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1.
Neurosci Lett ; : 134595, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682872

RESUMO

The pathogenesis of cancer induced bone pain (CIBP) is extremely complex, and glutamate receptor dysfunction plays an important role in the formation of CIBP. Synapse-associated protein 102 (SAP102) anchors glutamate receptors in the postsynaptic membrane. However, its effect on hyperalgesia formation in CIBP has not been clarified. This study investigated the role of SAP102 in the formation of hyperalgesia in rats with CIBP SAP102 is present in spinal dorsal horn neurons, but not in astrocytes or microglia. NMDAR-NR2B is localized with neurons. In addition, SAP102 and NMDAR-NR2B expression levels in spinal dorsal horn tissues were detected by Western blot and co-immunoprecipitation. Intrathecal injection of lentiviral vector of RNAi to knockdown SAP102 expression in the spinal dorsal horn significantly attenuated abnormal mechanic pain when compared to non-coding lentiviral vector. These findings indicate that SAP102 can anchor NMDA receptors to affect hyperalgesia formation in bone cancer pain.

2.
World J Pediatr ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31686366

RESUMO

BACKGROUND: Pulmonary hemorrhage (PH) is a life-threatening respiratory complication of extremely low-birth-weight infants (ELBWIs). However, the risk factors for PH are controversial. Therefore, the purpose of this study was to analyze the perinatal risk factors and short-term outcomes of PH in ELBWIs. METHODS: This was a retrospective cohort study of live born infants who had birth weights that were less than 1000 g, lived for at least 12 hours, and did not have major congenital anomalies. A logistic regression model was established to analyze the risk factors associated with PH. RESULTS: There were 168 ELBWIs born during this period. A total of 160 infants were included, and 30 infants were diagnosed with PH. Risk factors including gestational age, small for gestational age, intubation in the delivery room, surfactant in the delivery room, repeated use of surfactant, higher FiO2 during the first day, invasive ventilation during the first day and early onset sepsis (EOS) were associated with the occurrence of PH by univariate analysis. In the logistic regression model, EOS was found to be an independent risk factor for PH. The mortality and intraventricular hemorrhage rate of the group of ELBWIs with PH were significantly higher than those of the group of ELBWIs without PH. The rates of periventricular leukomalacia, moderate-to-severe bronchopulmonary dysplasia and severe retinopathy of prematurity, and the duration of the hospital stay were not significantly different between the PH and no-PH groups. CONCLUSIONS: Although PH did not extend hospital stay or increase the risk of bronchopulmonary dysplasia, it increased the mortality and intraventricular hemorrhage rate in ELBWIs. EOS was the independent risk factor for PH in ELBWIs.

3.
Ecotoxicol Environ Saf ; 188: 109894, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31706239

RESUMO

Modulation of plant salt tolerance has been drawing great attention. Thymol is a kind of natural chemical that has been developed as anti-microbial reagent and medicine. To date, we still have limited knowledge about thymol-modulated plant physiology. In this work, physiological, histochemical, and biochemical methods were adopted to study thymol-conferred salt resistance in the root of rice (Oryza sativa). Thymol significantly rescued root growth under salt stress. Thymol ameliorated cell membrane damage, oxidative stress, ROS accumulation, and cell death in roots under salt stress. Thymol-attenuated oxidative stress may be resulted from the activation of anti-oxidative capacity, including both enzymatic and non-enzymatic system. Thymol treatment significantly decreased Na+ content in root cells upon salt stress, which might be ascribed to the upregulation of OsSOS1 (salt overly sensitive 1) facilitating Na+ exclusion. In addition, thymol stimulated the expression of genes encoding tonoplast OsNHX (Na+/H+antiporter), which may help root cells to compartmentalize Na+ in vacuole. The results of these works evidenced that thymol was capable of inducing salt tolerance by reestablishing ROS homeostasis and modulating cellular Na+ flux in rice roots. These findings may be applicable to improve crop growth in salinity area.

5.
Nucleic Acids Res ; 47(15): e87, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31127310

RESUMO

Detection of cancer-associated somatic mutations has broad applications for oncology and precision medicine. However, this becomes challenging when cancer-derived DNA is in low abundance, such as in impure tissue specimens or in circulating cell-free DNA. Next-generation sequencing (NGS) is particularly prone to technical artefacts that can limit the accuracy for calling low-allele-frequency mutations. State-of-the-art methods to improve detection of low-frequency mutations often employ unique molecular identifiers (UMIs) for error suppression; however, these methods are highly inefficient as they depend on redundant sequencing to assemble consensus sequences. Here, we present a novel strategy to enhance the efficiency of UMI-based error suppression by retaining single reads (singletons) that can participate in consensus assembly. This 'Singleton Correction' methodology outperformed other UMI-based strategies in efficiency, leading to greater sensitivity with high specificity in a cell line dilution series. Significant benefits were seen with Singleton Correction at sequencing depths ≤16 000×. We validated the utility and generalizability of this approach in a cohort of >300 individuals whose peripheral blood DNA was subjected to hybrid capture sequencing at ∼5000× depth. Singleton Correction can be incorporated into existing UMI-based error suppression workflows to boost mutation detection accuracy, thus improving the cost-effectiveness and clinical impact of NGS.

6.
Mol Med Rep ; 19(6): 4727-4734, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059065

RESUMO

The aim of the present study was to investigate the protective effect of integrin ß1 in the treatment of stress urinary incontinence (SUI) by electrical stimulation, and the underlying mechanisms by which electrical stimulation regulates the collagen metabolism of female vaginal wall fibroblasts (FVWFs). FVWFs obtained from the vaginal wall tissue of patients with (Ingelman­Sundberg scale; grade II, n=8; grade III, n=10) or without (n=8) SUI during gynecological operations were isolated by enzymatic digestion and subsequently identified by immunocytochemistry. Following this, cultured FVWFs were treated with an inhibitor of integrin ß1, recombinant human integrin ß1 and electrical stimulation (100 mv/mm, 2 h, 20 Hz), followed by total mRNA and protein extraction. mRNA and protein expression levels of integrin ß1, transforming growth factor (TGF)­ß1 and collagen (COL) I and III in FVWFs were quantified by reverse transcription­quantitative PCR (RT­qPCR) and western blot analysis respectively. Integrin ß1, TGF­ß1 and COL I and III expression levels were decreased in patients with SUI compared with healthy controls, and the grade III group had lower levels than the grade II group. Following electrical stimulation treatment, the expression levels of TGF­ß1, COL I and III were enhanced in the grade II group, but not in the grade III group. Nevertheless, the inhibitor of integrin ß1 reduced the protective effect of electrical stimulation in the grade II group. In addition, electrical stimulation combined with recombinant human integrin ß1 could also protect cells from SUI in the grade III group. The present study provides evidence for the increased degradation of the extracellular matrix and integrin ß1 in the vaginal wall tissues of patients with SUI, and the protective effect of electrical stimulation against SUI via integrin ß1. These results provide a novel mechanism for the treatment of SUI using electrical stimulation.


Assuntos
Estimulação Elétrica/métodos , Integrina beta1/farmacologia , Integrina beta1/uso terapêutico , Incontinência Urinária por Estresse/tratamento farmacológico , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Fator de Crescimento Transformador beta1 , Incontinência Urinária , Vagina/metabolismo , Vagina/patologia
7.
Stem Cell Res Ther ; 10(1): 145, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113492

RESUMO

BACKGROUND: Glioblastoma (GBM) is the most common type of primary malignant brain tumor. Molecular hydrogen has been considered a preventive and therapeutic medical gas in many diseases including cancer. In our study, we sought to assess the potential role of molecular hydrogen on GBM. METHODS: The in vivo studies were performed using a rat orthotopic glioma model and a mouse subcutaneous xenograft model. Animals inhaled hydrogen gas (67%) 1 h two times per day. MR imaging studies were performed to determine the tumor volume. Immunohistochemistry (IHC), immunofluorescence staining, and flow cytometry analysis were conducted to determine the expression of surface markers. Sphere formation assay was performed to assess the cancer stem cell self-renewal capacity. Assays for cell migration, invasion, and colony formation were conducted. RESULTS: The in vivo study showed that hydrogen inhalation could effectively suppress GBM tumor growth and prolong the survival of mice with GBM. IHC and immunofluorescence staining demonstrated that hydrogen treatment markedly downregulated the expression of markers involved in stemness (CD133, Nestin), proliferation (ki67), and angiogenesis (CD34) and also upregulated GFAP expression, a marker of differentiation. Similar results were obtained in the in vitro studies. The sphere-forming ability of glioma cells was also suppressed by hydrogen treatment. Moreover, hydrogen treatment also suppressed the migration, invasion, and colony-forming ability of glioma cells. CONCLUSIONS: Together, these results indicated that molecular hydrogen may serve as a potential anti-tumor agent in the treatment of GBM.

8.
Eur J Pharmacol ; 856: 172352, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31004603

RESUMO

Nasopharyngeal Carcinoma is limited by the various severe side-effects and surgery is rarely performed. Iosliquiritigenin has a series of biological activities, such as antiviral, anti-free radical and antitumor. However, the role and underlying mechanism of isoliquiritigenin in nasopharyngeal carcinoma have not been understood yet. Herein, the results revealed that isoliquiritigenin could inhibit cell proliferation in nasopharyngeal carcinoma cell lines, including C666-1 and CNE2, in both Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assay. In addition, isoliquiritigenin promoted nasopharyngeal carcinoma cell apoptosis, with the up-regulations of Bax, Caspase-3 and Caspase-9 and the down-regulation of Bcl-2. Meanwhile, isoliquiritigenin suppressed nasopharyngeal carcinoma cells migration and invasion with the down-regulation of matrix metalloproteinases (MMP)-2 and MMP-9. Furthermore, the expression of miR-32 was up-regulated in the nasopharyngeal carcinoma tissues, while isoliquiritigenin could significantly down-regulate the expression of miR-32. And over-expression of miR-32 promoted the nasopharyngeal carcinoma cells growth, migration and invasion, and suppressed apoptosis. However, isoliquiritigenin treatment dramatically inhibited the effect of miR-32. Besides, luciferase reporter assay confirmed that large tumor suppressor 2 (LATS2) was a direct target of miR-32. And isoliquiritigenin increased the expression of LATS2, while silencing of LATS2 promoted the nasopharyngeal carcinoma cells growth. Moreover, western blotting discovered that isoliquiritigenin inhibited nasopharyngeal carcinoma cells growth via Wnt signaling pathway. Finally, CNE2 cells transplanted xenografts tumor model in nude mice were performed and it suggested that isoliquiritigenin could inhibit the development of xenografts nude mice, along with the decrease of tumor volume and the expression of miR-32 and LATS2. Overall, isoliquiritigenin was confirmed to be a potent anti-nasopharyngeal carcinoma compound both in vitro and in vivo, and accomplished by regulation of miR-32/LATS2/Wnt.

9.
Sci Adv ; 5(4): eaau6547, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30949574

RESUMO

The interaction between gastric epithelium and immune response plays key roles in H. pylori-associated pathology. We demonstrated a procolonization and proinflammation role of MMP-10 in H. pylori infection. MMP-10 is elevated in gastric mucosa and is produced by gastric epithelial cells synergistically induced by H. pylori and IL-22 via the ERK pathway. Human gastric MMP-10 was correlated with H. pylori colonization and the severity of gastritis, and mouse MMP-10 from non-BM-derived cells promoted bacteria colonization and inflammation. H. pylori colonization and inflammation were attenuated in IL-22-/-, MMP-10-/-, and IL-22-/-MMP-10-/- mice. MMP-10-associated inflammation is characterized by the influx of CD8+ T cells, whose migration is induced via MMP-10-CXCL16 axis by gastric epithelial cells. Under the influence of MMP-10, Reg3a, E-cadherin, and zonula occludens-1 proteins decrease, resulting in impaired host defense and increased H. pylori colonization. Our results suggest that MMP-10 facilitates H. pylori persistence and promotes gastritis.

10.
Ann Endocrinol (Paris) ; 80(2): 72-76, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30825997

RESUMO

OBJECTIVE: To investigate the relations of circulating adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) with carotid artery elasticity in patients with impaired glucose regulation (IGR). METHODS: A total of 208 subjects were enrolled from January 2013 to March 2014. One hundred forty-eight were IGR patients, and 60 had normal glucose tolerance (NGT). Carotid intima-media thickness (IMT), carotid artery pressure-strain elasticity coefficient (Eρ), stiffness (ß), arterial compliance (AC), and pulse wave velocity (PWVß), as well as blood pressure, body mass index, blood glucose, blood lipids, insulin resistance index, VCAM-1, and ICAM-1 were measured and compared between IGR and NGT patients. RESULTS: Eρ, ß and PWVß were significantly higher in the IGR group than in the NGT group (P<0.05), but the IMT showed no significant difference (P>0.05). VCAM-1 and ICAM-1 were significantly higher in the IGR group than in the NGT group (P<0.05). VCAM-1 and ICAM-1 were positively correlated with Eρ, ß, and PWVß and negatively correlated with AC in IGR patients. CONCLUSIONS: Changes in carotid artery elasticity and endothelial dysfunction are found in patients with IGR. Early comprehensive intervention should be performed in such IGR populations.


Assuntos
Artérias Carótidas/fisiopatologia , Intolerância à Glucose/sangue , Intolerância à Glucose/fisiopatologia , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Rigidez Vascular/fisiologia , Adulto , Idoso , Glicemia/metabolismo , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Elasticidade/fisiologia , Feminino , Intolerância à Glucose/diagnóstico , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/fisiopatologia , Análise de Onda de Pulso , Ultrassonografia , Adulto Jovem
11.
Sex Transm Infect ; 95(4): 246-250, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30926713

RESUMO

OBJECTIVE: Changes in microRNAs (miRNAs) in the cerebrospinal fluid (CSF) are associated with different neurological diseases. Since alternations of miRNAs in neurosyphilis are insufficiently investigated, we analysed miRNAs in the CSF of patients suffering from neurosyphilis. METHODS: Exosomes were isolated from serum and CSF. Levels of 44 miRNAs were determined using quantitative real-time PCR-based miRNA array. RESULTS: In patients with neurosyphilis (NSP), miR-590-5p, miR-570-3p and miR-570-5p were upregulated in the CSF and serum, when compared with patients with syphilis without neurosyphilis (SP). miR-590-5p and miR-570-3p were significantly upregulated (p<0.001). The expression of miR-21-5p was upregulated only in the CSF of NSP. Significant downregulation was observed for miR-93-3p in the CSF and serum of NSP. No statistical difference was found in the expression of miR-7-5p, miR-1307-5p, miR-203a-3p, miR-16, miR-23b-3p and miR-27b-5p in the CSF and serum of NSP and SP. CONCLUSION: For the first time, regulation profiles in miRNA in the CSF and serum were analysed in NSP. We found significant differences in upregulation and downregulation. Therefore, miRNAs may be potential biomarkers for the presence of neurosyphilis.


Assuntos
Exossomos/metabolismo , MicroRNAs/sangue , Neurossífilis/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Feminino , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , MicroRNAs/líquido cefalorraquidiano , Pessoa de Meia-Idade , Neurossífilis/sangue , Neurossífilis/líquido cefalorraquidiano , Reação em Cadeia da Polimerase , Análise de Sequência de RNA
12.
Environ Pollut ; 247: 1064-1070, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30823335

RESUMO

Microcystin (MC) elimination is a global challenge that is necessary for the health of humans and ecosystems. Biodegradation of MC, one of the most environmental-friendly methods, had previously been focused on the aerobic condition. In this study, two enrichment cultures from Taihu sediments possessed high capacity for MC-leucine arginine (MC-LR) anaerobic biodegradation. Meanwhile, it was firstly found that MC-LR underwent similar degradation process under anaerobic conditions to that in aerobic condition. Furthermore, a novel degradation pathway, hydrolyzing of Ala-Mdha to form a new linear MC-LR intermediate, was proposed under anaerobic conditions. Combining MC-LR degradation with microbial community analysis, this study deduced that Candidatus Cloacamonas acidaminovorans str. Evry may play an important role in the degradation of MC-LR. These findings suggest an additional pathway involved in the environmental cycle of MC-LR, which implies that the biotransformation of MC-LR might play an important role in eliminating MC-LR in eutrophic lake sediments under anaerobic conditions.


Assuntos
Anaerobiose , Bactérias/metabolismo , Biodegradação Ambiental , Biotransformação , Lagos/química , Microcistinas/metabolismo , China , Redes e Vias Metabólicas , Oxirredução
13.
Neurosci Lett ; 699: 151-159, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30708128

RESUMO

Treatment of cancer-induced bone pain (CIBP) is challenging in clinics. Oxycodone is used to treat CIBP. However, the lack of understanding of the mechanism of CIBP limits the application of oxycodone. In this study, proteomic profiling of oxycodone-treated spinal dorsal cord of rats with CIBP was performed. Briefly, a total of 3519 proteins were identified in the Sham group; 3505 proteins in the CIBP group; and 3530 proteins in the CIBP-OXY treatment group. The 2-fold cut-off value was used as the differential protein standard for abundance reduction or increase (p < 0.05). Significant differences were found in the abundance of 16 proteins between Sham and CIBP group; 11 proteins in the CIBP group had increased abundance while 5 proteins had reduced abundance. Furthermore, fifteen proteins with differential abundance were identified between the CIBP group and the OXY group. Compared with the CIBP group, there were six increased abundances and nine reduced abundances in the OXY group. In addition, a reduced expression of ADP-ribosylation factor-like 6 binding factor 1 (Arl6ip-1), an endoplasmic reticulum protein that has an important role in cell conduction and material transport, was found in the CIBP group compared with the Sham group. Its expression increased after the administration of OXY. Proteomics results were further verified by Western-blot. Fluorescent staining revealed that Arl6ip-1 co-localized with spinal dorsal horn neurons, but not with astrocytes or microglia. Based on the observed results, we believe that Arl6ip-1 may be a potential drug target for OXY treatment of CIBP rats.

14.
Anal Chim Acta ; 1053: 122-130, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30712557

RESUMO

Telomerase is an important biomarker for cancer diagnosis and a valuable target for cancer therapy. Most of the reported telomerase assays suffer from the repeating thermal cycles, laborious protocols, expensive instruments and the limited sensitivity. To solve these issues, we develop a new telomerase assay based on telomerization-driven release of fluorescent 2-aminopurine. We designed a 2-aminopurine molecular beacon in which the fluorescence of 2-aminopurine is quenched due to stacking interaction effect without the use of extra quenchers. The presence of target telomerase can open the 2-aminopurine molecular beacon, triggering a quadratic signal amplification reaction to digest abundant 2-aminopurine molecular beacons, releasing large amounts of free 2-aminopurine molecules with strong fluorescence emission. Due to the inherent low background signal of 2-aminopurine molecular beacon and the highly efficient telomerization-driven quadratic signal amplification, this method exhibits high sensitivity with a limit of detection equivalent to 1 human lung cancer A549 cell and a large dynamic range of 4 orders of magnitude from 1 to 10000 cells. Moreover, this method can be further applied for telomerase inhibition assay and the discrimination of cancer cells from normal cells, holding great potential in telomerase-related clinical diagnosis and drug discovery.


Assuntos
Técnicas Biossensoriais/métodos , Limite de Detecção , Neoplasias Pulmonares/patologia , Sondas de Oligonucleotídeos/metabolismo , Telomerase/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Estudos de Viabilidade , Humanos , Sondas de Oligonucleotídeos/genética , Telomerase/antagonistas & inibidores
15.
Am J Nephrol ; 49(3): 214-224, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30808834

RESUMO

BACKGROUND: Is the prognosis of immunoglobulin A nephropathy (IgAN) influenced by pregnancy and delivery? The answer to this question still remains to be a controversial topic. Here, we undertook a systematic review and meta-analysis to obtain the overall estimate of potential effect of IgAN and pregnancy on each other. METHODS: We systematically searched MEDLINE, EMBASE, Chinese Biological Medicine and Cochrane for cohort and case-control studies; a total of 1,378 articles were reviewed and 9 studies were included in the end. OR and mean difference (MD) were calculated with a random-effects model, kidney events and pregnancy outcomes were analyzed respectively. RESULTS: The key finding of the meta-analysis of 145 renal events in 1,198 participants was that there was no difference in renal outcomes (defined as doubling of serum creatinine (SCr), 50% decline in glomerular filtration rate [GFR] and end-stage kidney disease) of pregnant women compared with non-pregnant women who had IgAN (OR 0.90; 95% CI 0.59-1.37; p = 0.63). Subgroup analysis indicated that there was no significant difference between the 2 groups according to sample size, follow-up year, age, level of SCr and proteinuria at baseline. There was no difference in the change of the eGFR/creatinine clearance rate (mL/min/1.73 m2 per year) in IgAN patients with pregnancy compared with non-pregnancy (MD -0.11 mL/min; 95% CI -0.50-0.27; p = 0.57) as well. Women with IgAN had a higher likelihood of pregnancy outcomes compared with the Chinese general population, while they had a lower risk of preterm delivery, preeclampsia and low birth weight compared with those who had lupus nephritis or diabetic nephropathy. CONCLUSIONS: Pregnancy did not accelerate kidney disease deterioration in women with IgAN in stages of chronic kidney disease 1-3. Moreover, patients with IgAN had a relatively low risk of adverse pregnancy events compared with those with lupus nephritis or diabetic nephropathy.

16.
Cell Death Dis ; 10(2): 79, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30692510

RESUMO

Interleukin-17 receptor B (IL-17RB), a member of the IL-17 receptor family activated by IL-17B/IL-17E, has been shown to be involved in inflammatory diseases. However, the regulation and function of IL-17RB in Helicobacter pylori (H. pylori) infection, especially in the early-phase is still unknown. Here, we found that gastric IL-17RB mRNA and protein were decreased in gastric mucosa of both patients and mice infected with H. pylori. In vitro experiments show that IL-17RB expression was down regulated via PI3K/AKT pathway on gastric epithelial cells (GECs) stimulated with H. pylori in a cagA-involved manner, while in vivo studies showed that the effect was partially dependent on cagA expression. IL-17E was also decreased during the early-phase of H. pylori infection, and provision of exogenous IL-17E resulted in increased CD11b+CD11c- myeloid cells accumulation and decreased bacteria colonization within the gastric mucosa. In the early-phase of H. pylori infection, IL-17E-IL-17RB promoted gastric epithelial cell-derived CXCL1/2/5/6 to attract CD11b+CD11c- myeloid cells, and also contributed to host defense by promoting the production of antibacterial protein Reg3a. This study defines a negative regulatory network involving IL-17E, GECs, IL-17RB, CD11b+CD11c- myeloid cells, and Reg3a in the early-phase of H. pylori infection, which results in an impaired host defense within the gastric microenvironment, suggesting IL-17RB as a potential early intervening target in H. pylori infection.

17.
Stem Cell Res Ther ; 10(1): 9, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30630525

RESUMO

BACKGROUND: Mouse somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by defined factors known to regulate pluripotency, including Oct4, Sox2, Klf4, and c-Myc. It has been reported that Sirtuin 6 (Sirt6), a member of the sirtuin family of NAD+-dependent protein deacetylases, is involved in embryonic stem cell differentiation. However, whether and how Sirt6 influences epigenetic reprogramming remains unknown. METHODS: Mouse embryonic fibroblasts isolated from transgenic Oct4-GFP reporter mice with or without Sirt6 were used for reprogramming by Yamanaka factors. Alkaline phosphatase-positive and OCT4-GFP-positive colony were counted to calculate reprogramming efficiency. OP9 feeder cell co-culture system was used to measure the hematopoietic differentiation from mouse ES and iPS cells. RNA sequencing was measured to identify the differential expressed genes due to loss of Sirt6 in somatic and pluripotent cells. RESULTS: In this study, we provide evidence that Sirt6 is involved in mouse somatic reprogramming. We found that loss of function of Sirt6 could significantly decrease reprogramming efficiency. Furthermore, we showed that Sirt6-null iPS-like cell line has intrinsically a differentiation defect even though the establishment of normal self-renewal. Particularly, by performing transcriptome analysis, we observed that several pluripotent transcriptional factors increase in knockout cell line, which explains the underlying loss of pluripotency in Sirt6-null iPS-like cell line. CONCLUSIONS: Taken together, we have identified a new regulatory role of Sirt6 in reprogramming and maintenance of pluripotency.

18.
FASEB J ; 33(4): 5018-5033, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30596522

RESUMO

Cathepsin C (CtsC) functions as a central coordinator for activation of many serine proteases in immune cells. However, CtsC expression in gastric epithelial cells and its role in Helicobacter pylori infection remain unclear. Real-time PCR, Western blot, and immunohistochemistry analyses identified that CtsC was decreased in gastric mucosa of H. pylori-infected patients and mice. Isolated gastric epithelial cells and cell lines were stimulated with H. pylori and/or TGF-ß1 showed that down-regulation of CtsC in gastric epithelial cells largely depended on H. pylori cagA via Src/ERK and Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways, and the effect could be synergistically augmented by TGF-ß1 in an autocrine manner. In human gastric mucosa, CtsC expression was negatively correlated with bacteria colonization; accordingly, provision of exogenous active CtsC overwhelmed H. pylori persistence in gastric mucosa of mice. In the presence of active CtsC, isolated human neutrophils activated via NF-κB pathway with augmented bactericidal capacity in vitro. We also found that neutrophils activated and cleared bacteria in active CtsC-injected mice and that there was no bactericidal capacity in mice that were simultaneously neutrophil-depleted by Ly6G antibody. Our findings identified a mechanism that H. pylori abrogate CtsC to impair neutrophil activation and to ensure persistence in gastric mucosa. Efforts to enable and boost this neutrophil activation pathway by active CtsC may therefore become valuable strategies in treating H. pylori infection.-Liu, Y. G., Teng, Y. S., Cheng, P., Kong, H., Lv, Y. P., Mao, F. Y., Wu, X. L., Hao, C. J., Chen, W., Yang, S. M., Zhang, J. Y., Peng, L. S., Wang, T. T., Han, B., Ma, Q., Zou, Q. M., Zhuang, Y. Abrogation of cathepsin C by Helicobacter pylori impairs neutrophil activation to promote gastric infection.

19.
Aust Crit Care ; 32(1): 63-75, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30554939

RESUMO

OBJECTIVE: The objective of this study was to review English and Chinese randomised controlled trials (RCTs) to determine the effects of family-centred care (FCC) interventions on preterm infants' and parental outcomes in the neonatal intensive care units and to conduct a meta-analysis. REVIEW METHOD USED: Systematic review and meta-analysis. DATA SOURCES: Medline, CINAHL, Embase, PsycINFO, BNI, and AMED and the Chinese databases CNKI and Wanfang Data were searched in April 2017 and updated in August 2018. REVIEW METHODS: Only RCTs were included. Participants were preterm infants ≤37 weeks gestational age and parents. Interventions were related to FCC, and outcome measures were infant and parent clinical outcomes. Included studies were assessed for risk of bias using Cochrane Manual 5.1.0. Meta-analyses used mean differences (MDs), standardised mean differences (SMDs), or odds ratio (OR), followed by 95% confidence interval (CI). Heterogeneity was tested with Cochran's Q chi-squared test, tau-squared test, and inconsistency index (I2). RESULTS: Nineteen studies (10 from English and 9 from Chinese databases) were included; meta-analysis included 15 studies (7 English and 8 Chinese RCTs). Meta-analysis showed significant improvements in weight gain (7 studies: MD, 4.57; 95% CI, 2.80-6.34; P < 0.001; I2 94%); readmission (3 studies: OR, 0.23; 95% CI, 0.10-0.52; P < 0.001; I2 = 0%); parent satisfaction (5 studies: OR, 11.20; 95% CI, 4.76-26.34; p < 0.001; I2 = 0%); skills of parents (4 studies: SMD, 2.57; 95% CI, 2.19-2.96; P < 0.001; I2 = 53%); knowledge of parents (4 studies: SMD, 2.74; 95% CI, 2.47-3.00; P < 0.001; I2 = 0%); parental anxiety at follow-up (3 studies: SMD, -0.19; 95% CI, -0.28 to -0.09; P < 0.001; I2 = 0%); parent depression at follow-up (2 studies: SMD, 0.37; 95% CI, -0.63 to -0.12; P = 0.004; I2 = 44%); and parental stress (3 studies: MD, -0.20; 95% CI, -0.26 to -0.13; P < 0.001; I2 = 0%). No statistical differences were observed in neurobehavioural development (3 studies) and hospital length of stay (7 studies). CONCLUSIONS: FCC interventions can improve weight gain and readmission in preterm infants as well as parent satisfaction, knowledge, and skills, and possibly long-term anxiety, depression, and stress. Developing standardised outcome sets for testing family-centred care interventions is recommended.

20.
Med Sci Monit ; 24: 9136-9143, 2018 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-30554232

RESUMO

BACKGROUND This study aimed to investigate the relationship between serum profiles of prolactin and thyroid stimulating hormone (TSH) and sexual dysfunction in patients with schizophrenia treated with conventional antipsychotic medication. MATERIAL AND METHODS A hospital-based cross-sectional study included 118 patients, age range 18-57 years (55 men, 63 women), with a confirmed diagnosis of schizophrenia. All patients were stable after antipsychotic treatment. Serum levels of hormones, including prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone, testosterone, thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3) and free thyroxine (FT4), were detected in venous blood. The Positive and Negative Syndrome Scale (PANSS) score was used to measure symptom severity of patients with schizophrenia. The Mandarin Chinese version of the Arizona Sexual Experience Scale (ASEX), a 5-item scale, was used to measure sexual function. RESULTS There were 66 patients (55.9%) who had hyperprolactinemia, the prevalence of hyperprolactinemia was markedly higher in the sexual dysfunction group than the non-sexual dysfunction group (91.8% vs. 17.5%) (P<0.001). Mean prolactin levels were significantly increased in patients with sexual dysfunction compared with the patients without sexual dysfunction (P<0.001), with a higher incidence in female patients. Subclinical hypothyroidism and hyperprolactinemia were found to be independently associated with sexual dysfunction, and an increased PANSS negative score was an independent risk factor for the development of sexual dysfunction. CONCLUSIONS The incidence of sexual dysfunction was significantly increased in patients with schizophrenia. Hyperprolactinemia and subclinical hypothyroidism were associated with sexual dysfunction, especially in female patients.


Assuntos
Prolactina/análise , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/fisiopatologia , Adolescente , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , China , Estudos Transversais , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hiperprolactinemia/complicações , Hipotireoidismo/complicações , Masculino , Pessoa de Meia-Idade , Prolactina/sangue , Esquizofrenia/complicações , Testosterona/sangue , Testes de Função Tireóidea , Tireotropina/análise , Tireotropina/sangue , Tiroxina/sangue
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