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101.
102.
Beiping Zhong Bing Cheng Xiaoming Huang Qian Xiao Zhitong Niu Yu-feng Chen Qiang Yu Wenyu Wang Xiao-Jian Wu 《Cell death & disease》2022,13(1)
Cancer-associated fibroblasts (CAFs) have been shown to play a strong role in colorectal cancer metastasis, yet the underlying mechanism remains to be fully elucidated. Using CRC clinical samples together with ex vivo CAFs-CRC co-culture models, we found that CAFs induce expression of Leucine Rich Alpha-2-Glycoprotein 1(LRG1) in CRC, where it shows markedly higher expression in metastatic CRC tissues compared to primary tumors. We further show that CAFs-induced LRG1 promotes CRC migration and invasion that is concomitant with EMT (epithelial-mesenchymal transition) induction. In addition, this signaling axis has also been confirmed in the liver metastatic mouse model which displayed CAFs-induced LRG1 substantially accelerates metastasis. Mechanistically, we demonstrate that CAFs-secreted IL-6 (interleukin-6) is responsible for LRG1 up-regulation in CRC, which occurs through a direct transactivation by STAT3 following JAK2 activation. In clinical CRC tumor samples, LRG1 expression was positively correlated with CAFs-specific marker, α-SMA, and a higher LRG1 expression predicted poor clinical outcomes especially distant metastasis free survival, supporting the role of LRG1 in CRC progression. Collectively, this study provided a novel insight into CAFs-mediated metastasis in CRC and indicated that therapeutic targeting of CAFs-mediated IL-6-STAT3-LRG1 axis might be a potential strategy to mitigate metastasis in CRC.Subject terms: Colon cancer, Cancer microenvironment 相似文献
103.
Jingwen Ai Haocheng Zhang Qiran Zhang Yi Zhang Ke Lin Zhangfan Fu Jieyu Song Yuanhan Zhao Mingxiang Fan Hongyu Wang Chao Qiu Yang Zhou Wenhong Zhang 《Cell research》2022,32(1):103-106
Dear Editor,
As of October,2021,SARS-CoV-2 has infected more than 230 million people;promoting roll-out vaccinations could help build herd immunity for the pand... 相似文献
104.
Canyang Niu Xiaoying Sun Fang Hu Xiaowen Tang KeWei Wang 《The Journal of biological chemistry》2022,298(3)
Transient receptor potential vanilloid 3 (TRPV3), robustly expressed in the skin, is a nonselective calcium-permeable cation channel activated by warm temperature, voltage, and certain chemicals. Natural monoterpenoid carvacrol from plant oregano is a known skin sensitizer or allergen that specifically activates TRPV3 channel. However, how carvacrol activates TRPV3 mechanistically remains to be understood. Here, we describe the molecular determinants for chemical activation of TRPV3 by the agonist carvacrol. Patch clamp recordings reveal that carvacrol activates TRPV3 in a concentration-dependent manner, with an EC50 of 0.2 mM, by increasing the probability of single-channel open conformation. Molecular docking of carvacrol into cryo-EM structure of TRPV3 combined with site-directed mutagenesis further identified a unique binding pocket formed by the channel S2-S3 linker important for mediating this interaction. Within the binding pocket consisting of four residues (Ile505, Leu508, Arg509, and Asp512), we report that Leu508 is the most critical residue for the activation of TRPV3 by carvacrol, but not 2-APB, a widely used nonspecific agonist and TRP channel modulator. Our findings demonstrate a direct binding of carvacrol to TRPV3 by targeting the channel S2-S3 linker that serves as a critical domain for chemical-mediated activation of TRPV3. We also propose that carvacrol can function as a molecular tool in the design of novel specific TRPV3 modulators for the further understanding of TRPV3 channel pharmacology. 相似文献
105.
Yiwei Niu Xueyi Teng Honghong Zhou Yirong Shi Yanyan Li Yiheng Tang Peng Zhang Huaxia Luo Quan Kang Tao Xu Shunmin He 《Nucleic acids research》2022,50(5):2493
Mobile element insertions (MEIs) are a major class of structural variants (SVs) and have been linked to many human genetic disorders, including hemophilia, neurofibromatosis, and various cancers. However, human MEI resources from large-scale genome sequencing are still lacking compared to those for SNPs and SVs. Here, we report a comprehensive map of 36 699 non-reference MEIs constructed from 5675 genomes, comprising 2998 Chinese samples (∼26.2×, NyuWa) and 2677 samples from the 1000 Genomes Project (∼7.4×, 1KGP). We discovered that LINE-1 insertions were highly enriched in centromere regions, implying the role of chromosome context in retroelement insertion. After functional annotation, we estimated that MEIs are responsible for about 9.3% of all protein-truncating events per genome. Finally, we built a companion database named HMEID for public use. This resource represents the latest and largest genomewide study on MEIs and will have broad utility for exploration of human MEI findings. 相似文献
106.
Xinping Chen Hongyu Yuan Rongzhi Chen Lili Zhu Guangcun He 《Plant Growth Regulation》2003,40(3):249-256
Triacontanol (TRIA) increased the contents of total chlorophyll (Chl), Chl a and Chl b by 25.1%, 26.1% and 22.4% respectively 4 h after treatment in rice seedlings. The minimal fluorescence (F0), the maximal fluorescence (Fm) and Fv/Fm were also higher in TRIA-treated plants. In actinic light, other Chl fluorescence parameters were measured at different photon flux densities (PFD) to construct light response curves of the quantum yield of PSII electron transport (PSII), light response curves of photochemical quenching (qp), and light response curves of non-photochemical quenching (qN), respectively. The PSII and qp declined with the increasing PFD with a higher level present in TRIA-treated plants. The qN increased with the increasing PFD with a lower level present in TRIA-treated plants. Two-dimensional gel electrophoresis indicated a protein expression difference between TRIA-treated materials and the controls at the total-soluble-protein level. Rubisco was 30% higher in TRIA-treated plants than in controls. The quantity of other proteins was unchanged in response to TRIA. These data provide biochemical and photochemical evidence for the effects of TRIA on photosynthesis. 相似文献
107.
Intracellular phosphorus metabolism of Microcystis aeruginosa under various redox potential in darkness 总被引:2,自引:0,他引:2
Phosphorus metabolism of Microcystis aeruginosa was studied under gradient redox potential from 252 mV to –70 mV in darkness. The release of phosphorus occurred in all the treatments, and this process was accelerated in darkness when the redox potential was lowered. Low redox potential in darkness stimulated the accumulation of polyphosphate (PolyP) and the degradation of polyglucose. The synthesis of PolyP delayed the decrease of intracellular orthophosphate. The death of M. aeruginosa was slowered when the redox potential was low in darkness. The accumulation of PolyP under low redox potential in the dark was very important to M. aeruginosa for endurance through the unfavorable growth conditions for maintaining phosphorus concentration, energy storage, and other physiological functions. The ability to accumulate PolyP in the dark and negative redox potential may be of considerable advantage in the low-light, organically rich, and low-redox habitats. 相似文献
108.
109.
SNPkit: an efficient approach to systematic evaluation of candidate single nucleotide polymorphisms in public databases 总被引:7,自引:0,他引:7
There is widespread interest in devising genotyping methods for SNPs that are robust, inexpensive, and simple to perform. Although several high-throughput SNP genotyping technologies have been developed, including the oligonucleotide ligation assay, real-time PCR, and mass spectrometry, the issues of simplicity and cost-effectiveness have not been adequately addressed. Here we describe the application of a novel computer software package, SNPkit, which designs SNP genotyping assays based on a classical approach for discriminating alleles, restriction enzyme digestion. SNPkit can be used in genotyping assays for almost any SNPs including those that do not alter "natural" restriction sites. Using this method, 164 SNPs have been evaluated in DNA samples from 48 immortalized cell lines of randomly selected Chinese subjects. Sixty-two (37.8%) of the SNPs appeared to be common (frequencies of the minor alleles are > or = 5%) and were subsequently applied to a larger population-based sample. Overall, by using SNPkit, we have been able to validate and genotype accurately a large fraction of publicly available SNPs without sophisticated instrumentation. 相似文献
110.
Bingbing Li Yong Chen Xiaochun Chen Dong Liu Huanqing Niu Jian Xiong Jinglan Wu Jingjing Xie Jianxin Bai Hanjie Ying 《Process Biochemistry》2012,47(4):665-670
Microbial nuclease P1 from Penicllium citrinum was immobilized on macroporous absorbent resins: strong polar poly (styrene-co-DVB) resin (SPPSD), polymethacrylic ester resin and poly (styrene-co-DVB)-Br resin. The results showed that SPPSD was the best carrier. Three methods of glutaraldehyde cross-linking were used and simultaneous immobilization and cross-linking (CIS) was demonstrated to be the best method. The functional properties of immobilized nuclease P1 were studied and compared to those of the free enzyme. The highest enzyme activities of free and immobilized nuclease P1 were obtained in 0.2 M acetate buffer at pH 4.5 and a temperature of 70 °C. An increase in Km (from 3.165 to 18.125 mg mL?1) and a decrease in Vmax (from 1667.18 to 443.95 U min?1 mL?1) were recorded after immobilization. SPPSD-glutaraldehyde-nuclease P1 exhibited better thermal stability than the free enzyme. The apparent activation energy (Ea) of the free and immobilized nuclease P1 was 137.04 kJ mol?1 and 98.43 kJ mol?1, respectively, implying that the catalytic efficiency of the immobilized enzyme was restricted by mass-transfer rather than kinetic limit. 相似文献