The Pinx1 Gene Downregulates Telomerase and Inhibits Proliferation of CD133+ Cancer Stem Cells Isolated from a Nasopharyngeal Carcinoma Cell Line by Regulating Trfs and Mad1/C-Myc/p53 Pathways.

BACKGROUND/AIMS: Cancer stem cells (CSCs) are important factors for the continuous growth, recurrence, and metastasis of malignant tumors. They are responsible for the ineffectiveness of traditional radiotherapy and chemotherapy toward malignant tumors. Currently, stem cells or side-population cells have been isolated from many cancer cell lines and malignant tumor tissues, including nasopharyngeal carcinoma. Exploring the biological characteristics of CSCs for CSC-targeted therapy has gained importance. CSCs possess higher telomerase activity; thus, the use of the gene encoding telomerase inhibitor PinX1 gene to target telomerase in CSCs and inhibit proliferation, invasion, and metastasis of CSCs has become an important means for the treatment of malignant tumors. PinX1 may regulate complex pathways, including TRF1, Mad1/c-Myc, and p53. METHODS: In this study, nasopharyngeal CD133+ CSCs were sorted using CD133 immunomagnetic beads by flow cytometry The successful isolation of CD133+ CSCs was confirmed by examining their surface markers, namely CD44, NaNOG, and SOX2 as well as their ability to undergo in vivo tumorigenesis and in vitro sphere formation, proliferation, migration, and invasion. In addition, CD133+ CSCs were transfected with the constructed PinX1 overexpression plasmid or siRNA and the resulting effects on their proliferation, migration, invasion, and apoptosis were detected using cell counting kit-8 (CCK-8), transwell assay, and scratch test, respectively. Furthermore, their effects on mRNA and protein levels of TRF1, TRF2, Mad1, c-Myc, and p53 were examined using quantitative real-time PCR and western blot, respectively. RESULTS: The overexpression of PinX1 in CD133+ CSCs significantly decreased hTERT (P < 0.001), inhibited proliferation, migration, and invasion, induced apoptosis, and significantly decreased c-Myc mRNA levels (P < 0.001), while it increased TRF1, Mad1, and p53 mRNA levels (all P < 0.001). On the other hand, PinX1 silencing in CD133+ CSCs significantly decreased TRF1, Mad1, and p53 mRNA levels (all P < 0.01), while it increased hTERT and c-Myc mRNA levels (all P < 0.05). CONCLUSION: These results indicate that PinX1 downregulates telomerase activity in CD133+ CSCs, inhibits its proliferation, migration, and invasion, and induces apoptosis possibly through TRF1, Mad1/c-Myc, and p53-mediated pathways.

Joint quantitative measurement of hTERT mRNA in both peripheral blood and circulating tumor cells of patients with nasopharyngeal carcinoma and its clinical significance.

BACKGROUND: The study was aimed to quantitatively detect mRNA levels of the catalytic subunit of telomerase (hTERT) in both peripheral blood and circulating tumor cells (CTCs) of patients with nasopharyngeal carcinoma (NPC) and explore its significance in early diagnosis and treatment of NPC. METHODS: hTERT mRNA levels in peripheral blood and CTCs of 33 NPC patients before and after treatment with intensity-modulated radiation therapy (IMRT) or/and chemotherapy and 24 healthy controls were measured using real-time quantitative PCR (qPCR) and their correlations to clinic pathological factors of NPC were analyzed. RESULTS: Peripheral hTERT mRNA content was 10.75 ± 4.29 in NPC patients and 0.95 ± 0.37 in control subjects (P < 0.05), and had a significant correlation with patients' clinical stage, T stage, and N stage (P < 0.05). Treatment of NPC patients at stages I and II with simple IMRT significantly reduced hTERT mRNA level from 5.60 ± 2.33 to 3.43 ± 1.42 (P < 0.05) and treatment of patients at advanced stage (III and IV) with induction chemotherapy followed by IMRT significantly reduced hTERT mRNA levels from 12.68 ± 3.08 to 10.68 ± 2.48 to 3.13 ± 1.69 (P < 0.05), respectively. In addition, the study also showed that hTERT mRNA content in CTCs of NPC patients was 10.65 ± 4.28, evidently higher than that of 1.09 ± 0.40 in control subjects (P < 0.05) and hTERT mRNA level in CTCs of NPC patients was obviously correlated to patients' clinical stage, T stage and N stage (P < 0.05). After treatment, hTERT mRNA level in CTCs of NPC patients lowered from 10.65 ± 4.28 to 5.59 ± 2.32 (P < 0.05). The correlation analysis found that hTERT mRNA level in peripheral blood and CTCs of NPC patients were highly correlated with a correlation coefficient of 0.981. CONCLUSIONS: hTERT mRNA levels in peripheral blood and CTCs of NPC patients were significantly enhanced compared to that in healthy controls and highly correlated. Changes in hTERT mRNA level was closely correlated to patients' clinical stage and T stage. Radiochemotherapy could effectively reduce hTERT mRNA level in peripheral blood and CTCs. Thus, it is possible using the joint detection of hTERT mRNA level in peripheral blood and CTCs as a new biomarker for early diagnosis, treatment efficacy and prognosis of NPC.

[Influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin].

OBJECTIVE: To explore the influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin. METHODS: Transfected nasopharyngeal carcinoma 5-8F cell lines with pCDH-CMV-PinX1-copGFP vector constructed by lentivirus to generate Lenti-PinX1-5-8F cells containing PinX1 gene, using Lenti-Ctrl-5-8F cell (blank vector without PinX1 gene was used to transfect 5-8F cell lines) and 5-8F cell as controls. Expression of PinX1 gene, telomerase activity, the inhibition of cancer cells proliferation, combined anticancer effect with Cisplatin and the expression of lung resistance protein (LRP) and Bcl-2 were detected with fluorescent quantitation polymerase chain reaction (PCR), flow cytometry, thiazolyl blue (MTT) method, areole test, Western blot and drug sensitivity test, respectively, in four groups (Lenti-PinX1-5-8F cell + Cisplatin, Lenti-PinX1-5-8F cell, Cisplatin and 5-8F cell) so as to explore the influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin. RESULTS: The telomerase activity in Lenti-PinX1-5-8F cell (0.146 ± 0.004) was lower than those in the other two control cells (Lenti-Ctrl-5-8F cell: 0.967 ± 0.016, 5-8F cell: 1.000 ± 0.034, both P < 0.01). The cancer cell biological activity could be intensively inhibited by 16 µg/ml Cisplatin after lower level telomerase activity induced by PinX1 gene. Proliferation index (PI) (%) in Lenti-PinX1-5-8F cell + Cisplatin (14.39 ± 3.66) was also less than the other groups (Lenti-PinX1-5-8F cell, Cisplatin and 5-8F cell groups, 32.97 ± 3.00, 31.18 ± 4.24 and 47.19 ± 4.19, all P < 0.01). And same time, the expressions of LRP (0.64 ± 0.14) and Bcl-2 (0.57 ± 0.12) protein in Lenti-PinX1-5-8F cells were obviously reduced than those in other two group cells (Lenti-Ctrl-5-8F cell: 0.84 ± 0.19 and 0.81 ± 0.16; 5-8F cell: 0.83 ± 0.35 and 0.78 ± 0.27; all P < 0.01). CONCLUSIONS: PinX1 gene can enhance the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin, which may be mediated by the down-regulation of telomerase activity and the inhibition of LRP and Bcl-2 gene in nasopharyngeal carcinoma cells.

PinX1-Promoted Autophagy Inhibits Cell Proliferation and Induces Cell Apoptosis by Inhibiting the NF-κB/p65 Signaling Pathway in Nasopharyngeal Carcinoma.

BACKGROUND: The role of Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) in tumorigenesis and development has been extensively studied. As we previously demonstrated, PinX1 plays an important role in modulating epithelial-mesenchymal transition (EMT), stemness, cell proliferation, and apoptosis in nasopharyngeal carcinoma (NPC). However, the relationship between PinX1, autophagy, and cell function in NPC remains unclear. This study aimed to investigate the mechanisms by which PinX1 regulates autophagy in NPC, and to explore its biological role and clinical significance in disease progression. METHODS: The proliferative capacity of NPC cells was assessed by MTT and xenograft tumorigenicity assays. Autophagic flux was monitored using a tandem monomeric DAPI-FITC-LC3 reporter assay. The rates of apoptosis and the cell cycle in NPC cells were analyzed using flow cytometry. The activation of autophagy and the signaling status of the AKT/mTOR and NF-κB/p65 pathways were evaluated by Western blot analysis. RESULTS: In addition to promoting autophagy and apoptosis, PinX1 overexpression suppressed proliferation, migration, invasion, and decelerated cell-cycle progression in NPC cells. These effects were reversed by inhibiting autophagy with 3-methyladenine. Mechanistic investigations clarified that PinX1 overexpression significantly reduced the expression of p-AKT, p-mTOR, p65, and p-p65. Chloroquine treatment in PinX1-overexpressing cells did not significantly alter p-AKT and p-mTOR levels, whereas 3-MA treatment in PinX1-overexpressing cells resulted in increased p65 and p-p65 expression, relative to untreated PinX1-overexpressing cells. CONCLUSIONS: It appears that PinX1 promotes autophagy by inhibiting the AKT/mTOR signaling pathway, which then inhibits NF-κB/p65 pathways, and consequently inhibiting cell proliferation and causing cell apoptosis in NPC cells.

Effects of combination docetaxel with NO treatment to enhance the anti-nasopharyngeal carcinoma efficiency in vitro and in vivo.

Nasopharyngeal carcinoma (NPC) is one of the major causes of death in Southern China. Due to the insidious location of NPC, the therapeutic effect of locoregionally advanced NPC is still unsatisfactory. In this work, to improve the treatment efficiency, combining DOC and JS-K to inhibit NPC cells (HNE-1) in vitro was investigated, as well as its possible mechanisms. Moreover, the in vivo effects of DOC and JS-K combination treatment were also evaluated in a xenograft model with HNE-1 cells. In vitro experiments including cell proliferation, migration ability, apoptosis, and expression levels of apoptosis-associated proteins revealed that the combination of DOC and JS-K was able to enhance antitumor effects. In vivo results further confirmed a significant treatment effect without obvious toxicity on mice. The present work provides a promising idea for the treatment of locally advanced NPC.

Individualized treatment for allergic rhinitis based on key nasal clinical manifestations combined with histamine and leukotriene D4 levels.

INTRODUCTION: The types of allergic rhinitis are roughly classified based on the causative antigens, disease types, predilection time, and symptom severity. OBJECTIVE: To examine the clinical typing and individualized treatment approach for allergic rhinitis and to determine the optimal treatment method for this disease using various drug combination therapies. METHODS: A total of 108 participants with allergic rhinitis were divided into three groups based on symptoms. Subsequently, each group was further categorized into four subgroups based on the medications received. The efficacy of the treatments was evaluated using the visual analog scale VAS scores of the total and individual nasal symptoms, decline index of the symptom score, histamine and leukotriene levels, and mRNA and protein expression levels of histamine 1 and cysteinyl leukotriene 1 receptors. RESULTS: Loratadine+mometasone furoate and loratadine+mometasone furoate+montelukast significantly improved the sneezing symptom and reduced the histamine levels compared with the other combination therapies (p<0.05). Meanwhile, montelukast+mometasone furoate and montelukast+mometasone furoate+loratadine considerably improved the nasal obstruction symptom and decreased the leukotriene D4 levels compared with the other combination therapies (p<0.05). CONCLUSION: Clinical symptom evaluation combined with experimental detection of histamine and leukotriene levels can be an objective and accurate method to clinically classify the allergic rhinitis types. Furthermore, individualized treatment based on allergic rhinitis classification can result in a good treatment efficacy.

Transferrin-targeting redox hyperbranched poly(amido amine)-functionalized graphene oxide for sensitized chemotherapy combined with gene therapy to nasopharyngeal carcinoma.

A drug and gene co-delivery system with chemotherapeutic sensibilization was prepared and used for nasopharyngeal carcinoma therapy. For this purpose, the graphene oxide (GO) was conjugated with the redox hyperbranched poly(amido amine) (HPAA) and then the targeting molecule, transferrin (Tf), was also conjugated. The obtained Tf-HPAA-GO could co-deliver docetaxel (DOC) and MMP-9 shRNA plasmid (pMMP-9) effectively and showed the targeting effect to HNE-1 cells. The co-delivery system showed the effective drug and gene delivery ability with high cytotoxicity and gene transfection efficiency. Besides that, Tf-HPAA-GO/DOC also showed the chemotherapeutic sensibilization effect, the formulation containing HPAA segments showed much higher cytotoxicity than free DOC. Benefiting from the sensibilization effect and DOC/pMMP-9 co-delivery strategy, this Tf-HPAA-GO/DOC/pMMP-9 co-delivery system exhibited the significantly improved therapeutic efficacy to HNE-1 tumor in a combined manner which was confirmed by in vitro and in vivo assays. This strategy provided an easily delivery system combining the drug/gene co-delivery, chemotherapeutic sensibilization, and targeting into one single platform, which showed a promising application in cancer therapy.

A cationic polymeric prodrug with chemotherapeutic self-sensibilization co-delivering MMP-9 shRNA plasmid for a combined therapy to nasopharyngeal carcinoma.

To obtain a high-efficiency drug and gene co-delivery system to HNE-1 tumor therapy, a polymeric prodrug (PAAs-MTX) with chemotherapeutic sensibilization was synthesized consisting of a GSH-response hyperbranched poly(amido amine) (PAAs) and an antitumor drug of methotrexate (MTX). Then, the targeting molecule to HNE-1 cells, transferrin (Tf), was conjugated to form the Tf-PAAs-MTX. This polymeric prodrug could deliver MMP-9 shRNA plasmid (pMMP-9) again to form the drug and gene co-delivery system of Tf-PAAs-MTX/pMMP-9. The co-delivery system showed the effective drug and gene delivery ability with high cytotoxicity and gene transfection efficiency to HNE-1 cells. Besides that, Tf-PAAs-MTX also showed the chemotherapeutic sensibilization effect, the formulation containing PAAs segments showed much higher cytotoxicity than that of free MTX. Benefiting from the sensibilization effect and MTX/pMMP-9 co-delivery strategy, this Tf-PAAs-MTX/pMMP-9 co-delivery system exhibited the significantly improved therapeutic efficacy to HNE-1 tumor in a combined manner which was confirmed by in vitro and in vivo assays. Moreover, its biocompatibility, especially the blood compatibility was analyzed. This polymeric prodrug provided an easily delivery system combining the drug/gene co-delivery, chemotherapeutic sensibilization and targeting into one single platform, which showed a promising application in nasopharyngeal carcinoma therapy.

[Clinical features of advanced adenoid cystic carcinoma in the nasal cavity and paranasal sinuses: analysis of 21 cases].

OBJECTIVE: To evaluate the clinical characteristics, treatment and prognosis of advanced adenoid cystic carcinoma (ACC) in the nasal cavity and paranasal sinuses. METHODS: Twenty-one patients with advanced ACC in the nasal cavity and paranasal sinuses were treated in our department between February, 2007 and May, 2016. The clinical manifestations, T-stage, N-status, treatment, histological grade, recurrence and distant metastasis of the tumors were analyzed. Univariate survival analysis was performed with Kaplan-Meier method and Log-rank test, and the factors affecting the prognosis of the patients were explored using multivariate analysis with Cox proportional hazard model. RESULTS: Among the 21 patients, 10 (47.6%) had ACC containing less than 30% of solid tumor tissues and their overall survival rates at 1, 3, and 5 years were 100%, 100% and 70%, respectively; in the 11 cases (52.4%) with solid tumor tissues no less than 30%, the overall survival rates at 1, 3, and 5 years were 70%, 40% and 10%, respectively, showing significant differences between the two groups (P=0.02). The Log-rank test and survival analysis using the covariate variable model curve indicated a significant impact of the pathological classification on the patients' prognosis. The patients in T3 stage had slightly better prognosis than those in T4 stage; tumors originating from the maxillary sinus had a slightly better prognosis than those from the sphenoid sinus. Surgery combined with radiotherapy resulted in better outcomes of the patients than surgery or radiotherapy alone. Multiariable Cox regression model analysis showed that the pathological classification (P=0.045) and the disease course (P=0.028) were closely related with the prognosis of the patients. CONCLUSION: ACC in the nasal cavity and paranasal sinuses has a low incidence without specific symptoms. Its early diagnosis can be difficult, and most of the patients are in advanced stage upon diagnosis. We recommend comprehensive treatments combining surgery, postoperative radiotherapy and chemotherapy for these patients. The pathological classification, disease course, lesion site, clinical stage, treatment approache, compromise of the peripheral nerves, status at the edge of resection, and postoperative radiotherapy dose can all be factors affecting the prognosis of patients with advanced ACC.

[Effect of adipose-derived mesenchymal stem cells (ADSC) on the T cell immune status of allergic rhinitis mouse model].

OBJECTIVE: To investigate the regulation of adipose-derived mesenchymal stem cells (ADSC) on helper T cells and regulatory T cells in allergic rhinitis(AR) mouse model and the underlying mechanisms. METHODS: Using random number table, 60 Balb/c mice were divided into 6 groups (represented by: sensitized/challenged/treated ), they were the experimental group 1(OVA/OVA/high dose ADSC), the experimental group 2(OVA/OVA/low dose ADSC), the experimental group 3(OVA/OVA/PBS), the experimental group 4(OVA/OVA/0), the control group 1(PBS/PBS/0) and the control group 2(0/0/0). The mouse ADSC were isolated and cultured through conventional method, and AR mouse model was built with OVA and aluminum. The mice were injected with high (3×10(6)), low (1×10(6)) ADSC respectively labeled by CM-Dil for 3 consecutive days via tail-vein injection and sacrificed 48 hours later. Finally, levels of IL-4, IL-6, IL-10 and IFN -γ in serum were examined by ELISA; expressions of the four cytokines in spleen were examined by q RT-PCR; migration of ADSC to mouse model nasal mucosa were observed through fluorescence microscope; eosinophil infiltration were observed by the nasal HE staining. RESULTS: Mouse ADSC was isolated, cultured and identified successfully. There was significant difference in symptom scores of AR models (compared with 0/0/0 group, P<0.01). The IL-4 and IL-6 levels of OVA/OVA/high ADSC group were significantly lower than OVA/OVA/0 group (group 1: (17.95±7.78), (27.51±5.93) pg/ml; group 4: (56.82±9.12), (70.03±7.22) pg/ml), the IFN-γ and IL-10 levels increased significantly (group 1: (367.74±13.79), (417.10±72.40) pg/ml; group 4: (199.46±11.25), (122.50±15.57) pg/ml) in serum. These differences were statistically significant(P<0.01). Compared with OVA/OVA/low ADSC group, the IL-4 and IL-6 levels decreased significantly (group 1: (17.95±7.78), (27.51±5.93) pg/ml; group 2: (41.57±12.27), (56.21±9.23)pg/ml) of OVA / OVA / high ADSC group, and the IFN-γ and IL-10 increased significantly (group 1: (367.74±13.79), (417.10±72.40)pg/ml; group 2: (281.77±30.41), (203.45±87.10) pg/ml). These differences were statistically significant(P<0.01). At the same time, the corresponding changes observed at the levels of the cytokines' mRNA. ADSC labeled by CM-Dil could migrate to the mouse nasal mucosa. OVA/OVA/high ADSC group showed the more red fluorescence than the OVA/OVA/low ADSC group. The eosinophils in nasal mucosa of the two groups reduced compared with the normal control. CONCLUSION: ADSC injected via tail-vein can migrate to nasal mucosa and play non-specific immune effects, that may to effect the releases of some cytokines then to regulate the Th1/Th2 imbalance and the function of Treg cell, finally that be dose-related in a certain extent.

[Quantitative detection of plasma level of human telomerase reverse transcriptase mRNA in patients with nasopharyngeal carcinoma].

OBJECTIVE: To quantitatively measure plasma level of human telomerase reverse transcriptase (hTERT) mRNA in patients with nasopharyngeal carcinoma (NPC) and explore its implications for NPC diagnosis and treatment. METHODS: With 24 healthy volunteers serving as controls, the plasma level of hTERT mRNA was detected in 33 NPC patients by real-time PCR before and after treatments with chemotherapy or radiotherapy, and its association with the clinicopathological parameters of the patients were analyzed. RESULTS: The NPC patients showed a significantly higher mean plasma level of hTERT mRNA than the healthy volunteers (10.75 ± 4.29 vs 0.95 ± 0.37, P<0.05). The plasma hTERT mRNA level in the NPC patients was significantly correlated with clinical staging, tumor size, and degree of nodal metastasis (P<0.05) but with gender or age (P>0.05). In patients with stage I and II NPC, the plasma hTERT mRNA level decreased significantly after radiotherapy (5.60 ± 2.33 vs 3.43 ± 1.42); in patients in advanced stages (III and IV), plasma hTERT mRNA level decreased significantly from 12.68 ± 3.08 to 10.68 ± 2.48 (P<0.05) after chemotherapy and to 3.13 ± 1.69 (P<0.05) after radiotherapy. CONCLUSION: Radiotherapy and chemotherapy can effectively suppress elevated plasma hTERT mRNA levels in NPC patients. Plasma hTERT mRNA level is closely related to the clinicopathological factors and provides important information for early diagnosis and therapeutic effect evaluation of NPC.

[The role of Nods like receptors in the patients with allergic rhinitis].

OBJECTIVE: To explore role of Nods (nucleotide-binding oligomerization domain Nod Like receptors) kind of pattern recognition receptors (PRR) in patients with allergic rhinitis. METHOD: The mRNA and protein of Nod1, Nod2 of Nalp3 were analyzed in the turbinate mucosa of patients with allergic rhinitis, nasal septum deviation (NSD) nasal mucosa of patients and nasal polyp mucosa with Real-Time RT-PCR, Western blot and immunohistochemistry respectively, and Nod1 expression changes was explored in PBMC with wad explored Western-blot and then the level of IL-4, IL-6, IL-10, IFN-γ were detected in serum of AR after desensitization treatment. RESULT: These Nods like receptors, mainly found in nasal mucosa epithelial cells, glandular epithelium and inflammatory cells (e. g. plasma cells, eosinophils), were expressed in the nasal mucosa tissues. In AR group, Nod1 (mRNA and protein) expression were lower than NSD group (P<0.05), Nalp3 expression were higher than (P<0.05), while, there was no significant difference of Nod2 (mRNA and protein) between groups. After 6 months desensitization therapy, the change of Nod1 in PBMC was negatively correlated with the change of IL-10 in the peripheral blood, r=-0.88, P<0.05; while, change of Nod1 was positively correlated, with the change of IL-6, r=0.57, P>0.05. CONCLUSION: Nod1, Nod2 and Nalp3 expression were seen in the two groups,and the Nod1 expression in allergic rhinitis group was lower than other two groups, while, the Nalp3 was higher than other two groups. It showed Nod1, Nalp3 may be involved in the pathogenesis of allergic rhinitis. Expression of Nod1 in PBMC reduced after sublingual desensitization treatment. Besides, the change of Nod1 was negatively correlated with the change of IL-10 in PBMC. So,it seemed that Nod1 may regulate IL-10 changes and be involved in sublingual desensitization therapy.

Individualized treatment for allergic rhinitis based on key nasal clinical manifestations combined with histamine and leukotriene D4 levels / Tratamento individualizado para a rinite alérgica baseado nas principais manifestações clínicas nasais e dos níveis de histamina e leucotrieno D4

Abstract Introduction The types of allergic rhinitis are roughly classified based on the causative antigens, disease types, predilection time, and symptom severity. Objective To examine the clinical typing and individualized treatment approach for allergic rhinitis and to determine the optimal treatment method for this disease using various drug combination therapies. Methods A total of 108 participants with allergic rhinitis were divided into three groups based on symptoms. Subsequently, each group was further categorized into four subgroups based on the medications received. The efficacy of the treatments was evaluated using the visual analog scale VAS scores of the total and individual nasal symptoms, decline index of the symptom score, histamine and leukotriene levels, and mRNA and protein expression levels of histamine 1 and cysteinyl leukotriene 1 receptors. Results Loratadine + mometasone furoate and loratadine + mometasone furoate + montelukast significantly improved the sneezing symptom and reduced the histamine levels compared with the other combination therapies (p < 0.05). Meanwhile, montelukast + mometasone furoate and montelukast + mometasone furoate + loratadine considerably improved the nasal obstruction symptom and decreased the leukotriene D4 levels compared with the other combination therapies (p < 0.05). Conclusion Clinical symptom evaluation combined with experimental detection of histamine and leukotriene levels can be an objective and accurate method to clinically classify the allergic rhinitis types. Furthermore, individualized treatment based on allergic rhinitis classification can result in a good treatment efficacy.

Resumo Introdução A rinite alérgica é basicamente classificada de acordo com os antígenos causadores, tipos de doença, peridiocidade e gravidade dos sintomas. Objetivo Avaliar os tipos clínicos e a abordagem terapêutica individualizada para cada tipo de rinite alérgica e determinar o método de tratamento ideal utilizando várias terapias de combinação de fármacos. Método Um total de 108 participantes com rinite alérgica foram divididos em três grupos com base nos sintomas. Posteriormente, cada grupo foi subsequentemente categorizado em quatro subgrupos com base nos medicamentos recebidos. A eficácia dos tratamentos foi avaliada utilizando os escores da escala visual analógica EVA dos sintomas nasais totais e individualmente, índice de declínio do escore de sintomas, níveis de histamina e leucotrienos e níveis de expressão de mRNA e proteína dos receptores de histamina 1 e cisteinil-leucotrieno 1. Resultados As associações entre loratadina + furoato de mometasona, assim como a de loratadina + furoato de mometasona + montelucaste melhoraram significativamente o sintoma de espirros e reduziram os níveis de histamina em comparação às outras terapias combinadas (p < 0,05). Por outro lado, a associação montelucaste + furoato de mometasona, assim como a associação montelucaste + furoato de mometasone + loratadina melhoraram consideravelmente o sintoma de obstrução nasal e diminuíram os níveis de leucotrieno D4 em comparação com as outras combinações (p < 0,05). Conclusão A avaliação clínica dos sintomas combinada com a detecção experimental dos níveis de histamina e leucotrieno pode ser um método objetivo e preciso para classificar clinicamente os tipos de rinite alérgica. Além disso, o tratamento individualizado baseado na classificação da rinite alérgica pode resultar no aumento da eficácia do tratamento.

[Role of Nods like receptors in the patients with nasal polyps].

OBJECTIVE: To investigate the expression and role of a new pattern-recognition receptors (PRR), nucleotide binding oligomerization domain (Nod) like receptors (NLRs), in the patients with nasal polyps and nasal septum normal control group. METHOD: The expressions of Nod1, Nod2 and Nalp3 mRNA and protein were explored with real-time RT-PCR, Western-Blot and immunohistochemistry respectively. RESULT: The protein levels of Nod1, Nod2 and Nalp3 were expressed in nasal polyp and the control, but the expression of Nod1 and Nalp3 in nasal polyps were higher than those in control. No significant difference of Nod2 was seen between the two groups. And then, there was no significant difference of Nod1, Nod2, Nalp3 mRNA between two groups with Real-time RT-PCR. CONCLUSION: The expression of Nod1 and Nalp3 are increased in nasal polyp tissues and maybe a etiological factors in the formation of nasal polyps.

[Effect of nasal epithelial lining prognosis and turnover changed by vesicles molecular immuno-pathology after nasal endoscopic surgery].

OBJECTIVE: To observe Effect of nasal epithelial lining prognosis and turnover changed by vesicles molecular immuno-pathology after nasal endoscopic surgery. METHOD: Forty patients (80 sides) with chronic nasal polyps in accordance with the EPOS standard after endoscopic sinus surgery were randomly divided into treatment group and control group according to weather scraping the vesicles. Compared the speed of epithelialization of nasal cavity mucosa in the two groups. Observed the pathological features of vesicles through HE staining and transmission electron microscopy. Divided the treatment group into 1-3 weeks group, 6-8 weeks group and 11-14 weeks group. And make the inferior turbinate mucosa and nasal polyps during surgery the control group. Compared the level of vascular endothelial growth factor(VEGF) and transforming growth factor beta1 (TGF beta1) between the groups. RESULT: Vesicles were divided into mild groups and moderate to severe groups according to the sizes and amonts. Vesicles in moderate to severe groups were faster epithelialization than the mild groups, 1.5 weeks shortened on average (P < 0.05). There wes no significant difference between the two groups in mild group. The level of TGF beta1 in the nasal polyps, 1-3 weeks group and 6-8 weeks group were significantly higher than the inferior turbinate mucosa and 11-14 weeks group (P < 0.05). The level of VEGF in the nasal polyps, 6-8 weeks group were significantly higher than the inferior turbinate mucosa, 1-3 weeks group and 11-14 weeks group (P < 0.05). Vesicles were displayed discontinuous basal membranes, interstitial edama, infiltration of inflammatory cells, increased pathological glands, abnormal microtubule structure, reduction of mitochondrials. CONCLUSION: Vesicles is a dynamic process, which may predict the increased levels of inflammatory factors (VEGF and TGF beta1) and contribute to some of the patheologic changes observed in nasal polyps. The level of VEGF and TGF beta1 in vesicles after endoscopic sinus surgery can be used as indicators of prognosis. Treating the moderate to severe vesicles after surgery is benefit to the epithelium of the nasal mucosa.