miR-29a attenuates cardiac hypertrophy through inhibition of PPARδ expression

Although cardiac hypertrophy is widely recognized as a risk factor that leads to cardiac dysfunction and, ultimately, heart failure, the complex mechanisms underlying cardiac hypertrophy remain incompletely characterized. The nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ) is involved in the regulation of cardiac lipid metabolism. Here, we describe a novel PPARδ-dependent molecular cascade involving microRNA-29a (miR-29a) and atrial natriuretic factor (ANF), which is reactivated in cardiac hypertrophy. In addition, we identify a novel role of miR-29a, in which it has a cardioprotective function in isoproterenol hydrochloride-induced cardiac hypertrophy by targeting PPARδ and downregulating ANF. Finally, we provide evidence that miR-29a reduces the isoproterenol hydrochloride-induced cardiac hypertrophy response, thereby underlining the potential clinical relevance of miR-29a in which it may serve as a potent therapeutic target for heart hypertrophy treatment.     

Flooding-induced membrane damage, lipid oxidation and activated oxygen generation in corn leaves

Flooding effects on membrane permeability, lipid peroxidation and activated oxygen metabolism in corn (Zea mays L.) leaves were investigated to determine if activated oxygens are involved in corn flooding-injury. Potted corn plants were flooded at the 4-leaf stage in a controlled environment. A 7-day flooding treatment resulted in a significant increase in chlorophyll breakdown, lipid peroxidation (malondialdehye content), membrane permeability, and the production of superoxide (O ₂ ^- ) and hydrogen peroxide (H₂O₂) in corn leaves. The effects were much greater in older leaves than in younger ones. Spraying leaves with 8-hydroxyquinoline (an O ₂ ^- scavenger) and sodium benzoate (an .OH scavenger) reduced the oxidative damage and enhanced superoxide dismutase (SOD) activity. A short duration flooding treatment elevated the activities of SOD, catalase, ascorbate peroxidase (AP), and glutathione reductase (GR), while further flooding significantly reduced the enzyme activities but enhanced the concentrations of ascorbic acid and reduced form glutathione (GSH). It was noted that the decline in SOD activity was greater than that in H₂O₂ scavengers (AP and GR). The results suggested that O ₂ ^- induced lipid peroxidation and membrane damage, and that excessive accumulation of O ₂ ^- is due to the reduced activity of SOD under flooding stress.     

Studies on the Wound-Induced CN-Resistant Respiration in Potato Tuber Slices

The respiration of fresh potato slices was sensitive to CN-, and was not inhibited by m-CLAM in the presence or absence of CN-. By contrast, the wound-induced respiration of slices, incubated in air for 24 hours, was not only relatively resistant to CN-, but also markedly inhibited by m-CLAM in the presence or absence of CN-. When m-CLAM and CN- were added togather, the inhibitory effect was higher than that of them when used separately. The observations indicated that the alternate path is operative in aged potato slices. The data determined by the method of m-CLAM titration showed that the actual contribution of alternate path and cytochrome path in aged potato slices was approximately 28% and 54% of the total respiration respectively in the absence of CN-. When the cytochrome path was inhibited by CN-, the maximal capacity of alternate path (Valt was higher than the actual contribution of them (ρ·Valt). The increased contribution of alternate path in presence of CN- might be thought to indicate that there is a diversion of electron flux from the cytochrome path to the alternate path. When the respiratory flux of aged slices was reduced by treatment with iodoacetate and malonate, the proportions of respiration inhibited by CN- and m-CLAM respectively were not changed.     

抗癌药对黑胸大蠊淋巴细胞和生殖细胞核结构的损伤

噻替派浓度为0.1%、0.3%、0.5%时,黑胸大蠊精母细胞染色体断裂和裂隙率分别为6.3%、 10.5%和14.2%,显著地高于对卵母细胞的影响;和雄虫外周血淋巴细胞微核率呈平行关系,随微核率增多而增加。5-氟尿嘧啶浓度为0.1%、0.3%和0.5%时,卵母细胞染色体断裂和裂隙率分别为3.5%、9.8%和16.2%,和雌虫外周血淋巴细胞微核率呈平行关系,随微核率增多而增加,而对雄虫生殖细胞影响不显著。 Abstract:0.1%,0.3%,0.5% Thio-TEPA induced 6.3%,10.5% and 14.2% chromosome break or gap in spermatocyte of cockroach respectively.This was markedly higher than those in oocyte.In doses from 0.1 to 0.5 Tho-TEPA the frequency of micronucleus increased parallely with nuclear damage.0.1%,0.3%,0.5% 5-fluorouracil induced 3.5%,9.8%,16.2% chromosome break or gap in oocytes respectively.This was paralled with the frequency of micronucleus in lymphocytes of the female.5-fluorouracil showed not marked effect on spermatocyte.     

Electro-Enhancement of the Formation of Cell Clusters from Protoplasts of Tritium aestivum

Under the treatment of 0.5—2.0 μA direct electric currents, the number of cell clusters derived from wheat (Triticum aestivum L. ) protoplasts was dramatically increased. The effect was related to the time-length of the treatments, and appeared only when the timelength was more than the threshold. The threshold time decreased with increase of electric current intensity. The effect was not related to the starting time of the treatments in culture of the protoplasts.     

5-Azacytidine facilitates osteogenic gene expression and differentiation of mesenchymal stem cells by alteration in DNA methylation

Mesenchymal stem cells (MSCs) are considered to be one of the most promising therapeutic cell sources as they encompass a plasticity of multiple cell lineages. The challenge in using these cells lies in developing well-defined protocols for directing cellular differentiation to generate a desired lineage. In this study, we investigated the effect of 5-azacytidine, a DNA demethylating agent, on osteogenic differentiation of MSCs. The cells were exposed to 5-azacytidine in culture medium for 24 h prior to osteogenic induction. Osteogenic differentiation was determined by several the appearance of a number of osteogenesis characteristics, including gene expression, ALP activity, and calcium mineralization. Pretreatment of MSCs with 5-azacytidine significantly facilitated osteogenic differentiation and was accompanied by hypomethylation of genomic DNA and increased osteogenic gene expression. Taking dlx5 as a representative, methylation alterations of the “CpG island shore” in the promoter caused by 5-azacytidine appeared to contribute to osteogenic differentiation.     

Vaccinia virus infection attenuates innate immune responses and antigen presentation by epidermal dendritic cells

Langerhans cells (LCs) are antigen-presenting cells in the skin that play sentinel roles in host immune defense by secreting proinflammatory molecules and activating T cells. Here we studied the interaction of vaccinia virus with XS52 cells, a murine epidermis-derived dendritic cell line that serves as a surrogate model for LCs. We found that vaccinia virus productively infects XS52 cells, yet this infection displays an atypical response to anti-poxvirus agents. Whereas adenosine N1-oxide blocked virus production and viral protein synthesis during a synchronous infection, cytosine arabinoside had no effect at concentrations sufficient to prevent virus replication in BSC40 monkey kidney cells. Vaccinia virus infection of XS52 cells not only failed to elicit the production of various cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-10, IL-12 p40, alpha interferon (IFN-alpha), and IFN-gamma, it actively inhibited the production of proinflammatory cytokines TNF-alpha and IL-6 by XS52 cells in response to exogenous lipopolysaccharide (LPS) or poly(I:C). Infection with a vaccinia virus mutant lacking the E3L gene resulted in TNF-alpha secretion in the absence of applied stimuli. Infection of XS52 cells or BSC40 cells with the DeltaE3L virus, but not wild-type vaccinia virus, triggered proteolytic decay of IkappaBalpha. These results suggest a novel role for the E3L protein as an antagonist of the NF-kappaB signaling pathway. DeltaE3L-infected XS52 cells secreted higher levels of TNF-alpha and IL-6 in response to LPS and poly(I:C) than did cells infected with the wild-type virus. XS52 cells were productively infected by a vaccinia virus mutant lacking the K1L gene. DeltaK1L-infected cells secreted higher levels of TNF-alpha and IL-6 in response to LPS than wild-type virus-infected cells. Vaccinia virus infection of primary LCs harvested from mouse epidermis was nonpermissive, although a viral reporter protein was expressed in the infected LCs. Vaccinia virus infection of primary LCs strongly inhibited their capacity for antigen-specific activation of T cells. Our results highlight suppression of the skin immune response as a feature of orthopoxvirus infection.     

A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis

Ca(2+) binding to synaptotagmin 1 triggers fast exocytosis of synaptic vesicles that have been primed for release by SNARE-complex assembly. Besides synaptotagmin 1, fast Ca(2+)-triggered exocytosis requires complexins. Synaptotagmin 1 and complexins both bind to assembled SNARE complexes, but it is unclear how their functions are coupled. Here we propose that complexin binding activates SNARE complexes into a metastable state and that Ca(2+) binding to synaptotagmin 1 triggers fast exocytosis by displacing complexin from metastable SNARE complexes. Specifically, we demonstrate that, biochemically, synaptotagmin 1 competes with complexin for SNARE-complex binding, thereby dislodging complexin from SNARE complexes in a Ca(2+)-dependent manner. Physiologically, increasing the local concentration of complexin selectively impairs fast Ca(2+)-triggered exocytosis but retains other forms of SNARE-dependent fusion. The hypothesis that Ca(2+)-induced displacement of complexins from SNARE complexes triggers fast exocytosis accounts for the loss-of-function and gain-of-function phenotypes of complexins and provides a molecular explanation for the high speed and synchronicity of fast Ca(2+)-triggered neurotransmitter release.     

Quantifying ecosystem service trade‐offs for plantation forest management to benefit provisioning and regulating services

There is increasing interest worldwide regarding managing plantation forests in a manner that maintains or improves timber production, enhances ecosystem services, and promotes long‐term sustainability of forest resources. We selected the Gan River Basin, the largest catchment of Poyang Lake and a region with a typical plantation distribution in South China, as the study region. We evaluated and mapped four important forest ecosystem services, including wood volume, carbon storage, water yield, and soil retention at a 30 × 30 m resolution, then quantified their trade‐offs and synergies at the county and subwatershed scales. We found that the wood volume and carbon storage services, as well as the soil retention and water yield, exhibited synergistic relationships. However, the carbon storage displayed a trade‐off relationship with the water yield. Additionally, we compared the beneficial spatial characteristics among dominant species in the study region. The results showed that the Chinese fir forest and the pine forest exhibited lower overall benefits than natural forests including the broad‐leaved forest and the bamboo forest. To propose a suitable management strategy for the study region, method of spatial cluster analysis was used based on the four eco‐services at the subwatershed scale. The basin was divided into four management groups instead of treating the region as a homogenous management region. Finally, we proposed more specific and diverse management strategies to optimize forest benefits throughout the entire region.     

Phytoestrogen α-zearalanol antagonizes homocysteine-induced imbalance of nitric oxide/endothelin-1 and apoptosis in human umbilical vein endothelial cells

Although the issue of estrogen replacement therapy on cardiovascular health is debatable, it has presumable benefits for endothelial function in postmenopausal women. However, the fear of breast cancer has intimidated women contemplating estrogen treatment and limited its long-term application. An effective alternative remedy not associated with breast carcinoma is in serious demand. This study was designed to examine the effect of phytoestrogen alpha-zearalanol (alpha-ZAL) and 17beta-estradiol (E2) on nitric oxide (NO) and endothelin (ET)-1 levels, apoptosis, and apoptotic enzymes in human umbilical vein endothelial cells (HUVEC). HUVEC cells were challenged for 24 h with homocysteine (10-3 M), an independent risk factor for a variety of vascular diseases, in the presence of alpha-ZAL or E2 (10-9 to 10-6 M). Release of NO and ET-1 were measured with enzyme immunoassay. Apoptosis was evaluated by fluorescence-activated cell sorter analysis. Expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), Bax, and Bcl-2 were determined using Western blot. NOS activity was evaluated with 3H-arginine to 3H-citrulline conversion. Our results indicated that Hcy significantly reduced NO production, NOS activity, enhanced ET-1/NO ratio and apoptosis, upregulated iNOS, Bax, and downregulated eNOS, Bcl-2 expression. These effects were significantly attenuated by alpha-ZAL and E2. ZAL displayed a similar potency compared with E2 in antagonizing Hcy-induced effects. In summary, these results suggested that alpha-ZAL may effectively preserve Hcy-induced decrease in NO, increase in ET-1/NO ratio and apoptosis, which contributes to protective effects of phytoestrogens on endothelial function.