Atomic force microscope (AFM) is a powerful and prospective tool in the studies of the cellular deformability within a single cell. However, the reliability of using AFM in estimating the cellular average deformability was suspected. Hemorheology, one of common clinical examinations, can assess the deformability of erythrocytes. In order to validate the reliability in estimating the cellular deformability with AFM, the correlation was studied between the stiffness of the erythrocyte membrane with AFM and the deformation index with the hemorheology test. Blood samples were taken from 5 diabetes mellitus patients and 5 healthy non-obese people. The erythrocyte deformability was detected by AFM and the hemorheology test, respectively. Excellent correlation (r = 0.907, p = 0.000 < 0.01) was found between the average erythrocyte stiffness with AFM and the deformation index obtained from the hemorheology test. Besides, it was found that the average stiffness and the deformation index of diabetes mellitus patients were significantly higher than those of healthy non-obese people (p = 0.007 and p = 0.003). The result was consistent with the impairment of erythrocytes form diabetes mellitus patients. Therefore, it is the first time that the quantification relation of the erythrocyte deformability was investigated with AFM and the hemorheology test, and the feasible and reliable were validated that AFM is used to investigate the mechanical properties of different living cells qualitatively and quantitatively.
To investigate the association between the metalloproteinase-9 (MMP9) −1562C/T polymorphism and diabetic nephropathy (DN) in Han Chinese, the patients with type 2 diabetes were collected and divided into the non-DN (NDN) and DN groups; controls were recruited. Genotype and allele frequencies were assessed using polymerase chain reaction and restriction fragment length polymorphism. Results showed that SBP, DBP, HbA1c, UAER, Cr, BUN, TG, and TC were higher in the DN group compared with the control and NDN groups. SBP, HbA1c, and TC in DN patients with the TT and CT genotypes were lower than in those with CC. Compared with controls, the frequency of the T allele in the DN group was significantly lower. The MMP9 −1562C allele, SBP, Cr, BUN, TG, and TC were independent risk factors for DN. All of the above suggested that the MMP9 −1562C/T polymorphism was associated with DN in Han Chinese.
The human insulin-like growth factor-II (IGF-II) gene transcribes four mRNAs (P1 mRNA-P4 mRNA), and P3 mRNA overexpression contributes to hepatocarcinogenesis. IGF-II-derived miR-483-5p is implicated in the development of cancers. Here, we investigated the involvement of miR-483-5p in P3 mRNA overexpression regulation and its role in hepatocellular carcinoma. Our results showed that miR-483-5p up-regulated P3 mRNA transcription by targeting the 5′-untranslated region (5′UTR) of P3 mRNA in hepatocellular carcinoma. The mechanism was involved in recruiting of an argonaute 1(Ago1)-argonaute 2 (Ago2) complex to the P3 mRNA 5′UTR and the P3 promoter of IGF-II gene by miR-483-5p, accompanied by increased enrichment of RNA polymerase II and activating histone marks histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 27 acetylation (H3K27ac), and histone 4 lysine 5/8/12/16 acetylation (H4Kac) at the P3 promoter. High miR-483-5p expression was an independent predictor for shorter survival of HCC patients. The findings suggest that miR-483-5p promotes P3 mRNA transcription by recruiting the Ago1-Ago2 complex to the P3 mRNA 5′UTR and is associated with poor prognosis of HCC. Our results display a potential new model for miRNAs to up-regulate gene expression.
AimThe aim of this study was to estimate the feasibility and therapeutic effectiveness of percutaneous microwave ablation in the treatment of hypersplenism in cirrhosis.MethodsForty-one cirrhosis patients with hypersplenism were treated with ultrasonography-guided percutaneous microwave ablation between February 2007 and August 2011. Peripheral blood cell counts, portal vein diameter, splenic vein diameter, and blood flow of splenic vein were evaluated before and after the operation, and complications of the treatment were also investigated. All patients were followed up for 24 months.ResultsThe levels of platelets and white blood cells were increased, while the splenic vein diameter narrowed gradually after the therapy and 24 months later. Moreover, patients received percutaneous microwave ablation had much lower splenic venous flow velocity. The portal vein diameter did not change significantly 6 months after the treatment, although it narrowed gradually within 3 months after the treatment. Furthermore, no complications such as uncontrollable bleeding, splenic abscess, spleen rupture, and damage in surrounding organ happened after the therapy.ConclusionsGraded percutaneous microwave ablation, as a minimally invasive therapy, could damage the spleen, increase the levels of platelets and white blood cells, and reduce portal hypertension effectively without serious complications. Percutaneous microwave ablation is an effective, safe, and feasible method for cirrhosis patients with hypersplenism.
Imbalance of gut microbiota can induce or aggravate intestinal inflammation. To enhance our understanding of the molecular mechanisms of gut microbiota and inflammatory bowel disease (IBD), we studied the role of repulsive guidance molecule b (RGMb) in gut microbiota and colitis in mice. We generated Rgmb knockout mice and inducible Rgmb knockout mice and induced colitis using dextran sulfate sodium (DSS) in these mice. 16S ribosomal RNA (rRNA) high-throughput sequencing was performed to acquire the gut microbiota composition and abundance. We found that Rgmb deficiency significantly altered the diversity of gut microbiota and also induced dysbiosis. In sharp contrast to the balanced distribution of various bacteria in control mice, Prevotellaceae was almost exhausted in Rgmb-deficient mice under both basal and inflammatory conditions. Correlation analysis indicated that Prevotellaceae was negatively associated with inflammation in Rgmb-deficient mice with colitis. Similar results were obtained at the early inflammatory stage of colitis associated colon cancer (CAC). Taken together, our results reveal that Rgmb deficiency leads to dysbiosis of predominant gut microbiota under basal and inflammatory conditions. Rgmb-deficiency-mediated Prevotellaceae loss may render mice more susceptible to intestinal inflammation. Therefore, RGMb may be a novel potential target for reconstruction of the gut microbiota for the treatment of IBD.
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