Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 351
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Drug Des Devel Ther ; 13: 3171-3180, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564833

RESUMO

Background: Emodin, a major component of Polygonum multiflorum (PM), has been reported to exert both protective and toxic effects in several cell types. However, the effects and underlying mechanisms of action of emodin in hepatic cells are still obscure. Methods: The present study used the normal human liver cell line L02 to investigate the effects and mechanisms of emodin in hepatic cells. After treatment with emodin, L02 cells were examined for viability, apoptosis and autophagy with the Cell Counting Kit-8 (CCK-8), annexin V/PerCP staining and GFP-LC3 plasmid transfection. The expression of proteins including cleaved caspase-3, LC3B-I/II, p-PI3K, PI3K, p-AKT, AKT, p-mTOR, mTOR and actin was examined by using Western blot. Results: Emodin significantly inhibited the viability of and induced apoptosis in L02 cells in a dose- and time-dependent manner. In addition, emodin increased the number of GFP-LC3 puncta in L02 cells and upregulated the expression of LC3B-II compared to those in control cells. Furthermore, emodin significantly decreased the expression of p-PI3K, p-AKT and p-mTOR in a dose-dependent manner compared to that in control cells without altering the expression of PI3K, AKT and mTOR. Notably, cotreatment with emodin and 3-methyladenine (3-MA) or rapamycin significantly increased and decreased the apoptosis rate of L02 cells, respectively, compared to that of cells treated with emodin alone. Conclusion:  In conclusion, emodin exhibited cytotoxicity in the L02 human hepatic cell line by promoting apoptosis, and it also induced autophagy through the suppression of the PI3K/AKT/mTOR signalling pathway. The autophagy could play a protective role following emodin treatment.

2.
Acta Otolaryngol ; 139(11): 939-947, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31486693

RESUMO

Background: Inner gene therapy offers great promises as a potential treatment for hearing loss. Aims/objectives: One of the critical determinants of the success of inner ear gene therapy is to find a delivery method which results in consistent transduction efficiency of targeted cell types while minimizing hearing loss. Material and methods: Surgery was performed only in the right ear of each Bama miniature pig, and the left ear served as a control. The gene delivery to inner ear via round window membrane (RWM) and posterior semicircular canal (PSC) approach was performed with the viral vector AAV1-CMV-GFP. Results: The gene delivery through RWM and the PSC (canalostomy) is able to perfuse the inner ear. Conclusions and significance: The easy anatomic identification of the PSC, as to RWM, as well as minimal manipulation of the temporal bone required, make this surgical approach an attractive option for inner ear gene delivery in big animal model.

5.
Surgery ; 166(5): 835-843, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31353081

RESUMO

BACKGROUND: Critical errors increase postoperative morbidity and mortality. A trauma readiness index was used to evaluate critical errors in 4 trauma procedures. In comparison to practicing and expert surgeon benchmarks, we hypothesized that pretraining trauma readiness index including both vascular and nonvascular trauma surgical procedures can identify residents who will make critical errors. METHODS: In a prospective study, trained evaluators used a standardized script to evaluate performance of brachial, axillary, and femoral artery exposure and proximal control and lower-extremity fasciotomy on unpreserved cadavers. Forty residents were evaluated before and immediately after Advanced Surgical Skills for Exposure in Trauma training, and 38 were re-evaluated 14 months later. Residents were compared to 34 practicing surgeons evaluated once 30 months after training, and 10 experts. RESULTS: Resident trauma readiness index increased with training (P < .001), remained unchanged 14 month later and was higher, with lower variance than practicing surgeons (P < .05). Expert trauma readiness index was higher than residents (P < .004) and practicing surgeons (P < .001). Resident training decreased critical errors when evaluated immediately and 14 months after Advanced Surgical Skills for Exposure in Trauma training. Practicing surgeons had more critical errors and performance variability than residents or experts. Experts had 5 to 7 times better error recovery than practicing surgeons or residents. Trauma readiness index area under the receiver operating curve with Youden Index <0.60 or <6 decile in their cohort, predicts a surgeon will make a critical error. CONCLUSION: Low trauma readiness index was associated with critical errors occurring in all surgeon cohorts and can identify surgeons in need of remedial intervention.

6.
Cell Commun Signal ; 17(1): 63, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186051

RESUMO

Human telomerase reverse transcriptase (hTERT) is the core subunit of human telomerase and plays important roles in human cancers. Aberrant expression of hTERT is closely associated with tumorigenesis, cancer cell stemness maintaining, cell proliferation, apoptosis inhibition, senescence evasion and metastasis. The molecular basis of hTERT regulation is highly complicated and consists of various layers. A deep and full-scale comprehension of the regulatory mechanisms of hTERT is pivotal in understanding the pathogenesis and searching for therapeutic approaches. In this review, we summarize the recent advances regarding the diverse regulatory mechanisms of hTERT, including the transcriptional (promoter mutation, promoter region methylation and histone acetylation), post-transcriptional (mRNA alternative splicing and non-coding RNAs) and post-translational levels (phosphorylation and ubiquitination), which may provide novel perspectives for further translational diagnosis or therapeutic strategies targeting hTERT.

7.
J Trauma Acute Care Surg ; 87(1S Suppl 1): S146-S151, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31246919

RESUMO

BACKGROUND: Clinical data are lacking on the influence of chest trauma on the secondary injury process after traumatic brain injury (TBI), with some data suggesting that multiple trauma may worsens brain injury. Blunt chest trauma and TBI represent the two major single injury entities with the highest risk of complications and are potential biomarker targets. METHODS: Trauma patients with severe TBI were enrolled. Serum biomarker levels were obtained every 6 hours for 72 hours. Baseline, 6 hours and 24 hours CT head scans were evaluated. Neurologic worsening was defined as increased contusions, ischemia, compression of basal cisterns, and/or midline shift. The TBI patients with chest injury (Abbreviated Injury Scale chest score ≥1) and those without chest injury were compared. Wilcoxon rank sum test, univariate logistic regression and receiver operating characteristic were reported. RESULTS: Fifty-seven patients. Mean age of 40.5 years. Median motor Glasgow Coma Scale score at admission and 24 hours was 3 (interquartile range, 1-5) and 5 (interquartile range, 3-5). Of the patients enrolled, 12.2% patients underwent craniotomy within 6 hours from the time of admission and 22.8% within 12 hours. Patients with chest trauma, 24.5% had a chest Abbreviated Injury Scale score of 3 or greater, and 73.6% sustained blunt chest trauma. Stratifying TBI patients with and without chest injury revealed higher mean levels of IL-4, IL-5, IL-8, and IL-10 and lower mean IFN-γ and IL-7 levels in patient with chest injury. IL-7 levels adjusted for chest injury predicted neurological worsening with area under the receiver operating characteristic of 0.59 (p value = 0.011). The TBI and chest trauma patients' IL-4 and neuron-specific enolase levels were predictive of mortality (area under the receiver operating characteristic of 0.67 and 0.63, p = 0.0001, 0.003), respectively. CONCLUSION: Utilizing biomarkers for early identification of patients with TBI and chest trauma has the capability of modifying adverse factors affecting morbidity and mortality in this subset of TBI patients. LEVEL OF EVIDENCE: Level III.

8.
Phys Med ; 63: 87-97, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31221414

RESUMO

PURPOSE: A pixel-based range telescope for tracking particles during proton imaging is described. The detector applies a 3D matrix of stacked Monolithic Active Pixel Sensors with fast readout speeds. This study evaluates different design alternatives of the range telescope on basis of the protons' range accuracy and the track reconstruction efficiency. METHOD: Detector designs with different thicknesses of the energy-absorbing plates between each sensor layer are simulated using the GATE/Geant4 Monte Carlo software. Proton tracks traversing the detector layers are individually reconstructed, and a Bragg curve fitting procedure is applied for the calculation of each proton's range. RESULTS: Simulations show that the setups with 4 mm and thinner absorber layers of aluminum have a low range uncertainty compared to the physical range straggling, systematic errors below 0.3 mm water equivalent thickness and a track reconstruction capability exceeding ten million protons per second. CONCLUSIONS: In order to restrict the total number of layers and to yield the required tracking and range resolution properties, a design recommendation is reached where the proposed range telescope applies 3.5 mm thick aluminum absorber slabs between each sensor layer.

9.
Acta Otolaryngol ; 139(7): 547-551, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31050576

RESUMO

Background: Patients may suffer postoperative facial nerve injury, hearing loss, or other postoperative complications after the operation, which seriously affect their postoperative life quality. Aims/objectives: To investigate the differences in QOL (quality of life) of patients with acoustic neuroma resection by the translabyrinthine or retrosigmoid approach. Material and methods: Patients with acoustic neuroma resection in our department were enrolled in this experimental study, among which fifty patients underwent the translabyrinthine approach resection, the other 50 patients underwent the retrosigmoid approach resection. Different scores by the SF-36 scale between these two groups of patients one month after discharge were then analyzed. Results: Scores of patients undergoing the retrosigmoid approach were higher in the three dimensions of Social Functioning, Role-emotional and Mental Health than those of patients undergoing the translabyrinthine approach with statistical significance. However, scores of patients undergoing the translabyrinthine approach were higher in the two dimensions of Body Pain and Vitality than those of the patients undergoing the retrosigmoid approach. Conclusions and significance: The results indicated that individual nursing interventions for different patients are necessary to improve the QOL of patients after hospitalization. Moreover, the operated patients with translabyrinthine approach were more advantage than patients with retrosigmoid approach.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31016342

RESUMO

PURPOSE: The arterial pressure waveform is a composite of multiple interactions, and there may be more sensitive and specific features associated with hemorrhagic shock and intravascular volume depletion than systolic and/or diastolic blood pressure (BP) alone. The aim of this study was to characterize the arterial pressure waveform in differing grades of hemorrhage. METHODS: Ten anesthetized swine (70-90 kg) underwent a 40% controlled exponential hemorrhage. High-fidelity arterial waveform data were collected (500 Hz) and signal-processing techniques were used to extract key features. Regression modeling was used to assess the trend over time. Short-time Fourier transform (STFT) was utilized to assess waveform frequency and power spectrum density variance. RESULTS: All animals tolerated instrumentation and hemorrhage. The primary antegrade wave (P1) was relatively preserved while the renal (P2) and iliac (P3) reflection waves became noticeably attenuated during progressive hemorrhage. Several features mirrored changes in systolic and diastolic BP and plateaued at approximately 20% hemorrhage, and were best fit with non-linear sigmoidal regression modeling. The P1:P3 ratio continued to change during progressive hemorrhage (R2 = 0.51). Analysis of the first three harmonics during progressive hemorrhage via STFT demonstrated increasing variance with high coefficients of determination using linear regression in frequency (R2 = 0.70, 0.93, and 0.76, respectively) and power spectrum density (R2 = 0.90, 0.90, and 0.59, respectively). CONCLUSIONS: In this swine model of volume-controlled hemorrhage, hypotension was a predominating early feature. While most waveform features mirrored those of BP, specific features such as the variance may be able to distinguish differing magnitudes of hemorrhage despite little change in conventional measures.

11.
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.

12.
Acta Otolaryngol ; 139(6): 492-496, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30987493

RESUMO

BACKGROUND: In recent years, the otoendoscopic surgery for epitympanic cholesteatoma has achieved great development, but it still has some disadvantages. OBJECTIVE: This work aims to improve otoendoscopic surgery for epitympanic cholesteatoma invading the mastoid to retain the normal structure of the middle ear as much as possible. METHODS: We classified the patients according to the lesion scope and applied different strategies of using the combination of otoendoscope and microscope. The surgery was improved and the recurrence and residual of middle ear cholesteatoma after operation were observed preliminarily. RESULTS: Forty-six patients with middle ear cholesteatoma accepted surgical treatment, including 10 cases of independent otoendoscopic surgery, 29 cases of otoendoscope-microscope combined surgery, and seven cases of microscopic surgery assisted with an otoendoscope. All cases were treated with canal-up cholesteatoma surgery. The postoperative recurrent rate was 4/46. CONCLUSION: We improved existing otoendoscopic surgery to reduce or avoid bony defects of the acoustic meatus, and then decreased the proportion of canal-down surgery.

13.
Artigo em Inglês | MEDLINE | ID: mdl-30882765

RESUMO

INTRODUCTION: Clinical data is lacking on the influence of chest trauma on the secondary injury process after TBI, with some data suggesting multi-trauma may worsens brain injury. Blunt chest trauma and TBI represent the two major single injury entities with the highest risk of complications and are potential biomarker targets. METHODS: Trauma patients with severe TBI were enrolled. Serum biomarker levels were obtained every 6 hours for 72 hours. Baseline, 6 and 24 hours CT head scans were evaluated. Neurological worsening (NW) was defined as increased contusions, ischemia, compression of basal cisterns and/or midline shift. TBI patients with chest injury (Abbreviated Injury Scale (AIS) chest score ≥ 1) and those without chest injury were compared. Wilcoxon rank sum test, univariate logistic regression and Receiver Operating Characteristic (ROC) were reported. RESULTS: Fifty-seven patients. Mean age 40.5 years. Median motor Glasgow Coma Scale (GSC) score at admission and 24 hours was 3 (Interquartile range [IQR] 1 to 5) and 5 (IQR 3 to 5). Of the patients enrolled, 12.2% patients underwent craniotomy within 6 hours from the time of admission and 22.8% within 12 hours. Patients with chest trauma, 24.5% had a chest AIS score ≥ 3 and 73.6% sustained blunt chest trauma. Stratifying TBI patients with and without chest injury revealed higher mean levels of IL-4, IL-5, IL-8, and IL-10 and lower mean IFN-γ and IL-7 levels in patient with chest injury. IL-7 levels adjusted for chest injury predicted neurological worsening with AUROC of 0.59 (p-value = 0.011). TBI and chest trauma patients IL-4 and NSE levels were predictive of mortality (AUROC of 0.67 and 0.63, p-value = 0.0001, 0.003) respectfully. CONCLUSION: Utilizing biomarkers for early identification of patients with TBI and chest trauma has the capability of modifying adverse factors affecting morbidity and mortality in this subset of TBI patients.

14.
Crit Care Med ; 47(6): 840-848, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30920408

RESUMO

OBJECTIVES: Modern critical care amasses unprecedented amounts of clinical data-so called "big data"-on a minute-by-minute basis. Innovative processing of these data has the potential to revolutionize clinical prognostics and decision support in the care of the critically ill but also forces clinicians to depend on new and complex tools of which they may have limited understanding and over which they have little control. This concise review aims to provide bedside clinicians with ways to think about common methods being used to extract information from clinical big datasets and to judge the quality and utility of that information. DATA SOURCES: We searched the free-access search engines PubMed and Google Scholar using the MeSH terms "big data", "prediction", and "intensive care" with iterations of a range of additional potentially associated factors, along with published bibliographies, to find papers suggesting illustration of key points in the structuring and analysis of clinical "big data," with special focus on outcomes prediction and major clinical concerns in critical care. STUDY SELECTION: Three reviewers independently screened preliminary citation lists. DATA EXTRACTION: Summary data were tabulated for review. DATA SYNTHESIS: To date, most relevant big data research has focused on development of and attempts to validate patient outcome scoring systems and has yet to fully make use of the potential for automation and novel uses of continuous data streams such as those available from clinical care monitoring devices. CONCLUSIONS: Realizing the potential for big data to improve critical care patient outcomes will require unprecedented team building across disparate competencies. It will also require clinicians to develop statistical awareness and thinking as yet another critical judgment skill they bring to their patients' bedsides and to the array of evidence presented to them about their patients over the course of care.

15.
Curr Drug Targets ; 20(10): 1018-1028, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30827236

RESUMO

HACE1 belongs to the family of HECT domain-containing E3 ligases, which plays an important role in the occurrence, invasion and metastatic process in many human malignancies. HACE1 is a tumor suppressor gene that is reduced in most cancer tissues compared to adjacent normal tissue. The loss or knocking out of HACE1 leads to enhanced tumor growth, invasion, and metastasis; in contrast, the overexpression of HACE1 can inhibit the development of tumors. Hypermethylation reduces the expression of HACE1, thereby promoting tumor development. HACE1 can inhibit the development of inflammation or tumors via the ubiquitination pathway. Therefore, HACE1 may be a potential therapeutic target, providing new strategies for disease prevention and treatment.

16.
J Cell Physiol ; 2019 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-30710368

RESUMO

Heat shock proteins (HSPs) are crucial proteins in maintaining the homeostasis of human gastric epithelial cells. Tumor necrosis factor receptor-associated protein 1 (TRAP1), a member of the HSP90 family, has been shown to be involved in various crucial physiological processes, particularly against apoptosis. However, the regulation and function of TRAP1 in Helicobacter pylori infection is still unknown. Here, we found that TRAP1 expression was downregulated on human gastric epithelial cells during H. pylori infection by real-time polymerase chain reaction (PCR) and western blot analysis. Through virulence factors mutant H. pylori strains infection and inhibitors screening, we found that H. pylori vacuolating cytotoxin A ( vacA), but not cytotoxin-associated gene A ( cagA) protein, induced human gastric epithelial cells to downregulate TRAP1 via P38MAPK pathway by real-time PCR and western blot analysis. Furthermore, downregulation of TRAP1 with lentivirus carrying TRAP1 short hairpin RNA constructs impairs mitochondrial function, and increases apoptosis of gastric epithelial cells. The results indicate that H. pylori vacA downregulated TRAP1 is involved in the regulation of gastric epithelial cell apoptosis.

17.
Anat Rec (Hoboken) ; 302(6): 1024-1038, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30779320

RESUMO

This study was performed to investigate whether miniature pigs are a suitable animal model for studies of the Eustachian tube (ET). Sixteen Chinese experimental miniature pigs were used in this investigation. Ten animals were used for anatomical and morphometric analyses to obtain qualitative and quantitative information regarding the ET. Three animals were used for histological analysis to determine the fine structure of ET cross-sections. Three animals were used to investigate the feasibility of balloon dilation of the Eustachian tube (BDET). The anatomical study indicated that the pharyngeal orifice and tympanic orifice of the miniature pig ET are located at the posterior end of the nasal lateral wall and anterior wall of the middle ear cavity, respectively. The cartilaginous tube was seen to pass through the whole length of the ET, the length of the cartilaginous part of the ET and the diameter of the isthmus were similar between humans and miniature pigs. The inclination of the ET in miniature pigs was larger than that in humans. The gross histology seemed to be slightly different between miniature pig and human, but the fine structures were essentially the same in both species. BDET experiments verified that the miniature pig model is suitable as a model for clinical operations. The miniature pig ET corresponds very well to that of humans. In addition, the miniature pig ET is suitable as a model for clinical operations. Therefore, the miniature pig is a valid animal model for ET study. Anat Rec, 302:1024-1038, 2019. © 2019 Wiley Periodicals, Inc.

18.
Br J Pharmacol ; 176(11): 1700-1716, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30808064

RESUMO

BACKGROUND AND PURPOSE: As little is known about the effect of caffeine, one of the most widely consumed substances worldwide, on intestinal function, we aimed to study its action on intestinal anion secretion and the underlying molecular mechanisms. EXPERIMENTAL APPROACH: Anion secretion and channel expression were examined in mouse duodenal epithelium by Ussing chambers and immunocytochemistry. Ca2+ imaging was also performed in intestinal epithelial cells (IECs). KEY RESULTS: Caffeine (10 mM) markedly increased mouse duodenal short-circuit current (Isc ), which was attenuated by a removal of either Cl- or HCO3 - , Ca2+ -free serosal solutions and selective blockers of store-operated Ca2+ channels (SOC/Ca2+ release-activated Ca2+ channels), and knockdown of Orai1 channels on the serosal side of duodenal tissues. Caffeine induced SOC entry in IEC, which was inhibited by ruthenium red and selective blockers of SOC. Caffeine-stimulated duodenal Isc was inhibited by the endoplasmic reticulum Ca2+ chelator (N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine), selective blockers (ruthenium red and dantrolene) of ryanodine receptors (RyR), and of Ca2+ -activated Cl- channels (niflumic acid and T16A). There was synergism between cAMP and Ca2+ signalling, in which cAMP/PKA promoted caffeine/Ca2+ -mediated anion secretion. Expression of STIM1 and Orai1 was detected in mouse duodenal mucosa and human IECs. The Orai1 proteins were primarily co-located with the basolateral marker Na+ , K+ -ATPase. CONCLUSIONS AND IMPLICATIONS: Caffeine stimulated intestinal anion secretion mainly through the RyR/Orai1/Ca2+ signalling pathway. There is synergism between cAMP/PKA and caffeine/Ca2+ -mediated anion secretion. Our findings suggest that a caffeine-mediated RyR/Orai1/Ca2+ pathway could provide novel potential drug targets to control intestinal anion secretion.

19.
Acta Otolaryngol ; 139(2): 146-152, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30734622

RESUMO

BACKGROUND: Clinical trials of cell-based therapies using induced pluripotent stem (iPS) cells have already been started for several neurological diseases. OBJECTIVE: The purpose of the present study was to explore the characteristics and differentiation of somatic cells in vitro undergoing a low pH treatment, so as to provide new therapeutic strategies for treating sensorineural hearing loss. METHODS: Somatic cells were treated with low pH solution to alter their characteristics. In addition, a mouse model of the cochlear lesion was constructed using bilirubin. Subsequently, the characteristics and therapeutic effect of somatic cells undergoing low pH treatment were examined by morphology, alkaline phosphatase (AKP) activity, immunofluorescence assay and q-PCR. RESULTS: The cells in the experimental group grew better than those in the control group. The AKP activity in the experimental group was higher than that in the control group. The expression of Nanog and Oct4 was both positive in the two groups. When the cells were changed to neurobasal medium, the marker of nestin was positive. CONCLUSION: The human somatic cells undergoing a low pH treatment showed the similar characteristics as those of iPS cells, although the functions and therapeutic effect of these altered human somatic cells need to be further studied.


Assuntos
Ácidos/farmacologia , Células-Tronco Adultas/efeitos dos fármacos , Cóclea/citologia , Perda Auditiva Neurossensorial/terapia , Células-Tronco Pluripotentes Induzidas/transplante , Transplante de Células-Tronco/métodos , Células-Tronco Adultas/citologia , Células-Tronco Adultas/transplante , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Camundongos , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real , Medição de Risco , Sensibilidade e Especificidade
20.
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.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA