One half of the world's population relies on biomass fuel as the primary source of domestic energy. Biomass fuel exposure causes a high degree of morbidity and mortality in humans. This is especially true in the context of developing countries, which account for 99% of the world's biomass fuel use. Biomass fuel consists of fire wood, dung cakes, agricultural crop residues such as straw, grass, and shrubs, coal fuels and kerosene. Together, they supply 75% of the domestic energy in India. An estimated three-quarters of Indian households use biomass fuel as the primary means for domestic cooking. Ninety percent of rural households and 32% of urban households cook their meals on a biomass stove. There are wide variations between the rural and urban households regarding the specific type of biomass fuel used. Globally, almost 2 million deaths per year are attributable to solid fuel use, with more than 99% of these occurring in developing countries. Biomass fuel accounts for 5-6% of the national burden of disease. Burning biomass fuels emits toxic fumes into the air that consist of small solid particles, carbon monoxide, polyorganic and polyaromatic hydrocarbons, and formaldehyde. Exposure to biomass fuels has been found to be associated with many respiratory diseases such as acute lower respiratory infections, chronic obstructive pulmonary disease, lung cancer, pulmonary tuberculosis, and asthma. Biomass fuel exposure is closely related to the burden of disease in India. Hopes are that future studies will examine the morbidity associated with biomass exposure and seek to prevent it. Concerted efforts to improve stove design and transition to high-efficiency low-emission fuels may reduce respiratory disease associated with biomass fuel exposure.
Vascular abnormalities are one of the common features in rheumatic diseases, but their pathogenesis is still not known. Angiogenin, a molecule implicated in the angiogenic process, may play some roles in such vascular changes. Serum angiogenin concentrations were measured in 21 scleroderma patients, 10 patients with systemic lupus erythematosus (SLE), 21 patients with dermatomyositis (DM), 5 patients with polymyositis (PM), 11 patients with clinically amyopathic DM (CADM) and 12 normal subjects, with specific enzyme-linked immunosorbent assays. Angiogenin mRNA in vivo was determined in skin tissues of 5 DM patients, 4 CADM patients, 5 SLE patients and 7 normal subjects using quantitative real-time polymerase chain reactions. We could not find any significant differences in the serum angiogenin levels among normal subjects and patients with rheumatic diseases. However, when we evaluated the correlation of serum angiogenin levels with clinical features of 32 DM/CADM patients, the patients with increased angiogenin levels had significantly higher aldolase levels than those with decreased levels. On the other hand, angiogenin mRNA is significantly up-regulated in the involved skin of DM and CADM, suggesting that angiogenin expression is up-regulated locally in the skin but not in sera of patients with DM and CADM. In conclusion, dysregulated angiogenin expression may contribute to the pathogenesis of myositis as well as skin involvement via the vascular change in DM/CADM. Further studies with an increased number of patients may help to clarify the relationship between angiogenin and vascular abnormalities in rheumatic diseases and to develop new therapeutic strategies.
A coumarin-based prodrug system plays a significant role in preparing esterase-sensitive prodrugs of amines and peptides. The electronic structures of 27 coumarin-based prodrugs developed in our lab were calculated at a B3LYP/6-31+G (d,p) level with a Gaussian 03 establish five novel QSPR models. The SMLR linear model (q2 = 0.427, r2 = 0.516) and the PLS linear model (q2 = 0.584, r2 = 0.663) were developed with descriptors selected by an Unsupervised Forward Selection method. Another three nonlinear QSPR models were established by a Polynomial Neural Network (PNN) Simulation method (q2 = 0.692, 0.675, 0.663; r2 = 0.700, 0.688, 0.672). We suggest that the QSPR models derived here, especially the PNN models, can be used to predict the release kinetics of coumarin-based prodrugs as well as design new derivatives of coumarin-based prodrug candidates.
An easy fluorimetric assay for measuring D-amino acid oxidase (DAAO) activity by using one of the D-amino acids – D-kynurenine (D-KYN) – as a substrate was applied to assess DAAO activity in the cerebrum, cerebellum, and brainstem of Sprague-Dawley (SD) male rats. In this assay, DAAO produces kynurenic acid (KYNA) from D-KYN, and the fluorescence originating from KYNA can then be used to evaluate DAAO activity. Here, pellet fractions obtained by centrifugation of brain homogenates were allowed to react enzymatically with D-KYN. The addition of specific DAAO inhibitors, such as 3-methylpyrazole-5-carboxylic acid and 4H-thieno [3, 2-b] pyrrole-5-carboxylic acid (Compound 8), significantly attenuated the fluorescence intensity of KYNA, suggesting that DAAO present in the rat brain homogenates was responsible for the production of KYNA. In contrast, an inhibitor of aminotransferase (AT), aminooxyacetic acid, did not decrease KYNA production from D-KYN, meaning that AT could not metabolize D-KYN to KYNA under the present conditions. Moreover, the DAAO activity measured by the proposed assay correlated well with DAAO mRNA expression (r = 0.9982) determined by real-time polymerase chain reaction. Taken together, these findings show that the proposed fluorimetric assay can be used to evaluate DAAO activity in rat brain.
MIWI is one of the PIWI subfamily of proteins mainly expressed in mouse germ cells, and associates with pachytene piRNAs. MIWI has been thought to play an essential role in spermatogenesis and spermiogenesis via biogenesis and/or stability of pachytene piRNAs, retrotransposon silencing, and post-transcriptional regulation of target mRNAs. However, MIWI's detailed role and function are not well understood. In this study, we produced an anti-MIWI mouse monoclonal antibody and identified MIWI-associated poly(A) RNAs by immunoprecipitation from adult mouse testes lysates. Approximately 70% of the MIWI-associated poly(A) RNAs were known mRNAs and 30% of them were unknown non-coding RNAs. These poly(A) RNAs contained piRNA-encoding RNAs transcribed from piRNA cluster regions and piRNA-encoding mRNA, such as Aym1 mRNA. Mature piRNAs specifically encoded in these piRNA-encoding RNAs were generated in pachytene spermatocytes and not detected in Miwi-deficient (Miwi-/-) testes. Moreover, MIWI associated with a large number of known mRNAs whose expression levels were increased in pachytene spermatocytes, and the expression of these mRNAs was decreased in Miwi-/-testes at 20 days postpartum when pachytene spermatocytes were most abundant. These results strongly suggest that MIWI is involved in pachytene piRNA biogenesis and the positive regulation of target mRNA metabolism in pachytene spermatocytes via association with pachytene piRNA precursors and target mRNAs.
Xiaoqinglong decoction (XQLD) has been used for centuries in Asia to effectively treat patients with chronic obstructive pulmonary disease (COPD). However, its mechanisms remain unknown. To elucidate this problem, we analyzed the effects of XQLD on gene expressions profiles in COPD rats. In the study, 20 male Wistar rats were injected with lipopolysaccharide (LPS), exposed to cigarette smoke and kept at −20°C for 5 min/day for a successive 8 days to establish COPD animals. Trachea ultramicrostructure and histomorphology were observed to determine whether these models were established successfully. Gene expression profiles were detected using cDNA microarrays. We found 56 differentially expressed genes associated with COPD progression, including 32 up-regulated genes and 24 down-regulated genes. These genes were confirmed to be involved in immune and inflammation reactions, metabolism, cell transportation and the cell cycle, signal transduction and gene regulation. Comparison of gene expression between the therapy group and control group showed that there were only 11 differentially expressed genes, including 5 up-regulated genes and 6 down-regulated genes. We concluded that XQLD had therapeutic effects in COPD rats by affecting gene expression. Pharmacological or targeted expression of some genes might be found useful as novel therapy in COPD management.
The present study investigated the effect of the VEGF165 gene on adhesion, migration, and proliferation of endothelial progenitor cells (EPCs) derived from peripheral blood of rabbits. Peripheral blood mononuclear cells were isolated from rabbits by density gradient centrifugation with Ficoll-Plaque Plus. EPCs were characterized by immunofluorescence and immunostaining. A pcDNA 3.0-hVEGF165 expression vector was constructed and EPCs were transfected with the pcDNA 3.0-hVEGF165 gene. The EPCs derived from peripheral blood of rabbits were successfully transfected with pcDNA 3.0-hVEGF165. ELISA showed that the expression of VEGF165 increased significantly in the EPCs transfected with the hVEGF165 gene compared to control cells. Compared to control EPCs, EPCs transfected with the hVEGF165 gene had significantly enhanced adhesion, migration, and proliferative ability in vitro.
Deep hypothermic circulatory arrest (DHCA) with retrograde cerebral perfusion (RCP) under high central venous pressure (CVP) is often used in aortic arch surgery under cardiopulmonary bypass (CPB). We hypothesized that DHCA with RCP under high CVP causes cerebral vascular compression because of increased perivascular pressure due to extravasation of fluid into intracranial tissue. In a retrospective study, we evaluated the pulsatility index (PI) and resistance index (RI) of the internal carotid arteries (ICA) and external carotid arteries (ECA) before and after CPB in 15 patients who underwent DHCA/RCP (group 1) and 17 patients who underwent regular CPB without DHCA/RCP (group 2). Both indices are known to reflect vascular resistance distal to the measurement point. The PI and RI of the ICA increased significantly after the procedure in group 1 but did not change in group 2. The PI and RI of the ECA did not change in either group. In group 1, the rate of increase in PI and RI correlated with the duration of RCP, which was significantly higher in patients who had postoperative delirium than in patients who did not experience postoperative delirium. As increases in PI/RI after DHCA/RCP occurred only in the ICA, we concluded that the changes were due to compression of vessels as a result of increased perivascular pressure. The greater increase in the PI/RI in patients who experienced postoperative delirium indicates that increased perivascular pressure plays a role in the occurrence of postoperative delirium after DHCA/RCP.