Objective The aim of the current study was to investigate which is the most suitable classification for colorectal cancer, log odds of positive lymph nodes (LODDS) classification or the classifications based on the number of positive lymph nodes (pN) and positive lymph node ratio(LNR) in a Chinese single institutional population. Design Clinicopathologic and prognostic data of 1297 patients with colorectal cancer were retrospectively studied. The log-rank statistics, Cox's proportional hazards model, the Nagelkerke R2 index and a Harrell's C statistic were used. Results Univariate and three-step multivariate analyses identified that LNR was a significant prognostic factor and LNR classification was superior to both the pN and LODDS classifications. Moreover, the results of the Nagelkerke R2 index (0.130) and a Harrell's C statistic (0.707) of LNR showed that LNR and LODDS classifications were similar and LNR was a little better than the other two classifications. Furthermore, for patients in each LNR classification, prognosis was homologous between those in different pN or LODDS classifications. However, for patients in pN1a, pN1b, LODDS2 and LODDS3 classifications, significant differences in survival were observed among patients in different LNR classifications. Conclusions For patients with colorectal cancer, the LNR classification is more suitable than pN and LODDS classifications for prognostic assessment in a Chinese single institutional population.
CARMA3 was recently reported to be overexpressed in several cancers and associated with malignant behavior of cancer cells. However, the expression pattern and biological roles of CARMA3 in breast cancer have not been reported. In the present study, we found that CARMA3 was overexpressed in 41.9 % of breast cancer specimens. Significant association was observed between CARMA3 overexpression and TNM stage (p = 0.0223), tumor size (p = 0.0227), and ErbB-2 status (p = 0.0049). Furthermore, knockdown of CARMA3 expression in MDA-MB-435 cells with high endogenous expression decreased cell proliferation and sensitized cell to paclitaxel-induced apoptosis, while overexpression of CARMA3 in MDA-MB-231 cell line promoted cell proliferation and inhibited apoptosis. Further analysis showed that CARMA3 depletion downregulated, and its overexpression upregulated cyclin D1, Bcl-2, and p-IκB levels. In conclusion, our study demonstrated that CARMA3 is overexpressed in breast cancers. CARMA3 facilitates proliferation and inhibits apoptosis through nuclear factor-kappaB signaling.
Caries is considered to be the most prevalent non-communicable disease in humans, mainly deriving from acidogenic bacterial biofilm and resulting in the demineralization and decomposition of hard dental tissue. Herein, a composite responsive foam brace loaded with magnesium organic framework (MPC) is designed for caries prevention and tooth remineralization. MPC can intelligently release organic antibacterial molecules (gallic acid) and mineralized ions (Mg2+, Ca2+ and PO43-) under acidic conditions (pH < 5.5) of biofilm infection, regulating pH and killing bacteria. Additionally, due to the excellent photothermal conversion efficiency, MPC can further enhance the destruction of bacterial biofilm by inhibiting virulence genes and destroying bacterial adhesion under near-infrared light irradiation (808 nm). More importantly, MPC can not only reverse the cariogenic environment at both pH and microbial levels, but also promote self-healing of demineralized teeth in terms of both the micro-structure and mechanical properties.
Chondroitinase ABC-type I (CSase ABC I), which can digest both chondroitin sulfate (CS) and dermatan sulfate (DS) in an endolytic manner, is an essential tool in structural and functional studies of CS/DS. Although a few CSase ABC I have been identified from bacteria, the substrate-degrading pattern and regulatory mechanisms of them have rarely been investigated. Herein, two CSase ABC I, IM3796 and IM1634, were identified from the intestinal metagenome of CS-fed mice. They show high sequence homology (query coverage: 88.00%, percent identity: 90.10%) except for an extra peptide (Met1-His109) at the N-terminus in IM1634, but their enzymatic properties are very different. IM3796 prefers to degrade 6-O-sulfated GalNAc residue-enriched CS into tetra- and disaccharides. In contrast, IM1634 exhibits nearly a thousand times more activity than IM3796 and can completely digest CS/DS with various sulfation patterns to produce disaccharides, unlike most CSase ABC I. Structure modeling showed that IM3796 did not contain an N-terminal domain composed of two β-sheets, which is found in IM1634 and other CSase ABC I. Furthermore, deletion of the N-terminal domain (Met1-His109) from IM1634 caused the enzymatic properties of the variant IM1634-T109 to be similar to those of IM3796, and conversely, grafting this domain to IM3796 increased the similarity of the variant IM3796-A109 to IM1634. In conclusion, the comparative study of the new CSase ABC I provides two unique tools for CS/DS-related studies and applications and, more importantly, reveals the critical role of the N-terminal domain in regulating the substrate binding and degradation of these enzymes.
Since the agriculture has been regarded as the material production object,few people regard the agricultural landscape as an esthetic object.The modern ecological agriculture not only pays great attention to produce the benefit,but also pays more attention to its ecological benefit and the esthetic function.Ecological agriculture's esthetic nature is not sole,but complex,which isrelated to its own characteristic,mainly manifests in the features of culture and living,and more in its ecological art.
Background: Cisplatin is an effective anti-cancer drug with limited clinical applications due to ototoxicity. Resveratrol, known for its antioxidant and anti-inflammatory properties, has been reported to mitigate these adverse effects, although the underlying mechanism remains under-researched. Objective: This study aimed to investigate the effects and underlying mechanisms of resveratrol on cisplatin-induced ototoxicity. Methods: Ototoxicity was modeled in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells by cisplatin exposure, followed by interventions using thioredoxin-interacting protein (TXNIP) siRNA transfection, MitoQ, or resveratrol. Apoptosis and proliferation were quantitatively assessed using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and Ki67 immunostaining. Quantitative real-time PCR (qRT-PCR) and western blotting were used to measure the changes in mRNA and protein levels. Flow cytometry and enzyme- linked immunosorbent assay (ELISA) were used to analyze pyroptotic cells and inflammatory responses. Reactive oxygen species (ROS) production was tracked using 2', 7'- dichlorofluorescein diacetate (DCFH-DA) staining and flow cytometry. Mitochondrial Membrane Potential (MMP) and mitochondrial permeability transition pore (MPTP) opening levels were analyzed through tetramethylrhodamine ethyl ester (TMRE) staining and specific reagent kits, respectively. Lastly, immunofluorescence staining and co-immunoprecipitation were employed to investigate the co-localization and interactions between TXNIP and thioredoxin (TRX)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) proteins. Results: Cisplatin exacerbated apoptosis, suppressed cell proliferation, and upregulated NLRP3, pro-Caspase-1, cleaved Caspase-1, Gasdermin D (GSDMD), GSDMD-N, and TXNIP expression. Concurrently, cisplatin resulted in increased pyroptotic cells and increased interleukin-6 (IL-6), IL-18, IL-1β, and tumor necrosis factor-α (TNF-α) levels. These effects were mitigated by TXNIP knockdown. Furthermore, cisplatin led to elevated cellular ROS and mitochondrial ROS (mtROS), decreased MMP, and inhibited MPTP opening. Cisplatin reduced the colocalization and interaction between TRX and TXNIP while enhancing those between TXNIP and NLRP3. These changes were attenuated by MitoQ. Resveratrol displayed effects similar to those of TXNIP knockdown and MitoQ treatment. result: Cisplatin exacerbated cell apoptosis, suppressed cell proliferation, and up-regulated NLRP3, pro-Caspase 1, cleaved-Caspase 1, GSDMD, GSDMD-N, and TXNIP expressions. Concurrently, cisplatin resulted in increased pyroptotic cells and heightened IL-1β, IL-18, IL-6, and TNF-α levels. These effects were mitigated through TXNIP knockdown. Furthermore, cisplatin led to elevated ROS, decreased MMP and inhibited the opening of MPTP. Cisplatin reduced the co-localization and interaction between TRX and TXNIP while enhancing those between TXNIP and NLRP3. MitoQ reversed these changes. Resveratrol displayed similar effects to those of TXNIP knockdown and MitoQ treatment. Conclusion: Resveratrol alleviated the toxic effects of cisplatin on cochlear hair cells by inhibiting cell pyroptosis process mediated by the mtROS/TXNIP/NLRP3 pathway.
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