Targeting NLRP3 inflammasome improved the neurogenesis and post-stroke cognition in a mouse model of photothrombotic stroke.

Post-stroke cognitive impairment (PSCI) severely affects the quality of a survivor's life, but its neurophysiological basis remains unknown. Neuroinflammation has been considered as an important contributor to PSCI, which could be induced or exacerbated by system inflammation. NACHT-LRR- and pyrin-domain-containing protein 3 (NLRP3) inflammasome is the most widely studied in the initiation of inflammation. Here, using a mouse model of photothrombotic stroke, we demonstrated that NLRP3 activation plays a critical role in PSCI. Intraperitoneal injection of the lipopolysaccharide-activated NLRP3 inflammasome, exacerbated the microglial activation and decreased the number of neurons, impaired the hippocampal neurogenesis, eventually aggravated PSCI. Intraperitoneal injection of MCC950 inhibited the NLRP3 activation, decreased the number of microglia, increased the number of neurons and promoted the hippocampal neurogenesis, eventually improved PSCI. Our results identified NLRP3 inflammasome as an important modifier of neuropathology in PSCI, which could be a could be a potential therapeutic target for PSCI treatment.

[Mechanism of 5'-to-3' degradation of eukaryotic and prokaryotic mRNA].

RNA degradation plays an important role in modulating gene expression and it affects multiple biological processes. There are three common degradation mechanisms of eukaryotic and prokaryotic mRNA: endonucleolytic, 5'-to-3' and 3'-to-5' exonucleolytic degradation. Differences do exist between the two kingdoms. For example, although the 5'-to-3' exoribonucleolytic degradation is the primary degradation mechanism of eukaryotic mRNA, it plays a minimal role in bacteria, and only in Gram-positive bacteria. Recently, novel RNA degradation mechanisms have been revealed, such as a new eukaryotic mRNA decapping mode mediated by 3'-uridylation and a new 3'-to-5' degradation pathway independent of exosome. These accumulating discoveries not only deepen the insight of mRNA degradation mechanisms, but also may contribute to the development of novel therapeutic drugs targeting parasites, viruses or cancer. In this review, we summarize the current knowledge of 5'-to-3' exonucleolytic degradation pathway of eukaryotic and prokaryotic mRNA, and its future therapeutic perspectives.

[A new target of antibacterial drugs: bacterial mRNA degradation pathways].

In bacteria, mRNA degradation plays an essential role, not only in recycling nucleotides but also in controlling gene expression in response to rapid changing growth conditions. In addition, many ribonucleases in this process can control pathogenesis by regulation of virulent factors' expression and secretion, bacterial motility and invasion, or host cell apoptosis induction. Because a great difference in mRNA degradation machinery and ribonucleases exists between bacteria and eukaryotes, it makes mRNA degradation pathways possible to serve as a potential target for exploiting antimicrobial drugs, or new platform to reduce their virulence for vaccine preparation, for combating rapid emergence of bacteria drug-resistance. In this review, the general bacterial mRNA degradation pathways and the role of RNase R, PNPase, RNase Y, RNase III, and RNase E in pathogenesis were discussed. Furthermore, the perspective of application of mRNA decay machinery for exploiting novel antibacterial targets was also speculated.

[The fidelity mechanism of DNA synthesis].

Accurate DNA synthesis is vital to maintain genome stability and ensure propagation of species. Synthetic errors have far reaching consequences. Therefore, DNA synthesis is remarkably accurate. The high fidelity is mainly achieved through three steps: ① nucleotide selection, which is based on hydrogen, base pair shape, or some other elements; ② 3'→5' exonuclease proofreading, which removes mis-incorporated nucleotides in cis or trans; ③ repair process, which could correct mismatched nucleotides escaping from proofreading, such as mismatch repair, excission repair, homologous recombination repair, and translesion DNA synthesis. Because all polymerases are suitable targets for anticancer or antiviral drugs, their fidelity is involved in drug resistance and side effects. Understanding the molecular basis of synthesis fidelity is of vital importance. In this review, the fidelity mechanisms of DNA synthesis will be discussed in detail. Furthermore, their application perspective was discussed.

The structural organization of the liver in the Chinese fire-bellied newt (Cynops orientalis) / Organización estructural del hígado en el tritón de vientre de fuego chino (Cynops orientalis)

The morphology of Chinese fire-bellied newt liver consists of 5 lobes, with exception of a few individual differences present, which are composed by a number of hepatic lobules. Passing through the center of the lobules, a central vein radiates and is arranged in orderly row from one to several layers. The interval of the hepatic cords or masses are irregular and variable sinusoid. The hepatic sinusoidal wall consists of one layer endothelial cells or Macrophagocytus stellatus (Kupffer cells), which have protrusions and elongations. The intervals of the hepatic cells have perisinusoidal space (space of Disse). The hepatic cell is polygonal in shape with uniform, round or oval nucleus, 17.8­12.4um in diameter, mean 14.2 um 2-6 nucleoli, nuclear-cytoplasmic volume ratio was 0.24:1. There is a lot of pigmentation in the hepatic parenchyma.

La morfología del hígado del tritón de vientre de fuego chino está constituida por 5 lóbulos, excepto unos pocos que presentan diferencias individuales, los cuales se componen de una gran cantidad de lóbulos hepáticos. Pasando por el centro de los lóbulos, se encuentra una vena central radial y los organiza en cordones o placas hepáticas. La vena central es delgada de 61,6-30,2 um de diámetro, con una media 42 de um. Los hepatocitos alrededor de la vena central están organizados en filas ordenadas por una a varias capas. El intervalo de los cordones hepáticos o masas es irregular y sinusoidal variable. La pared del sinusoide hepático está formada por una capa de células endoteliales o macrófagos hepáticos (células de Kupffer) que tienen protuberancias y elongaciones. El intervalo de las células hepáticas tienen el espacio perisinusoidal (de Disse). La célula hepática es de forma poligonal con un núcleo redondo u oval uniforme de 17,8-12,4 um de diámetro, con una media 14,2um. 2 a 6 nucléolos, con un radio de volumen nuclear-citoplasmático de 0,24:1. Hay una gran cantidad de pigmentación en el parénquima hepático.

5-allyl-7-gen-difluoromethoxychrysin enhances TRAIL-induced apoptosis in human lung carcinoma A549 cells.

BACKGROUND: 5-allyl-7-gen-difluoromethoxychrysin (AFMC) is a novel synthetic analogue of chrysin that has been reported to inhibit proliferation in various cancer cell lines. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent. METHODS: The cytotoxicity of A549 and WI-38 cells were determined using colorimetry. Apoptosis was detected by flow cytometry (FCM) after propidium iodide (PI) fluorescence staining and agarose gel electrophoresis. Caspase activities were evaluated using enzyme-linked immunosorbent assay (ELISA).The expressions of DR4 and DR5 were analyzed using FCM and western blot. RESULTS: Subtoxic concentrations of AFMC sensitize human non-small cell lung cancer (NSCLC) A549 cells to TRAIL-mediated apoptosis. Combined treatment of A549 cells with AFMC and TRAIL significantly activated caspase-3, -8 and -9. The caspase-3 inhibitor zDEVD-fmk and the caspase-8 inhibitor zIETD-fmk blocked the apoptosis of A549 cells induced by co-treatment with AFMC and TRAIL. In addition, we found that treatment of A549 cells with AFMC significantly induced the expression of death receptor 5 (DR5). AFMC-mediated sensitization of A549 cells to TRAIL was efficiently reduced by administration of a blocking antibody or small interfering RNAs against DR5. AFMC also caused increase of the Sub-G1 cells by TRAIL treatment and increased the expression levels of DR5 in other NSCLC H460 and H157 cell lines. In contrast, AFMC-mediated induction of DR5 expression was not observed in human embryo lung WI-38 cells, and AFMC did not sensitize WI-38 cells to TRAIL-induced apoptosis. CONCLUSIONS: AFMC synergistically enhances TRAIL-mediated apoptosis in NSCLC cells through up-regulating DR5 expression.

[The roles of RNA silencing in plant biotic stress].

RNA silencing is a common strategy shared by eukaryotic organisms to regulate gene expression, and also can operate as a defense mechanism against biotic stress. In plants, small RNAs play an important role in defensing against viruses, bacteria or herbivore attack, such as miRNAs and siRNAs. As a response to this defense system, both viruses and bacteria have evolved viral suppressors of RNA silencing (VSRs) or bacterial suppressors of RNA silencing (BSRs) to overcome the host silencing response, which can act at various steps of the different silencing pathways. This review highlights the current understanding and the new insights concerning of the roles of small RNAs in defensing against biotic stress and the mechanism of VSRs and BSRs in suppressing host RNA silencing in plants.

[The development of gene concepts].

One hundred years has passed since the term of "gene" was coined in 1909, the gene definition has been revised many times in the past 100 years. Gene has changed from an abstract symbol to a specific segment, which can produce protein or functional RNA, and finally became one of the most important biological words. With the accomplishment of the genome project, particularly the project of Encyclopedia of DNA Elements (ENCODE), our knowledge about the the complexity and diversity of genomic organization and dynamics of genomes posed important challenges to the classical molecular gene concept. As is becoming more evident that the relations between information stored at DNA level and functional products are very intricate, some people consider that it was time to make a redefinition of gene. In this review, we briefly outline gene definition of this history and the development of gene concept these days.

[Natural antisense transcript and its mechanism of gene regulation].

Natural antisense transcripts (NATs) are coding or non-coding RNAs with sequence complementarity to other transcripts (sense transcripts). These RNAs could potentially regulate the expression of their sense partner(s) at either the transcriptional or post-transcriptional level through a variety of biological mechanisms, such as transcription interference, RNA masking, dsRNA-dependent mechanisms, and chromatin remodelling (modification). We speculated that both of sense and antisense transcripts may be sliced to form small RNAs, which is also an important mechanism for NATs to regulate gene expression, such as rasiRNAs in "ping-pong". Experimental and computational analyses have demonstrated the wide-spread occurrence of NATs in a wide range of species. Here, we reviewed the current understanding of NATs function and its mechanistic basis. We hypothesized that the regulation of antisense transcription and small RNAs were derived from NATs.

[The role of endogenous small RNAs in plant stress responses].

Crop yields are significantly reduced by biotic and abiotic stresses throughout the world. A better understanding of adaptive responses will lead to new strategies for improving plant stress tolerance. The molecular response of plants to stresses has been often considered as a complex process mainly based on the modulation of transcriptional activity of stress-related genes. Nevertheless, recently discovered endogenous small RNAs, such as miRNAs, nat-siRNAs and lisiRNAs, not only have a vital role in regulating plant development, but also have emerged as important players in plant stress responses. This review discusses recent advances in the field of small RNAs guided adaption to various stress responses, including oxidative stress, mineral nutrient deficiency, drought stress, salinity stress, ABA stress, mechanical stress, heavy metals stresses, biotic stresses, and other environmental stresses.

[Advances in mechanism of small RNAs].

The discovery of RNA interference (RNAi) heralded a revolution in RNA biology. Researchers uncovered 'hidden' layers of regulation of gene expression, in which many previously unidentified families of small RNAs (consisting of approximately 20-30 nucleotides) mediate gene silencing in transcriptional and post-transcriptional levels. In eukaryotes, these small RNAs, including siRNAs, miRNAs, piRNAs, scnRNAs, 21U-RNAs, and some others, regulate gene expression, helping to control cellular metabolism, growth, and differentiation, to maintain genome integrity, to regulate stem cell renewal, and to combat viruses and mobile genetic elements. This review summarizes the current advancement in the identification and biosynthesis of small RNAs and their roles in gene regulation.

The cranial cervical ganglion and its branches in the yak (Bos grunniens).

The heads and necks of 10 yaks were dissected to study the shape, location, arrangement, and branches of the cranial cervical ganglion. The ganglion was a greyish fusiform structure, mean length 19.72 mm, width 7.65 mm and depth 4.55 mm, located on the rostrolateral surface of the m. longus capitis. Approximately 25% of the ganglion was covered by the tympanic bulla, the rest by the m. stylohyoideus. The branches of the cranial cervical ganglion included the internal and external carotid nerves, sympathetic trunk and the branches connecting with the glossopharyngeal, vagus and hypoglossal nerves. In one animal the right cranial cervical ganglia was a greyish pyramidal structure 10 mm long, 8 mm wide and 5 mm thick but the left ganglion was similar to those found in the other specimens examined.