To test the hypothesis that exogenous purified angiotensin II (ANG) might cause apoptosis of alveolar epithelial cells (AECs) and acute lung injury, male Wistar rats were intratracheally instilled with purified ANG (10 mumol/L), ANG plus the caspase inhibitor ZVAD-fmk (60 mumol/L), ANG plus the ANG receptor AT1 antagonist losartan (LOS, 100 mumol/L) or sterile phosphate-buffered saline (PBS) vehicle alone. Six or 20 h later, the lungs were lavaged in situ for determination of bronchoalveolar lavage (BAL) fluid content of hemoglobin (Hb) and fluorescent (BODIPY)-albumin, a bolus of which was injected intravenously 15 min prior to BAL. Terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) revealed that instillation of ANG, but not PBS alone, increased labeling of fragmented DNA in bronchiolar epithelial cells and in AECs (P<0.05) at 6 h post-ANG. Increased TUNEL was abrogated by concurrent instillation of ZVAD-fmk or LOS. Significant increased numbers of caspase-positive cells were observed by anti-caspase 3 immunolabeling after instillation of ANG (P<0.01); the same doses of LOS or ZVAD-fmk that blocked TUNEL also blocked the activation of caspase 3 (P<0.01). Intratracheal instillation of ANG also remarkably increased BAL BODIPY-albumin (P< 0.01) and Hb (P<0.05), both of which were eliminated by ZVAD-fmk or LOS. These data indicate that exposure of AECs to ANG in vivo is sufficient to induce apoptosis and alveolar epithelial barrier injury mediated by ANG receptor AT1.
Amino Acid Chloromethyl Ketones ; pharmacology ; Angiotensin II ; adverse effects ; Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Animals ; Apoptosis ; Caspase 3 ; metabolism ; Caspase Inhibitors ; pharmacology ; Epithelial Cells ; pathology ; Losartan ; pharmacology ; Lung Injury ; chemically induced ; pathology ; Male ; Rats ; Rats, Wistar ; Receptor, Angiotensin, Type 1 ; metabolism

Adult ; Carbolines ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Middle Aged ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Semen ; Sildenafil Citrate ; Specimen Handling ; Sulfones ; therapeutic use ; Tadalafil

Exogenous calcium can enhance the resistance of certain plants to abiotic stress. Research have demonstrated that exogenous calcium could enhances the resistance of honeysuckle under salt stress by promoting the transmission of photosynthetic electrons.The aim of this study was to investigate the effects of exogenous calcium on the contents of Na~+,K~+,Ca~(2+),Mg~(2+)and the expression of photosynthetic related genes Cab and rbc L. In this study,we used ICP-OES to analysis ion contents and used qRT-PCR to analysis the expression patterns of Cab and rbc L. The results showed that CaCl_2 significantly enhanced the K~+-Na~+,Ca~(2+)-Na~+,Mg~(2+)-Na+ratio of honeysuckle treated with 50 and 100 mmol·L~(-1) NaCl. Meanwhile,Cab and rbc L were significantly up-regulated under short-term salt stress,and CaCl_2 promoted this trend. From the two gene expression patterns,rbc L rapidly up-regulated on the first day of stress and then decreased,and was more sensitive to environmental changes. In summary,exogenous calcium could alleviate salt stress and increase plant development by increasing intracellular K~+-Na~+,Ca~(2+)-Na~+,Mg~(2+)-Na+ratio,and the transient overexpression of Cab and rbc L.
Calcium ; physiology ; Cations ; analysis ; Lonicera ; physiology ; Photosynthesis ; Salt Stress

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome