Purpose In recent years, the relationship between malignant tumors and atrial fibrillation has attracted more and more attention. Atrial fibrillation can also cause a series of adverse events, such as the risk of thromboembolism. Also, Warfarin is often used here. But, the relationship between cutaneous melanoma and atrial fibrillation, and between cutaneous melanoma and warfarin is still unclear. Therefore, we used a two-sample Mendelian randomization to assess the causal relationship between atrial fibrillation/warfarin and cutaneous melanoma (cM). Methods Firstly, atrial fibrillation (ukb-b-11550; n Case = 3,518, n Control = 459,415) and warfarin (ukb-b-13248; n Case = 4,623, n Control = 458,310) as exposures, with genome-wide association studies (GWAS) data from the United Kingdom Biobank. And cM (ieu-b-4969; n Case = 3,751, n Control = 372,016) as outcome, with GWAS data from the IEU Open GWAS project. Subsequently, single-nucleotide polymorphisms (SNPs) were filtered from GWAS studies using quality control measures. In addition, two-sample Mendelian randomization (MR) analysis was performed to explore the causal relationship between atrial fibrillation or warfarin and cM and used inverse variance weighting (IVW) as the primary analytical method. Finally, relevant heterogeneity and sensitivity analysis were performed to ensure the accuracy of the results. Results A causal relationship between atrial fibrillation and cutaneous melanoma was observed, and between warfarin and cutaneous melanoma. Conclusion The atrial fibrillation may play a causal role in the development of cutaneous melanoma, but the mechanism and the causal relationship between warfarin and cutaneous melanoma needs to be further elucidated.
The surface defects of the board not only directly affect the appearance and quality of the product, but also one of the important factors affecting the classification of the board. Due to the wide variety of surface defects on the board, similar defects also differ in size and appearance. This detection method is susceptible to human factors and cannot avoid detection errors, omissions, and other situations, which can affect the quality of the board. Therefore, this article proposes a surface defect detection algorithm based on mixed texture features, which can accurately and robustly detect whether there are defects in the surface image of the board. Based on mixed texture feature vectors, a BP artificial neural network is used to train and detect the sample set. The average detection success rate of this method is 97.4%, which meets the requirements of the enterprise, improves detection efficiency, reduces costs, and enhances the competitive advantage of the product. This detection technology is worth promoting and applying.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Abstract Background: The incidence of breast cancer (BC) worldwide has increased substantially in recent years. Epithelial-mesenchymal transition (EMT) refers to a crucial event impacting tumor heterogeneity. Although cinobufagin acts as an effective anticancer agent, the clinical use of cinobufagin is limited due to its strong toxicity. Acetyl-cinobufagin, a pre-drug of cinobufagin, was developed and prepared with greater efficacy and lower toxicity. Methods: A heterograft mouse model using triple negative breast cancer ( TNBC) cell lines, was used to evaluate the potency of acetyl-cinobufagin. Signal transducer and stimulator of transcription 3 (STAT3)/EMT involvement was investigated by gene knockout experiments using siRNA and Western blot analysis. Results: Acetyl-cinobufagin inhibited proliferation, migration, and cell cycle S/G2 transition and promoted apoptosis in TNBC cells in vitro . In general, IL6 triggered the phosphorylation of the transcription factor STAT3 thereby activating the STAT3 pathway and inducing EMT. Mechanistically, acetyl-cinobufagin suppressed the phosphorylation of the transcription factor STAT3 and blocked the interleukin (IL6)-triggered translocation of STAT3 to the cell nucleus. In addition, acetyl-cinobufagin suppressed EMT in TNBC by inhibiting the STAT3 pathway. Experiments in an animal modelof breast cancer clearly showed that acetyl-cinobufagin was able to reduce tumor growth. Conclusions: The findings of this study support the potential clinical use of acetyl-cinobufagin as a STAT3 inhibitor in TNBC adjuvant therapy.
Previous studies have shown that gastrointestinal microbiome is associated with the development of esophageal cancer, but the relationship and molecular mechanism between esophageal microbiota and the early development of esophageal cancer remain unclear. Here, we found that Lactobacillus, Escherichia-Shigella, Rikenellaceae-RC9-gut-group, Morganella, and Fusobacterium were more abundant in early-stage esophageal cancer (EEC) tissues compared with normal esophageal tissues. The abundance of bacteria such as Prevotella, Fusobacterium, Porphyromonas, Actinobacillus, and Neisseria in advanced esophageal cancer (AEC) was higher than that in EEC. Then, we further verified that Fusobacterium nucleatum (Fn) was enriched in EEC tissues and that its abundance increased with the progression of esophageal cancer by FISH and RT-PCR. Next, we demonstrated that Fn promoted the proliferation of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. Finally, we confirmed that Fn promoted ESCC proliferation by upregulating the expression of interleukin (IL)-32/proteinase 3 (PRTN3) and then activating the PI3K/AKT signaling pathway. In conclusion, Fn promoted the early development of ESCC by upregulating the expression of IL-32/PRTN3 and thereby activating the PI3K/AKT signaling pathway. A better understanding of the molecular mechanism of Fn in early esophageal cancer may contribute to the development of early screening markers to diagnose ESCC and provide new targets for treatment.
Organic anion transporting polypeptides (OATPs, gene symbol SLCO) are membrane proteins that mediate the sodium-independent transport of a wide range of endogenous and exogenous compounds. Due to their broad substrate specificity, wide tissue distribution, and involvement in drug-drug interactions, OATPs have been considered as key players in drug absorption, distribution, and excretion. Transmembrane domains (TMs) are crucial structural features involved in proper functions of many transporters. According to computer-based modeling and previous studies of our laboratory and others, TM11 of OATP1B1 may face the substrate interaction pocket and thus play an important role in the transport function of the protein. Alanine-scanning of the transmembrane domain identified seven critical amino acid residues within the region. Further analysis revealed that alanine substitution of these residues resulted in reduced protein stability, which led to significantly decreased protein expression on the plasma membrane. In addition, all mutants exhibited an altered Km for ES uptake (either high affinity or low affinity component, or both), though Km for taurocholate transport only changed in R580A, G584A, and F591A. These results suggested that critical residues in TM11 not only affect protein stability of the transporter, but its interaction with substrates as well. The identification of seven essential residues out of 21 TM amino acids highlighted the importance of this transmembrane domain in the proper function of OATP1B1.
Objective To investigate the effect and mechanism of interleukin-1β (IL-1β) on the contraction of isolated small intestinal smooth muscle from guinea pig.Methods Smooth muscle segments with mucosa were removed from the ileum far away ileocecal junction 10 cm,and divided into four groups:IL-1β added to Tyrode solution; acetylcholine(ACH) and IL-1β added; tetrodotoxin (TTX)and IL-1β added; interstitial cells of Cajal specially destroyed by methylene blue incubation and intensive illumination and IL-1β.Results The amplitude and tension of contraction were decreased by IL-1β in a dose-independent manner. The amplitude of contraction precaused by ACH was not influenced by IL-1β(P0.05),as the same as when addition with IL-1β the contraction caused by ACH was no significant difference with contraction precaused by ACH independly(P0.05). Influence of IL-1β nearly disappeared after blocking enteric nerve with tetrodotoxin (P0.05). The contraction of smooth muscle was nearly abolished when interstitial cells of Cajal were destroyed by melene blue incubation and intensive illumination (P0.01). Although IL-1β was administered,there was no significant difference in the amplitude and frequency of the contraction of smooth muscle segments when interstitial cells of Cajal were destroyed by melene blue incubation and intensive illumination (P0.05).Conclusion IL-1β is able to decrease the contraction of small intestinal smooth muscle. Effects of IL-1β on contraction are mainly induced by the enteric nerve system. Terstitial cells of Cajal play an essential role in the activation of smooth muscle by IL-1β. IL-1β also has no significant acute influence on the contraction caused by ACH.
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