Effect of a complex lutein formula in an animal model for light-induced retinal degeneration.

Several retinal degenerative diseases cause vision loss and retinal cell death. Currently, people face prolonged exposure to digital screens, rendering vision protection from light exposure a critical topic. In this study, we designed a complex lutein formula (CLF) by combining several natural compounds: Calendula officinalis, Lycium barbarum, Vaccinium myrtillus, Cassia obtusifolia, and Rhodiola rosea. In addition, we evaluated the protective effects of the formula on retinal functions in an animal model for light-induced retinal degeneration. We employed electroretinography to analyse retinal function, and conducted a histological examination of the morphological changes in the retina treated under various conditions. We revealed that the retinal function in animals exposed to light for 7 days decreased significantly; however, the retinal function of animals that had received the CLF exhibited superior performance, despite light exposure. In addition, a greater portion of the outer nuclear layer (ONL) (i.e. the nuclei of photoreceptors) in these animals was preserved compared with the animals that had not received the formula after 7 days of light exposure. These results revealed that our dietary CLF supplement attenuated retinal function loss resulting from long-term light exposure.

Taurine improves the spatial learning and memory ability impaired by sub-chronic manganese exposure.

BACKGROUND: Excessive manganese exposure induced cognitive deficit. Several lines of evidence have demonstrated that taurine improves cognitive impairment induced by numerous neurotoxins. However, the role of taurine on manganese-induced damages in learning and memory is still elusive. This goal of this study was to investigate the beneficial effect of taurine on learning and memory capacity impairment by manganese exposure in an animal model. RESULTS: The escape latency in the Morris Water Maze test was significantly longer in the rats injected with manganese than that in the rats received both taurine and manganese. Similarly, the probe trial showed that the annulus crossings were significantly greater in the taurine plus manganese treated rats than those in the manganese-treated rats. However, the blood level of manganese was not altered by the taurine treatment. Interestingly, the exposure of manganese led to a significant increase in the acetylcholinesterase activity and an evidently decrease in the choline acetyltransferase activity, which were partially restored by the addition of taurine. Additionally, we identified 9 differentially expressed proteins between the rat hippocampus treated by manganese and the control or the manganese plus taurine in the proteomic analysis using the 2-dimensional gel electrophoresis followed by the tandem mass spectrometry (MS/MS). Most of these proteins play a role in energy metabolism, oxidative stress, inflammation, and neuron synapse. CONCLUSIONS: In summary, taurine restores the activity of AChE and ChAT, which are critical for the regulation of acetylcholine. We have identified seven differentially expressed proteins specifically induced by manganese and two proteins induced by taurine from the rat hippocampus. Our results support that taurine improves the impaired learning and memory ability caused by excessive exposure of manganese.

A blind area of family planning services in China: unintended pregnancy among unmarried graduate students.

BACKGROUND: Status of premarital sex, unintended pregnancy and associated factors among Chinese graduate students remain unclear. And unmarried graduate students' needs of family planning services seem to be ignored. In the present study, we ascertained the prevalence rate of premarital sex and unintended pregnancy, as well as estimated the possible factors associated with unintended pregnancy among unmarried Chinese graduate students, and evaluated their reproductive health needs. METHODS: We obtained the representative sample of graduate students using a multistage, stratified, cluster design, and collected data using a questionnaire. RESULTS: We obtained 11936 responders. Premarital sexual intercourse was acknowledged by 24.2% of responders; unintended pregnancy was acknowledged by 4.8% of responders (19.8% of students active in premarital sex); and abortion was acknowledged by 4.6% of responders (96.7% of pregnant students). In multivariate analysis, the identified risk factors for unintended pregnancy among both genders that were active in premarital sex were: (1) having no steady lover [for males: odds ratio (OR), 1.96, 95% confidence interval (CI), 1.41-2.70; for females: OR, 2.65; 95%CI, 1.56-4.84]; (2) younger age at the first sexual intercourse (for males: OR, 1.62, 95% CI, 1.22-2.15; for females: OR, 2.57; 95% CI, 1.64-4.02); (3) lack of condom use at the first sex (for males: OR, 1.13, 95% CI, 1.09-1.37; for females: OR, 2.81; 95% CI, 1.81-4.39); (4) unaware of the conditions of conception (for males: OR, 1.69, 95% CI, 1.31-2.19; for females: OR, 1.75; 95% CI, 1.16-2.65); and (5) unaware that abortion endangers women's future pregnancy (for males: OR, 2.98, 95% CI, 2.15-4.14; for females: OR, 2.34; 95% CI, 1.23-4.46). Medical graduates were not less likely to have unintended pregnancy than nonmedical graduates for both genders. CONCLUSIONS: The avoidable risk of being unintended pregnancy among graduate students in China indicates that an urgent need to take action on how to delay the age of first sex, promote condom use at first sex, and acquire accurate contraceptive information, as well as improve skills to use reliable contraception among graduate students.

Prevalence and risk factors associated with psoriatic arthritis among patients with psoriasis.

INTRODUCTION: Psoriatic arthritis is a chronic, autoimmune inflammatory arthritis that occurs with psoriasis and has profound impact on patients' physical and psychological well-being. This study aims to determine the prevalence and risk factors associated with psoriatic arthritis among patients with psoriasis. METHODS: A single-center, cross-sectional study was conducted over a 12-month period at the Dermatology Clinic, Hospital Pulau Pinang, Malaysia involving all consecutive psoriasis patients. CASPAR (ClASsification of Psoriatic ARthritis) criteria were used to diagnose psoriatic arthritis. RESULTS: A total of 360 patients with psoriasis were recruited, of whom 107 (29.7%) had psoriatic arthritis. Psoriatic arthritis patients had equal gender distribution and the mean age of arthritis onset was 40.7 ± 12.8 years. Psoriasis preceded arthritis in 81.3% of patients (n = 87) with a mean latency interval of 10.5 years. Polyarthropathy was the predominant subtype affecting 46.8% (n = 50) of patients, followed by oligoarthropathy (22.4%, n = 24), axial joint disease (5.6%, n = 6), predominant distal interphalangeal joint disease (2.8%, n = 3), and mixed subtype (22.4%, n = 24). Enthesitis and dactylitis occurred in 12.1% (n = 13) and 20.6% (n = 22) of arthritis patients, respectively, and deformity was present in 37.4% (n = 40). Psoriatic arthritis was significantly associated with being an ever smoker (adjusted odds ratio [aOR] 0.41; 95% confidence interval [CI] 0.18-0.91, p = .029), genital psoriasis (aOR 2.25; 95% CI 1.17-4.33, p = .015), and increased erythrocyte sedimentation rate (ESR) (aOR 1.02; 95% CI 1.01-1.04, p = .005) and C-reactive protein [CRP] (aOR 1.04; 95% CI 1.00-1.08, p = .040). CONCLUSION: Our study showed a high prevalence of psoriatic arthritis among the psoriasis cohort. Genital involvement, and increased ESR and CRP were associated with psoriatic arthritis among patients with psoriasis.

Simplified Rapid Hydration Prevents Contrast-Associated Acute Kidney Injury Among CKD Patients Undergoing Coronary Angiography.

BACKGROUND: Patients with chronic kidney disease (CKD) undergoing coronary angiography (CAG) are at high risk of contrast-associated acute kidney injury (CA-AKI) and mortality. Therefore, there is a clinical need to explore safe, convenient, and effective strategies for preventing CA-AKI. OBJECTIVES: This study sought to assess whether simplified rapid hydration is noninferior to standard hydration for CA-AKI prevention in patients with CKD. METHODS: This multicenter, open-label, randomized controlled study was conducted across 21 teaching hospitals and included 1,002 patients with CKD. Patients were randomized to either simplified hydration (SH) (SH group, with normal saline from 1 hour before to 4 hours after CAG at a rate of 3 mL/kg/h) or standard hydration (control group, with normal saline 12 hours before and 12 hours after CAG at a rate of 1 mL/kg/h). The primary endpoint of CA-AKI was a ≥25% or 0.5-mg/dL rise in serum creatinine from baseline within 48 to 72 hours. RESULTS: CA-AKI occurred in 29 of 466 (6.2%) patients in the SH group and in 38 of 455 (8.4%) patients in the control group (relative risk: 0.8; 95% CI: 0.5-1.2; P = 0.216). In addition, the risk of acute heart failure and 1-year major adverse cardiovascular events did not differ significantly between the groups. However, the median hydration duration was significantly shorter in the SH group than in the control group (6 vs 25 hours; P < 0.001). CONCLUSIONS: In CKD patients undergoing CAG, SH is noninferior to standard hydration in preventing CA-AKI with a shorter hydration duration.

Genome-wide association and follow-up replication studies identified ADAMTS18 and TGFBR3 as bone mass candidate genes in different ethnic groups.

To identify and validate genes associated with bone mineral density (BMD), which is a prominent osteoporosis risk factor, we tested 379,319 SNPs in 1000 unrelated white U.S. subjects for associations with BMD. For replication, we genotyped the most significant SNPs in 593 white U.S. families (1972 subjects), a Chinese hip fracture (HF) sample (350 cases, 350 controls), a Chinese BMD sample (2955 subjects), and a Tobago cohort of African ancestry (908 males). Publicly available Framingham genome-wide association study (GWAS) data (2953 whites) were also used for in silico replication. The GWAS detected two BMD candidate genes, ADAMTS18 (ADAM metallopeptidase with thrombospondin type 1 motif, 18) and TGFBR3 (transforming growth factor, beta receptor III). Replication studies verified the significant findings by GWAS. We also detected significant associations with hip fracture for ADAMTS18 SNPs in the Chinese HF sample. Meta-analyses supported the significant associations of ADAMTS18 and TGFBR3 with BMD (p values: 2.56 x 10(-5) to 2.13 x 10(-8); total sample size: n = 5925 to 9828). Electrophoretic mobility shift assay suggested that the minor allele of one significant ADAMTS18 SNP might promote binding of the TEL2 factor, which may repress ADAMTS18 expression. The data from NCBI GEO expression profiles also showed that ADAMTS18 and TGFBR3 genes were differentially expressed in subjects with normal skeletal fracture versus subjects with nonunion skeletal fracture. Overall, the evidence supports that ADAMTS18 and TGFBR3 might underlie BMD determination in the major human ethnic groups.

Altered regional brain white matter in dry eye patients: a brain imaging study.

This study aimed to investigate the regional changes of brain white matter (WM) in DE patients using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). A total of 25 dry eye patients (PAT) and 25 healthy controls (HC) were recruited. All subjects underwent DTI and NODDI, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), isotropic volume fraction (FISO), intra-cellular volume fraction (FICVF), and orientation dispersion index (ODI) were obtained respectively. Then complete Hospital Anxiety and Depression Scale (HADS), anxiety score (AS) or depression scores (DS) were obtained. Receiver operating characteristic (ROC) curve analysis was used to evaluate the reliability of DTI and NODDI in distinguishing the two groups. DTI revealed that PAT had lower FA in both the left superior longitudinal fasciculus (LSLF) and the corpus callosum (CC), and higher MD in the LSLF, the right posterior limb of the internal capsule and the right posterior thalamic radiation. PAT had significant AD changes in regions including the genu of the CC, the right posterior limb of internal capsule, and the right splenium of the CC. From NODDI, PAT showed increased ODI in the LSLF and increased FISO in the right splenium of the CC. FICVF showed a significant decrease in the LSLF while increased in the left anterior corona radiata and the CC. Furthermore, the average values of MD and FICVF were significantly correlated with DS and AS. Hence the results of this study suggest that there are regional changes in WM in DE patients which may contribute to further understanding of the pathological mechanism of DE.

Natural product chemistry of gorgonian corals of genus Junceella--part II.

The structures, names, bioactivities, and references of 81 new secondary metabolites obtained from gorgonian corals belonging to the genus Junceella are described in this review. All compounds mentioned in this review were obtained from sea whip gorgonian corals Junceella fragilis and Junceella juncea, collected from the tropical and subtropical Indo-Pacific Ocean.

Urgent need for contraceptive education and services in Chinese unmarried undergraduates: a multi-campus survey.

In order to ascertain prevalence rate of premarital sexual intercourse, unintended pregnancy and abortion, and evaluate associated factors of unintended pregnancy among undergraduates from all over China, the representative sample of unmarried undergraduates was obtained by using a multi-stage, stratified, probability cluster design, and data were collected by using a survey questionnaire. 62 326 available responders were gained. 11.6% of them acknowledged having experiences of premarital sexual intercourse (standardized prevalence rate of sexual intercourse was 13.8%). 31.5% of students active in premarital sex acknowledged undergoing unintended pregnancy. 76.2% of pregnant students selected abortion to end it. Of students active in premarital sex, 46.2% used contraception at the first sexual intercourse, 28.2% replied "always" using contraception in sexual intercourse. The rate of using condoms, oral contraceptives (OCs), and withdrawal among students who had used contraception was 52.0%, 31.0%, and 27.2% respectively. "No preparation for sex" (40.3%), "pleasure decrement" (32.1%), "won't-be-pregnancy in occasional sexual intercourse" (30.2%) were their common excuses for using no contraception. The identified risk factors for unintended pregnancy among students active in premarital sex by multivariate analysis were as follows: having no steady lover [having no steady lover vs having a steady lover: odds ratio (OR), 1.875; 95% confidence interval (CI), 1.629-2.158], unaware of the course of conception (unaware vs aware: OR, 2.023; 95% CI, 1.811-2.260), considering abortion not endanger women's physical and mental health (no endangerment vs endangerment: OR, 2.659; 95% CI, 2.265-3.121), nonuse of contraception (never use vs always use: OR, 1.682; 95% CI, 1.295-2.185). Medical students were not less likely to experience an unintended pregnancy than nonmedical students (OR, 1.111; 95% CI, 0.906-1.287). The substantial proportion of unintended pregnancy among undergraduates indicates a need for convenient and targeted contraceptive education and services.

Circular RNA circ-TNPO3 suppresses metastasis of GC by acting as a protein decoy for IGF2BP3 to regulate the expression of MYC and SNAIL.

Gastric cancer (GC) continues to be the most common gastrointestinal malignancy in China, and tumor metastases are a major reason for poor prognosis. Circular RNAs (circRNAs) are an intriguing type of noncoding RNAs with important regulatory roles. However, the roles of circRNAs in GC metastasis have not been fully elucidated. Here, we reported that circ-transportin 3 (TNPO3) was significantly downregulated in 103 pairs of GC tissues compared with matched noncancerous tissues. The level of circ-TNPO3 expression correlated with differentiation of GC, and plasma circ-TNPO3 could serve as a potential diagnostic biomarker. Functionally, circ-TNPO3 inhibited proliferation and migration of GC in vitro and in vivo. We further verified that circ-TNPO3 competitively interacted with insulin-like growth factor 2 binding protein 3 (IGF2BP3) protein; thus, the role of IGF2BP3 in stabilizing MYC mRNA was weakened, which inhibited the expression of MYC and its target SNAIL. Taken together, circ-TNPO3 acts as a protein decoy for IGF2BP3 to regulate the MYC-SNAIL axis, thereby suppressing the proliferation and metastasis of GC. Therefore, circ-TNPO3 has the potential to serve as a therapeutic target for GC.

High incidence of NMDAR encephalitis among Austronesians: A population-based study in Sabah, Malaysia.

NMDAR encephalitis may be more common among non-Caucasians. A population-based study was conducted to estimate its incidence in Sabah, Malaysia, where the population consists predominantly of Austronesians (84%), and with a Chinese minority. Registries of NMDAR encephalitis at neurology referral centers were reviewed for case ascertainment. The annual incidence was 2.29/million (Austronesians: 2.56/million, Chinese: 1.31/million). Among pediatric population, the incidence was: Austronesians: 3.63/million, Chinese: 2.59/million. Our study demonstrated a higher incidence of NMDAR encephalitis among Austronesians than the predominantly Caucasian populations in Europe (0.5-0.9/million; pediatric: 0.7-1.5/million). Racial and genetic factors may contribute to risks of developing NMDAR encephalitis.

RGS5 decreases the proliferation of human ovarian carcinoma­derived primary endothelial cells through the MAPK/ERK signaling pathway in hypoxia.

Regulator of G­protein signaling 5 (RGS5), a tissue­specific signal­regulating molecule, plays a key role in the development of the vasculature. It was recently found that RGS5 is abundantly expressed in epithelial ovarian cancer (EOC) compared with the normal ovaries. However, the distribution of RGS5 in EOC and its significance require further investigation. The aim of the present study was to investigate the expression of RGS5 in EOC, as well as its association with cancer differentiation, metastasis and clinicopathological parameters. Immunohistochemistry (IHC), western blotting, RT­PCR, wound­healing, cell proliferation and flow cytometric assays were the methods used in the present study. RGS5 was highly expressed in the cytoplasm of ovarian carcinoma cells and in microvascular structures. The expression of RGS5 in EOC was negatively associated with peritoneal metastasis (P=0.004), but it was not found to be associated with age, tumor size, clinical stage or lymph node metastasis (P>0.05). EOC patients with high RGS5 expression had a prolonged progression­free survival (72.34±8.41 vs. 43.56±5.41 months, P<0.001). High expression of RGS5 was correlated with significantly lower microvascular density (MVD) as indicated by the expression of CD34, whereas the opposite was observed in tissues with low RGS5 expression (P<0.05). Hypoxia increased RGS5 expression in ovarian carcinoma­derived endothelial cells (ODMECs), whereas the proliferative capacity of ODMECs exhibited a significant increase following RNAi­mediated reduction of RGS5 expression. These data indicated that RGS5 plays a key role in angiogenesis in ovarian carcinoma. In addition, RGS5 downregulated the expression of the downstream proteins CDC25A, CDK2 and cyclin E, which are mediated by the mitogen­activated protein kinase/extracellular signal­regulated kinase pathway, causing ODMEC arrest in the G1 phase of the cell cycle under hypoxic conditions. Collectively, our data indicated that RGS5 is crucial for the occurrence and development of ovarian cancer, and that RGS5 and its signaling pathway may serve as anti­angiogenesis targets for the treatment of ovarian cancer.

Correlation of serum vitamin D, adipose tissue vitamin D receptor, and peroxisome proliferator-activated receptor γ in women with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common complication during pregnancy. Obesity and overweight are closely related to metabolic diseases and diabetes. However, the role of adipose tissue in the pathogenesis of GDM remains to be studied. The aim of this study was to investigate the correlation of vitamin D (VD) levels, VD receptor (VDR), and peroxisome proliferator-activated receptor γ (PPARγ) expression with GDM in overweight or obese women. METHODS: One hundred and forty pregnant women with full-term single-birth cesarean-section were selected as the study subjects and grouped (70 GDM women, including 35 non-overweight/non-obese women [group G1] and 35 women with overweight or obesity [group G2]; 70 pregnant women with normal glucose tolerance, including 35 non-overweight/non-obese women [group N1] and 35 overweight/obese women [group N2]). The levels of serum VD, blood biochemistry, and adiponectin were compared in these women. Subcutaneous adipose tissue was isolated from the abdominal wall incision. VDR and PPARγ messenger RNA (mRNA) transcript levels in these adipose tissues were quantified by real-time polymerase chain reaction. The differences between the levels of PPARγ protein and phosphorylated PPARγ Ser273 were detected by Western blotting. RESULTS: The serum VD level of GDM women was lower in comparison to that of women with normal glucose tolerance (G1 vs. N1: 20.62 ±â€Š7.87 ng/mL vs. 25.85 ±â€Š7.29 ng/mL, G2 vs. N2: 17.06 ±â€Š6.74 ng/mL vs. 21.62 ±â€Š7.18 ng/mL, P < 0.05), and the lowest in overweight/obese GDM women. VDR and PPARγ mRNA expression was higher in the adipose tissues of GDM women in comparison to that of women with normal glucose tolerance (VDR mRNA: G1 vs. N1: 210.00 [90.58-311.46] vs. 89.34 [63.74-159.92], G2 vs. N2: 298.67 [170.84-451.25] vs. 198.28 [119.46-261.23], PPARγ mRNA: G1 vs. N1: 100.72 [88.61-123.87] vs. 87.52 [66.37-100.04], G2 vs. N2: 117.33 [100.08-149.00] vs. 89.90 [76.95-109.09], P < 0.05), and their expression was the highest in GDM + overweight/obese women. VDR mRNA levels positively correlated with the pre-pregnancy body mass index (BMI), pre-delivery BMI, fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and PPARγ mRNA while it negatively correlated with the VD and the adiponectin levels (r = 0.395, 0.336, 0.240, 0.190, 0.235, -0.350, -0.294, respectively, P < 0.05). The degree of PPARγ Ser273 phosphorylation increased in obese and GDM pregnant women. PPARγ mRNA levels positively correlated with pre-pregnancy BMI, pre-delivery BMI, FBG, HOMA-IR, serum total cholesterol, triglyceride, free fatty acid, and VDR mRNA, while it negatively correlated with the VD and adiponectin levels (r = 0.276, 0.199, 0.210, 0.230, 0.182, 0.214, 0.270, 0.235, -0.232, -0.199, respectively, P < 0.05). CONCLUSIONS: Both GDM and overweight/obese women had decreased serum VD levels and up-regulated VDR and PPARγ mRNA expression in adipose tissue, which was further higher in the overweight or obese women with GDM. VD may regulate the formation and differentiation of adipocytes through the VDR and PPARγ pathways and participate in the occurrence of GDM.

[Association among circulating endothelial progenitor cells, insulin resistance and severity of coronary lesions in patients with coronary artery disease].

OBJECTIVE: To investigate the correlation between the number and activity of circulating endothelial progenitor cells (EPCs), insulin resistance and severity of coronary lesions in patients with coronary artery disease (CAD). METHODS: Patients with coronary angiography evidenced CAD were divided in insulin resistance group (IR, n = 25) and insulin sensitive group (IS, n = 44) according to insulin level, 25 health volunteers served as control. Circulating EPCs were marked as KDR/CD133+ cells via fluorescence-activated cell sorter analysis. EPCs were also isolated from peripheral blood and cultured in vitro for 7 days, identified by DiI-acLDL uptake and lectin staining methods. EPCs migration activities were determined by modified Boyden chamber assay, EPCs proliferation activities were determined by MTT assay. RESULT: Circulating EPCs number was significantly lower in IR group compared with IS group [(0.34 +/- 0.08) per thousand vs. (0.47 +/- 0.09) per thousand, P < 0.01] and control group (P < 0.05). Both insulin resistance index (r = -0.291, P = 0.01)and Gensini score (r = -0.3984, P = 0.006)were negatively correlated with number of circulating EPCs. Proliferation and migration capacities of EPCs were also significantly lower in IR group compared to those in IS group (all P < 0.05) and control group (all P < 0.05). CONCLUSIONS: Insulin resistance/hyperinsulinemia could aggravate severity of coronary artery lesions via reducing the number and activities of circulating EPCs in patients with CAD.

Haemolytic-uraemic syndrome caused by a non-O157 : H7 Escherichia coli strain in experimentally inoculated dogs.

Both O157 : H7 and non-O157 : H7 Escherichia coli strains are reported to cause haemolytic-uraemic syndrome (HUS). This study was carried out to explore the pathogenicity of O157 : H7 and non-O157 : H7 E. coli strains in experimentally inoculated dogs. Twenty 40-day-old dogs were randomly divided into four groups, and the groups (n=5) were administrated orally with E. coli O157 : H7 strains HJ2001-1 (from a patient with serious haemorrhagic diarrhoea) and HZ2001-4 (from a domestic sheep kept in the house of a patient who died from diarrhoea and subsequent acute renal failure), HZ2001-9 (a non-O157 : H7 strain, from a 6-month-old child who died from diarrhoea and subsequent acute renal failure) or a control strain, EC8099. HJ2001-1 and HZ2001-4 caused slight diarrhoea, and the dogs recovered without any complications. However, HZ2001-9 resulted in watery diarrhoea accompanied with slightly bloody stools, followed by death on the fifth or sixth day. In the fatally infected experimental animals, necrotic lesions in the liver and bacterial embolism in the kidney were observed. The primary cause of death was microvascular thrombosis caused by the bacteria, leading to renal and multiple organ failure. Therefore, the non-O157 : H7 E. coli strain HZ2001-9 causes clinical signs and pathological lesions in dogs that are consistent with those in acute renal failure or HUS in humans.

[The role of cyclooxygenase on angiogenesis and endothelial progenitor cell mobilization in rat ischemic myocardium].

OBJECTIVE: To investigate the effect of COX1 and COX2 on angiogenesis and endothelial progenitor cell mobilization in rats with experimental myocardial infarction (MI). METHODS: The rats were randomly divided into 3 groups: MI group, MI plus rofecoxib group and MI plus valeryl salicylate group. At the 7th day after operation, circulating EPCs, plasma VEGF and HIF-1alpha mRNA of ischemic myocardium were measured. At the 28th day post operation, capillary densities were also measured in ischemic myocardium. RESULT: Compared with the MI group and the MI plus valeryl salicylate group, circulating EPCs, plasma VEGF, HIF-1alpha mRNA and capillary densities of ischemic myocardium were all decreased in MI plus rofecoxib group. CONCLUSION: The present study revealed that COX2 play an important role with angiogenesis and endothelial progenitor cell mobilization in rat with experimental MI by modulating expression of VEGF and HIF-1alpha.

[Sirolimus inhibits the differentiation, proliferation and migration of endothelial progenitor cells in vitro].

OBJECTIVE: To investigate the effect of sirolimus on differentiation, proliferation, adhesion and migration of endothelial progenitor cells (EPC) in vitro. METHODS: (1) Mononuclear cells (MNC) were isolated from rat bone marrow by Ficoll density gradient centrifugation and cultured on fibronectin-coated culture dishes with or without sirolimus (0.01 - 100 ng/ml) for 12 days. (2) After 8 days cultured, attached cells were treated with sirolimus (0.1 - 200 ng/ml) or vehicle for various time points (12 h, 24 h, 48 h and 96 h). EPC were identified as adherent cells double positive stained for FITC-UEA-I and DiI-acLDL under laser confocal immunofluence microscope. EPC proliferation, migration were assayed with MTT assay and modified Boyden chamber assay respectively. RESULTS: EPC number differentiated from MNC at 12 days was significantly lower in sirolimus treated cells in a dose-dependent manner than that of vehicle-treated cells. Sirolimus also significantly inhibited the proliferative, migratory and adhesive capacity of EPC in a time and dose dependent manner. CONCLUSION: Present results suggested that sirolimus could inhibit EPC differentiation from MNC and reduce the proliferation, migration and adhesion capacities of EPC.

Autocrine interleukin-23 promotes self-renewal of CD133+ ovarian cancer stem-like cells.

Cancer stem cells (CSCs) are a group of cells which possess the ability of self-renewing and unlimited proliferation. And these CSCs are thought to be the cause of metastasis, recurrence and resistance. Recent study has found that pro-inflammatory cytokine and chemotactic factor mediate the self-renewing and differentiation of most of CSCs. Thus we speculate that ovarian cancer stem cells (OCSCs) can also maintain the ability of self-renewing and differentiation by releasing inflammatory factor. This report we discuss the biological characteristics and the specific molecular mechanism mediated by interleukin-23 (IL-23) and its receptor on the self-renewing of OCSCs. We found that OCSCs had high expression of IL-23 and IL-23R. IL-23 could promote the self-renewal ability of OCSCs and played a very important role to maintain the stable expression of stem cell markers in vitro. Moreover, we verified that IL-23 could maintain the potential tumorigenic of OCSCs in vivo and mediate the self-renewal ability and the formation of tumor in OCSCs by activating the signal pathways of STAT3 and NF-κB. In addition, human low differentiation tissues showed overexpression of IL-23. And IL-23 positively correlated to the expression level of CD133, Nanog and Oct4. In conclusion, Our discoveries demonstrate that autocrine IL-23 contribute to ovarian cancer malignancy through promoting the self-renewal of CD133+ ovarian cancer stem-like cells, and this suggests that IL-23 and its signaling pathway might serve as therapeutic targets for the treatment of ovarian cancer.

Let­7a suppresses cell proliferation via the TGF­ß/SMAD signaling pathway in cervical cancer.

Cervical cancer is the second most commonly diagnosed type of cancer among women after breast cancer. Recent research has addressed the role of microRNAs in cervical cancer. In the present study, we aimed to determine the effect of let­7a on the regulation of the cell proliferation of cervical cancer and the related signaling pathway. Real­time RT­PCR was used to detect the expression of let­7a in the blood of cervical cancer patients and normal controls. The expression of let­7a was also assessed in cervical cancer cell lines: HeLa, SiHa and normal human immortalized keratinocyes HaCaT. Cell proliferation was tested by MTT assay, and cell apoptosis and cell cycle were examined by flow cytometric analysis in HeLa cells. Moreover, bioinformatic analysis, dual­luciferase reporter assay and western blotting were used to confirm the target gene for let­7a. In addition, the expression of TGF­ß1, SMAD4 and p53 were assessed by western blotting and real­time PCR. Our studies showed that the expression of let­7a in cervical cancer was significantly reduced in cervical cancer patients compared with the expression in the normal control group. Cell proliferation of HeLa cells was inhibited by overexpression of let­7a. The cell cycle analysis showed that an increased population was arrested in the G2 phase in the let­7a mimic group when compared with that in the mimic control and untreated groups. In addition, the cell cycle­related factor p53 was increased in the let­7a overexpression group compared with that in the control and untreated groups. Furthermore, TGFBR1 was confirmed to be a target of let­7a. Moreover, the expression of TGF­ß1 and SMAD4 proteins was elevated in cervical squamous carcinoma and cervical adenocarcinoma tissues. However, the expression of TGF­ß1 and SMAD4 was decreased in the let­7a­overexpressing cervical cancer cell lines (HeLa, SiHa and CaSki). Our data suggest that let­7a may play a role in the cell proliferation of cervical cancer by regulating the TGF­ß/SMAD pathway, and may participate in the regulation of the occurrence and development of cervical cancer.