Protective effect of Lycium barbarum polysaccharides against high-fat diet-induced renal injury and lipid deposition in rat kidneys.

This study aimed to explore the protective effect of Lycium barbarum polysaccharides (LBPs) against hyperlipidemia and lipid-induced renal injury in a rat model. Male Sprague-Dawley rats (n=30) were randomly divided into three equal groups: a control group (fed a regular diet) and two experimental groups (fed a high-fat diet). By feeding rats a high-fat diet for 12 weeks, an animal model of hyperlipidemia was established, after which one experimental group received oral LBPs at a dose of 300 mg/kg per day. Blood lipids, renal function, and urinary proteins were measured after 12 weeks. Changes in renal pathology and expression levels of sterol regulatory element binding transcription factor 1 (SREBP-1), interleukin-6 (IL- 6), tumor necrosis factor-alpha (TNF-α), AMP-activated protein kinase (AMPK) were determined. Rats with hyperlipidemia induced by a high-fat diet showed increases in blood lipids and blood urea nitrogen, serum creatinine, and urinary protein, as well as increases in renal levels of SREBP-1, TNF-α, and IL-6 and decreases in renal levels of adiponectin and AMPK. Administration of LBPs restored blood lipid, blood urea nitrogen, serum creatinine, and urinary protein levels, downregulated renal levels of SREBP-1, TNF-α, and IL-6, and upregulated renal levels of adiponectin and AMPK. These results indicate that LBPs may mediate lipid metabolism, enhance anti-inflammatory responses, and ameliorate renal injury caused by lipid metabolism isorders in a rat model of hyperlipidemia.

MicroRNA-1294 targets HOXA9 and has a tumor suppressive role in osteosarcoma.

OBJECTIVE: MicroRNA-1294 (miR-1294) was reported to act as a tumor suppressor in several cancers. However, the biological function of miR-1294 in osteosarcoma (OS) has not been investigated. We, therefore, investigated the clinical significance and underlying mechanisms of miR-1294 in OS. PATIENTS AND METHODS: Quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR) was conducted to detect the levels of miR-1294. Targets of miR-1294 were validated by luciferase reporter assay and Western blot. In vitro functional assays were performed to investigate the effects of miR-217 on cell proliferation and invasion. RESULTS: We found miR-1294 was downregulated in OS tissues and cell lines. Downregulation of miR-1294 has a significant negative impact on the overall survival of OS patients. Overexpression of miR-1294 suppresses OS cell proliferation and invasion in vitro. Then, luciferase reporter assay validated Homeobox A9 (HOXA9) was a downstream target of miR-1294. Expression patterns of miR-1294 were inversely correlated with HOXA9 in OS tissues, strengthening the findings from the luciferase reporter assay. Further functional assays revealed that overexpression of HOXA9 could reverse the inhibition effects of miR-1294 on cell proliferation and invasion. CONCLUSIONS: These results suggested miR-1294 functions as a tumor suppressor in OS progression by targeting HOXA9.

[Analysis of risk factors for acute lung injury/acute respiratory distress syndrome after esophagectomy].

OBJECTIVE: To explore the incidence and risk factors for the acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) after resection of esophageal carcinoma. METHODS: We retrospectively analyzed 422 consecutive patients admitted to the Department of Critical Care Medicine with esophageal carcinoma undergoing esophagectomy from January 2010 to December 2016 in Peking University Cancer Hospital. ALI/ARDS were diagnosed, the patients were divided into ALI/ARDS group and control group without ALI/ARDS, the differences of clinical features were contrasted between the two groups, and the multivariate Logistic regression modeling was used to identify the independent risk factors for ALI/ARDS. RESULTS: In the study, 41 ALI/ARDS cases were diagnosed, making up 9.7% (41/422) of all the enrolled patients undergoing esophagectomy. Comparisons of the ALI/ARDS group and the control group indicated significant statistical differences in the average length of their hospital stay [(18.9±9.7) d vs. (14.8±3.6) d, P=0.011], the proportion of the patients who needed mechanical ventilation support [51.2% (21/41) vs. 9.4% (36/381), P<0.001] and in-hospital mortality [31.7% (13/41) vs. 5.0% (19/381), P<0.001]. Univariate analysis showed significant differences between the patients with ALI/ARDS and without ALI/ARDS in smoking history (P=0.064), preoperative forced expiratory volume in one second/forced vital capacity (FEV1/FVC) (P=0.020), diffusing capacity of the lung for carbon monoxide (DLCO) (P=0.011), body weight index (BMI) (P=0.044), American Society of Anesthesiologists (ASA) physical status classification (P=0.049) and one lung ventilation duration (P=0.008), while multivariate Logistic regression analysis indicated that preoperative FEV1/FVC (OR=1.053, P=0.016, 95%CI 1.010-1.098), ASA physical status classification (OR=2.392, P=0.033, 95%CI 1.073-5.335) and one lung ventilation duration (OR=0.994, P=0.028, 95%CI 0.989-0.999) were the independent risk factors for ALI/ARDS after esophagectomy. CONCLUSION: ALI/ARDS was a serious complication in patients undergoing esophagectomy associated with increment in length of hospital stay and in-hospital mortality. Multivariate Logistic regression analysis indicated that preoperative FEV1/FVC, ASA classification and one lung ventilation duration were the independent risk factors for ALI/ARDS after esophagectomy. Carefully assessing the patient before operation, shortening one lung ventilation duration were the key points in preventing ALI/ARDS after esophagectomy.

Systemic gene delivery transduces the enteric nervous system of guinea pigs and cynomolgus macaques.

Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or phosphate-buffered saline. Piglets were euthanized three weeks post injection and tissues were harvested for immunofluorescent analysis. GFP expression was detected in myenteric and submucosal neurons along the length of the gastrointestinal tract in AAV8 injected guinea pigs. GFP-positive neurons were found in dorsal motor nucleus of the vagus and dorsal root ganglia. Less transduction occurred in AAV9-treated tissues. Gastrointestinal tissues were analyzed from young cynomolgus macaques that received systemic injection of AAV9 GFP. GFP expression was detected in myenteric neurons of the stomach, small and large intestine. These data demonstrate that ENS gene delivery translates to larger species. This work develops tools for the field of neurogastroenterology to explore gut physiology and anatomy using emerging technologies such as optogenetics and gene editing. It also provides a basis to develop novel therapies for chronic gut disorders.

TRIM59 is a key regulator of growth and migration inrenal cell carcinoma.

Renal cell carcinoma (RCC) is the most common renal neoplasms and metastatic is common. Previous data have shown that the tripartite motif (TRIM) family proteinswere implicated in human tumoriogenesis. In this study, we aimed to investigate the role of TRIM59 in the cell growth and migration in RCC. The expression of TRIM59 in human RCC tissues was initially examined by qRT-PCR. Alentivirus-based shRNA against TRIM59 (Lv-shTRIM59) was constructed. The effects of TRIM59 knockdown on cell proliferation were examined by in vitro MTT assay, colony formation assay and in vivo a mouse xenograft model of RCC. Cell migration and invasion after knockdown of TRIM59 were also examined by transwell assay. Our data showed that the mRNA level of TRIM59 in cancerous tissues was 2-fold increased as compared with non-cancerous tissues. Knockdown of TRIM59 in a RCC cell line 786-O significantly slowed down cell proliferative rate and decreased both the colony number and sizes. In the mouse model, knockdown of TRIM59 consistently inhibited tumor growth in vivo. Moreover, it was shown that cell migration and invasion were suppressed by 68% and 50%, respectively in TRIM59-depleted 786-O cells. Our data suggest that TRIM59 may serve as a pro-oncogenic protein in promoting the progression of RCC. Knockdown of TRIM59 may be a promising strategy concerning the early detection and treatment of RCC.

Pivotal role of microRNA-9 in osteosarcoma tumorigenesis and tumor progression.

MicroRNA-9 (miR-9) has a well-established role in various tumors; the clinical significance and potential mechanism of miR-9 in human osteosarcoma (OS) has not been elucidated. The aim of this study was to investigate the mechanism and role of miR-9 expression in osteosarcoma cells. miR-9 expression in the OS cell line MG-63 and OS tissues was compared to that in a human osteoblastic cell line (hFOB 1.19) and adjacent normal tissues, respectively, by reverse transcriptase-polymerase chain reaction. miR-9 expression was downregulated by introducing small interfering RNA against miR-9 (si-miR-9) into the cells, and the proliferative, migratory, and invasive capacities of si-miR-9-transfected MG-63 cells were compared to those of control MG-63 cells. miR-9 was significantly upregulated in OS tissues and cell lines compared to the corresponding non-cancerous bone tissues (P < 0.05) and human osteoblastic cell line (P < 0.05), respectively. Upregulated miR-9 expression was also associated with increased cell proliferation (P < 0.05), migration (P < 0.05), and invasion (P < 0.05), and decreased apoptotic ability (P < 0.05). These results suggest that miR-9 may play a pivotal role in tumorigenesis and tumor progression in osteosarcoma.

[Effect of 2-methoxyestradiol combined with quercetin on prostate cancer in vitro].

OBJECTIVE: To detect the effects of quercetin (Que) combined with 2-methoxyestradiol (2-ME) on the proliferation of androgen-dependent LNCaP human prostate cancer cells line and androgen-independent PC-3 human prostate cancer cells line, and to evaluate the antitumor effects of different combos of the two drugs. METHODS: After LNCaP and PC-3 cells were treated with different concentration of quercetin (0, 3.125, 6.25, 12.5, 25, 50, 100, 200 µmol/L) or 2-ME (0, 0.312 5, 0.625, 1.25, 2.5, 5, 10 µmol/L) for 48 h, the inhibitory rates of cell growth were tested using trypan blue staining method respectively. Then the concentration-effect curves were drawn and IC(50) values were calculated. According to the fitted dose-effect curves and IC(50) values, appropriate concentrations of quercetin and 2-ME were selected to compose 16 different combos. Then cells were treated with different combos of Que and 2-ME for 48 h, and then the growth inhibitory rates of cell growth were detected. According to the equation and median-effect principle, the CI values of 16 different combos of Que and 2-ME were calculated to evaluate their antitumor effects. RESULTS: The inhibition rate of LNCaP or PC-3 cell growth treated with varying doses of quercetin or 2-ME alone showed a dose-dependent increase respectively. The IC(50) values of quercetin and 2-ME were 23.29 µmol/L and 1.89 µmol/L for LNCaP cells; and 22.12 µmol/L and 1.74 µmol/L for PC-3 cells respectively. After treated with 16 combos of Que (5, 10, 20, 40 µmol/L) and 2-ME (0.5, 1, 3, 5 µmol/L) for 48 h, for LNCaP cells, lower dose of Que (5 and 10 µmol/L) with higher dose of 2-ME (3 and 5 µmol/L) showed synergistic activity, whereas for PC-3 cells, besides the above combination of Que 10 µmol/L and 2-ME 3 µmol/L, higher dose of quercetin (20 and 40 µmol/L) with higher dose of 2-ME (3 and 5 µmol/L) also showed synergistic activity. CONCLUSIONS: Both quercetin and 2-methoxyestradiol could inhibit the growth of LNCaP and PC-3 human prostate cancer cells in a dose dependent manner. We confirmed that combinations of quercetin and 2-ME at appropriate concentrations have the potential for synergetic antiproliferative activity in vitro.

Potential gains in life expectancy from reducing heart disease, cancer, Alzheimer's disease, kidney disease or HIV/AIDS as major causes of death in the USA.

OBJECTIVES: Potential gains in life expectancy (PGLEs) that give proper consideration to competing risks are an effective indicator for measuring the impact of multiple causes of death on a defined population. This study aimed to assess PGLE by hypothetically reducing the major causes of death in the USA from 2001 to 2008. STUDY DESIGN: PGLEs due to the reduction and elimination of heart disease, cancer, Alzheimer's disease, kidney disease or human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) were calculated by age, gender and race. METHODS: Age-specific mortality rates for the above diseases from the National Center for Health Statistics were used, and multiple decremental life tables were constructed to compute the corresponding PGLEs. RESULTS: PGLEs due to the elimination of heart disease, cancer or HIV/AIDS decreased from 2001 to 2008, but PGLEs due to the elimination of Alzheimer's disease or kidney disease increased over time. For heart disease, PGLE in 2001-2008 for all races was 2.78-2.15 for females vs 2.41-2.06 for males. For cancer, PGLE in 2001-2008 for all races was 2.97-2.81 for females vs 3.02-2.85 for males. HIV/AIDS has a greater impact on people of working age, whereas Alzheimer's disease has a greater impact on the elderly population. To compare the impacts of these diseases on life expectancy, partial multiple decremental life tables were constructed, and PGLEs were computed by a partial reduction or complete elimination of various causes of death for the entire life span as well as for certain working ages. CONCLUSION: This study outlined a picture of how each category of diseases could affect life expectancy in the US population by age, race or sex. The findings may assist in evaluating current public health improvements, and also provide useful information for directing future research and disease control programmes.

Neurogenic mucosal bicarbonate secretion in guinea pig duodenum.

BACKGROUND AND PURPOSE: To test a hypothesis that: (i) duodenal pH and osmolarity are individually controlled at constant set points by negative feedback control centred in the enteric nervous system (ENS); (ii) the purinergic P2Y(1) receptor subtype is expressed by non-cholinergic secretomotor/vasodilator neurons, which represent the final common excitatory pathway from the ENS to the bicarbonate secretory glands. EXPERIMENTAL APPROACH: Ussing chamber and pH-stat methods investigated involvement of the P2Y(1) receptor in neurogenic stimulation of mucosal bicarbonate (HCO(3)(-)) secretion in guinea pig duodenum. KEY RESULTS: ATP increased HCO(3)(-) secretion with an EC(50) of 160 nM. MRS2179, a selective P2Y(1) purinergic receptor antagonist, suppressed ATP-evoked HCO(3)(-) secretion by 47% and Cl(-) secretion by 63%. Enteric neuronal blockade by tetrodotoxin or exposure to a selective vasoactive intestinal peptide (VIP, VPAC(1)) receptor antagonist suppressed ATP-evoked HCO(3)(-) secretion by 61 and 41%, respectively, and Cl- by 97 and 70% respectively. Pretreatment with the muscarinic antagonist, scopolamine did not alter ATP-evoked HCO3(-) or Cl(-) secretion. CONCLUSION AND IMPLICATIONS: Whereas acid directly stimulates the mucosa to release ATP and stimulate HCO(3)(-) secretion in a cytoprotective manner, neurogenically evoked HCO(3)(-) secretion accounts for feedback control of optimal luminal pH for digestion. ATP stimulates duodenal HCO(3)(-) secretion through an excitatory action at purinergic P2Y(1) receptors on neurons in the submucosal division of the ENS. Stimulation of the VIPergic non-cholinergic secretomotor/vasodilator neurons, which are one of three classes of secretomotor neurons, accounts for most, if not all, of the neurogenic secretory response evoked by ATP.

Effect of processing route on the surface properties of amorphous indomethacin measured by inverse gas chromatography.

The aim of this study was to investigate the effect of processing route (i.e., quench cooling and ball milling) on the surface energy heterogeneity and surface chemistry of indomethacin (IMC). Recently developed inverse gas chromatography (IGC) methodology at finite concentrations was employed to determine the surface energy distributions of crystalline, quench cooled and milled IMC samples. Surface properties of crystalline and processed IMC were measurably different as determined by the IGC and other conventional characterization techniques: differential scanning calorimetry and powder X-ray diffraction. Quench cooled IMC was in fully amorphous form. Milled IMC showed no amorphous character by calorimetric or X-ray diffraction studies. It was demonstrated that both processed IMC samples were energetically more active than the crystalline IMC. In particular, milled IMC exhibited a relatively higher dispersive surface energy and higher surface basicity (electron donor capability). This may be attributed to the creation of surface defect sites or exposure of higher energy crystal facets during the milling process. This study confirms that processing route has notable influence on the surface energy distribution and surface acid-base character. IGC was demonstrated as a powerful technique for investigating surface properties of real-world, heterogeneous pharmaceutical materials.

Analysis of 13 cases of venous compromise in 178 radial forearm free flaps for intraoral reconstruction.

The purpose of this study was to analyse the causes of venous compromise and flap failure in radial forearm free flap (RFFF) surgery for intraoral reconstruction. One hundred seventy-eight RFFF reconstructions were reviewed retrospectively for intraoral defects. Of the 13 flaps with venous obstruction, 9 flaps were salvaged, and 4 were lost, with a salvage rate of 69.2%. Eleven venous occlusions occurred within the first 72h. The main reasons for venous failure were mechanical obstruction or technical errors due to inadequate pedicle length and geometry, inadequate venous drainage, compression and kinking of the vein. The main cause of failure for oropharynx reconstruction was unrecognized vascular events due to the lack of reliable monitoring for buried flap. Oozing of dusky blood from the flap margin may be directly related to venous congestion in the early postoperative period and a late indication of a change in skin colour. In conclusion, a thorough operative plan, including carefully selected drainage vein for the flap and recipient vessels, adequate pedicle length and geometry, precise surgical technique, avoidance of haematoma, and expert monitoring of buried flaps may improve the success rate of RFFF transfer in intraoral reconstruction.

Enema reduction of intussusception by hydrostatic pressure under ultrasound guidance: a report of 377 cases.

Three hundred seventy-seven pediatric intussusception patients were treated by normal saline hydrostatic enema under ultrasound guidance from October 1985 to April 1987. Before reduction, the rate of correct diagnosis by ultrasonography was 100%, and the rate of successful reduction was 95.5% in this group. With this technique there is no risk of x-ray exposure to the patient. The definite criteria for reduction are discussed. Clear echogram was shown during reduction and the ileo-ileo-coli intussusception can be diagnosed. Intestinal perforation, if any, can be accurately recognized at once. This technique is believed to be one of the most promising methods in nonoperative treatment of pediatric intussusception.

Serologic diagnosis of nasopharyngeal carcinoma. A double-blind study of four EB virus antibodies with evaluation by sequential discrimination.

It is generally known that a close relationship exists between Epstein-Barr Virus (EBV) and nasopharyngeal carcinoma (NPC). Recently, patients with early lesions of NPC have been detected in the general population by use of serologic mass survey. Using the double-blind method, we have studied the diagnostic value of the four EBV antibody titers, VCA-IgA, VCA-IgG, EA-IgA and EA-IgG, in four groups of subjects, each consisting of 50 persons: patients with nasopharyngeal carcinoma (NPC group), patients with cancers other than NPC in the head and neck regions (HNC group), patients with cancers outside of head and neck regions (OC group) and normal individuals (NS group). The results of these four antibodies were evaluated both singularly and together by multivariate sequential discrimination. Taking 1:10 as the criterion of being positive, in the NPC group, the positive rate of VCA-IgA is 88%, the VCA-IgG rate is 100%, the EA-IgA rate is 48% and the EA-IgG rate is 74%. In the non-NPC group, the positive rates of VCA-IgA are as high as 86%-92%, but those of the other antibodies are as low as 0-42%. The positive rates and the geometric mean titers of these four antibodies were all elevated as compared with those in the three non-NPC groups. These differences are statistically significant. VCA-IgG is unimportant in the diagnosis of NPC because of its low specificity. By treating the antibody titers of VCA-IgA, VCA-IgG, EA-IgA and EA-IgG with sequential discrimination, the correlation rate between the serology and pathology of NPC is 88% and the false positive rate is 7.3%.