Campothecin suppresses cell proliferation and migration in head and neck squamous cell carcinoma by blocking RAB27A-mediated phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway.

Camptothecin (CPT), a naturally occurring alkaloid derived from the Camptotheca acuminate plant, exerts anti-tumor properties. However, its specific impact on head and neck squamous cell carcinoma (HNSCC) remains uncertain. The study was to explore the action and mechanism of CPT on HNSCC cells. First, two HNSCC cell lines (FaDu and TU686) and a normal immortalized keratinocyte (HEK001) cell line, were exposed to a spectrum of CPT concentrations (ranging from 10 to 50 µM) for durations of 24 h and 48 h. Cell viability, proliferation, migration, and invasion were assessed by CCK-8 assay, EdU incorporation assay, wound healing assay and transwell assay. Subsequently, si-RAB27A or negative control (NC) was introduced into FaDu and TU686 cells through transfection, and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway was manipulated with L740Y-P, an activator of this pathway. The expression of proliferating cell nuclear antigen (PCNA), E-cadherin, PI3K/AKT signaling factors and RAB27A were determined by Western blot analysis. RAB27A was detected by immunofluorescence assay. It was found that CPT significantly hindered the viability, proliferation (p<0.01), migration (p<0.001), and invasion (p<0.001) of FaDu and TU686 cells. At the molecular level, administration of CPT caused a decline in the expression of PCNA, P-PI3K, P-AKT, and RAB27A, alongside an elevation in E-cadherin levels within HNSCC cells (p<0.05, p<0.01 and p<0.001). Reducing RAB27A expression enhanced the suppressive impacts of CPT on HNSCC cell viability (p<0.05 and p<0.01), migration (p<0.001) and invasion (p<0.01), these effects that were reversed upon treatment with L740Y-P in HNSCC cells (p<0.001). In summary, our study highlights the efficacy of CPT in HNSCC, demonstrating its influence on cell processes via the RAB27A-mediated PI3K/AKT pathway.

Risk factors of common bile duct stones recurrence and nomogram for predicting recurrence after endoscopic retrograde cholangiopancreatography: a dual-center retrospective cohort study.

OBJECTIVE: Common bile duct stone (CBDS) is one of the common diseases in the digestive system, for which endoscopic retrograde cholangiopancreatography (ERCP) is a treatment procedure. However, the risk factors for CBDS recurrence after ERCP remains unclear. This study aims to compare the risk factors of CBDS recurrence after ERCP, and to set up a nomogram model to predict the long-term risk. PATIENTS AND METHODS: A retrospective analysis of 355 patients was reviewed. Univariate and multivariate analyses were performed to identify the risk factors for recurrence. The R packages were used for the model building. The validation set contained 100 patients. RESULTS: The patients were divided into three subgroups: treated by cholecystectomy after ERCP (11.76% recurrence rate), treated without surgery after ERCP (19.70%), and with a prior history of cholecystectomy (43.64%). Each of them has different independent risk factors, and high body mass index (BMI) is correlated with an increased risk among all the subgroups. A prior history of cholecystectomy is a candidate factor that increases the risk of CBDS recurrence in patients older than 60 years, with a greater BMI, or receiving ERCP combined with EPBD. We built a nomogram model to predict the risk of long-term CBDS recurrence based on the risk factors including age, BMI, CBD diameter, the number of CBDS, and the gallbladder- or biliary tract-related events. CONCLUSIONS: CBDS recurrence is related to congenital and anatomical factors. Cholecystectomy would not be helpful to prevent CBDS recurrence, and a prior history of cholecystectomy may indicate a high risk of recurrence.

[Mortality of drowning and road traffic injury among children aged 5-14 in China from 2008 to 2019].

Objective: To analyze the trajectory of drowning and road traffic injury mortality among children aged 5-14 years in China from 2008 to 2019. Methods: Mortality data of unintentional injuries were from the Mortality Surveillance Data Set of National Disease Surveillance System from 2009 to 2018 and grouped by regions, urban and rural areas, genders, and age groups. The trajectory model was used to analyze the trend of drowning and road traffic injury mortality with years. Results: The mortality of drowning and road traffic injury showed a similar trend. In the trajectory model of drowning mortality, east, middle and west rural boys and western urban boys of all ages belonged to the high mortality group. The moderate mortality group included eastern urban boys and western girls aged 5-9 years and also contained eastern and middle urban boys and western urban girls aged 10-14 years. The other combinations belonged to the low mortality group. In the trajectory model of road traffic injury mortality, western urban boys, all rural boys and western rural girls aged 5-9 years, middle and western rural boys and western urban boys aged 10-14 years belonged to the high mortality group. Eastern urban girls aged 5-9 years and 10-14 years belonged to the low mortality group. The other combinations belonged to the moderate mortality group. Conclusion: There are different groups in the trajectory model of drowning and road traffic injury mortality among children in China. Identifying the trajectory of injury mortality is helpful to carry out more targeted prevention in China.

Evaluation of physiological and molecular responses to acute heat stress in two chicken breeds.

High environmental temperatures are a foremost concern affecting poultry production; thus, understanding and controlling such conditions are vital to successful production and welfare of poultry. In view of this, a completely randomized design with a 2 × 2 factorial arrangement involving two local strains (Kirin chicken (KC) and Three-yellow chicken (TYC)) and two temperature groups (normal/control = 30 ±â€¯2 °C and acute heat stress (AHS) = 35 ±â€¯1 °C for 8-h with 70% humidity) was used to assess the main regulatory factors such as heat shock protein (HSP70) gene, cytokine genes (IL-1ß, IL-6, IL-10), muscle development gene (IGF-1) and tissue histopathological changes. At 56 days old, the temperatures of the comb (CT), feet (FT), eyelid (ET) and rectal (RT) from each group were taken thrice at 0, 2, 4 and 8-h during AHS, and 1 and 3-h recovery period after AHS. At 80 days old, the slaughter weight was also analyzed. The CT and ET of the AHS groups increased during the 8-h trial, while the RT of both strains decreased significantly at 4 h but increased at 8 h in the TYC group. All temperature recordings dropped in the AHS groups of both strains during the recovery period. The results revealed that the mRNA expression of HSP70 in the liver was higher in the heat-stressed group of both strains compared to the control. The expression of HSP70 was shown in the AHS-KC group to be significantly high compared to the control (P < 0.05). Moreover, the IGF1 gene in the liver, breast muscle and leg muscle was downregulated in the AHS-TYC group compared to the control (P < 0.05), although that in the AHS-KC was downregulated in the breast muscle. The mRNA expression of spleen IL-1ß significantly decreased in the AHS-TYC group (P < 0.01), whereas that of the AHS-KC had no significant difference (P > 0.05). The mRNA expression of spleen IL-6 and IL-10 was increased in the AHS-KC group but did not exhibit obvious changes in the AHS-TYC. Correspondingly, the histopathological examinations revealed tissue injury in the AHS groups of both strains, with the TYC strain experiencing more severe changes. The final live and carcass weights showed a significant enhancement in the treatments (P < 0.01 and P < 0.05, respectively) and treatment×strain interaction (P < 0.05) with breast muscle rate significantly reducing among the treatments (P < 0.01) at 80 days. In conclusion, the differential response to AHS after physiological, molecular and immune response portrays KC to have better thermal tolerance than the TYC.

[A multicenter, randomized, open and positive parallel controlled clinical study of clotrimazole vaginal expansion suppository and vaginal tablet in the treatment of mild and moderate vulvovaginal candidiasis].

Objective: Using clotrimazole vaginal tablet as a positive control, to evaluate the results of clotrimazole vaginal expansion suppository in the treatment of mild and moderate vulvovaginal candidiasis in terms of efficacy, patient satisfaction, side effects, and recurrence rate. Methods: This study was jointly conducted by 5 hospitals from August 2017 to October 2018, patients with mild and moderate vulvovaginal candidiasis confirmed by fungal culture and symptoms scores were selected. They were randomized to experimental group and control group as 1∶1 ratio. In the experimental group (n=105), the subjects applied clotrimazole vaginal expansion suppository (150 mg) daily at night for 7 days. In the control group (n=106), the subjects used a single dose of clotrimazole vaginal tablet (500 mg). Follow-ups were performed at (8±3) and (30±5) days after the discontinuation of the drugs, respectively. The difference in clinical symptoms and signs scores was used to evaluate the improvement of clinical symptoms, and the patient's satisfaction and side effects were recorded. Results: At the first follow-up, the experimental group and control group were followed up by fungal culture on the cure rate [66.7% (70/105) versus 63.2% (67/106), P>0.05] and total effective rate [98.1% (103/105) versus 99.1% (105/106), P>0.05], the differences were not statistically significant. At the second follow-up, the recurrence rates of the experimental group and the control group were 5.7% (4/70) and 14.9% (10/67), respectively, with no significant difference (P>0.05). In the evaluation of patient satisfaction, the leakage of the drug in the experimental group was significantly better than that in the control group (P<0.01). The side effects mainly included vaginal stimulation, itching and burning sensation, and there was no statistical difference between the two groups (χ2=1.070, P=0.586). Conclusions: In the treatment of mild and moderate vulvovaginal candidiasis, clotrimazole vaginal expansion suppository is no less effective than clotrimazole vaginal tablet, and there is no significant difference in the recurrence rate between the two. In terms of patient satisfaction, clotrimazole vaginal expansion suppository is superior to clotrimazole vaginal tablet.

[Evaluation of the safety of diphtheria, tetanus and acellular pertussis containing combination vaccines in Chengdu, 2015-2019].

Objective: To evaluate the safety of diphtheria, tetanus and acellular pertussis (DTaP) containing combination vaccines used in Chengdu. Methods: The AEFI reports data of DTaP vaccine, DTaP-Haemophilus influenza type b combined vaccine (DTaP-Hib) and DTaP-inactivated poliovirus-Hib combined vaccine (DTaP-IPV-Hib) in Chengdu from 2015 to 2019 were collected through the national immunization management system. Description epidemiological method was used to analyze the data. Results: From 2015 to 2019, a total of 8 234 cases of AEFI of DTaP containing combination vaccines were reported in Chengdu, with a reported incidence of 194.55/100 000 doses, including 7 897 cases of common adverse reaction (168.59 per 100 000) and 234 cases of rare adverse reaction (5.53 per 100 000). The DTaP vaccine reported 4 240 cases AEFI (140.63 per 100 000), the DTaP-Hib vaccine reported 2 490 cases AEFI (399.09 per 100 000) and the DTaP-IPV-Hib vaccine reported 1 504 cases AEFI (253.49 per 100 000). All the three vaccines had the highest incidence for the booster doses; the rare adverse reaction were mainly Anaphylactic Reaction (6.27 per 100 000). Conclusions: The AEFI monitor system had high sensitivity, and the rare adverse reaction rate was extremely low, all the vaccines had good safety profiles. The Thrombocytopenic purpura and Laryngeal Edema should be paid more attention to.

The relationship between intestinal flora changes and osteoporosis in rats with inflammatory bowel disease and the improvement effect of probiotics.

OBJECTIVE: The aim of this study was to investigate the relationship between the changes in intestinal flora and the occurrence of osteoporosis in rats with inflammatory bowel disease and the improvement effect of probiotics. MATERIALS AND METHODS: A total of 100 Sprague Dawley (SD) model rats with colitis were selected as research objects. All rats were randomly divided into two groups, including: bowel disease group and osteoporosis group, with 50 rats in each group. Stool samples were collected from all rats, and Lactobacillus, Escherichia coli and Bifidobacteria were cultured and counted. The relationship between the occurrence of related osteoporosis and intestinal flora was analyzed as well. Thereafter, the rats in osteoporosis group were randomly divided into two subgroups, namely, control group (n=25) and observation group (n=25). Observation group was treated with probiotics by gastrogavage, while the control group was treated with the same volume of physiological saline. Next, the changes in serum osteoprotegerin (OPG), osteoprotegerin ligand [receptor activator of nuclear factor-kappa B ligand (RANKL)], procollagen type I carboxy-terminal propeptide (PICP), bone mineral density (BMD), bone alkaline phosphatase (BALP), tartrate-resistant acid phosphatase (TRACP), calcium concentration (Ca), and inflammatory cytokine levels were compared between the two groups after intervention. RESULTS: Osteoporosis group had significantly more Escherichia coli and notably fewer Lactobacillus and Bifidobacteria than bowel disease group (p<0.05). Pearson correlation analysis revealed that the occurrence of osteoporosis in rats with inflammatory bowel disease was negatively correlated with the count of Escherichia coli, whereas was positively related to the counts of Lactobacillus and Bifidobacteria (p<0.05). Moreover, the levels of serum OPG, PICP, TRACP, and Ca in observation group were remarkably higher than those in the control group (p<0.05). However, the levels of serum RANKL, BALP, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (INF-γ) were markedly lower than those in the control group (p<0.05). CONCLUSIONS: Osteoporosis in rats with inflammatory bowel disease has a negative association with the count of Escherichia coli, and a positive correlation with the counts of Lactobacillus and Bifidobacteria. In addition, treatment with probiotics can effectively alleviate osteoporosis symptoms in rats with inflammatory bowel disease by influencing the level of corresponding cytokines.

[Detection rate, antimicrobial resistance and molecular types of Klebsiella pneumoniae from stool samples of outpatients with diarrhea-syndrome in Tai'an].

Objective: To investigate the isolation rate, antimicrobial resistance phenotype, and molecular type characteristics of Klebsiella pneumoniae from infectious diarrhea outpatients in Tai'an. Methods: A total of 866 stool samples were collected from infectious diarrhea cases in sentinel hospitals in 6 counties of Tai'an from 2013 to 2017. The strains were isolated from stool samples of the cases and identified by biochemical test. Micro broth dilution method was used to detect the drug resistance of the strains. The molecular typing was conducted by using pulsed field gel electrophoresis (PFGE). Results: The detection rate of Klebsiella pneumoniae in the stool samples was 7.97% (69/866), with significant differences among the 6 counties (χ(2)=39.627, P=0.000). Sixty- eight out of the 69 strains were resistant to 15 antibiotics with resistance rate 98.55%(68/69). The resistance to ampicillin (AMP) was highest (84.06%) (58/69), followed by sulfamethoxazole (SOX) (72.46%)(50/69). There were 40 drug resistance profiles, and the predominant resistance profile was AMP-SOX detected (n=10). The multi-drug resistant (MDR) strains accounted for 33.33% (23/69). The 69 strains could be divided into 65 PFGE patterns, and no predominant PFGE pattern or cluster was observed. Conclusions: Klebsiella pneumoniae was detected in the stool samples of diarrhea- syndrome outpatients, indicating the risk for community-acquired infection; the strains were resistant to multiplex antibiotics, with wide drug-resistance profiles and high multi-drug resistance rates. The PFGE patterns were diverse, which showed no correlation with drug resistance profiles. Our study indicated that it necessary to strengthen the surveillance and detection of Klebsiella pneumoniae from diarrhea outpatients, which could facilitate the prevention of the emergence and spread of drug resistance strains and the protection of susceptible population.

Roles of chicken growth hormone receptor antisense transcript in chicken muscle development and myoblast differentiation.

Muscle is one of the important economic traits in poultry production, and its production depends on the increased number of muscle fibers during the embryonic stage. Chicken GHR gene can transcribe in double directions, possessing not only GHR-S but also GHR-AS. The 2 kinds of transcripts are partially complementation in sequences and interact with each other. Until now, the roles and mechanisms of GHR-AS in myoblast differentiation was still unknown. In this study, we not only analyzed the GHR-AS expression patterns in myoblast differentiation phase but also clarified that GHR-AS promoted myoblast differentiation via GH-GHR-IGF1 signal pathway. Quantitative PCR analysis indicated that GHR-AS was increased during myoblast differentiation. Sub-cellular localization showed that GHR-AS and GHR-S were expressed at a higher level in the nucleus than that in the cytoplasm. The expression of MyoD and MyHC and the myoblast differentiation significantly increased after GHR-AS overexpression, while the distance between wounds decreased, suggesting that GHR-AS repressed myoblast migration and promoted differentiation. Additionally, the expression of GHR-AS, IGF1 and MyHC increased after GH protein treated, and the myoblast differentiation also increased. In conclusion, GHR-AS promoted myoblast differentiation by enhancing fusion and inhibiting migration possibly via GH-GHR-IGF1 signal pathway.

MiR-32-5p regulates the proliferation and metastasis of cervical cancer cells by targeting HOXB8.

OBJECTIVE: To investigate the effects of miR-32-5p on the biological behaviors of cervical cancer (CCa), the relevant mechanism was studied in CCa cell lines (HeLa) in vitro. PATIENTS AND METHODS: The expression level of miR-32-5p was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). TargetScan, miRDB, microRNA databases and Luciferase method were conducted to predict and validate the target gene of miR-32-5p; the effects of miR-32-5p on cell proliferation, clone formation, invasion and migration capacity were analyzed in vitro study. RESULTS: We found miR-32-5p to be significantly inhibited in CCa tissues and cells. Bioinformatics approach together with Luciferase method screened Homeobox B8 (HOXB8) as a downstream regulatory target of miR-32-5p. Besides, HOXB8 was incredibly high expression in CCa tissues and cells. After transfection in HeLa cells by miR-32-5p mimics, HOXB8 expression was indicated to be negatively correlated with miR-32-5p both in qRT-PCR and Western blot (WB) assays. The subsequent experiments showed that decreased expression of HOXB8 resulting from up-regulation of miR-32-5p could weaken the cell proliferation, clone formation, invasion and migration ability of HeLa cells. CONCLUSIONS: MiR-32-5p could inhibit the cellular malignant behavior through regulating the expression of HOXB8 in HeLa cells. We provide a new clue for the study of molecular mechanisms of CCa. MiR-32-5p/HOXB8 axis might serve as potential target for the clinical diagnosis and treatment of CCa.

Rs13405728 is associated with slow ovarian response in assisted reproductive technology.

OBJECTIVE: To explore the association between rs13405728 with slow ovarian response in assisted reproductive technology (ART). PATIENTS AND METHODS: 236 women, aged 21 to 35 years, were enrolled and grouped according to their genotypes, The polymorphism of rs13405728 was genotyped by DNA sequencing. RESULTS: There was no evidence of any difference in anti-Müllerian hormone (AMH), antral follicle count (AFC) among the three genotypes (p>0.05). The occurrence of slow response in genotype GG was lower than those in the other two genotypes (p<0.05). There were independent correlations between slow ovarian response with the dose of luteinizing hormone (LH) required and the genotypes of rs13405728 (p<0.05). CONCLUSIONS: There were significant independent correlations between slow ovarian response with the dose of LH required and the genotypes of rs13405728. Different mechanisms may be involved in poor response and slow response.

Synthesis of substituted aromatic heterocyclic sulfonyl hydrazone compounds and in vitro anti-hepatoma activity: preliminary results.

OBJECTIVE: Hydrazone compounds and their derivatives are a kind of special Schiff bases. The multiple hydrazone compounds and their derivatives have a variety of biological activities. This study aims to report the synthesis of diverse hydrazone derivatives and to explore the potent antitumor activities. MATERIALS AND METHODS: A series of aromatic heterocyclic sulfonyl hydrazones W1-W15 synthesized from hydrazine or acylhydrazine and aldehydes or ketones were estimated for their in vitro antitumor activities against human cancers. Through the spectral (FT-IR, 1H-NMR, MS) methods, the structure of the compounds was determined. Using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) method, the effects of different concentrations of compounds on growth inhibition and viability of HepG-2 cells were detected. RESULTS: Compound W9 exhibited anti-proliferation activity with IC50 values of 63.91 µmol/L in HepG-2 cell line. In addition, mechanism studies indicated that compound W9 could distinctly prohibit the propagation of HepG-2 cells by arresting the cell cycle at G2/M and inducing apoptosis. Furthermore, we investigated the effectiveness of drug combination treatment with W9 and cis-platinum (cis-DDP) or 5-fluorouracil (5-FU) on HepG-2 cell line. CONCLUSIONS: Our results indicated that W9 with synergic treatment of 5-FU or cis-DDP shows better inhibitory cell growth. The combination of the two drugs blocks HepG-2 cells in the G2/M phase. The inhibitory effect of W9 on cell apoptosis was decreased with the increase of drug concentration.

Works on heart, how about brain? Effect of hyperkalemia on focal cerebral ischemia/reperfusion injury in rats.

OBJECTIVE: To investigate the effects of hyperkalemia on the brain after I/R in h transient middle cerebral artery occlusion (tMCAO) model. MATERIALS AND METHODS: A total of 120 adult male SD rats were randomly assigned to four groups: (1) hyperkalemia 80 µg/g (HK80) group; (2) hyperkalemia 40 µg/g (HK40) group; (3) normal saline (NS) group; (4) sham (SH) group. The concentration of serum K+ was elevated in HK80 and HK40 groups. The transient middle cerebral artery occlusion (tMCAO) model was used to assess the effect of hyperkalemia on the brain after I/R. After 24 h reperfusion, the infarct volume and cell damage of rat's I/R brain tissue sections were analyzed. The concentration of K+, Ca2+ and calmodulin (CaM), the activity of Ca-ATPase, the expression of Western blot of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Na+/Ca2+ exchanger 1 (NCX1), were also measured. RESULTS: After 24 h reperfusion, compared with NS group, the two-hyperkalemia groups (HK80 and HK40) were with less infarct volume and cell damage, higher concentration of K+ but lower Ca2+ and CaM compared with NS group. The activity of Ca-ATPase was also elevated, the expression of CaMK II and NCX1 were down-regulated in the two hyperkalemia groups. CONCLUSIONS: Hyperkalemia could also ameliorate the brain I/R injury by alleviating calcium overload inhibiting the activity of NCX1, lowering the concentration of Ca2+.

LncRNA MALAT1 promotes proliferation and metastasis in epithelial ovarian cancer via the PI3K-AKT pathway.

OBJECTIVE: The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that plays a key role in the malignant phenotype of tumors. Although abnormal regulation of lncRNA MALAT1 impacts clinical prognostic and tumor metastasis, its function remains unclear in ovarian cancer. PATIENTS AND METHODS: We collected 64 samples of surgical EOC tissues and 30 samples of normal ovarian tissues at the Department of Gynecology of Harbin Medical University (Harbin, China). The 30 control samples of ovarian surface epithelial tissues were obtained from patients diagnosed with uterine fibroids and scheduled hysterectomy with oophorectomy. RESULTS: The present study discovered that MALAT1 was upregulated in tumor tissues and ovarian cancer cell lines. Further, the 5-year overall survival was higher in the lower expression of the MALAT1 group. MALAT1 inhibition impeded cell proliferation, invasion and metastasis, and promoted cell apoptosis in both in vivo and in vitro. Furthermore, silencing of MALAT1 hindered the expression of epithelial-to-mesenchymal transition (EMT)-related genes and MMPS. The evidence showed that MALAT1 induce EMT via PI3K/AKT pathway. CONCLUSIONS: Our research suggests that MALAT1 transforms metastasis in EOC and may be a prospective therapeutic target.

Paracrine effect of bone marrow mesenchymal stem cells on proliferation, apoptosis, and alpha-actin-2 expression in hepatic stellate cells.

We investigated the paracrine effects of bone marrow mesenchymal stem cells (BMSCs) on the proliferation, apoptosis, and alpha-actin-2 (ACTA2) expression of hepatic stellate cells (HSCs), and explored the possible mechanisms of hepatocyte growth factor (HGF). We established a co-culture system by culturing BMSCs on the upper layer and HSCs on the lower layer of a 6-well Transwell plate. Normal HSCs were cultured alone as a control. Cell apoptosis was determined by flow cytometry. We detected the expression of ACTA2 mRNA and ACTA2 protein in HSC using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. ACTA2 in HSCs was detected by fluorescent staining, and HGF in the co-culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA). The apoptotic rate of HSCs in the experiment group was 2.6 times that in the control group (P < 0.05). The expression levels of ACTA2 mRNA and ACTA2 protein were significantly inhibited in HSCs compared with the control group (P < 0.05). HGF concentration in the co-culture supernatant was 0.43 ± 0.47 mM in the experimental group, which was significantly higher than in the control group (0.16 ± 0.43 mM) (P < 0.05). The paracrine effect of BMSCs, which was caused by the suppression of ACTA2 and HGF expression, induced HSC apoptosis.

Decreased REG1α expression suppresses growth, invasion and angiogenesis of bladder cancer.

BACKGROUND: Previous study has indicated association between REG1α and bladder cancer. The aim of this study was to investigate the role of Regenerating gene I alpha (REG1α) in bladder cancer. METHODS: The role of REG1α in bladder cancer cell proliferation, migration and VEGF-induced angiogenesis was explored in vitro and in vivo. Immunohistochemistry (IHC) analysis was assessed to determine the expression of REG1α in ten paired bladder cancer and adjacent non-cancerous tissues, and in 296 bladder cancer samples. RESULTS: Down-regulation of REG1α expression significantly reduced the proliferation, migration, invasion and VEGF-induced angiogenesis in vitro and the growth of xenograft tumors in vivo. VEGF expression in bladder cancer is associated with REG1α expression and recurrence. REG1α was overexpressed in bladder cancer tissues compared with adjacent normal samples. Patients with elevated REG1α exhibited shorter recurrence times and poor survival. CONCLUSION: Downregulation of REG1α expression can reduce tumor growth, migration, invasion and angiogenesis. Our study demonstrates that REG1α can be used as a marker of recurrence and prognosis in bladder cancer. Therefore, REG1α targeting in bladder cancer patients represents a promising therapeutic strategy.

Defective expression of polarity protein Par3 promotes cervical tumorigenesis and metastasis.

OBJECTIVES: The aim of this study was to investigate whether the partition-defective 3 protein (Par3) regulates cervical carcinoma growth and metastasis. MATERIALS AND METHODS: Immunohistochemistry (IHC) was used to analyze the expression of Par3 protein in samples from 89 cervical squamous cell carcinoma (CSCC) patients among Uyghur women. The specific short hairpin (shRNA) vector as well as eu- karyotic expression vector of PARD3 was transfected into SiHa cell lines. The variation of migration and invasion after transfection was determined using Transwell assays, cell cycle, and apoptosis were assayed by flow cytometry, respectively. RESULTS: The incidence of CSCC was associated with reduced expression of Par3. Downregulation of Par3 was significantly associated with more advanced tumors (i.e., higher histological grade, lymph node involvement, and higher tumor stages) (p < 0.05 for all). Lost expression of Par3 promotes prolif- eration, inhibits apoptosis, and enhances migration and invasion. Loss of Par3 induces MMP9 expression and epithelial to mesenchymal transition (EMT) related genes (N-cadherin, E-cadherin, and ß-catenin) expression changed in SiHa cells. CONCLUSIONS: The reduced Par3 expression in cervical cancer indicates tumor-suppressive properties of Par3 that may be a marker of poor prognosis in cervical cancer patients, and the molecular determinants of epithelial polarity which have tumorigenesis enhancing impact, might through EMT.

Tegafur gimeracil oter combined with oxaliplatin for advanced colorectal cancer.

OBJECTIVE: To analyze the therapeutic actions of tegafur gimeracil oteracil combined with oxaliplatin for treating patients with advanced colorectal cancer, and its effects on the K-ras gene mutation and the CK20 mRNA. PATIENTS AND METHODS: Forty-one patients with advanced colorectal cancer from our hospital, from October 2013 to October 2014, were enrolled in this study. After obtaining consent from the hospital Ethics Committee and the patients as well as their relatives, all 41 patients were divided into two groups. The control group, which consisted of 20 cases, were treated with capecitabine combined with oxaliplatin. The study group, which comprised of 21 cases, were treated with tegafur gimeracil oteracil combined with oxaliplatin. Both groups were followed-up after six months to evaluate the treatment outcomes. RESULTS: The survival rate in the observation group was higher than that in the control group. The progression-free survival time (PFS) in the observation group was longer than that in the control group. The objective response rate (ORR) and disease control rate (DCR) were higher for the observation group. The differences had statistical significance (p < 0.05). The proportion of K-ras gene mutation in the observation group was substantially superior to that in the control group. The positive expression rate of CK 20 mRNA in the observation group was significantly lower than that in the control group. The differences had statistical significance (p < 0.05). The incidence of adverse reaction in the observation group was lower than that of the control group, and the differences had statistical significance (p < 0.05). CONCLUSIONS: Tegafur/gimeracil/oteracil combined with oxaliplatin therapy had better treatment outcomes than capecitabine combined oxaliplatin for advanced colorectal cancer. This maybe related to K-ras gene mutation and the reduction of CK20 mRNA expression.