Botulinum toxin type A counteracts neuropathic pain by countering the increase of GlyT2 expression in the spinal cord of CCI rats.

Botulinum toxin type A (BoNT/A) is a potent toxin, acts by cleaving synaptosome-associated-protein-25 (SNAP-25) to regulate the release of the neural transmitter and shows analgesic effect in neuropathic pain. However, the mechanisms of BoNT/A actions involved in nociceptions remain unclear. Glycine transporter 2 (GlyT2) is an isoform of glycine transporters, which plays an important role in the regulation of glycinergic neurotransmission. Inhibition of GlyTs could decrease pain sensation in neuropathic pain, the role of GlyT2 in the analgesic effect of BoNT/A has not been studied yet. In our present study, we demonstrated that the protein levels of GlyT2 and SNAP-25 were upregulated in the spinal cord after the development of chronic constriction injury (CCI)-induced neuropathic pain. Intraplantar application of BoNT/A (20 U/kg) attenuated mechanical allodynia induced by CCI and downregulated GlyT2 expression in the spinal cord. The application of BoNT/A s also decreased the expression of GlyT2 in pheochromocytoma (PC12) cells. Moreover, intrathecal application of lentivirus-mediated GlyT2 reversed the antinociceptive effect of BoNT/A in CCI rats. These findings indicate that GlyT2 contributes to the antinociceptive effect of BoNT/A and suggest a novel mechanism underlying BoNT/A's antinociception action.

Short report: nasal obstruction recovery after septoplasty in patients with nasal septal deviation affected by anxiety and depression.

This research was aimed to explore whether the recovery of subjective symptoms and objective examination in nasal septum deviation (NSD) patients after septoplasty were related to the degree of preoperative anxiety or depression, in the hope of providing new ideas for clinical treatment. A total of 150 NSD patients were included in this prospective research. Visual analogue scale (VAS) scores, Nasal Obstruction Symptom Evaluation (NOSE) scores, self-rating anxiety scale (SAS) scores, self-rating depression scale (SDS) scores, total inspiratory and expiratory nasal resistance were recorded before and 6 months after operation. The results showed preoperative anxiety or depression was not statistically different between groups in terms of age, gender and course, but positively correlated with nasal obstruction (VAS and NOSE). The recovery of nasal obstruction in patients with anxiety or depression was worse than that in normal NSD patients 6 months after surgery, and was decreased with the increase of anxiety or depression degree. And no significant difference showed in the reduction of total inspiratory and expiratory nasal resistance between groups. In conclusion, anxiety and depression affected the improvement of nasal obstruction feeling in NSD patients after septoplasty, and the improvement was negatively correlated with the degree of anxiety and depression. It is necessary to evaluate the anxiety and depression of NSD patients before septoplasty.

Identification of circular RNA expression profiles in renal fibrosis induced by obstructive injury.

INTRODUCTION: Advancing renal fibrosis is the common histopathological feature of chronic obstructive nephropathy, representing the final pathway of nearly all chronic and progressive nephropathies. Increasing evidences suggest that circular RNAs (circRNAs) are crucial regulatory molecules present at virtually every level of the cellular pathophysiological process. Nonetheless, there are a few evidences for the role of circRNAs in renal fibrosis induced by obstructive nephropathy. AIMS: We performed RNA-seq analysis to analyze the expression profiles of circRNAs in the obstructed kidneys to identify the potential circRNAs and their network. METHODS: With silk ligated the left ureter to establish a mice unilateral ureteral obstruction (UUO) model. Renal tissue circRNAs were obtained and were screened by a circRNA microarray. The circRNA-miRNA-mRNA regulatory network and the target genes were visualized using Cytoscape software. RESULTS: The microarray results showed that 5454 and 2935 circRNAs were detected in the control and UUO group, respectively. There were 605 circRNAs up-regulated and 745 circRNAs down-regulated in the obstructive kidneys. The top 5 up-regulated and down-regulated circRNAs were chosen for predicting the circRNA/miRNA/target mRNAs triple network. The GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that these circRNAs and the triple network were enriched in the process of apoptosis, p53 signaling pathway, cell growth and cell death, which might participate in the pathogenesis of obstructive nephrology. CONCLUSION: Our results show that the dis-regulated circRNAs might play crucial roles in the pathogenesis of obstructive nephropathy, which proceeds to identify novel therapeutic targets for chronic kidney disease.

Pharmacological inhibition of SETD7 by PFI-2 attenuates renal fibrosis following folic acid and obstruction injury.

Renal fibrosis is the common pathological hallmark of chronic kidney disease, and SET domain containing lysine methyltransferase 7 (SETD7) promote considerably renal fibrosis. However, the signaling mechanisms underlying SETD7 driving renal fibrosis are not fully understood. Here, we investigated the role of SETD7 in M2 macrophages-myofibroblasts transition and the myeloid fibroblasts activation in folic acid and obstruction-induced renal fibrosis. Mice treated with PFI-2, an inhibitor of SETD7, presented less bone marrow-derived myofibroblasts, fewer CD206+/α-smooth muscle actin + cells and developed less renal fibrosis (P＜0.01). Furthermore, SETD7 inhibition reduced the infiltration of inflammatory cells and decreased the production of pro-inflammatory cytokines and chemokines in the kidneys after folic acid treatment (P＜0.01). Finally, SETD7 inhibition suppressed the accumulation of NF-κB p65+ cells in folic acid nephropathy (P＜0.01). Taken together, SETD7 mediates M2 macrophages-myofibroblasts transition, bone marrow-derived myofibroblasts activation, and inflammation response in the development of renal fibrosis.

Microglial annexin A3 downregulation alleviates bone cancer-induced pain through inhibiting the Hif-1α/vascular endothelial growth factor signaling pathway.

Bone cancer-induced pain (BCP) is a challenging clinical problem because traditional therapies are often only partially effective. Annexin A3 (ANXA3) is highly expressed in microglia in the spinal cord, and its expression is upregulated during BCP. However, the roles of microglial ANXA3 in the development and maintenance of BCP and the underlying molecular mechanisms remain unclear. This study was performed on male mice using a metastatic lung BCP model. Adeno-associated virus shANXA3 (AAV-shANXA3) was injected intrathecally 14 days before and 7 days after bone cancer induction, and relevant pain behaviors were assessed by measuring the paw withdrawal mechanical threshold, paw withdrawal thermal latency, and spontaneous hind limb lifting. ANXA3 protein expression was downregulated in microglial N9 cells by lentiviral transfection (LV-shANXA3). ANXA3, hypoxia-inducible factor-1α (Hif-1α), vascular endothelial growth factor (VEGF) expression levels, and Hif-1α transactivation activity regulated by ANXA3 were measured. As a result, ANXA3 was expressed in microglia, and its expression significantly increased during BCP. ANXA3 knockdown reversed pain behaviors but did not prevent pain development. Moreover, ANXA3 knockdown significantly reduced Hif-1α and VEGF expression levels in vitro and in vivo. And overexpression of Hif-1α or VEGF blocked the effects of AAV-shANXA3 on BCP. ANXA3 knockdown in N9 cells significantly decreased the p-PKC protein expression in the cocultured neurons. Finally, ANXA3 overexpression significantly increased Hif-1α transactivation activity in 293T cells. Therefore, microglial ANXA3 downregulation alleviates BCP by inhibiting the Hif-1α/VEGF signaling pathway, which indicates that ANXA3 may be a potential target for the treatment of BCP.

SNAP-25 Contributes to Neuropathic Pain by Regulation of VGLuT2 Expression in Rats.

Synaptosomal-associated protein 25 (SNAP-25) plays an important role in neuropathic pain. However, the underlying mechanism is largely unknown. Vesicular glutamate transporter 2 (VGluT2) is an isoform of vesicular glutamate transporters that controls the storage and release of glutamate. In the present study, we found the expression levels of VGluT2 correlated with the upregulation of SNAP-25 in the spinal cord of rats following chronic constriction injury (CCI)-induced neuropathic pain. Cleavage of SNAP-25 by Botulinum toxin A (BoNT/A) attenuated mechanical allodynia, downregulated the expression of VGluT2 and reduced glutamate release. Overexpression of VGluT2 abolished the antinociceptive effect of BoNT/A. Upregulation of SNAP-25 in naive rats increased VGluT2 expression and induced pain-responsive behaviors. In pheochromocytoma (PC12) cells, the expression of VGluT2 was also depended on SNAP-25 dysregulation. Moreover, we found VGluT2 was involved in SNAP-25-mediated regulation of astrocyte expression and activation of the PKA/p-CREB pathway mediated the upregulation of SNAP-25 in neuropathic pain. The findings of our study indicate that VGluT2 contributes to the effect of SNAP-25 in maintaining the development of neuropathic pain and suggests a novel mechanism underlying SNAP-25 regulation of neuropathic pain.

Emerging roles of microRNAs in morphine tolerance.

Morphine is commonly used in clinical management to alleviate moderate-to-severe pain. However, prolonged and repeated use of morphine leads to tolerance. Morphine tolerance is a challenging clinical problem that limits its clinical application in pain treatment. The mechanisms underlying morphine tolerance are still not completely understood. MicroRNAs (miRNAs) are small noncoding RNAs containing 18~22 nucleotides that modulate gene expression in a post-transcriptional manner, and their dysregulation causes various diseases. miRNAs bind to the 3'-UTR (untranslated region) of target gene mRNA, inhibiting or destabilizing translation of the transcripts. Morphine causes differential miRNA upregulation or downregulation. This review will present evidence for the contribution of miRNAs to tolerance of the antinociception effect of opioids.

Risk factors and outcomes of urosepsis in patients with calculous pyonephrosis receiving surgical intervention: a single-center retrospective study.

BACKGROUND: Urosepsis is a catastrophic complication, which can easily develop into septic shock and lead to death if not diagnosed early and effectively treated in time. However, there is a lack of evidence on the risk factors and outcomes in calculous pyonephrosis patients. Therefore, this study was conducted to identify risk factors and outcomes of intra- and postoperative urosepsis in this particular population. METHODS: Clinical data of 287 patients with calculous pyonephrosis were collected. In the univariate and multivariate analysis, all patients were divided into urosepsis group and non-urosepsis group. The diagnosis of urosepsis was mainly on the basis of the criteria of American College of Chest Physicians (ACCP)/Society of Critical Care Medicine (SCCM). Patient characteristics and outcomes data were analyzed, and risk factors were assessed by binary logistic regression analysis. RESULTS: Of 287 patients, 41 (14.3%) acquired urosepsis. Univariate analysis showed that white blood cell (WBC > 10*10^9/L) before surgery (P = 0.027), surgery types (P = 0.009), hypotension during surgery (P < 0.001) and urgent surgery (P < 0.001) were associated with intra- and postoperative urosepsis for calculous pyonephrosis patients. In multivariate analysis, hypotension during surgery and urgent surgery were closely related to intra- and postoperative urosepsis. Outcome analysis suggested that patients developing urosepsis had a longer intensive care unit (ICU) stay and postoperative hospital stay and higher mortality. CONCLUSIONS: Hypotension during surgery and urgent surgery were risk factors of intra- and postoperative urosepsis for calculous pyonephrosis patients, which may lead to a prolonged ICU stay, postoperative hospital stay and higher mortality.

miR-873a-5p Targets A20 to Facilitate Morphine Tolerance in Mice.

Long-term morphine administration leads to tolerance and a gradual reduction in analgesic potency. Noncoding microRNAs (miRNAs) modulate gene expression in a posttranscriptional manner, and their dysregulation causes various diseases. Emerging evidence suggests that miRNAs play a regulatory role in the development of morphine tolerance. In the present study, we hypothesized that miR-873a-5p is a key functional small RNA that participates in the development and maintenance of morphine tolerance through the regulation of A20 (tumor necrosis factor α-induced protein 3, TNFAIP3) in mice. We measured the percentage of maximum possible effect (MPE %) to evaluate the analgesic effect of morphine. The expression of miR-873a-5p and its target gene A20 were determined after the morphine-tolerant model was successfully established. Intrathecal injection with lentivirus to intervene in the expression of A20 and the miR-873a-5p antagomir was used to explore the role of miR-873a-5p in the development of morphine tolerance. Chronic morphine administration significantly increased the expression of miR-873a-5p, which was inversely correlated with decreased A20 expression in the spinal cord of morphine-tolerant mice. Downregulation of miR-873a-5p in the spinal cord attenuated and partly reversed the development of morphine tolerance accompanied by overexpression of A20. Similarly, A20 was upregulated by a recombinant lentivirus vector, which attenuated and reversed the pathology of morphine tolerance by inhibiting the activation of nuclear factor (NF)-κB. Collectively, our results indicated that miR-873a-5p targets A20 in the spinal cord to facilitate the development of morphine tolerance in mice. Downregulating the expression of miR-873a-5p may be a potential strategy to ameliorate morphine tolerance.

Oral Lactobacillus reuteri LR06 or Bifidobacterium BL5b supplement do not produce analgesic effects on neuropathic and inflammatory pain in rats.

BACKGROUND: Previous studies have reported that certain bacteria exert visceral antinociceptive activity in visceral pain and may also help to relieve neuropathic and inflammatory pain. OBJECTIVE: The aim of this study was to explore the analgesic effect of Lactobacillus reuteri LR06 (LR06) or Bifidobacterium BL5b (BL5b) in chronic pain in vivo. DESIGN: Rats were randomly assigned into four groups: sham, Chronic Constriction Injury (CCI)/Complete Freund's Adjuvant (CFA) + control, CCI/CFA + LR06, and CCI/CFA + BL5b. Rats from the probiotic groups were treated with 1 x 109 cfu (LR06 or BL5b) daily through gavage for 14 days after a pain model was successfully established. Mechanical and thermal hyperalgesia were used to assess the analgesic effect of the probiotics. Iba1 was used to verify the microglial inflammatory reaction in the different groups. RESULTS: The results showed that probiotics L. reuteri LR06 or Bifidobacterium BL5b had no significant antinociception effects in chronic pain rats. The chronic pain-induced activation of microglia (Iba1) was not relieved by probiotics in CCI/CFA-induced neuropathic or inflammatory pain rats. CONCLUSION: Our results suggested that L. reuteri LR06 or Bifidobacterium BL5b had no antinociceptive effects on CCI-induced neuropathic pain and CFA-induced inflammatory pain in rats.

Identification of lncRNA expression profiles and ceRNA analysis in the spinal cord of morphine-tolerant rats.

Morphine tolerance is a challenging clinical problem that limits the use of morphine in pain treatment, but the mechanisms of morphine tolerance remain unclear. Recent research indicates that long noncoding RNAs (lncRNAs) might be a novel and promising target in the pathogeneses of diseases. Therefore, we hypothesized that lncRNAs might play a role in the development of morphine tolerance. Male Sprague-Dawley rats were intrathecally injected with 10 µg morphine twice daily for 7 consecutive days. The animals were then sacrificed for lncRNA microarray tests, and the results were validated by RT-qPCR. Next, functional predictions for the differentially expressed mRNAs (DEmRNAs) were made with the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG), and predictions for the differentially expressed lncRNAs (DElncRNAs) were made based on competitive endogenous RNA (ceRNA) analyses. The rats successfully developed morphine tolerance. LncRNA microarray analysis revealed that, according to the criteria of a log2 (fold change) > 1.5 and a P-value < 0.05, 136 lncRNAs and 278 mRNAs were differentially expressed in the morphine tolerance group (MT) compared with the normal saline group (NS). The functions of the DEmRNAs likely involve in the processes of the ion channel transport, pain transmission and immune response. The ceRNA analysis indicated that several possible interacting networks existed, including (MRAK150340, MRAK161211)/miR-219b/Tollip.Further annotations of the potential target mRNAs of the miRNAs according to the gene database suggested that the possible functions of these mRNAs primarily involved the regulation of ubiquitylation, G protein-linked receptors, and Toll-like receptors, which play roles in the development of morphine tolerance. Our findings revealed the profiles of differentially expressed lncRNAs in morphine tolerance conditions, and among these lncRNAs, some DElncRNAs might be new therapeutic targets for morphine tolerance.

Differential Expression of the Aryl Hydrocarbon Receptor and Transforming Growth Factor Beta 1 in Chronic Rhinosinusitis with Nasal Polyps with Allergic Rhinitis.

OBJECTIVE: This study aimed to determine the aryl hydrocarbon receptor (AhR) and transforming growth factor beta 1 (TGF-ß1) expression levels in chronic rhinosinusitis (CRS) and their possible correlation with allergic state and tissue remodeling. METHODS: Patients were enrolled and divided into the following groups: CRS without nasal polyps (NP) without allergic rhinitis (AR) (CRSsNPsAR; n = 20), CRS with NP with AR (CRSwNPwAR; n = 20), CRS with NP without AR (CRSwNPsAR; n = 20), and controls (n = 15). Tissue samples were analyzed by Masson trichrome staining for collagen, while the location and expression of AhR and TGF-ß1 were analyzed by immunohistochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blotting. RESULTS: The collagen amounts as well as AhR and TGF-ß1 mRNA and protein expression levels were significantly increased in the CRSsNPsAR group compared with the CRSwNP (CRSwNPsAR and CRSwNPwAR) samples (p < 0.01). However, higher collagen amounts (p < 0.05) and higher TGF-ß1 (p < 0.05) but lower AhR expression levels (p < 0.05) were detected in the CRSwNPwAR versus the CRSwNPsAR patients. Both AhR and TGF-ß1 expression were positively correlated with the collagen level in CRS samples (p < 0.01). CONCLUSIONS: Elevated AhR expression may be involved in the progression of tissue remodeling in CRSsNPsAR similar to TGF-ß1 expression. Conversely, lower AhR expression may be involved in allergic reactions in CRSwNPwAR.

miR-219-5p targets CaMKIIγ to attenuate morphine tolerance in rats.

Morphine tolerance is a clinical challenge in pain management. Emerging evidence suggests that microRNA (miRNA) plays a regulatory role in the development of morphine tolerance. miR-219-5p (miR-219) targets calmodulin-dependent protein kinase II γ (CaMKIIγ) to activate central pain sensitization via N-methyl-D-aspartate (NMDA) receptor. Therefore, we hypothesized that miR-219-5p attenuates morphine tolerance by targeting CaMKIIγ. We found that the expression of miR-219-5p was decreased significantly after chronic morphine treatment. Overexpression of miR-219-5p by lentivirus injection prevents the development of morphine tolerance. CaMKIIγ, the target gene of miR-219-5p was downregulated by overexpression of miR-219-5p both in vivo and in vitro. Furthermore, we found that lentiviral-mediated miR-219-5p decreased the expression of NMDA receptor subunit 1 (NR1), leading to attenuation of morphine tolerance. Overall, the data demonstrate that miR-219-5p plays a crucial role in alleviating morphine tolerance by inhibiting the CaMKII/NMDA receptor pathway. Overexpression of miR-219-5p may be a potential strategy to ameliorate morphine tolerance.

[One case report of primary sphenoid sinus tuberculosis].

We report a case of primary sinonasal tuberculosis in a 23-year old man. He had a half-year history of headache and eye pain on the left side, and found the neoplasm of nasopharynx 15 days ago. Previously denied history of tuberculosis and contact history. After be admitted to hospital, twice biopsy from neoplasm of na- sopharynx were both of chronic inflammation. Coronal CT scan of the lesion when admission found the left parasellar region and the left sphenoid sinus soft tissue density increased, about 20 mm X 32 mm X 34 mm, left inferior wall between sella bone defects, and bone sclerosis, plain CT value was about 34 HU, the lesion protruded downward left the nasopharynx. Eight days after he was admissioned in hospital of sphenoid sinus biopsy showed granulomatous inflammation and tuberculosis diagnosis was considered. Review of the lesion is partial absorbed after 11 months of anti-tuberculosis treatment and now is still in follow-up.

Bencycloquidium bromide inhibits nasal hypersecretion in a rat model of allergic rhinitis.

OBJECT AND DESIGN: This study is aimed at exploring the effect of Bencycloquidium bromide (BCQB), a novel M1/M3 receptor antagonist, on mucus secretion in a murine model of allergic rhinitis (AR). MATERIALS AND METHODS: Sprague-Dawley rats were sensitized with ovalbumin to induce AR. After BCQB treatment, nasal symptoms were evaluated. Nasal lavage fluid was used to detect the protein level of cytokines and histamine by the method of enzyme-linked immunosorbent assay. The nasal mucosa of all animals was prepared for western blot, quantitative real-time polymerase chain reaction and histochemical analysis. RESULTS: BCQB could not only alleviate typical AR symptoms including rhinorrhea, nasal itching and sneezing, but also inhibit the overexpression of mucin 5AC at the level of protein and mRNA. The release of histamine, the mRNA and protein level of IL-6, IL-13 and TNF-α, and the nuclear translocation of NF-κB (p65 and p50) were inhibited by BCQB. In addition, histological studies showed BCQB dramatically inhibited ovalbumin-induced nasal lesions, eosinophil infiltration, aggregation of mast cells, globlet cell hyperplasia and metaplasia. CONCLUSIONS: BCQB attenuates mucus hypersecretion in AR, possibly involving in the NF-κB signaling pathway.

Management of infected carotid artery rupture.

Carotid artery rupture (CAR) is a life-threatening complication of head and neck cancer, and infection complicates its management. The purpose of this study was to review our experience with the treatment of infected CAR and to summarize the existing literature on this topic. We retrospectively reviewed the medical records of patients treated in our department from 2000 to 2011 and re-analyzed cases reported in the literature during the same time period. We analyzed etiology, anatomic location, treatment, and rates of recurrent hemorrhage for each case. A total of 46 episodes of infected CAR occurred in the four patients in our own records and 27 patients described in the literature. Twenty-eight patients suffered from various head and neck cancers and underwent surgical resection, and 27 of them subsequently received radiotherapy or radiotherapy combined with chemotherapy (the 28th patient died before radiotherapy due to severe blood loss). The most common site of bleeding was the common carotid artery (33/46, 71.7%). Seventeen cases (17/45, 37.8%) were treated with surgical ligation, 20 (44.4%) with stent placement, and 7 (15.6%) with embolization. Surgical ligation had a lower rate of recurrent bleeding (2/17, 11.8%) than stent placement (12/20, 60.0%) when used for the treatment of infected CAR (P = 0.037, Chi squared test). Our results suggest that surgical ligation is an effective option in the management of infected CAR and may be the best choice to prevent recurrent hemorrhage. The complication rates, however, may be high when the common carotid or the internal carotid arteries are ligated.

[Effect of ginseng polysaccharide-induced wnt/beta-catenin signal transduction pathway on apoptosis of human nasopharyngeal cancer cells CNE-2].

OBJECTIVE: To observe the effect of ginseng polysaccharide (GPS) on the proliferation and apoptosis of human nasopharyngeal cancer cells CNE-2, and discuss the possible mechanism. METHOD: The effect of GPS on the growth of CNE-2 cells was observed by CCK8 assay. CNE-2 cells in the logarithmic phase were collected and processed respectively with different concentrations (0, 0. 1, 0. 2, 0. 3. 0. 4 g L-1) of GPS for 48 h. The flow cytometry was used to detect its induction effect on CNE-2 cell apoptosis. Hoechst-33258 cell staining and electron microscope were used to observe the morphological changes of cells. The beta-catenin mRNA expression was detected by Real-time PCR. The protein localizations and expressions of beta-catenin and TCF4 were tested by the immunofluorescence staining. The expressions of beta-catenin, Bcl-2 and Bax proteins were detected by Western blot. RESULT: CCK8 assay results showed that GPS could remarkably inhibit the proliferation of CNE-2 cells, with dose-time dependence. IC50 of cells induced with GPS for 48 h was 0. 39 g L-1. After being processed with GPS with concentrations of 0.1, 0. 2, 0. 3, 0. 4 g L-1 for 48 h, the cell apoptosis rates of human nasopharyngeal cancer cells CNE-2 were (5. 69 +/- 0. 29)% , (10. 3 +/- 0. 63)% , (15. 4 +/- 0. 74 ) % and (35. 7 +/- 1. 86)% , respectively. Significant difference was observed compared with the control group (2. 08 +/- 0. 11) % (P <0. 05). The results of Hoechst-33258 staining showed the characteristics of cell apoptosis. Under the electron microscope, apoptosis bodies could be observed among CNE-2 cells induced with GPS with the concentration of 0. 4 g L -1 for 48 h. The results of Real-time PCR showed a significant reduction in beta-catenin mRNA expression. The results of laser confocal microscopy revealed notable decrease of beta-catenin and TCF4 expression in nucleus and transfer from nucleus to cell membranes in beta-catenin expression areas after being processed with GPS for 48 h. Western blot showed significant decrease in the expressions of beta-catenin and anti-apoptosis protein Bcl-2, with an increasing expression in apoptosis-promoting protein Bax (P <0. 05). CONCLUSION: GPS could significantly inhibit the proliferation of CNE-2 cells and promote thier apoptosis. The obstruction of Wnt/beta-catenin signaling pathway may be an important mechanism for GPS to induce the apoptosis of human nasopharyngeal cancer cells CNE-2.

Protective effects of combined Mycobacterium bovis BCG and interleukin-12 vaccination on airway inflammation in a murine model of allergic asthma.

PURPOSE: Allergic asthma is characterized by chronic airway inflammation and airway hyperresponsiveness driven by allergen-specific T helper (Th)2 cells. Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination has been documented to suppress Th2 responses and allergic airway inflammation in animal models. Since interleukin (IL)-12 is capable of inhibiting Th2 responses, we sought to investigate whether IL-12 could function as an adjuvant to increase the efficacy of BCG vaccination against allergic asthma. METHODS: BALB/c neonatal mice (24 mice, 48-72 h old) were randomly divided into 3 subgroups (n = 8 for each group) to be immunized with PBS (control) or BCG with or without DNA plasmid-expressing IL-12. All of the mice were then sensitized and provoked with ovalbumin (OVA) to establish a model of allergic asthma. RESULTS: Mice vaccinated with BCG alone showed a significant reduction in airway inflammation, percentage of eosinophils in bronchoalveolar lavage (BAL) fluid, and serum OVA-specific immunoglobulin E (IgE) levels in comparison with control animals. The suppressive effects of BCG were substantially augmented by the combination with IL-12. Furthermore, a decreased IL-4 and increased interferon-gamma (IFN-gamma) production in BAL fluid were observed in animals inoculated with BCG alone or with IL-12 relative to control animals. CONCLUSION: Our data indicate that the combined vaccination with BCG and IL-12 yields a favorable outcome in prevention of experimental allergic airway inflammation, which is likely mediated through triggering a shift from a Th2 response to a Th1 response.