Effect of metformin on the mortality of colorectal cancer patients with T2DM: meta-analysis of sex differences.

PURPOSE: To evaluate the effect of metformin as a treatment for the mortality of colorectal cancer (CRC) patients with type 2 diabetes mellitus (T2DM). METHODS: We searched Medline, PubMed, EMBASE, Clinical Trials.gov (http://www.clinicaltrials.gov), and the Cochrane Collaboration Library from inception to November 2019. To analyze the relationship between metformin and the overall mortality, specific mortality, and sex differences in CRC patients with T2DM, hazard ratios (HRs) with 95% confidence intervals (CIs) were used. Egger's test and Begg's test were used to assess publication bias. RESULTS: We included 8 cohort studies in our meta-analysis. CRC patients with T2DM treated with metformin had a lower overall mortality than CRC patients with T2DM who did not receive metformin (HR = 0.80, 95% CI 0.67-0.95). There was no significant difference in CRC-specific mortality between CRC patients with T2DM who used metformin and those who did not (HR = 0.84, 95% CI 0.65-1.08). However, females had a lower CRC-specific mortality among CRC patients with T2DM than males (HR = 0.63, 95% CI 0.41-0.97). CONCLUSION: Metformin reduced the overall mortality of CRC patients with T2DM. Moreover, female CRC patients with T2DM using metformin had lower CRC-specific mortality than male CRC patients with T2DM.

Effect of dihydroartemisinin on UHRF1 gene expression in human prostate cancer PC-3 cells.

As the second most common cancer in men around the world, prostate cancer is increasingly gaining more attention. Dihydroartemisinin (DHA) has been proven to be a promising anticancer agent in vitro as well as in vivo in accumulating data. However, the detailed mechanisms of how DHA action in human prostate cancer PC-3 cells remain elusive. This study aimed to investigate the effects of DHA, a novel anticancer agent, by inhibiting the expression of ubiquitin like containing PHD and ring finger 1 (UHRF1) in PC-3 cells. The apoptosis and cell-cycle distribution were detected by flow cytometry. Quantitative real-time PCR was performed to examine both UHRF1 and DNA methyltransferase 1 (DNMT1) expressions at mRNA levels, whereas the expressions of UHRF1, DNMT1, and p16 proteins at protein levels were detected by Western blotting. Methylation levels of p16 CpG islands were determined by bisulfite genomic sequencing. We showed that DHA induced the downregulation of UHRF1 and DNMT1, accompanied by an upregulation of p16 in PC-3 cells. Decreased p16 promoter methylation levels in DHA-treated groups were also observed in PC-3 cells. Furthermore, DHA significantly induced apoptosis and G1/S cell-cycle arrest in PC-3 cells. Our results suggested that downregulation of UHRF1/DNMT1 is upstream to many cellular events, including G1 cell arrest, demethylation of p16, and apoptosis. Together, our study provides new evidence that DHA may serve as a potential therapeutic agent in the treatment of prostate cancer.

Changes in myelinated fibers in the hippocampus of streptozotocin-induced diabetic rats: a stereological investigation.

Diabetes causes cognitive impairment, and the hippocampus is important for long-term and permanent memory function. However, the mechanism of their interaction is still unclear. In this study, rat models of diabetes mellitus were generated by a single injection of streptozotocin (STZ). This study aims to explore the changes in myelinated fibers in the hippocampus of type 1 diabetic rats. The unbiased stereological methods and transmission electron microscopy were used to obtain the total volume of the hippocampus, the total volume of the myelin sheath, the total length of the myelinated nerve fibers, the distribution of the length with different diameters of the myelinated fibers, and the distribution of the length with different thickness of the myelin sheath. Stereological analysis revealed that, compared to that of the control group, the total myelinated fibers volumes and the total myelinated fibers length were decreased slightly, while the total volume and the thickness of myelin sheaths were significantly decreased in the diabetic group. Finally, when compared with the control group, the total length of myelinated fibers in the diabetes group was significantly reduced, with diameters ranging from 0.7 to 1.1 µm and thicknesses of myelin sheaths from 0.15 to 0.17 µm. This study provides the first experimental evidence by stereological means to demonstrate that myelinated nerve fibers may be the key factor in cognitive dysfunction in diabetes.

Changes in hippocampal capillaries in transgenic type 2 diabetic mice: A stereological investigation.

The cognitive dysfunction associated with type 2 diabetes mellitus (T2DM) has been widely studied, and many structures in the hippocampus, such as neurons and synapses, have been shown to play a crucial role in the cognitive decline. However, the mechanism of these changes remains unknown. To further explore this issue, we investigated the changes in the blood supply of the hippocampus in transgenic T2DM mice. In the current study, histochemistry, immunohistochemistry, and unbiased stereological methods were utilized to research the effects of T2DM on hippocampal capillaries of transgenic db/db mice. Twenty (Leprdb ) mut/mut mice and twenty (Leprdb ) wt/wt mice were used in this study. The learning and memory ability was appraised by Morris water maze test.

[Determination of 104 volatile organic compounds in air by double column gas chromatography-mass spectrometry/flame ionization detector coupled with electronically controlled cryo-focusing unit].

A method for the determination of 104 volatile organic compounds (VOCs) in ambient air based on double column multi dean switching gas chromatography-mass spectrometry/flame ionization detector (GC-MS/FID) coupled with sorbent assisted electronically controlled cryo-focusing unit was developed and evaluated. The sorbent assisted electronically controlled cryo-focusing unit was used for trapping, dehydration and focusing of VOCs sampled in summa canisters. The VOCs were split into two parts by the multi dean switching unit in GC-MS/FID. The C2-C3 components were determined in a PLOT capillary column with an FID detector, while the C4-C12 components were determined in an Intercap-624 capillary column with a MS detector. The C2-C3 components were qualitatively confirmed from the retention time and quantified by the calibration curves, while the C4-C12 components were qualitatively confirmed from the retention time and the relative abundance ratio of characteristic ions, and quantified by the internal standard calibration curves. The major factors influencing the cryo-focusing performance including the type of sorbent tube, the pressure employed in assisted pressure control unit (APC), and the split point in multi dean switching unit were investigated. The chromatographic and MS parameters were optimized. Under optimum conditions, a linear relationship was observed with the content of VOCs ranging from 0.0446 to 0.892 µmol/m3, and correlation coefficients (r) no less than 0.9984. The average spiked recoveries of the six VOCs at two levels of 0.0446 µmol/m3 and 0.223 µmol/m3 were 86.4%-116.1%, with relative standard deviations in the range of 0.9%-11.3% The method detection limits (MDLs) and the limits of quantification (LOQs) were 0.145-1.90 µg/m3 and 0.435-5.70 µg/m3, respectively. The method is accurate, sensitive and simple, and is suitable for the determination of the 104 VOCs in ambient air.

Mechanism of dihydroartemisinin-induced apoptosis in prostate cancer PC3 cells: An iTRAQ-based proteomic analysis.

AIMS: Prostate cancer (PCa) is one of the most common cancers in men in the world. Advanced PCa, especially castration-resistant PCa (CRPC), is difficult to cure. There is an urgent need to develop novel agents for CPRC. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin and is a well-known antimalarial drug. DHA has been documented to be a potential anticancer agent for PCa. However, the mechanisms underlying the anticancer activity of DHA are still unknown. MAIN METHODS: Proteomics analysis based on iTRAQ technology was performed to determine the protein profile changes in human prostate cancer PC3 cells treated by DHA, and apoptosis was detected by flow cytometry and transmission electron microscopy. KEY FINDINGS: DHA induced obvious apoptosis in PC3 cells. Using iTRAQ technology, we found 86 differentially expressed proteins linked to the cytotoxicity of DHA in PC3 cells. Gene ontology analysis showed the differentially expressed proteins were mainly associated with the protein synthesis and translation. Protein interaction network analysis and KEGG pathway analysis revealed altered aminoacyl-tRNA biosynthesis and metabolic pathways. Moreover, one candidate protein, heat shock protein HSP70 (HSPA1A), was identified by western blot analysis. SIGNIFICANCE: Our results indicate that multiple mechanisms involved in the anticancer activity of DHA in PC3 cells. Decreased HSP70 expression may have an important role in DHA-induced apoptosis in PC3 cells. Our data also provide novel insights into the anticancer mechanisms of DHA.

Enantioseparation of lomefloxacin hydrochloride by high-speed counter-current chromatography using sulfated-ß-cyclodextrin as a chiral selector.

Enantiomers of lomefloxacin hydrochloride were separated by high-speed counter-current chromatography (HSCCC) using sulfated-ß-cyclodextrin as a chiral selector (CS). The separation was performed with a two-phase solvent system composed of ethyl acetate-methanol-water (10:1:10, v/v) containing CS at 0-60mmol/l in a head-to-tail elution mode, while obtained fractions were identified by polarimeter and spectropolarimeter. The results show that the concentration of the CS in the system strongly affects the peak resolution (Rs). As the concentration of CS increases, the Rs first increases reaching the maximum at 50mmol/l and then decreases. When the CS concentration is kept constant in the solvent systems, the Rs decreases as the concentration of the lomefloxacin hydrochloride increases. The overall results of our studies indicated that sulfated-ß-cyclodextrin is very useful for the chiral separation by HSCCC.