Hypoxia and the acidic microenvironment play av ital role in tumor metastasis and angiogenesis,g enerally compromising the chemotherapeutic efficacy.T his provides atantalizing angle for the design of platinum(IV) prodrugs for the effective and selective killing of solid tumors.H erein, two carbonic anhydrase IX (CAIX)-targeting platinum(IV) prodrugs have been developed, named as CAIXplatins.Based on their strong affinity for and inhibition of CAIX, CAIXplatins can not only overcome hypoxiaa nd the acidic microenvironment, but also inhibit metabolic pathways of hypoxic cancer cells,resulting in asignificantly enhanced therapeutic effect on hypoxic MDA-MB-231 tumors both in vitro and in vivo compared with cisplatin/oxaliplatin, accompanied with excellent anti-metastasis and anti-angiogenesis activities.F urthermore,t he cancer selectivity indexes of CAIXplatins are 70-90 times higher than those of cisplatin/oxaliplatin with effectively alleviated side-effects.
Background: Chronic kidney disease (CKD) disease affects gut flora by causing dysbiosis and lead to systemic inflammatory conditions. Here, we provide intestinal flora changes of CKD patients undertook different hemodialysis therapy. Methods: From 2017 to 2019, a total of 166 patients from Guangzhou Red Cross Hospital were recruited and divided into four groups with 17 cases in healthy control group, 47 cases in CKD non-dialysis group, 49 cases in HD group, and 53 cases in PD group. Intestinal flora genome 16S rDNA sequencing and further bio-informatic analysis were performed.Results: Decreased diversity and altered communities of intestinal flora in PD patients, in which microbial diversity was positive correlated with the albumin level were observed. A total of 20 intestinal flora phyla were detected in 166 fecal samples, divided into 3 dominant intestinal types including Bacteroides-dominant gut type, Firmicutesdominant type and Proteobacteria-dominant gut type. Further analyses found 198 genera, the abundance of 86 genera were significantly different. Butyrate-producing taxa as Faecalibacterium in genera level and Bifidobacteriaceae and Prevotellaceae in family level were dominant genus in CT, CKD, and HD groups, while urease containing-, indole-and p-cresol-forming taxa as Escherichia in genera and Enterobacteriaceae, Enterococcaceae in family level was dominated genus in PD group. Number of differential expressed genes in KEGG enrichment pathways were significantly different in PD group in carbohydrate metabolism, amino acid metabolism, energy metabolism, translation, and membrane transport. Conclusion: Our results suggest peritoneal dialysis therapy could result in reduced diversity and altered microbial communities, with reduced probiotic butyrate-producing taxa and increased urease containing-, indole-and pcresol-forming taxa. The disordered intestinal flora can seriously affect the nutrition level in CKD patients with PD therapy.
Although carcinoma associated antigen in blood or stool, microsatellite DNA instability for high risk familial history, molecular biology technology for stool oncogene or antioncogene, telomerase activity and exfoliative cytological examination for tumor marker, are utilized, none of them is used in mass screening by now.
Two cationic molecular rotors, 1 and 2, capable of real-time cell-cycle imaging by specifically dynamic monitoring of nucleolus and chromosome changes were developed. A further study shows that fluorescence enhancements in the nucleolus and chromosome are attributed to a combination effect of interaction with nucleic acid and high condensation of the nucleolus and chromosome.
We have developed a strategy "charge-driven tripod somersault on DNA" realizing both in vitro and in vivo ratiometric fluorescence imaging of the variations of endogenous SO2 derivatives in the nucleus for the first time.
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