[Retracted] Upregulation of microRNA­181b inhibits CCL18­induced breast cancer cell metastasis and invasion via the NF­κB signaling pathway.

[This retracts the article DOI: 10.3892/ol.2016.5230.].

Prevalence and causes of visual impairment in population more than 50 years old: The Shaanxi Eye Study.

To assess the prevalence and causes of visual impairment (VI) in the elderly Chinese rural population in Shaanxi Province.A population-based, cross-sectional study design was used to determine the extent of VI in Chinese people over the age of 50 years in Shaanxi Province. Visual acuity and best-corrected visual acuity were measured using the logarithm of minimum angle of resolution chart. Blindness and low vision were defined according to WHO criteria. The major cause of VI was identified for all participants who were visually impaired.A total of 1912 residents completed a standard questionnaire and underwent a detailed eye examination, and the response rate was 90%. The overall prevalence of blindness and low vision were 1.5% and 8.2%. There was no statistically significant differences between genders in the prevalence of blindness and low vision (P > .05). The prevalence of blindness and low vision was higher among older individuals (P < .05) and lower (P < .05) among those with the highest education level. Cataract, corneal opacity, and glaucoma were considered as the main causes of blindness, which accounted for 67.9%, 10.7%, and 7.1%, respectively. Cataract, refractive error, and age-related macular degeneration were always considered as the leading causes of low vision, which accounted for 66%, 14.7%, and 5.8%, respectively.Cataract, corneal opacity, and glaucoma were the main causes of blindness and low vision in the population aged 50 years or more. The prevalence of these diseases that causes blindness and low vision was higher than that reported in other studies.

IL-10 inhibits retinal pigment epithelium cell proliferation and migration through regulation of VEGF in rhegmatogenous retinal detachment.

Rhegmatogenous retinal detachment (RRD) is a disorder of the eye that affects physical and mental health. Retinal pigment epithelium (RPE) is closely associated with RRD, and it is hypothesized that RPE-secreted inflammatory cytokines may induce early pathological changes of RRD and may participate in RPE proliferation and migration. The present study determined a role for interleukin (IL)­10 as an RPE­secreted immune regulatory factor that contributes to RRD. A rat RRD model was established and RPE cells were isolated and cultivated. RPE cells were randomly divided into four groups, three treated with different concentrations of IL­10 (100, 50, and 20 mM) and one untreated. RPE cell proliferation was evaluated by MTT assay and the activity of caspase­3 was also measured. RPE cell invasion was determined by Transwell assay. Vascular endothelial growth factor A (VEGF) expression was examined by reverse transcription­quantitative polymerase chain reaction and western blotting; IL­1 and IL­6 levels were measured by ELISA. IL­10 treatment suppressed RPE cell proliferation and migration, promoted caspase­3 activity, inhibited VEGF mRNA and protein expression, and downregulated the secretion of inflammatory cytokines IL­1 and IL­6 in RRD group compared with the untreated Model group. The aforementioned effects of IL­10 became more evident with increasing IL­10 concentration. IL­10 suppressed inflammation, facilitated RPE cell apoptosis and inhibited cell proliferation and migration through the regulation of VEGF expression.

Effects of drug combination on optic disc parameters and retinal nerve fiber layer thickness of high intraocular pressure type POAG patients / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM:To study the effects of timolol and latanoprost on optic disc parameters and retinal nerve fiber layer thickness of high intraocular pressure type POAG patients, and to provide guidance for clinical research.·METHODS: Totally 240 patients ( 336 eyes ) with high intraocular pressure type POAG in our hospital from November 2013 to November 2015 were randomly divided into control group and observation group, and each with a total of 120 cases (170 and 166 eyes, respectively). The patients in control group only received latanoprost treatment, while the observation group was treated with timolol and latanoprost treatment. After 3mo of treatment, we observed the therapeutic effects, and measured the optic disc parameters and retinal nerve fiber layer thickness. The incidence of adverse reactions was observed in the following 1a.·RESULTS: The patients of observation group and the control group after treatment showed the improvement rates of 97. 6% and 80. 6%, respectively, and the observation group was significantly better than the control group, the two groups showed statistically significant (P<0. 05). The eye rim area, rim volume, rim volume and diameter of two groups after treatment were higher than before ( P < 0. 05 ) , while those of the observation group was significantly higher than control group ( P<0. 05 ) . Two groups of patients with vertical cup to disc diameter decreased obviously ( P<0. 05 ) , the observation group was significantly lower than the control group, the difference was statistically significant ( P<0. 05 ) . Between the two groups of patients, during the period, incidences of dry eyes, corneal and conjunctival hyperemia, infiltration blurred vision and other complications had no significant difference ( P>0. 05), and the 1a follow-up of patients showed no other adverse reactions.·CONCLUSION: The use of timolol and latanoprost therapy for high intraocular pressure type POAG patients showed that the patients improve obviously, the visual acuity has more improved and the parameters of optic disc and retinal nerve fiber layer thickness are also improved.

Clinical observation of Conbercept intravitreal injection combined with retinal laser photocoagulation therapy on macular edema secondary to retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To study the efficacy of conbercept intravitreal injection combined with retinal laser photocoagulation therapy and simple laser photocoagulation therapy on macular edema (ME) secondary to retinal vein occlusion (RVO).METHODS:Forty-eight patients (53 eyes) with macular edema secondary to retinal vein occlusion diagnosed by clinical examination from October 2014 to March 2015 were retrospectively analyzed.Among them,28 patients (31 eyes) were treated with conbercept intravitreal injection combined with retinal laser photocoagulation,which was defined as Group A.And simple laser group contained 20 patients (22 eyes),which was defined as Group B.The clinical data including the patients' best-corrected visual acuity (BCVA) and central retinal thickness (CMT) before treatment and 1wk and 3mo after treatment were observed.RESULTS:Followed up for 3mo,the average BCVA values of A and B were 0.44±0.25,0.56±0.24,respectively and the average CMT were 330.50 ± 121.71,354.67 ± 102.79μm at first week of treatment.There was no significant difference in BCVA and CMT of Group A compared with Group B.There was statistically significant in BCVA and CMT of Group A and Group B compared with before treatment (P＜0.05).The average BCVA values of A and B were 0.24±0.18,0.39±0.20,respectively and the average CMT were 252.62 ± 83.01,332.67 ± 102.33μ m at third month of treatment.There were statistically significant differences between the two groups and compared with before treatment (P＜0.05),and Group A was superior to Group B.CONCLUSION:Conbercept intravitreal injection combined with retinal laser photocoagulation therapy and simple laser photocoagulation treatment of macular edema secondary to retinal vein occlusion are both effective that macular edema is significantly reduced,and vision is stable and improved.But for serious cases,conbercept intravitreal injection can reduce retinal edema at first,then combine with retinal laser photocoagulation which has obvious therapeutic effect and it is better than simple laser photocoagulation treatment.

Antidiabetic activities of a cucurbitane­type triterpenoid compound from Momordica charantia in alloxan­induced diabetic mice.

Momordica charantia has been used to treat a variety of diseases, including inflammation, diabetes and cancer. A cucurbitane­type triterpenoid [(19R,23E)­5ß, 19­epoxy­19­methoxy­cucurbita­6,23,25­trien­3 ß­o­l] previously isolated from M. charantia was demonstrated to possess significant cytotoxicity against cancer cells. The current study investigated the effects of this compound (referred to as compound K16) on diabetes using an alloxan­induced diabetic mouse model. C57BL/6J mice were intraperitoneally injected with alloxan (10 mg/kg body weight), and those with blood glucose concentration higher than 10 mM were selected for further experiments. Diabetic C57BL/6J mice induced by alloxan were administered 0.9% saline solution, metformine (10 mg/kg body weight), or K16 (25 or 50 mg/kg body weight) by gavage for 4 weeks, followed by analysis of blood glucose level, glucose tolerance, serum lipid levels and organ indexes. The results demonstrated that compound K16 significantly reduced blood glucose (31­48.6%) and blood lipids (13.5­42.8%; triglycerides and cholesterol), while improving glucose tolerance compared with diabetic mice treated with saline solution, suggesting a positive improvement in glucose and lipid metabolism following K16 treatment. Furthermore, similarly to metformine, compound K16 markedly upregulated the expression of a number of insulin signaling pathway­associated proteins, including insulin receptor, insulin receptor substrate 1, glycogen synthase kinase 3ß, Akt serine/threonine kinase, and the transcript levels of glucose transporter type 4 and AMP­activated protein kinase α1. The results of the current study demonstrated that compound K16 alleviated diabetic metabolic symptoms in alloxan­induced diabetic mice, potentially by affecting genes and proteins involved in insulin metabolism signaling.

Protective effect of Xuebijing injection against acute lung injury induced by left ventricular ischemia/reperfusion in rabbits.

Xuebijing (XBJ) is a Chinese herbal preparation. Previous studies have demonstrated that XBJ injection is able to inhibit the uncontrolled release of endogenous inflammatory mediators, attenuate inflammation, and alleviate organ damage. However, there are no relevant reports on the protective effect of XBJ against left ventricular ischemia/reperfusion (I/R)-induced acute lung injury (ALI). Therefore, the aim of the present study was to evaluate the protective effect of XBJ on ALI induced by left ventricular I/R, and provide evidence for the clinical application of XBJ. In the present study, 120 healthy rabbits of mixed gender were randomly assigned to a normal control group, ischemia group, I/R group (I/RG) and XBJ-injection treatment group (TG). In addition, each group was further divided into three subgroups (n=10/subgroup), namely, 30 min pre-ischemia, 30 min post-ischemia and 30 min post-reperfusion subgroups. Blood samples (5 ml) were collected from the jugularis externa and carotis communis of the rabbits at the three time points, and a blood gas analyzer was used to measure the arterial partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2). Following sacrifice, the lungs of the rabbits were removed and a bronchoalveolar lavage (BAL) was immediately performed. An enzyme-linked immunosorbent assay was used to measure the expression levels of tumor necrosis factor-α (TNF-α) in the BAL fluid (BALF) and peripheral blood. In addition, the lower lobe of the right lung was removed in order to measure the protein expression levels of intercellular adhesion molecule-1 (ICAM-1) and TNF-α. The results demonstrated that in the rabbits of the TG PaO2 was increased, PaCO2 was decreased, the lung tissue congestion edema was attenuated, the expression levels of TNF-α in the peripheral blood and BALF were reduced and the protein expression levels of ICAM-1 and TNF-α in the lung tissue samples were decreased, as compared with those in the I/RG rabbits. These results suggest that XBJ may protect against left ventricular I/R-induced ALI by regulating the expression of the inflammatory mediators TNF-α and ICAM-1.

Upregulation of microRNA-181b inhibits CCL18-induced breast cancer cell metastasis and invasion via the NF-κB signaling pathway.

The purpose of the present study was to investigate the effects of upregulating microRNA (miR)-181b expression in tumor-associated macrophages regarding breast cancer cell metastasis and to identify the target gene. Ectopic miR-181b was transfected into MDA-MB-231 and MCF-7 breast cancer cell lines with or without chemokine ligand 18 (CCL18) stimulation. Cell proliferation, migration/invasion and apoptosis rate were investigated. The binding effects of miR-181b to the 3'-untranslated region (UTR) of the nuclear factor (NF)-κB gene were detected with the dual luciferase reporter system. Immunofluorescent staining of the NF-κB key component P65 was performed. The messenger (m) RNA and protein expression of NF-κB induced by CCL18 with or without miR-181b stimulation was evaluated with reverse transcription-quantitative polymerase chain reaction and western blot analysis. When compared with the CCL18-stimulated group, miR-181b mimic-transfected cells exhibited significantly inhibited proliferation and migration, with an increased cell apoptosis percentage in a dose-dependent manner. Furthermore, the luciferase activity was reduced for cells with NF-κB 3'-UTR wild-type that were co-transfected with miR-181b mimics. Immunofluorescent staining of NF-κB demonstrably weakened the P65 signal in stimulated miR-181b mimic cells when compared with parental and CCL18-treated cells. The increased expression level of NF-κB induced by CCL18 in MDA-MB-231 and MCF-7 cells was suppressed by miR-181b mimics. Overexpression of miR-181b suppressed cell survival rate and migration. This overexpression may achieve this goal by regulating the NF-κB pathway in breast cancer cells. Our study demonstrated a potential therapeutic application of miR-181b in the treatment of breast cancer.

Cytoplasm estrogen receptor ß5 as an improved prognostic factor in thymoma and thymic carcinoma progression.

A number of previous studies have reported that sex steroid hormones, including estrogens, are involved in the regulation of the thymic function. The aim of the present study was to investigate the expression of estrogen receptor ß5 (ERß5) in thymic tumors and the correlation between ERß5 expression and thymoma biological characteristics. The expression levels of ERß5 in thymic epithelial tumors was evaluated in 103 patents using immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction. In addition, an indirect immunofluorescence assay was performed to evaluate the ERß5 expression levels in the TC1889 and T1682 cell lines. The survival outcome was estimated using Kaplan-Meier plots. The results indicated that ERß5 expression was mainly located in the thymic tumor cell cytoplasm (87.37%; 90/103 cases) and overexpression was observed in thymic tumors compared with normal thymic tissues (P=0.001). Using the Kruskal-Wallis test, a statistically significant association was observed between cytoplasmic ERß5 (cERß5) expression and thymic tumor subtypes (P=0.024) and stages (P=0.003 and R=-0.376). The Kaplan-Meier plots revealed that cERß5 expression was significantly associated with improved overall and progression-free survival (P=0.008 and P=0.004, respectively). The present study suggested that overexpression of cERß5 may indicate an improved prognosis and may be involved in the underlying mechanism through which estrogen inhibits thymoma and thymic carcinoma development.

Neurotoxicity of prenatal alcohol exposure on medullary pre-Bötzinger complex neurons in neonatal rats.

Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytryptamine 2A receptor (5-HT2AR) is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10% (v/v) throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2AR protein and mRNA levels in the pre-Bötzinger complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduction was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10% alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These findings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2AR protein and mRNA levels.

Characteristics of human umbilical cord mesenchymal stem cells during ex vivo expansion.

Human umbilical cord mesenchymal stem cells (hUCMSCs) have potential clinical applications in different types of diseases. In order to acquire enough cells, hUCMSCs have to be expanded ex vivo. However, it remains to be elucidated whether the characteristics of hUCMSCs are altered during ex vivo expansion. In the present study, the quality of hUCMSCs, which is important for successful therapeutic use, was systematically examined during hUCMSC expansion ex vivo. Morphologically, hUCMSCs exhibited no visible changes during culture. In addition, hUCMSCs retained their proliferative ability between passages 0-5. At the molecular level, the cells continued expressing the specific positive surface markers, CD29, CD73 and CD90, and did not express the negative surface markers, CD14, CD34 or CD45, during culture ex vivo. Furthermore, the hUCMSCs exhibited low immunogenicity, which was maintained when cultured for five passages. However, the immunological properties of hUCMSCs were altered at passage 10, at which the percentage of hUCMSCs expressing human leukocyte antigen­I was significantly increased. Collectively, these results suggested that hUCMSCs used for cell-based therapies require obtaining from cells, which have been expanded for fewer than five passages.

[Effect of prenatal alcohol exposure on rhythmic respiratory discharge activity in medullary slices of neonatal rats].

OBJECTIVE: To investigate the effects of prenatal alcohol exposure on rhythmic respiratory discharge activity (RRDA) in the medullary slices of neonatal rats. METHODS: Ten pregnant female SD rats were exposed to 0, 4%, 6%, 8%, and 10% alcohol in drinking water from 1 week before till 3 days after delivery. The medullary slices of the neonatal rats containing the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve rootlets were prepared and perfused with modified Kreb's solution to record RRDA from the hypoglossal nerve rootlets using suction electrodes. RESULTS: No significant difference was found in RRDA in 50 min among the neonatal rats with prenatal exposure to 0, 4%, 6%, and 8% alcohol, but the RRDA in 10% alcohol exposure group became irregular. Prenatal exposure to increased alcohol concentrations caused attenuated RRDA attenuated in the neonatal rats, shown by shortened inspiratory time (TI), decreased respiratory frequency (RF), and reduced integral amplitude (IA) as compared with those in the control group. CONCLUSION: Prenatal alcohol exposure inhibits RRDA in medullary slices of neonatal rats, which might be a mechanism by which maternal alcohol exposure causes suppressed offspring respiratory functions.

Up-regulation of ICAM-1mRNA and IL-1ßmRNA in lung tissues of a rat model of COPD.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by airflow obstruction that is usually progressive and not fully reversible. It is accompanied by the abnormal inflammatory response of lung to toxic particles or gas. Studies indicate that chronic inflammatory injuries of airway, pulmonary parenchyma and pulmonary vessels are the characteristic changes of COPD. Adhesion of inflammatory cells is the important link of pulmonary infection. Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein involved in binding with mediated cells or with the extracellular matrix in the process called cell adhesion. IL-1ß is an important inflammatory mediator as well as the promoter and critical inducer of cytokine cascade reaction. In this study, the rat model of COPD was established by smoking + intratracheal instillation of LPS (the experimental group). PaO2 and PaCO2 were measured. ICAM-1mRNA and IL-1ßmRNA level in lung homogenate were detected by immunohistochemistry and RT-PCR and were compared with those of the rats treated by smoke exposure (the control group) and the healthy rats (the blank group) in order to investigate the effect of ICAM-1 and IL-1ß in lung injury of COPD. This study showed that the respiratory function of rats with COPD was decreased. PaO2 of rats in the experimental group, the control group and the blank group decreased successively, and the comparison between any two groups had significant difference. PaCO2 increased successively, and the comparison between any two groups had significant difference. Immunohistochemistry results showed that protein expression of ICAM-1 and IL-1ß in lung tissues of rats in the experimental group was higher than that in the control group and the blank group, and the comparison between any two groups had significant difference. RT-PCR results showed that ICAM-1mRNA and IL-1ßmRNA level of rats in the experimental group was higher than that in the control group and the blank group, and the comparison between any two groups had significant difference. This study indicated that the decreased respiratory function of rats with COPD was associated with the imbalance of inflammatory cascade and the up-regulation of ICAM-1mRNA and IL-1ßmRNA in lung tissues and cells caused inflammatory injury and decreased respiratory function.

Xuebijing injection improves the respiratory function in rabbits with oleic acid-induced acute lung injury by inhibiting IL-6 expression and promoting IL-10 expression at the protein and mRNA levels.

Xuebijing injection is a complex herbal medicine, and clinical and experimental studies have shown that it has a significant effect on acute respiratory distress syndrome and multiple organ dysfunction syndrome. However, the majority of studies regarding Xuebijing injection have focused on serum inflammatory factors, and few studies have been carried out from the perspective of the protein and mRNA expression of inflammatory cytokines. In this study, 60 healthy rabbits of mixed gender were randomly assigned to a normal control group (CG), oleic acid group (model group; MG) and oleic acid + Xuebijing injection group (treatment group; TG). Rabbits of the CG were treated with normal saline through the ear vein, rabbits of the MG were injected with oleic acid (0.4 ml/kg) and rabbits of the TG received 0.4 ml/kg oleic acid + 10 ml/kg Xuebijing injection. Blood samples were collected from the common carotid artery of all rabbits of all groups 1 h after the ear vein was injected with the corresponding reagent, and was used to measure the arterial partial pressure of oxygen (PaO2) and of carbon dioxide (PaCO2). The activity of myeloperoxidase (MPO) was tested, and the protein and mRNA expression levels of interleukin (IL)-6 and IL-10 were determined. Rabbits of the MG exhibited evident respiratory dysfunction (PaO2 and PaCO2 were low), histopathological lung damage and overactive inflammatory responses (the expression of the proinflammatory cytokine IL-6 and the anti-inflammatory cytokine IL-10 was increased at the protein and mRNA levels). Following the administration of the Xuebijing injection, the inflammatory response of the rabbits was significantly reduced. Xuebijing injection raised PaO2 and PaCO2, weakened the activity of MPO in the lung tissue, downregulated the expression of the proinflammatory cytokine IL-6 and further increased the expression of the anti-inflammatory cytokine IL-10. These results demonstrated that Xuebijing injection improved the respiratory function of rabbits with acute oleic acid-induced lung injury by inhibiting IL-6 expression and promoting IL-10 expression.

Breviscapine reduces acute lung injury induced by left heart ischemic reperfusion in rats by inhibiting the expression of ICAM-1 and IL-18.

It has been demonstrated that breviscapine is able to treat coronary disease and reduce the inflammatory response; however, there are no relevant reports concerning its effects on the expression of inflammatory factors in acute lung injury induced by left heart ischemic reperfusion and the underlying mechanisms. In this study, we created a left heart ischemia-reperfusion model in rats to investigate the effects of breviscapine on the expression of interleukin 18 (IL-18) and intercellular adhesion molecule-1 (ICAM-1), as well as to determine the possible mechanisms involved in the protective effects of breviscapine on respiratory function. The left heart ischemia-reperfusion model was created by ligating the anterior descending branch of the coronary artery for 30 mins followed by reperfusion. Rats in the treatment group (TG) were treated with breviscapine (10 mg/kg) and the rats in the control group (CG) received normal saline. Ten rats in the two groups were sacrificed at three points: 30 min after ligating (T1), 30 min after reperfusion (T2) and 60 min after reperfusion (T3). A respiration curve was produced and the arterial partial pressure of oxygen (PaO2) was measured for all rats. Additionally, the expression levels of IL-18 and ICAM-1 were determined and the correlation between IL-18 and ICAM-1 expression in lung tissue was analyzed. The level of IL-18 in peripheral blood and bronchialalveolar lavage fluid (BALF) was also measured. The respiration amplitude was lower and the duration time was shorter in the TG rats than in the CG rats at T1, T2 and T3. The expression levels of IL-18 and ICAM-1 in the TG group were clearly reduced. The level of IL-18 in the peripheral blood and BALF was downregulated following the administration of breviscapine. These results demonstrate that breviscapine inhibits the expression of IL-18 and ICAM-1, thereby protecting the lungs from inflammatory cascade responses.