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1.
Gynecol Obstet Invest ; : 1-7, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31487707

RESUMO

OBJECTIVES: To explore the expression of Galectin-1 and -9 and clinicopathological features in endometrial carcinoma (EC). METHODS: Normal endometrium (NE), atypical endometrial hyperplasia (AH), and endometrial cancer were collected, and immunohistochemistry was used to detect the expression of Galectin-1 and -9 in all specimens in the same condition. RESULTS: The positive rate of Galectin-1 expression in NE, AH, and endometrial cancer was 30, 70, and 90.2%. The positive rate of Galectin-9 expression in them was 20, 75, and 78.4%, respectively. The expression of Galectin-1 and -9 in the EC and AH was significantly higher than that in the NE (p< 0.05). However, there was no significant difference between the EC and the AH (p > 0.05). The expression of Galectin-1 in endometrial adenocarcinoma was significantly different among tissues of different histological grades, pathological stages, degrees of myometrial infiltration, or lymph node metastasis (p > 0.05). The expression of Galectin-9 in endometrial adenocarcinoma was significantly different among different historical grades, pathological stages, degrees of myometrial infiltration, and lymph node metastasis (p < 0.05). The expression of Galectin-9 in tissues at an early stage, with the degree of myometrial infiltration <1/2, and without lymph node metastasis, was significantly stronger than in those in the late stage, with a degree of myometrial infiltration ≥1/2 and lymph node metastasis. CONCLUSION: Both Galectin-1 and -9 were associated with the occurrence of EC and its pathological behavior. High expression of Galectin-1 suggests a poor prognosis, whereas high expression of Galectin-9 was associated with early pathological changes. Galectin-1 and -9 can provide references for early screening and indicate the prognosis of endometrial lesions, which are of great significance for patients' quality of life.

2.
J Am Chem Soc ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31507176

RESUMO

The isolation and characterization of the first silicon analogue of the aromatic cyclobutadiene dication is reported. The aromatic 2-electron tetrasilacyclobutadiene dication in [(LPhSi)4](BPh4)2 (LPh = PhC(NtBu)2) has been obtained in a simple and straightforward synthesis, from [LPhSiCl], [LPhSiSiLPh] and NaBPh4, and fully characterized. The molecular structure reveals a four-membered Si4 dication in an almost perfect square-planar geometry. Theoretical calculations support the interpretation of the title compound as a classical 2-aromatic compound with a singlet ground state.

3.
Eur Spine J ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31428861

RESUMO

PURPOSE: We have introduced a novel surgery technique named anterior controllable antedisplacement and fusion (ACAF) for the treatment of ossification of the posterior longitudinal ligament. As reported, the satisfactory postoperative outcome can be attributed to the larger decompression width. However, it may associate with high prevalence of vertebral artery injury (VAI) theoretically. Thus, assessment of the vulnerability of vertebral artery in ACAF is of great importance. METHODS: Computed tomographic scan data of 28 patients were retrospectively studied. Seven radiographic parameters were evaluated: uncinate process (UP) tips distance, transverse foramen (TF)-UP tips distance, TF-LWL (the ipsilateral limited wedging line) distance, the limited distance of lateral decompression, the maximum oblique angle of LWL, TF-LWG (the lateral wall of groove) distance, and width of groove. Eleven fresh cadaveric spines undergoing ACAF surgery were also studied. Two anatomic parameters were evaluated: width of groove and LWG-TF distance. RESULTS: The UP tips distance increased from C3 to C6 and tended to be larger in males. The UP tip-TF distance and LWL-TF distance were smallest at C4, but both were larger than 2 mm. Maximum oblique angle decreased from C3 to C6. Postoperatively, both radiographic and cadaveric measurements showed the width of groove was larger than UP tips distance, but LWG-TF distance was larger than 2 mm in all levels. CONCLUSION: UP can be used as anatomical landmarks to avoid VAI during ACAF surgery. Radiographic and cadaveric measurements verified the safety of ACAF surgery, even for those cases with wedging and lateral slotting.

4.
Cell Rep ; 27(6): 1755-1768.e4, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067461

RESUMO

Preterm birth (PTB) is a syndrome with many origins. Among them, infection or inflammation are major risk factors for PTB; however, local defense mechanisms to mount anti-inflammatory responses against inflammation-induced PTB are poorly understood. Here, we show that endothelial TLR4 in the decidual bed is critical for sensing inflammation during pregnancy because mice with endothelial Tlr4 deletion are resistant to lipopolysaccharide (LPS)-induced PTB. Under inflammatory conditions, IL-6 is readily expressed in decidual endothelial cells with signal transducer and activator of transcription 3 (Stat3) phosphorylation in perivascular stromal cells, which then regulates expression of anti-inflammatory IL-10. Our observation that administration of an IL-10 neutralizing antibody predisposing mice to PTB shows IL-10's anti-inflammatory role to prevent PTB. We show that the integration of endothelial and perivascular stromal signaling can determine pregnancy outcomes. These findings highlight a role for endothelial TLR4 in inflammation-induced PTB and may offer a potential therapeutic target to prevent PTB.

5.
Photodiagnosis Photodyn Ther ; 27: 92-94, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31100448

RESUMO

Extramammary Paget's disease (EMPD) is a rare intraepithelial neoplasm arising in apocrine rich area of the skin. Surgery is the standard treatment but relapse is common. The postoperative skin defects, penile reconstruction, functional effects and old age are also challenges for curing disease. Herein, a case of postoperative recurrent EMPD, which was treated by combination therapy of non-invasive repeatable ALA-PDT and deep penetrated holmium laser is reported. Ultrasonography monitor of lesions showed light vascularity and the formerly hypoechoic lesion disappeared after treatment.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30953139

RESUMO

BACKGROUND: The aim of this study was to compare the clinical efficacy and radiological outcomes of skip corpectomy and fusion (SCF) with anterior controllable antedisplacement and fusion (ACAF) for treating multilevel ossification of the posterior longitudinal ligament (OPLL). METHODS: 62 patients with multilevel OPLL who had undergone SCF or ACAF were analyzed retrospectively. Types of OPLL, occupying ratio (OR), Japanese Orthopaedic Association (JOA) score, Recovery Rate (RR), Neck Disability Index (NDI) score, Cobb's angles of C2-C7, operation time, blood loss, hospital stay, ratings for fusion assessment and complications were recorded and assessed. RESULTS: Postoperative C2-C7 Cobb's angle (11.1 ± 3.2° vs. 13.7 ± 2.5°; P < 0.05), NDI scores at final follow-up (14.3 ± 1.6 vs. 13.3 ± 1.3; P < 0.05), and rate of cerebral fluid (CSF) leakage (5, 16.7% vs. 0,0%; P < 0.05) were significantly better in the ACAF group. At 6 months, bone graft fusion rate was significantly greater in the ACAF group (24.75% vs. 15.50%; P < 0.05). CONCLUSIONS: Surgical treatment of multilevel OPLL by SCF or ACAF showed no significant differences in clinical outcomes, with the exception of better NDI scores at final follow-up in ACAF. In addition, ACAF is better than SCF in terms of early bone graft fusion rate, lordotic curvature improvement, risk of CSF leakage.

7.
Macromol Rapid Commun ; 40(13): e1900120, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31021506

RESUMO

A wide-bandgap conjugated polymer, PNQx-2F2T, based on a ring-fused unit of quinoxalino[6,5-f ]quinoxaline (NQx), is synthesized for use as electron donor in polymer solar cells (PSCs). The polymer shows intense light absorption in the range from 300 to 740 nm and favorable energy levels of frontier molecular orbitals. The polymer has afforded decent device performance when blended with either fullerene-based acceptor [6,6]-phenyl-C71 -butylric acid methyl ester ([70]PCBM) or non-fullerene acceptor 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone-methyl))-5,5,11,11-tetrakis(4-n-hexylphenyl)-dithieno[2,3-d: 2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (IT-M). The highest PCEs of 7.9% and 7.5% have been achieved for [70]PCBM or IT-M based PSCs, respectively. Moreover, the influence of molecular weight of PNQx-2F2T on solar cell performance has been investigated. It is found that fullerene-based devices prefer higher polymer molecular weight, while non-fullerene devices are not susceptible to the molecular weight of PNQx-2F2T. The device results are extensively explained by electrical and morphological characterizations. This work not only evidences the potential of NQx for constructing high-performance photovoltaic polymers but also demonstrates a useful structure-performance relationship for efficiency enhancement of non-fullerene PSCs via the development of new conjugated polymers.

8.
World Neurosurg ; 127: e288-e298, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30902779

RESUMO

OBJECTIVE: This retrospective cohort study aimed to investigate the change of spinal cord displacements and the occurrence of C5 palsy between anterior controllable antedisplacement and fusion (ACAF) (group A) and single open-door laminoplasty (group L). METHODS: From January 2016 to December 2017, a total of 80 patients with cervical ossification of the posterior longitudinal ligament (OPLL) were enrolled. All patients underwent computed tomography and magnetic resonance imaging. The types and extent of OPLL, spinal cord rotation, deviation angle, and distance between the vertebral arteries line and spinal cord (DVS) were measured. Patients with postoperative C5 palsy were recorded. Neurologic function was evaluated by Japanese Orthopaedic Association (JOA) score. RESULTS: Three days after surgery, patients in group A had better recovery (6.7° ± 2.4°) of spinal cord rotation than group L (3.1° ± 0.8°; P < 0.05). Deviation angle showed similar changes to spinal cord rotation. At the final follow-up, patients in group A had decreased DVS (11.0 ± 0.7 mm), whereas patients in group L had increased DVS (15.1 ± 0.8 mm) compared with preoperation (P < 0.05). Five patients (1 in group A and 4 in group L) developed postoperative C5 palsy (P > 0.05). Patients in group A had a higher JOA score at the final follow-up than those in group L (P < 0.05). CONCLUSIONS: ACAF could achieve in situ decompression in terms of spinal cord rotation, deviation angle, and spinal cord shift with better clinical outcomes and relatively lower incidence of C5 palsy compared with single open-door laminoplasty.

9.
Environ Sci Pollut Res Int ; 26(15): 14932-14942, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30919188

RESUMO

Heavy metal(loid) extraction from soils in overlapped areas of farmland and coal resources (OAFCR) is crucial in understanding heavy metal bioavailability in soil and the subsequent risks to crops and consumers. However, limited attention has been paid to the extraction procedure of heavy metal(loid)s in OAFCR soils in the research. This study therefore explored different single and mixed extraction procedures, such as acetic acid (HOAc), citric acid, ammonium bicarbonate-diethylenetriaminepentaacetic acid (AB-DTPA), ethylene diamine tetraacetic acid + ammonium acetate (EDTA+NH4OAc), and total digestion (HNO3-HClO4-HF) to determine the bioavailability of As, Cd, Cr, Cu, Pb, and Zn in OAFCR soil in Xuzhou, China. The results showed the metal(loid) extraction capacity from soil of the different procedures could be ranked as AB-DTPA > EDTA+NH4OAc > HOAC > citric acid. The transfer ability of heavy metal(loid)s from soil to wheat tissues and from wheat roots to aerial parts was analyzed by calculating the bioconcentration factor and transfer factor, respectively. Transfer factors of all metal(loid)s were < 1 except Cr whose transfer factor from root to shell and straw were > 1. It is suspected that foliar uptake plays a dominant role in Cr uptake. Correlation analysis between the bioavailability of heavy metal(loid)s in soil and uptake in respective wheat tissues was performed to recommend the best extraction procedures for different studies. The results show that AB-DTPA extraction is recommended for Cu uptake to wheat roots, straws, shells and grains, Zn uptake to roots, and Cd uptake to roots and straws.


Assuntos
Fracionamento Químico/métodos , Metais Pesados/farmacocinética , Poluentes do Solo/farmacocinética , Triticum/química , Disponibilidade Biológica , China , Carvão Mineral , Ácido Edético/química , Fazendas , Metais Pesados/análise , Ácido Pentético/química , Solo/química , Poluentes do Solo/análise , Triticum/efeitos dos fármacos , Triticum/metabolismo
10.
Endocrinology ; 160(4): 938-946, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30776303

RESUMO

Cannabinoid/endocannabinoid signaling is primarily mediated by cannabinoid receptor type 1 (CB1; encoded by Cnr1) and/or type 2 (CB2; encoded by Cnr2). Here, we show that Cnr1-/-Cnr2-/- mice are subfertile as a result of compromised implantation. Upon implantation, the epithelium is smooth and adhered to the blastocyst trophectoderm within the implantation chamber (crypt) in wild-type mice, whereas the epithelium in Cnr1-/-Cnr2-/- mice is ruffled, which compromises appropriate blastocyst-uterine interactions. The suboptimal implantation leads to higher incidence of pregnancy failure in Cnr1-/-Cnr2-/- mice. Histological analysis revealed heightened edema around the implantation chamber in these deleted females. With the use of a reporter mouse line, we observed that CB2 is present on endothelial cells of uterine blood vessels, and its absence leads to blood vessel leakage during implantation. These results suggest that appropriately regulated uterine edema is important to optimal implantation.

11.
Behav Neurosci ; 133(2): 212-224, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30714802

RESUMO

The GABAergic neuroplasticity dysfunction (GND) has been proposed as a distinct pathology for late-life anxiety disorder (LLAD). Brain-derived neurotrophic factor (BDNF) is a critical signaling molecule that regulates the GABAergic neuroplasticity. This research was designed to explore our hypothesis that the reduction of BDNF along with aging could induce GND, which might contribute to LLAD, and application of exogenous BDNF might reverse LLAD by restoring the GABAergic neuroplasticity. We focused on the hippocampus because it is the neural core of mood regulation and can be affected by aging. Compared to young mice, BDNF messenger RNA (mRNA) and protein levels and those core neuroplasticity factors (neurotransmitter γ-aminobutyric acid [GABA] level, GABAA-R α2 and α5 subunits expression and GABA+ neurons) in hippocampus markedly decreased with anxiety-like behavior in aged mice. Knocking down BDNF mRNA in aged mice resulted in further dysfunction of GABAergic neuroplasticity and higher anxiety phenotype. Inversely, chronic exogenous BDNF treatment attenuated anxiety-like behavior, improved the cognitive function, and increased the neuroplasticity factors. We demonstrated that the basic function of BDNF in hippocampus was negatively correlated with GND and anxiety-like behavior of aged mice. These results provided evidence of a causal relationship between the reduced BDNF function in hippocampus and the anxiety susceptibility of aged mice. Gene knockdown mice model indicates the mechanism of low BDNF function in LLAD, particularly affecting GABA neurons, therefore bridging the neurotrophic factor and GABAergic neuroplasticity hypotheses of LLAD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Envelhecimento , Transtornos de Ansiedade/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Neurônios GABAérgicos/metabolismo , Hipocampo/fisiologia , Plasticidade Neuronal , Receptores de GABA-A/metabolismo , Animais , Transtornos de Ansiedade/etiologia , Técnicas de Silenciamento de Genes , Hipocampo/metabolismo , Masculino , Camundongos , RNA Mensageiro/metabolismo
12.
Sci Rep ; 8(1): 17085, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30459453

RESUMO

Bifidobacterium longum strain BBMN68 is sensitive to low concentrations of oxygen. A transcriptomic study was performed to identify candidate genes for B. longum BBMN68's response to oxygen treatment (3%, v/v). Expression of genes and pathways of B. longum BBMN68 involved in nucleotide metabolism, amino acid transport, protein turnover and chaperones increased, and that of carbohydrate metabolism, translation and biogenesis decreased to adapt to the oxidative stress. Notably, expression of two classes of ribonucleotide reductase (RNR), which are important for deoxyribonucleotide biosynthesis, was rapidly and persistently induced. First, the class Ib RNR NrdHIEF was immediately upregulated after 5 min oxygen exposure, followed by the class III RNR NrdDG, which was upregulated after 20 min of exposure. The upregulated expression of branched-chain amino acids and tetrahydrofolate biosynthesis-related genes occurred in bifidobacteria in response to oxidative stress. These change toward to compensate for DNA and protein damaged by reactive oxygen species (ROS). In addition, oxidative stress resulted in improved B. longum BBMN68 cell hydrophobicity and autoaggregation. These results provide a rich resource for our understanding of the response mechanisms to oxidative stress in bifidobacteria.

13.
Neuropsychiatr Dis Treat ; 14: 2609-2615, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30349259

RESUMO

Background: Alexithymia is a multifaceted personality trait and a risk factor for several mental and physical diseases. Methods: In this study, 21 alexithymic students and 21 nonalexithymic students were recruited from the local university and assigned to the alexithymic group and the control group, respectively. Then, the functional connectivity and the structural connectivity among the brain regions of the students were investigated using resting-state functional magnetic resonance imaging (rsfMRI), function connection (FC) analysis, and diffusion tensor imaging (DTI). Results: The rsfMRI results revealed 14 brain regions showing significant differences in the amplitude of low-frequency fluctuations between the two groups. Comparative analysis of the FC and DTI data in these brain regions between the two groups identified altered levels of functional and structural connectivity between the following four pairs of regions in the alexithymic subjects: the right inferior temporal gyrus and the central posterior gyrus, the left temporal gyrus and the insula, and the bilateral superior frontal gyrus and the anterior cingulate gyrus. Conclusion: Compared with single MRI analysis, the multiple MRI analysis identified more precisely the brain regions that could play a key role in the development of alexithymia.

14.
World Neurosurg ; 2018 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-30326311

RESUMO

OBJECTIVE: We investigated whether the cerebrospinal fluid (CSF) space on magnetic resonance imaging (MRI) correlates with the outcomes of anterior controllable antedisplacement and fusion (ACAF) for ossification of the posterior longitudinal ligament (OPLL). METHODS: A total of 53 patients with OPLL who had undergone ACAF were enrolled. The Japanese Orthopaedic Association (JOA) scale, visual analog scale, and neck disability index were used to evaluate the clinical outcomes. The area of CSF space and spinal cord on T2-weighted MRI, the occupying rate of the CSF space and spinal cord, and the postoperative MRI score of the CSF space were measured. The patients were divided into 2 groups according to the JOA score improvement rate (IR). The relationship between the postoperative MRI score and the JOA score IR was analyzed. RESULTS: The patients in group A experienced better recovery compared with those in group B regarding the JOA, visual analog scale, and neck disability index score at the final follow-up visit. On both axial and sagittal T2-weighed MRI, patients in group A experienced lower improvement of the area of the spinal cord than in group B (P > 0.05). However, the mean improvement in the CSF space in group A was better than that in group B (62.86 ± 30.05 mm2 vs. -6.36 ± 24.58 mm2; P < 0.05), with a greater occupying rate of CSF space in group A at the final visit. A strong correlation was noted between the JOA score IR and postoperative CSF space score (P < 0.01). CONCLUSION: These results suggest that ACAF could provide good decompression of the spinal cord and neurological improvement. Also, recovery of the CSF space correlated closely with the surgical ACAF outcomes for cervical myelopathy due to OPLL.

15.
Artigo em Inglês | MEDLINE | ID: mdl-30244159

RESUMO

PURPOSE: The objective of this study was to reveal the long-term sequelae in survivors of childhood and adolescent nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS AND MATERIALS: We reviewed the medical records of NPC patients younger than 18 years old who were treated at XXX from February 1991 to October 2010. Data concerning clinical characteristics, treatment, outcomes, and late morbidities were extracted. Chi-squared tests and binary regression analysis were used to compare the cumulative incidence (CI) of treatment comorbidities between different groups of survivors. RESULTS: A total of 94 patients survived. They had a median follow-up time of 10 years (5∼27 years). When compared with that of the survivors treated with convention radiotherapy treatment (CRT), the CI of xerostomia, dysphagia and chronic otitis media was significantly decreased in the survivors treated with intensity-modulated radiotherapy treatment (IMRT). The CI of blurred vision in patients younger than 10 years old and in patients 10∼18 years old were 33.3% and 2.3%, respectively (P = 0.006). Survivors who received a nasopharynx dose > 72 Gray (Gy), compared with a nasopharynx dose = 60∼72 Gy, had a significantly higher CI of hearing loss (P = 0.008), lalopathy (P = 0.013) and cranial nerve injury (CNI) (P = 0.029). We also had records of height, weight, education level, annual income, marital and fertility status, and menstruation state for 59 of the survivors. 22% of the survivors had a body mass index (BMI) lower than 18.5. 62.5% (11/16) of the female survivors had menstrual or fertility problems. CONCLUSION: Compared with CRT, IMRT can potentially ameliorate xerostomia, dysphagia and chronic otitis media. In addition, patients younger than 10 years old had a higher CI of blurred vision. Moreover, a dose of more than 72 Gy to primary tumor increased the CI of hearing loss, lalopathy and CNI.

16.
Food Microbiol ; 76: 21-28, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30166144

RESUMO

This study evaluated the fate of Listeria innocua, a non-pathogenic species closely related to Listeria monocytogenes, on Fuji apple fruit surfaces during commercial cold storage with and without continuous low doses of gaseous ozone. Unwaxed Fuji apples of commercially acceptable maturity were inoculated with 6.0-7.0 Log10 CFU L. innocua/apple, and subjected to refrigerated air (RA, 33 °F), controlled atmosphere (CA, 33 °F, 2% O2, 1% CO2), or CA with low doses of ozone gas (50.0 -87.0 ppb ) storage in a commercial facility for 30 weeks. A set of uninoculated apples was simultaneously subjected to the above storage conditions for total plate count and yeasts and molds enumeration. L. innocua survival under RA and CA storage was similar, which led to 2.5-3.0 Log10 CFU/apple reduction during storage. Continuous gaseous ozone application decreased L. innocua population on Fuji apples to ∼1.0 Log10 CFU/apple after 30-week storage, and suppressed apple native flora. CA storage delayed apple fruit ripening through reduction of apple firmness and titratable acidity loss, and low dose gaseous ozone application had no negative influence on apple visual quality, including both external and internal disorders. In summary, L. innocua decreased on Fuji apple surfaces during commercial long-term RA and CA storage. Ozone gas has the potential to be used as a supplemental intervention method to control Listeria spp. and to ensure fresh apple safety.

17.
Artigo em Inglês | MEDLINE | ID: mdl-30111250

RESUMO

Signalized intersections have been identified as vehicle emission hotspots, where drivers decelerate, idle, and accelerate their vehicles in response to signal changes. Advanced traffic signal status warning systems (ATSSWSs) can be applied to reduce traffic emissions at intersections by mitigating unnecessary braking and acceleration. In this study, two types of ATSSWSs - variable message sign (VMS)-based and vehicle-to-infrastructure (V2I)-based were designed, and their environmental effectiveness was evaluated through driving simulator-based experiments. Three scenarios were designed and tested: 1) baseline without an ATSSWS, 2) with the VMS-based ATSSWS, and 3) with the V2I-based ATSSWS. The Motor Vehicle Emission Simulator model was used to evaluate and compare the environmental effectiveness of these two types of ATSSWSs. The results indicate that the proposed ATSSWSs can reduce traffic emissions at signalized intersections. In particular, the V2I-based ATSSWS can substantially reduce CO2, NOx, CO, and HC emissions. The results will help transportation practitioners with implementing advanced driver information systems and decision-makings on emission reduction policies.

18.
Tissue Barriers ; 6(2): 1-13, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30130441

RESUMO

Gut epithelium covers the inner layer of the gastrointestinal tract and provides a physical barrier to separate the host from its external environment, and its barrier function is critical for maintaining host health. AMP-activated protein kinase (AMPK) as a master regulator of energy metabolism plays a critical role in epithelial barrier function. AMPK activation promotes epithelial differentiation and facilitates cell polarity establishment, both of which strengthen epithelial barrier. In addition, AMPK promotes the assembly of tight junctions and adherens junctions by direct phosphorylation of proteins composing apical junctions, junctional anchors, and cytoskeletons. Pharmacological and nutraceutical compounds, as well as physiological states triggering AMPK activation strengthen epithelial barrier function. This review summarized recent progress in delineating the regulatory roles of AMPK in apical junction formation and barrier function of intestinal epithelium.

19.
PLoS Genet ; 14(8): e1007630, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30142194

RESUMO

Mutation of the tumor suppressor Pten often leads to tumorigenesis in various organs including the uterus. We previously showed that Pten deletion in the mouse uterus using a Pgr-Cre driver (Ptenf/fPgrCre/+) results in rapid development of endometrial carcinoma (EMC) with full penetration. We also reported that Pten deletion in the stroma and myometrium using Amhr2-Cre failed to initiate EMC. Since the Ptenf/fPgrCre/+ uterine epithelium was primarily affected by tumorigenesis despite its loss in both the epithelium and stroma, we wanted to know if Pten deletion in epithelia alone will induce tumorigenesis. We found that mice with uterine epithelial loss of Pten under a Ltf-iCre driver (Ptenf/f/LtfCre/+) develop uterine complex atypical hyperplasia (CAH), but rarely EMC even at 6 months of age. We observed that Ptenf/fPgrCre/+ uteri exhibit a unique population of cytokeratin 5 (CK5) and transformation related protein 63 (p63)-positive epithelial cells; these cells mark stratified epithelia and squamous differentiation. In contrast, Ptenf/fLtfCre/+ hyperplastic epithelia do not undergo stratification, but extensive epithelial cell apoptosis. This increased apoptosis is associated with elevation of TGFß levels and activation of downstream effectors, SMAD2/3 in the uterine stroma. Our results suggest that stromal PTEN via TGFß signaling restrains epithelial cell transformation from hyperplasia to carcinoma. In conclusion, this study, using tissue-specific deletion of Pten, highlights the epithelial-mesenchymal cross-talk in the genesis of endometrial carcinoma.

20.
Am J Hematol ; 93(12): 1467-1473, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30160789

RESUMO

Intravenous arsenic trioxide (ATO) has been adopted as the first-line treatment for acute promyelocytic leukemia (APL). Another arsenic compound named the Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine containing As4 S4 , has been shown to be highly effective in treating adult APL. In the treatment of pediatric APL, the safety and efficacy of RIF remains to be confirmed. This randomized, multicenter, and noninferiority trial was conducted to determine whether intravenous ATO can be substituted by oral RIF in the treatment of pediatric APL. From September 2011 to January 2017, among 92 patients who were 16 years old or younger with newly diagnosed PML-RARa positive APL, 82 met eligible criteria and were randomly assigned to ATO (n = 42) or RIF (n = 40) group. The remaining 10 patients did not fulfilled eligible criteria because five did not accept randomization, four died and one had hemiplegia prior to arsenic randomization due to intracranial hemorrhage or cerebral thrombosis. Induction and consolidation treatment contained ATO or RIF, all-trans-retinoic acid and low intensity chemotherapy. End points included event-free survival (EFS), adverse events and hospital days. After a median 3-year follow-up, the estimated 5-year EFS was 100% in both groups, and adverse events were mild. However, patients in the RIF group had significantly less hospital stay than those in the ATO group. This interim analysis shows that oral RIF is as effective and safe as intravenous ATO for the treatment of pediatric APL, with the advantage of reducing hospital stay. Final trial analysis will reveal mature outcome data.

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