ABSTRACT
Neurodegenerative disorders are known to be associated with neuroinflammation caused by microglia. Therefore, regulation of microglia activation and polarization to inhibit neuroinflammatory reactions seems to hold promise as a therapeutic approach in neurodegenerative disorders. Spatholobus suberectus Dunn (SSD) has been utilized as a traditional Chinese medicine remedy for brain diseases for thousands of years. SSD possesses various pharmacological activities, such as circulation invigoration, neuroprotection, and anti-inflammatory. The objective of this research was to examine the anti-neuroinflammatory effects and molecular mechanisms of an active fraction from SSD (ASSD) in vitro culture BV2 cells, a type of mouse microglia cell line. The inflammatory responses in BV2 cells were induced by stimulating them with 1 µg/mL lipopolysaccharide (LPS) and the effects of ASSD on LPS-stimulated inflammation were monitored. Besides, by using the methods of Western blot, immunofluorescence, and RT-PCR, the mechanisms of ASSD on microglia activation, M1/M2 polarization, and the TLR4/MyD88/NF-κB pathway were investigated. Our findings demonstrate that the treatment doses of ASSD neither induce cytotoxicity nor promote the production of inflammatory cytokines. In addition, immunofluorescence analysis show that ASSD inhibited the expression of ionized calcium-binding adapter molecule 1(Iba1) and inducible nitricoxide synthase (iNOS), and induced arginase 1 (Arg1) expression. Moreover, Western blot analysis indicated that ASSD significantly down-regulated TLR4, MyD88, p-IκB, NF-κB p65, and NF-κB p-p65 protein expression levels. Furthermore, RT-qPCR assay show that ASSD significantly down-regulated iNOS, TLR4, MyD88, and NF-κB mRNA expression levels, and up-regulated Arg1 mRNA expression level. According to the findings, ASSD can suppress microglia-mediated inflammatory responses by modulating microglia activation, inducing a shift from M1 to M2 polarization, and inhibiting the TLR4/MyD88/NF-κB signaling pathway.
ABSTRACT
AIM: Intensity-modulated radiotherapy (IMRT) is a widely accepted therapy for nasopharyngeal carcinoma (NPC), but it inevitably brings out radiation-related complications and seriously affects the quality of life (QoL). Endoscopic nasopharyngectomy (ENPG) has been successfully conducted in locally recurred NPC, but few studies evaluated its application in early NPC. This study aims to assess the feasibility and safety of ENPG combined with low-dose radiotherapy (LDRT) in T1-2 NPC. PATIENTS AND METHODS: We recruited 37 newly diagnosed localized T1-2 NPC patients who voluntarily accepted ENPG +LDRT from June 2013 to September 2016. Meanwhile, the data of 132 T1-2 NPC patients treated with IMRT were collected and used as control group. The survival outcomes, QoL score and late RT-related sequelaes were compared between the 2 groups. RESULTS: After a median follow-up of 54 months, only 1 patient in ENPG+LDRT group died along with hepatic metastases. The 5-year overall survival, distant metastasis-free survival, local relapse-free survival and regional relapse-free survival in ENPG+LDRT group were 97.3%, 97.3%, 100% and 100%, which were not statistically different from the control group (97.7%, 90.2%, 95. 5%, 97.0%, respectively, all P > 0.05). In comparison with IMRT group, ENPG+LDRT exhibited better QoL and less rate of late RT-related sequlaes including hearing loss (53.8% vs 27.0%, P = 0.005), xerostomia (46.2% vs 24.3%, P = 0.023) and dysphagia (25.8% vs 8.1%, P = 0.024). CONCLUSIONS: ENPG+LDRT provided satisfactory survival outcomes, and improved the QoL and reduced the incidence of sequelae for T1-2 NPC patients.
Subject(s)
Carcinoma/therapy , Nasopharyngeal Neoplasms/therapy , Neoplasm Recurrence, Local , Pharyngectomy/methods , Adult , Carcinoma/secondary , Combined Modality Therapy , Deglutition Disorders/etiology , Endoscopy , Female , Follow-Up Studies , Hearing Loss/etiology , Humans , Male , Middle Aged , Nasopharyngeal Neoplasms/pathology , Nasopharynx/surgery , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Pharyngectomy/adverse effects , Quality of Life , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective Studies , Survival Rate , Xerostomia/etiologyABSTRACT
Objective:To investigate the characteristics of allergic rhinitisï¼ARï¼ in the Nanning area and its correlation with meteorological factors. Methods:The characteristics of 16 969 cases of AR in Nanning from May 2011 to June 2018 were analyzed. Meteorological parameters were collected from the official website of the Nanning Meteorological Bureau, including weather conditions, temperature, and wind direction. The relationship between the onset characteristics of AR patients and meteorological factors were also analyzed. Results:Among the 16 969 patients with AR, the top three inhalation allergens were dust miteï¼56.0%ï¼, house dust miteï¼50.5%ï¼, and cockroachï¼37.4%ï¼. The skin indexï¼SIï¼ of dust mite, house dust mite, cockroach is correlated with sex. The SI of dust mite, house dust mite, mugwort, cockroach are correlated with age, and inhaled allergens are correlated with disease courseï¼P<0.05ï¼. However, those relationships were not significantï¼r<0.2ï¼. The proportion of AR patients visiting the clinic in summer was the highestï¼3.9%ï¼ in all of the four seasons. Gender was found to be related to the grade-4 positive results of dust miteï¼OR=0.826, 95%CI: 0.724-0.942ï¼, the grade-4 house dust miteï¼OR=0.777, 95%CI: 0.677-0.891ï¼ and the grade-3 positive results of cockroachï¼OR=1.236, 95%CI: 1.060-1.443ï¼, respectively. The the daytime weather conditions were related to the grade-4 positive results of dust miteï¼OR=0.830, 95%CI: 0.728-0.947ï¼ and the grade 1 positive results of house dust miteï¼OR=0.803, 95%CI: 0.694-0.929ï¼, respectively. The highest temperature was related to the grade-4 positive result of dust miteï¼OR=1.032, 95%CI: 1.020-1.043ï¼, grade-1ï¼OR=1.028, 95%CI: 1.001-1.056ï¼ and grade-4 ï¼OR=1.047, 95%CI: 1.021-1.075ï¼ positive result of house dust mite, grade 1ï¼OR=1.023, 95%CI: 1.001-1.047ï¼ and grade-4ï¼OR=1.050, 95%CI: 1.008-1.094ï¼ positive result of cockroach, respectively. The minimum temperature was related to the positive results of house dust mites at all grades and the grade-1 positive results of cockroachï¼OR=0.947, 95%CI: 0.924-0.971ï¼, but not to dust mites. The daytime wind direction was related to the grade-3 positive results of cockroachï¼OR=1.437, 95%CI: 1.157-1.785ï¼. Conclusion:The number of AR patients in Nanning is highest in summer. The female is more likely to suffer from dust mite and house dust mite, while the male is more likely to suffer from cockroach. Meteorological factors are correlated with the incidence of AR.The highertemperature, the rain and the southerly wind could cause the occurrence or aggravation of AR.
Subject(s)
Mites , Rhinitis, Allergic , Allergens , Animals , Cockroaches , Dust , Female , Humans , Male , Pyroglyphidae , WeatherABSTRACT
The purpose of this study was to use a murine model to determine if melatonin can protect the inner ear from radiation-induced damage. A total of 81 4-week-old Balb/c mice were randomly divided into five groups: control group; 50 mg/kg melatonin group; 5 mg/kg melatonin+radiotherapy group; 50 mg/kg melatonin+radiotherapy group; radiotherapy group. The radiotherapy groups received 16 Gy irradiation and melatonin was administered by intraperitoneal injection 30 min before radiotherapy. On days 3 and 7 after irradiation the function of outer hair cells was determined by auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) testing, pathological changes of inner ear cells were observed by light microscopy, and the expression of prestin mRNA was determined. ABR thresholds were increased and wave I latencies were extended after radiotherapy; however, the increases were lower in the groups that received melatonin (P < 0.05). DPOAEs showed radiotherapy-induced hearing loss at 8-12 kHz, and hearing loss was greater on day 7 than day 3. However, hearing loss was less in the melatonin groups (P < 0.05). Histopathological examination showed irradiation resulted in breaks and distortion of the cochlear basement membrane, disruption of the stria vascularis, and swelling of outer hair cells. Melatonin reduced these changes. Radiotherapy upregulated prestin mRNA expression. Radiotherapy-induced upregulation of prestin was decreased in the melatonin groups (P < 0.05), and the decrease was greater in the 50 mg/kg melatonin group (P < 0.05). Melatonin protects against radiation-induced cochlear damage by reducing damage to outer hair cells.