Repositioning baloxavir marboxil as VISTA agonist that ameliorates experimental asthma.

V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA), a novel negative checkpoint regulator, plays an essential role in allergic pulmonary inflammation in mice. Treatment with a VISTA agonistic antibody could significantly improve asthma symptoms. Thus, for allergic asthma treatment, VISTA targeting may be a compelling approach. In this study, we examined the functional mechanism of VISTA in allergic pulmonary inflammation and screened the FDA-approved drugs for VISTA agonists. By using mass cytometry (CyTOF), we found that VISTA deficiency primarily increased lung macrophage infiltration in the OVA-induced asthma model, accompanied by an increased proportion of M1 macrophages (CD11b+F4/80+CD86+) and a decreased proportion of M2 macrophages (CD11b+F4/80+CD206+). Further in vitro studies showed that VISTA deficiency promoted M1 polarization and inhibited M2 polarization of bone marrow-derived macrophages (BMDMs). Importantly, we discovered baloxavir marboxil (BXM) as a VISTA agonist by virtual screening of FDA-approved drugs. The surface plasmon resonance (SPR) assays revealed that BXM (KD = 1.07 µM) as well as its active form, baloxavir acid (BXA) (KD = 0.21 µM), could directly bind to VISTA with high affinity. Notably, treatment with BXM significantly ameliorated asthma symptoms, including less lung inflammation, mucus secretion, and the generation of Th2 cytokines (IL-5, IL-13, and IL-4), which were dramatically attenuated by anti-VISTA monoclonal antibody treatment. BXM administration also reduced the pulmonary infiltration of M1 macrophages and raised M2 macrophages. Collectively, our study indicates that VISTA regulates pulmonary inflammation in allergic asthma by regulating macrophage polarization and baloxavir marboxil, and an old drug might be a new treatment for allergic asthma through targeting VISTA.

C188-9, a small-molecule STAT3 inhibitor, exerts an antitumor effect on head and neck squamous cell carcinoma.

Abnormal activation of signal transducer and activator of transcription 3 (STAT3) is complicated in the tumor progression of multiple cancers including human head and neck squamous cell carcinoma (HNSCC) and, therefore, serves as a potent therapeutic target. In this study, we identify that C188-9, a small-molecule STAT3 inhibitor, exhibits an antitumor effect on HNSCC in vitro. C188-9 significantly inhibits cell growth, arrests cell cycle at G0/G1 phase, and induces apoptosis in HNSCC. Besides, the capacities of migration and invasion of HNSCC cells are impaired with the exposure to C188-9. In addition, C188-9 treatment enhanced the chemosensitivity of HNSCC cellsin vitro. Moreover, C188-9 inactivates STAT3 by reducing its phosphorylation at Tyr705. Taken together, these results indicate that C188-9 could be a promising therapeutic strategy for patients suffered from HNSCC by suppressing the STAT3 pathway.

Factors associated with mortality risk for malignant colonic obstruction in elderly patients.

BACKGROUND: Acute colonic obstruction is the most common complication of colorectal cancer (CRC) in elderly patients. Medical treatment has been associated with higher perioperative morbidity and mortality rates. There is a need for identification of elderly CRC patients who will do poorly so that results can be improved. The purpose of this study is to assess the 30-day outcome of elderly patients undergoing malignant colonic obstruction procedures and identify the associated factors of mortality. METHODS: A review of 233 elderly patients who received medical procedures for malignant colonic obstruction between April 2000 and April 2012 was conducted. Data regarding clinical variables, surgical procedures and outcomes, complications, and mortality were studied. Univariate and logistic regression analyses were performed on mortality risk factors. RESULTS: Patients had a mean age of 78.2 years (range 70-95). A total of 126 (54.1%) patients were classified ASA III and above. Eighty (34.3%) patients had right-sided colonic obstruction. In the 153 (65.7%) patients with left-sided colonic obstruction, 40 patients received self-expandable metallic stent (SEMS) treatment and 193 patients received surgery. A total of 62.2% (n = 145) patients had post operation complications. The overall 30-day mortality was 24.5% (n = 57). ASA grading, peritonitis and Dukes staging were independent risk factors for mortality. CONCLUSIONS: Medical procedures in elderly patients with malignant colonic obstruction are associated with significant complications and mortality. Identifying these high-risk patients and treating promptly may improve outcomes. SEMS treatment provides a useful alternative to surgical intervention.

Histological complete response to a combined docetaxel/cisplatin/fluorouracil neoadjuvant chemotherapy for T4 stage gastric adenocarcinoma.

Local advanced gastric carcinoma has a very poor prognosis. When a T4 gastric carcinoma has invaded the surrounding tissues and organs, curative resection is unlikely. We present here a case of a 63-year-old woman with a T4 unresectable gastric adenocarcinoma. She underwent two 3-week cycles of docetaxel/cisplatin/fluorouracil chemotherapy, followed by radical gastric resection. Each cycle consisted of 75 mg/m2 docetaxel and 75 mg/m2 cisplatin on day 1, and 200 mg/m2 leucovorin and 500 mg/m2 fluorouracil on days 1 through 5. The patient exhibited a complete histologic response. Our results indicate that docetaxel/cisplatin/fluorouracil neoadjuvant chemotherapy is a promising method of treatment for advanced gastric cancer.

[Reevaluating the role of dilation and curettage in the diagnosis of ectopic pregnancy].

OBJECTIVE: To evaluate the clinical role of dilation and curettage (DC) in the diagnosis of ectopic pregnancy (EP). METHODS: We retrospectively reviewed the clinical data of 108 patients with pregnancy of unknown location who underwent a DC with an abnormal rise in ß-human chorionic gonadotropin (ß-HCG) level and without visible intrauterine pregnancy (IUP) on transvaginal ultrasound and 24 patients who did not receive DC with ß-HCG>5 000 IU/L.The final diagnosis depended on ß-HCG trend review after DC and the pathologic and laparoscopic findings. RESULTS: Overall, 65.3% of the patients were finally diagnosed with EP and 34.7% were found to have a nonviable IUP.Those with EP had significantly higher initial ß-HCG than those with nonviable IUP.IUP patients were more likely to have had a history of delivery.Among the patients with ß-HCG<2 000 IU/L, 40.0% of EP and 11.0% of IUP had endometrial echo complex no more than 5 mm (P=0.035). In ß-HCG<2 000 IU/L and 2 000 IU/L<ß-HCG<5 000 IU/L groups, the diagnostic rate of EP was 42.6% and 68.3% respectively (P=0.012). Among the patients with ß-HCG>5 000 IU/L, there was no significant difference between those with DC and those without DC (96.7% vs.96%, P=0.915). CONCLUSIONS: Ultrasound findings such as a thin endometrial echo complex and the presence of pelvic mass are associated with but are not diagnostic of an ectopic pregnancy.The patients with the suspected diagnosis of EP are 2 000 IU/L<ß-HCG<5 000 IU/L, whereas DC remains important valuable to differentiate EP from nonviable IUP and to avoid misdiagnosis and unnecessary exposure to methotrexate. Because EP is the common final diagnosis in most of the patients with ß-HCG>5 000 IU/L and pelvic mass and without intrauterine gestational sac, the value of DC decreases and laparoscopy can be considered directly.

Isolated tubal torsion in the third trimester of pregnancy: A case report and review of the literature.

Isolated torsion of a fallopian tube in the third trimester of pregnancy is an uncommon event. Its common symptoms are lower abdominal pain, vomiting, and nausea. Because these symptoms are nonspecific, isolated torsion of a fallopian tube may be misdiagnosed, delaying treatment and the opportunity to preserve the tube. This is a case report of a primipara in her third trimester, whowas misdiagnosed as having acute appendicitis and ovarian cyst torsion. The ultrasound-assisted examination was useful, but the specific diagnosis was made after laparotomy and histopathology. The patient was managed by simultaneous salpingectomy and cesarean section. This surgical intervention prevented adverse obstetric sequelae. We summarize our experience, provide our conclusions, and review 17 relevant studies from the literature to aid clinicians in understanding, diagnosing, and managing this condition in a timely fashion.

Transient dataset of household appliances with Intensive switching events.

With the development of Non-Intrusive Load Monitoring (NILM), it has become feasible to perform device identification, energy consumption decomposition, and load switching detection using Deep Learning (DL) methods. Similar to other machine learning problems, the research and validation of NILM necessitate substantial data support. Moreover, different regions exhibit distinct characteristics in their electricity environments. Therefore, there is a need to provide open datasets tailored to different regions. In this paper, we introduce the Transient Dataset of Household Appliances with Intensive Switching Events (TDHA25). This dataset comprises switch instantaneous data from 10 typical household appliances in China. The TDHA dataset features a high sampling rate, accurate labelling, and realistic representation of actual appliance start-up waveforms. Additionally, appliance switching is achieved through precise control of relay switches, thus mitigating interference caused by mechanical switches. By furnishing such a dataset, we aim not only to enhance the recognition accuracy of existing NILM algorithms but also to facilitate the application of NILM algorithms in regions sharing similar electricity consumption characteristics to those of China.

DDX3X interacts with SIRT7 to promote PD-L1 expression to facilitate PDAC progression.

Pancreatic ductal adenocarcinoma (PDAC) is recognized as the most aggressive and fatal malignancy. A previous study reported that PDAC patients who exhibit elevated levels of DDX3X have a poor prognosis and low overall survival rate. However, the underlying molecular mechanism remains unclear. This study aimed to investigate the specific roles of DDX3X in PDAC. Multiple bioinformatics analyses were used to evaluate DDX3X expression and its potential role in PDAC. In vitro and in vivo studies were performed to assess the effects of DDX3X on PDAC cell growth. Furthermore, Western blotting, quantitative PCR, immunohistochemistry, immunofluorescence, mass spectrometry, coimmunoprecipitation and multiplexed immunohistochemical staining were conducted to identify the specific regulatory mechanism in PDAC. The results verified that DDX3X expression is notably upregulated in the tumor tissue vs. normal tissue of PDAC patients. DDX3X knockdown markedly suppressed the proliferation, invasion and migration of PDAC cells in vitro and inhibited tumor growth in vivo. Conversely, overexpression of DDX3X induced the opposite effect. Further studies supported that the DDX3X protein can associate with sirtuin 7 (SIRT7) to stimulate PDAC carcinogenesis and progression. Furthermore, SIRT7 inhibition significantly impeded DDX3X-mediated tumor growth both ex vivo and in vivo. The results also revealed that programmed death ligand 1 (PD-L1) expression is positively correlated with DDX3X expression. These results reveal significant involvement of the DDX3X-SIRT7 axis in the initiation and advancement of PDAC and offer previously undiscovered therapeutic options for PDAC management.

Convex Temporal Convolutional Network-Based Distributed Cooperative Learning Control for Multiagent Systems.

Due to its great efficiency, scalability, and inclusivity, distributed cooperative learning control has gotten a lot of attention. For complex uncertain multiagent systems, it is challenging to model the uncertainties and exploit the cooperative learning ability of the systems. To address these issues, we proposed a novel convex temporal convolutional network-based distributed cooperative learning control for uncertain discrete-time nonlinear multiagent systems. A new concept of using a convex temporal convolutional network (CTCNet) is proposed for estimating the uncertain agent dynamics in a cooperative way. Unlike previous methods that require adjustment of network weights for different control tasks, the proposed CTCNet can map the high-dimensional input-output space into a deep space spanned by basis features that represent the inherent properties of the system, so it has good robustness for different tasks. Consequently, to improve the control performance, a CTCNet-based distributed cooperative learning control method that shares learned knowledge through the communication topology among adaptive laws of CTCNet is proposed. Furthermore, the asymptotic convergence of system tracking errors to an arbitrarily small neighborhood of the origin is strictly proved. Finally, the simulation results are given to illustrate that our suggested method has higher control accuracy, stronger robustness, and anti-interference ability than the existing methods.

Neuroimaging and neuroendocrine insights into food cravings and appetite interventions in obesity.

This article reviews the previous studies on the distinction between food cravings and appetite, and how they are regulated by hormones and reflected in brain activity. Based on existing research, food cravings are defined as individual preferences influenced by hormones and psychological factors, which differ from appetite, as they are not necessarily related to hunger or nutritional needs. The article also evaluates the neuroimaging findings about food cravings, and interventions to reduce food cravings, such as mindfulness training, alternative sweeteners, non-invasive brain stimulation techniques, cognitive-behavioral therapy, and imaginal retraining, and points out their advantages, disadvantages, and limitations. Furthermore, the article delves into the potential future directions in the field, emphasizing the need for a neuroendocrine perspective, considerations for associated psychiatric disorders, innovative clinical interventions, and emerging therapeutic frontiers in obesity management. The article outlines the neuro-endocrine basis of food cravings, including ghrelin, leptin, melanocortin, oxytocin, glucagon-like peptide-1, baclofen, and other hormones and their brain regions of action. The article argues that food cravings are an important target for obesity, and more research is needed to explore their complex characteristics and mechanisms, and how to effectively interact with their neuro-endocrine pathways. The article provides a new perspective and approach to the prevention and treatment of obesity.

Functional evaluation of the insulin/insulin-like growth factor signaling pathway in determination of wing polyphenism in pea aphid.

Wing polyphenism is a common phenomenon that plays key roles in environmental adaptation of insects. Insulin/insulin-like growth factor signaling (IIS) pathway is a highly conserved pathway in regulation of metabolism, development, and growth in metazoans. It has been reported that IIS is required for switching of wing morph in brown planthopper via regulating the development of the wing pad. However, it remains elusive whether and how IIS pathway regulates transgenerational wing dimorphism in aphid. In this study, we found that pairing and solitary treatments can induce pea aphids to produce high and low percentage winged offspring, respectively. The expression level of ILP5 (insulin-like peptide 5) in maternal head was significantly higher upon solitary treatment in comparison with pairing, while silencing of ILP5 caused no obvious change in the winged offspring ratio. RNA interference-mediated knockdown of FoxO (Forkhead transcription factor subgroup O) in stage 20 embryos significantly increased the winged offspring ratio. The results of pharmacological and quantitative polymerase chain reaction experiments showed that the embryonic insulin receptors may not be involved in wing polyphenism. Additionally, ILP4 and ILP11 exhibited higher expression levels in 1st wingless offspring than in winged offspring. We demonstrate that FoxO negatively regulates the wing morph development in embryos. ILPs may regulate aphid wing polyphenism in a developmental stage-specific manner. However, the regulation may be not mediated by the canonical IIS pathway. The findings advance our understanding of IIS pathway in insect transgenerational wing polyphenism.

Development of Chinese food picture library for inducing food cravings.

Cue-induced food cravings are strong desires directed toward specific foods, usually ones with high caloric content, and can lead to overeating. However, although food cravings vary according to individual preferences for specific high-calorie food subtypes, a structured library of food craving-inducing pictures including multiple categories of high-calorie foods does not yet exist. Here, we developed and validated a picture library of Chinese foods (PLCF) consisting of five subtypes of high-calorie foods (i.e., sweets, starches, salty foods, fatty foods, and sugary drinks) to allow for more nuanced future investigations in food craving research, particularly in Chinese cultural contexts. We collected 100 food images representing these five subtypes, with four food items per subtype depicted in five high-resolution photographs each. We recruited 241 individuals with overweight or obesity to rate the food pictures based on craving, familiarity, valence, and arousal dimensions. Of these participants, 213 reported the severity of problematic eating behaviors as a clinical characteristic. Under the condition of mixing multiple subtypes of high-calorie foods, we did not observe significant differences in craving ratings for high- and low-calorie food images (p tukey > 0.05). Then, we compared each subtype of high-calorie food images to low-calorie ones, and found craving ratings were greater for the images of salty foods and sugary drinks (ps < 0.05). Furthermore, we conducted a subgroup analysis of individuals according to whether they did or did not meet the criteria for food addiction (FA) and found that greater cravings induced by the images of high-calorie food subtypes (i.e., salty foods and sugary drinks) only appeared in the subgroup that met the FA criteria. The results show that the PLCF is practical for investigating food cravings.

Delayed surgery for rectal cancer patients receiving neoadjuvant chemoradiotherapy: a promising method in its infancy.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is used to downstage locally advanced rectal cancer before surgery. Accumulating data suggest that tumor response to nCRT is time dependent. A delay between nCRT and surgery may increase the proportion of patients that achieve a favorable response. However, delayed surgery beyond 6-8 weeks may increase the technical difficulty, and the risks of surgical complications and recurrence or metastasis. This article briefly reviews the relevant literature to evaluate the efficiency and safety of delayed surgery. METHODS: Two non-cohort studies and 10 cohort studies were reviewed. The results were analyzed and the limitations discussed. RESULTS: Although debatable, the findings of the included studies are promising. Delayed surgery may increase the proportion of favorable tumor response without compromising prognosis. However, most of the studies were retrospective, which introduces bias into the evaluation. CONCLUSION: Delayed surgery is potentially useful, but this needs to be verified by further well-designed prospective trials.

[Effect of cyclooxygenase-2 on bone loss in ovariectomized rats].

OBJECTIVE: To investigate mechanism of cyclooxygenase-2 (COX-2) in bone loss in a postmenopausal osteoporosis (PMOP) rat mode with ovarietomy (OVX). METHODS: Forty female Sprague Dawley adult rats at age of 3 months were randomly divided into 4 groups, 10 in each group, including sham-operated (sham) group, OVX group, OVX treated with nilesteriol (OVX + E) group and OVX treated with aspirin (OVX + P) group. All rats in OVX, OVX + E and OVX + P groups underwent ovarietomy under abdominal anesthesia with 10% chloral hydrate. Rats in sham group were only taken with fat tissue with same weight under bilateral ovary. After surgery, penicillin was administered to prevent infection. At day 7 after surgery, agents were given by intragastric administration for 12 weeks. Nilestriol at 1.0 mg/kg was used in OVX + E group once a week, aspirin at 45 mg×kg⁻¹(×d⁻¹ was used in OVX + P group once a day. Saline with same volume was used in rats in sham and OVX groups. All agents were administered one time per day. Dose of agents were adjusted by weight per week. At end of study, bone mineral density (BMD) of right femurs and lumbar vertebrae 3-5 (L(3-5)) were measured. Morphology of bone was detected by hematoxylineosin, and expression of COX-2 was determined by immunohistochemistry staining. RESULTS: (1) BMD:BMD of right femur and L(3-5) was (0.209 ± 0.010) g/cm² and (0.230 ± 0.012) g/cm² in sham group and (0.181 ± 0.008) g/cm² and (0.201 ± 0.016) g/cm² in OVX group, which reached statistical difference (P < 0.01). BMD of right femur and L(3-5) was (0.203 ± 0.009) g/cm² and (0.224 ± 0.028) g/cm² in OVX + E group and (0.200 ± 0.011) g/cm² and (0.204 ± 0.003) g/cm² in OVX + P group, which were all higher than those in OVX group (P < 0.01, P < 0.05). However, there was no statistical difference in BMD between OVX + E and OVX + P group (P > 0.05). (2) Morphology of bone:bone trabeculae became fewer and degenerated in OVX group. However, bone trabeculae were regular and dense in OVX + P group and OVX + E group, which were similar to those in sham group. (3) Expression of COX-2:cells with COX-2 positive and expression of COX-2 around bone trabeculae in OVX group were more than those in sham, OVX + E and OVX + P group. CONCLUSION: COX-2 plays an important role in PMOP. Aspirin could prevent bone loss by decreasing COX-2 expression in OVX rats.

Comparison of self-expanding metal stents and urgent surgery for left-sided malignant colonic obstruction in elderly patients.

BACKGROUND: Acute left-sided malignant colonic obstruction is common in elderly patients and multiple treatment options exist. To date, the use of self-expanding metallic stents (SEMS) in elderly patients has not been adequately described. AIMS: The purpose of this study was to compare mortality, avoidance of stoma, and short-term survival in elderly patients with malignant bowel obstruction treated with either colonic stenting or surgery. METHODS: In this retrospective review, elderly patients with acute left-sided colonic obstruction cancer underwent either insertion of a SEMS (n = 34) or primary surgery (n = 58). The two groups were compared for clinic variables, surgical procedures and outcome, acute mortality, and complications. RESULTS: Both groups were similar in terms of age, sex, tumor distribution, ASA grade, and comorbidities. The SEMS were successful placed in 91% of patients,and surgery was effective in relieving obstruction in 100% of the patients. Primary anastomosis was 79% in the SEMS group compared to 47% in the primary surgery group (P = 0.002). Secondary reanastomosis was 31% in the primary surgery group but only 3% in the SEMS surgery group (P = 0.001). Patients in the SEMS group had less 30-day mortality compared to the primary surgery group (3% vs. 19%, P = 0.03). Postoperative complications were similar. CONCLUSIONS: In elderly patients with acute left-sided colonic obstruction cancer due to colorectal cancer, SEMS provide an effective and safe therapeutic option compared to emergent surgery.

Synthesis and Characterization of Anatase TiO2 Microspheres Self-Assembled by Ultrathin Nanosheets.

In this paper, we report a novel anCd simple method for synthesizing the microspheres self-assembled from ultrathin anatase TiO2 nanosheets with a high percentage of (001) facets via the hydrolysis process of the single-reagent (potassium fluorotitanate). We then used optical microscopy, scanning electron microscopy, and high-resolution confocal laser Raman spectroscopy to characterize the microspheres generated under different conditions. The study found that the size of the anatase TiO2 microspheres synthesized was 0.5-3 µm. As the synthesis time increased, the corroded surface of the microspheres gradually increased, resulting in the gradual disappearance of the edges and corners of the anatase nanosheets. The exposure percentage of the (001) facets of ultrathin anatase nanosheets synthesized for 2 h at 180-200 °C are close to 100%. The microsphere whose surface is completely covered by these anatase nanosheets also has nearly 100% exposed (001) facets. This new anatase nanosheet-based self-assembled microsphere will have great application potential in pollution prevention, environmental protection, and energy fields.

Association of genetic polymorphisms in STAT1 gene with increased risk of hepatocellular carcinoma.

OBJECTIVE: Although signal transducer and activator of transcription 1 (STAT1), a transcription factor, plays a critical role in carcinogenesis and has been implicated as a tumor suppressor, few studies have investigated the associations between polymorphisms of this gene and the risk of cancer development. The aim of this study was to examine whether STAT1 gene polymorphisms are associated with the risk of hepatocellular carcinoma (HCC). METHODS: Ten single nucleotide polymorphisms in the STAT1 gene were genotyped by TaqMan assays in 469 HCC cases and 558 age-, sex- and HBsAg-matched controls in a Chinese population. RESULTS: Minor allele homozygous genotypes at rs867637 (9,046 bp 3' of STP A>G), rs3771300 (IVS24-153T>G), and rs2280235 (IVS20-103G>A), compared with their homozygote genotypes of common alleles, were associated with 1.6- (95% CI 1.1-2.3), 1.6- (95% CI 1.1-2.4), and 1.4-fold (95% CI 0.95-1.9) increased risk of HCC, respectively. The GGA haplotype, comprised of risk alleles at rs867637, rs3771300 and rs2280235, conferred a 1.2-fold (95% CI 1.0-1.5) increased risk of HCC, as compared to the most common haplotype of ATG. Diplotype GGA/GGA conferred a 1.6-fold (95% CI 1.0-2.5) increased risk of HCC compared with diplotype ATG/ATG. CONCLUSION: Our results demonstrate for the first time that polymorphisms in the STAT1 gene are associated with HCC susceptibility.

The RNA-binding protein RBM47 inhibits non-small cell lung carcinoma metastasis through modulation of AXIN1 mRNA stability and Wnt/ß-catentin signaling.

BACKGROUND: Non-small-cell lung cancer (NSCLC) remains a highly prevalent and deadly form of cancer, with efforts to better understand the molecular basis of the progression of this disease being essential to its effective treatment. Several recent studies have highlighted the ability of RNA-binding proteins (RBPs) to regulate a wide range of cellular processes in both healthy and pathogenic contexts. Among these RBPs, RNA binding motif protein 47 (RBM47) has recently been identified as a tumor suppressor in both breast and colon cancers, whereas its role in NSCLC is poorly understood. METHODS: RBM47 expression in NSCLC samples was evaluated by RT-PCR, western blotting and immunohistochemistry analysis. Molecular and cellular techniques including lentiviral vector-mediated knockdown were used to elucidate the functions and mechanisms of RBM47. RESULTS: This study sought to analyze the expression and role of RBM47 in NSCLC. In the present study, we observed reduced levels of RBM47 expression in NSCLC, with these reductions corresponding to a poorer prognosis and more advanced disease including a higher TNM stage (p = 0.022), a higher likelihood of tumor thrombus (p = 0.001), and pleural invasion (p = 0.033). Through functional analyses in vitro and in vivo, we further demonstrated that these RBP was able to disrupt the proliferation, migration, and invasion of NSCLC cells. At a molecular level, we determined that RBM47 was able to bind the AXIN1 mRNA, stabilizing it and thereby enhancing the consequent suppression of Wnt/ß-catentin signaling. CONCLUSION: Together our findings reveal that RBM47 targets AXIN1 in order to disrupt Wnt/ß-catenin signaling in NSCLC and thereby disrupting tumor progression. These results thus offer new insights into the molecular biology of NSCLC, and suggest that RBM47 may also have value as a prognostic biomarker and/or therapeutic target in NSCLC patients.

[Expression of omentin in adipose tissues in obese and type 2 diabetic patients].

OBJECTIVE: To analyze the mRNA expression of omentin mRNA level in subcutaneous and omental adipose tissues of normal, obese, and type 2 diabetic individuals and to investigate the relationship between omentin mRNA expression and serum omentin level, body fat parameters, glucose and lipid metabolism, and insulin resistance indexes. METHODS: 36 patients with benign diseases undergoing selective abdominal operation, 19 males and 17 females, aged 20 - 65, included 12 with normal glucose regulation and normal weight (NGR-NW group), 12 with normal glucose regulation and overweight/obesity (NGR-OW/OB group), and 12 with type 2 diabetes and overweight/obesity (T2DM-OW/OB group). Abdominal subcutaneous and omental adipose tissues were obtained during operation. Real-time quantitative PCR was used to measure the omentin mRNA level. The level of fasting serum omentin was measured by ELISA. Meanwhile blood glucose, HbA(1C), lipids and insulin levels were measured. Body weight, BMI and waist hip ratio (WHR) were evaluated and insulin sensitivity was assessed by homeostasis model assessment insulin resistance index (HOMA-IR). RESULTS: The omentin mRNA level in omental adipose tissue of the NGR-NW group was (1.52 +/- 0.32), significantly higher than that in subcutaneous adipose tissue [(0.019 +/- 0.006), P < 0.01]. The omentin mRNA level of the males was (1.46 +/- 0.31), not statistically different from that of the female [(1.58 +/- 0.29), P = 0.416]. The omentin mRNA level of the NGR-OW/OB group was (1.18 +/- 0.29), significantly lower than that of the NGR-NW group [(1.52 +/- 0.32), P < 0.05], and the omentin mRNA level of the T2DM-OW/OB group was (0.98 +/- 0.37), both significantly lower than those of the other 2 groups (both P < 0.05). Partial correlation analysis showed that the omentin mRNA was negatively correlated with HOMA-IR, body weight, WHR, triglyceride, BMI, and fasting insulin, and positively correlated to serum omentin level and HDL-C. Multiple linear regression analysis showed that serum omentin level, HOMA-IR, and body weight were independent variables of omentin. CONCLUSION: Omentin mRNA is highly expressed in omental adipose tissue. The omentin mRNA expression level decreases in the overweight/obese individuals and decreases further when overweight/obesity is combined with type 2 diabetes. Omentin mRNA is positively correlated to serum omentin level, obese indexes, insulin resistance, and lipid metabolism parameters. Decreased omentin gene expression may contribute to the underlying pathophysiology of insulin resistance syndrome.

[The expressions and clinical significance of IGFBP-2, -3 in both serum and tumor tissues in patients with epithelial ovarian cancer].

OBJECTIVE: To explore the serum levels of IGFBP-2, -3 and their proper roles in the regulation of IGF-II bioavailability in patients with ovarian tumor, and to investigate the correlation between the expressions of IGFBP-2 and IGFBP-3 in ovarian tumor tissues and related clinicopathological characteristics. METHODS: Serum levels of IGFBP-2, -3 and big/mature IGF-II were measured by Western ligand blot (WLB) and Western blot (WB) in patients with ovarian tumor (10 cases of benign tumor, 6 cases of borderline tumor and 10 cases of malignant tumor) and 10 cases of normal control. The expressions of IGFBP-2 and IGFBP-3 were examined in 39 specimens of ovarian tumor (8 cases of benign tumor, 8 cases of borderline tumor and 23 cases of malignant tumor) and 4 cases of normal ovarian tissues by immunohistochemical staining. RESULTS: The serum levels of both big and mature IGF-II in epithelial ovarian cancer (ovarian cancer) patients were significantly decreased compared with those of normal control and benign and borderline tumor (P<0.001 or P<0.01). The increased serum level of IGFBP-2 and decreased IGFBP-3 level were observed in patients with malignant ovarian tumors by comparing with those of patients with normal controls, benign and borderline tumor (P<0.001 or P<0.01). The expression of IGFBP-2 was significantly higher in malignant ovarian tumor tissues than those in normal control and benign ovarian tumors tissues (P<0.0001, P<0.001, and the expression of IGFBP-3 decreased significantly in lower differentiated ovarian cancer tissues compared with that in high and moderate differentiated ovarian cancer tissues (P<0. 05). CONCLUION: IGFBP-2 predominantly presents in the circulation of malignant patients in contrast to IGFBP-3, which may result in altered bioavailability of IGF-II in ovarian cancer, leading to the progress of tumor. The serum levels of both IGFBP-2 and IGFBP-3 and their expressions in tumor tissues are correlated with the clinicopathological characteristics of ovarian cancer patients. Our findings suggest that the presence of new mechanisms in the regulation of IGF-II bioavailability, and provide the evidence for the possibility to use IGFBP-2/IGFBP-3 as biological markers in diagnosis and prognosis of ovarian cancer.