Cocaine Use Prediction With Tensor-Based Machine Learning on Multimodal MRI Connectome Data.

This letter considers the use of machine learning algorithms for predicting cocaine use based on magnetic resonance imaging (MRI) connectomic data. The study used functional MRI (fMRI) and diffusion MRI (dMRI) data collected from 275 individuals, which was then parcellated into 246 regions of interest (ROIs) using the Brainnetome atlas. After data preprocessing, the data sets were transformed into tensor form. We developed a tensor-based unsupervised machine learning algorithm to reduce the size of the data tensor from 275 (individuals) × 2 (fMRI and dMRI) × 246 (ROIs) × 246 (ROIs) to 275 (individuals) × 2 (fMRI and dMRI) × 6 (clusters) × 6 (clusters). This was achieved by applying the high-order Lloyd algorithm to group the ROI data into six clusters. Features were extracted from the reduced tensor and combined with demographic features (age, gender, race, and HIV status). The resulting data set was used to train a Catboost model using subsampling and nested cross-validation techniques, which achieved a prediction accuracy of 0.857 for identifying cocaine users. The model was also compared with other models, and the feature importance of the model was presented. Overall, this study highlights the potential for using tensor-based machine learning algorithms to predict cocaine use based on MRI connectomic data and presents a promising approach for identifying individuals at risk of substance abuse.

The amino acid residue E96 of Ghd8 is crucial for the formation of the flowering repression complex Ghd7-Ghd8-OsHAP5C in rice.

Ghd7 is an important gene involved in the photoperiod flowering pathway in rice. A Ghd7-involved transcriptional regulatory network has been established, but its translational regulatory pathway is poorly understood. The mutant suppressor of overexpression of Ghd7 (sog7) was identified from EMS-induced mutagenesis on the background of ZH11 overexpressing Ghd7. MutMap analysis revealed that SOG7 is allelic to Ghd8 and delayed flowering under long-day (LD) conditions. Biochemical assays showed that Ghd8 interacts with OsHAP5C and Ghd7 both in vivo and in vitro. Surprisingly, a point mutation E96K in the α2 helix of the Ghd8 histone fold domain (HFD) destroyed its ability to interact with Ghd7. The prediction of the structure shows that mutated amino acid is located in the interaction region of CCT/NF-YB/YC complexes, which alter the structure of α4 of Ghd8. This structural difference prevents the formation of complex NF-YB/YC. The triple complex of Ghd8-OsHAP5C-Ghd7 directly bound to the promotor of Hd3a and downregulated the expression of Ehd1, Hd3a and RFT1, and finally resulted in a delayed heading. These findings are helpful in deeply understanding the Ghd7-involved photoperiod flowering pathway and promote the elucidation of rice heading.

Autophagy blockade potentiates cancer-associated immunosuppression through programmed death ligand-1 upregulation in bladder cancer.

A high basal level of autophagic flux in bladder cancer (BC) cells prevents cell death and weakens chemotherapy efficacy. However, how autophagy influences cancer-associated immunosuppression in BC remains undetermined. In this study, we observed a negative correlation between the autophagy-related markers LC3-II and programmed death ligand-1 (PD-L1) in BC cells. The autophagy inhibitors chloroquine (CQ) and bafilomycin A1 (Baf-A1) increased PD-L1 expression in BC cells through the ERK-JNK-c-Jun signal-transduction pathway. Moreover, the treatment of BC cells with CQ and Baf-A1 inhibited hsa-microRNA-34a (miR-34a) expression and miR-34a overexpression in BC cells prevented the autophagy blockade-induced PD-L1 expression; a negative correlation between miR-34a and PD-L1 expression was observed during treatment with autophagy inhibitors. Furthermore, miR-34a overexpression induced the cytotoxic activity of natural killer cells against BC cells. Our results provide evidence that autophagy blockade and its regulatory pathway affect cancer-associated immunosuppression through PD-L1 elevation. Thus, the coadministration of autophagy inhibitors and a PD-L1 immune checkpoint blockade provides a potential therapeutic approach for treating BC.

Depressive Symptoms among US Adults during the Great Recession and Economic Recovery.

BACKGROUND AND AIMS: We study the trajectory of depressive symptoms among US adults before, during, and after the 2008/2009 Great Recession. METHODS: We use repeated cross-sectional surveys of the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. Mental health is assessed with the Patient Health Questionnaire-9 (PHQ-9), with the following categorization for depressive symptoms: none or mild (score 0-9), moderate or severe (score 10-27). A parallel time series was calculated from the Behavioral Risk Factor Surveillance System (BRFSS) on self-reported number of days with poor mental health. RESULTS: NHANES data show a statistically significant increase in depressive symptoms from 2005/2006 to 2007/2008 (the beginning of the Great Recession), but there were no significant or consistent changes after 2007/2008. In particular, the deterioration in the adjusted predicted PHQ-9 scores occurred prior to the large increase in unemployment rate (2009/2010). As the macroeconomic situations improved and unemployment rates recovered, mental health did not return to the previous level. In the latest wave of NHANES (2017/2018), unemployment rates were at the lowest level over the analysis period; however, the adjusted predicted PHQ-9 scores were higher than that at the beginning of the Great Recession. Trends of PHQ-9 scores were similar across income groups - all groups had an increase in depressive symptoms after 2005/2006 and PHQ-9 scores were still high in 2017/2018 after controlling for sociodemographic status. Group with the lowest income had higher levels of depressive symptoms at every time point. BRFSS data shows no consistent changes in the number of days with poor mental health that parallel economic conditions. DISCUSSION: Depressive symptoms at the population level did not match the economic cycle before, during and after the Great Recession. Future research is needed to better understand the lack of correlation between population mental health and macroeconomic conditions.

Berberine ameliorates pulmonary inflammation in mice with influenza viral pneumonia by inhibiting NLRP3 inflammasome activation and gasdermin D-mediated pyroptosis.

Viral pneumonia is a common complication caused by Influenza A virus infection and is characterized by severe pulmonary inflammation. A previous study showed that berberine (BBR) significantly ameliorated the pulmonary inflammation in mice with influenza viral pneumonia but its underlying mechanism is not entirely understood. In this study, we reproduced the mouse model of influenza viral pneumonia through intranasal infection of A/Puerto Rico/8/34 (H1N1), to further investigate the anti-inflammatory mechanism of BBR based on nucleotide-binding oligomerization domain-like receptor protein (NLRP) 3 inflammasome activation and Gasdermin D (GSDMD)-mediated pyroptosis. Consistent with MCC950 (10 mg/kg, a specific NLRP3 inflammasome inhibitor), BBR (10 mg/kg) obviously improved the weight loss and survival rate of infected mice, alleviated their pulmonary inflammation, and suppressed the accumulation of tumor necrosis factor and interleukin (IL)-6 in lungs without obvious inhibition on viral multiplication (hemagglutinin titer and nucleoprotein messenger RNA). Moreover, BBR (10 mg/kg) reduced the expressions of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and cysteinyl aspartate-specific proteinase (Caspase)1 (Caspase1 precursor [Pro-caspase1] + Caspase1p20 subunit) and the ratio of Caspase1p20 subunit to Caspase1, thus inhibiting the NLRP3 inflammasome activation and resulting in the decreased contents of mature IL-1ß and IL-18 in lungs. The GSDMD expression (GSDMD precursor [Pro-GSDMD] + GSDMD-N terminal [NT]) and the ratio of GSDMD-NT to GSDMD were also declined by BBR (10 mg/kg). These evidence indicate that BBR may ameliorate pulmonary inflammation in mice with influenza viral pneumonia through inhibiting NLRP3 inflammasome activation, as well as depressing GSDMD-mediated pyroptosis via declining GSDMD expression and restraining NLRP3 inflammasome-mediated GSDMD activation.

Thrombospondin-4 promotes bladder cancer cell migration and invasion via MMP2 production.

Bladder cancer (BC) is the second most common urological tumour in Western countries. Approximately, 80% of patients with BC will present with non-muscle invasive bladder cancer (NMIBC), whereas a quarter will have muscle invasive disease (MIBC) at the time of BC diagnosis. However, patients with NMIBC are at risk of BC recurrence or progression into MIBC, and an MIBC prognosis is determined by the presence of progression and metastasis. Matrix metalloproteinase 2 (MMP2), a type of matrix metalloproteinase (MMP), plays a major role in tumour invasion and is well-characterized in BC prognosis. In BC, the mechanisms regulating MMP2 expression, and, in turn, promote cancer invasion, have hardly been explored. Thrombospondin-4 (THBS4/TSP4) is a matricellular glycoprotein that regulates multiple biological functions, including proliferation, angiogenesis, cell adhesion and extracellular matrix modelling. Based on the results of a meta-analysis in the Gene Expression Profiling Interactive Analysis 2 database, we observed that TSP4 expression levels were consistent with overall survival (OS) rate and BC progression, with the highest expression levels observed in the advanced stages of BC and associated with poor OS rate. In our pilot experiments, incubation with recombinant TSP4 promoted the migration and invasion in BC cells. Furthermore, MMP2 expression levels increased after recombinant TSP4 incubation. TSP4-induced-MMP2 expression and cell motility were regulated via the AKT signalling pathway. Our findings facilitate further investigation into TSP4 silencing-based therapeutic strategies for BC.

Melatonin impedes prostate cancer metastasis by suppressing MMP-13 expression.

Prostate cancer has high metastatic potential. Men with higher urinary levels of the sleep hormone melatonin are much less likely to develop advanced prostate cancer compared with men with lower levels of melatonin. Melatonin has shown anticancer activity in experimental investigations. Nevertheless, the therapeutic effect of melatonin in metastatic prostate cancer has largely remained a mystery. Analyses of Gene Expression Omnibus data and human tissue samples indicated that levels of matrix metallopeptidase 13 (MMP-13) expression are higher in prostate cancer patients than in healthy cancer-free individuals. Mechanistic investigations revealed that melatonin inhibits MMP-13 expression and the migratory and invasive capacities of prostate cancer cells via the MT1 receptor and the phospholipase C, p38, and c-Jun signaling cascades. Importantly, tumor growth rate and metastasis to distant organs were suppressed by melatonin in an orthotopic prostate cancer model. This is the first demonstration showing that melatonin impedes metastasis of prostate cancer by suppressing MMP-13 expression in both in vitro and in vivo models. Thus, melatonin is promising in the management of prostate cancer metastasis and deserves to undergo clinical investigations.

Attenuation of chloroquine and hydroxychloroquine on the invasive potential of bladder cancer through targeting matrix metalloproteinase 2 expression.

Bladder cancer (BC), one of the most common urological neoplastic disorders in men, has an extremely low survival rate because of its tendency to metastasize. The anticancer drugs chloroquine (CQ) and hydroxy CQ (HCQ) might inhibit tumor progression and invasiveness. However, the mechanism by which CQ and HCQ influence BC is undetermined. In this study, CQ and HCQ treatments inhibited the migration and invasion of two BC cell types (5637 and T24) through expression modulation of matrix metalloproteinase-2 (MMP-2), which belongs to the matrix MMP family and is a key mediator of cancer progression. Moreover, additional data revealed that the migrative and invasive effects of BC cells treated with CQ or HCQ were abolished after treatment with rapamycin, which induces autophagy, demonstrating that CQ and HCQ functions in BC are based on autophagy inhibition. In conclusion, our research demonstrated that CQ and HCQ regulated cell motility in BC through MMP-2 downregulation by targeting autophagy functions, providing a novel therapeutic strategy for BC treatment.

Miconazole induces protective autophagy in bladder cancer cells.

Autophagy plays a dual function in cancer progression; autophagy activation can support cancer cell survival or contribute to cell death. Miconazole, a Food and Drug Administration-approved antifungal drug, has been implicated in oncology research recently. Miconazole was found to exert antitumor effects in various tumors, including bladder cancer (BC). However, whether it provokes protective autophagy has been never discussed. We provide evidence that miconazole induces protective autophagy in BC for the first time. The results indicated that 1A/1B-light chain 3 (LC3)-II processing and p62 expression were elevated after miconazole exposure. Also, adenosine monophosphate-activated protein kinase phosphorylation was increased after miconazole treatment. We also confirmed the autophagy-promoting effect of miconazole in the presence of bafilomycin A1 (Baf A1). The result indicates that a combination treatment of miconazole and Baf A1 improved LC3-II processing, confirming that miconazole promoted autophagic flux. The acridine orange, Lysotracker, and cathepsin D staining results indicate that miconazole increased lysosome formation, revealing its autophagy-promoting function. Finally, miconazole and autophagy inhibitor 3-methyladenine cotreatment further reduced the cell viability and induced apoptosis in BC cells, proving that miconazole provokes protective autophagy in BC cells. Our findings approve that miconazole has an antitumor effect in promoting cell apoptosis; however, its function of protective autophagy is needed to be concerned in cancer treatment.

Melatonin Inhibits Osteoclastogenesis and Osteolytic Bone Metastasis: Implications for Osteoporosis.

Osteoblasts and osteoclasts are major cellular components in the bone microenvironment and they play a key role in the bone turnover cycle. Many risk factors interfere with this cycle and contribute to bone-wasting diseases that progressively destroy bone and markedly reduce quality of life. Melatonin (N-acetyl-5-methoxy-tryptamine) has demonstrated intriguing therapeutic potential in the bone microenvironment, with reported effects that include the regulation of bone metabolism, acceleration of osteoblastogenesis, inhibition of osteoclastogenesis and the induction of apoptosis in mature osteoclasts, as well as the suppression of osteolytic bone metastasis. This review aims to shed light on molecular and clinical evidence that points to possibilities of melatonin for the treatment of both osteoporosis and osteolytic bone metastasis. It appears that the therapeutic qualities of melatonin supplementation may enable existing antiresorptive osteoporotic drugs to treat osteolytic metastasis.

Influence of the arrangement of vacuum chuck holes on the transmittance wavefront of large-aperture KDP in single-point diamond turning.

Serious edge effects of potassium dihydrogen phosphate (${{\rm KH}_2}{{\rm PO}_4}$KH2PO4, KDP) manufactured using single-point diamond turning (SPDT) often result in disqualification of the transmittance wavefront for high-power laser systems. In this paper, based on the theoretical analysis of sucker hole configuration and the pressure distribution law under the vacuum chuck condition of crystal elements, the influence of sucker hole configuration on the transmittance wavefront root-mean-square gradient (GRMS) is verified through fly-cutting experiments. By adopting the newly designed vacuum chuck, the vacuum-chucking quality is effectively improved, and the edge effect is accordingly suppressed in the SPDT. Moreover, the accuracy of the transmittance wavefront GRMS has an improvement of about 25% under the same processing parameters.

Negative regulation of the RLR-mediated IFN signaling pathway by duck ubiquitin-specific protease 18 (USP18).

Ubiquitin-specific protease 18 (USP18) plays an important role in regulating type I interferon (IFN) signaling in innate immunity, and has a crucial impact on the IFN therapeutic effect. Although significant progress has been made in elucidating USP18 function in mammals, the role of USP18 in ducks (duUSP18) remains poorly understood. In this study, we cloned the USP18 gene from white crested ducks by reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of complementary DNA (cDNA) ends. We determined that duUSP18 cDNA contains a 52-bp 5'UTR, a 1,131-bp open reading frame and a 356-bp 3'UTR, and encodes a 376-amino acid protein. Multiple sequence alignments showed that duUSP18 shares high similarity with USP18 from other vertebrates. Overexpression of duUSP18 inhibited nuclear factor-κB (NF-κB) and interferon regulatory factor 1 (IRF1) activity, and reduced IFN-ß production following 5' triphosphate double-stranded RNA (5'ppp dsRNA) or lipopolysaccharide (LPS) stimulation. duUSP18 knockdown significantly activated 5'ppp dsRNA-induced and LPS-induced NF-κB and IRF1 activation, and induced IFN-ß expression in duck embryo fibroblasts. Furthermore, Quantitative real-time PCR (qRT-PCR) revealed that overexpression or knockdown of duUSP18 could alter the expression of genes related to the RLR-mediated IFN signaling pathway following the treatment with 5'ppp dsRNA. In addition, site-directed mutation analysis revealed that cysteine 66 (C66), histidine 313 (H313), and histidine 321 (H321) of duUSP18 were critical for inhibiting IFN-ß activity. Taken together, these results suggest that duck USP18 plays an important role in innate immune responses against double-stranded RNA viruses in the RLR-mediated IFN signaling pathway, and that further studies are warranted to elucidate its underlying mechanisms, which could provide molecular insights into the effect of the treatment of duck diseases.

CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression.

In recent years, osteosarcoma survival rates have failed to improve significantly with conventional treatment modalities because of the development of chemotherapeutic resistance. The human breast cancer resistance protein/ATP binding cassette subfamily G member 2 (BCRP/ABCG2), a member of the ATP-binding cassette family, uses ATP hydrolysis to expel xenobiotics and chemotherapeutics from cells. CCN family member 2 (CCN2) is a secreted protein that modulates the biological function of cancer cells, enhanced ABCG2 protein expression and activation in this study via the α6ß1 integrin receptor and increased osteosarcoma cell viability. CCN2 treatment downregulated miR-519d expression, which promoted ABCG2 expression. In a mouse xenograft model, knockdown of CCN2 expression increased the therapeutic effect of doxorubicin, which was reversed by ABCG2 overexpression. Our data show that CCN2 increases ABCG2 expression and promotes drug resistance through the α6ß1 integrin receptor, whereas CCN2 downregulates miR-519d. CCN2 inhibition may represent a new therapeutic concept in osteosarcoma.

MDA5 and LGP2 acts as a key regulator though activating NF-κB and IRF3 in RLRs signaling of mandarinfish.

RIG-I-like receptors (RLRs), as key cytoplasmic sensors of viral pathogen-associated molecular patterns, can recognise viral RNA and enhance the antiviral response. Some investigations have focused on the roles of RLRs in the innate immune response in grass carp, large yellow croaker, and rainbow trout. However, little is known about the function of RLRs in mandarinfish (Siniperca chuatsi), an important economic fish in Perciformes. Here, we functionally characterized the RLRs involved in the immune responses of mandarinfish (Siniperca chuatsi), by evaluating three RLRs, namely, RIG-I, MDA5, and LGP2. The results revealed that MDA5 and LGP2 were present in mandarinfish, whereas RIG-I was absent. The MDA5 and LGP2 cDNA sequences contained 2976 and 2046 bp and encoded 991 and 681 amino acids, respectively. Multiple sequence alignments showed that MDA5 and LGP2 of mandarinfish were clustered together with their homologs from other teleost fishes and shared high similarities with those from other vertebrates, and RIG-I of mandarinfish was absent. Moreover, quantitative real-time PCR (qPCR) analysis suggested that MDA5 and LGP2 were constitutively expressed in all tissues tested, and MDA5 mRNA expression was relatively high in the gill, and spleen, whereas LGP2 mRNA expression was high in the liver, gill, and head kidney. After stimulation with lipopolysaccharide or poly I:C, the expression of MDA5 and LGP2 was upregulated in spleen, gill and head kidney, but the pattern was not exactly the same, MDA5 transcripts generally increased and then declined with the prolonged infection, while LGP2 transcripts went up continuously, which showed that mandarinfish MDA5 and LGP2 may play independent roles in antiviral response. Besides, it is further revealed that the MDA5 could activate NF-κB and IRF3 to inducing the production of IFN-ß by constructing tet-on stable strain of 293T cell, however over-expression of LGP2 resulted in decreased NF-κB, IRF3 and IFN-ß production in cells challenged with LPS and polyI:C Taken together, our results demonstrated that MDA5 and LGP2, as a positive and negative regulator, respectively, played an important role in modulating antibacterial andantiviral immune responses though activating NF-κB and IRF3 in RLRs signaling of mandarinfish.

Wernicke's Encephalopathy after Bariatric Surgery with Atypical Magnetic Resonance Imaging: A Case Report.

Wernicke's encephalopathy (WE) is a disease caused by thiamine deficiency related to alcoholism, hyperemesis, or thiamine malabsorption. The clinical manifestations of WE are mental change, ataxia, and ophthalmoplegia. The typical magnetic resonance imaging (MRI) findings of WE are symmetrical involvement of medial thalamus, periventricular region of the third ventricle, periaqueductal area, and mammillary body. The atypical MRI findings are more common in nonalcoholic WE. Since the increasing population of obesity and the preference of weight loss surgery, the risk of developing thiamine deficiencies associated with weight loss surgery has become a considerable etiology of WE. We herein reported a case reminds clinicians that WE can be a possible diagnosis in patient who developed acute altered mental status with atypical MRI lesion involving bilateral centrum semiovale and corona radiata after receiving bariatric surgery.

Prevalence, risk factors, and the desire for help of distressed newly diagnosed cancer patients: A large-sample study.

OBJECTIVE: Beginning in 2007, all newly diagnosed cancer patients at the Koo Foundation Sun Yat-Sen Cancer Center (KF-SYSCC) were screened for psychosocial distress. Our social workers, as part of the psychosocial care team (PCT), have engaged in proactive outreach with patients identified as distressed. The goal of the present study was to assess the prevalence of psychosocial distress and the extent of contact between the PCT and distressed patients. METHOD: Newly diagnosed patients who were treated at KF-SYSCC between 2007 and 2010 for cancer were eligible if there were at least 100 patients with the same type of cancer. Before treatment began, they were screened with the Pain Scale and the Distress Thermometer (DT) and had the option to specify a desire for help. The rates of distress were analyzed by cancer type and by probable related factors. Information regarding contact with the PCT was retrieved from computerized databases. RESULTS: Overall, some 5,335 cancer patients representing 12 major cancer types were included in our study. Of these, 1,771 (33.20%) were significantly distressed. By multivariate logistic regression, younger age, female gender, higher pain score, and disease stage, but not cancer type, were found to be associated with higher rates of distress. Among these distressed patients, 628 (36%) had some contact with the PCT. SIGNIFICANCE OF RESULTS: This Taiwanese study with a large sample size revealed a prevalence rate of psychosocial distress similar to rates found in Western countries. Contact with the PCT was established in only 36% of significantly distressed patients, despite a proactive outreach program. It is very important to have screening results made available in a timely fashion to the psycho-oncology team so that appropriate care can be offered promptly.

Pleural fluid osteopontin, vascular endothelial growth factor, and urokinase-type plasminogen activator levels as predictors of pleurodesis outcome and prognosticators in patients with malignant pleural effusion: a prospective cohort study.

BACKGROUND: Rapidly growing cancer cells secrete growth-promoting polypeptides and have increased proteolytic activity, contributing to tumor progression and metastasis. Their presentation in malignant pleural effusion (MPE) and their predictive value for the outcome of pleurodesis and survival were studied. METHODS: Between February 2011 and March 2012, MPE samples were prospectively collected from 61 patients. Twenty-five patients with non-malignant pleural effusion in the same period were included as controls. Pleural fluid osteopontin (OPN), vascular endothelial growth factor (VEGF), and urokinase-type plasminogen activator (uPA) concentrations were measured. RESULTS: Patients with MPE had higher pleural fluid OPN, VEGF, and uPA concentrations than those with non-malignant pleural effusion, but only differences in VEGF were statistically significant (p = 0.045). Patients with distant metastases had significantly elevated pleural fluid VEGF concentrations than those without (p = 0.004). Pleural fluid OPN, VEGF, and uPA concentrations were positively correlated in most patients. However, there was no significant difference in pleural fluid OPN, VEGF, and uPA concentrations between patients with successful pleurodesis and those without. There was also no significant difference in cancer-specific survival between sub-groups with higher and lower pleural fluid OPN, VEGF, or uPA concentrations. Patients with successful pleurodesis had significantly longer cancer-specific survival than those without (p = 0.015). CONCLUSIONS: Pleural fluid OPN, VEGF, and uPA concentrations are elevated in MPE but are not satisfactory predictors of pleurodesis outcome or survival. Patients with higher pleural fluid VEGF concentration have higher risk of distant metastasis. Evaluating the benefits of therapy targeting the VEGF pathway in these patients warrants further studies.

Adiponectin promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-27b through a CaMKII/AMPK/p38 signaling pathway in human chondrosarcoma cells.

Chondrosarcoma is the second most frequently occurring type of bone malignancy characterized by distant metastatic propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumour lymphangiogenesis and lymphatic metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. In recent years, adiponectin has also been indicated as facilitating tumorigenesis, angiogenesis and metastasis. However, the effect of adiponectin on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has remained largely a mystery. In the present study, we have shown a clinical correlation between adiponectin and VEGF-C, as well as tumour stage, in human chondrosarcoma tissues. We further demonstrated that adiponectin promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium from adiponectin-treated cells significantly induced tube formation and migration of human lymphatic endothelial cells. In addition, adiponectin knock down inhibited lymphangiogenesis in vitro and in vivo We also found that adiponectin-induced VEGF-C is mediated by the calmodulin-dependent protein kinase II (CaMKII), AMP-activated protein kinase (AMPK) and p38 signaling pathway. Furthermore, the expression of miR-27b was negatively regulated by adiponectin via the CaMKII, AMPK and p38 cascade. The present study is the first to describe the mechanism of adiponectin-promoted lymphangiogenesis by up-regulating VEGF-C expression in chondrosarcomas. Thus, adiponectin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis.

Genetic Testing and Post-Testing Decision Making among BRCA-Positive Mutation Women: A Psychosocial Approach.

Through an analysis of an online survey of women who tested positive for the BRCA genetic mutation for breast cancer, this research uses a social constructionist and feminist standpoint lens to understand the decision-making process that leads BRCA-positive women to choose genetic testing. Additionally, this research examines how they socially construct and understand their risk for developing breast cancer, as well as which treatment options they undergo post-testing. BRCA-positive women re-frame their statistical medical risk for developing cancer and their post-testing treatment choices through a broad psychosocial context of engagement that also includes their social networks. Important psychosocial factors drive women's medical decisions, such as individual feelings of guilt and vulnerability, and the degree of perceived social support. Women who felt guilty and fearful that they might pass the BRCA gene to their children were more likely to undergo risk reducing surgery. Women with at least one daughter and women without children were more inclined toward the risk reducing surgery compared to those with only sons. These psychosocial factors and social network engagements serve as a "nexus of decision making" that does not, for the most part, mirror the medical assessments of statistical odds for hereditary cancer development, nor the specific treatment protocols outlined by the medical establishment.

Estrogen adversely affects the prognosis of patients with lung adenocarcinoma.

Estrogen has been postulated to contribute to the development and progression of lung cancer. We examined the epidemiologic evidence, explored the characteristics of estrogen receptors (ER) in lung adenocarcinoma, and investigated the effect of estrogen on lung cancer cell migration, including the signaling pathway involved. For epidemiologic evidence, a total of 1434 consecutive non-small cell lung cancer patients who underwent standardized staging and homogenous treatment were prospectively enrolled from January 2002 to December 2008, and followed until December 2012. The possible prognostic factors to be analyzed included stage, age, gender, menopausal status, smoking history and histology. For laboratory study, lung cancer cell lines A549 and PE089 and malignant pleural effusions from the patients with lung adenocarcinoma were used. We found that the premenopausal patients had more advanced disease and a shorter survival among the never-smoking female patients with lung adenocarcinoma. ERß was the predominant ER in the lung cancer cell lines. We proposed a different pathway that estrogen upregulated the expression of osteopontin and then promoted cell migration through αvß3 integrin binding and activated MEK-ERK signaling pathway, which is a common downstream pathway with epidermal growth factor receptor (EGFR) activation. An additive effect of ER antagonists and EGFR antagonists on the inhibition of cell migration was also noted. Our results suggest that estrogen adversely affects the prognosis of patients with lung adenocarcinoma. Osteopontin contributed to the cross-talk between ER and EGFR signaling pathways. Estrogen, with its receptor, has the potential to be a prognosticator and a therapeutic target in lung cancer.