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.

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.

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.

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.

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.

COVID-19 information propagation dynamics in the Chinese Sina-microblog.

The outbreak of a novel coronavirus (COVID-19) generated an outbreak of public opinions in the Chinese Sina-microblog. To help in designing effective communication strategies during a major public health emergency, we propose a multiple-information susceptible-discussing-immune (M-SDI) model in order to understand the patterns of key information propagation on social networks. We develop the M-SDI model, based on the public discussion quantity and take into account of the behavior that users may re-enter another related topic or Weibo after discussing one. Data fitting using the real data of COVID-19 public opinion obtained from Chinese Sina-microblog can parameterize the model to make accurate prediction of the public opinion trend until the next major news item occurs. The reproduction ratio has fallen from 1.7769 and maintained around 0.97, which reflects the peak of public opinion has passed but it will continue for a period of time.

Management of Low-Energy Basicervical Proximal Femoral Fractures by Proximal Femoral Nail Anti-Rotation.

OBJECTIVE: To evaluate clinical and radiological outcomes of proximal femoral nail anti-rotation (PFNA-II) devices and demonstrate the effectiveness of PFNA-II for the treatment of basicervical fractures in elderly patients. METHODS: A retrospective review of all patients treated with PFNA-II for a proximal femoral fracture between January 2013 and February 2017 at three different institutions (Shanghai General Hospital, Shanghai Punan Hospital and Shanghai Seventh People's Hospital) was conducted. The X-ray films were strictly reviewed by three trauma surgeons and a professional radiology doctor. Patients over 60 years of age who met the following criteria were included: (i) sustained low-energy trauma; (ii) a two-part fracture; (iii) fracture line located at the base of the femoral neck and that was medial to the intertrochanteric line and exited above the lesser trochanter but was more lateral than a classic transcervical fracture. Follow-up time should be longer than 6 months. A total of 52 patients who met the inclusion criteria were selected. The average age at diagnosis was 75.1 years (range, 63-91 years); 13 patients were men and 39 were women. The same proximal femoral nail anti-rotation devices and the same surgical procedures were applied to all patients. Postoperative radiographic union time and modified Harris hip scores were used as major indicators for evaluating the effectiveness of surgery. RESULTS: The average follow-up period was 22.5 months (18.5, 23.9, and 21.2 months, respectively) and radiographic unions were observed at an average of 19.6 weeks (range, 12-28 weeks). The patients were evaluated immediately after surgery, as well as 6 weeks, 3 months, 6 months, 1 year, and 2 years postoperatively. Of the 49 patients, 38 had good reduction qualities (75.5%), 9 acceptable (18.3%), and 3 poor (6.1%). Radiographic union was confirmed in all fractures at an average of 19.6 weeks (range, 12-28 weeks). The mean Harris hip score was 84.9 (range, 65-99): excellent in 9 patients (18.36%), good in 30 (61.22%), medium in 8 (16.32%), and poor in 2 (4.08%). Slight persistent pain occurred in 3 patients, but these patients could still walk with the help of a cane. Two patients had symptoms of excessive telescoping. Eight patients experienced postoperative medical complications, mainly pneumonia and urinary tract infection. CONCLUSION: Based on the clinical and radiological outcomes, the PFNA-II devices provide strong rotational stability and excellent clinical prognosis, and are an appropriate treatment option for basicervical proximal femoral fracture in elderly patients.

Implication of sexual transmission of Zika on dengue and Zika outbreaks.

Dengue and Zika viruses belong to the same Flavivirus family and usually cocirculate within the same area. Both the viruses can be transmitted by a common mosquito species Aedes aegypti. However, non-vector-borne transmission of Zika virus, such as sexual transmission and vertical transmission, has been reported in recent studies. In this study, we develop a dengue-Zika coinfection model with a particular focus on the impact of Zika sexual transmission to the transmission dynamics of both dengue and Zika. Our sensitivity analysis shows that Zika sexual transmission has a significant influence on the Zika basic reproduction number. Consequently, Zika sexual transmission can lead Zika to be endemic within an area where vector-borne transmission only cannot. Theoretically, we prove that the disease-free equilibrium for dengue only model is always globally stable if the dengue basic reproduction number is less than 1. However, our cascade analysis and numerical simulations show that increasing the sexual transmission coefficient of Zika can also result in the persistence of dengue even though the dengue basic reproduction number is less than 1, due to the cocirculation of dengue and Zika and the antibody-dependent enhancement of Zika infection for dengue infection. Our numerical analyses also show that the endemic levels of Zika increase as the Zika sexual transmission probability increases.

Nearcasting forwarding behaviors and information propagation in Chinese Sina-Microblog.

As the largest social media in China, the Sina-Microblog plays an important role in public opinion dissemination. Despite intensive efforts in understanding the information propagation dynamics, the use of a simple outbreak model to generate summative indices that can be used to characterize the time series of a single Weibo event has not been attempted. This work fills this gap, and illustrates the potential of using a simple outbreak model in conjunction with the historical data about the cumulative forwarding users for nearcasting the propagation trend.

The human cost of global warming: Deadly landslides and their triggers (1995-2014).

Worldwide, landslides incur catastrophic and significant economic and human losses. Previous studies have characterized the patterns in landslides' fatalities, from all kinds of triggering causes, at a continental or global scale, but they were based on data from periods of <10 years. The research herein presented hypothesizes that climate change associated with extreme rainfall and population distribution is contributing to a higher number of deadly landslides worldwide. This study maps and identified deadly landslides in 128 countries and it encompasses their role, for a 20 years' period from January/1995 to December/2014, considered representative for establishing a relationship between landslides and their meteorological triggers. A database of georeferenced landslides, their date, and casualties' information, duly validated, was implemented. A hot spot analysis for the daily record of landslide locations was performed, as well as a percentile-based approach to evaluate the trend of extreme rainfall events for each occurrence. The relationship between casualty, population distribution, and rainfall was also evaluated. For 20 years, 3876 landslides caused a total of 163,658 deaths and 11,689 injuries globally. They occurred most frequently between June and December in the Northern Hemisphere, and between December and February in the Southern Hemisphere. A significant global rise in the number of deadly landslides and hotspots across the studied period was observed. Analysis of daily rainfall confirmed that more than half of the events were in areas exposed to the risk of extreme rainfall. The relationships established between extreme rainfall, population distribution, seasonality, and landslides provide a useful basis for efforts to model the adverse impacts of extreme rainfall due to climate change and human activities and thus contribute towards a more resilient society.

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.

Improved Fertility Following Enucleation of Intramural Myomas in Infertile Women.

BACKGROUND: The relationship between intramural myomas and fertility remains unclear. The main debate rests on whether cavity-distorting intramural myomas (CDMs) adversely affect fertility more than non-CDMs. We aimed to compare the effects of enucleating non-CDMs and CDMs on fertility improvement in females with unexplained infertility. METHODS: We prospectively recruited 83 women undergoing myomectomy for unexplained infertility with intramural myomas between June 2008 and November 2012 and classified them into non-CDMs group (n = 45) and CDMs group (n = 38). We then compared postoperative infertility rates, spontaneous pregnancy rates, pregnancy outcomes, live birth rates, and obstetric complications. For continuous variables, we calculated the mean ± standard deviation, median and interquartile range, and analyzed the data using Student's t-test and the Mann-Whitney U-test. For categorical variables, the Pearson's Chi-square test, the continuity correction test, and Fisher's exact test were used. RESULTS: Patients' demographics and myoma characteristics were comparable between the two groups. The overall spontaneous pregnancy rate increased from 0% to 68.42% following myomectomy. The postoperative infertility rate was significantly higher in the non-CDMs group than that in the CDMs group (50.00% vs. 23.53%, t = 5.579, P = 0.018), whereas the postoperative spontaneous pregnancy rate was significantly lower in the non-CDMs group than that in the CDMs group (47.62% vs. 70.59%, t = 4.067, P = 0.044). Compared with the enucleation of non-CDM, the enucleation of CDM patients was a protective factor for the fertility restoration (risk ratio [RR] = 3.717, 95% confidence interval [CI]: 1.284-10.753, P = 0.015), although postoperative fertility restoration declined with age (RR = 1.141, 95% CI: 1.005-1.295, P = 0.041). CONCLUSIONS: Intramural myomas are associated with impaired fertility. Women experiencing unexplained infertility, and possessing intramural myomas, have a better chance of conception following myomectomy, and these benefits are more obvious for younger patients and patients with CDM.

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.

[Factors of prognosis in cervical spondylotic myelopathy: a review].

Cervical spondylotic myelopathy (CSM) is a common cause of spinal cord dysfunction clinical disease. Surgery is the main therapeutic tool for CSM. However, there are obvious differences in clinical functional recovery after operation. For the past few years, the influence factors of prognosis in cervical spondylosis myelopathic has been widely concerned. Age, nerve function, course of desease, imaging findings,surgical method and related factors became the investigative point for prognosis of cervical spondylotic myelopathy. Present viewpoint showed that the older patient, preoperative worse nerve function, longer the course of disease would result in worse outcomes. Imaging examination maybe can indicate the prognosis, but the correlation is unclear. Selection of surgical method and approach should be based on the principles of sufficient decompression, stabilize the alignment of the cervical spine, keeping backward extension of cervical spine, maintain effective decompression, preventing complications. Therefore, the treatment of cervical spondylotic myelopathy should be on the basis of pathogenic condition and imaging examination at early stage and a suitable usrgical procedure should be performed to obtain a better prognosis.

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.

Centipeda minima (Ebushicao) extract inhibits PI3K-Akt-mTOR signaling in nasopharyngeal carcinoma CNE-1 cells.

BACKGROUND: Centipeda minima (Ebushicao) has been used for the treatment of various diseases, such as nasal allergies, rhinitis and sinusitis, nasopharyngeal carcinoma, cough, and headache. This study aims to investigate the anticancer activities of Centipeda minima ethanol extracts (CME) against nasopharyngeal carcinoma cell CNE-1 and their underlying mechanism. METHODS: CNE-1 cells were treated with different concentrations (15-50 µg/mL) of CME for different time intervals (24, 48, and 72 h). Cytotoxicity of CME was determined by MTT assay. Cell morphological changes were observed by fluorescence microscopy after HO 33258 staining. Cell cycle status was evaluated by flow cytometry following propidium iodide staining. Apoptosis was detected by flow cytometry following annexin V-FITC/PI staining. The levels of apoptosis-associated and PI3K-Akt-mTOR signaling related proteins were measured by western blotting analysis. RESULTS: CME (15-50 µg/mL) significantly inhibited the proliferation of CNE-1 in a dose- and time-dependent manner (P = 0.026 for 15 µg/mL, P < 0.001 for 25, 30, 40, and 50 µg/mL, respectively); the IC50 values (µg/mL) were 41.57 ± 0.17, 30.34 ± 0.06 and 24.98 ± 0.08 for 24, 48 and 72 h treatments, respectively. Significant morphological changes of CNE-1 cells displaying apoptosis were observed after CME treatment. CME showed low cytotoxicity toward normal LO2 cells. CNE-1 cells were arrested in the G2/M phase while treated with 15, 25, 40 µg/mL of CME, respectively (P = 0.032, P = 0.0053, P < 0.001). CME (15, 25, 40 µg/mL) down-regulated Bcl-2 expression (P = 0.032, P = 0.0074, P < 0.001), and up-regulated Bax (P = 0.026, P = 0.0056, P < 0.001) with activation of caspase-3, caspase-8, caspase-9, and PARP observed in CNE-1 cells (P = 0.015, P = 0.0067, P < 0.001 for caspase 3; P = 0.210, 0.028, < 0.001 for caspase 8; P = 0.152, 0.082, 0.0080 for caspase 9; P = 0.265, 0.0072, < 0.001 for PARP). CME suppressed the activation of the PI3K-AKT-mTOR pathway (P = 0.03, 0.0007, 0.004, 0.006, 0.022 for p-PI3K, p-Akt-Ser(473), p-Akt-Thr(308), p-mTOR-Ser(2448), p-mTOR-Ser(2481), respectively after 40 µg/mL of CME treated for 24 h). CONCLUSION: CME inhibited the proliferation of CNE-1 cells and activation of the PI3K-AKT-mTOR signaling pathway.

Macrophage-secreted Exosomes Delivering miRNA-21 Inhibitor can Regulate BGC-823 Cell Proliferation.

Exosomes, membranous nanovesicles, naturally carry bio-macromolecules or miRNA and play impoetant roles in tumor pathogenesis. Here, we showed that macrophages cell-derived exosomes can function as vehicles to deliver exogenous miR-21 inhibitor into BGC-823 gastric cancer cells. Exosomes loaded with miR-21 inhibitor significantly increased miR-21 levels in BGC-823, but miR-21 inhibitor loaded in exosomes exerted an opposite effect. miRNA transfected with exosomes had less cellular toxicity to host cells compared to conventional transfection methods. The miR-21 inhibitor loaded exosomes promoted the migration ability and reduced apoptosis of BGC-823 gastric cancer cells. These observations indicate that miR-21 acts as a tumor promoter by targeting the PDCD4 gene and preventing apoptosis of gastric cancer cells through inhibition of PDCD4 expression. Furthermore, exosome -mediated miR-21 inhibitor delivery resulted in functionally more efficient inhibition and less cellular toxicity compared to conventional transfection methods. Similar approaches could be useful in modification of target biomolecules in vitro and in vivo. These findings contribute to our understanding of the functions of miR-21 and exosomes as a carrier for therapy of gastric cancer.