ObjectiveTo clarify why accelarated atheroslcerosis is complicated in chronic kidney disease patients, and to investigate whether endoplasmic reticuhm (ER) stress can be observed in acetylated low density lipepmtein (ACLDL)-induced apoptosis in THP-1 macrophages differentiated by 160 nmol/L PMA for five days. Methods Hoechst 33258 stain and caspase 3,7 assay were used to detect apeptosis. Oil red O was used to examine the lipid droplet. High performance liquid chromatography was used to measure intracelhlar free cholesterol (FC) and cholesterol ester (CE). Western blot was applied to demonstrate the protein level of acylcoenzyme A cholesterol acyltransferase(ACAT)1, growth arrest and DNA damage(CHOP) and Bcl-2. Real-time PCR was used to detect the changes of mRNAs. Results ACLDL could induce THP-1 macrophages apoptosis in time-and dose-dependent manner. After exposure to 100 mg/L ACLDL for 24 hours, the level of free cholesterol and cholesterol ester mass had a significant increment by 1.5-and 2.4-fold respectively (P＜0.01). CHOP increased and Bcl-2 decreased both in protein and mRNA levels. ACLDL loading also resulted in an increase of ACAT1 protein without any change in mRNA level. ConclusionIn THP-1 macrophages foam cell, apoptosis can be induced by ACLDL accompanied by ER stress pathway activation.

Objective To investigate the chemical preventive effect of matrine on ethyl nitrate nitroguanidine nitrate induced gastric cancer in rats. Methods 100 male Wistar rats were selected and randomly divided into four groups,each had 25 rats ,treated with different drugs respectively.Rats in the negative control group (group A)freely drunk water;each rat in gastric carcer model group (group B)drunk ethyl nitrate nitroguanidine nitrate (ENNG)1.5 mg/d by themselves;gastric cancer model rats of experimental group (group C)drunk matrine 150 mg/(kg · d)ethyl nitrate nitroguanidine nitrate (ENNG)150mg/(kg·d)by themselves;negative control group (group D)rats drunk matrine for injection 150 mg/(kg·d)by themselves.Rats were killed after 24 weeks,rats were observed on gastric mucosa change by naked eye and microscope ,and detected proliferating cell nucleus antigen (PCNA)of stomach tissue ,levels of serum transforming growth factorβ1 (TGF-β1 )and B cell lymphoma/leukemia-2 (Bcl-2).Results Canceration rate [64.00% (16/25)]of the rat gastric mucosa in Group B was significantly higher than that in group C [12.00% (3/25)],and the difference was statistically significant (P<0.05 );PCNA,TGF-β1 and the Bcl-2 level of rats in group C was lower than those in group B,and the difference was statistically significant (P<0.05 );after raising 24 weeks,change rate of gastric mucosa atrophy and hyperplasia in group B were significantly higher than those of group C,and the difference was statistically significant (P<0.05 );after raising 24 weeks,there was no cancerous changes on gastric mucosa in group A and D ,and the change of gastric mucosa atrophy and hyperplasia had no obvious difference,there was no statistically significant difference.Conclusion Matrine could inhibit rat gastric cancer induced by ENNG by lowering PCNA,TGF-β1 and the Bcl-2 levels,which provides evidence for the potential chemical preventive effect on human gastric cancer.

The effect of pioglitazone on mRNA expression of advanced glycosylation end products(AGE) receptor(RAGE)was observed in renal cortex of streptozotocin-induced diabetic rats.The RAGE mRNA expression was significantly raised in diabetic control group as compared with that in the normal control group(P

This study is to investigate therapeutic effect of astaxanthin on acetic acid-induced gastric ulcer in rats. Rats were divided into control group, ulcer control group, and astaxanthin (5, 10, and 25 mg x kg(-1)) groups at random, 8 rats in each group. After administered for 10 days consecutively, all the rats were sacrificed. The area of ulcer and the levels of MDA, SOD, CAT and GSH-Px in gastric mucosa were measured. Compared with ulcer control group, in astaxanthin (5, 10, and 25 mg x kg(-1)) groups, the area of ulcer was decreased significantly. Level of MDA decreased while activities of SOD, CAT and GSH-Px increased (P < 0.05). Astaxanthin has good therapeutic effect on acetic acid-induced gastric ulcer in rats. Eliminating free radical and improving local blood circulation of the ulcer may be the mechanism of action.
Acetic Acid ; Animals ; Anti-Ulcer Agents ; therapeutic use ; Antioxidants ; therapeutic use ; Catalase ; metabolism ; Gastric Mucosa ; metabolism ; pathology ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer ; chemically induced ; drug therapy ; metabolism ; pathology ; Superoxide Dismutase ; metabolism ; Xanthophylls ; therapeutic use

Recent clinical research shows that a prolonged infusion administration strategy of β-lactam antibiotics compared with intermittent infusion,may improve microbiologic and clinical cure,especially when pathogens demonstrate higher minimum inhibitory concentrations (MIC).This article reviews β-lactam pharmacodynamic background and advantages,clinical benefits and risks,clinical efficacy and potential drawbacks of prolonged infusion β-lactam antibiotics.

Objective: To explore the trichloroethylene-induced alteration of methylation on the promoter region of SET and related mechanisms in hepatic L-02 cells. Methods: L-02 cells were treated with different concentrations of TCE(0 mmol/L, 1 mmol/L, 2 mmol/L, 4 mmol/L, 8 mmol/L) for 24 h. The genomic DNA were then extracted and modified by bisulfite sodium. The DNA methylation was then analyzed using bisulfite sequencing PCR (BSP). Results: The overall methylation on promoter region of SET was decreased along with the increased concentrations of TCE in hepatic L-02 cells. Moreover, 73 CpG islands were found abnormally altered, among which 9 were predicted in transcriptional factor binding regions. Conclusion The decreased levels of CpG islands in the transcriptional factor binding region may contribute to the elevation of SET in TCE-induced hepatotoxicity.

OBJECTIVETo compare the clinical effects and radiographic outcomes of mini-open trans-spatium intermuscular and percutaneous short-segment pedicle fixation in treating thoracolumbar mono-segmental vertebral fractures without neurological deficits.

METHODSFrom August 2009 and August 2012, 95 patients with thoracolumbar mono-segmental vertebral fractures without neurological deficits were treated with short-segment pedicle fixation through mini-open trans-spatium intermuscular or percutaneous approach. There were 65 males and 30 females, aged from 16 to 60 years old with an average of 42 years. The mini-open trans-spatium intermuscular approach was used in 58 cases (group A) and the percutaneous approach was used in 37 cases (group B). Total incision length, operative time, intraoperative bleeding, fluoroscopy, hospitalization cost were compared between two groups. Visual analog scale (VAS) and radiographic outcomes were compared between two groups.

RESULTSAll patients were followed up from 12 to 36 months with an average of 19.6 months. No complications such as incision infection, internal fixation loosening and breakage were found. In group A, fluoroscopy time was short and hospitalization cost was lower than that of group B (P<0.05). But the total incision length in group B was smaller than that of group A (P<0.05). There was no significant differences in operative time, intraoperative bleeding, postoperative VAS and radiographic outcomes between two groups (P>0.05). Postoperative VAS and radiographic outcomes were improved than that of preoperative (P<0.05).

CONCLUSIONThe mini-open trans-spatium intermuscular and percutaneous short-segment pedicle fixation have similar clinical effects and radiographic outcomes in treating thoracolumbar mono-segmental vertebral fractures without neurological deficits. However, in this study, the mini-open trans-spatium intermuscular approach has a short learning curve and more advantages in hospitalization cost and intraoperative radiation exposure times, and is recommendable.

Adolescent ; Adult ; Female ; Fluoroscopy ; Fracture Fixation, Internal ; methods ; Humans ; Lumbar Vertebrae ; injuries ; surgery ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; Spinal Fractures ; surgery ; Thoracic Vertebrae ; injuries ; surgery ; Visual Analog Scale

OBJECTIVETo investigate the killing effect of ZD6474 combined with adriamycin (ADM) on MCF-7 human breast cancer cells.

METHODSThe inhibitory effects of ZD6474 and ADM alone and in combination on the proliferation of MCF-7 cells were assessed by MTT assay. The cell cycle and cell apoptosis were detected by flow cytometry.

RESULTSZD6474 and ADM both significantly inhibited the proliferation of MCF-7 cells, showing a synergistic effect of their reactions in combined use (P<0.05). ZD6474 or ADM alone caused cell cycle arrest at G0/G1 and S phases, respectively. Combined use of the two drugs resulted in significant reduction of the M-phase cell percentage and cell cycle arrest at G0/G1 and S phases. The coadministration of the drugs significantly increased the apoptosis rate of the cells as compared with ZD6474 or ADM treatment alone (P<0.05).

CONCLUSIONSZD6474 and ADM show a synergistic effect in inhibiting the proliferation and inducing apoptosis of MCF-7 cells.

Antibiotics, Antineoplastic ; pharmacology ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Breast Neoplasms ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Doxorubicin ; pharmacology ; Drug Synergism ; Female ; Humans ; Piperidines ; pharmacology ; Quinazolines ; pharmacology

Objective:To compare the clinical efficacy of ileocecal-preserving laparoscopic subtotal colectomy, antegrade peristaltic ascending colorectal anastomosis with antiperistalsis cecorectal anastomosis in the treatment of severe slow transit constipation.Methods:The clinical data of 42 patients with severe slow transit constipation undergoing surgery in Shulan (Hangzhou) Hospital from Jan 2016 to Oct 2021 were retrospectively analyzed. All 42 patients underwent ileocecal-preserving laparoscopic subtotal colectomy. Among them, 25 patients underwent antegrade peristaltic anastomosis of ascending colon and rectum, 17 patients underwent antiperistaltic anastomosis of cecum and rectum.Results:There was no significant difference in the operation time and hospitalization time between the two groups ( t=-0.464, P=0.645; t=0.010, P=0.992); Wexner constipation scores in both groups were significantly reduced at 6 and 12 months after surgery. There was no significant difference in the Wexner constipation scores ( t=-1.181, P=0.240; t=-1.717, P=0.090), the number of bowel movenents per day ( t=0.179, P=0.860; t=0.545, P=0.590) and stool shapes scores ( t=-0.316, P=0.750; t=0.447, P=0.660) between the two groups at 6 and 12 months after surgery. Gastrointestinal quality of life index scores in the antegrade peristaltic anastomosis group were significantly higher than those in the antiperistalsis anastomosis group at 6 and 12 months after surgery ( t=4.329, P<0.05; t=3.988, P<0.05), while abdominal pain scores were significantly lower than those in the antiperistalsis anastomosis group ( t=-4.386, P<0.05; t=-5.740, P<0.05). Conclusions:For patients with severe slow transit constipation, ileocecal-preserving laparoscopic subtotal colectomy has good surgical safety and near-to-medium-term clinical efficacy, whether it is antegrade peristaltic ascending colorectal anastomosis (the stump of the ascending colon is turned from front to back) or antiperistalsis cecorectal anastomosis. The antegrade peristaltic ascending colorectal anastomosis has lower abdominal pain score and better gastrointestinal quality of life than antiperistalsis cecorectal anastomosis, which should be recommended first. During the operation, the ileocolic mesentery should be fully separated to the root of mesentery and the ileocecal part should be turned from front to back to avoid the occurrence of mesenteric vascular torsion and small intestinal obstruction.

BACKGROUNDCardiovascular disease is a major cause of mortality and morbidity in patients with chronic kidney disease. Macrophage death in advanced atherosclerosis promotes necrosis and plaque destabilization. In vitro data from peritoneal macrophages show apoptosis triggered through endoplasmic reticulum (ER) stress caused by free cholesterol accumulation plays an important role. Here we used THP-1 cells differentiated by 100 ng/ml of phorbol 12-myristate 13-acetate (PMA) for five days as an in vitro model, to investigate if acetylated low-density lipoprotein (AcLDL) loading could also induce apoptosis and its underlying mechanisms.

METHODSOil red O staining was used to examine the lipid droplets. Confocal microscopy was used to visualize the uptake of AcLDL. Hoechst 33258 stain and the caspase 3,7 assay were used to detect apoptosis. High performance liquid chromatography was used in the intracellular free cholesterol (FC) and cholesterol ester (CE) assay. Western blotting was used to demonstrate the protein level. Real-time PCR was used to detect the changes of mRNAs. ER free cholesterol was also assayed.

RESULTSConfocal microscopy showed THP-1 cells differentiated by 100 ng/ml of PMA for five days uptake more AcLDL than differentiated for two days. Hoechst 33258 stain showed AcLDL could induce apoptosis in THP-1 macrophages in a time and dose dependent manner. Exposure of THP-1 macrophages to 100 microg/ml of AcLDL for 24 hours resulted in a significant increase in caspase 3,7 activity, a significant increase in FC and CE mass of 1.5 and 2.4-fold, meanwhile, a significant increase in transcription factor C/EBP homologous protein and a decrease in Bcl-2 both in protein and mRNA levels were observed with an 8-fold rise of free cholesterol in the ER.

CONCLUSIONER stress is involved in AcLDL induced apoptosis in THP-1 macrophages with free cholesterol accumulation in the ER.

Apoptosis ; drug effects ; Blotting, Western ; Cell Differentiation ; physiology ; Cell Line ; Cholesterol ; metabolism ; Chromatography, High Pressure Liquid ; Endoplasmic Reticulum ; metabolism ; Humans ; Lipoproteins, LDL ; pharmacology ; Macrophages ; cytology ; drug effects ; Microscopy, Confocal ; Polymerase Chain Reaction ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; Transcription Factor CHOP ; genetics