Keratinocyte growth factor (KGF) induces rapid and transient hyperplasia of alveolar epithelial type II cells. We sought to determine components of the apoptotic process involved in the resolution of this hyperplasia and the fate of the apoptotic cells. Rats received intrabronchial instillation of 5 mg KGF/kg body weight or diluent. Lungs were fixed 1, 2, 3, 5, and 7 days later. Apoptosis was identified by TdT-mediated dUTP nick-end labeling (TUNEL), double-labeling for TUNEL and the type II cell marker MNF116, and electron microscopy. Fas, FasL, Bax, Bcl-2, and pro- and active caspase-3 were studied by immunohistochemistry. Changes were quantified by stereology. Cell type specificity was investigated by immunofluorescence double staining. Type II cells exhibited Fas, FasL, Bcl-2, and procaspase-3 irrespective of treatment and time. Immunoelectron microscopy revealed Fas at the apical type II cell membrane. Bax staining was prominent in controls (45-95% of type II cell surface fraction), markedly decreased during hyperplasia at days 2 (20-40%) and 3 (0-10%), and reappeared at day 7 (25-45%) when apoptosis was prominent. Remnants of apoptotic type II cells were incorporated in membrane-bound vacuoles of type II cell neighbors as well as alveolar macrophages. The results indicate that type II cells can enter the Fas/FasL/caspase-3 pathway regulated by Bax and Bcl-2. High Bcl-2:Bax levels favor type II cell survival and a low rate of apoptosis during hyperplasia. Low Bcl-2:Bax levels favor type II cell apoptosis during resolution. Because of time-dependent changes that occur within a short time, the KGF-treated rat lung provides a useful in vivo model to investigate apoptosis in the context of tissue remodeling and repair. 相似文献
To investigate the effects of Lycium barbarum polysaccharide (LBP) on pathological symptoms and behavioral deficits in a Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) mouse model. The therapeutic effects of LBP were monitored with an Open field test, a Rotarod test and a Morris water maze test. We also investigated the mechanisms with qRT-PCR and Western blotting analyses. After a relatively short-term LBP treatment, the total distance and walking time of PD mice significantly increased. The staying duration on the rod of PD mice increased in the Rotarod test. LBP can up-regulate levels of SOD2, CAT and GPX1 and inhibit the abnormal aggregation of α-synuclein induced by MPTP. LBP treatment can also up-regulate the phosphorylation of AKT and mTOR, and may play its protective role by activating the PTEN/AKT/mTOR signaling axis. These results suggest that LBP can effectively alleviate the degeneration in the nigrostriatal system induced by MPTP treatment. It may be a potential candidate for the treatment of Parkinson’s disease. 相似文献
Soybean is a leguminous crop that provides oil and protein. Exploring the genomic signatures of soybean evolution is crucial for breeding varieties with improved adaptability to environmental extremes. We analyzed the genome sequences of 2,214 soybeans and proposed a soybean evolutionary route, i.e., the expansion of annual wild soybean (Glycine soja Sieb. & Zucc.) from southern China and its domestication in central China, followed by the expansion and local breeding selection of its landraces (G. max (L.) Merr.). We observed that the genetic introgression in soybean landraces was mostly derived from sympatric rather than allopatric wild populations during the geographic expansion. Soybean expansion and breeding were accompanied by the positive selection of flowering time genes, including GmSPA3c. Our study sheds light on the evolutionary history of soybean and provides valuable genetic resources for its future breeding.
Recent studies suggest that paired box 5 (PAX5) is down‐regulated in multiple tumours through its promoter methylation. However, the role of PAX5 in non‐small cell lung cancer (NSCLC) pathogenesis remains unclear. The aim of this study is to examine PAX5 expression, its methylation status, biological functions and related molecular mechanism in NSCLC. We found that PAX5 was widely expressed in normal adult tissues but silenced or down‐regulated in 88% (7/8) of NSCLC cell lines. PAX5 expression level was significantly lower in NSCLC than that in adjacent non‐cancerous tissues (P = 0.0201). PAX5 down‐regulation was closely associated with its promoter hypermethylation status and PAX5 expression could be restored by demethylation treatment. Frequent PAX5 promoter methylation in primary tumours (70%) was correlated with lung tumour histological types (P = 0.006). Ectopic expression of PAX5 in silenced lung cancer cell lines (A549 and H1975) inhibited their colony formation and cell viability, arrested cell cycle at G2 phase and suppressed cell migration/invasion as well as tumorigenicity in nude mice. Restoration of PAX5 expression resulted in the down‐regulation of β‐catenin and up‐regulation of tissue inhibitors of metalloproteinase 2, GADD45G in lung tumour cells. In summary, PAX5 was found to be an epigenetically inactivated tumour suppressor that inhibits NSCLC cell proliferation and metastasis, through down‐regulating the β‐catenin pathway and up‐regulating GADD45G expression. 相似文献
The antibiotic-resistant Klebsiella pneumoniae (Kp) has become a significant crisis in treating pneumonia. Low-frequency ultrasound (LFU) is promising to overcome the obstacles. Mice were infected with bioluminescent Kp Xen39 by intratracheal injection to study the therapeutic effect of LFU in combination with antibiotics. The counts per second (CPS) were assessed with an animal biophoton imaging system. Bacterial clearance, histopathology, and the concentrations of cytokines were determined to evaluate the therapeutic effect. LC–MS/MS was used to detect the distribution of antibiotics in the lung and plasma. LFU in combination with meropenem (MEM) or amikacin (AMK) significantly improved the behavioural state of mice. The CPS of the LFU combination group were more significantly decreased compared with those of the antibiotic alone groups. The average colony-forming units of lung tissue in the LFU combination groups were also lower than those of the antibiotic groups. Although no significant changes of cytokines (IL-6 and TNF-α) in plasma and bronchoalveolar lavage fluid were observed, LFU in combination with antibiotics showed less inflammatory damage from histopathological results compared with the antibiotic-alone groups. Moreover, 10 min of LFU treatment promoted the distribution of MEM and AMK in mouse lung tissue at 60 and 30 min, respectively, after dosage. LFU could enhance the effectiveness of MEM and AMK in the treatment of Kp-induced pneumonia, which might be attributed to the fact that LFU could promote the distribution of antibiotics in lung tissue and reduce inflammatory injury. 相似文献
The present study investigated the abundance, richness, diversity, and community composition of denitrifiers (based on nirS and nosZ genes) in the stratified water columns and sediments in eutrophic Dianchi Lake and mesotrophic Erhai Lake using quantitative PCR assay and high-throughput sequencing analysis. Both nirS- and nosZ denitrifiers were detected in waters of these two lakes. Surface water showed higher nosZ gene density than bottom water, and Dianchi Lake waters had larger nirS gene abundance than Erhai Lake waters. The abundance of sediment nirS- and nosZ denitrifiers in Dianchi Lake was larger than that in Erhai Lake. nirS richness and diversity and nosZ richness tended to increase with increasing sediment layer depth in both lakes. The distinct structure difference of sediment nirS- and nosZ denitrifier communities was found between in Dianchi Lake and Erhai Lake. These two lakes also differed greatly in water denitrifier community structure. Moreover, phylogenetic analysis indicated the presence of several different groups of nirS- or nosZ denitrifiers in both lakes. The novel nirS denitrifiers were abundant in both Dianchi Lake and Erhai Lake, while most of the obtained nosZ sequences could be affiliated with known genera.
Crop breeding during the Green Revolution resulted in high yields largely due to the creation of plants with semi-dwarf architectures that could tolerate high-density planting. Although semi-dwarf varieties have been developed in rice, wheat and maize, none was reported in soybean(Glycine max), and few genes controlling plant architecture have been characterized in soybean. Here, we demonstrate that the auxin efflux transporter PINFORMED1(GmPIN1), which determines polar auxin transport, regulate... 相似文献
Alicyclobacillus are spoilage microbes of many juice products, but contamination of kiwi products by Alicyclobacillus is seldom reported. This study aims to investigate the whole production line of kiwi products in China to assess the potential risk of their contamination. A total of 401 samples from 18 commercial products, 1 processing plant and 16 raw material orchards were tested, and 76 samples were positive, from which 76 strains of microbes were isolated and identified as 4 species of Alicyclobacillus, including Alicyclobacillus acidoterrestris, Alicyclobacillus contaminans, Alicyclobacillus herbarius and Alicyclobacillus cycloheptanicus, and another 9 strains as 3 species of Bacillus by sequencing of their 16S rDNA. Through phylogenetic tree construction and RAPD-PCR amplification, it was found that there exist genotypic diversities to some extent among these isolates. Four test strains (each from one species of the 4 Alicyclobacillus species isolated in this study) could spoil pH adjusted kiwi fruit juice and some commercial kiwi fruit products with producing guaiacol (11–34 ppb). 相似文献