Purpose:To investigate the relation between the expression of cyclinB1 gene and drug resistance in patient with acute leukemia. Methods:Cyclin B1 gene mRNA expression in 13 cases of drug resistant and 14 drug non-resistant acute leukemia patients’ peripheral blood have been determinated by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).The expression of mdr1 gene mRNA in these patients was measured with fluorescence -quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results:The expression of cyclin B1 mRNA in the drug resistant group was significantly higher than the drug non-resistant group cyclin B1 mRNA (P

AIM: To investigate whether glucosylceramide synthase (GCS) regulates apoptosis-related gene bcl-2 expression via MEK/ERK signaling pathway , thus enhancing drug resistance of K 562/A02 human leukemia multidrug resistant cell line.METHODS:siRNA targeting GCS was transfected into K562/A02 cells.Bcl-2, p-ERK and total ERK expression at mRNA and protein levels after GCS knockdown were detected by real-time PCR and Western blotting .After exposed to MEK-ERK pathway inhibitor U0126, the expression of Bcl-2 at mRNA and protein levels also was analyzed by real-time PCR and Western blotting , respectively.The viability of the cells was evaluated by CCK-8 assay.RESULTS:The expression of GCS and Bcl-2, as well as MEK/ERK signaling were significantly inhibited in K 562/A02 cells by GCS siRNA transfection compared with negative control group .Inactivation of MEK/ERK signaling due to U0126 treatment de-creased Bcl-2 mRNA and protein levels in a concentration-dependent manner , and sensitized K562/A02 cells to adriamy-cin.CONCLUSION:GCS may affect the expression of apoptosis-related gene bcl-2 by MEK/ERK signaling pathway , thus regulating multidrug resistance of human leukemia K 562/A02 cells.

OBJECTIVETo investigate whether transcription factor-kappaB (NF-κ B) is involved in the modulation of P-glycoprotein (P-gp) by glucosylceramide synthase (GCS) in a multidrug resistance leukemia cell line K562/A02 and to explore the relationship between NF-κ B and extracelluar signal-regulated kinase (ERK).

METHODSK562/A02 cells were treated with GCSsiRNA, pyrrolidine dithiocarbamate (PDTC, a NF-κ B specific inhibitor) and U0126 (a MEK1/2 inhibitor), respectively. The expression of GCS and multidrug resistance protein 1 (MDR1) mRNA were analyzed with qRT-PCR. Various proteins of different groups were measured by Western blotting.

RESULTSAfter transfected with GCSsiRNA for 48 h, GCS mRNA were reduced by 62% (51%-73%) and MDR1 mRNA was reduced by 52% (43%-61%) in the K562/A02 cells. Compared with the negative control, relative expression of NF-κ B p65 in nuclear and P-ERK1/2 were both down-regulated, and P-gp was also inhibited significantly at 72 h after transfected with GCSsiRNA (P< 0.05). In addition, the expression of P-gp was decreased at 24 h with 80 &mu; mol/L PDTC and 48 h with 20 &mu; mol/L PDTC. P-ERK1/2 was inhibited significantly when the cells were treated with 20 &mu; mol/L U0126 for 48 h. The expression of NF-κ B p65 in nuclear and P-gp were also down-regulated.

CONCLUSIONNF-κ B can modulate the effect of GCS on P-gp in K562/A02 cells. P-ERK1/2 can activate NF-κ B in above signal transduction pathway.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Cell Line, Tumor ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Glucosyltransferases ; genetics ; metabolism ; Humans ; K562 Cells ; Leukemia ; genetics ; NF-kappa B ; genetics ; metabolism

Objective:To evaluate the effect of the positive P-glycoprotein expression on the efficacy of patient-controlled intravenous analgesia (PCIA) with sufentanil or pentazocine in patients with cancer pain.Methods:This was a retrospective cohort study. The medical records of patients with cancer pain of either sex, aged 54-71 yr, weighing 49-67 kg, with TNM stage Ⅱ-Ⅳ, who were treated in People′s Hospital of Lishui from January 2020 to January 2024, were collected. The expression of P-glycoprotein in tumor tissues was determined by the immunohistochemical method. Patients with negative P-glycoprotein expression in tumor tissues were divided into 2 groups: sufentanil group (group S 1) and pentazocine group (group P 1). Patients with positive P-glycoprotein expression in tumor tissues were divided into 2 groups: sufentanil group (group S 2) and pentazocine group (group P 2). The patients in 4 groups received 48 h of PCIA when visual analogue scale > 5 cm. The PCIA solution contained sufentanil 2 &mu;g/kg and tropisetron 10 mg in 100 ml of normal saline in S 1 and S 2 groups or pentazocine 3 mg/kg+ tropisetron 10 mg in 100 ml of normal saline in P 1 and P 2 groups. The PCIA pump was set up to deliver a 1 ml bolus dose with a 10-min lockout interval and background infusion at 2 ml/h after a loading dose of 5 ml. Flurbiprofen 50 mg was intravenously injected when visual analogue scale > 3 cm during analgesia. The consumption of sufentanil, pentazocine and flurbiprofen within 4 h, >4-12 h, > 12-24 h and > 24-48 h of PCIA was recorded. The occurrence of adverse reactions such as respiratory depression (SpO 2<90%), nausea or/and vomiting, pruritus and bradycardia was recorded. Results:One hundred patients were finally included, with 25 in each group. There was no significant difference in the consumption of sufentanil, usage rate of flurbiprofen and incidence of respiratory depression, nausea and vomiting, pruritus and bradycardia during analgesia at each time period during PCIA between group S 1 and group S 2 ( P>0.05). Compared with group P 1, the consumption of pentazocinein was significantly increased within 4 h, > 4-12 h, and > 24-48 h of PCIA ( P<0.05), and no significant change was found in the usage rate of flurbiprofen at each time period and the incidence of respiratory depression, nausea or/and vomiting, pruritus and bradycardia during analgesia in group P 2 ( P>0.05). Conclusions:Positive P-glycoprotein expression may weaken the efficacy of PCIA with pentazocine, but exerts no effect on the efficacy of PCIA with sufentanil in patients with cancer pain.

Background Phenolic compounds may adversely affect human health, but the current relevant studies are mostly limited to the impact of single phenolic compound exposure on human health, and there is still a lack of studies on the population-based association between combined exposure to multiple common phenolic compounds and dyslipidemia. Objective To explore the association of phenolic compound combined exposure and dyslipidemia based on principal component analysis-random forest (PCA-RF) strategy. Methods The data were from the National Health and Nutrition Examination Survey (2013–2016). A total of 1301 adult residents aged ≥ 20 years with complete information on demographics and lifestyle, urine phenol concentrations (bisphenol A, bisphenol F, bisphenol S, triclocarban, benzophenone, and triclosan), and serum concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were included in this study. The concentrations of six urinary phenolic compounds were determined by solid phase extraction coupled with high performance liquid chromatography and tandem mass spectrometry, and the lipid indicators were determined by enzymatic methods. Principal component analysis combined with random forest model was used for model construction. First, principal component analysis was performed on 18 original variables including 6 phenolic compounds and 12 basic characteristic indicators, and then random forest model was established with dyslipidemia and its four evaluation indicators as dependent variables and the extracted principal components as independent variables, respectively. Results The PCA-RF analysis showed that bisphenol A, bisphenol F, and benzophenone may be important factors for dyslipidemia in the study subjects; bisphenol A, bisphenol F, and triclosan may be important factors for TC level in the study subjects; bisphenol A, bisphenol F, triclocarban, and benzophenone may be important factors for TG level in the study subjects; bisphenol A may be an important factor for LDL-C level in the study subjects; bisphenol F and benzophenone may be important factors for HDL-C level in the study subjects. Conclusion Phenolic compound exposure may be an important risk factor for the development of dyslipidemia. PCA-RF strategy can be effectively used to explore the association between phenolic compound exposure and dyslipidemia in the population.