Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.853
Filtrar
1.
Chin Med J (Engl) ; 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31567476

RESUMO

BACKGROUND: Primary spontaneous pneumothorax (PSP) is a common manifestation of Birt-Hogg-Dubé (BHD) syndrome, which is an autosomal dominant disorder caused by mutation of the folliculin (FLCN) gene. This study was established to investigate the mutation of the FLCN gene and the phenotype in a family with PSP. METHODS: We investigated the clinical and genetic characteristics of a large Chinese family with recurrent spontaneous pneumothorax. Genetic testing was performed by Sanger sequencing of the coding exons (4-14 exons) of the FLCN gene. RESULTS: Among ten affected members in a multi-generational PSP kindred, with a total of 18 episodes of spontaneous pneumothorax, the median age for the initial onset of pneumothorax was 42.5 years (interquartile range: 28.8-57.2 years). Chest computed tomography scan of the proband showed pulmonary cysts and pneumothorax. A novel nonsense mutation (c.1273C>T) in exon 11 of FLCN gene that leads to a pre-mature stop codon (p.Gln425*) was identified in the family. The genetic analysis confirmed the diagnosis of BHD syndrome in this family in the absence of skin lesions or renal tumors. CONCLUSIONS: A novel nonsense mutation of FLCN gene was found in a large family with PSP in China. Our results expand the mutational spectrum of FLCN gene in patients with BHD syndrome.

2.
Theranostics ; 9(22): 6587-6600, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588237

RESUMO

It has been demonstrated that mesenchymal stem cells (MSCs) differentiated from human embryonic stem cells (hESCs), name EMSCs, can treat a variety of autoimmune and inflammatory diseases, with similar efficacies to those achieved with MSCs derived from somatic tissues such as bone marrow (BMSCs). The chance increases even higher for EMSCs, than somatic tissue derived MSCs​, to become a cell drug as the former can be produced in large scale from an unlimited hESC line with easier quality control and less biosafety concern. We have further demonstrated that both human ESCs and EMSCs, after aggregation to form spheroids, can tolerate hypoxic and ambient conditions (AC) for over 4 and 10 days, respectively, without loss of their viability and alteration of their functions. Based on these advantages, we decided to test whether EMSC spheroids, made in large quantity and delivered through a long-term distance at AC, can treat osteoarthritis spontaneously developed in rhesus macaques (M. mulatta) monkeys as well as the allogenic MSCs. Methods: Xenogeneic AC-transported EMSC spheroids or allogenic BMSCs were injected into the articular cavity of both knees of the monkeys at 3 animals per group. Another two macaques were injected the same way with saline as controls. Results: Both EMSCs and BMSCs groups showed significant amelioration indicated by the reduction of swelling joint size and amplification of keen flare angle post-treatment, compared to the control group. Examinations via X-ray and MRI also indicated the decrease of inflammation and osteophyma, and recovery of the synovium and cartilage in both treated groups. No sign of allergy or graft versus host disease was observed in the animals. Conclusion: Our results demonstrate that human EMSC spheroids can prevent the osteoarthtitis progression and ameliorate osteoarthritis in the rhesus macaques as well as allogenic BMSCs, and this study shall help advance the clinical application of EMSCs.

3.
Breast J ; 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31588665

RESUMO

The incidence of involved intramammary lymph node (intra-MLN) with breast carcinoma (BC) is rare. Its clinical significance and impact on the clinical decision making is unclear. A total of 113 BC cases with at least one positive intra-MLN were collected from 11 academic institutions. The inclusion criteria were subsequent axillary lymph node dissection, and the availability of information on T-stage, size of node metastasis, extranodal extension status, biomarkers status, and clinical follow-up. Stage 4 cases and/or neo-adjuvant treated patients were excluded. AJCC TN-stage was calculated twice, with and without intra-MLN. Five-year overall survival (OS) and relapse (local and/or distant)-free survival (RFS) were calculated and correlated with the clinicopathologic variables. Excluding intra-MLN, TN-stage correlated with OS (P = .016) but not with RFS (P = .19). However, when intra-MLN was included, TN-stage correlated with both OS (P < .001) and RFS (P = .016). In the multivariate analysis, when intra-MLN was excluded, only radiation therapy (RT) correlated with RFS (HR = 0.19, 95% CI: 0.054-0.66, P = .009). However, when intra-MLN was included in the TN-stage both RT (HR = 0.13, 95% CI: 0.04-0.45, P = .001) and TN-stage 3 (HR = 8.92, 95% CI: 1.47-54, P = .017) correlated with RFS. Tumor multifocality was the only variable correlated with OS when the intra-MLN involvement was excluded. When intra-MLN was included, multifocality became insignificant but TN-stage 3 correlated with OS (HR = 8.59, 95% CI: 1.06-69.71, P = .044). Positive intra-MLN is an independent factor in predicting both RFS and OS.

4.
Int J Clin Oncol ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584107

RESUMO

BACKGROUND: Non-hematopoietic malignancies first presented as an axillary mass constitute a unique clinical presentation. We investigated the incidence of various types of malignancies and aimed to define clinicopathologic variables that may assist in the diagnosis, with focus on occult breast carcinoma (OBC). DESIGN: We reviewed the pathology reports of cases with non-hematopoietic malignancies of the axillary region in our institution between 2000 and 2016. We included patients who presented first with axillary mass and with the absence of a known primary. We recorded patients' age and gender, tumor characteristics including size, histologic type, number of positive lymph nodes, and the clinical management. Then we focused on BC which were divided into OBC or primary BC (PBC). RESULTS: There were 100 cases that met our criteria (28 melanoma, 7 sarcoma and 65 carcinoma). For carcinoma cases, there were 42 BC (19 OBC, 17 PBC, and 6 possible OBC), 17 non-BC, and 6 carcinoma of unknown primary (CUP). Tumors found incidentally were more likely to be of breast primary (p = 0.01). Larger tumor size (in mm) favored melanoma or sarcoma over BC, non-BC carcinoma or CUP with median and range 61 (15, 180), 60 (23, 80), 30 (15, 75), 31 (17, 90), 26 (20, 55), respectively (p < 0.001). There were no differences in the histopathologic findings or clinical presentation. CONCLUSIONS: More than half of the patients with axillary malignancy have a tumor of non-breast origin. Therefore, clinical and pathologic studies are warranted to identify the primary site.

5.
BMC Womens Health ; 19(1): 117, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590639

RESUMO

BACKGROUND: Women with a higher number of pregnancies have a higher risk of developing cardiovascular diseases. Subtle fluctuations in albumin excretion could be related to pathophysiologic changes in the vascular system. We aimed to investigate the possible association of parity with low-grade albuminuria. METHODS: We conducted a community-based study in 6495 women aged 40 years or older. Low-grade albuminuria was defined according to the highest quartile of urine albumin-to-creatinine ratio in participants free of micro- or macro-albuminuria. RESULTS: Parous women with a higher number of pregnancies had increased age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), fasting plasma glucose (FPG), and fasting insulin, as well as decreased high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR) levels, and proportion of menopause. The prevalence of low-grade albuminuria in parous women gradually increased with parity number. Compared with women with one childbirth, those with more than two childbirths were independently associated with a higher prevalent low-grade albuminuria (odds ratios [ORs] 1.41, 95% confidence interval [CI], 1.09-1.81) after multiple adjustments. In subgroup analysis after multiple adjustments, significant relation between parity number and prevalent low-grade albuminuria was detected in subjects age 55 years or older. CONCLUSION: Number of parity is associated with prevalent low-grade albuminuria in middle-aged and elderly Chinese women without micro- or macro-albuminuria.

6.
Am J Clin Pathol ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31602455

RESUMO

OBJECTIVES: Women with atypical ductal hyperplasia (ADH), unlike those with ductal carcinoma in situ (DCIS), are denied eligibility for active surveillance clinical trials. METHODS: We applied the inclusion criteria of the Comparison of Operative to Monitoring and Endocrine Therapy (COMET) trial to the cases of women (n = 165) at the Roswell Park Cancer Institute who had a diagnosis of ADH, ADH bordering on DCIS, or low- to intermediate-grade DCIS on core biopsy taken during screening mammography. Upgrade of lesions to high risk was based on invasive carcinoma, high-grade DCIS, or DCIS with comedo necrosis. RESULTS: In total, nine (5.5%) lesions were upgraded: two (1.7%) reported ADH, one (5.9%) reported ADH bordering on DCIS, and six (19.4%) reported DCIS (P = .002); and two (1.6%) reclassified ADH vs seven (17.1%) reclassified DCIS (P < .001). In multivariate analysis, only increased number of foci had the potential to predict high risk (odds ratio: 1.39; P = .06). CONCLUSIONS: We conclude that ADH and ADH bordering on DCIS have lower upgrade rates than DCIS. We recommend opening an active surveillance clinical trial for women with these diagnoses.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31595321

RESUMO

A hydroponic experiment was carried out to study the accumulation characteristics of copper (Cu) and lead (Pb) combined pollution in three ornamental plants. The results showed that these tested ornamental plants had higher tolerance to Cu-Pb combined pollution and could effectively accumulate the heavy metals. The Cu and Pb concentrations were higher in the roots of the ornamental plants than that in the shoots. For Panax notoginseng (P. notoginseng), Chlorophytum comosum (C. comosum) and Calendula officinalis (C. officinalis), the average Cu and Pb concentration in the three ornamental plants were 1402.1 mg/kg, 829.5 mg/kg, and 1473.4 mg/kg for Cu and 2710.4 mg/kg, 4250.3 mg/kg, and 4303.6 mg/kg for Pb, respectively. The three ornamental plants accumulation and tolerance to Cu-Pb were demonstrated through the hydroponic-culture method in this study. Therefore, the three ornamental plants should have great potential to be used in remediation of soils contaminated by Cu and Pb and beautifying the environment simultaneously.

8.
Cell Cycle ; : 1-15, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31595820

RESUMO

Retinoic acid inducible gene-I (Rig-I) has been well documented as a cytosolic pattern recognition receptor that can sense viral RNA ligands to initiate the interferon-mediated antiviral immunity. However, little is known about the biological behaviors of Rig-I devoid of viral infection. Herein, we investigated the roles of Rig-I in the regulation of cellular senescence. In comparison to wild-type counterparts, Rig-I-/- mice displayed the accelerated loss of hair, less responsiveness to gentle physical stimuli and shorten survival time. Likewise, Rig-I deficiency rendered mouse embryonic fibroblasts (MEFs) more susceptible to the serial passages-associated replicative senescence. By performing a transcriptome analysis, we identified integrins at the intersections of biological pathways affected by Rig-I. Among these, integrin ß3 was negatively regulated by Rig-I, and significantly upregulated with the occurrence of senescence. Gene silencing of Itgb3 (encoding integrin ß3) retarded the progression of cellular senescence in both WT and Rig-I-/- MEFs. Notably, this effect was more prominent in Rig-I-/- MEFs. Furthermore, p38 MAPK was a key downstream molecule for integrin ß3-mediated senescence, and overactivated in senescent Rig-I-/- MEFs. Taken together, Rig-I deficiency contributes to cellular senescence through amplifying integrin ß3/p38 MAPK signaling. Our findings provide the evidence that Rig-I is a key regulator of cellular senescence, which will be helpful in better understanding its function without viral infection. Abbreviations: Rig-I: retinoic acid inducible gene-I; SASP: senescence-associated secretory phenotype; ECM: extracellular matrix; Itgb3: integrin beta 3; PRR: pattern recognition receptor; MEFs: mouse embryonic fibroblasts; Il-1ß: interleukin-1 beta; Il-6: interleukin-6; Il-8: interleukin-8; Cxcl1: chemokine (C-X-C motif) ligand 1; Ccl2: chemokine (C-C motif) ligand 2; WT, wild type; BM: bone marrow; MAPK: mitogen-activated protein kinase; ERK: extracellular signal-regulated kinases; JNK: Jun N-terminal kinases; SA-ß-gal: senescence-associated ß-galactosidase; qPCR: quantitative reverse-transcription PCR; PBS: phosphate-buffered saline.

9.
Chin Med J (Engl) ; 132(19): 2278-2285, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31567379

RESUMO

BACKGROUND: Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers. The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15 (GDF-15) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in assessing hospitalized patients with acute heart failure (AHF). METHODS: In total, 260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016. Medical history and blood samples were collected within 24 h after the admission. The primary endpoint was the all-cause mortality within 1 year. The patients were divided into survival group and death group based on the endpoint. With established mortality risk factors and serum GDF-15 level, receiver-operator characteristic (ROC) analyses were performed. Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15. RESULTS: Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors (P < 0.001). In ROC analyses, area under curve (AUC) for GDF-15 to predict 1-year mortality was 0.707 (95% confidence interval [CI]: 0.648-0.762, P < 0.001), and for NT-proBNP was 0.682 (95% CI: 0.622-0.738, P < 0.001). No statistically significant difference was found between the two markers (P = 0.650). Based on the optimal cut-offs (GDF-15: 4526.0 ng/L; NT-proBNP: 1978.0 ng/L), the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction (AUC = 0.743, 95% CI: 0.685-0.795, P < 0.001). CONCLUSIONS: GDF-15, as a prognostic marker in patients with AHF, is not inferior to NT-proBNP. Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis. CLINICAL TRIAL REGISTRATION: ChiCTR-ONC-12001944, http://www.chictr.org.cn.

10.
Technol Cancer Res Treat ; 18: 1533033819851833, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31570091

RESUMO

OBJECTIVE: To investigate the role of miR-26a-5p in cell proliferation and doxorubicin sensitivity in hepatocellular carcinoma. METHODS: We evaluated miR-26a-5p expression in hepatocellular carcinoma tissues and cell lines by reverse transcription polymerase chain reaction. Cell Counting Kit-8 was used to examine cell proliferation. Relationship between miR-26a-5p and aurora kinase A was evaluated by luciferase report system. Western blot was used to detect expression of aurora kinase A. RESULTS: In this study, we observed miR-26a-5p was downregulated in hepatocellular carcinoma tissues and cell lines. Gain-of-function experiments showed that proliferation rate of hepatocellular carcinoma cells decreased under condition of miR-26a-5p mimics. We found miR-26a-5p mimics could enhance doxorubicin sensitivity of hepatocellular carcinoma cells. Further study showed that aurora kinase A was target gene of miR-26a-5p. Suppression of aurora kinase A could lead to lower cell proliferation and higher doxorubicin sensitivity of hepatocellular carcinoma cells. CONCLUSION: Our study found that miR-26a-5p could inhibit cell proliferation and enhance doxorubicin sensitivity in hepatocellular carcinoma cells by targeting aurora kinase A.

11.
J Am Coll Cardiol ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31487545

RESUMO

BACKGROUND: Low detection and nonadherence are major problems in current management approaches for patients with suspected atrial fibrillation (AF). Mobile health (mHealth) devices may enable earlier AF detection, and improved AF management. OBJECTIVES: To investigate the effectiveness of AF screening in a large population-based cohort using smart device based photoplethysmography (PPG) technology, combined with a clinical care AF management pathway using a mHealth approach. METHODS: AF screening was performed with smart devices using PPG technology (Huawei Technologies Co., Ltd., Shenzhen, China) which were made available for the population aged over 18 years across China. Monitoring for at least 14-days with a wristband (HONOR BAND 4) or wristwatch (HUAWEI WATCH GT, HONOR WATCH), was allowed. The patients with 'possible AF' episodes using the PPG algorithm were further confirmed by health providers among the MAFA (mobile AF App) Telecare center and network hospitals, with clinical evaluation, electrocardiogram (ECG), or 24-h Holter. RESULTS: There were 246,541 individuals who downloaded the PPG screening App, and 187,912 individuals used smart devices to monitor their pulse rhythm between October 26, 2018 and May 20, 2019. Among those with PPG monitoring (mean age 35 years, 86.7% male), 424 (mean age 54 years, 87.0% male) received a 'suspected AF' notification (424/187,912, 0.23%). Of those effectively followed up, 227 individuals (227/262, 87.0%) were confirmed as having AF, with the positive predictive value (PPV) of PPG signals being 91.6% (95% confidential interval (CI) 91.5%-91.8%). Both 'suspected AF' and 'identified AF' markedly increased with age (p for trend <0.001), and individuals in Northeast China had the highest proportion of detected AF of 0.28% (95%CI 0.20-0.39). Of the individuals with identified AF, 216 (216/227, 95.1%) subsequently entered a programme of integrated AF management using a mobile AF application (mAFA); approximately 80% of 'high risk' patients were successfully anticoagulated. CONCLUSIONS: Based on the present study, continuous home-monitoring with smart device based PPG technology could be a feasible approach for AF screening. This would help efforts at screening and detection of AF, as well as early interventions to reduce stroke and other AF-related complications.

12.
Math Biosci Eng ; 16(5): 4559-4580, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31499677

RESUMO

In this paper, we propose a robust video steganographic method, which can efficiently hide confidential messages in video sequences, and ensure that these messages are perfectly reconstructed by recipient. To apply proposed scheme to video sequences, we must be faced with two nontrivial problems: (a) how to effectively minimize the total steganographic distortion for each video frame? (b) how to recover the hidden messages if some frames are lost or damaged? We tackle the first question by designing a new distortion function, which employs two continuous adjacent frames with the same scene as side-information. The second question is addressed by data sharing. In this mechanism, the original data is expanded and split into multiple shares by using multi-ary Vandermonde matrix. Since these shares contain a lot of data redundancy, the recipient can recover the hidden data even if some frames are damaged or lost during delivery. Extensive experiments show that proposed scheme outperforms the state-of-the-arts in terms of robustness and diverse attacks.

13.
J Asthma ; : 1-9, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31539289

RESUMO

Objective: We compared the pharmacokinetic exposure following a single subcutaneous dose of benralizumab 30 mg using either autoinjectors (AI) or accessorized prefilled syringes (APFS). APFS and AI functionality and reliability for at-home benralizumab delivery have been demonstrated in the GREGALE and GRECO studies, respectively. Methods: In the open-label AMES study (NCT02968914), 180 healthy adult men and women were randomized to one of two device (AI or APFS) and three injection site (upper arm, abdomen, or thigh) combinations. Randomization was stratified by weight (<70 kg, 70-84.9 kg, and ≥85 kg). Blood eosinophil counts were measured on Days 1, 8, 29, and 57. Results: Benralizumab pharmacokinetic exposure was similar between AI and APFS. Geometric mean ratios (AI/APFS) (90% CI) were 92.8% (87.4-98.6) and 94.5% (88.2-101.2) for two area under the concentration‒time curve measurements (AUClast and AUCinf). Benralizumab exposure was approximately 15-30% greater for thigh vs. abdomen or upper arm administration. Exposure was slightly greater for APFS vs. AI regardless of injection site or weight class. These differences were unlikely to be clinically relevant, as eosinophil depletion was achieved consistently with both devices at all injection sites. No device malfunctions were reported. No new or unexpected safety findings were observed. Conclusion: Benralizumab pharmacokinetic exposure was similar between AI and APFS, with consistent blood eosinophil count depletion observed with both devices. These results support benralizumab administration with either AI or APFS, providing patients and physicians increased choice, flexibility, and convenience for potential at-home delivery.

14.
Theranostics ; 9(21): 6112-6128, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534540

RESUMO

Mesenchymal stem cells (MSC) derived from adult tissues effectively promote wound healing. However, MSC quality varies, and the quantity of MSC is limited, as MSC are acquired through donations. Moreover, the survival and functioning of dissociated MSC delivered to an inflammatory lesion are subject to challenges. Methods: Here, spheres (EMSCSp) generated from human embryonic stem cell-derived MSC (EMSC) were directly dropped onto excised wounds in mice; the effects of EMSCSp were compared to those of dissociated EMSC (EMSCDiss). Following transplantation, we measured the extent of wound closure, dissected the histological features of the wounds, determined transcriptomic changes in cells isolated from the treated and control wounds, and evaluated the molecular mechanism of the effects of EMSC. Results: The application of EMSCSp onto murine dermal wounds substantially increased survival and efficacy of EMSC compared to the topical application of EMSCDiss. RNA sequencing (RNA-Seq) of cells isolated from the wounds highlighted the involvement of CXCL12-CXCR4 signaling in the effects of EMSCSp, which was verified in EMSC via CXCL12 knockdown and in target cells (vascular endothelial cells, epithelial keratinocytes, and macrophages) via CXCR4 inhibition. Finally, we enhanced the biosafety of EMSCSp by engineering cells with an inducible suicide gene. Conclusions: Together, these data suggest the topical application of EMSCSp as an unlimited, quality-assured, safe, and noninvasive therapy for wound healing and the CXCL12-CXCR4 axis as a key player in this treatment.

15.
Plant Cell Rep ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31473792

RESUMO

KEY MESSAGE: CrCOMT, a COMT gene in Carex rigescens, was verified to enhance salt stress tolerance in transgenic Arabidopsis. High salinity severely restricts plant growth and development while melatonin can alleviate salt damage. Caffeic acid O-methyltransferase (COMT) plays an important role in regulating plant growth, development, and stress responses. COMT could also participate in melatonin biosynthesis. The objective of this study was to identify CrCOMT from Carex rigescens (Franch.) V. Krecz, a stress-tolerant grass species with a widespread distribution in north China, and to determine its physiological functions and regulatory mechanisms that impart tolerance to salt stress. The results showed that the transcription of CrCOMT exhibited different expression patterns under salt, drought, and ABA treatments. Transgenic Arabidopsis with the overexpression of CrCOMT exhibited improved growth and physiological performance under salt stress, such as higher lateral root numbers, proline level, and chlorophyll content, than in the wild type (WT). Overexpression of CrCOMT also increased dehydration tolerance in Arabidopsis. The transcription of salt response genes was more highly activated in transgenic plants than in the WT under salt stress conditions. In addition, the melatonin content in transgenic plants was higher than that in the WT after stress treatment. Taken together, our results indicated that CrCOMT may positively regulate stress responses and melatonin synthesis under salt stress.

16.
J Invest Dermatol ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31494092

RESUMO

Dermis harbor distinct mesenchymal stem cell populations, which play equally important roles as epidermal stem cells in skin homeostasis and regeneration. However, to reliably identify and directly isolate the in vivo counterpart of these cells is still challenging. Using the epidermal stem cell marker CD49f, we defined CD49fhigh distinct mesenchymal subpopulation in the dermis. In vitro and in vivo differentiation assays and transcriptome analysis demonstrated that CD49fhigh cells possess neural crest-like cell characteristics. Further results showed that the formation of hair follicle-like budding structure and the expressions of key genes regulating hair follicle development were induced when hair follicle epithelial cells were co-cultured with CD49fhigh cells. Moreover, we found that CD49fhigh cells activated Notch signaling in co-cultured hair follicle epithelial cells, whereas inhibition of Notch signaling resulted in epidermal cysts-like spheres and loss maintenance of hair follicle epithelial cells characteristics. Furthermore, we identified Itga7 and CD49f as an efficient biomarker panel for direct selection of CD49fhigh skin mesenchymal stem cells. Our results lead to a deeper understanding of heterogeneity and the function of mesenchymal cells in the skin and may facilitate potential translational applications of these cells.

17.
Sci Rep ; 9(1): 13303, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527770

RESUMO

Gyroviruses (GyVs) are small, single-stranded, circular DNA viruses in the genus Gyrovirus, which consists of the chicken anemia virus (CAV) prototype and nine other viral species. These different GyV species have been reported in chickens, humans, mice, and companion animals. To date, CAV has been identified in the feces of domestic cats, while the circulation of other GyV species in cats is currently unknown. In the present study, 197 fecal samples were collected from pet cats in northeast China, and samples were screened for different GyV species by PCR. Twelve GyV strains were identified from the feces of pet cats. These included 4 positive for CAV, 3 for HGyV/AGV2, 3 for GyV3 and 2 positive for GyV6. The complete genome sequences of the 12 cat-sourced GyV strains showed 93.9-99.7% nucleotide identities to the homologous reference GyV strains. Phylogenetic analyses based on the complete genomes, VP1, VP2 and VP3 genes showed the identical classification of GyV species with previous reports. Moreover, one and four unique amino acid substitutions were identified in the VP1 protein of the cat-sourced HGyV/AGV2 and GyV6 strains, respectively, and one substitution was also observed in the VP2 protein of one GyV6 strain identified in this study. In conclusion, our investigation demonstrates that the diverse GyV species were circulating in domestic cats, and provides the first molecular evidence for the circulation of HGyV/AGV2, GyV3 and GyV6 in domestic cats. These cat-origin GyVs possessed considerable genetic diversity. This study also raises the possibility that domestic cats, as reservoirs for gyroviruses, may inadvertently disseminate viruses to other species, e.g., humans and chickens.

18.
Sci Rep ; 9(1): 13455, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530839

RESUMO

Due to the loss of DNA repair mechanisms in colorectal cancer (CRC) with microsatellite instability (MSI), somatic mutations accumulate within DNA; making them more prone to attack by tumor infiltrating lymphocytes (TIL) and macrophages. We hypothesize that MSI-High (MSI-H) patients have favorable survival due to increased tumor immunogenicity. The Cancer Genome Atlas (TCGA) was used to evaluate gene expression from 283 patients with CRC, comparing MSI-H and microsatellite stable (MSS) patients. CIBERSORT algorithm estimated the fraction of immune cell types. We found that low expression of DNA repair genes (MLH1, MLH3, PMS1, PMS2, ATR, PRKDC, ATM, BRCA2) associated with MSI-H. MSI-H was directly associated with Helper T-cells (p = 0.034) and M1 macrophages (p < 0.0001). MSI-H tumors associated with diminished intra-tumoral heterogeneity as well as higher expression of checkpoint molecules PD-1, PD-L1, CTLA4, LAG3 and TIM3 (p < 0.0001). Improved OS was seen in patients with low ATM, PMS2 and MLH3. In the TCGA CRC cohort, decreased expression of DNA repair genes associated with MSI-H. MSI-H patients had improved survival, likely due to higher TIL and M1 macrophage infiltration as well as lower intra-tumoral heterogeneity. MSI-H also associates with expression of immune checkpoint molecules with potential for development of therapeutic targets.

19.
Cells ; 8(10)2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547622

RESUMO

After ovulation, mammalian oocytes will undergo a time-dependent process of aging if they are not fertilized. This postovulatory aging (POA) seriously affects the oocyte quality and then impairs the subsequent fertilization and early embryo development, which should be avoided especially in assisted reproductive technology (ART). Resveratrol is an antioxidant substance that can scavenge free radicals and is effective in improving ovary functions. Here, mouse oocytes were used to investigate the effects and mechanisms of resveratrol on POA oocytes in vitro. With 1.0 µM resveratrol treatment during aging process, the rates of fertilization and blastocyst in POA oocytes increased significantly compared with those in the POA group. Resveratrol can reduce the loss of sperm binding sites by stabilizing Juno. Resveratrol can maintain the normal morphology of spindle and mitochondrion distribution and alleviate the levels of ROS and early apoptosis. Additionally, resveratrol can reduce the changes of H3K9me2. Therefore, resveratrol can significantly improve the quality of POA oocytes in vitro to enhance the rates of fertilization and blastocyst, which may be very helpful during the ART process.

20.
Nanotechnology ; 30(49): 495201, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31476738

RESUMO

By means of density functional theory calculations, we successfully predict two stable 2D triangular borophenes, namely B3H and B6O. Our results indicate that B3H is a Dirac material and its cone point is located at the K point of the Brillouin zone (BZ). B6O is identified as having a node-line ring and Dirac cones together. Its node-line ring formed by the intersection of the extended energy band from the two Dirac cones located on K point. This modified 2D borophene has great thermal and dynamic stability due to the electron transfer from the triangular boron lattice to the O atoms. The electronic structure of B6O nanofilm demonstrates novel properties such as two Dirac cones, more than 1.3 eV linear dispersion bands at some points of the BZ, as well as excellent transport properties for the extremely high mobility brought by the combination of the node-line semimetal and Dirac cones. Our study may motivate potential applications of 2D materials in nanoelectronics.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA