Low Dose of Emodin Inhibits Hypercholesterolemia in a Rat Model of High Cholesterol.

BACKGROUND Emodin has been widely used in traditional Chinese medicine, but few studies have tried to understand the mechanism of its anti-hypercholesterolemic effect. MATERIAL AND METHODS To delineate the underlying pathways, high-cholesterol diet (HCD)-fed Sprague-Dawley rats were orally administrated emodin or the lipid-lowering medicine simvastatin. Emodin was administered at 10, 30, or 100 mg/kg, while simvastatin was administered at 10 mg/kg. Parameters measured included lipid profiles (serum total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, aorta endothelium-dependent vasorelaxation in response to acetylcholine, and nitric oxide (NO) production. RT-qPCR and western blotting were performed to evaluate aortic endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), and hepatic LDL receptor (LDLR). Indices of liver and serum oxidation were also measured. RESULTS The atherogenic index was increased by the HCD but significantly reduced in all treatment groups. The HCD-fed experimental group treated with emodin at 10 mg/kg had significantly lower serum total-C and LDL-C and improved aorta vasorelaxation and enhanced NO production. Also, emodin significantly attenuated the lipid profiles and restored endothelial function, as reflected by upregulated expression of hepatic LDLR and p-eNOS, respectively. Furthermore, emodin at 10 mg/kg significantly enhanced superoxide dismutase activity, lowered the malondialdehyde level in both liver and serum, and enhanced catalase activity in serum. CONCLUSIONS The ability of emodin to inhibit hypercholesterolemia in HCD-fed rats was associated with lower serum total-C and LDL-C, restoration of aortic endothelial function, and improved antioxidant capacity. Low-dose emodin showed better protection of aortic endothelium and better antioxidant activity than did higher doses.

Intussusception after reconstruction following gastrectomy for gastric cancer.

BACKGROUND: Gastric cancer is the most prevalent tumor in Chinese men, and surgery is currently the most important treatment. Billroth II and Roux-en-Y are the anastomosis methods used for reconstruction after gastrectomy. Jejunal intussusception is a rare complication after gastric surgery. MAIN BODY: Intussusception after gastric surgery occurs mostly at the gastrojejunostomy site for Billroth II reconstruction, and the Y-anastomosis site for Roux-en-Y reconstruction. Many studies have reported that postoperative intussusception appears at the anastomosis after bariatric surgery, while a few have reported intussusception at the anastomosis and its distal end after radical gastrectomy. CONCLUSION: A review was carried out to analyze intussusception after radical gastrectomy with roux-en-y anastomosis during the current situation. And the relevant mechanisms, diagnosis, treatment methods, etc. are described, hoping to provide better guidance for clinicians.

Surgical exposures of the distal humeral fractures: An anatomical study of the anterior, posterior, medial and lateral approaches.

PURPOSE: Exposure of the articular surface is the key to the successful treatment of intra-articular fractures of distal humerus. Anterior, posterior olecranon osteotomy as well as medial and lateral approaches are the four main approaches to the elbow. The aim of this study was to compare the exposure of distal articular surfaces of these surgical approaches. METHODS: Twelve cadavers were used in this study. Each approach was performed on six elbows according to previously published procedures. After completion of each approach, the exposed articular surfaces were marked by inserting 0.5 mm K-wires along the margins. The elbow was then disarticulated and the exposed articular surfaces were painted. The distal humeral articular surfaces were then closely wrapped using a piece of fibre-glass screen net with meshes. The exposed articular surfaces and the total articular surfaces were calculated by counting the number of meshes, respectively. RESULTS: The average percentages of the exposed articular surfaces for the anterior, posterior olecranon osteotomy, medial and lateral approaches were 45.7% ± 2.0%, 53.9% ± 7.1%, 20.6% ± 4.9% and 28.5% ± 6.3%, respectively. CONCLUSION: The anterior and posterior approaches provide greater exposures of distal humeral articular surface than the medial and lateral ones in the treatment of distal humeral fractures.

Characteristics and potentials of stem cells derived from human degenerated nucleus pulposus: potential for regeneration of the intervertebral disc.

BACKGROUND: Eliminating the symptoms during treatment of intervertebral disc degeneration (IVDD) is only a temporary solution that does not cure the underlying cause. A biological method to treat this disorder may be possible by the newly discovered nucleus pulposus derived stem cells (NPDCs). However, the uncertain characteristics and potential of NPDCs calls for a comprehensive study. METHODS: In the present study, nucleus pulposus samples were obtained from 5 patients with IVDD undergoing discectomy procedure and NPDCs were harvested using fluorescence activated cell sorting (FACS) by the co-expression of GD2+ and Tie2+. After in vitro expansion, the properties of NPDCs were compared with those of bone marrow mesenchyme stem cells (BMSCs) from the same subjects. RESULTS: NPDCs performed similar properties in cell colony-forming ability, cell proliferation rate, cell cycle and stem cell gene expression similar to those of BMSCs. In addition, NPDCs could be differentiated into osteoblasts, adipocytes, and chondrocytes, and are found to be superior in chondrogenesis but inferior in adipocyte differentiation. CONCLUSIONS: NPDCs derived from the degenerated intervertebral disc still keep the regeneration ability similar to BMSCs. Besides, the superior capacity in chondrogenesis may provide a promising cell candidate for cell-based regenerative medicine and tissue engineering in IVDD.

[PI3K/p110ß-specific inhibitors in castration-resistant prostate cancer].

Advanced prostate cancer, especially at the castration-resistant stage, remains incurable clinically and, therefore, urgently requires new therapeutics for the patients. PI3K is a family of critical cell signal transduction molecules and their over-activation is an important factor in cancer development and progression. It has been demonstrated that class IA PI3K p110 is drastically overexpressed in prostate cancer and involved in androgen receptor-mediated gene expression and castration-resistant progression and regarded as a potential therapeutic target for prostate cancer. Several p110-specific inhibitors have been reported recently and two of them, GSK2636771 and AZD8186, are being tested in clinical trials.

Security authentication using the reflective glass pattern imaging effect.

The reflective glass pattern imaging effect is investigated experimentally for the utility in forming a synthetic 3D image as a security authentication device in this Letter. An array of homogeneously randomly distributed reflective elements and a corresponding micropattern array are integrated onto a thin layer of polyester film aiming to create a vivid image floating over a substrate surface, which can be clearly visible to the naked eye. By using the reflective-type configuration, the micro-optic system can be realized on a thinner substrate and is immune to external stain due to its flat working plane. A novel gravure-like doctor blading technique can realize a resolution up to 12,000 dpi and a stringent 2D alignment requirement should be imposed. Such devices can find applications in document security and banknotes or other valuable items to protect them against forgery.

Anti-miR-362-3p Inhibits Migration and Invasion of Human Gastric Cancer Cells by Its Target CD82.

AIM: This study was to investigate the effects and mechanisms of miR-362-3p on regulation of gastric cancer (GC) cell metastasis potential. METHODS: We detected miR-362-3p level in GC and adjacent normal tissues and investigated the relationship with clinicopathological factors. Next, we analyzed the level of miR-362-3p expression and CD82 in different differentiated GC cells compared with a normal gastric mucosa cell by RT-PCR and Western blot. Dual-luciferase reporter assay and Western blot confirmed a direct interaction between miR-362-3p and CD82 3'UTR. After miR-362-3p and CD82 were silenced in GC cells, we compared the transfected GC cells migration and invasion capacity by transwell assay. In addition, we detected the effects on cells angiogenesis by tube formation assay. Western blot was used to detect the impact of CD82 and miR-362-3p on epithelial-to-mesenchymal transition markers in treated GC cells. RESULTS: Level of miR-362-3p expression was much higher in GC cells than in normal gastric mucosa cell, and miR-362-3p expression negatively correlated with CD82 mRNA expression in these cell lines. Furthermore, miR-362-3p expression induced [corrected] GC cell metastasis capacity by suppression of CD82 expression. Level of miR-362-3p may mediate E-cadherin, N-cadherin, and vimentin expression in GC cells. CONCLUSION: This study illuminated that downregulation of miR-362-3p along with the upregulation of CD82 in GC cells resulted in the inhibition of GC migration and invasion. Thus, our results suggested that miR-362-3p or CD82 can be exploited as a new potential target for control of GC in the future.

Advanced glycation end products promote differentiation of CD4(+) T helper cells toward pro-inflammatory response.

This study investigated the effect of advanced glycation end products (AGEs) on differentiation of naïve CD4(+) T cells and the role of the receptor of AGEs (RAGE) and peroxisome proliferator-activated receptors (PPARs) activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin (BSA) with glucose. Human naïve CD4(+) T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin (sh) RNA knock-down experiment, naïve CD4(+) T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-X(TM) 293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4(+) T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T (Treg) cells was determined by a [(3)H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from naïve CD4(+) T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in naïve CD4(+) T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4(+) T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα PPARγ agonist, PGJ2, inhibited the effect of AGEs on naïve CD4(+) T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It was concluded that AGEs may promote CD4(+) T cells development toward pro-inflammatory state, which is associated with increased RAGE mRNA expression and reduced PPARγ activity.

[Spatial and Temporal Scale Effects of Landscape Pattern on Riverine Nitrogen and Phosphorus Nutrients in the Qingshan Lake Watershed].

The influences of landscape pattern on water quality are dependent on spatial-temporal scales. However, the effects of landscape composition, landscape configuration, and landscape slope metrics on seasonal water quality at different spatial scales remain unclear. Based on the total nitrogen, total phosphorus, nitrate-N, and ammonium-N data from 26 sampling sites in the Qingshan Lake watershed, this study coupled landscape pattern analysis, redundancy analysis, and partial redundancy analysis to quantify the spatiotemporal scale effects of landscape pattern on riverine nitrogen （N） and phosphorus （P） concentrations. The results showed that： ① The explanatory ability of landscape pattern at the sub-watershed scale on riverine N and P concentrations was 6.8%-8.4% higher than that at the buffer scale, and this effect was more obvious in the dry season. ② At the sub-watershed scale, the percentage of forestland and the interspersion and juxtaposition degree of residential land had a greater influence on riverine N and P concentrations. At the buffer scale, the slope of farmland and residential land and the aggregation degree of forestland patches were the key factors affecting riverine N and P concentrations. ③ The contribution rate of landscape configuration to riverine N and P concentration variations （20.1%-36.5%） was the highest. The sensitivity of the effect of landscape configuration on riverine N and P concentrations to seasonal changes was the highest, and the effect of landscape slope on riverine N and P concentrations had the highest sensitivity to spatial scale changes. Therefore, landscape pattern-regulated non-point source pollution should be considered from a multi-scale perspective. These results can provide scientific basis for the formulation of landscape pattern optimization measures aiming at non-point source pollution control.

XRCC1 polymorphisms increase bladder cancer risk in Asians: a meta-analysis.

X-ray cross complementing group 1 (XRCC1) polymorphisms and bladder cancer risk has been investigated for years, but the result in Asian population is till inconclusive. Thus, we performed this meta-analysis to determine the association of XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphisms with bladder cancer risk in the Asian population. PubMed, EMBASE, and China National Knowledge Infrastructure were searched up to January 2013 to identify eligible studies. The association strength was measured with odd ratios (ORs) and 95 % confidence intervals (95 % CIs). A total of nine eligible studies, including 1,931 bladder cancer patients and 2,192 controls, were identified. Significant increased risk of bladder cancer was observed for Arg194Trp polymorphism (allele comparison OR = 1.20, 95 % CI: 1.06-1.36, P heterogeneity = 0.11; dominant model OR = 1.20, 95 % CI: 1.02-1.41, P heterogeneity = 0.37) and Arg280His polymorphism (heterozygote comparison OR = 1.87, 95 % CI: 1.21-2.90, P heterogeneity = 0.01; dominant model OR = 1.75, 95 % CI: 1.05-2.90, P heterogeneity = 0.01); however, Arg399Gln was not associated with susceptibility to bladder cancer. No evidence of publication bias was detected. Our meta-analysis results suggest that XRCC1 Arg194Trp and Arg280His polymorphisms are associated with significantly increased risk of bladder cancer in Asians.

[Types of primary cyclins expressed in gastric carcinoma and their relationship with clinicopathological features].

OBJECTIVE: To characterize the human primary cyclins (D1, E, A, B1) expressed in gastric carcinoma, and to clarify the relationship between the types of expressed primary cyclins and clinicopathological features of gastric carcinoma. METHODS: Primary cyclins (D1, E, A, B1) expressed in single cells separated from 68 cases gastric carcinoma tissues were analyzed by flow cytometry. We classified the gastric carcinomas by different types of the expressed primary cyclins, and explore the roles of primary cyclins expressed in cell cycle and the expression patterns of the cyclins. The results were analyzed together with clinicopathological features. RESULTS: The patterns of expressed primary cyclins could be classified into five types. The proportion was 10.3% (7/68), 22.1% (15/68), 25.0% (17/68), 29.4% (20/68), and 13.2% (9/68), respectively, from type I to type V. Each type could be, according to the degree of in-cycle cyclins expressed, divided into different sub-types. The types of primary cyclins expressed were strongly linked to invasive depth and lymph node metastasis of the gastric carcinoma (P < 0.01). The rates of lymph node metastasis were 26.6%, 43.8%, 82.3%, 95.0%, and 100.0%, respectively, from type I to type V. The type of primary cyclins expressed was also significantly associated with disease stage (TNM stage). The proportion of stage IV disease was 0, 6.7%, 17.6%, 25.0% and 55.6%, respectively, from type I to type V. It was shown that there were relationships between the sub-types of primary cyclins expressed and different growth-types, degree of cell differentiation, or, the tumor gross types (P < 0.01). CONCLUSIONS: The types of primary cyclins expression are different in the process of the occurrence, development and metastasis of gastric carcinoma, and are correlated with clinicopathological features of gastric carcinoma.

Predictive Value of Flank Pain and Gross Hematuria on Long-Term Survival in Patients With Upper Tract Urothelial Carcinoma Treated by Radical Nephroureterectomy.

Background: Assessing the prognosis preoperatively in patients with upper tract urothelial carcinoma (UTUC) remains a challenge for urologists. Gross hematuria (GH) and flank pain (FP) are the 2 most common and easily perceived symptoms of UTUC. Therefore, we aimed to investigate the prognostic values of GH and FP in patients with UTUC after undergoing radical nephroureterectomy (RNU). Methods: This article retrospectively analyzed 179 patients with UTUC who underwent RNU and examined the associations between the FP, GH, and long-term survival. After dividing patients into 4 subgroups (presenting as GH without FP, FP without GH, no FP and GH, FP with GH), we focused on the prognostic values of the 4 subgroups using univariate and multivariate analyses. We then proposed a risk stratification model for UTUC based on the independent prognostic factors for cancer-specific survival (CSS) with external validation (146 additional UTUC patients formed the validation cohort). Results: Patients with FP had worse oncological outcomes than those without FP (P < .05). After dividing the 179 patients into 4 subgroups, the "FP without GH" subgroup suffered the worst oncological outcomes (P < .001). The Cox multivariate regression analysis showed that "FP without GH" (P < .001), tumor multifocality (P = .005), and pathological stage (P = .004) were independent prognostic factors for CSS. Good performance of the risk stratification model was achieved in both the training and external validation cohorts. Conclusion: The presence of "flank pain without gross hematuria" was one of the independent risk factors of CSS and OS besides the pathological stage and tumor multifocality. To our knowledge, this is the first study that adding complaint to risk stratification model in UTUC.

Quantitative mass spectrometry combined with separation and enrichment of phosphopeptides by titania coated magnetic mesoporous silica microspheres for screening of protein kinase inhibitors.

We describe herein the development of a matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) approach for screening of protein kinase inhibitors (PKIs). MS quantification of phosphopeptides, the kinase-catalyzed products of nonphosphorylated substrates, is a great challenge due to the ion suppression effect of highly abundant nonphosphorylated peptides in enzymatic reaction mixtures. To address this issue, a novel type of titania coated magnetic hollow mesoporous silica spheres (TiO(2)/MHMSS) material was fabricated for capturing phosphopeptides from the enzymatic reaction mixtures prior to MS analysis. Under optimized conditions, even in the presence of 1000-fold of a substrate peptide of tyrosine kinase epidermal growth factor receptor (EGFR), the phosphorylated substrates at the femtomole level can be detected with high accuracy and reproducibility. With a synthetic nonisotopic labeled phosphopeptide, of which the sequence is similar to that of the phosphorylated substrate, as the internal standard, the MS signal ratio of the phosphorylated substrate to the standard is linearly correlated with the molar ratio of the two phosphopeptides in peptide mixtures over the range of 0.1 to 4 with r(2) being 0.99. The IC(50) values of three EGFR inhibitors synthesized in our laboratory were then determined, and the results are consistent with those determined by an enzyme-linked immunosorbent assay (ELISA). The developed method is sensitive, cost/time-effective, and operationally simple and does not require isotope/radioative-labeling, providing an ideal alterative for screening of PKIs as therapeutic agents.

Serum nitric oxide synthase activity is a novel predictor of impaired vasorelaxation in rats.

1. It is well documented that both acetylcholine (ACh)-evoked arterial relaxation and brachial artery flow-mediated vasodilatation are blunted in hypercholesterolaemic patients. However, there are no simple diagnostic methods to detect the pathology of blood vessels of patients. 2. To establish the use of serum nitric oxide synthase (NOS) activity as a diagnostic parameter for impaired vasorelaxation, animals with different levels of vascular healthiness were made by feeding Sprague-Dawley rats a normal diet, a high-cholesterol diet (HCD) or an HCD supplemented with 10 mg/kg per day, p.o., simvastatin, a cholesterol-lowering drug, for 30 days. Serum total cholesterol levels, serum NOS activity and ACh-induced vasorelaxation of the isolated aorta were determined at the end of the experiment. 3. Consumption of HCD for 30 days resulted in an increase in serum total cholesterol, attenuated ACh-induced nitric oxide/endothelium-dependent aortic relaxation and decreased NOS activity. Concomitant administration of simvastatin lowered the elevated blood cholesterol levels with complete reversal of the attenuated ACh-induced aortic relaxation and serum NOS activity. An attempt was made to correlate serum NOS activity and the magnitude of ACh-elicited vascular relaxation among the different groups. A positive correlation (r = 0.8329; P < 0.001; n = 30) was found between serum NOS activity and vascular relaxation. 4. This finding is a good foundation for the development of a simple and low-cost alternative for diagnosing vascular diseases and evaluating the effectiveness of drugs on the vascular system in patients.

Suppression of diet-induced hypercholesterolemia by turtle jelly, a traditional chinese functional food, in rats.

Consumption of functional foods for lowering serum cholesterol has globally gained acceptance by the general public. Turtle jelly (TJ), also called gui-ling-gao, is a popular traditional functional food in southern China. The hypocholesterolemic effect of consuming TJ was investigated in rats fed with normal diet, high-cholesterol diet or high-cholesterol diet supplemented with simvastatin (3 mg/kg bw per day, p.o.) or TJ (3.3 or 10 mL/kg bw per day, p.o.) for 30 days. TJ markedly reversed the increased serum total cholesterol, increased high-density lipoprotein, and decreased high-density lipoprotein induced by hypercholesterolemic diet with a dose-dependent improvement on the atherogenic index. It also demonstrated good hepatoprotective function by reducing fat depositions and overall lipid contents in the liver and increasing the activities of hepatic antioxidative enzymes. The blunted nitric oxide/endothelium-mediated aortic relaxation in rats fed with hypercholesterolemic diet was partially restored after TJ consumption. It is postulated that the hypocholesterolemic effect is the primary beneficial effect given by TJ; it then leads to secondary beneficial effects such as vasoprotective and hepatoprotective functions. The results revealed that TJ could block the downregulation of LDLR and PEPCK and upregulation of PPARα mRNA and protein expressions in the livers of rats fed with hypercholesterolemic diet.

A review of the anticancer and immunomodulatory effects of Lycium barbarum fruit.

The anticancer effects of traditional Chinese medicine (TCM) have attracted the attention of the public vis-à-vis existing cancer therapies with various side effects. Lycium barbarum fruit, commonly known as Gou Qi Zi in China, is a potential anticancer agent/adjuvant. Its major active ingredients, L. barbarum polysaccharides (LBP), scopoletin and 2-O-ß-D-glucopyranosyl-L-ascorbic acid (AA-2ßG), are found to have apoptotic and antiproliferative effects on cancer cell lines. Moreover, LBP also contributes to body's immunomodulatory effects and enhances effects of other cancer therapies. It is not known whether there are any undesirable effects. Further studies on its pharmacological mechanisms and toxicology could facilitate a safe usage of this TCM herb.

Change of uterine leiomyoma size during pregnancy and the influencing factors: A cohort study.

OBJECTIVE: To evaluate the changes of uterine leiomyoma size during pregnancy and determine the factors influencing it. METHODS: A prospective study was conducted from June 2016 to June 2018. Women with pregnancies complicated by leiomyoma were recruited. Ultrasound examinations were conducted to measure the size of leiomyoma during 6-7, 11-14, 22-24, 28-34 weeks of pregnancy and before delivery. The clinical characteristics and delivery details of the pregnant women were collected. Changes in leiomyoma size during different gestation periods and the influencing factors were analyzed. RESULTS: Leiomyoma size commonly increased before 22-24 weeks of pregnancy and the fastest growth occurred before 11-14 weeks. From 22-24 weeks to the date of delivery, the size of leiomyoma remained unchanged. The initial size of the leiomyoma showed negative correlation with the changes in leiomyoma diameters during pregnancy. Pre-pregnancy body mass index, fetus number, leiomyoma location, and parity were positively correlated with the size changes in leiomyoma from 22-24 to 28-34 weeks of pregnancy. CONCLUSION: Before 22-24 weeks of pregnancy, the size of the leiomyoma was gestation-dependent, which increases with gestational weeks. The fastest growth rate was before 11-14 weeks. The growth of leiomyoma is affected by multiple factors, and different factors can play different roles during different periods of the pregnancy.

Human umbilical cord Wharton's jelly-derived mesenchymal stem cell transplantation could improve diabetic intracavernosal pressure.

Mesenchymal stem cells (MSCs) secrete various cytokines with angiogenic and neuroprotective effects. This study aimed to assess the effects of human umbilical cord Wharton's jelly-derived MSCs (hWJ-MSCs) on diabetes-related intracavernosal pressure (ICP) impairment in rats. hWJ-MSCs were isolated from human umbilical cord Wharton's jelly and transplanted into the corpus cavernosum of streptozotocin (STZ)-induced diabetic rats by unilateral injection. The erectile function was evaluated at 4 weeks, as well as the expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endothelial nitric oxide synthase (eNOS), and insulin-like growth factor 1 (IGF1). STZ-induced diabetic rats showed impaired ICP, which was significantly improved by hWJ-MSC treatment. VEGF, eNOS, IGF1, and bFGF expression levels were higher in hWJ-MSC injection sites than those in control ones in STZ-induced diabetic rats. These results suggest that hWJ-MSC transplantation might improve diabetic erectile dysfunction through increased production of paracrine growth factors, highlighting a novel potential therapeutic option for erectile dysfunction.

Exosome-Mediated miR-4792 Transfer Promotes Bladder Cancer Cell Proliferation via Enhanced FOXC1/c-Myc Signaling and Warburg Effect.

Bladder cancer is the second-most common malignancy in the urogenital system and the most common in men. However, our understanding of the driving mechanisms of bladder cancer remains incomplete. The forkhead box (FOX) family of transcription factors is implicated in urogenital development and bladder malignancies. Many exosomal microRNAs have been identified as regulators and mediators of the expression of FOX, including the expression of FOXC1. miR-4792 has been known as a tumor miRNA suppressor. However, the function of miR-4792/FOXC1 signaling in bladder cancer development remains unknown. Here, we studied the role of miR-4792/FOXC1 signaling in bladder cancer by using multiple bladder cancer cell lines and bladder cancer mouse models through in vitro and in vivo approaches. We showed that FOXC1 is highly expressed in multiple bladder cancer cell lines and bladder tumor tissues. The knockdown of FOXC1 expression in bladder cancer cell lines decreases c-Myc expression levels, retards cell growth, and reduces aerobic glycolysis (also known as the Warburg effect) and lactic acid content. By contrast, the overexpression of FOXC1 elicits the opposite effects. FOXC1-downregulated bladder cancer cells form significantly smaller tumors in vivo. The inhibition of c-Myc reverses the effects of FOXC1 overexpression and leads to reduced cell proliferation, aerobic glycolysis, and lactic acid content. miR-4792 expression is downregulated in bladder tumor tissues. miR-4792 exposure to bladder cancer cells reduces the expression levels of FOXC1 and c-Myc, slows down cell growth, and decreases aerobic glycolysis and lactic acid content. However, the enhanced miR-4792 expression elicits opposite effects. These findings provided the first evidence that the exosome-mediated delivery of miR-4792 could play an important role in bladder cancer development through the downregulation of FOXC1 and c-Myc, which further inhibited aerobic glycolysis and lactic acid content.

Interferon alpha on expression of hTERT mRNA in peripheral blood mononuclear cells of patients with chronic hepatitis B.

Cell division is closely related to telomerase activity (hTERT mRNA). Lower expression of lymphocitic hTERT mRNA may easily cause cell aging, which is not beneficial to maintaining a durable lymphocyte division. To date, there is no study to investigate IFNα therapy on hTERT mRNA expression in PBMCs of patients with chronic hepatitis B (CHB). We quantitatively detected hTERT mRNA from study subjects and made each hTERT mRNA normalized (NhTERT mRNA). Mean NhTERT mRNA level was lower in either CHB group, but it significantly increased in IFNα-treated group compared with CHB control group, and a longer duration of IFNα therapy could increase the level. Moreover, the mean NhTERT mRNA in subgroup with HBeAg loss was significantly higher than that in subgroup without. NhTERT mRNA was markedly correlated with CD3(+) T lymphocyte count and CD4(+)/CD8(+) ratio. The results showed that IFNα therapy could upregulate the expression of hTERT mRNA in PBMCs.