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1.
Medicine (Baltimore) ; 98(40): e17454, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577773

RESUMO

To examine the current situation of patient delay and to identify factors associated with patient delay among women with breast cancer in China.A total of 283 women, aged 23 to 83 years old and with histologically confirmed breast cancer, were investigated in this cross-sectional study. The women were recruited from seven selected hospitals in Sichuan Province, China. Face-to-face interviews using a structured questionnaire were performed.Among the 283 participants, the range of patient delay was 0.2 to 900 days with a median patient delay of 50 days. A total of 35.8% of patients waited ≥90 days to access medical treatment after symptom onset. Binary logistic regression analysis showed that the main predictors of patient delay were knowledge of breast cancer symptoms (OR = 0.716, 95%CI:0.637-0.804, P = .000), external health locus of control (OR = 1.173, 95%CI:1.087-1.266, P = .000), breast self-examination/physical examination (OR = 0.065, 95%CI: 0.007-0.590, P = .015), perceived health competence (OR = 0.873, 95%CI:0.808-0.944, P = .000), family support (OR = 0.911,95%CI:0.847-0.981, P = .013), pain stimulation (OR = 0.191, 95%CI:0.046-0.792, P = .023) and age (OR = 1.028, 95%CI:1.000-1.058, P = .049).These factors explained 41.0% of the variance.Information on the current situation and predictors of patient delay in Chinese women with breast cancer might provide meaning insights into the early diagnosis of breast cancer. The results of this study may help health professionals develop specific clinical practice strategies to reduce patient delay of initial treatment as a way to improve outcomes for women with breast cancer.

2.
Ren Fail ; 41(1): 921-929, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31573378

RESUMO

Objectives: The aim of the study was to evaluate the laboratory parameters and symptoms after parathyroidectomy (PTX) in dialysis patients with secondary hyperparathyroidism (SHPT), and to briefly analyze the different therapeutic effects of the three surgical methods. Methods: A total of 182 dialysis patients who underwent PTX between February 2012 and January 2018 at the Second Affiliated Hospital of Soochow University were included in this study and followed for 12 months. Laboratory parameters such as calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH) were measured before and after operation. According to the follow-up time and type of operation, we calculated the percentage of laboratory indicators reaching the recommended range of the KDIGO guidelines after surgery. We also analyzed the improvement of bone pain and pruritus, as well as surgical complications. Results: After the operation, the levels of iPTH, Ca, and P decreased significantly at each time point. ALP increased at the first postoperative week and gradually decreased to normal range after 3 months. Symptoms, such as bone pain and pruritus, were significantly relieved. According to the follow-up time and three surgical methods (subtotal parathyroidectomy, total parathyroidectomy, total parathyroidectomy plus autologous transplantation), we found that the ratio of each laboratory parameter reaching the recommended range of KDIGO guidelines was significantly different. Conclusion: PTX is a safe and effective therapy for treating SHPT that is refractory to medical therapies and accompanied by related signs and symptoms in dialysis patients. All three operative techniques were effective in controlling SHPT.

3.
J Neurosci Methods ; : 108441, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31574288

RESUMO

BACKGROUND: Recombinant adeno-associated virus (rAAV) is increasingly applied in neuroscience research or gene therapy. However, there is no simple and efficient tool for specific transfection of rAAV into cerebrovascular tissues. It has been reported that fluorescent tracers or beta-amyloid protein can enter the brain through perivascular spaces, named as "glymphatic system". The purpose of this study was to explore whether rAAV could transduce the cerebral vasculature through the glymphatic pathway. NEW METHOD: An AAV1-GFP vector suspension (15 µL) was injected into the intracisternal space of anesthetized mice (n = 2) and 5 µL was injected into the bulbus medullae (n = 2). As controls, 15 µL of artificial cerebrospinal fluid (aCSF) was injected into the cisterna magna. The endothelial specific transduction was verified by Glut1 or PDGFRß immunofluorescent staining. Immunofluorescence images for all groups were captured with a laser microscope. RESULTS: It was observed that infection with rAAV1 vectors encoding green fluorescence protein resulted in a successful cerebrovascular transduction when injected into cisterna magna, compared to aCSF or intra-parenchymal injection at 30 days post-transduction in adult mice. In addition, GFP was co-localized with Glut1 based on immuno-fluorescence. These results indicate that glymphatic system delivery enhances the transduction efficiency of AAV1 to brain endothelial cells. COMPARISON WITH EXISTING METHODS: The AAV1vector is simple and efficiently transduces the cerebral endothelial cells through the glymphatic pathway. CONCLUSION: The findings of this study reveal that rAAV1-based vectors have high application potential for endothelial-targeted neurologic disease research or gene-based therapies.

4.
Medicine (Baltimore) ; 98(39): e17221, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574832

RESUMO

To investigate the clinicopathological features and prognostic impact of Fusobacterium nucleatum (F nucleatum) status in patients with colorectal cancer (CRC) and its relationships with microsatellite instability (MSI) status.Retrospective analysis of consecutive 91 CRC tissues from surgically resected specimens of stage III or high-risk stage II CRC patients who had received curative surgery in Wuhan Union Hospital from January, 2017 to January, 2019 was conducted. F nucleatum DNA was quantitatively measured and classified into 1 of the 2 categories: F nucleatum-high, or F nucleatum-low/negative. The Cox risk ratio model analysis was performed to identify independent risk factors of F nucleatum. F nucleatum-high group was compared with the F nucleatum-low/negative group with respect to clinicopathological features and their relationships with MSI status. Kaplan-Meier method and log-rank test were used for univariate analysis of prognostic factors in patients with CRC.The number of total lymph node acquisition and positive lymph nodes, neurological invasion, vascular tumor thrombus were higher in F nucleatum-high group (27.44 ±â€Š25.213 vs 20.70 ±â€Š10.141; P = .018; 3.80 ±â€Š7.974 vs 1.74 ±â€Š3.531; P = .001; 68.0% vs 33.3%; P = .003; 60.0% vs 25.8%; P = .002). Moreover, microsatellite mutations were more frequent in patients with F nucleatum-high (84.0% vs 60.6%; P = .034). A higher abundance of F nucleatum in CRC is associated with a shorter survival time. The F nucleatum status, peripheral nerve invasion, vascular tumor thrombus, lymph node metastasis, and TNM staging were related factors affecting the prognosis of patients with CRC. The Cox risk ratio model analysis showed that the F nucleatum (odds ratio [OR] 2.094, 95% confidence interval [CI] 1.178-8.122, P = .032) and MSI status (OR 2.243, 95% CI 1.136-5.865, P = 0.039) were independent prognostic factors.Intratumoral F nucleatum load has a poor prognostic effect of CRC by increasing nerve invasion, vascular tumor thrombus, and microsatellite mutation.

5.
Mol Med Rep ; 20(4): 3820-3828, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485670

RESUMO

Primary human hepatocytes (PHHs) are the 'gold standard' for investigating hepatitis B virus (HBV) infection and antiviral drugs. However, poor availability, variation between batches and ethical issues regarding PHHs limit their applications. The discovery of human sodium taurocholate co­transporting polypeptide (hNTCP) as a functional HBV receptor has enabled the development of a surrogate model to supplement the use of PHHs. In the present study, the evolutionary distance of seven species was assessed based on single­copy homologous genes. Based on the evolutionary distance and availability, PHHs and primary rabbit hepatocytes (PRHs) were isolated and infected with hNTCP­recombinant lentivirus, and susceptibility to HBV infection in the two cell types was tested and compared. In addition, HBV infection efficiency of hNTCP­expressing PPHs with pooled HBV­positive serum and purified particles was determined. The potential use of HBV­infected hNTCP­expressing PPHs for drug screening was assessed. The results demonstrated that pigs and rabbits are closer to humans in the divergence tree compared with mice and rats, indicating that pigs and rabbits were more likely to facilitate the HBV post­entry lifecycle. Following hNTCP complementation and HBV infection, PPHs and Huh7D human hepatocellular carcinoma cells, but not PRHs, exhibited increased hepatitis B surface antigen and hepatitis B e­antigen secretion, covalently closed circular DNA formation and infectious particle secretion. hNTCP­expressing PPHs were susceptible to infection with HBV particles purified from pooled HBV­positive sera, but were poisoned by raw HBV­positive sera. The use of HBV­infected hNTCP­expressing PPHs for viral entry inhibitor screening was revealed to be applicable and reproducible. In conclusion, hNTCP­expressing PPHs may be valuable tool for investigating HBV infection and antiviral drugs.

7.
J Clin Densitom ; 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31558404

RESUMO

In preparation for the International Society for Clinical Densitometry Position Development Conference (PDC) 2019 in Kuala Lumpur, Malaysia, a cross-calibration and precision task force was assembled and tasked to review the literature, summarize the findings, and generate positions to answer 4 related questions provided by the PDC Steering Committee, which expand upon the current ISCD official positions on these subjects. (1) How should a provider with multiple dual-energy X-ray absorptiometry (DXA) scanners of the same make and model calculate least significant change (LSC)? (2) How should a provider with multiple DXA systems with the same manufacturer but different models calculate LSC? (3) How should a provider with multiple DXA systems from different manufacturers and models calculate LSC? (4) Are there specific phantom procedures that one can use to provide trustworthy in vitro cross calibration for same models, different models, and different makes? Based on task force deliberations and the resulting systematic literature reviews, 3 new positions were developed to address these more complex scenarios not addressed by current official positions on single scanner cross calibration and LSC. These new positions provide appropriate guidance to large multiple DXA scanner providers wishing to offer patients flexibility and convenience, and clearly define good clinical practice requirements to that end.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31545873

RESUMO

Cerebral ischemia is caused by various disorders, such as stroke, myocardial infarction or peripheral vascular disease. The purpose of this paper was to investigate the effects of glycyrrhizic acid (GA) on cerebral ischemia/reperfusion (I/R) injury. Middle cerebral artery occlusion (MCAO) was established to evaluate the effects of GA on cerebral ischemia. In this study, our results showed that GA could dramatically decrease cerebral edema, reduce the neurological deficits, and smaller brain infarct volume was found in the GA treatment group. In serum and brain tissue, GA also increased superoxide dismutase (SOD) activity. In addition, in serum and brain tissue, GA also dramatically inhibited the secretion of inflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α). Moreover, GA inhibited the expressions of high-mobility group protein box-1 (HMGB1) mediated TLR4/NF-κB pathway. Our data determined that GA may provide protective effect on the I/R-induced cerebral ischemia disease. This article is protected by copyright. All rights reserved.

9.
Theranostics ; 9(20): 5937-5955, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534530

RESUMO

Prolonged occlusion of multiple microvessels causes microvascular injury. G protein-coupled receptor 124 (GPR124) has been reported to be required for maintaining central nervous system (CNS) angiogenesis and blood-brain barrier integrity. However, the molecular mechanisms by which GPR124 regulates pericytes during ischemia have remained elusive. Methods: A microsphere embolism-induced ischemia model was used to evaluate the expression of GPR124 following microsphere embolism. Immunocytochemistry and stochastic optical reconstruction microscopy imaging were used to assess the expression and distribution of GPR124 in human brain vascular pericytes (HBVPs) and after the treatment with 3-morpholino-sydnonimine (SIN-1) or oxygen-glucose deprivation (OGD). The effect of GPR124 knockdown or overexpression on HBVP migration was analyzed in vitro using wound healing assays and a microfluidic device. GPR124 loss-of-function studies were performed in HBVPs and HEK293 cells using CRISPR-Cas9-mediated gene deletion. Time-lapse imaging was used to assess dynamic changes in the formation of filopodia in an individual cell. Finally, to explore the functional domains required for GPR124 activity, deletion mutants were constructed for each of the N-terminal domains. Results: GPR124 expression was increased in pericytes following microsphere embolism. Morphological analysis showed localization of GPR124 to focal adhesions where GPR124 bound directly to the actin binding protein vinculin and upregulated Cdc42. SIN-1 or OGD treatment redistributed GPR124 to the leading edges of HBVPs where GPR124 signaling was required for pericyte filopodia formation and directional migration. Partial deletion of GPR124 domains decreased SIN-1-induced filopodia formation and cell migration. Conclusion: Taken together, our results provide the first evidence for a role of GPR124 in pericyte migration under ischemic conditions and suggest that GPR124 was essential for Cdc42 activation and filopodia formation.

10.
Brain Res ; 1724: 146464, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31536729

RESUMO

Visceral pain is a complex and common symptom of inflammatory bowel disease (IBD) patients. Developing novel efficient therapeutics is still a common interest for clinicians. Increasing evidence have shown that tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) contributes to the pathological pain state in some pain models. Resveratrol (RSV) has showed promising potential for the treatment of neuropathic pain and inflammatory pain. However, whether RSV has analgesic effect on visceral pain and the underlying mechanisms remain unclear. In this study, we established the colitis model through intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS), and found that TNBS induced colonic inflammation and visceral hypersensitivity. Meanwhile, astroglial marker glial fibrillary acidic protein (GFAP), TRAF6, phosphorylation of NF-κB (pNF-κB), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels were increased in L6-S1 spinal cord after TNBS enema. Then, intrathecal injection of TRAF6 siRNA attenuated visceral pain, blocked the upregulation of pNF-κB, TNF-α and IL-1ß levels in the spinal cord in TNBS mice. Furthermore, spinal administration of NF-κB inhibitor, BAY11-7082 reversed the pain behavior and suppressed spinal TNF-α and IL-1ß expression in TNBS mice. Finally, repeated intrathecal injection of RSV reversed TNBS-induced visceral pain hypersensitivity in a dose-dependent manner. Meanwhile, TNBS-induced enhancement of spinal GFAP, TRAF6, pNF-κB, TNF-α and IL-1ß were reduced by the same treatment of RSV. In conclusion, our results suggest that RSV exerts the effects of antinociception on colitis-induced visceral hyperalgesia through inhibition of spinal TRAF6/NF-κB signaling pathway and the production of inflammatory mediators in the spinal cord, suggesting a new application of RSV for the treatment of visceral pain.

11.
Immunopharmacol Immunotoxicol ; 41(5): 549-557, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31530042

RESUMO

Objective: To investigate the role of miR-146a-5p in the effects of resveratrol (RSV) on inflammatory response in BV2 mouse microglial cells. Materials and methods: BV2 cells were pretreated by RSV and stimulated with lipopolysaccharide (LPS). Cell Viability was checked using a MTT assay. Real-Time PCR was performed to detect the levels of pro-inflammatory cytokines (tumor necrosisfactor-α-TNF-α, interleukin-1ß-IL-1ß and interleukin-6 - IL-6) and miR-146a-5p expression. Western blot was used to analyze the protein expression of TNF receptor associated factor 6 (TRAF6) and phospho-nuclear factor kappa B (pNF-κB). Gain-of-function and loss-of-function analysis of miR-146a-5p was performed using transfection of miR-146a-5p mimic and miR-146a-5p inhibitor, respectively. Results: Pretreatment with RSV significantly and dose dependently inhibited LPS-induced production of TNF-α, IL-1ß and IL-6 in BV2 cells. MiR-146a-5p was significantly upregulated after LPS treatment, and further increased in RSV and LPS-co-treated cells. MiR-146a-5p overexpression via miR-146a-5p mimic transfection downregulated the mRNA level of TNF-α, IL-1ß and IL-6, as well as abrogated the protein expression of TRAF6 and pNF-κB in BV2 cells exposed to LPS. More importantly, the reducion of TNF-α, IL-1ß and IL-6 level by RSV were reversed by miR-146a-5p silence via miR-146a-5p inhibitor transfection. Furthermore, silencing miR-146a-5p attenuated the inhibitory effect of RSV on the TRAF6/NF-κB pathway which was activated after induction with LPS. Conclusions: RSV can suppress LPS-induced inflammatory injury via modulating the miR-146a-5p/TRAF6/NF-κB axis in BV2 mouse microglial cells.

12.
J Periodontol ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31487049

RESUMO

BACKGROUND: Occlusal trauma is an important factor promoting bone loss caused by periodontal diseases. Although there are reports of traumatic force promoting bone resorption in periodontal diseases, no studies examining the inhibition of bone formation by traumatic force and the underlying mechanism have been reported. The aim of this study was to investigate the mechanism whereby traumatic force inhibits bone formation. METHODS: MC3T3-E1 cells were induced to undergo osteogenic differentiation and subjected to cyclic uniaxial compressive stress with or without stimulation with Pg. LPS. The expression of osteoblast markers and the activation of IKK-NF-κB signaling were evaluated in vitro. Then, MC3T3-E1 cells were induced to undergo osteogenic differentiation and subjected to cyclic uniaxial compressive stress with or without IKK-2 Inhibitor VI. The expression of osteoblast markers was determined. Then, the classic Wnt signaling pathway (ß-catenin, Gsk3ß, p-Gsk3ß, and Dkk1) was further evaluated in vitro. Finally, occlusal trauma was induced in Wistar rats with or without the injection of IKK-2 Inhibitor VI, to evaluate changes in bone mass and IKK-NF-κB and Wnt/ß-catenin signaling in vivo. RESULTS: After stimulation with Pg. LPS and traumatic force, IKK-NF-κB signaling was significantly activated in vitro. The expression of osteoblast markers and the activity of alkaline phosphatase in MC3T3-E1 cells declined after traumatic force loading and were rescued when IKK-NF-κB signaling was blocked. Wnt/ß-catenin signaling was accordingly inhibited upon force loading, but this inhibition was reversed when IKK-NF-κB was antagonized in vitro. X-ray and Micro-CT analysis of the mandibles of the rats as well as HE and TRAP staining showed that bone loss induced by occlusal trauma declined after IKK-NF-κB was inhibited. The expression of p65 and IκBα was increased when occlusal trauma was induced in Wistar rats, whereas ß-catenin, OCN, and Runx2 levels were decreased. After blocking IKK-NF-κB, significant upregulation of ß-catenin, OCN, and Runx2 was observed in rats suffering from occlusal trauma. CONCLUSIONS: IKK-NF-κB signaling could be activated by traumatic force or occlusal trauma. Its activation promoted the degradation of ß-catenin, ultimately inhibiting osteogenic differentiation in vitro and bone formation in vivo.

13.
J Vis Exp ; (150)2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31475978

RESUMO

Xenotransplantation is a promising way to resolve the shortage of human organs for patients with end-stage organ failure, and the pig is considered as a suitable organ source. Immune rejection and coagulation are two major hurdles for the success of xenotransplantation. Vascular endothelial cell (EC) injury and dysfunction are important for the development of the inflammation and coagulation responses in xenotransplantation. Thus, isolation of porcine aortic endothelial cells (pAECs) is necessary for investigating the immune rejection and coagulation responses. Here, we have developed a simple enzymatic approach for the isolation, characterization, and expansion of highly purified pAECs from miniature pigs. First, the miniature pig was anaesthetized with ketamine, and a length of aorta was excised. Second, the endothelial surface of aorta was exposed to 0.005% collagenase IV digestive solution for 15 min. Third, the endothelial surface of the aorta was scraped in only one direction with a cell scraper (<10 times), and was not compressed during the process of scraping. Finally, the isolated pAECs of Day 3, and after passage 1 and passage 2, were identified by flow cytometry with an anti-CD31 antibody. The percentages of CD31-positive cells were 97.4% ± 1.2%, 94.4% ± 1.1%, and 92.4% ± 1.7% (mean ± SD), respectively. The concentration of Collagenase IV, the digestive time, the direction, and frequency and intensity of scraping are critical for decreasing fibroblast contamination and obtaining high-purity and a large number of ECs. In conclusion, our enzymatic method is a highly-effctive method for isolating ECs from the miniature pig aorta, and the cells can be expanded in vitro to investigate the immune and coagulation responses in xenotransplantation.

14.
Appl Opt ; 58(21): 5800-5806, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31503884

RESUMO

A high-sensitivity magnetic field sensor based on a dual-core photonic crystal fiber has been designed with an extremely short device length of 2000 µm in this paper. The two cores of the fiber are separated by one air hole filled with magnetic fluid. The sensitive properties are investigated by the full-vector finite element method. Simulation results illustrate that the highest sensitivity can reach -442.7 pm/Oe in the magnetic field strength range of 30-520 Oe. The photonic crystal fiber filled with magnetic fluid, serving as an excellent platform for magnetic field sensing, has great potential applications in complex environments, remote sensing, and real-time monitoring fields.

15.
Ambio ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506845

RESUMO

China has over 1320 freshwater fish species, 877 of which are endemic. In recent decades, over-exploitation and landscape pressures have threatened them and led to a severe aquatic biodiversity crisis. In response, large-scale fishing bans have been promulgated to protect freshwater biodiversity in major Chinese rivers since the early 1980s. Here, we present the historical background and current challenges to the fishing bans. Implementing large-scale fishing bans may help improve China's current freshwater biological resources and biodiversity to some extent. But implementing fishing bans alone is not sufficient to solve the crisis because of shortcomings of the current bans and expanding human pressures in most river basins. Thus, we recommend regulating other anthropogenic pressures, expanding duration and extent of current fishing regulations, establishing a comprehensive monitoring program, and initiating basin-scale ecological rehabilitation. These programs are also needed in other developing countries facing similar biodiversity crises and human pressures.

16.
J Comput Biol ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31502860

RESUMO

We aimed to identify differentially expressed genes (DEGs) in epidermal stem cells (epiSCs) in response to high fat diet (HFD). DEGs were identified by time-series analysis of the gene expression profile (GSE84510) in Gene Expression Omnibus (GEO) database. Functions and pathways affected by HFD were identified by functional annotation of DEGs. Key factors responding to HFD was identified by protein-protein interaction (PPI) network analysis. Two groups of genes with the same tendency in response to HFD were identified. ECM-related processes and PI3K pathway were altered in the early stage of obesity. A PPI network was constructed to delineate the interactions among proteins encoded by DEGs and ICAM1 and RELA were key epiSC factors respond to HFD. Our studies may provide valuable insights into the molecular mechanisms underlying how obesity affects the functions of epiSC.

17.
Med Sci Monit ; 25: 6894-6904, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31518341

RESUMO

BACKGROUND Acute pancreatitis (AP) has a high mortality rate and often has serious complications. The Hippo-YAP signaling pathway is mainly involved in cell proliferation and stem cell self-renewal. Recent studies have reported that YAP1 plays a crucial role in pancreatic cancer initiation and acute and chronic pancreatitis (CP). However, the role of YAP1 in AP still needs to be clarified. MATERIAL AND METHODS To assess the role of YAP1 in the progression of AP, we established a cell model of AP in AR42J cells. AR42J, a rat pancreatic acinar cell line, was stimulated with caerulein to mimic AP-like acinar cell injury. Levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) were measured by ELISA to investigate the role of YAP1 in the progression of AP. RESULTS The results showed that YAP1 and MALAT1 were the targets of miR-194 and were upregulated in caerulein-treated AR42J cells. Overexpression of MALAT1 or YAP1 can increase the levels of IL-6 and TNF-alpha secreted by AR42J cells, while miR-194 dramatically counteracts this enhancement effect. CONCLUSIONS Our results demonstrated a regulation loop among MATAL1, miR-194, and YAP1, which dynamically regulates the progression of AP, providing a new therapeutic target for treatment of this disease.

18.
Dev Dyn ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31487081

RESUMO

BACKGROUND: Conditional loss-of-function studies are widely conducted using the Cre/Loxp system because this helps circumvent embryonic or neonatal lethality problems. However, Cre strains specific to the inner ear are lacking, and thus lethality frequently occurs even in conditional knockout studies. RESULTS: Here, we report a Rorb-IRES-Cre knockin mouse strain in which the Cre recapitulates the expression pattern of endogenous Rorb (RAR-related orphan receptor beta). Analyzing Rorb-IRES-Cre/+; Rosa26-CAG-LSL-tdTomato/+ cochlear samples revealed that tdTomato was expressed at the apical turn only by E12.5. TdTomato was observed in the apical and middle turns but was minimally expressed in the basal turn at E15.5, E18.5, and P5. However, most of the auditory hair cells (HCs) and supporting cells (SCs) in all three turns were tdTomato+ at P15 and P30. Intriguingly, no tdTomato+ vestibular cells were detected until P5 and a few cells were present at P15 and P30. Lastly, we also confirmed Rorb mRNA and protein expression in cochlear HCs and SCs at P30. CONCLUSIONS: We reveal that Rorb expression exhibits an apical-to-basal gradient in cochleae. The cochlear-specific and apical-to-basal-gradient Rorb Cre activity should enable discrimination of gene functions in cochlear vs vestibular regions as well as low- vs high-frequency regions in the cochlea. This article is protected by copyright. All rights reserved.

19.
Tumori ; : 300891619871103, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31478461

RESUMO

BACKGROUND: An integral and well-functioning vascular system is essential for tumor progression and chemotherapy infusion. However, the lumen integrity of the microvessels and its significance in prognosis has not been studied. In this study, we found that the proportion of collapsed microvessels is suggested to be a novel biomarker for predicting prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: In this study, immunohistochemical CD31 staining was performed to identify the microvessels in tumor specimens. Proportions of collapsed vessels were estimated in CD31-stained tumor specimens from 100 patients with NSCLC. The correlation between collapsed microvessel proportion and survival time were evaluated by univariate and multivariate analysis. RESULTS: Data from 99 patients were analyzed and a wide range of collapse-microvessel fraction was observed in 96 patients (1.4%-70%). Elevated collapse proportion (⩾6.5%) indicated poor overall survival in both univariate analysis (p = 0.042) and multivariate analysis (p = 0.014). CONCLUSIONS: Elevated proportion of collapsed microvessels indicted poor survival outcome in patients with NSCLC.

20.
J Immunotoxicol ; 16(1): 155-163, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31403359

RESUMO

Exposure to the widely-used phthalate plasticizer di-(2-ethylhexyl)-phthalate (DEHP) has been shown to be closely related to an increased prevalence of allergic diseases in infants and juveniles. Earlier work in our laboratory found that DEHP-related anaphylactic responses could be ascribed to T-follicular helper (Tfh) cell hyperfunction directly. The Tfh cell, a newly identified CD4+ TH cell subset, until recently has been considered as a key player in humoral immunity. Tfh cells can respond to stimulation through various receptors. Signaling lymphocytic activation molecule family member-1 (SLAMF1, CD150) is a surface co-stimulatory receptor that can bind to an intracytoplasmic adaptor signaling lymphocytic activation molecule-associated protein (SAP) to initiate downstream signaling cascades, regulating some events of immune response. The present study explored the role of SLAMF1 in Tfh cell differentiation and cytokine secretion under the condition of DEHP exposure. Using a weanling mice model of DEHP gavage with ovalbumin (OVA) sensitization, it was found that DEHP acted as an immunoadjuvant to elevate SLAMF1 and SAP expression in host Tfh cells. Ex vivo studies of effects from DEHP exposure on Tfh cells from OVA-sensitized hosts showed that DEHP acted in an adjuvant-like manner to promote the expression of adaptor protein SAP, transcription factors Bcl-6 and c-MAF, and cytokines interleukin (IL)-21 and IL-4 in Tfh cells. Transfection of these Tfh cells with Slamf1 small interfering RNA prior to exposure to the DEHP attenuated the over-expression of these molecules that was caused by the DEHP. In conclusion, this study demonstrated that DEHP, via a SLAMF1-mediated pathway, can impact on Tfh cell differentiation and their ability to form select cytokines.

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