Background & Aims
Insulin resistance is strongly associated with non‐alcoholic fatty liver disease, a chronic, obesity–related liver disease. Increased endoplasmic reticulum (ER) stress plays an ...important role in the development of insulin resistance. In this study, we investigated the roles of miRNAs in regulating ER stress in the liver of rats with obesity.
Methods
We used miRNA microarray to determine the miRNA expression profiles in the liver of rats fed with a high fat diet (HFD). We used prediction algorithms and luciferase reporter assay to identify the target gene of miRNAs. To overexpress the miRNA miR‐30b or inhibit miR‐30b rats were injected with lentivirus particles containing PGLV3‐miR‐30b or PGLV3‐miR‐30b antimiR through tail vein. Hepatic steatosis was measured using transient elastography in human subjects.
Results
Our data showed that miR‐30b was markedly up‐regulated in the liver of HFD–treated rats. Bioinformatic and in vitro and in vivo studies led us to identify sarco(endo)plasmic reticulum Ca2+‐ATPase 2b (SERCA2b), as a novel target of miR‐30b. Overexpression of miR‐30b induced ER stress and insulin resistance in rats fed with normal diet, whereas inhibition of miR‐30b by miR‐30b antimiR suppressed ER stress and insulin resistance in HFD–treated rats. Finally, our data demonstrated that there was a positive correlation between serum miR‐30b levels and hepatic steatosis or homoeostasis model assessment of insulin resistance (HOMA‐IR) in human subjects.
Conclusions
Our findings suggest that miR‐30b represents not only a potential target for the treatment of insulin resistance, but also a non‐invasive disease biomarker of NAFLD.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
To investigate the roles of matrix metalloproteinase-9, -2 (MMP-9, 2), and tissue inhibitors of metalloproteinase-1, 2 (TIMP-1, 2) in pathogenesis of the accretio placenta.
The women with the ...placenta accrete were recruited and the placenta (23) and deciduas tissues (9) after labor were obtained, and the placenta (28) and deciduas (11) from women without the placenta accreta were obtained as control to get, too. The expressions of MMP-9, -2, TIMP-1, 2 in the placental and decidual tissues were analyzed by real-time PCR.
mRNA expression of MMP-9 in the placenta accreta was (3.21 +/- 0.76) copies/microg total RNA, significantly higher (P < 0.05) than that of normal placenta (3.84 +/- 0.24) copies/microg total RNA). MMP-9 transcription in the decidua accreta was (2.50 +/- 0.49) copies/microg total RNA, significantly higher (P < 0.05) than that of normal decidua (3.81 +/- 0.66) copies/microg total RNA. mRNA expression of TIMP-1 in normal placenta and placenta accreta was (5.91 +/- 0.56) and (5.92 +/- 0.46) co
Aim： Huanglian-Jie-Du decoction （HUDD） is an important multiherb remedy in TCM, which is recently demonstrated to be effective to treat ischemic stroke. Here, we aimed to investigate the ...pharmacological mechanisms of HUDD in the treatment of ischemic stroke using systems biology approaches. Methods： Putative targets of HUDD were predicted using MetaDrug. An interaction network of putative HLIDD targets and known therapeutic targets for the treatment of ischemic stroke was then constructed, and candidate HUDD targets were identified by calculating topological features, including ＇Degree＇, ＇Node-betweenness＇, ＇Closeness＇, and ＇K-coreness＇. The binding efficiencies of the candidate HLJDD targets with the corresponding compositive compounds were further validated by a molecular docking simulation. Results： A total of 809 putative targets were obtained for 168 compositive compounds in HUDD. Additionally, 39 putative targets were common to all four herbs of HUDD. Next, 49 major nodes were identified as candidate HUDD targets due to their network topological importance. The enrichment analysis based on the Gene Ontology （GO） annotation system and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway demonstrated that candidate HLJDD targets were more frequently involved in G-protein-coupled receptor signaling pathways, neuroactive ligand-receptor interactions and gap junctions, which all played important roles in the progression of ischemic stroke. Finally, the molecular docking simulation showed that 170 pairs of chemical components and candidate HUDD targets had strong binding efficiencies. Conclusion： This study has developed for the first time a comprehensive systems approach integrating drug target prediction, network analysis and molecular docking simulation to reveal the relationships between the herbs contained in HUDD and their putative targets and ischemic stroke-related pathways.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract The cytochrome P450 monooxygenase (cytochrome P450) gene superfamily comprises many genes that may be involved in the biotransformations of pesticides and other xenobiotics. To date, very ...little is known about cytochrome P450 genes in the oriental migratory locust, Locusta migratoria manilensis. In this study, we carried out a genome‐wide analysis of cytochrome P450 genes of the locust to identify putative cytochrome P450 genes and characterize their expression responses to insecticide exposures. We identified 15 cytochrome P450‐like genes from a locust expressed sequence tag database (LocustDB). Reverse transcription polymerase chain reaction (RT‐PCR) analysis showed that most cytochrome P450‐like genes displayed different tissue and developmental stage expression patterns. However, most of them were predominantly expressed in the midgut, gastric caeca, fatbodies, and/or hindgut. Biochemical analysis showed that cytochrome P450 was differentially affected by three different insecticides. Deltamethrin caused significant inductions in 12 h at LD30 (dose to kill 30% of the tested individuals) in the nymphs, whereas malathion and carbaryl did not have significant effect on cytochrome P450 enzyme activity. Further RT‐PCR analysis showed significant increases of transcriptions of several cytochrome P450 genes in deltamethrin‐treated locusts. Thus, the increased cytochrome P450 enzyme activity is likely due to increased transcriptions of multiple cytochrome P450 genes in response to deltamethrin exposure. These results are expected to help us better understand the interactions between insecticides and major detoxification enzymes, and possible changes of the susceptibility to other insecticides in deltamethrin‐treated insects at various molecular levels.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background： Ovarian cancer is a leading gynecological malignancy. We investigated the prognostic value of programmed cell death 5 （PDCD5） in patients with ovarian cancer. Methods： Expression levels ...of PDCD5 mRNA and protein were examined in six ovarian cancer cell lines （SKOV3, CAOV3, ES2, OV1, 3AO, and HOC 1 A） and one normal ovarian epithelial cell line （T29） using reverse transcription polymerase chain reaction, Western blotting, and flow cytolnetry. Alter inducing PDCD5 induction in SKOV3 cells or treating this cell line with taxol or doxorubicin （either alone or combined）, apoptosis was measured by Annexin V-FITC/propidium iodide staining. Correlations between PDCD5 protein expression and pathological features, histological grade, FIGO stage, effective cytoreductive surgery, and serum cancer antigen-125 values were evaluated in patients with ovarian cancer. Results： PDCD5 mRNA and protein expression were downregulated in ovarian cancer cells. Recombinant human PDCD5 increased doxorubicin-induced apoptosis in SKOV3 cells （15.96 ± 2.07%, vs. 3.17 ± 1.45% in controls）. In patients with ovarian cancer, PDCD5 expression was inversely correlated with FIGO stage, pathological grade, and patient survival （P 〈 0.05, R = 0.7139 for survival）. Conclusions： PDCD5 expression is negatively correlated with disease progression and stage in ovarian cancer. Therefore, measuring PDCD5 expression may be a good method of determining the prognosis of ovarian cancer patients.
Spatial shifts in the organisation and pattern of ecological networks may be driven by species composition turnover, changes in species abundance and/or abiotic effects on species interactions.
To ...test the above assumptions, we collected arboreal ants and recorded host tree species from five latitudinal sites in Xishuangbanna, China. We constructed bipartite networks and compared spatial variation in species composition, interactions and stability change. We also analysed the relationship between network structure metrics and network stability.
Results showed that ant composition differed significantly among the five sites, primarily determined by weaver ants (Oecophylla smaragdina) and Crematogaster ant species. Dominant tree species included Ficus (32 individuals), Hevea (14 individuals), Castanopsis (11 individuals) and Pittosporopsis (8 individuals). Ant richness was positively correlated with tree richness, suggesting that host trees support ant diversity as a fundamental environment. The ant–tree bipartite networks showed low connectance, high specificity and low niche overlap. Links per species and network node were positively correlated with network stability, whereas connectance, nestedness, specificity and niche overlap were not.
Ants and trees formed a nonspecific and sparse bipartite network, and the number of nodes and links per species promoted network stability. Because plant richness was positively related to ant richness, and because arboreal ants feed predominantly on extrafloral nectaries, seeds, insects and honeydew secreted from hemipteran insects, we believe the bottom‐up process plays a central role in determining ant–tree interaction networks.
We collected 83 ant species from 144 tree species at the 5 study sites in Xishuangbanna, Yunnan province, China.
The ant–tree bipartite networks showed low connectance, high specificity and low niche overlap.
Because plant richness was positively related to ant richness, and because arboreal ants feed predominantly on extrafloral nectaries, seeds, insects and honeydew secreted from hemipteran insects, we believe the bottom‐up process plays a central role in determining ant–tree interaction networks.
A weaver ant, Oecophylla smaragdina, foraging in Ficus racemosa.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The nuclear-encoded light-harvesting chlorophyll a/b-binding proteins（LHCPs） are specifically translocated from the stroma into the thylakoid membrane through the chloroplast signal recognition ...particle（cp SRP） pathway. The cp SRP is composed of a cp SRP43 protein and a cp SRP54 protein, and it forms a soluble transit complex with LHCP in the chloroplast stroma. Here, we identified the YGL9 gene that is predicted to encode the probable rice cp SRP43 protein from a rice yellow-green leaf mutant. A phylogenetic tree showed that an important conserved protein family, cp SRP43, is present in almost all green photosynthetic organisms such as higher plants and green algae. Sequence analysis showed that YGL9 comprises a chloroplast transit peptide, three chromodomains and four ankyrin repeats, and the chromodomains and ankyrin repeats are probably involved in protein-protein interactions. Subcellular localization showed that YGL9 is localized in the chloroplast. Expression pattern analysis indicated that YGL9 is mainly expressed in green leaf sheaths and leaves. Quantitative real-time PCR analysis showed that the expression levels of genes associated with pigment metabolism, chloroplast development and photosynthesis were distinctly affected in the ygl9 mutant. These results indicated that YGL9 is possibly involved in pigment metabolism, chloroplast development and photosynthesis in rice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Color, infrared and flash images captured in different fields can be employed to effectively eliminate noise and other visual artifacts. We propose a two-image restoration framework considering input ...images from different fields, for example, one noisy color image and one dark-flashed near-infrared image. The major issue in such a framework is to handle all structure divergence and find commonly usable edges and smooth transitions for visually plausible image reconstruction. We introduce a novel scale map as a competent representation to explicitly model derivative-level confidence and propose new functions and a numerical solver to effectively infer it following our important structural observations. Multispectral shadow detection is also used to make our system more robust. Our method is general and shows a principled way to solve multispectral restoration problems.
Cancer stem-like cells (CSCs) contribute to bladder cancer chemotherapy resistance and progression, but the associated mechanisms have not been elucidated. This study determined whether blocking an ...autocrine signaling loop in CSCs improves the therapeutic effects of
-platinum on bladder cancer.
The expression of the epithelial marker OV6 and other markers in human bladder cancer specimens was examined by IHC. The CSC properties of magnetic-activated cell sorting (MACS)-isolated OV6
and OV6
bladder cancer cells were examined. Molecular mechanisms were assessed through RNA-Seq, cytokine antibody arrays, co-immunoprecipitation (co-IP), chromatin immunoprecipitation (ChIP) and other assays. An orthotopic bladder cancer mouse model was established to evaluate the
effects of a YAP inhibitor (verteporfin) and a PDGFR inhibitor (CP-673451) on the
-platinum resistance of OV6
CSCs in bladder cancer.
Upregulated OV6 expression positively associated with disease progression and poor prognosis for bladder cancer patients. Compared with OV6
cells, OV6
bladder cancer cells exhibited strong CSC characteristics, including self-renewal, tumor initiation in NOD/SCID mice, and chemotherapy resistance. YAP, which maintains the stemness of OV6
CSCs, triggered PDGFB transcription by recruiting TEAD1. Autocrine PDGF-BB signaling through its receptor PDGFR stabilized YAP and facilitated YAP nuclear translocation. Furthermore, blocking the YAP/TEAD1/PDGF-BB/PDGFR loop with verteporfin or CP-673451 inhibited the
-platinum resistance of OV6
bladder cancer CSCs in an orthotopic bladder cancer model.
OV6 could be a helpful indicator of disease progression and prognosis for patients with bladder cancer, and targeting the autocrine YAP/TEAD1/PDGF-BB/PDGFR loop might serve as a remedy for
-platinum resistance in patients with advanced bladder cancer.
Gene variants are responsible for more than half of hearing loss, particularly in nonsyndromic hearing loss (NSHL). The most common pathogenic variant in SLC26A4 gene found in East Asian populations ...is c.919-2A > G followed by c.2168A > G (p.H723R). This study was to evaluate their variant frequencies in patients with NSHL from special education schools in nine different areas of Southwest China's Yunnan.
We performed molecular characterization by PCR-products directly Sanger sequencing of the SLC26A4 c.919-2AG and c.2168 A > G variants in 1167 patients with NSHL including 533 Han Chinese and 634 ethnic minorities.
The SLC26A4 c.919-2A > G variant was discovered in 8 patients with a homozygous state (0.69%) and twenty-five heterozygous (2.14%) in 1167 patients with NSHL. The total carrier rate of the c.919-2A > G variant was found in Han Chinese patients with 4.50% and ethnic minority patients with 1.42%. A significant difference existed between the two groups (P < 0.05). The c.919-2A > G allele variant frequency was ranged from 3.93% in Kunming to zero in Lincang and Nvjiang areas of Yunnan. We further detected the SLC26A4 c.2168 A > G variant in this cohort with one homozygotes (0.09%) and seven heterozygotes (0.60%), which was detected in Baoshan, Honghe, Licang and Pu`er areas. Between Han Chinese group (0.94%) and ethnic minority group (0.47%), there was no statistical significance (P > 0.05). Three Han Chinese patients (0.26%) carried compound heterozygosity for c.919-2A > G and c.2168 A > G.
These data suggest that the variants in both SLC26A4 c.919-2A > G and c.2168 A > G were relatively less frequencies in this cohort compared to the average levels in most regions of China, as well as significantly lower than that in Han-Chinese patients. These results broadened Chinese population genetic information resources and provided more detailed information for regional genetic counselling for Yunnan.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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