p300/p53/Smad3 pathway involved in aging-related atrial fibrosis in human atrial fibroblasts

AIM To investigate the role of p300 in aging-related atrial fibrosis in human atrial fibroblasts （HAFs） and its potential mechanism. METHODS HAFs were obtained from human left atrial tissue, and the senescence model was established by cell passage. Senescence-associated β-galactosidase （SA-β-Gal） staining was used to detect the cell senescence, and Western blot was used to determine the protein levels of p300, p53, Smad3 and other senescence and fibrosis associated proteins in HAFs. RESULTS Compared to passage 3 HAFs, the proportion of senescent cells, and the protein levels of p300, p53, p-Smad3 and other senescence and fibrosis associated proteins were increased in HAFs at passage 7 and 11 （P<0.05）. After treated with curcumin （a p300 inhibitor） or transfection with p300 small-hairpin （sh） RNA plasmid, the protein levels of p300, and the senescence and fibrosis associated proteins were decreased in HAFs at passage 7（P<0.05）. Up-regulation of p300 by transfection with p300 over-expression plasmid increased the protein levels of p53, Smad3 and MMP-2 in HAFs at passage 3 （P<0.05）. CONCLUSION p300/p53/Smad3 signaling pathway plays an important role in aging-related atrial fibrosis in HAFs.     

Effects of naringenin on PI3K/AKT signaling pathway and endoplasmic reticulum stress and its related apoptotic pathways in rats with myocardial ischemia/reperfusion injury

AIM To observe the effect of naringenin on cardiac injury in ischemia/reperfusion （I/R） rats, and to explore whether the role of naringenin is involved in PI3K/AKT signaling pathway and endoplasmic reticulum stress and its related apoptotic pathways. METHODS SD rats （n=48） were randomly divided into sham operation （sham） group, model （I/R） group, naringenin treatment （NAR） group and naringenin+LY294002 （NL） group. Myocardial I/R injury model was prepared by ligation of left anterior descending coronary artery of rats for 30 min followed by reperfusion for 120 min. After reperfusion, the serum levels of cardiac troponin I （cTnI） was measured by ELISA. HE staining, TTC staining and TUNEL staining were used to detect the myocardial histopathological changes, myocardial infarction area and myocardial cell apoptotic rate. The mRNA levels of endoplasmic reticulum stress-related indicators glucose-regulated protein 78 （GRP78）, C/EBP homologous protein （CHOP） and caspase-12 were detected by RT-qPCR. The protein levels of cleaved caspase-3, GRP78, CHOP, caspase-12, p-PI3K and p-AKT were determined by Western blot. RESULTS Compared with I/R group, the serum content of cTnI, myocardial pathological damage, myocardial infarction area and myocardial cell apoptotic rate were significantly reduced （P<0.05）, the protein levels of cleaved caspase-3, GRP78, CHOP and caspase-12 were decreased （P<0.05）, and the protein levels of p-PI3K and p-AKT were increased in NAR group （P<0.05）. LY294002 attenuated the protective effect of naringenin to some extent. CONCLUSION Naringenin reduces myocardial I/R injury in rats possibly by activating PI3K/AKT signaling pathway and subsequently regulating endoplasmic reticulum stress and its related apoptotic pathways.     

The Exploitation of Nematode-Responsive Plant Genes in Novel Nematode Control Methods

The molecular interactions between plants and sedentary nematodes are undergoing intense study, not only for reasons of fundamental research but also for the potential benefits to agriculture. The present technology allows the transformation of an increasing number of crop plants, providing new ways to introduce resistance against plant-parasitic nematodes. The ability of sedentary nematodes to induce specialized feeding sites in plant roots is one of the most fascinating aspects of this host–parasite interaction. Molecular approaches have been initiated to identify and characterize plant genes altered in expression after infection by sedentary nematodes. The results obtained indicate that many genes indeed become up-regulated upon nematode infection. Surprisingly, several so-called constitutive promoters that are normally used to achieve high expression in plant cells are completely ‘silenced’ in the feeding sites within days after nematode infection. Generally, there are two options available for the genetic engineering of nematode resistance: the synthesis of anti-nematode proteins or the localized production of a cytotoxic protein that interferes with the development of feeding cells. Nematode-induced promoters are very useful for the production by plants of sufficiently high levels of anti-nematode proteins at feeding sites. Alternatively, interfering with feeding-cell development is somewhat similar to the hypersensitive response evoked by nematodes in a naturally resistant plant. Here, destruction of specific plant cells can be achieved by the localized expression of a cytotoxin such as barnase, a potent ribonuclease. This approach, however, calls for a highly specific ‘non-leaky’ promoter, which is active only in the feeding cells. Another possibility is to use a two-component system, where the leakiness of the promoter in other tissues is counterbalanced by the constitutive expression of a neutralizing gene.     

Synthesis and Anthelmintic Activity of 7-Hydroxy- 5-oxo-5H-thieno[3,2-b]pyran-6-carboxanilides and -6-thiocarboxanilides

7-Hydroxy-5-oxo-5H-thieno[3,2-b]pyran-6-carboxanilides and -6-thio-carboxanilides represent a novel series of anthelmintic compounds, with broad-spectrum activity against important parasitic nematodes in sheep and dogs. In particular, an improved efficacy against Trichostrongylus colubriformis in sheep over the related 3-carbamoyl-4-hydroxycoumarins has been noted. New synthetic routes to the key intermediate, 7-hydroxythieno[3,2-b]pyran-5-one, have been developed.     

半乳凝素-3在鼠发育中的生物学作用研究进展

半乳凝素-3是在鼠发育过程中产生的重要影响因素之一。半乳凝素-3在鼠骨骼、甲状腺、气管及吞噬细胞等组织细胞中表达水平的高低,可作为鼠发育过程中生理指标正常与否的检测标准。半乳凝素-3还与自身免疫性疾病、癌症等病理学过程的发生发展有着密切的内在联系,呈现“双刃剑”的作用。文章就半乳凝素-3在动物发育中表达的生物学作用进行综述。     

果蔗芽段和芽片育苗移栽新技术

利用黔糖3号果蔗蔗茎梢部芽段和芽片作种源,经不同调节剂催芽促根、杀菌剂灭菌消毒的复式浸种处理后,进行土壤浅层密植育苗技术试验。结果表明:用蔗茎梢部芽段复式浸种处理育苗移栽的综合农艺性状优于用芽片育苗移栽,其中,又以乙烯利浸种处理的芽段表现较好,出苗时间仅9 d,出苗率达97.5%,分蘖率为246.3%,成茎率为96%,且具有长势旺、抗病强的优势,在同批试验中综合性能最优。     

Antiplatelet and Antithrombotic Effects of Isaridin E Isolated from the Marine-Derived Fungus via Downregulating the PI3K/Akt Signaling Pathway

Isaridin E, a cyclodepsipeptide isolated from the marine-derived fungus Amphichorda felina (syn. Beauveria felina) SYSU-MS7908, has been demonstrated to possess anti-inflammatory and insecticidal activities. Here, we first found that isaridin E concentration-dependently inhibited ADP-induced platelet aggregation, activation, and secretion in vitro, but did not affect collagen- or thrombin-induced platelet aggregation. Furthermore, isaridin E dose-dependently reduced thrombosis formation in an FeCl₃-induced mouse carotid model without increasing the bleeding time. Mechanistically, isaridin E significantly decreased the ADP-mediated phosphorylation of PI3K and Akt. In conclusion, these results suggest that isaridin E exerts potent antithrombotic effects in vivo without increasing the risk of bleeding, which may be due to its important role in inhibiting ADP-induced platelet activation, secretion and aggregation via the PI3K/Akt pathways.     

Effects of tris(1,3-dichloro-2-propyl) phosphate on epididymal sperm parameters in adult male rats

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is widely used as a flame retardant and is known to exhibit anti-androgenic effects in vitro and in vivo. To assess the reproductive toxicity potency of TDCIPP, we investigated the effects of 7 days of TDCIPP oral administration on epididymal sperm motion and concentration in adult male Wistar–Imamichi rats. Thirty-five days after the final administration, sperm parameters were evaluated by computer-assisted sperm analysis. Results showed that sperm swimming progression and vigor and sperm concentration in TDCIPP-treated rats were unexpectedly higher than those in control rats. TDCIPP did not significantly affect the percentage of motile sperms or sperm swimming pattern. These results contribute to the understanding of the biological effects of TDCIPP.     

A 13CO2 Enrichment Experiment to Study the Synthesis Pathways of Polyunsaturated Fatty Acids of the Haptophyte Tisochrysis lutea

The production of polyunsaturated fatty acids (PUFA) in Tisochrysis lutea was studied using the gradual incorporation of a ¹³C-enriched isotopic marker, ¹³CO₂, for 24 h during the exponential growth of the algae. The ¹³C enrichment of eleven fatty acids was followed to understand the synthetic pathways the most likely to form the essential polyunsaturated fatty acids 20:5n-3 (EPA) and 22:6n-3 (DHA) in T. lutea. The fatty acids 16:0, 18:1n-9 + 18:3n-3, 18:2n-6, and 22:5n-6 were the most enriched in ¹³C. On the contrary, 18:4n-3 and 18:5n-3 were the least enriched in ¹³C after long chain polyunsaturated fatty acids such as 20:5n-3 or 22:5n-3. The algae appeared to use different routes in parallel to form its polyunsaturated fatty acids. The use of the PKS pathway was hypothesized for polyunsaturated fatty acids with n-6 configuration (such as 22:5n-6) but might also exist for n-3 PUFA (especially 20:5n-3). With regard to the conventional n-3 PUFA pathway, Δ6 desaturation of 18:3n-3 appeared to be the most limiting step for T. lutea, “stopping” at the synthesis of 18:4n-3 and 18:5n-3. These two fatty acids were hypothesized to not undergo any further reaction of elongation and desaturation after being formed and were therefore considered “end-products”. To circumvent this limiting synthetic route, Tisochrysis lutea seemed to have developed an alternative route via Δ8 desaturation to produce longer chain fatty acids such as 20:5n-3 and 22:5n-3. 22:6n-3 presented a lower enrichment and appeared to be produced by a combination of different pathways: the conventional n-3 PUFA pathway by desaturation of 22:5n-3, the alternative route of ω-3 desaturase using 22:5n-6 as precursor, and possibly the PKS pathway. In this study, PKS synthesis looked particularly effective for producing long chain polyunsaturated fatty acids. The rate of enrichment of these compounds hypothetically synthesized by PKS is remarkably fast, making undetectable the ¹³C incorporation into their precursors. Finally, we identified a protein cluster gathering PKS sequences of proteins that are hypothesized allowing n-3 PUFA synthesis.     

基于三参数最佳动力性换档规律的制定与仿真研究

通过对汽车自动变速器三参数最佳动力性换档规律的研究,找出最佳动力性换档规律产生循环换档的原因,提出一种改进的动态三参数最佳动力性换档规律。应用MATLAB/SIMIULINK建立的换档规律仿真模型对改进的换档规律进行仿真分析。仿真表明经改进的动态三参数最佳动力性换档规律可以减少循环换档,使汽车获得更好的行驶性能。