Animals ; Aorta ; drug effects ; physiology ; Blood Pressure ; drug effects ; Cadmium ; toxicity ; Female ; In Vitro Techniques ; Male ; Muscle, Smooth, Vascular ; drug effects ; physiology ; Rabbits ; Vasoconstriction ; drug effects

OBJECTIVETo assess the value of determination of urine kidney injury molecule-1 (KIM-1) protein content in the early diagnosis of radiocontrast-induced nephropathy (RCIN) in rats.

METHODSSeventy-two adult male SD rats were randomly divided into groups A, B, C (n=8) and D group (which was subdivided into 2, 6, 12, 24, 48 h and 7 days groups, n=8). Group A was subject to injections via the tail vein of PBS and normal saline (NS), group B received injections of PBS, NS, and contrast medium (CM), group C with indomethacin (INDO), nitric oxide synthase inhibitor (L-NAME), and NS, and group D with INDO, L-NAME and CM. Each injection was given at the interval of 15 min.

RESULTSIn group D, serum creatinine (Scr) and urea nitrogen (BUN) were significantly increased at 6 h after the injections (P<0.001), peaked at 24 h and recovered normal levels at 48 h. Histological examination revealed significant pathological changes in the kidneys at 6 h, showing diffuse tubulointerstitial hyperemia and hemorrhage, marked tubular necrosis and tubular structure destruction; at 12 h, significant tubular necrosis was still present with tubular structure destruction, but the tubulointerstitial hemorrhage was alleviated; at 24 h, tubular regeneration occurred in the renal medulla, but even till 7 days the tubular structures failed to show full recovery. In group D, urine KIM-1 level began to increase at 2 h, reached the peak level at 24 h, and lasted till 7 days (P<0.001); urine N-acetly-β-D-glucosaminidase (NAG) value began to increase at 6 h and became normal at 48 h. Urine MMP-9 level underwent no significant changes in group D over the time points of observation.

CONCLUSIONThe results show that urinary KIM-1 levels can be used as an indicator for early diagnosis of RCIN.

Animals ; Biomarkers ; urine ; Cell Adhesion Molecules ; urine ; Contrast Media ; adverse effects ; Early Diagnosis ; Kidney Diseases ; chemically induced ; diagnosis ; urine ; Male ; Radiopharmaceuticals ; adverse effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Animals ; Apoptosis ; drug effects ; Azo Compounds ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Drug Delivery Systems ; Humans ; Liver ; metabolism ; Liver Neoplasms ; pathology ; Nitrates ; chemical synthesis ; pharmacology ; Nitric Oxide Donors ; chemical synthesis ; pharmacology ; Oleanolic Acid ; analogs & derivatives ; chemical synthesis ; pharmacology ; Piperazines ; chemical synthesis ; pharmacology ; Ursodeoxycholic Acid ; analogs & derivatives ; chemical synthesis ; pharmacology

Objective To compare the prophylactic efficacy of combination of ganciclovir and acy- clovir or acyclovir alone against cytomegalovirus pneumonia in renal transplant recipients.Methods A to- tal of 217 renal transplant recipient(124 men and 93 women;mean age,32 years;age range,16-72 years) were divided into 3 groups randomly.In 51 cases,acyclovir was taken orally at a dose of 400 mg,3/d,from the third d to 3 months after transplantation.In 74 cases,ganciclovir was administered at a dose of 250 mg/d intravenously from the 21st d to 27th d to replace Acyclovir.In 92 cases,no prophylaxis against eytomegalov- irus pneumonia was performed.All patients were followed 3 months after transplantation.Comparison of the incidence rates of cytomegalovirus pneumonia among the 3 groups was performed using Fisher's exact test. Results Cytomegalovirus pneumonia developed in 20 cases in the 3 groups,including 4 cases(5.4%) in combined use group,2 cases(3.9%)in acyclovir alone group,and 14 cases(15.2%)in control group. Significant difference existed between the 2 experimental and control groups(P＜0.05).However,no signifi- cant difference existed between the 2 experimental groups(P＞0.05).Of the 20 cases,17(85.0%)were cured,and 3 died of respiratory failure.Conclusions Ganciclovir and acyclovir have prophylactic effect a- gainst cytomegalovirus pneumonia in renal transplant recipients.These 2 medications are inexpensive,and the patients have good compliance.

Objective To detect the mutations of ATP2C1 gene in patients with Hailey-Hailey dis- ease (HHD).Methods PCR and direct sequencing were performed in 17 patients and 120 healthy controls to screen the mutations in the exons of ATP2C1 gene.Results Eight mutations were identified in nine probands, including three deletion mutations (nt1464-1487 del/nt1462-1485del,1523delAT,2375delTTGT),three splice site mutations (360—2A→G,1415—2A→T,2243+2T→C) and two missence mutations (C920T and G1942T).None of the above mutations was found in the controls.Conclusion Eight specific novel mutations were identified in nine probands of HHD,which could be causative factors of the disease.

Objective The aim of this study is to investigate the prognostic molecular features to predict the prognosis of gastric cancer(GC)and its relationship with immune cell infiltration based on comprehensive analysis of telomere-related gene(TRG)expression data.Methods The survival and prognostic correlation of GC telomere-related gene were analyzed by combining TCGA and GEO database.Two telomere related gene clusters were identified by unsupervised clustering,a prognostic model was constructed based on Lasso regression and multi-factor cox regression analysis,and a nomogram was constructed combined with clinical traits to predict the survival of patients.Meanwhile,risk difference analysis was performed,ROC curve was used to evaluate the prediction accuracy of the model,and immune cell infiltration analysis was performed on the samples.Results A prognostic model containing 12 genes,including HEYL,SPC25,SRPX2,PDK4,LOXL4,SOX15,SLC39A4,MAGEA3,SHISA2,DEFB1,SLC27A2 and C1QTNF5,was constructed to evaluate the prognosis of GC patients.An integrated risk profile was constructed to predict 1-year,3-year,and 5-year overall survival(OS)of GC patients.The survival rate in the high-risk group was significantly lower than that in the low-risk group(P＜0.05),and the proportion of immune cell subtypes in different risk groups was different.Conclusion This study identifies a TRG-derived molecular subtype in GC and develops a new prognostic scoring model,highlighting the potential value of TRG in GC prognosis and immunotherapy.

A heat shock treatment was studied in glycerol fermentation of osmotolerant yeast Candida krusei. The experiment results showed that the optimal temperature and duration time for heat shock is 45℃ and 30 min respectively,and the optimal start time of the treatment is at the mid term in exponential growth stage. With such treatment, glycerol yield was enhanced greatly,while no signficant effects on both cell growth and glucose consumption were observed.

BACKGROUNDRecent clinical and preclinical studies have suggested that deep brain stimulation (DBS) can be used as a tool to enhance cognitive functions. The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit, including the anterior nucleus of thalamus (ANT), the entorhinal cortex (EC), and the fornix (FX), on cognitive behaviors in an Alzheimer's disease (AD) rat model.

METHODSForty-eight rats were subjected to an intrahippocampal injection of amyloid peptides 1-42 to induce an AD model. Rats were divided into six groups: DBS and sham DBS groups of ANT, EC, and FX. Spatial learning and memory were assessed by the Morris water maze (MWM). Recognition memory was investigated by the novel object recognition memory test (NORM). Locomotor and anxiety-related behaviors were detected by the open field test (OF). By using two-way analysis of variance (ANOVA), behavior differences between the six groups were analyzed.

RESULTSIn the MWM, the ANT, EC, and FX DBS groups performed differently in terms of the time spent in the platform zone (F(2,23) = 6.04, P < 0.01), the frequency of platform crossing (F(2,23) = 11.53, P < 0.001), and the percent time spent within the platform quadrant (F(2,23) = 6.29, P < 0.01). In the NORM, the EC and FX DBS groups spent more time with the novel object, although the ANT DBS group did not (F(2,23) = 10.03, P < 0.001). In the OF, all of the groups showed a similar total distance moved (F (1,42) = 1.14, P = 0.29) and relative time spent in the center (F(2,42) = 0.56, P = 0.58).

CONCLUSIONSOur results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently than ANT DBS. In addition, hippocampus-independent recognition memory was enhanced by EC and FX DBS. None of the targets showed side-effects of anxiety or locomotor behaviors.

Alzheimer Disease ; physiopathology ; therapy ; Animals ; Anterior Thalamic Nuclei ; physiology ; Deep Brain Stimulation ; methods ; Entorhinal Cortex ; physiology ; Fornix, Brain ; physiology ; Male ; Memory ; physiology ; Rats ; Rats, Sprague-Dawley ; Spatial Learning ; physiology

OBJECTIVETo investigate the role of protein kinase C (PKC) in the down-regulation of fibroblast proliferation in normal skin (NFb) and hyperplastic scar (SFb) by adrenaline.

METHODSHuman NFb and SFb cells were cultured in vitro. Phentolamine (in final concentrations of 0 and 3 x 10(-6) micromol/L) was added to the culture medium. One hour later, adrenaline in different final concentrations (0.00, 0.05, 0.10, 0.20 micromol/L) was added to the culture medium and incubated for 24 hours. The cellular proliferation activity and cell viability rate were determined with MTT. The cell culture supernatant was harvested for the determination of LDH activity to assess the toxicity of phentolamine and adrenaline. The phosph-PKC activity was determined with Western-blotting and was semiquantitatively analyzed.

RESULTS(1) After stimulation with adrenaline alone, or combined 0.20 micromol/L adrenaline with 3 x 10(-6) micromol/L phentolamine, the cell viability of both NFb and SFb decreased significantly (P < 0.05 or 0.01). (2) There was no difference in the LDH activity between the cells either stimulated by adrenaline in all concentrations or by combination of adrenaline and phentolamine (P > 0.05). (3) The phosphorylation of PKC in NFb and SFb cells stimulated by 0.05, 0.10, 0.20 micromol/L adrenaline was obviously higher than that before stimulation (P < 0.01). When phentolamine in the concentration of 3 x 10(-6) micromol/L was used alone for stimulation, the phosphorylation of PKC in NFb cells (123 +/- 5) was also evidently higher than that before stimulation (80 +/- 5, P < 0.01). But there was no such effect on SFb cells (P > 0.05). When adrenaline in the concentration of 0.05, 0.10 or 0.20 micromol/L was separately added together with phentolamine in the dose of 3 x 10(6) micromol/L for the stimulation, the phosphorylation of PKC in NFb and SFb cells was evidently lower than that when 3 different concentrations of adrenaline was used alone for stimulation (P < 0.01).

CONCLUSIONAdrenaline can inhibit the proliferation of NFb and SFb by activating PKC through binding alpha adrenaline receptor.

Cell Proliferation ; drug effects ; Cells, Cultured ; Cicatrix, Hypertrophic ; metabolism ; Down-Regulation ; Epinephrine ; adverse effects ; Fibroblasts ; cytology ; Humans ; Phentolamine ; adverse effects ; Phosphorylation ; Protein Kinase C ; metabolism ; Skin ; drug effects

OBJECTIVETo investigate the influence of adrenaline on the expression of TGFbeta1, bFGF and procollagen for human normal and hypertrophic scar dermal fibroblasts cultured in vitro.

METHODSHuman normal and hypertrophic scar dermal fibroblasts were propagated in a serum-free in vitro model with adrenaline for 24 hours. The human mRNA levels of bFGF, TGF-beta1 and I procollagen in fibroblasts were determined by RT-PCR. Levels of bFGF and TGF-beta1 in the supernatants of fibroblasts cultured in vitro were determined by enzyme-linked immunosorbent assay (ELISA).

RESULTSIn our study, adrenaline caused statistically significant increase in the peak levels of bFGF for normal and hypertrophic scar fibroblast cell lines (P < 0.01). It also caused statistically significant decrease in the level of TGF-beta1 for normal and hypertrophic scar fibroblast cell lines. Modulation of normal fibroblasts with 0.05, 0.10 and 0.20 micromol/L adrenaline resulted in a statistically significant (P < 0.01) decrease in the expression of I procollagen mRNA. However, only 0.20 micromol/L adrenaline can decreased the mRNA expression of I procollagen in the hypertrophic scar fibroblasts.

CONCLUSIONSWe conclude from these results that adrenaline can increase the production of bFGF and decrease production of TGF-beta1 and I procollagen in human normal dermal and hypertrophic scar fibroblasts cultured in vitro.

Cells, Cultured ; Cicatrix, Hypertrophic ; metabolism ; Collagen Type I ; metabolism ; Epinephrine ; pharmacology ; Fibroblast Growth Factor 2 ; metabolism ; Fibroblasts ; drug effects ; metabolism ; Humans ; Procollagen ; metabolism ; RNA, Messenger ; metabolism ; Transforming Growth Factor beta1 ; metabolism