Mechanisms of Targeted Regulation of p53-mediated Ferroptosis by Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Ferroptosis is a newly discovered non-apoptotic regulatory form of cell death characterized by accumulation of iron-dependent lipid peroxides and reactive oxygen species （ROS）. p53 is a tumor suppressor gene that can induce cell cycle arrest， apoptosis， autophagy， and senescence to maintain genomic stability by mediating transcriptional regulation of a variety of key cellular genes. Recent studies have found that p53 can also regulate ferroptosis bidirectionally by multiple cellular responses including iron metabolism， polyunsaturated fatty acid （PUFAs） metabolism， amino acid metabolism and nicotinamide adenine dinucleotide phosphate （NADPH）-mediated metabolisms， and participate in the pathological progression of diseases such as tumors， nervous system diseases， cardiovascular diseases， liver disease， and kidney disease. This paper provided a systematic review of the mechanism of p53-mediated ferroptosis in the outcome of related diseases and its influencing factors. And the research advance in the mechanisms of targeted regulation of p53-mediated ferroptosis in the prevention and treatment of cancer， stroke， acute ischemic cardiomyopathy， chronic heart failure， atherosclerosis， ulcerative colitis， and adjuvant arthritis by traditional Chinese medicine was also elaborated. This paper was expected to provide new ideas for the prevention and treatment against related diseases.

Extract of Naotaifang, a compound Chinese herbal medicine, protects neuron ferroptosis induced by acute cerebral ischemia in rats / 中西医结合学报

OBJECTIVE@#Our previous research showed that Naotaifang (a compound traditional Chinese herbal medicine) extract (NTE) has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia. In this study, we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4 (GPX4) and iron metabolism.@*METHODS@#We established an acute brain injury model of middle cerebral artery occlusion (MCAO) in rats, in which we could observe the accumulation of iron in neurons, as detected by Perl's staining. Using assay kits, we measured expression levels of ferroptosis biomarkers, such as iron, glutathione (GSH), reactive oxygen species (ROS) and malonaldehyde (MDA); further the expression levels of transferrin receptor 1 (TFR1), divalent metal transporter 1 (DMT1), solute carrier family 7 member 11 (SLC7A11) and GPX4 were determined using immunohistochemical analysis, real-time quantitative polymerase chain reaction and Western blot assays.@*RESULTS@#We found that treatment with NTE reduced the expression levels of TFR1 and DMT1, reduced ROS, MDA and iron accumulation and reduced neurobehavioral scores, relative to untreated MCAO rats. Treatment with NTE increased the expression levels of SLC7A11, GPX4 and GSH, and the number of Nissl bodies in the MCAO rats.@*CONCLUSION@#Taken together, our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7A11/GPX4 pathways.

Risk factors for early allograft dysfunction after deceased donor liver transplantation / 医学研究生学报

Objective The incidence of early allograft dysfunction (EAD) following deceased donor liver transplantation (DDLT) is high and affects the prognosis of the recipient. This study aimed to investigate the risk factors for EAD following DDLT. Methods This retrospective study included 79 cases of liver transplantation performed in the No. 900 Hospital of PLA Joint Logistic Support Force from January 2015 to December 2017. We collected the clinical data on the donors and recipients, propensity-score matched the pre- and intra-operative data on the recipients, and analyzed the risk factors for EAD identified among 17 donor-related variables. Results EAD was found in 26 (32.9%) of the recipients. Univariate analysis showed statistically significant differences between the EAD and non-EAD groups in the body mass index, warm ischemia time, and cold ischemia time of the donors (P < 0.05), and so did multivariate logistic regression analysis in the levels of serum sodium and alanine aminotransferase and warm ischemia time of the donors (P < 0.05). The best cut-off values of the serum sodium level and warm ischemia time of the donors for predicting post-operative EAD were 152.7 mmol/L and 8 min, respectively. Conclusion The serum sodium and alanine aminotransferase levels and warm ischemia time of the donors are independent risk factors for EAD after DDLT. The serum sodium level and warm ischemia time of the donors play an important role in evaluating the quality of deceased donor organs.

Synthesis of mucunaguanide / 中国药科大学学报

The aim of this study was to synthesize 1-(5-(hydroxymethyl)-4-methyl-3-oxo-3,4-dihydro-pyrazin-2-yl) guanidine (mucunaguanide),a pyrazinone alkaloid compound extracted from the seed of Stizotobium cochinchinensis.Starting from benzyloxy acetaldehyde,following four steps in reaction including condensation,cyclization,substitution and hydrogenation reaction,mucunaguanide was synthesized with total yield of 27.9％,and purity of more than 97.5％.Structures of all the intermediates and target compound were confirmed by IR,1H NMR and MS.This synthetic process was characterized with raw materials available,simple in operation with much milder reaction conditions,and was an ideal method of synthesis of this compound.

Comparative study on the quality of life in patients with prevertebral or retrosternal reconstruction after cervical tubular gastroesophagostomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the quality of life in patients with prevertebral or retrosternal reconstruction after cervical tubular gastroesophagostomy.</p><p><b>METHODS</b>A total of 167 patients enrolled in this prospective study from July 2008 to June 2012 in Shantou Central Hospital, and divided into prevertebral route group(85 cases) and retrosternal route group(82 cases) according to the random number table method. Quality of life questionnaire was investigated 1, 3, 6, 9, and 12 months after operation respectively.</p><p><b>RESULTS</b>The incidence of anastomotic stenosis was lower in the prevertebral route group (P<0.05). However, the differences in perioperative general conditions between the two groups were not statistically significant(all P>0.05). One hundred and forty-nine patients completed the postoperative quality of life questionnaire. Dysphagia and swallowing retching symptom were better, while acid reflux and heartburn symptom were more serious in prevertebral route group as compared to retrosternal route group(all P<0.05). Overall quality of life score difference between the two groups was not statistically significant(P>0.05).</p><p><b>CONCLUSIONS</b>For digestive tract reconstruction after resection of esophageal cancer, tubular gastroesophagostomy by prevertebral or retrosternal route both can obtain better quality of life after surgery. Swallowing function after surgery of the former is superior to the latter, but the reflux symptoms is more serious. Therefore the two mehods have their own advantages and disadvantages, and the choice of route should be depended on clinical experience and patient condition.</p>

Surgical strategy for ectopic kidneys: analysis of 35 cases / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the surgical strategy for ectopic kidney and evaluate the clinical outcomes.</p><p><b>METHODS</b>From January 2000 to October 2009, 35 cases of ectopic kidney were treated surgically in our hospital. Definite diagnoses were established in all the cases by ultrasound, intravenous urography (IVU), cystoscope, CT, magnetic resonance urography (MRU) and radionuclide imaging before the surgery. In these patients, 26 had ipsilateral ectopic ureteral orifice (including 5 with bilateral duplicated kidneys and ureter), 9 had moderate or severe hydronephrosis (including 3 with ectopic kidney calculi), and 24 had dysplastic kidney (24/35). All the patients underwent operations, including 26 with ectopic nephrectomy, 7 with ectopic ureterovesical reimplantation, and 3 with ectopic renal pelvis incision.</p><p><b>RESULTS</b>The clinical effect was satisfactory in all the cases during the follow up of 7 to 29 months.</p><p><b>CONCLUSION</b>Appropriate surgical approaches according to the concurrent deformities and complications can achieve good clinical results in patients with ectopic kidneys.</p>

Predict value of clinical risk score, thrombolysis in myocardial infarction flow grade and combined clinical risk score plus TIMI flow on outcome evaluation of patients with acute coronary syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the prognostic value of clinical risk score and thrombolysis in myocardial infarction (TIMI) flow grade alone or combined on outcome of acute coronary syndrome (ACS).</p><p><b>METHODS</b>A total of 206 eligible patients [135 males, mean age (67.57 +/- 9.88) years] were enrolled. The primary endpoints included cardiac death and non-cardiac death. The secondary endpoints included non-fatal stroke, reinfarction, heart failure and recurrent angina. Receiver operating characteristic curve (ROC) established by using different endpoints and clinical risk score, TIMI flow grade or combined risk scores. The prognostic value for different endpoint expressed as the area under the curve (AUC).</p><p><b>RESULTS</b>Eleven patients lost during the (11.41 +/- 5.33) months follow up and data were available for 195 patients, 8 patients reached the primary endpoints, and 17 patients reached the secondary end-points at the end of follow up. The AUC was 0.67 (95% CI = 0.557 approximately 0.786), P = 0.006; 0.68 (95% CI = 0.557 approximately 0.786), P = 0.004 and 0.730 (95% CI = 0.691 approximately 0.815), P < 0.001, respectively for clinical risk score, TIMI flow grade and the combined risk score respectively. There were no significant differences among clinical risk score, TIMI flow grade and combined risk score (all P > 0.05) for AUC and for primary end point and the secondary end point.</p><p><b>CONCLUSION</b>The result from this study suggests that the efficacy of predicting the total events based on clinical risk score, TIMI flow grade and combined risk score was similar.</p>

Relationship between body mass index, waist circumference and blood pressure among 5246 residents in Chongqing area / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the relationship between body mass index, waist circumference and blood pressure among residents in Chongqing area.</p><p><b>METHODS</b>A total of 5246 residents aged 15 and over in Chongqing area were enrolled in this study by use of stratified sampling and cluster sampling methods. Data on blood pressure (SBP, DBP), pulse, height, body weight, waist and hip circumferences as well as questionnaire survey were analyzed.</p><p><b>RESULTS</b>The level of SBP and DBP and hypertension prevalence rate were significantly positively correlated with BMI (all P < 0.01). SBP, DBP levels and hypertension prevalence rate were significantly higher in people with abdomen obesity than people with normal waist circumference (all P < 0.01). BMI, waist circumference in hypertensive residents were significantly higher than non-hypertensive residents (all P < 0.01).</p><p><b>CONCLUSION</b>Blood pressure level and hypertension prevalence rate were closely related with BMI and waist circumference among residents in Chongqing area.</p>

Chronic effects on the prevention of atrial fibrillation recurrence in patients with lone paroxysmal atrial fibrillation treated with amiodarone, segmental pulmonary vein ablation, or amiodarone plus losartan: a prospective cohort study / 中华心血管病杂志

<p><b>OBJECTIVE</b>This study was designed to compare clinical efficacy of segmental pulmonary vein ablation (SPVI), amiodarone or amiodarone plus losartan on sinus rhythm maintenance in patients with lone paroxysmal atrial fibrillation (PAF).</p><p><b>METHODS</b>Patients with lone PAF were treated with amiodarone alone (A, n = 52), segmental pulmonary vein isolation (SPVI, n = 51), or amiodarone plus losartan (AL, n = 51). The primary endpoint of this study was the incidence of symptomatic atrial tachyarrhythmia (> 30 s) documented by 12 lead ECG or Holter during 12 months follow-up period.</p><p><b>RESULTS</b>During follow-up, AF was documented in 24 patients (46.2%) in A group, 11 patients (21.6%) in SPVI group and 12 (23.5%) in AL group (P < 0.05 vs. A group). The Kaplan-Meier survival analysis demonstrated a significant equally reduction in AF recurrence in SPVI and AL groups (P = 0.009, log-rank test and P = 0.018, log-rank test, respectively) compared with A group. The hazard ratio for AF recurrence in patients treated with SPVI and amiodarone plus losartan was 0.41 (95% CI 0.200 to 0.848, P = 0.016) and 0.46 (95% CI 0.225 to 0.953, P = 0.036), respectively. Incidences of major adverse cardiac events were similar among the groups (9.6% in A, 3.9% in SPVI and 7.8% in AL group, P > 0.05).</p><p><b>CONCLUSION</b>The results of this study suggest that the segmental pulmonary vein isolation and amiodarone plus losartan are superior to amiodarone alone for preventing AF recurrence in patients with lone PAF.</p>

Polo like kinase 1 expression and prognostic value in gastric carcinomas / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To identify the expression of polo like kinase 1 (plk1) and to discuss its relationship with the clinicopathological parameters and prognosis in gastric carcinoma.</p><p><b>METHODS</b>Plk1 protein expression levels in 89 cases of resected gastric carcinomas were detected by immunohistochemistry method, the relations between plk1 expression levels and the survival periods were estimated by Kaplan-Meier curve.</p><p><b>RESULTS</b>The positive rate of plk1 expression in gastric cancer tissues was 42.7% (38/89), significantly higher than that (13.5%) in the adjacent noncancerous tissues (12/89) (P<0.01). The expression levels of plk1 were closely related to tumor differentiation, invasion and TNM stage (P<0.05). Patients with plk1-positive expression had worse prognosis than those with plk1-negative expression in gastric cancer patients (P<0.05).</p><p><b>CONCLUSIONS</b>Plk1 may promote carcinogenesis and gastric cancer development, its overexpression can be a novel marker for diagnosing certain biological behaviours and predicting prognosis in gastric cancer.</p>

Slowing progression of chronic allograft nephropathy by conversion from cyclosporin A to tacrolimus / 中南大学学报(医学版)

OBJECTIVE@#To investigate the feasibility and safety of substituting tacrolimus(FK506) for cyclosporin A(CsA) on delaying the pace of renal dysfunction in patients with biopsy-proven chronic allograft nephropathy(CAN).@*METHODS@#Seventy-three renal transplantation patients with CAN proved by allograft biopsy were collected in this study. Patients were randomly divided into 2 groups. Patients were either converted to FK506(FK506 group, n=43) or remained on their initial CsA-based immunosuppression(CsA group, n=30). The clinical data at study entry and after 12 months including blood urea nitrogen(BUN), serum creatinine(SCr), glomerular filtration rate(GFR), 24-hour urine protein excretion, serum total cholesterol(TC), triglyceride(TG), low density lipoprotein(LDL) and the side effects of calcineurin inhibitors were monitored during a follow-up of over 12 months.@*RESULTS@#Twelve months later, the level of SCr was statistically reduced and GFR levels were obviously elevated in the FK506 group as compared with CsA group [(194.8+/-42.5)micromol/L vs. (245.4+/-52.8)micromol/L and (50.14+/-3.92)mL/(min.1.73 m(2)) vs. (40.58+/-2.49)mL/(min.1.73 m2), P<0.01]. Quantity of 24-hour urine protein excretion in the FK506 group was (2.0+/-0.5)g which is significantly lower than (3.9+/-0.7)g in the CsA group(P<0.01). TC, TG, and LDL levels remained unchanged in the CsA group, while those were statistically reduced in the FK506 group respectively [(5.19+/-0.73)mmol/L vs. (6.94+/-1.37)mmol/L, (1.86+/-0.84)mmol/L vs. (3.14+/-1.38)mmol/L, (3.03+/-0.71)mmol/L vs. (3.82+/-0.89)mmol/L, P<0.01]. Tremor obviously increased (P<0.01) and hypertension obviously decreased (P<0.05) in the FK506 group compared with the CsA group.@*CONCLUSION@#FK506 treatment can greatly improve the proteinuria and hyperlipidemia. Conversion from CsA to FK506 is an effective and safe alternative therapy for delaying the progression of renal dysfunction induced by CAN.

Inhibition of polo like kinase gene expression induces apoptosis in gastric cancer cells / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To observe the effect of inhibition of polo like kinase1 (plk1) gene expression on apoptosis induction in gastric cancer cell line-MKN45 and discuss the vital role of plk1 proliferation and viability of gastric cancer cells.</p><p><b>METHODS</b>The plk1 expression was inhibited by chemically synthesized siRNA. The plk1 mRNA and protein level were respectively measured by real-time quantitative PCR and Western blotting. The spindle morphological change was observed by immunofluorescence staining and confocal microscopy. The change of cell cycle distribution and apoptosis rate was detected by flow-cytometry. Pro caspase3 level was also detected by western blotting.</p><p><b>RESULTS</b>After treatment by siRNA targeting plk1, plk1 mRNA and protein level decreased obviously, the cell mitotic spindle became obscure and lost cohesiveness, more MKN45 cells accumulated at G(2)/M phase (P< 0.05), apoptosis rate of plk1 siRNA treated MKN45 cells was higher than that of control cells at 48 h and 72 h (P< 0.05) with pro-caspase3 level decreasing at 72 h.</p><p><b>CONCLUSIONS</b>Inhibition of plk1 gene expression induces apoptosis in MKN45 cells through the pathway of caspase3. Plk1 gene play a key role in viability of MKN45 cells.</p>

Analysis of gene expression profiles in gastric cancer cell cycle / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the gene expression profile in gastric cancer cell cycle and explain the mechanism of gastric cancer cell proliferation by a genomic study.</p><p><b>METHODS</b>Gastric cancer cells MKN45 were synchronized at G2/M and G1/S point by nocodazole-thymidine and double thymidine methods. The synchronizing degree of cells was monitored by flow cytometry. The gene expression profiles at G2/M point, M/G1 transition, G1 early phase, G1 late phase, G1/S point, S early phase, S late phase, G2 early phase and G2 late phase in MKN45 cell cycling were examined using cDNA microarray chips. Hierarchy analysis was conducted with a professional software package and the up-regulated genes at G1 late and G2 phase were analyzed according to gene database. Furthermore, the mRNA level of cyclin E, cyclin B, plk1 and STK15 in above mentioned nine points were measured by quatitative PCR.</p><p><b>RESULTS</b>2001 genes were detected to be available at all 9 points via software processing, out of which 959 appeared up-regulated or down-regulated. 379 genes showed to be up-regulated at late G1 (147) or G2 phases (232), 40 at S and M phases (also up-regulated at G1 late and G2 phases). The 147 up-regulated genes at G1 late phase are involved in DNA metabolism, transcription and translation, protein transportation, ubiquitination and signal transduction, etc. The 232 up-regulated genes in G2 phase are involved in RNA synthesis and processing, intracellular protein transportation, cytoskeleton synthesis, signal transduction, apoptosis and anti-apoptosis, transcription regulation, ubiquitination, mitosis regulation and oncogene expression, etc. The mRNA level of 4 genes detected by quantitative PCR during cell cycle was in agreement with that detected by microarray.</p><p><b>CONCLUSION</b>During MKN45 cell cycling, the preparation for DNA synthesis and chromosome separation are conducted in G1 and G2, which are implicated in multiple genes, may be the main impetus of driving MKN45 cell cycle. Some of these genes may be related to tumor over-proliferation. The cDNA microarray technique has characteristic features such as reliability and can provide a great deal for future research on cell cycle related genes in gastric cancer.</p>

Inhibition of serine/threonine kinase 15 gene expression induces apoptosis of gastric cancer cells / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To observe the effect of inhibition of serine/threonine kinase15 (STK15) gene expression on apoptosis induction in gastric cancer cell line-MKN45 and discuss the role of STK15 in viability of gastric cancer cells.</p><p><b>METHODS</b>The STK15 expression was inhibited by chemically synthesized siRNA. The STK15 mRNA and protein level were respectively measured by real-time quantitative PCR and western blotting,the change of cell cycle distribution and apoptosis rate were detected by flow-cytometry, cell morphological change was observed by Hoechst staining,and pro-caspase 3 level was also detected by western blot.</p><p><b>RESULTS</b>After treatment by siRNA targeting STK15 after 48 h, STK15 mRNA and protein level decreased obviously. More MKN45 cells accumulated at G(2)/M phase (P< 0.05). The apoptosis rate of STK15 siRNA treated MKN45 cells was higher than that of control cells(P< 0.05) with the pro-caspase 3 level decreased.</p><p><b>CONCLUSIONS</b>Inhibition of STK15 gene expression may induce apoptosis in MKN45 cells through the pathway of caspase3. STK15 gene play a key role in proliferation and viability of MKN45 cells.</p>

Correlation between pressure-derived coronary collateral flow and Rentrop grade after primary percutaneous intervention of acute myocardial infarction / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the correlation between pressure-derived collateral coronary flow (PDCF) and Rentrop grade of patients with acute myocardial infarction (AMI).</p><p><b>METHODS</b>PDCF, determined by the ratio of P(w)/P(a), was measured in 29 patients with AMI of the first onset who received primary percutaneous coronary intervention (PCI) within 12 h after the onset. Sufficient collateral flow (group A, n=19) was defined as PDCF>0.24 and insufficient collateral flow (group B, n=10) as PDCF< or =0.24. Rentrop grade of the collateral flow was evaluated by coronary angiography. Echocardiography was performed on the 3rd and 30th day after PCI. The left ventricular ejection fraction, end-systolic and end-diastolic volumes, and the related indexes were obtained.</p><p><b>RESULT</b>Rentrop grade was significantly related to PDCF (r=0.75, P<0.01), but a wide range of PDCF was observed in patients with Rentrop grade< or =1.</p><p><b>CONCLUSION</b>PDCF measurement allows quantitative evaluation of the collateral flow in patients with AMI.</p>

Mitosis arrest caused by inhibition of PLK1 expression in gastric cancer MKN45 cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the effect of polo-like kinase 1 (PLK1) gene depletion on mitosis phenotype and elucidate its vital role in gastric cancer cell line (MKN45) mitosis.</p><p><b>METHODS</b>The PLK1 expression in MKN45 cells was blocked by RNA interference (RNAi), the expression level of PLK1 mRNA and protein were measured by real-time quantitative PCR and Western blot, respectively. The morphological change of microtubules and mitosis phenotype in MKN45 cells were observed by immunofluorescence staining and laser confocal microscopy, the morphological changes of cells were observed by reverse microscopy, the variation of cell cycle distribution was detected by flow-cytometry.</p><p><b>RESULTS</b>After RNAi targeting PLK1, PLK1 mRNA and protein level decreased obviously, the cell microtubules became obscure and lost cohesiveness, the mitosis phenotype also varied substantially (P < 0.05), more gastric cancer cells became rounded and showed G(2) phase cell DNA content (P < 0.05).</p><p><b>CONCLUSION</b>PLK1 gene plays a key role in mitosis and its inhibition can lead to mitosis arrest in MKN45 cells.</p>

Long-term clinical efficacy of losartan or perindopril combination therapy with low-dose amiodarone in patients with paroxysmal atrial fibrillation / 中华心血管病杂志

<p><b>OBJECTIVE</b>The purpose of the present study was to evaluate the clinical efficacy of perindopril or losartan in combination with low-dose amiodarone on maintenance of sinus rhythm in patients with idiopathic paroxysmal atrial fibrillation (PAF).</p><p><b>METHODS</b>One hundred and eighty-one patients with idiopathic PAF were included in the study and randomly divided into three groups: group 1 (amiodarone group, n = 61) was treated with amiodarone alone, group 2 (amiodarone plus losartan, n = 59) was treated with amiodarone and perindopril in combination, and group 3 (amiodarone plus perindopril group, n = 61) was treated with amiodarone and perindopril in combination. The left atrial diameter (LAD) was measured with transthoracic echocardiogram at before and after 6, 12, 18 and 24-month of treatment. The duration of observation was up to two years and the primary end point of the study was the first recurrence of AF.</p><p><b>RESULTS</b>During the 6 month following up, there was no difference in LAD among the three groups. After 12 months, LAD in group 1 was significantly larger than group 2 and group 3 (P < 0.05). At 7th-month, the sinus rhythm maintenance of group 1 was lower significantly than group 2 and group 3. At the end of the study, the maintenance of sinus rhythm in group 2 and group 3 was higher significantly than in group 1 (83.05% and 80.33% vs 59.01%, P < 0.05), nevertheless, there was no significant difference between group 2 and group 3.</p><p><b>CONCLUSIONS</b>The results of this study suggest that the combination of amiodarone with angiotensin converting enzyme inhibitor perindopril or with angiotensin II receptor antagonist losartan are more effective than amiodarone alone in sinus rhythm maintenance for idiopathic PAF. ACEI and ARB can inhibit the enlargement of left atrium and reduce recurrence rate in patients with idiopathic PAF.</p>

Mitotic arrest of gastric cancer cells induced by silencing of STK15 gene / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the role of STK15 in regulating mitosis of gastric cancer cells (MKN45) by gene silencing through RNA interference mechanism.</p><p><b>METHODS</b>RNA interference technique was used to inhibit STK15 expression in MKN45 cells. The expression levels of STK15 mRNA and protein were measured by real-time quantitative RT-PCR and Western blot respectively and cell morphological changes were investigated by reverse microscopy. In addition, cell cycle distribution and cellular proliferation were determined by flow-cytometry and MTT assay respectively. Finally, the mitotic phenotype of MKN45 cells was studied by immunofluorescence staining and confocal microscopy.</p><p><b>RESULTS</b>Silencing of STK15 gene by RNA interference was confirmed by marked decrease of STK15 mRNA and protein levels in the treated MKN45 cells. This silencing correlated with rounding of the cells, decreasing of DNA content in G(2) phase (P < 0.05) and a lowered proliferation index (P < 0.05), along with alterations of mitotic phenotype of MKN45 (P < 0.05).</p><p><b>CONCLUSION</b>STK15 gene may play a key role in regulating cellular mitosis and its inhibition by RNA interference leading to mitosis arrest in MKN45 cells.</p>

Study of growth inhibition of gastric cancer cells by sRNA targeting polo like kinase 1 in vitro and vivo / 中华外科杂志

<p><b>OBJECTIVE</b>To observe the effect of polo like kinase 1 (plk1) gene depletion on the growth of gastric cancer cell line-MKN45 cells in vitro and vivo and discuss the feasibility and effectiveness of arranging plk1 as gene therapeutic target for gastric cancer.</p><p><b>METHODS</b>The plk1 expression of MKN45 cells was inhibited by RNA interference (RNAi). The plk1 mRNA and protein level were measured by real-time quantitative PCR and western blotting, and the change of cell cycle distribution and apoptosis rate were detected by flow-cytometry, and the MKN45 cells proliferation was measured by MTT method. MKN45 cells treated with plk1 siRNA were transplanted subcutaneously in nude mice and their tumorgenesis ability were observed, the plk1 protein levels of the samples from nude mice in different groups were compared.</p><p><b>RESULTS</b>After treatment with plk1 siRNA, plk1 mRNA and protein level decreased obviously in certain time, more MKN45 cells accumulated at G(2)/M (P < 0.05). Apoptosis rate of MKN45 cells treated with plk1 siRNA was higher than that of control cells at 48 h and 72 h (P < 0.05), and MKN45 cells proliferated slowly than control groups (P < 0.05), while the tumorgenesis ability obviously decreased, but the plk1 protein levels of the samples from nude mice in different groups were not different.</p><p><b>CONCLUSIONS</b>siRNA targeting plk1 can inhibit the proliferation of MKN45 cells in vitro and vivo. Plk1 may be a novel therapeutic target for gastric cancer.</p>

Analysis of gene expression profile of G1/S transition in gastric cancer cell cycle / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To detect the variation of gene expression profile of G1/S transition and elucidate the role of related genes regulating cell cycle from G1 to S phase in gastric cancer.</p><p><b>METHODS</b>Nocodazole-thymidine and double thymidine methods were used to synchronize gastric cells at G2/M and G1/S point, cDNA microarray chips was applied to examine the gene expression profile at G1 early and late phase, S early and late phase during the cell cycle, hierarchy analysis was conducted by a professional software package.</p><p><b>RESULTS</b>A total of 2001 genes were detected available, 959 genes appeared to be upregulated or downregulated, including 147 genes upregulated at G1 late phase. These 147 genes are involved in DNA metabolism, transcription and translation,posttranslational modification, ubiquitination, signal transduction etc, which all affected cell cycle from different aspects.</p><p><b>CONCLUSION</b>Complex multiple gene processes, such as DNA metabolism, transcription and translation, posttranslational modification, ubiquitination, signal transduction etc,are implicated in and also essential for G1/S transition during gastric cancer cell cycle, part of these genes are significantly associate with overproliferation in gastric cancer.</p>