barriers to WES at the time of enrollment (67% public payer, 26% private payer). Forty-two of 66 (64%) received insurance denial for clinician-ordered WES, 19/66 (29%) had health insurance through a payer known not to cover WES, and 5/66 (8%) had previous payer denial of other genetic tests. Clinical WES results yielded a molecular diagnosis in 23 of 66 patients (35% [78% pediatric, 65% neurologic indication]). Molecular diagnosis resulted in clinical actions in 14 of 23 patients (61%). CONCLUSIONS: These data demonstrate that a substantial proportion of patients who encountered insurance coverage barriers to WES had a clinically actionable molecular diagnosis, supporting the notion that WES has value as a covered benefit for patients who remain undiagnosed despite objective clinical findings.

6.
PLoS One ; 14(9): e0222338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31527891

RESUMO

Rhesus macaque is an important animal model in biomedical research, especially human disease, developmental, translational, and pre-clinical research. Blood physiological and biochemical parameters are important markers for physiology, pathology, and toxicology research. However, these parameters have not been systematically reported for Chinese rhesus macaques. To characterize the reference for these parameters, this study collected 1805 Chinese rhesus macaques living in Southwestern China. A total of 24 blood physiological indexes and 27 biochemical parameters were determined. Sex and age were found to affect these parameters. In conclusion, a comprehensive and systematic reference of hematological and biochemical parameters for Chinese rhesus macaque was established in this work on the basis of a large cohort. Such reference will benefit biomedical research employing rhesus macaques as animal models.

7.
Opt Express ; 27(15): 20525-20540, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31510145

RESUMO

We propose a quasi-counterfactual quantum swap gate for exchanging Alice's unknown photon state and Bob's unknown atomic state under the condition that only Alice's photon may appear in the transmission channel between Alice and Bob, while the probability of the existence of photon in the transmission channel is controllable and can tend to zero. Unlike standard counterfactual quantum communication protocols, quantum states exchange in present scenario is achieved by multiple phase operations, rather than multiple measurements. The total effect of those operations can be considered as a unitary time evolution operator. Therefore, the communication fidelity and efficiency of our protocol are always one if system imperfection and channel noise are not considered. Compared to standard counterfactual communication protocols, our protocol is easy to implement. We also show that it can be easily converted to a standard counterfactual one.

8.
J Zhejiang Univ Sci B ; 20(10): 816-827, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489801

RESUMO

Catalpol is the main active ingredient of an extract from Radix rehmanniae, which in a previous study showed a protective effect against various types of tissue injury. However, a protective effect of catalpol on uterine inflammation has not been reported. In this study, to investigate the protective mechanism of catalpol on lipopolysaccharide (LPS)-induced bovine endometrial epithelial cells (bEECs) and mouse endometritis, in vitro and in vivo inflammation models were established. The Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway and its downstream inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), western blot (WB), and immunofluorescence techniques. The results from ELISA and qRT-PCR showed that catalpol dose-dependently reduced the expression of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, and IL-6, and chemokines such as C-X-C motif chemokine ligand 8 (CXCL8) and CXCL5, both in bEECs and in uterine tissue. From the experimental results of WB, qRT-PCR, and immunofluorescence, the expression of TLR4 and the phosphorylation of NF-κB p65 were markedly inhibited by catalpol compared with the LPS group. The inflammatory damage to the mouse uterus caused by LPS was greatly reduced and was accompanied by a decline in myeloperoxidase (MPO) activity. The results of this study suggest that catalpol can exert an anti-inflammatory impact on LPS-induced bEECs and mouse endometritis by inhibiting inflammation and activation of the TLR4/NF-κB signaling pathway.

9.
PLoS One ; 14(9): e0222344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31550256

RESUMO

Around the world, pansies are one of the most popular garden flowers, but they are generally sensitive to high temperatures, and this limits the practicality of planting them during the warmest days of the year. However, a few pansy germplasms with improved heat tolerance have been discovered or bred, but the mechanisms of their heat resistance are not understood. In this study, we investigated the transcript profiles of a heat-tolerant pansy inbred line, DFM16, in response to high temperatures using RNAseq. Approximately 55.48 Gb of nucleotide data were obtained and assembled into 167,576 unigenes with an average length of 959 bp, of which, 5,708 genes were found to be differentially expressed after heat treatments. Real-time qPCR was performed to validate the expression profiles of the selected genes. Nine metabolic pathways were found to be significantly enriched, in the analysis of the differentially expressed genes. Several potentially interesting genes that encoded putative transcription regulators or key components involving heat shock protein (HSP), heat shock transcription factors (HSF), and antioxidants biosynthesis, were identified. These genes were highlighted to indicate their significance in response to heat stress and will be used as candidate genes to improve pansy heat-tolerance in the future.

10.
Ann Surg Oncol ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31429019

RESUMO

BACKGROUND: This randomized controlled trial aimed to investigate the effects of circumferential shaving on reducing the intraoperative margin positivity rate (MPR) during breast-conserving surgery (BCS). METHODS: Eligible breast cancer patients were randomly assigned into no-shave and shave groups. In the no-shave group, the cavity margins were collected for assessment after the tumor resection, whereas in the shave group, a circumferential shaving was performed before collecting the cavity margins. The primary outcome was the intraoperative MPR by frozen section analysis. RESULTS: A total of 181 patients, with a median age of 49 years, were randomized. Patient characteristics at baseline were well-balanced between the two groups. The intraoperative MPRs (12.1% vs. 7.8%, p = 0.38), postoperative MPRs (16.5% vs. 7.8%, p = 0.073), intraoperative re-excision rates (26.4% vs. 23.3%, p = 0.64), second operation rates (4.4% vs. 1.1%, p = 0.34), and successful BCS rate (93.4% vs. 94.4%, p = 0.94) were all similar between the no-shave and the shave groups. The volume of the shaved tissues was significantly increased in patients with larger breast volume (p < 0.01). In patients with C-E cup breasts, the no-shave and shave groups had 16.7% and 0% (p = 0.03) intraoperative MPRs, and 22.0% and 0% (p = 0.01) postoperative MPRs, respectively. In patients with A-B cup breasts, the MPRs were similar between the two groups. The presence of the ductal carcinoma in situ component is the only determinant of margin positivity. CONCLUSIONS: Circumferential shaving did not significantly reduce the MPR in BCS. Its benefit depends on the volume of the shaved tissues and the breast. Trial registration This trial was registered at ClinicalTrials.gov (NCT02648802).

11.
Oxid Med Cell Longev ; 2019: 8407206, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379990

RESUMO

Purpose: Oxidative stress induced by reduced blood circulation is a critical pathological damage to retinal ganglion cells (RGCs) in glaucoma. We previously showed that green tea extract (GTE) and its catechin constituents alleviate sodium iodate-induced retinal degeneration in rats. Here, we investigated the therapeutic effect of GTE on ischemia-induced RGC degeneration in rats. Methods: RGC degeneration was induced by ischemic reperfusion in adult Fischer F344 rats. Green tea extract (Theaphenon E) was intragastrically administered 4 times within 48 hours after ischemia. RGC survival, pupillary light reflex, expressions of cell apoptosis, oxidative stress, and inflammation-related proteins were studied. Results: Ischemic reperfusion significantly induced apoptotic RGCs, RGC loss, and larger constricted pupil area compared to the untreated normal rats. Expressions of activated caspase-3 and caspase-8, Sod2, and inflammation-related proteins as well as p38 phosphorylation were significantly upregulated in the ischemia-injured rats. Compared to the saline-fed ischemic rats, significantly higher number of surviving RGCs, less apoptotic RGCs, and smaller constricted pupil area were observed in the GTE-fed ischemic rats. GTE also reduced the increased protein expressions caused by ischemic injury but enhanced the Jak phosphorylation in the retina. Notably, green tea extract did not affect the survival of RGCs in the uninjured normal rats. Conclusions: In summary, GTE offers neuroprotection to RGCs under ischemic challenge, suggesting a potential therapeutic strategy for glaucoma and optic neuropathies.

12.
Genome Med ; 11(1): 48, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349857

RESUMO

BACKGROUND: Although mosaic variation has been known to cause disease for decades, high-throughput sequencing technologies with the analytical sensitivity to consistently detect variants at reduced allelic fractions have only recently emerged as routine clinical diagnostic tests. To date, few systematic analyses of mosaic variants detected by diagnostic exome sequencing for diverse clinical indications have been performed. METHODS: To investigate the frequency, type, allelic fraction, and phenotypic consequences of clinically relevant somatic mosaic single nucleotide variants (SNVs) and characteristics of the corresponding genes, we retrospectively queried reported mosaic variants from a cohort of ~ 12,000 samples submitted for clinical exome sequencing (ES) at Baylor Genetics. RESULTS: We found 120 mosaic variants involving 107 genes, including 80 mosaic SNVs in proband samples and 40 in parental/grandparental samples. Average mosaic alternate allele fraction (AAF) detected in autosomes and in X-linked disease genes in females was 18.2% compared with 34.8% in X-linked disease genes in males. Of these mosaic variants, 74 variants (61.7%) were classified as pathogenic or likely pathogenic and 46 (38.3%) as variants of uncertain significance. Mosaic variants occurred in disease genes associated with autosomal dominant (AD) or AD/autosomal recessive (AR) (67/120, 55.8%), X-linked (33/120, 27.5%), AD/somatic (10/120, 8.3%), and AR (8/120, 6.7%) inheritance. Of note, 1.7% (2/120) of variants were found in genes in which only somatic events have been described. Nine genes had recurrent mosaic events in unrelated individuals which accounted for 18.3% (22/120) of all detected mosaic variants in this study. The proband group was enriched for mosaicism affecting Ras signaling pathway genes. CONCLUSIONS: In sum, an estimated 1.5% of all molecular diagnoses made in this cohort could be attributed to a mosaic variant detected in the proband, while parental mosaicism was identified in 0.3% of families analyzed. As ES design favors breadth over depth of coverage, this estimate of the prevalence of mosaic variants likely represents an underestimate of the total number of clinically relevant mosaic variants in our cohort.

13.
Genet Med ; 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31263215

RESUMO

PURPOSE: Haploinsufficiency of DYRK1A causes a recognizable clinical syndrome. The goal of this paper is to investigate congenital anomalies of the kidney and urinary tract (CAKUT) and genital defects (GD) in patients with DYRK1A variants. METHODS: A large database of clinical exome sequencing (ES) was queried for de novo DYRK1A variants and CAKUT/GD phenotypes were characterized. Xenopus laevis (frog) was chosen as a model organism to assess Dyrk1a's role in renal development. RESULTS: Phenotypic details and variants of 19 patients were compiled after an initial observation that one patient with a de novo pathogenic variant in DYRK1A had GD. CAKUT/GD data were available from 15 patients, 11 of whom presented with CAKUT/GD. Studies in Xenopus embryos demonstrated that knockdown of Dyrk1a, which is expressed in forming nephrons, disrupts the development of segments of embryonic nephrons, which ultimately give rise to the entire genitourinary (GU) tract. These defects could be rescued by coinjecting wild-type human DYRK1A RNA, but not with DYRK1AR205* or DYRK1AL245R RNA. CONCLUSION: Evidence supports routine GU screening of all individuals with de novo DYRK1A pathogenic variants to ensure optimized clinical management. Collectively, the reported clinical data and loss-of-function studies in Xenopus substantiate a novel role for DYRK1A in GU development.

14.
Metab Eng ; 55: 191-200, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31348998

RESUMO

Microbial-based chemical synthesis serves as a promising approach for sustainable production of industrially important products. However, limited production performance caused by metabolic burden or genetic variations poses one of the major challenges in achieving an economically viable biomanufacturing process. To address this issue, one superior strategy is to couple the product synthesis with cellular growth, which renders production obligatory for cell survival. Here we create a pyruvate-driven metabolic scenario in engineered Escherichia coli for growth-coupled bioproduction, with which we demonstrate its application in boosting production of anthranilate and its derivatives. Deletion of a minimal set of endogenous pyruvate-releasing pathways engenders anthranilate synthesis as the salvage route for pyruvate generation to support cell growth, concomitant with simultaneous anthranilate production. Further introduction of native and non-native downstream pathways affords production enhancement of two anthranilate-derived high-value products including L-tryptophan and cis, cis-muconic acid from different carbon sources. The work reported here presents a new growth-coupled strategy with demonstrated feasibility for promoting microbial production.

15.
J Biomol Struct Dyn ; : 1-17, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31203730

RESUMO

The superoxide-generating activity of Nox5 is regulated by Ca2+ flux, primarily through its self-contained calcium binding domain (EFD). Upon Ca2+ binding, Nox5's EFD undergoes a conformational change that exposes its buried hydrophobic residues. Previously, we determined the Ca2+ binding constants of the N-terminal half domain (N-EFD). Here we performed a similar characterization with its C-terminal lobe (C-EFD). Our studies revealed that the binding affinities (Ka's) of the EFD are in the range of 108-105 M-1 with a strong Ca2+ binding that occurs in the C-EFD. The 3rd Ca2+ binding site also binds Mg2+ (Ka = 4.53 × 103 M-1), where its high Ca2+ binding affinity becomes moderate in cellular conditions. The essential hydrophobic exposure upon metal binding was assessed with the analysis of the 1-anilino-8-naphthalene sulfonate (ANS) interaction via fluorescence and calorimetry. While the ANS fluorescence and binding studies agree with each other in general, the results do not correlate to the actual hydrophobic exposure content. The heat capacity change (ΔCp) of Ca2+ binding for EFD is -24.1 cal/mol.K, while those of N-EFD and C-EFD are -56.3 and -41.6 cal/mol·K, respectively, indicating a significant hydrophobic exposure and polar burial. The latter was confirmed by limited trypsin digestion. The comparison of Nox5's EFD to calmodulin, including homology modeling, was discussed in the report. Communicated by Ramaswamy H. Sarma.

16.
Small ; 15(28): e1900924, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31165562

RESUMO

An ideal photoelectrochemical (PEC) anode should process effective light absorption, charge transport, and separation efficiency. Here, a novel 3D brochosomes-like TiO2 /WO3 /BiVO4 array as an efficient photoanode by combining a colloid polystyrene sphere template and electrochemical deposition routes for PEC hydrogen generation is reported. The as-fabricated 3D TiO2 /WO3 /BiVO4 brochosomes photoanode yields excellent PEC performance with photocurrent densities of ≈3.13 and ≈4.27 mA cm-2 with FeOOH/NiOOH catalyst, respectively, measured in 0.5 m Na2 SO4 solution with 0.1 m Na2 SO3 at 1.23 V versus reversible hydrogen electrode (RHE) under simulated AM1.5 light illumination, which is ≈6 times the reference sample of a planar WO3 /BiVO4 film electrode. The significantly improved performance could be benefited from the ordered hollow porous structure that provides enhanced light absorption and efficient charge transport as well as improved charge separation efficiency by WO3 /BiVO4 "host-guest" heterojunctions.

17.
Metab Eng ; 55: 85-91, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31229565

RESUMO

Plasmid-based microbial systems have been a major workhorse for chemical and pharmaceutical production. The biosafety issues and elevated industrial cost of antibiotic usage have led to the development of alternative strategies for plasmid selection and maintenance. Such strategies, including auxotrophy complementation, post-segregational killing, operator-repressor and RNA-based interactions often require extensive engineering of various elements and may result in extra metabolic burden in the cells. Herein, we report a design of synthetic symbiosis combining plasmid displacement to construct a phenotype-stable microbial system. By sequestrating an endogenous essential gene folP, cells obtained long-term plasmid maintenance with minimum cost. The phenotype performance was also inherited for up to 80 generations demonstrated by the production of salicylic acid in Escherichia coli. Meanwhile, the temperature-induced curing method of the intermediate plasmids enables rapid engineering. This design can lead to broad applications as a reliable and convenient plasmid-based expression system.

18.
BMC Cancer ; 19(1): 541, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170946

RESUMO

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive and heterogeneous disease. Nomograms predicting outcomes of TNBC are needed for risk management. METHODS: Nomograms were based on an analysis of 296 non-metastatic TNBC patients treated at Sun Yat-sen Memorial Hospital from 2002 to 2014. The end points were disease-free survival (DFS) and overall survival (OS). Predictive accuracy and discriminative ability were evaluated by concordance index (C-index), area under the curve (AUC) and calibration curve, and compared with the American Joint Committee on Cancer (AJCC) staging system, PREDICT and CancerMath. Models were subjected to bootstrap internal validation and external validation using independent cohorts of 191 patients from the second Xiangya Hospital and Peking University Shenzhen Hospital between 2007 and 2012. RESULTS: On multivariable analysis of training cohort, independent prognostic factors were stromal tumor-infiltrating lymphocytes (TILs), tumor size, node status, and Ki67 index, which were then selected into the nomograms. The calibration curves for probability of DFS and OS showed optimal agreement between nomogram prediction and actual observation. The C-index of nomograms was significantly higher than that of the seventh and eighth AJCC staging system for predicting DFS (training: 0.743 vs 0.666 (P = 0.003) and 0.664 (P = 0.024); validation: 0.784 vs 0.632 (P = 0.02) and 0.607 (P = 0.002)) and OS (training: 0.791 vs 0.683 (P = 0.004) and 0.677 (P < 0.001); validation: 0.783 vs 0.656 (P = 0.006) and 0.606 (P = 0.001)). Our nomograms had larger AUCs compared with PREDICT and CancerMath. In addition, the nomograms showed good performance in stratifying different risk groups of patients both in the training and validation cohorts. CONCLUSION: We have developed novel and practical nomograms that can provide individual prediction of DFS and OS for TNBC based on stromal TILs, tumor size, node status, and Ki67 index. Our nomograms may help clinicians in risk consulting and selection of long term survivors.

19.
BMC Med Genomics ; 12(1): 76, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138263

RESUMO

BACKGROUND: Congenital hearing loss affects approximately 1-2 infants out of every 1000, with 50% of the cases resulting from genetic factors. Targeted gene panels have been widely used for genetic diagnosis of hearing loss. This study aims to reveal new diagnoses via reanalyzing historical data of a multigene panel, and exam the reasons for new diagnoses. METHODS: A total of 210 samples were enlisted, including clinical reports and sequencing data of patients with congenital/prelingual hearing loss who were referred to clinical genetic testing from October 2014 to June 2017. All variants listed on the original clinical reports were reinterpreted according to the standards and guidelines recommended by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP). Expanded analysis of raw data were performed in undiagnosed cases. RESULTS: Re-analysis resulted in nine new diagnoses, improving the overall diagnostic rate from 39 to 43%. New diagnoses were attributed to newly published clinical evidence in the literature, adoption of new interpretation guidelines and expanded analysis range. CONCLUSION: This work demonstrates benefits of reanalysis of targeted gene panel data, indicating that periodical reanalysis should be performed in clinical practice.

20.
Microb Pathog ; 132: 302-312, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059756

RESUMO

Acute lung injury (ALI) is clinically characterized by excessive inflammation leading to acute respiratory distress syndrome (ARDS), having high morbidity and mortality both in human and animals. Ginsenoside Rb1 (Rb1) is a major primary bioactive component extracted by Panax ginseng, which has numerous pharmacological functions such as anti-cancer, anti-inflammatory, and antioxidant. However, the anti-inflammatory effects of Rb1 in Staphylococcus aureus (S. aureus)-induced ALI in mice have not been investigated. The aim of the current study was to determine the anti-inflammatory influence of Rb1 on S. aureus-induced ALI in mice, and to explore its possible underlying principle mechanisms in RAW 264.7 macrophage cells. The results of physical morphology, histopathological variation and wet-to-dry weight ratio of lungs revealed that Rb1 significantly attenuated S. aureus-induced lung injury. Furthermore, qPCR results displayed that Rb1 inhibited IL-1ß, IL-6 and TNF-α production both in vivo and in vitro. The activation of Toll-like receptor 2 (TLR2) by S. aureus was inhibited by application of Rb1 as confirmed by results of immunofluorescence assay. The expression of NF-kB and MAPK signaling proteins revealed that Rb1 significantly attenuated the phosphorylation of p65, ERK, as well as JNK. Altogether, the results of this experiment presented that Rb1 has ability to protect S. aureus-induced ALI in mice by attenuating TLR-2-mediated NF-kB and MAPK signaling pathways. Consequently, Rb-1 might be a potential medicine in the treatment of S. aureus-induced lung inflammation.


Assuntos
Lesão Pulmonar Aguda/microbiologia , Ginsenosídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pulmão/patologia , Masculino , Camundongos , Panax/química , Pneumonia , Células RAW 264.7/efeitos dos fármacos , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA