Congestive heart failure in COX2 deficient rats

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin (PG) formation by targeting cyclooxygenase (COX) 1 and 2.Long-term use of NSAIDs that selectively inhibit COX2 increases the risk for thrombotic events,cardiac failure,and hypertension.However,the underlying mechanisms remain unclear.In this study,COX1- and COX2-deficient rats were created via Cas9/RNA-mediated gene targeting.DNA genotyping and Western blot analysis confirmed successful generation of COX1~(-/-)and COX2~(-/-)rats.Adult COX1~(-/-)rats grew normally,while more than 70%of COX2~(-/-)rats after wean died within 2 months.Echocardiography showed markedly reduced left ventricular ejection fraction and fractional shortening in adult COX2~(-/-)rats compared to those in wildtype (WT) controls.Histological analysis revealed accumulation of inflammatory cells and severe interstitial and perivascular fibrosis in COX2~(-/-)cardiac tissues.Moreover,cardiac ATP and acetyl-Co A production was dramatically decreased in COX2~(-/-)rats.Consistently,the expression of genes related to mitochondrial oxidation,such as those that encode for subunits of pyruvate dehydrogenase complex and acyl Co A dehydrogenases,were downregulated,while glycolytic hexokinase 1 (HK1) was upregulated in COX2~(-/-)heart tissues.These observations indicate that COX2-deficient rats developed spontaneously heart failure,likely as a result of dysregulated cardiac energy metabolism.     

Th2 polarization in target organs is involved in the alleviation of pathological damage mediated by transplanting granulocyte colony-stimulating factor-primed donor T cells

Acute graft-versus-host disease(a GVHD) is caused by allo-activated donor T cells infiltrating target organs. As a regulator of immune function, granulocyte colony-stimulating factor(G-CSF) has been demonstrated to relieve the a GVHD reaction.However, the role of G-CSF-primed donor Tcells in specific target organs is still unknown. In this study, we employed a classical MHC-mismatched transplantation mouse model(C57BL/6 into BALB/c) and found that recipient mice transplanted with GCSF-primed T cells exhibited prolonged survival compared with that of the PBS-treated group. This protective function against GVHD mediated by G-CSF-primed donor T cells was further confirmed by decreased clinical and pathological scores in this a GVHD mouse model, especially in the lung and gut. Moreover, we found that Tcells polarized towards Th2 cells and regulatory T cells were increased in specific target organs. In addition, G-CSF treatment inhibited inducible co-stimulator(ICOS) expression and increased the expression of tolerance-related genes in recipient mice. Our study provides new insight into the immune regulatory effects of G-CSF on T cell-mediated a GVHD, especially for its precise regulation in GVHD target organs.     

A cyclin protein governs the infectious and sexual life cycles of Cryptococcus neoformans

Science China Life Sciences - Cell cycle is a fundamental process underlying growth and development in evolutionarily diverse organisms, including fungi. In human fungal pathogens, cell cycle...     

First record of organic-walled microfossils from the Tonian Shiwangzhuang Formation of the Tumen Group in western Shandong,North China

Organic-walled microfossils offer important information on the biospheric evolution in pre-Cryogenian and provide biostratigraphic implications for many Proterozoic fossiliferous sequences that are poorly age constrained for the lack of reliable radiometric date. Recently, macroscopic carbonaceous compression fossils have been reported for the first time from the Tonian Shiwangzhuang Formation of the Tumen Group in western Shandong, North China. However, organic-walled microfossils have never been discovered from this formation up till now. To improve our knowledge about Proterozoic biodiversity in North China, we conducted a micropaleontological survey on the argillaceous limestone samples of the Shiwangzhuang Formation, which also contain macroscopic carbonaceous compression fossils, from the Baishicun section in Anqiu, western Shandong, North China. Our investigation shows that the Shiwangzhuang microfossil assemblage is dominated by smooth-walled sphaeromorphic acritarchs and cyanobacterium-like filaments and relatively low abundance of other acritarchs, including 16 taxa, such as Polysphaeroides filliformis, Ostiana microcystis, Simia annulare, ?Jacutianema sp., Arctacellularia tetragonala, Pellicularia tenera, Polythrichoides lineatus, and Navifusa actinomorpha. The Shiwangzhuang organic-walled microfossil assemblage, although consisting of long-ranging and not age diagnostic taxa, is consistent with a Tonian age suggested by macroscopic carbonaceous compression fossils, including the Chuaria-Tawuia and Sinosabellidites-Protoarenicola-Pararenicola assemblages, revealed from the same fossiliferous horizon of the Shiwangzhuang Formation and by organic-walled microfossil assemblage, including the late Mesoproterozoic to Tonian index fossil Trachyhystrichosphaera aimika, from the underlying Tongjiazhuang Formation. However, it is also worth noting that a Cryogenian or Ediacaran age cannot be completely excluded based just on the Shiwangzhuang microfossils because of their limited biostratigraphic utility.     

Nanoparticle formulation of mycophenolate mofetil achieves enhanced efficacy against hepatocellular carcinoma by targeting tumour-associated fibroblast

Hepatocellular carcinoma (HCC) is one of the most aggressive tumours with marked fibrosis. Mycophenolate mofetil (MMF) was well-established to have antitumour and anti-fibrotic properties. To overcome the poor bioavailability of MMF, this study constructed two MMF nanosystems, MMF-LA@DSPE-PEG and MMF-LA@PEG-PLA, by covalently conjugating linoleic acid (LA) to MMF and then loading the conjugate into polymer materials, PEG_5k-PLA_8k and DSPE- PEG_2k, respectively. Hepatocellular carcinoma cell lines and C57BL/6 xenograft model were used to examine the anti-HCC efficacy of nanoparticles (NPs), whereas NIH-3T3 fibroblasts and highly-fibrotic HCC models were used to explore the anti-fibrotic efficacy. Administration of NPs dramatically inhibited the proliferation of HCC cells and fibroblasts in vitro. Animal experiments revealed that MMF-LA@DSPE-PEG achieved significantly higher anti-HCC efficacy than free MMF and MMF-LA@PEG-PLA both in C57BL/6 HCC model and highly-fibrotic HCC models. Immunohistochemistry further confirmed that MMF-LA@DSPE-PEG dramatically reduced cancer-associated fibroblast (CAF) density in tumours, as the expression levels of alpha-smooth muscle actin (α-SMA), fibroblast activation protein (FAP) and collagen IV were significantly downregulated. In addition, we found the presence of CAF strongly correlated with increased HCC recurrence risk after liver transplantation. MMF-LA@DSPE-PEG might act as a rational therapeutic strategy in treating HCC and preventing post-transplant HCC recurrence.     

采自西藏和新疆的7种中国新记录植物

本文报道了6个中国被子植物新记录种及1个新记录亚种, 分别是采自西藏的灰滨藜(Atriplex pallida)、类球花藜(Blitum litwinowii)、滨藜状藜(Chenopodium atripliciforme)、土耳其针茅(Stipa turkestanica)、扁果岩蓼(Polygonum cognatum subsp. chitralicum)及新疆的宝格达黄芪(Astragalus baitagensis)和神香草叶千屈菜(Lythrum hyssopifolia), 观察了部分类群的微形态特征并提供了生境或形态图。凭证标本均存放于内蒙古大学植物标本馆(HIMC)。