Diallyl disulfide downregulating RhoGDI2 induces differentiation and inhibit invasion via the Rac1/Pak1/LIMK1 pathway in human leukemia HL-60 cells.

Leukemia is a type of disease in which hematopoietic stem cells proliferate clonally at the genetic level. We discovered previously by high-resolution mass spectrometry that diallyl disulfide (DADS), which is one of the effective ingredients of garlic, reduces the performance of RhoGDI2 from APL HL-60 cells. Although RhoGDI2 is oversubscribed in several cancer categories, the effect of RhoGDI2 in HL-60 cells has remained unexplained. We aimed to investigate the influence of RhoGDI2 on DADS-induced differentiation of HL-60 cells to elucidate the association among the effect of inhibition or over-expression of RhoGDI2 with HL-60 cell polarization, migration and invasion, which is important for establishing a novel generation of inducers to elicit leukemia cell polarization. Co-transfection with RhoGDI2-targeted miRNAs apparently decreases the malignant biological behavior of cells and upregulates cytopenias in DADS-treated HL-60 cell lines, which increases CD11b and decreases CD33 and mRNA levels of Rac1, PAK1 and LIMK1. Meanwhile, we generated HL-60 cell lines with high-expressing RhoGDI2. The proliferation, migration and invasion capacity of such cells were significantly increased by the treated with DADS, while the reduction capacity of the cells was decreased. There was a reduction in CD11b and an increase in CD33 production, as well as an increase in the mRNA levels of Rac1, PAK1 and LIMK1. It also confirmed that inhibition of RhoGDI2 attenuates the EMT cascade via the Rac1/Pak1/LIMK1 pathway, thereby inhibiting the malignant biological behavior of HL-60 cells. Thus, we considered that inhibition of RhoGDI2 expression might be a new therapeutic direction for the treatment of human promyelocytic leukemia. The anti-cancer property of DADS against HL-60 leukemia cells might be regulated by RhoGDI2 through the Rac1-Pak1-LIMK1 pathway, which provides new evidence for DADS as a clinical anti-cancer medicine.

Research advances on the correlation between frailty and chronic pain in the elderly / 中华老年医学杂志

Frailty is currently one of the hot research topics in geriatric medicine.With decreased physiological reserve of multiple systems and reduced anti-stress ability as its main manifestations, frailty results in a range of adverse outcomes.On the other hand, chronic pain is a common clinical syndrome that threatens physical and mental health of the elderly.The relationship between frailty and chronic pain is receiving increasing attention because both of them are important risk factors for impaired quality of life of elderly individuals.In this review, we summarize the correlation between frailty and chronic pain, and its possible underlying mechanisms, in order to provide new ideas for frailty identification and intervention and effective chronic pain management.

6-Shogaol reduces progression of experimental endometriosis in vivo and in vitro via regulation of VGEF and inhibition of COX-2 and PGE2-mediated inflammatory responses

Endometriosis (EM) is one of the most common gynaecological disorder affecting women in their reproductive age. Mechanisms involved in the pathogenesis of EM remains poorly understood, however inflammatory responses have been reported to be significantly involved. The efficacy of 6-shogaol on proliferation of endometriotic lesions and inflammatory pathways in experimentally-induced EM model was explored in this study. EM was stimulated in Sprague-Dawley rats by implantation of autologous endometrium onto the peritoneum abdominal wall. Separate groups were treated with 6-shogaol (50, 100 or 150 mg/kg b.wt/day) via oral gavage for one month period. Gestrinone (GTN) group received GTN (0.5 mg/kg/day) as positive control. Five weeks after implantation, the spherical volume of ecto-uterine tissues was determined. Treatment with 6-shogaol significantly reduced the implant size. Histological analysis reported atrophy and regression of the lesions. 6-shogaol administration effectively down-regulated NF-κB signaling, VEGF and VEGFR-2 (Flk-1) expression in the endometriotic lesions. Excess production of IL-1β and IL-6 (pro-inflammatory cytokines), PGE2 and nitric oxide (NO) were reduced. Overall, the results of the study reveal the efficacy of 6-shogaol against endometriosis via effectively suppressing proliferation of the lesions and modulating angiogenesis and COX-2/NF-κB-mediated inflammatory cascades.

Effects of Dexmedetomidine Pretreatment on Hepatic Ischemia-reperfusion Injury in Patients with Hepatocellular Carcinoma Radical Surgery / 中国药房

OBJECTIVE:To investigate the effects of dexmedetomidine pretreatment on hepatic ischemia-reperfusion injury in patients with hepatocellular carcinoma radical surgery (HCRS).METHODS:A total of 40 patients underwent elective HCRS were randomly divided into control group (20 cases) and observation group (20 cases).Before operation,observation group was given Dexmedetomidine hydrochloride injection with loading dose of 0.7 μg/kg within 10 min,maintained at 0.4 μg/(kg.h) until the end of surgery.Control group was given constant volume of 0.9％ Sodium chloride injection as observation group and same anesthetic scheme.The levels ofALT,AST,IL-1,IL-6,CRP and TNF-α,the occurrence of ADR were observed in 2 groups before surgery,4 h,24 h,72 h after surgery.RESULTS:Before surgery,there was no statistical significance in the levels ofAST,ALT,IL-1,IL-6,CRP and TNF-α between 2 groups at different time points (P＞0.05).After surgery,the levels of AST and ALT in 2 groups were significantly higher than before surgery,and the observation group was significantly lower than the control group,with statisti-cal significance (P＜0.05).The levels of AST and ALT in 2 groups were decreasing gradually as time.4,24,72 h after surgery,the levels of IL-1 and IL-6 in 2 groups,TNF-α levels 4,24 h after surgery and CRP levels 24,72 h after surgery were significantly higher than before surgery,and the observation group was significantly lower than the control group;the levels of TNF-α in 2 groups 72 h after surgery were significantly lower than before surgery,with statistical significance (P＜0.05).The levels of IL-1,IL-6 and TNF-α were decreasing gradually as time.There was no statistical significance in the incidence of ADR between 2 groups (P＞0.05).CONCLUSIONS:Dexmedeptomidine pretreatment can relieve hepatic ischemia-reperfusion injury in HCRS patients,reduce the level of inflammatory cells without increasing the occurrence of ADR.

Preventing Effect of Different Dosages of Progynova in Intrauterine Adhesions After TCRS Under Laparoscope / 医药导报

Objective To explore the effect of different dosages of progynova in preventing intrauterine adhesions after transcervical resection of septum ( TCRS) under laparoscope. Methods Clinical data of 213 TCRS patients under laparoscope were retrospectively analyzed, and these cases were divided into four groups according to the dosages of progynova. Except for group A (n=26), group B, C, D were given 4,6,8 mg.d-1 of progynova.Endometrial thickness, menstrual blood volume, incidence rates of residual septal and intrauterine adhesions, rate of adverse effect, pregnancy rate after operation and rate of spontaneous abortion were compared among the four groups. Results The incidence rate of residual septal in group A, B, C, D was 11.5%, 6.9%, 6.0% and 6.3%, respectively.Incidence rate of intrauterine adhesions after operation was 46.2%, 12.5%, 9.0% and 4.2%, respectively.The pregnancy rate in group A, B, C and D was 30.8%, 59.7%, 58.2% and 60.4%, respectively. There were significant differences between group A and the other groups(all P<0.05).The high dose of progynova(8 mg.d-1) significantly increased endometrial thickness ( P<0. 05 ) and menstrual blood volume ( P<0. 05 ) . But the incidence rates of gastrointestinal tract reaction, hepatic damage and vaginal spotting in the high dose group of progynova increased obviously( P<0.05) . Conclusion Progynova is a safe and effective drug in preventing intrauterine adhesions after TCRS. It can effectively prevent intrauterine adhesions, increase pregnancy rate and improve pregnant outcome.

Hemolysis test of the five kinds of impeller blood pumps in vitro / 生物医学工程学杂志

Hemolysis caused by blood pumps is a very important characteristic. In vitro hemolysis test circuits were constructed to operate the model I centrifugal pump, the model II axial flow pump, the magnetic coupling pump and the model I & II spiral mixed pump. The output of all pumps was set at flow 5 L/min, an average pressure of 100 mmHg. Experiments were conducted for 4 hours at room temperature(25 degrees C) with 500 ml fresh anticoagulant sheep blood. Blood samples were taken for plasma free-hemoglobin measurement, and the change in temperature at the pump outlet port was measured during the experiment. Calculate the normalized index of hemolysis (NIH). The results showed that there was no relationship either between the pump rotational speed and the NIH in five types of blood pumps, or between change in temperature at the pump outlet port and NIH. The dynamic fluid field caused by pump design and structure could be the main cause of blood damage.