Nucleobase adducts bind MR1 and stimulate MR1-restricted T cells.

MR1T cells are a recently found class of T cells that recognize antigens presented by the major histocompatibility complex-I-related molecule MR1 in the absence of microbial infection. The nature of the self-antigens that stimulate MR1T cells remains unclear, hampering our understanding of their physiological role and therapeutic potential. By combining genetic, pharmacological, and biochemical approaches, we found that carbonyl stress and changes in nucleobase metabolism in target cells promote MR1T cell activation. Stimulatory compounds formed by carbonyl adducts of nucleobases were detected within MR1 molecules produced by tumor cells, and their abundance and antigenicity were enhanced by drugs that induce carbonyl accumulation. Our data reveal carbonyl-nucleobase adducts as MR1T cell antigens. Recognizing cells under carbonyl stress allows MR1T cells to monitor cellular metabolic changes with physiological and therapeutic implications.

[Umbilical moxibustion for patients with idiopathic pulmonary fibrosis complicated with gastroesophageal reflux of lung-spleen qi deficiency].

OBJECTIVE: To evaluate the clinical efficacy of umbilical moxibustion in the treatment of patients with idiopathic pulmonary interstitial fibrosis complicated with gastroesophageal reflux of lung-spleen qi deficiency. METHODS: A total of 116 patients with idiopathic pulmonary fibrosis complicated with gastroesophageal reflux of lung spleen-deficiency were randomized into an observation group (58 cases) and a control group (58 cases). In the control group, the routine treatment was applied; in the observation group, on the base of the treatment as the control group, the umbilical moxibustion was used. The treatment was given 2 times a week, 2 h each time for 12 weeks, and followed up for 12 weeks after treatment. The composite physiological indicators (CPI), TCM syndrome scores, the St. George respiratory questionnaire score (SGRQ) and 6-minute walk test (6MWT) were compared before and after treatment in the two groups. RESULTS: The improvement of the TCM syndrome scores (cough, post-activity shortness of breath, fatigue, heartburn, acid reflux), CPI score and 6MWT in the observation group was better than those in the control group (all P<0.05). There was no significant difference in the scores of SGRQ scale between the two groups after treatment (P>0.05). There was no significant difference in the scores of CPI scores and syndromes (cough and fatigue) between the two groups at 12 weeks after treatment (all P>0.05). The 6MWT, SGRQ scale scores and syndrome scores (post-activity shortness of breath, acid reflux, heartburn) were better than those in the control group in the follow up (all P<0.05). CONCLUSION: Umbilical moxibustion can improve the ventilation and diffusion function of lung in patients with idiopathic pulmonary fibrosis and gastroesophageal reflux of lung-spleen qi deficiency, reduce clinical symptoms and improve patients' quality of life and activity endurance. And it has long-term effect.

Effect of asiatic acid on epithelial-mesenchymal transition of human alveolar epithelium A549 cells induced by TGF-ß1.

Asiatic acid (AA) is a pentacyclic triterpenoid isolated from Centella asiatica (L.) Urban that possesses significant antitumor activities. In the present study, the mechanism of AA on transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) was investigated in the lung cancer cell line A549. To do so, cell morphological alterations were observed and recorded at different time periods. Cells treated with TGF-ß1 were spindle-shaped and characterized as stromal cells, whereas AA-treated cells exhibited epithelial cell characteristics and increased intercellular adhesion. The MTT assay demonstrated that the high concentration of AA inhibited the viability of A549 cells treated with TGF-ß. In addition, the wound healing and Transwell assays revealed that AA inhibited TGF-ß1-induced invasion and migration of A549 cells. Furthermore, AA treatment increased the mRNA and protein expression levels of E-cadherin, and decreased the expression levels of snail family transcriptional repressor (Snail), N-cadherin, vimentin and ß-catenin in TGF-ß1-treated A549 cells. In conclusion, these results suggested that AA may inhibit TGF-ß1-induced EMT in lung cancer through increased expression of E-cadherin, and inhibition of Snail, N-cadherin and vimentin expression.

Link between neurodegeneration and trabecular meshwork injury in glaucomatous patients.

BACKGROUND: Glaucoma is classified as a neurodegenerative disease. However, the biomarkers of neurodegeneration in the aqueous humour of primary open angle glaucoma (POAG) eyes have not been quantitatively examined yet. In this study, levels of neurodegeneration-related cytokines in the aqueous humour of POAG eyes were measured and compared with those of non-glaucoma (senile cataract) control eyes. METHODS: This cross-sectional study included 24 patients (24 eyes) with POAG and 22 patients (22 eyes) with cataract. Aqueous humour samples were collected before the commencement of phacoemulsification surgery. The concentrations of brain-derived neurotrophic factor (BDNF), cathepsin D, myeloperoxidase (MPO), soluble intercellular adhesion molecule-1 (sICAM-1), soluble neural cell adhesion molecule (sNCAM), soluble vascular cell adhesion molecule-1 (sVCAM-1), and plasminogen activator inhibitor-1 (PAI-1) were measured using the Luminex suspension array technique. The clinical characteristics of the patients were also obtained for correlation analysis. RESULTS: Compared with the cataract group, the levels of cathepsin D (P < 0.001), sNCAM (P < 0.001) and sVCAM-1 (P = 0.007) were significantly higher in the aqueous humour samples from POAG. The levels of BDNF, sICAM-1, MPO and PAI-1 did not differ among the groups. Mean deviation (MD) values measured by the Humphrey Visual Field Analyzer were significantly associated with levels of cathepsin D (P < 0.001; ρ= - 0.668), sICAM-1 (P = 0.003; ρ= - 0.579), sVCAM-1(P < 0.001; ρ= - 0.695), and PAI-1 (P = 0.007; ρ= - 0.533). The cytokines showed a positive correlation among each other (P < 0.0083). CONCLUSION: These data suggest that POAG patients had elevated levels of multiple biomarkers of neurodegeneration in the aqueous humour, and these elevated biomarkers may be related to trabecular meshwork injury. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry ( ChiCTR-OOC-16008516 ) on May 22, 2016.

[Moxibustion on the Governor Vessel for lung and kidney qi deficiency type in chronic obstructive pulmonary disease: a randomized controlled trial].

OBJECTIVE: To observe the difference between the therapeutic effect of Du-moxibustion (Moxibustion on the Governor Vessel) combined with western medicine and that of simple western medication for the remission stage of chronic obstructive pulmonary disease. METHODS: Two hundred and ten cases were randomly divided into an observation group (108 cases)and a control group (102 cases). The observation group was treated by routine treatment of western medicine combined with herb-partitioned spread moxibustion on the Governor Vessel between Dazhui (GV 14)and Yaoshu (GV 2). Simple western medicine was used in control group. The therapeutic effects of two groups were compared with the changes of symptom scores and pulmonary function before and after treatment. RESULTS: The total effective rate of observation group (90.7%, 98/108) was higher than that of control group (74.5%, 76/102) (P < 0.01). The symptom scores and some pulmonary function indices such as forced vital capacity (FVC), forced expiratory volume in one second (FEV1), the percentage of force expiratory volume in one second in predicted value(FEV1%) and maximal expiratory flow(PEF) after treatment were improved obviously than those before treatment in observation group (P < 0.05, P < 0.01), and the improvement degree was better than that of control group (all P < 0.01). CONCLUSION: Moxibustion on the Governor Vessel combined with western medicine can improve the clinical symptoms and pulmonary function of chronic obstructive pulmonary disease of lung and kidney qi deficiency type effectively,and the effect is better than that of simple western medication.