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1.
Stem Cell Res Ther ; 12(1): 94, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514430

RESUMO

BACKGROUND: The long-term survival after vascularized composite allotransplantation (VCA) is often limited by systemic rejection as well as the adverse effects of immunosuppressants. The stromal vascular fraction (SVF) can be expanded to produce adipose-derived stem cells (ADSC) which represents a combination of endothelial cells, preadipocytes, immune cells, and ADSC. It has been demonstrated that ADSC possess consistently reliable clinical results. However, literature is scarce regarding SVF in VCA. This study seeks to determine the impact of ex vivo allograft pretreatment in combination with SVF cells in the ability to promote composite tissue allotransplantation immunotolerance. METHODS: A rat hind limb allotransplant model was used to investigate the influence of ex vivo pretreatment of SVF and ADSC on VCA survival. Intravascular cell-free saline, ADSC, or SVF was infused into the models with immunosuppressants. The histopathological examination and duration that the allografts went without displaying symptoms of rejection was documented. Peripheral T lymphocytes and Tregs were quantified with flow cytometry while allotissue expressions of CD31 were quantified with immunohistochemical staining (IHC). ELISA was used to detect vascular endothelial growth factor (VEGF)-A as well as anti- and pro-inflammatory cytokines. RESULTS: We demonstrated that ex vivo treatment of allografts with SVF or ADSC prolonged allograft survival in contrast to medium control cohorts. There were also enhanced levels of immunomodulatory cytokines and increased VEGF-A and CD31 expression as well as reduced infiltration and proliferation of T lymphocytes along with raised Treg expressions. CONCLUSION: These studies demonstrated that adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model and have the potential to establish immunotolerance.

2.
ACS Nano ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33428394

RESUMO

Fibrous energy-autonomy electronics are highly desired for wearable soft electronics, human-machine interfaces, and the Internet of Things. How to effectively integrate various functional energy fibers into them and realize versatile applications is an urgent need to be fulfilled. Here, a multifunctional coaxial energy fiber has been developed toward energy harvesting, energy storage, and energy utilization. The energy fiber is composed of an all fiber-shaped triboelectric nanogenerator (TENG), supercapacitor (SC), and pressure sensor in a coaxial geometry. The inner core is a fibrous SC by a green activation strategy for energy storage; the outer sheath is a fibrous TENG in single-electrode mode for energy harvesting, and the outer friction layer and inner layer (covered with Ag) constitute a self-powered pressure sensor. The electrical performances of each energy component are systematically investigated. The fibrous SC shows a length specific capacitance density of 13.42 mF·cm-1, good charging/discharging rate capability, and excellent cycling stability (∼96.6% retention). The fibrous TENG shows a maximum power of 2.5 µW to power an electronic watch and temperature sensor. The pressure sensor has a good enough sensitivity of 1.003 V·kPa-1 to readily monitor the real-time finger motions and work as a tactile interface. The demonstrated energy fibers have exhibited stable electrochemical and mechanical performances under mechanical deformation, which make them attractive for wearable electronics. The demonstrated soft and multifunctional coaxial energy fiber is also of great significance in a sustainable human-machine interactive system, intelligent robotic skin, security tactile switches, etc.

3.
Health Qual Life Outcomes ; 19(1): 5, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407525

RESUMO

PURPOSE: We aimed to conduct psychometric tests for the Chinese version of ICECAP-A and compare the differences between ICECAP-A and EQ-5D-3L for patients with T2DM and explore the relationship between clinical conditions and ICECAP-A through diabetes-related clinical indicators. METHODS: Data were collected from a sample of 492 Chinese T2DM patients. The reliability and validity of the ICECAP-A were verified. Exploratory factor analysis (EFA), correlation analysis and regression analysis were conducted for both the ICECAP-A and EQ-5D-3L. RESULTS: Our results show that the Chinese version of ICECAP-A has good internal consistency with an overall Cronbach's Alpha coefficient of 0.721. The mean scores of ICECAP-A and EQ-5D-3L are 0.85 vs. 0.94. A weak correlation (r = 0.116) was found between the ICECAP-A tariff and EQ-5D-3L utility. EFA showed that although the five dimensions of the ICECAP-A and EQ-5D-3L scales were loaded into two different factors respectively. However, the two scales captured different dimensions of quality of life and can complement each other. The ICECAP-A, EQ-5D-3L, and EQ-VAS scores showed differences across different socio-demographic characteristics and clinic conditions groups. CONCLUSION: The Chinese version of the ICECAP-A capability instrument can be for assessing outcomes in adults with T2DM. It may capture more dimensions of QoL than traditional Health-related QoL (HRQoL) instruments and may be useful for economic evaluations of health care and social care for people with T2DM or other chronic diseases.

4.
J Cell Mol Med ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201593

RESUMO

Studies have reported that non-receptive endometrium or abnormal decidualization was closely related to recurrent implantation failure (RIF). MLL1 is a histone H3 lysine 4 trimethylation (H3K4me3) transferase that regulates the transcriptional activation of target genes. The role of MLL1 has been underexplored during decidualization. In our research, we found the expression of MLL1 was closely related to endometrial receptivity, and it was responsible to hormone stimulation. Inhibiting the function of MLL1 by MM102 reduced the transformation of HESCs. Furthermore, down-regulation of MLL1 by siRNA transfection significantly decreased PGR and its target genes expression. MLL1 act as a co-activator of ERα, and both of them were recruited to PGR regulatory regions, thus promote PGR transcription. Our study showed that MLL1 plays a key role in promoting progesterone signalling transmission.

5.
J Mol Endocrinol ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33151904

RESUMO

The aberrant histone methylation patterns contribute to the pathogenesis of endometriosis (EM). Mixed lineage leukemia 1 (MLL1), a histone methyltransferase, is crucial for gene expression by catalyzing the trimethylation of histone 3 lysine 4 (H3K4me3) in gene promoter. This study aimed to explore whether MLL1 is involved in EM-related infertility. The expressions of MLL1 and H3K4me3 were analyzed in the eutopic endometria from EM women with infertility (n=22) and the normal endometria from EM-free women (n=22). Mouse EM model was established. The MLL1 and H3K4me3 expression patterns in mice endometria of early pregnancy were also investigated. Immortalized human endometrial stromal cells (iESCs) were cultured and underwent in vitro decidualization. The chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) was performed to find the target gene of MLL1 during decidual process. Results showed that both MLL1 and H3K4me3 decreased in the eutopic endometrium from EM patients compared to that in the normal endometrium. During early pregnancy and the decidual process, MLL1 and H3K4me3 were significantly upregulated in stromal cells. ChIP-seq and ChIP-qPCR found that the cytochrome c oxidase subunit 4I 2 (COX4I2) was directly targeted by MLL1. The dominance of COX4I2-containing enzyme induced the expression of hypoxia-inducible factor-2α (HIF-2α), whose expression in the peri-implantation endometrium is essential for embryo implantation. Further results showed that MLL1 was directly regulated by progesterone (P4) - P4 receptors (PRs). Our study proved that MLL1 was involved in EM-related infertility, which may provide a novel approach to treat the nonreceptive endometrium in EM patients.

6.
Biomed Pharmacother ; 131: 110769, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152931

RESUMO

OBJECTIVES: Pomegranate flower is a kind of uygur medicine with anti - type 2 diabetes, anti - lipid, anti - inflammation, anti - oxidation. We investigated the effect of pomegranate flower extract (PFE) on the proliferation, differentiation and apoptosis of 3T3-L1 preadipocytes, as well as the effects of five compounds in PF on cell differentiation. METHODS: 3T3-L1 preadipocytes were treated with PFE (0.5, 1, 2, 5, 10, 20, 50, 100 µg/mL), quercetin, luteolin, ursolic acid, apigenin and kaempferol (5, 10, 20, 40, 80 µM), and cell viability was measured at 24, 48 and 72 h by Cell Counting Kit-8. The modified cocktail induction method induced the differentiation of 3T3-L1 preadipocytes, and treated them with PFE and the compounds. The lipid accumulation was determined by oil red O staining, and the intracellular triglyceride content was determined by commercial kit. The expressions of PPARγ, C/EBP, LPL, DGAT and aP2 mRNA in mature adipocyte were determined by q-PCR, and the expressions of PPARγ, Akt, p-akt and PI3K protein were determined by western blot. 3T3-L1 preadipocytes were treated with PFE (5, 10, 20 µg/mL) while induced apoptosis by palmitate (300 µM), Hoechst staining to observe apoptosis morphology, Annexin Ⅴ- FITC/PI staining with flow cytometry instrument to detect the number of early and late apoptosis cells, the q-PCR and western blot for determining the Bcl-2, Bax, caspase 3 mRNA and protein expression. RESULTS: PFE (5, 10, 20 µg/mL) promoted or did not affect the proliferation and differentiation of 3T3-L1 preadipocytes, and reduced the number of early and late apoptotic cells, increased the expression of Bcl-2 mRNA and protein, and inhibited the expression of Bax and caspase-3 mRNA and protein. Furthermore, PFE (40, 60 µg/mL), quercetin (10, 20, 40 µM), luteolin (5, 10, 20 µM), apigenin(20,40 µM), kaempferol (20, 40 µM) significantly restrain the 3T3-L1 different extent proliferation and differentiation of preadipocyte, reduce the accumulation of lipids in adipocyte, reduce expression of adipogenesis factor, PFE(40, 60 µg/mL) inhibited the activation of the PI3K-Akt pathway by inhibiting the expression of PI3K and p-Akt proteins, and inhibited preadipocyte differentiation by reduce the expression of PPARγ protein. CONCLUSION: PFE has a concentration-related bidirectional effect on the proliferation, differentiation and apoptosis of 3T3-L1 preadipocytes, which depends on the regulation of PI3K-Akt pathway, which is of guiding role for PFE in the treatment of type 2 diabetes, hyperlipidemia, obesity and other diseases.

7.
J Ophthalmol ; 2020: 5125243, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062312

RESUMO

Purpose: To investigate the influences of atropine on changes in anterior segment geometry, as measured by ultrasound biomicroscopy in children. Methods: A prospective observational study was performed. Anterior segment parameters were obtained by UBM before and after the instillation of 1% atropine. Univariate linear regression was performed to identify the variables contributing to the changes in the trabecular meshwork-iris angle (TIA). Results: The study included 21 boys and 37 girls with a mean age of 10.79 ± 2.53 years. Anterior chamber parameters including the central anterior chamber depth, TIA, angle opening distance at 500 µm from the scleral spur, iris thickness 750 µm and 1500 µm from the scleral spur, trabecular-ciliary angle (TCA), trabecular-ciliary process distance, sclera-iris angle (SIA), and sclera-ciliary process angle significantly increased after cycloplegia (P < 0.05). In contrast, the lens vault, iris cross-sectional area, and maximum ciliary muscle thickness significantly decreased after cycloplegia. Univariate analysis identified the change in TCA and the change in SIA and the TIA before mydriasis as determinants of the change in TIA. Conclusions: Atropine causes statistically significant changes in various anterior segment parameters in children. The change in anterior chamber angle is associated with the change in TCA and the change in SIA and the TIA before mydriasis.

8.
Int J Med Sci ; 17(15): 2362-2372, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922202

RESUMO

Cervical cancer is the most common gynecologic malignant tumor, with a high incidence in 50-55-year-olds. This study aims to investigate the potential molecular mechanism of RRM2 for promoting the development of cervical cancer based on The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). RRM2 was found to be significant upregulated in cervical tissue (P<0.05) by extracting the expression of RRM2 from TCGA, GSE63514, GSE7410, GSE7803 and GSE9750. Survival analysis indicated that the overall survival was significantly worse in the patients with high-expression of RRM2 (P<0.05). The top 1000 positively/negatively correlated genes with RRM2 by Pearson Correlation test were extracted. The gene co-expression network by Weighted Gene Co-Expression Network Analysis (WGCNA) with these genes and the clinical characteristics (lymphocyte infiltration, monocyte infiltration, necrosis, neutrophil infiltration, the number of normal/stromal/tumor cells and the number of tumor nuclei) was constructed. By screening the hub nodes from the co-expression network, results suggested that RRM2 may co-express with relevant genes to regulate the number of stromal/tumor cells and the process of lymphocyte infiltration to promote the progression of cervical cancer. RRM2 is likely to become a novel potential diagnostic and prognostic biomarker of cervical cancer and provide evidence to support the study of mechanisms for cervical cancer.

9.
Ann Transl Med ; 8(14): 867, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32793711

RESUMO

Background: Vascularized composite tissue allotransplantation (VCA) has increasingly been adopted for the reconstruction of tissues following severe injury. However, the side effects of the post-operative use of immunosuppressants may outweigh the benefits of VCA. In order to overcome this obstacle, ex-vivo pretreatment of allografts combined with mesenchymal stem cell-based therapy may help induce immunotolerance in composite tissue allotransplantation. Methods: A hind-limb allotransplantation model of Brown-Norway to Lewis rats was established, and the allografts were infused with adipose-derived stem cells (ADSCs) and hypoxia primed ADSCs, which were injected through the vascular system along with short-term immunosuppressant treatment. The rejection-free survival of the allografts was monitored, and the histopathological examination of allografts was performed. The peripheral T lymphocytes and cytokines were analyzed using flow cytometry and ELISA, while Tregs infiltration in allotissue was detected using immunohistochemical staining (IHC). Results: This study found that the ex-vivo treatment of allografts using ADSCs prolonged the survival of the allografts, compared with the medium control, suppressed the proliferation and infiltration of T lymphocytes and improved the secretion of immunomodulatory cytokines, such as IL-10, as well as induced regulatory T cells (Tregs) expression in the allografts. Conclusions: The ex-vivo pretreatment of allografts using ADSCs may function as an important adjunctive therapy for the induction of immunotolerance in VCA.

10.
Bioinformatics ; 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32756939

RESUMO

MOTIVATION: Despite of the lack of folded structure, intrinsically disordered regions (IDRs) of proteins play versatile roles in various biological processes, and many nonsynonymous single nucleotide variants (nsSNVs) in IDRs are associated with human diseases. The continuous accumulation of nsSNVs resulted from the wide application of NGS has driven the development of disease-association prediction methods for decades. However, their performance on nsSNVs in IDRs remains inferior, possibly due to the domination of nsSNVs from structured regions in training data. Therefore, it is highly demanding to build a disease-association predictor specifically for nsSNVs in IDRs with better performance. RESULTS: We present IDRMutPred, a machine learning-based tool specifically for predicting disease-associated germline nsSNVs in IDRs. Based on 17 selected optimal features that are extracted from sequence alignments, protein annotations, hydrophobicity indices, and disorder scores, IDRMutPred was trained using three ensemble learning algorithms on the training dataset containing only IDR nsSNVs. The evaluation on the two testing datasets shows that all the three prediction models outperform 17 other popular general predictors significantly, achieving the ACC between 0.856 and 0.868 and MCC between 0.713 and 0.737. IDRMutPred will prioritize disease-associated IDR germline nsSNVs more reliably than general predictors. AVAILABILITY: The software is freely available at http://www.wdspdb.com/IDRMutPred. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

11.
J Org Chem ; 85(19): 12108-12116, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-32829632

RESUMO

An effective design strategy with an efficient synthetic route to xanthene-based far-red to near-infrared dyes is reported. The dyes were prepared by the Suzuki cross-coupling of the electron-poor fluorescein ditriflate with the electron-rich boronic acid/ester-functionalized pyrrole (2C/3C) and indole (2D/3D) moieties. Upon treatment with trifluoroacetic acid, the closed nonfluorescent forms of the dyes (2C and 2D) ring-opened to their fluorescent forms (3C and 3D). The absorption maxima were 665 and 704 nm, while the emission maxima were 717 and 719 nm for 3C and 3D, respectively. The closed forms of the dyes were soluble in chloroform and acetonitrile. To test the efficacy of the dyes as probes, a turn-off fluoride ion probe was prepared from 3C, which consisted of a silyl ester receptor. The probe responded strongly to low concentrations of fluoride, carbonate, and acetate ions, weakly to phosphate ions, but not to the other halogens. Moreover, the probe can detect the minimum concentration of F- in water.

12.
Neoplasia ; 22(9): 431-440, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32652442

RESUMO

Pamiparib, an investigational Poly (ADP-ribose) polymerase (PARP) inhibitor in clinical development, demonstrates excellent selectivity for both PARP1 and PARP2, and superb anti-proliferation activities in tumor cell lines with BRCA1/2 mutations or HR pathway deficiency (HRD). Pamiparib has good bioavailability and is 16-fold more potent than olaparib in an efficacy study using BRCA1 mutated MDA-MB-436 breast cancer xenograft model. Pamiparib also shows strong anti-tumor synergy with temozolomide (TMZ), a DNA alkylating agent used to treat brain tumors. Compared to other PARP inhibitors, pamiparib demonstrated improved penetration across the blood brain barrier (BBB) in mice. Oral administration of pamiparib at a dose as low as 3 mg/kg is sufficient to abrogate PARylation in brain tumor tissues. In SCLC-derived, TMZ-resistant H209 intracranial xenograft model, combination of pamiparib with TMZ overcomes its resistance and shows significant tumor inhibitory effects and prolonged life span. Our data suggests that combination of pamiparib with TMZ has unique potential for treatment of brain tumors. Currently, the combination therapy of pamiparib with TMZ is evaluated in clinical trial [NCT03150862].

13.
J Med Virol ; 2020 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-32621617

RESUMO

In the past several months, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated infection (coronavirus disease 2019 [COVID-19]) developed rapidly and has turned into a global pandemic. Although SARS-CoV-2 mainly attacks respiratory systems, manifestations of multiple organs have been observed. A great concern was raised about whether COVID-19 may affect male reproductive functions. In this study, we collected semen specimens from 12 male COVID-19 patients for virus detection and semen characteristics analysis. No SARS-CoV-2 was found in semen specimens. Eight out of 12 patients had normal semen quality. We also compared the sex-related hormone levels between 119 reproductive-aged men with SARS-CoV-2 infection and 273 age-matched control men. A higher serum luteinizing hormone (LH) and a lower ratio of testosterone (T) to LH were observed in the COVID-19 group. Multiple regression analysis indicated that serum T: LH ratio was negatively associated with white blood cell counts and C-reactive protein levels in COVID-19 patients. It's the first report about semen assessment and sex-hormone evaluation in reproductive-aged male COVID-19 patients. Although further study is needed to clarify the reasons and underlying mechanisms, our study presents an abnormal sex hormone secretion among COVID-19 patients, suggesting that attention should be paid to reproductive function evaluation in the follow-up.

14.
World J Clin Cases ; 8(10): 1979-1987, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32518790

RESUMO

BACKGROUND: Heterotopic pancreas is a common lesion found in the gastrointestinal tract and is usually considered a benign disease. Reports of malignant change of heterotopic pancreas are scarce. CASE SUMMARY: A 44-year-old Chinese female underwent a gastroscopy to assess abdominal distension that had persisted for 2 months. A protruding lesion in the gastric antrum was revealed but no malignant tissue was found in the biopsy specimen. The patient's symptom persisted and progressed to repeated vomiting. Endoscopy after 4 months revealed obstruction of the gastric outlet caused by the protruding lesion. A distal gastrectomy was performed. Histopathological examination of the surgical specimen showed the malignant transformation of aberrant pancreas in the stomach. Chemotherapy consisting of folinic acid, fluorouracil, and oxaliplatin was administered for three cycles, and was changed to gemcitabine monotherapy because of adverse effects and increased serum tumor marker levels. The patient remained asymptomatic during a 12-month follow-up. CONCLUSION: Pancreatic heterotopy should be considered as source of a potentially malignant lesion, and early treatment or close monitoring for aberrant pancreas is recommended.

15.
Am J Cancer Res ; 10(3): 856-869, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32266095

RESUMO

Neurofibromatosis type 1 (NF1) and Neurofibromatosis type 2 (NF2) are two dominantly inherited disorders that cause tumors in Schwann cells. NF1 patients have a high risk for malignant peripheral nerve sheath tumors (MPNST), which are often inoperable and do not respond well to current chemotherapies or radiation. NF2 patients have a high risk for schwannomas. To identify potential therapeutic targets in these two tumors, we screened the NF1 MPNST cell line, ST88-14, and the NF2 schwannoma cell line, HEI-193, against ~2000 drugs of known mechanisms of action (including ~600 cancer relevant drugs), and also screened the cell lines against an siRNA library targeting most protein kinases. Both the drug screen and the siRNA screen identified Polo-like kinase 1 (PLK1) among the most potent hits in both cell lines. Since PLK1 acts on the cell cycle primarily at the G2/M transition, the same stage where aurora kinase (AURKA) acts, we explored PLK1 and its relationship to aurora kinase in MPNST. Quantitative profiling of PLK1 inhibitors against a panel of 10 neurofibromatosis cell lines found that they were potent inhibitors and, unlike AURKA inhibitors, were not more selective for NF1 over NF2 tumor cells. Furthermore, one PLK1 inhibitor, BI6727 stabilized tumor volume in MPNST xenografts. We conclude that PLK1 is a therapeutic target for MPNSTs and schwannomas, but inhibitors may have a narrow therapeutic index that limits their use as a single agent.

16.
Opt Express ; 28(3): 4225-4233, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32122079

RESUMO

Metasurface with thin planar resonant elements offers great capability in manipulating electromagnetic waves and their interaction with semiconductors. Split-ring resonator (SRR), as the basic building block, has been extensively investigated for myriad applications owing to its multiple electric and magnetic resonant modes. In this work, we report a rotated fourfold U-shape SRR metasurface for polarization-insensitive strong enhancement of mid-infrared photodetection. The integrated photodetector consists of a rotated fourfold SRR array and an InAsSb based heterojunction photodiode. A photosensitivity enhancement factor as high as 11 has been achieved by adoption of superimposed high order magnetic and electric resonant modes in the SRR metasurface. This work provides a promising pathway for exploring high performance polarization-insensitive photodetection in different electromagnetic wave ranges.

17.
J Steroid Biochem Mol Biol ; 200: 105640, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32087250

RESUMO

Bisphenol A(BPA) is one of the most widespread endocrine disruptors in the environment and is associated with reproductive diseases. In this study, we focused on the correlation between environmentally relevant levels of BPA exposure and histone modification during endometrial stromal cells decidualization. BPA exposure changed the morphology of decidualized endometrial stromal cells, with inhibition of mixed-lineage leukemia 1(MLL1) and induction of enhancer of zeste homolog2 (EZH2) during in vitro decidualization. The expression of HOXA10, PRL and IGFBP-1 was down-regulated upon BPA treatment. Furthermore, chromatin immunoprecipitation quantitative PCR(ChIP-qPCR) was performed to evaluate the recruitment of histone-3, lysine-4 trimethylation (H3K4me3) and histone-3, lysine-27 trimethylation (H3K27me3) at the gene promoters. The decreased H3K4me3 and the increased H3K27me3 at HOXA10, PRL and IGFBP-1 promoter regions were consistent with the expression of MLL1 and EZH2 respectively. The effect of BPA on MLL1 and EZH2 could be abrogated by ICI 182,780. Our study provides the first indication that environmentally relevant levels of BPA exposure can regulate the expression of decidualization-related genes by affecting histone modification, impairing endometrial decidualization.


Assuntos
Compostos Benzidrílicos/farmacologia , Disruptores Endócrinos/farmacologia , Fenóis/farmacologia , Células Estromais/efeitos dos fármacos , Adulto , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Endométrio/citologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Epigênese Genética , Feminino , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Humanos , Pessoa de Meia-Idade , Proteína de Leucina Linfoide-Mieloide/metabolismo , Regiões Promotoras Genéticas , Células Estromais/metabolismo , Células Estromais/fisiologia
18.
Reprod Sci ; 27(1): 46-54, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32046406

RESUMO

Chemokine CXCL12 and its receptors CXCR4/CXCR7 play a pivotal role in many physiological and pathological situations, while the expression and function in human term trophoblast cells remain largely unknown. In the study, the expression and function of CXCL12 and its receptors CXCR4/CXCR7 in human term trophoblast cells were investigated. Immunocytochemistry and flow cytometry showed that the expression of CXCL12/CXCR4/CXCR7 could be detected in term trophoblast cells while expression level differed. The secretion of CXCL12 in human term trophoblast cells was confirmed by enzyme-linked immunosorbent assay (ELISA). In order to reveal the function of CXCL12, exogenetic recombinant human CXCL12 protein (rhCXCL12) was added to the cultured term trophoblast cells; results showed that cell proliferation ability was increased while cell apoptosis rate was decreased. Moreover, the effects of rhCXCL12 on term trophoblast cells could be diminished or attenuated by antibodies against CXCL12, CXCR4, or CXCR7, respectively. Therefore, these results revealed the important role of CXCL12 on human term trophoblast cells. Our study will provide new insights into understanding the role of CXCL12 on human term trophoblast cells.


Assuntos
Quimiocina CXCL12/metabolismo , Receptores CXCR4/metabolismo , Receptores CXCR/metabolismo , Trofoblastos/metabolismo , Apoptose/fisiologia , Proliferação de Células/fisiologia , Quimiocina CXCL12/genética , Humanos , Receptores CXCR/genética , Receptores CXCR4/genética , Nascimento a Termo
19.
Reprod Sci ; 27(2): 704-712, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32046440

RESUMO

Results of previous epidemiology studies on BPA exposure and endometriosis (EMs) risk were inconsistent, and were limited by inappropriate control selection, incorrect BPA detection method, and the generalization of different subtypes of EMs. Upregulated matrix metalloproteinase (MMP) 2 and MMP9 are involved in the development of EMs. We conducted a case-control study among 120 EMs patients and 100 healthy women to evaluate the relationships between BPA exposure and MMP2, MMP9 expressions, and the risk of EMs subtypes. Besides, we used human endometrial stromal cell lines (HESCs) to investigate the underlying mechanisms. Creatinine-adjusted urinary BPA concentrations were positively correlated with serum MMP2, MMP9 levels, and the risk of peritoneal EMs (third vs lowest quartile: OR 4.92, 95% CI 1.47, 16.50; fourth versus lowest quartile: OR 3.70, 95% CI 1.07, 12.74, Ptrend = 0.030). The risk of peritoneal EMs increased approximately tenfold when creatinine-adjusted urinary BPA concentration was 2 µg/g. In vitro study found that BPA exposure increased MMP2, MMP9 expressions in a dose-dependent manner. The effects of BPA on HESCs could be blocked by G protein-coupled estrogen receptor (GPER) inhibitor or mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) inhibitor. This study provides evidence that BPA exposure promotes peritoneal EMs, and raises a concern about the potential toxicity of BPA on the female reproductive system.

20.
Transpl Int ; 33(4): 450-461, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31930539

RESUMO

Systemic immunosuppression is indispensable for vascularized composite allotransplantation (VCA). Daily administration of standard triple therapy regimen of tacrolimus (FK506), mycophenolate mofetil (MMF), and steroid has severe side effects and reduces the compliance of VCA recipients. To overcome these hurdles, FK506/MMF/prednisolone (PDNN) was loaded into PLGA microspheres (PGLA MS). A single injection of FK506/MMF/PDNN-PLGA MS significantly prolonged the survival time of allograft in a rat hind limb transplantation model with a median survival time (MST) of more than 150 days compared to 34.5 days in the group treated orally with FK506/MMF/PDNN and 11 days in the nontreatment allograft and MS control groups. Analysis of showed that FK506/MMF/PDNN-PLGA MS could maintain relatively higher plasma and tissue drug concentrations for a long time. Moreover, histopathology and flow cytometry of circulating mononuclear cells revealed significantly prolonged immunosuppression by the FK506/MMF/PDNN-PLGA MS compared with the orally given FK506/MMF/PDNN. In conclusion, a single injection of FK506/MMF/PDNN-PLGA MS may provide a new approach for long-term prevention of immune rejection in VCA.

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