Accumulating evidence implies that N6‐methyladenosine (m6A) methylation participated in the tumorigenesis of gastric cancer (GC). Here we synthetically analyzing the prognostic value and expression ...profile of seven m6A methylation‐relevant genes through silico analysis of sequencing data downloaded from The Cancer Genome Atlas, Kaplan–Meier plotter, and Gene Expression Omnibus database. We explored the methyltransferase‐like 3 (METTL3) expression in GC cell line and tumor tissues by reverse transcription quantitative polymerase chain reaction and western blot analysis. The m6A methylation status of total RNA was measured by m6A RNA methylation quantification kit. Small interfering RNA was used to establish METTL3 knockdown cell lines. We also measure the proliferation and migration capability GC cell. Furthermore, we detect the epithelial cell mesenchymal transition marker and m6A methylation level after METTL3 knock down. Our result revealed that METTL3 was significantly increased in GC tissues compared with control in big crowd data sets. Survival analysis showed that METTL3 serve as a poor prognostic factor for GC patients. The expression level of METTL3 gradually increased with the progress of tumor stage and grade. GFI1 is an important transcription factor associated with METTL3. We verified the up‐trend of METTL3 in messenger RNA and protein expression and observed a significant increase in the m6A methylation status of total RNA in the GC cells and tissues. METTL3 knockdown inhibited total RNA m6A methylation level, as well as cell proliferation and migration capacity. Moreover, METTL3 knockdown decreased α‐smooth muscle actin. Taken together, our finding revealed that m6A methylation writer METTL3 serve as an oncogene in tumorigenesis of GC.
Identify METTL3 as the main research target molecule.
Bright n‐ZnO nanowire/p‐GaN film hybrid heterojunction light‐emitting‐diode (LED) devices are fabricated by directly growing n‐type ZnO‐nanowire arrays on p‐GaN wafers. UV–blue electroluminescence ...emission was observed from the heterojunction diodes, and the heterojunction LED device exhibited a high sensitivity in responding to UV irradiation.
Polycystic ovary syndrome (PCOS) is one of the most prevalent reproductive disorders in women worldwide. Despite rigorous research, the exact molecular mechanism that governs PCOS pathogenesis ...remains unclear. To investigate the potential roles of circular RNAs (circRNAs), this study sequenced ribosomal RNA‐depleted total RNA from exosomes of follicle fluids obtained from PCOS patients using non‐PCOS samples as controls. Bioinformatic analysis identified 167 upregulated and 245 downregulated circRNAs from a total of 16,771 detected candidates. Functional analysis suggests that pathways related to bacterial infection, associated chronic inflammation, and oxidative stress could be targeted by the differential circRNAs in PCOS patients. The obtained sequencing results were further validated by quantitative reverse‐transcription polymerase chain reaction and a circRNA–microRNA interaction network was constructed. The obtained results provide a valuable addition to the published studies on the mechanism of PCOS pathogenesis by revealing a wide variety of new circRNAs, miRNA, and gene targets that merit further investigation.
We have provided the first study on the dysregulation of circRNAs in patients with polycystic ovary syndrome using RNA sequencing and bioinformatic analysis. We identified over 16,771 differentially expressed circRNA candidates, many of which showed implication in pathological processes such as bacterial infection, oxidative stress, and autophagy.
Healable, electrically conductive materials are highly desirable and valuable for the development of various modern electronics. But the preparation of a material combining good mechanical ...elasticity, functional properties, and intrinsic self‐healing ability remains a great challenge. Here, we design composites by connecting a polymer network and single‐walled carbon nanotubes (SWCNTs) through host–guest interactions. The resulting materials show bulk electrical conductivity, proximity sensitivity, humidity sensitivity and are able to self‐heal without external stimulus under ambient conditions rapidly. Furthermore, they also possess elasticity comparable to commercial rubbers.
Candidates for smart robotics: Self‐healing conductive composites were prepared by connecting single‐walled carbon nanotubes (SWCNTs) to a polymer network through host–guest interactions (see picture). The poly(2‐hydroxyethyl methacrylate)–SWCNT composite combines bulk electrical conductivity, proximity sensitivity, humidity sensitivity, and autonomic self‐healing properties.
A wide range of structurally diverse 3,3'-thiopyrrolidonyl spirooxindoles bearing three contiguous stereogenic centers can be smoothly obtained via a domino Michael/cyclization reaction between ...3-isothiocyanato oxindoles and 3-methyl-4-nitro-5-alkenyl-isoxazoles with commercially available quinine as the catalyst under mild conditions. The protocol is significantly characterized by high reactivity, a low catalyst loading (1 mol %), and an excellent diastereo- and enantioselectivity (up to >99:1 dr and 98% ee).
Emerging evidence suggests that epithelial‐mesenchymal transitions (EMTs) play important roles in tumor metastasis and recurrence. Understanding molecular mechanisms that regulate the EMT process is ...crucial for improving treatment of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play important roles in HCC; however, the mechanisms by which miRNAs target the EMT and their therapeutic potential remains largely unknown. To better explore the roles of miRNAs in the EMT process, we established an EMT model in HCC cells by transforming growth factor beta 1 treatment and found that several tumor‐related miRNAs were significantly decreased. Among these miRNAs, miR‐125b expression was most strongly suppressed. We also found down‐regulation of miR‐125b in most HCC cells and clinical specimens, which correlated with cellular differentiation in HCC patients. We then demonstrated that miR‐125b overexpression attenuated EMT phenotype in HCC cancer cells, whereas knockdown of miR‐125b promoted the EMT phenotype in vitro and in vivo. Moreover, we found that miR‐125b attenuated EMT‐associated traits, including chemoresistance, migration, and stemness in HCC cells, and negatively correlated with EMT and cancer stem cell (CSC) marker expressions in HCC specimens. miR‐125b overexpression could inhibit CSC generation and decrease tumor incidence in the mouse xenograft model. Mechanistically, our data revealed that miR‐125b suppressed EMT and EMT‐associated traits of HCC cells by targeting small mothers against decapentaplegic (SMAD)2 and 4. Most important, the therapeutic delivery of synthetic miR‐125b mimics decreased the target molecule of CSC and inhibited metastasis in the mice model. These findings suggest a potential therapeutic treatment of miR‐125b for liver cancer. Conclusion: miR‐125b exerts inhibitory effects on EMT and EMT‐associated traits in HCC by SMAD2 and 4. Ectopic expression of miR‐125b provides a promising strategy to treat HCC. (Hepatology 2015;62:801–815)
Cancer‐associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer‐associated MSCs (LC‐MSCs) and hepatocellular ...carcinoma (HCC) remain unreported. Here, we identified the presence of MSCs in HCC tissues. We also showed that LC‐MSCs significantly enhanced tumor growth in vivo and promoted tumor sphere formation in vitro. LC‐MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. Complementary DNA (cDNA) microarray analysis showed that S100A4 expression was significantly higher in LC‐MSCs compared with liver normal MSCs (LN‐MSCs) from adjacent cancer‐free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC‐MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic microRNA (miR)‐155 in HCC cells was significantly up‐regulated by coculture with LC‐MSCs and by S100A4 ectopic overexpression. The invasion‐promoting effects of S100A4 were significantly attenuated by a miR‐155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR‐155 expression in HCC cells. We demonstrate that S100A4 secreted from LC‐MSCs promotes the expression of miR‐155, which mediates the down‐regulation of suppressor of cytokine signaling 1, leading to the subsequent activation of STAT3 signaling. This promotes the expression of matrix metalloproteinases 9, which results in increased tumor invasiveness. Conclusion: S100A4 secreted from LC‐MSCs is involved in the modulation of HCC progression, and may be a potential therapeutic target. (HEPATOLOGY 2013)
Paeoniflorin (PF), the main active glucoside of Paeonia Lactiflora, has many pharmacological activities, such as inhibition of vasodilation, hypoglycemia, and immunomodulation. Although the current ...evidence has suggested the therapeutic effects of PF on diabetic nephropathy (DN), its potential mechanism of action is still unclear. A systematic review and meta-analysis of the existing literature on paeoniflorin treatment in DN animal models was performed to evaluate the efficacy and mechanism of PF in DN animal models. The risk of bias in each study was judged using the CAMARADES 10-item quality checklist with the number of criteria met varying from 4 / 10 to 7 / 10, with an average of 5.44. From inception to July 2022, We searched eight databases. We used the Cochrane Collaboration's 10-item checklist and RevMan 5.3 software to assess the risk of bias and analyze the data. Three-dimensional dose/time-effect analyses were conducted to examine the dosage/time-response relations between PF and DN. Nine animal studies were systematically reviewed to evaluate the effectiveness of PF in improving animal models of DN. Meta-analysis data and intergroup comparisons indicated that PF slowed the index of mesangial expansion and tubulointerstitial injury, 24-h urinary protein excretion rate, expression of anti-inflammatory mediators (mRNA of MCP-1, TNF-alpha, iNOS, and IL-1 beta), and expression of immune downstream factors (P-IRAK1, TIRF, P-IRF3, MyD88, and NF-kappaBp-p65). Furthermore, modeling methods, animal species, treatment duration, thickness of tissue sections during the experiment, and experimental procedures were subjected to subgroup analyses. The present study demonstrated that the reno-protective effects of PF were associated with its inhibition on macrophage infiltration, reduction of inflammatory mediators, and immunomodulatory effects. In conclusion, PF can effectively slow down the progression of DN and hold promise as a protective drug for the treatment of DN. Due to the low bioavailability of PF, further studies on renal histology in animals are urgently needed. We therefore recommend an active exploration of the dose and therapeutic time frame of PF in the clinic and in animals. Moreover, it is suggested to actively explore methods to improve the bioavailability of PF to expand the application of PF in the clinic.
Catalytic asymmetric dearomative 3+2 cycloaddition of
-imino
-lactones with either 3-nitroindoles or 2-nitrobenzofurans by using a chiral copper complex as the catalyst was developed. A wide range of ...structurally diverse polyheterocyclic compounds containing spirocyclic-fused butyrolactone-pyrrolidine-indoline and butyrolactone-pyrrolidine-dihydrobenzofuran skeletons could be smoothly obtained with excellent results (>99:1 dr and 98% ee). The potential synthetic applications of this methodology were also demonstrated by the scale-up experiment and by the diverse transformations of one product. This method is characterized by high asymmetric induction, wide functional group tolerance and scalability, and attractive product diversification.
A highly diastereo‐ and enantioselective dearomative 3+2 cycloaddition reaction of 3‐nitrobenzothiophenes and 3‐nitrothieno2,3‐bwith 3‐isothiocyanato oxindoles is developed. The reaction is catalyzed ...by the chiral Zn(OTf)2/bis(oxazoline, and is the second example of a catalytic asymmetric dearomative cycloaddition reaction of 3‐nitrobenzothiophene derivatives. A range of complex heterocyclic compounds containing three contiguous stereocenters, one of which is spirocyclic center, can be obtained in quantitative yields with excellent stereoselectivities.
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