Interstitial pulmonary fibrosis is characterized by an altered cellular composition of the alveolar region with excessive deposition of collagen. Lung inflammation is also common in pulmonary fibrosis. This study aims to test the inhibition of 5-lipooxygenase (5-LOX) by boswellic acid (BA) extract in an experimental model of pulmonary fibrosis using bleomycin (BL).
Methods
Boswellic acid extract (1 g/kg) was force-fed to rats seven days prior to administration of BL or gamma irradiation or both. BL (0.15 U/rat) in 25 μl of 0.9% normal saline (NS) or 0.9% NS alone was administered intratracheally. Rats were exposed to two fractionated doses of gamma irradiation (0.5 Gy/dose/week) with a gamma cell-40 (Cesium-137 irradiation units, Canada) during the last two weeks of the experiment. BA was administered during BL or irradiation treatment or both. After the animals were sacrificed, bronchoalveolar lavage was performed; lungs were weighed and processed separately for biochemical and histological studies.
Results
In rats treated with BL, levels of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) were significantly elevated (P = 0.05 and P = 0.005). Hydroxyproline was highly and extensively expressed. Immunoreactive compounds were abundantly expressed, represented in the levels of macrophages infiltrate, accumulation of eosinophils and neutrophils in the lung as well as the aggregation of fibroblasts in the fibrotic area. The levels of lipoxygenase enzyme activity were significantly increased (P = 0.005). Antioxidant activities measured in BL-treated rats deteriorated, coupled with the elevation of both levels of plasma lipid peroxide (LP) content and bronchoalveolar lavage lactate dehydrogenase activity. BA-treated rats had reduced number of macrophages, (P = 0.01), neutrophils in bronchoalveolar lavage (P = 0.01) and protein (P = 0.0001). Moreover, the hydroxyproline content was significantly lowered in BA-treated rats (P = 0.005). BA extract inhibited the TGF-ß induced fibrosis (P = 0.01) and 5-LOX activity levels (P = 0.005). Histologically, BA reduced the number of infiltrating cells, ameliorated the destruction of lung architecture and attenuated lung fibrosis.
Conclusion
BA attenuates the BL-induced injury response in rats, such as collagen accumulation, airway dysfunction and injury. This study suggests that the blocking of 5-LOX may prevent the progression of fibrosis. 相似文献
CD44(+)/CD24(-) cells have been associated with breast cancer stem/progenitor cell features. However, the status of this phenotype cells in normal, benign and malignant breast tissues has not been studied, and the clinical correlation of this subpopulation in breast cancer is not fully understood. The present study sought to identify these cells in a series of normal, benign, and malignant breast tissues and explore their correlation to the molecular subtypes of breast carcinoma and conventional pathological features. Double-staining immunohistochemistry (DIHC) of CD44 and CD24 was performed on 30 normal breast tissues, 30 breast fibroadenomas (FA), 60 breast invasive ductal carcinomas (IDC), and 3 breast cancer cell lines (MCF-7, MDA-MB-468, and MDA-MB-231). In the normal breast tissues and FAs, three phenotypes were observed including CD44(+)/CD24(+), CD44(+)/CD24(-), and CD44(-)/CD24(-) cells. In the IDCs, CD44(-)/CD24(+) cells were detected, in addition to the three aforementioned phenotypes. The strong positive rate (+++, incidence >60%) of CD44(+)/CD24(-) was significantly increased from normal breast tissue, FAs to IDCs (0.0%-->6.7%-->21.7%). However, the CD44(+)/CD24(-) cells didn't correlate with ages of patients, lymph node metastasis, tumor size, molecular subtypes, and the expression of ER, PR, HER-2, PS2, Bcl-2, nm23. The proportion of CD44(+)/CD24(-) cells in MCF-7, MDA-MB-468, and MDA-MB-231 was about 1, 5, and 80%, respectively. The results indicate that the CD44(+)/CD24(-) cells are transit progenitors and have no association with the molecular subtypes and clinicopathological parameters in the IDCs. 相似文献
DSCs are a promising alternative to conventional silicon‐based solar cells owing to their low cost and relatively high efficiency. However, the utilization of a liquid electrolyte containing the iodine/iodide redox couple in traditional DSCs brings practical problems for their long‐term application, which leads to rapid development of SDSCs based on inorganic p‐type semiconductors or organic HTMs. In this review, we summarize the current research on SDSCs using conjugated polymer as HTM. Special attention is paid to understand the effects of polymer HTM structure and deposition process on SDSC performance. The limiting factors for SDSC energy conversion efficiency are discussed and strategies to improve device performance are proposed.
Schistosomiasis remains a major public health problem and it is an immune disease. The schistosome egg is the primary parasite
factor responsible for the overt disease. The eggs release the soluble antigen, which induces intensive tissue reaction, a
granulomatous reaction to the eggs. If granuloma formation could be suppressed, overt disease might not develop. Praziquantel
is an effective antischistosomal drug especially for adult worms. However, whether praziquantel has a suppressing effect on
granuloma formation around schistosome eggs directly remains unclear. The purpose of the present study was to investigate
the effect of praziquantel, especially administered persistently, on granuloma formation around Schistosoma japonicum eggs in the lung of sensitized mice. Thirty-six mice were divided into three groups averagely. Group A was a control group.
First, the mice were injected with schistosomal eggs hypodermically in abdomen, and 10 days later injected with schistosomal
eggs intravenously via a tail vein. Group B was a praziquantel short administration group. In addition to the injections of
schistosomal eggs as the same of Group A, the mice were administered with praziquantel in a daily dose of 300 mg/kg for 3 days,
from 1 day before the intravenous injection of the eggs. Group C was a praziquantel prolonged administration group. In addition
to the injections of schistosomal eggs as the same of Group A, the mice were administered with praziquantel in a daily dose
of 150 mg/kg for 5 days weekly until the mice were sacrificed. Three mice of each group were sacrificed on days 7, 14, 28,
and 56, respectively after the intravenous injection of the eggs, and the lung tissues were fixed with formalin and the slices
were HE stained. The granulomas containing eggs in their centers were selected, and 25–30 granulomas from the animals of each
group were measured at each time period. The mean areas of egg granulomas of each group were calculated, and the neutrophilic
granulocytes, eosinocytes, lymphocytes, fibroblasts, and macrophages within the egg granulomas were counted. The mean numbers
of them of each group were calculated. All the data of each group were analyzed and compared statistically. On day 56 after
the intravenous injection of the eggs, the mean area of schistosomal egg granulomas in group B was (227.4 ± 728.0) × 103 μm2, less than that of [(297.9 ± 153.3) × 103 μm2] in group A, and the suppression rate was 23.7% (P < 0.05). On days 7, 14, 28, and 56, the mean areas of schistosomal egg granulomas in group C were (575.8 ± 155.6) × 103 μm2, (310.5 ± 854.0) × 103 μm2, (267.7 ± 513.3) × 103 μm2, and (214.9 ± 446.4) × 103 μm2, respectively, significantly less than those of [(692.7 ± 232.6) × 103 μm2, (439.4 ± 165.0) × 103 μm2, (385.7 ± 129.3) × 103 μm2, and (297.9 ± 153.3) × 103 μm2] in group A. The suppression rates were 16.9%, 29.3%, 30.6%, and 27.9%, respectively (P values <0.05). On day 56, the mean numbers of neutrophilic granulocytes were 11.4 ± 5.0 in group A and 5.2 ± 3.1 in group
C, respectively, with the suppression rate of 54.4% in group C (P < 0.05). On day 56, the mean numbers of eosinocytes within the egg granulomas were 2.3 ± 2.0, 0.1 ± 0.3, and 0.3 ± 0.6 in
groups A, B, and C, respectively, with the suppression rate of 95.7% in group B and 87.0% in group C (P values <0.05). On day 56, the mean numbers of macrophages within egg granulomas were 14.3 ± 6.9 in group C, compared with
18.6 ± 8.2 in group A, the suppression rate was 23.1% (P < 0.05). On day 56, the mean numbers of fibroblasts within the egg granulomas were 6.6 ± 4.4 and 5.8 ± 2.6 in groups B and
C, respectively, and compared with 14.3 ± 7.8 in group A, the increasing extents decreased by 53.8% and 59.4%, respectively
(P values <0.05). Therefore, the administration of praziquantel, especially the prolonged administration, can suppress the formation
of schistosomal egg granulomas, including reduction in the areas of granulomas and suppression of the inflammatory cells and
the hyperplasia of fibroblasts within granulomas. 相似文献
