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Flavonoids are a large group of nonnutrient compounds naturally produced from plants as part of their defence mechanisms against stresses of different origins. They emerged from being considered an agricultural oddity only after it was observed that these compounds possess a potential protective function against several human degenerative diseases. This has led to recommending the consumption of food containing high concentrations of flavonoids, which at present, especially as soy isoflavones, are even available as overthecounter nutraceuticals. The increased use of flavonoids has occurred even though their mechanisms are not completely understood, in particular those involving the flavonoid impact on estrogen signals. In fact, most of the human health protective effects of flavonoids are described either as estrogenmimetic, or as antiestrogenic, while others do not involve estrogen signaling at all. Thus, the same molecule is reported as an endocrine disruptor, an estrogen mimetic or as an antioxidant without estrogenic effects. This is due in part to the complexity of the estrogen mechanism, which is conducted by different pathways and involves two different receptor isoforms. These pathways can be modulated by flavonoids and should be considered for a reliable evaluation of flavonoid, both estrogenicity and antiestrogenicity, and for a correct prediction of their effects on human health. [ABSTRACT FROM AUTHOR]

To ensure the success of systemic gene therapy, it is critical to enhance the tumor specificity and activity of the promoter. In the current study, we determined that topoisomerase IIα promoter is selectively activated in breast cancer cells. An element containing an inverted CCAAT box (ICB) was shown to be responsible for the breast cancer specificity. When the ICB-harboring topoisomerase IIα minimal promoter was linked with an enhancer sequence from the cytomegalovirus immediate early gene promoter (CMV promoter), this composite promoter, CT90, exhibited activity comparable to or higher than the CMV promoter in breast cancer cells in vitro and in vivo, yet expresses much lower activity in normal cell lines and normal organs than the CMV promoter. A CT90-driven construct expressing BikDD, a potent proapoptotic gene, was shown to selectively kill breast cancer cells in vitro, and to suppress mammary tumor development in an animal model of intravenously administrated, liposome-delivered gene therapy. Expression of BikDD was readily detectable in the tumors but not in the normal organs (such as heart) of CT90-BikDD-treated animals. The results indicate that liposomal CT90-BikDD is an effective systemic breast cancer-targeting gene therapy.Cancer Gene Therapy (2006) 13, 706–719. doi:10.1038/sj.cgt.7700945; published online 3 March 2006 [ABSTRACT FROM AUTHOR]

Flow cytometric analysis of synthetic galactosyl polymers, asialofetuin and LDL derivatives labeled with FITC (Fluorescein Isothiocyanate) was carried out to determine the phenotypes of endocytic receptors, such as asialoglycoprotein (ASPG) and the LDL receptor, on various types of cells. When FITC-labeled galactosyl polystyrene (GalCPS), being a synthetic ligand of ASPG, was applied to rat hepatocytes and human cancer cells (Hep G2 and Chang Liver), surface fluorescence intensities varied according to receptor expression on the cells. The fluorescence intensity originates from the calcium-dependent binding of the FITC-labeled GalCPS. Although unaltered by pre-treatment with glucosyl polystyrene (GluCPS), fetuin and LDL, the fluorescence intensity was suppressed by pre-treatment with (non-labeled) GalCPS and asialofetuin. Flow cytometry allowed us to demonstrate that the calcium-dependent binding of FITC-labeled LDL (prepared from rabbits) upon the addition of 17α-ethinyl estradiol enhances LDL receptor expression, and the expression is suppressed upon the addition of a monoclonal antibody to the LDL receptor. The binding efficiency based on the combination of FITC-labeled ligands suggests a possible application for the classification of cell types and conditions corresponding to endocytic receptor expression without the need for immuno-active antibodies or radiolabeled substances. Furthermore, the synthetic glycoconjugate (GalCPS) is shown to be a sensitive and useful marker for classification based on cell phenotype using flow cytometry. [ABSTRACT FROM PUBLISHER]

Indirubin is a natural arylhydrocarbon receptor (AhR) ligand isolated from human urine. We previously reported that it was more potent than the prototypical ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a yeast assay system. Here we compared gene expression changes in HepG2 cells exposed to 10 nM of indirubin or TCDD using nylon-membrane-based cDNA arrays with 1176 genes to elucidate the toxic differences at the transcriptional level. The gene expression profiles for TCDD and indirubin were very similar. The number of up-regulated genes (fold change ≥2.0) was 11 and 4 and the number of down-regulated genes (fold change ≤0.5) was 17 and 21 in TCDD-treated and indirubin-treated cells, respectively. Cytochrome P450 (CYP) 1A1, 1A2, 19A1, insulin-like growth factor binding protein 1 (IGFBP1), and IGFBP10 were confirmed to be up-regulated using real-time reverse transcription polymerase chain reaction. CYP1A1 and CYP1A2 mRNAs were induced by as little as 1 pM of indirubin, whereas they were not induced by 10 pM of TCDD. In the time-course experiment, CYP1A1 mRNA was induced by indirubin transiently. Indirubin was also metabolized by CYP1A1 and lost its ligand activity. Indirubin would appear to be a good substrate of CYP1A1 given its low dissociation constant. Our results suggest that indirubin rapidly activates its own metabolism via AhR-mediated induction of CYP1A1 and this characteristic is consistent with the notion that indirubin is a physiological ligand of AhR. [ABSTRACT FROM AUTHOR]

Background. The risk of skin cancer is lower in females than in males, and photoimmunosuppression caused by ultraviolet (UV) radiation is thought to be involved in the progression of skin cancer. Objectives. To determine the effect of 17β-estradiol on immunosuppression and contact hypersensitivity (CHS) caused by ultraviolet B (UVB) irradiation. Methods. Systemic immunosuppression was induced in C57BL mice that had been sensitized with 0.5% fluorescein isothiocyanate (FITC) through the skin by a single exposure to UVB (10 kJ/m2). The CHS response was assessed after applying FITC to mice treated intraperitoneally with 17β-estradiol, tamoxifen (17β-estradiol antagonist), or antiestradiol antibody. Levels of serum interleukin-10 (IL-10) were measured in treated mice and control mice using an enzyme-linked immunosorbent assay (ELISA). To assess the effect of 17β-estradiol on keratinocytes, Pam-212 cells were exposed in vitro to UVB radiation and treated for 24 h with 17β-estradiol. The IL-10 content of the supernatant was measured using an ELISA. Results. The CHS response in UVB-irradiated mice was significantly suppressed in comparison to that in nonirradiated mice. Consecutive intraperitoneal injections of 17β-estradiol significantly reduced UVB-induced suppression of the CHS response in male mice, whereas injection of tamoxifen or antiestradiol antibody significantly promoted UVB-induced suppression in female mice. Treatment with 17β-estradiol decreased the serum IL-10 levels in CHS-suppressed male mice after UVB irradiation, but treatment with tamoxifen or antiestradiol antibody increased the serum IL-10 levels in female mice. Treatment with 17β-estradiol reduced IL-10 production by UVB-irradiated Pam-212 cells in a dose-dependent manner. Conclusions. These results suggest that 17β-estradiol prevents UVB-induced suppression of the CHS response caused by immunosuppressive cytokines produced by keratinocytes. [ABSTRACT FROM AUTHOR]

Compares the regulatory role of molecular chaperones in cellular senescence, apoptosis and necrosis. Data on chaperone level and function in aging cells; Possible therapeutic interventions; Involvement of chaperone function in cellular senescence; Changes of chaperone function in cellular senescence.

Provides information on a study that examined the distribution of the nucleolar protein p14[supArf] in two morphologically distinct HeLa clones. Results and discussion on the study; Methodology of the study.

Evaluates the application of sex hormone adjuvanting therapy in rheumatoid arthritis. Circulating plasma concentrations of sex hormones; Ratio of androgens to estrogens; Influence of different types of psychosocial stressors on neuroendocrine and immune mechanisms.

Discusses the role of DNA methylation in breast carcinogenesis. Details on DNA methylation and the establishment of six novel capabilities towards breast carcinogenesis; Information on DNA methylation, memory and breast carcinogenesis; Prevention of breast cancer.

Presents information on a study which have undertaken a high resolution differential proteomic analysis aimed at identifying proteins that were differentially expressed upon replicative senescence to identify the underlying mechanisms that limit the mitotic potential of normal somatic cells. Insight on the process of replicative senescence; Materials and methodology of the study; Results and discussion.

Presents a study which showed that a 31 bp sequence within the 2.2-kb region of the human helix-loop-helix protein Id-1 promoter is responsible for the constitutive expression of Id-1 in metastatic human breast cancer cells. Review of related literature; Materials and methods used; Results.

Focuses on a cyclin-dependent kinase inhibitor and its potential as a tumor suppressor. Demonstration of a role for the Ets1 and Ets2 transcription factors in the process; Implication of the kinase inhibitor in replicative senescence; Reference to the lifespan of human diploid fibroblasts.

Simple Summary: For the last decade, the most successful approach for treating cancer has been the use of monoclonal antibodies to immune checkpoint inhibitors (ICI), also known as immune checkpoint blockers (ICB). Unfortunately, many cancers do not respond to these treatments. "Hot" tumors are those that show signs of inflammation, meaning they have been invaded by effector T cells rushing to fight the cancerous cells. Evidence suggests that the limited success of ICI-based immunotherapies is related to attempts to treat patients with "cold tumors" that either do not contain effector T cells or in which these cells are markedly suppressed by regulatory T cells (Tregs). Chemokines are a well-defined group of proteins with chemotactic properties. We focus on key chemokines that not only attract leukocytes to tumor sites but also shape their biological properties. We propose using stabilized forms of two of them: CXL9 and CXCL10, to enhance anti-tumor immunity and possibly transform cold tumors into hot ones. Additionally, we discuss the possibility of targeting or deleting a key subset of Tregs that are CCR8+ Tregs and are highly dominant at the tumor site of several cold tumors. This may convert these cold tumors into hot tumors, and thus extend the success of immunotherapy beyond its current limits. Over the last decade, monoclonal antibodies to immune checkpoint inhibitors (ICI), also known as immune checkpoint blockers (ICB), have been the most successful approach for cancer therapy. Starting with mAb to cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors in metastatic melanoma and continuing with blockers of the interactions between program cell death 1 (PD-1) and its ligand program cell death ligand 1 (PDL-1) or program cell death ligand 2 (PDL-2), that have been approved for about 20 different indications. Yet for many cancers, ICI shows limited success. Several lines of evidence imply that the limited success in cancer immunotherapy is associated with attempts to treat patients with "cold tumors" that either lack effector T cells, or in which these cells are markedly suppressed by regulatory T cells (Tregs). Chemokines are a well-defined group of proteins that were so named due to their chemotactic properties. The current review focuses on key chemokines that not only attract leukocytes but also shape their biological properties. CXCR3 is a chemokine receptor with 3 ligands. We suggest using Ig-based fusion proteins of two of them: CXL9 and CXCL10, to enhance anti-tumor immunity and perhaps transform cold tumors into hot tumors. Potential differences between CXCL9 and CXCL10 regarding ICI are discussed. We also discuss the possibility of targeting the function or deleting a key subset of Tregs that are CCR8+ by monoclonal antibodies to CCR8. These cells are preferentially abundant in several tumors and are likely to be the key drivers in suppressing anti-cancer immune reactivity. [ABSTRACT FROM AUTHOR]

The occurrence and development of breast cancer are closely related to dietary factors, especially dietary patterns. This study was to investigate the effects of dietary patterns on the process of tumor metastasis by in vivo circulating tumor cell (CTC) capture strategy and monitoring changes of CTC numbers in breast tumor mice model. Meanwhile, the effects of different dietary patterns on the development of lung metastases of breast cancer and the volume and weight of carcinoma in situ were investigated. In this study, the increase in the number of CTCs was significantly promoted by dietary patterns such as high-salt diet, high-sugar diet, and high-fat diet, while it was delayed by ketogenic diet, low-fat diet, low-protein diet, diet restriction, and Mediterranean diet. These results indicated that the in vivo capture and detection of CTCs provides a convenient method for real-time cancer metastasis monitoring, and through in-depth study of the effects of different dietary patterns on tumor growth and metastasis, it can expand a new horizon in future cancer treatments. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that the DNA-binding efficiency of Sp1 is greatly decreased in nuclear extracts from 30-month-old rat tissues compared to those from young ones, although its gene appears to be normally expressed. As reactive oxygen intermediates are known to accumulate in aged animals, we investigated the effect of oxidation on the Sp1 DNA-binding activity. Electrophoretic mobility shift assays and DNase I footprintings showed that high concentrations of dithiothreitol, added to the aged tissue extracts, fully restore the Sp1 DNA-binding efficiency. However, in young nuclear extracts hydrogen peroxide treatment strongly decreases the Sp1 DNA-binding activity that is restored by the treatment with high dithiothreitol concentrations. To ascertain whether the oxidative stress is directed toward the Sp1 molecule alone, or whether it acts on unknown Sp1 cofactor(s) necessary for DNA binding, we purified Sp1 from young rat liver and demonstrated that when the purified protein is added to aged nuclear extracts, it efficiently binds to its DNA cis-element. Moreover, purified Sp1 treated with hydrogen peroxide lost its ability to bind its cis-element and the DNA-binding efficiency was fully restored after incubation with dithiothreitol. [ABSTRACT FROM AUTHOR]

Expression of proteins encoded by the ras proto-oncogenes was examined in extracts from normal rat organs using anti-ras p21 antibodies generated against synthetic peptides. The highest level of ras p21 was found in brain (cerebrum) and was predominantly of c-Ha-ras origin. Levels of brain ras p21 did not vary from the newborn period of 3 months of age. Moderate levels of ras p21s were detected in lung, spleen and thymus. In contrast to the p21 in brain, these levels varied with the age of the rats and were encoded by other members of ras proto-oncogene family (Ki-ras or N-ras). This organ specific expression of different ras genes might be related to developmental control of gene expressions. [ABSTRACT FROM AUTHOR]

Simple Summary: The hormone estrogen is well known for its role in promoting breast and ovarian cancer. Estrogen has the opposite effect on the liver, which it protects from cancer. We show that this protection requires Estrogen Receptor α, but not Estrogen Receptor β, and correlates with a female pattern of liver gene expression. Female expression in the liver requires Estrogen Receptor α expressed in non-liver cells. Surgical removal of the ovaries, which protect females from liver cancer at least in part through their production of estrogen, does not affect the female-specific liver gene expression pattern. Estrogen may therefore influence liver carcinogenesis through multiple independent mechanisms. We identify six genes that are strong candidates for mediating Esr1′s protection against liver cancer. Estrogen protects females from hepatocellular carcinoma (HCC). To determine whether this protection is mediated by classic estrogen receptors, we tested HCC susceptibility in estrogen receptor-deficient mice. In contrast to a previous study, we found that diethylnitrosamine induces hepatocarcinogenesis to a significantly greater extent when females lack Esr1, which encodes Estrogen Receptor-α. Relative to wild-type littermates, Esr1 knockout females developed 9-fold more tumors. Deficiency of Esr2, which encodes Estrogen Receptor-β, did not affect liver carcinogenesis in females. Using microarrays and QPCR to examine estrogen receptor effects on hepatic gene expression patterns, we found that germline Esr1 deficiency resulted in the masculinization of gene expression in the female liver. Six of the most dysregulated genes have previously been implicated in HCC. In contrast, Esr1 deletion specifically in hepatocytes of Esr1 conditional null female mice (in which Cre was expressed from the albumin promoter) resulted in the maintenance of female-specific liver gene expression. Wild-type adult females lacking ovarian estrogen due to ovariectomy, which is known to make females susceptible to HCC, also maintained female-specific expression in the liver of females. These studies indicate that Esr1 mediates liver cancer risk, and its control of sex-specific liver gene expression involves cells other than hepatocytes. [ABSTRACT FROM AUTHOR]

Simple Summary: Today, we know that estrogen hormones are required for the development and function of many organs, such as the liver, in both males and females. However, in some circumstances, estrogen excess may be implicated in the appearance of various chronic diseases, including cancer. This review will inspect the results of several studies to better understand the mechanisms responsible for estrogens to change from protective into harmful hormones in human liver. Estrogens are recognized as key players in physiological regulation of various, classical and non-classical, target organs, and tissues, including liver development, homeostasis, and function. On the other hand, multiple, though dispersed, experimental evidence is highly suggestive for the implication of estrogen in development and progression of hepatocellular carcinoma. In this paper, data from our own studies and the current literature are reviewed to help understanding this apparent discrepancy. [ABSTRACT FROM AUTHOR]

The association between dermatomyositis (DM) and various types of malignancies has been reported in several studies, with an estimated frequency of about 20–25%. Cancer may appear before the onset of DM, concurrently with DM or after its onset. In the present report, the occurrence of typical DM in concomitance with development of skin metastases from previously treated breast cancer is described, suggesting the role of DM as paraneoplastic marker not only in association with the primary tumor but also in case of cutaneous involvement by cancer. [ABSTRACT FROM AUTHOR]

The Mediterranean diet (MD) may provide metabolic benefits but no systematic review to date has examined its effect on a multitude of outcomes related to metabolic health. This systematic review with meta-analysis (International Prospective Register of Systematic Reviews, PROSPERO; number CRD42019141459) aimed to examine the MD's effect on metabolic syndrome (MetSyn) incidence, components and risk factors (primary outcomes), and incidence and/or mortality from MetSyn-related comorbidities and receipt of pharmacologic treatment for MetSyn components and comorbidities (secondary outcomes). We searched Pubmed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science for controlled trials published until June 2019, comparing the MD with no treatment, usual care, or different diets in adults. Studies not published in English and not promoting the whole MD were excluded. Two authors independently extracted data and assessed risk of bias using the Cochrane Collaboration's and Risk of Bias in non-randomised studies (ROBINS-I) tools. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random-effects meta-analyses, subgroup analyses and meta-regressions were performed, and heterogeneity was quantified using the I2 statistic. We identified 2654 reports and included 84 articles reporting 57 trials (n = 36,983). In random effects meta-analyses, the MD resulted in greater beneficial changes in 18 of 28 MetSyn components and risk factors (body weight, body mass index, waist circumference, systolic and diastolic blood pressure, glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR) index, total-, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, triglycerides, alanine transaminase, hepatic fat mass, C-reactive protein, interleukin-6, tumour necrosis factor-a, and flow-mediated dilatation) and lower risk of cardiovascular disease incidence (risk ratio (RR) = 0.61, 95% confidence intervals (CI) 0.42–0.80; I2 = 0%), and stroke (RR = 0.67, 95% CI 0.35–0.98; I2 = 0%). Only six studies reported effects on pharmacotherapy use, and pooled analysis indicated no differences between diet groups. Lack of consistency in comparator groups and other study characteristics across studies resulted in high heterogeneity for some outcomes, which could not be considerably explained by meta-regressions. However, a consistent direction of beneficial effect of the MD was observed for the vast majority of outcomes examined. Findings support MD's beneficial effect on all components and most risk factors of the MetSyn, in addition to cardiovascular disease and stroke incidence. More studies are needed to establish effects on other clinical outcomes and use of pharmacotherapy for MetSyn components and comorbidities. Despite the high levels of heterogeneity for some outcomes, this meta-analysis enabled the comparison of findings across studies and the examination of consistency of effects. The consistent direction of effect, suggesting the MD's benefits on metabolic health, supports the need to promote this dietary pattern to adult populations. [ABSTRACT FROM AUTHOR]

Since ancient times, the quality of nourishment is a milestone for the maintenance of health and as it is stated 'prevention is better than cure', amongst the so-called 'healthy' diets Mediterranean diet (MD) claims the lion's share. It stands in good stead because of a variety of valuable macro- and micronutrients. So, adherence to a MD is associated with the reduction of inflammation and non-communicable (NCD) OR chronic diseases. Numerous studies try to scrutinize the role of MD components as regards reducing inflammation, lowering rate, and mortality for disorders and illnesses, and preventing NCD. MD regime of the inhabitants of the Mediterranean basin includes a variety of ethnic nutritional habits and regulates an array of effects and epigenetic changes that affect human wellbeing. The research is still ongoing and endeavors to elucidate every aspect of this issue. This review focuses on the impact of MD on inflammation highlights positive results regarding NCD and indicates the need for more high-quality experiments and trials in order to overcome any discrepancies. [ABSTRACT FROM AUTHOR]

Introduction: Analysis of quality of life (QOL) outcomes is an important aspect of lymphedema treatment since this disease can substantially impact QOL in affected individuals. There are a growing number of studies reporting patient-reported outcomes (PROMs) for patients with lymphedema. The purpose of this study was to conduct a systematic review of outcomes and utilization of PROMs following surgical treatment of lymphedema. Methods: A literature search of four databases was performed up to and including March, 2019. Studies included reported on QOL outcomes after physiologic procedures, defined as either lymphovenous bypass (LVB) or vascularized lymph node transplant (VLNT), to treat upper and/or lower extremity primary or secondary lymphedema. Results: In total, 850 studies were screened—of which, 32 studies were included in this review. Lymphovenous bypass was the surgical intervention in 16 studies, VLNT in 11 studies, and both in 5 studies. Of the 32 total studies, 16 used validated survey tools. The most commonly used PROM was the lymph quality of life measure for limb lymphedema (LYMQOL) (12 studies). In the remaining four studies, the upper limb lymphedema 27 scale (ULL27), the short form 36 questionnaire (SF-36), the lymphedema functioning, disability and health questionnaire (Lymph-ICF), and lymphedema life impact scale (LLIS) were each used once. QOL improvement following surgical treatment was noted in all studies. Conclusions: Physiologic surgical treatment of lymphedema results in improved QOL outcomes in most patients. The use of validated PROM tools is increasing but there is no current consensus on use. Future research to evaluate the psychometric properties of PROMs in lymphedema is needed to guide the development and use of lymphedema-specific tools. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer in women globally, and the risk of developing breast cancer is associated with inflammation. The present study aimed to examine the association between the Dietary Inflammatory Index (DII®) and breast cancer in Korean women and investigate whether the tumor's hormone receptor status affects this association. In this case-control study, we enrolled 364 breast cancer patients and 364 age-matched controls. DII scores were calculated from dietary intake evaluated by a 106-item food frequency questionnaire. The DII score was significantly higher in cases than in controls. After adjusting for potential confounders, the odds ratio (OR) of breast cancer was higher in the highest DII tertile (OR = 3.68, 95% confidence interval (CI): 2.34–5.80, p for trend < 0.0001) than in the lowest tertile. We found that higher DII scores were related to an increased risk of breast cancer for estrogen receptor (ER)+/progesterone receptor (PR)+ tumors regardless of menopausal status (OR = 2.59, 95% CI: 1.37–4.88 in the highest DII category, p for trend = 0.01 for premenopausal women; OR = 11.00, 95% CI: 2.93–41.30 in the highest DII category, p for trend = 0.0004 for postmenopausal women), but not for ER−/PR− status. Our results suggested that the DII scores are positively associated with breast cancer risk in Korean women and that this relationship is more robust in ER+/PR+ tumors. [ABSTRACT FROM AUTHOR]

Estrogen evidently involves critically in the pathogenesis of gynaecological-cancers. Reports reveal that interference in estrogen-signalling can influence cell-cycle associated regulatory-processes in female reproductive-organs. The major determinants that influence E2-signallings are estrogen-receptor (ER), estrogen-sulfotransferase (SULT1E1), sulfatase (STS), and a formylglycine-generating-enzyme (FGE) which regulates STS activity. The purpose of this mini review was to critically analyze the correlation between oxidative-threats and redox-regulation in the process of estrogen signalling. It is extensively investigated and reported that oxidative-stress is linked to cancer. But no definite mechanism has been explored till date. The adverse effects of oxidative-threat/free-radicals (like genotoxic-effects, gene-regulation, and mitochondrial impairment) have been linked to several diseases like diabetes/cardiovascular-syndrome/stroke and cancer. However, a significant correlation between oxidative-stress and gynaecological-cancers are repeatedly reported without pointing a definite mechanism. For the first time in our study we have investigated the relationship between oxidative stress and the regulation of estrogen via estrogen metabolizing proteins. Reports reveal that ER, SULT1E1, STS and FGE are target-molecules of oxidative-stress and may function differently in oxidizing and reducing environment. In addition, estrogen itself can induce oxidative-stress. This fact necessitates identifying the critical connecting events between oxidative-stress and regulation of estrogen-associated-molecules (ER, SULT1E1, STS, and FGE) that favors tumorigenesis/carcinogenesis. The current review focus is on unique redox-regulation of estrogen and its regulatory-molecules via oxidative-stress. This mechanistic-layout may identify new therapeutic-targets and open further scopes to treat gynecological-cancers more effectively. [ABSTRACT FROM AUTHOR]

Superconducting radiofrequency (SRF) cavities that could provide a higher quality factor as well as a higher operational accelerating gradient at an affordable cost are in high demand for the future generation of particle accelerators. This study aims to demonstrate the potential of Nb3Sn as material of choice for such SRF applications. Due to its brittle nature, the only way to produce an Nb3Sn SFR cavity is to synthesise a thin layer inside a cavity made of niobium or copper. In this work, direct current magnetron sputtering using a stoichiometric target of Nb3Sn was employed to produce films on copper samples. Assessment of the morphology, microstructure and superconducting properties were performed in order to ensure that this approach is suitable for SRF applications. The potential of the method is proven by obtaining films, which exhibit a crack-free surface, dense morphology and critical temperatures (Tc) up to 16 K. The essential properties of the films have also been investigated with respect to the deposition and annealing conditions. The use of krypton as working gas during deposition increases the atomic percent of Sn in the film compared to argon. However, in contrast to argon, higher krypton pressures reduce the atomic percent of Sn. It was also found that long-lasting high-temperature annealing leads to higher superconducting critical temperatures due to an increased crystallographic order. Particular attention was given to the influence of the copper substrate on the film growth as well as the microstructural and superconducting characteristics. We discuss the main constraints introduced by the copper substrate, such as copper interdiffusion during annealing, lattice mismatch and difference in thermal expansion coefficients and methods to overcome them. [ABSTRACT FROM AUTHOR]

Overexpression of Sonic Hedgehog signaling (Shh) pathway molecules is associated with invasiveness and recurrence in breast carcinoma. Therefore, inhibition of the Shh pathway downstream molecule Glioma-associated Oncogene Homolog (Gli) was investigated for its ability to reduce progression and invasiveness of patient-derived breast cancer cells and cell lines. Human primary breast cancer T2 cells with high expression of Shh signaling pathway molecules were compared with breast cancer line MDA-MB-231 cells. The therapeutic effects of Gli inhibitors were examined in terms of the cell proliferation, apoptosis, cancer stem cells, cell migration and gene expression. Blockade of the Shh signaling pathway could reduce cell proliferation and migration only in MDA-MB-231 cells. Hh pathway inhibitor-1 (HPI-1) increased the percentages of late apoptotic cells in MDA-MB-231 cells and early apoptotic cells in T2 cells. It reduced Bcl2 expression for cell proliferation and increased Bim expression for apoptosis. In addition, Gli inhibitor HPI-1 decreased significantly the percentages of cancer stem cells in T2 cells. HPI-1 worked more effectively than GANT-58 against breast carcinoma cells. In conclusion, HPI-1 could inhibit cell proliferation, reduce cell invasion and decrease cancer stem cell population in breast cancer cells. To target Gli-1 could be a potential strategy to suppress breast cancer stem cells. [ABSTRACT FROM AUTHOR]

Background: Food consumption and nutritional status affect an individual’s health throughout their life-course and an unhealthy diet is a major risk factor for the current global burden of chronic disease. The promotion of health and good nutrition through healthy eating requires the active involvement of all health professionals including chiropractors. This paper reports findings from the first nationally representative examination of the use of nutritional guidance within chiropractic patient management in Australia. Methods: A sample of 1000 practising chiropractors was randomly selected from the Australian Chiropractic Research Network (ACORN) practice-based research network database for a cross-sectional study and 33% participated in the online survey in November 2016. The questionnaire, based on previous designs used in similar surveys and nutrition resources developed by the National Health and Medical Research Council, was pretested prior to the survey. Pearson’s Chi square and bivariate logistic regression were undertaken to explore relationships with variables of interest. Results: The demographic details of the respondents are similar to those of the chiropractic workforce registered in Australia. Most chiropractors provided nutritional advice as part of their patient care and around a quarter provided specific dietary advice to their patients, including the use of nutrition supplements. Nutrition-related conditions most commonly encountered by the chiropractors were musculoskeletal, usually inflammatory in origin. Common nutritional assessment methods used included questioning patients to assess their nutritional and health status and physical appearance. Most of the participants provided nutritional resources to their patients in their clinics. However, the Australian Dietary Guidelines and the accompanying Australian Guide to Healthy Eating were not well utilised by the respondents. Australian chiropractors often referred patients with nutrition issues to qualified dietitians and other health professionals when deemed necessary. Conclusions: Australian chiropractors regularly provide nutritional advice and appear to acknowledge the importance of nutrition in their clinical practice especially for patients presenting with chronic disease. If chiropractors are to fulfil their potential in providing such wider public health and preventative health advice to patients, further research examining the utilisation of evidence-based nutrition resources within chiropractic patient management is recommended. [ABSTRACT FROM AUTHOR]

Point contact tunneling and low energy muon spin rotation are used to probe, on the same samples, the surface superconducting properties of micrometer thick niobium films deposited onto copper substrates using different sputtering techniques: diode, dc magnetron and HIPIMS. The combined results are compared to radio-frequency tests performances of RF cavities made with the same processes. Degraded surface superconducting properties are found to correlate to lower quality factors and stronger Q-slope. In addition, both techniques find evidence for surface paramagnetism on all samples and particularly on Nb films prepared by HIPIMS. [ABSTRACT FROM AUTHOR]

Research and development for superconducting radio-frequency cavities has made enormous progress over the last decades from the understanding of theoretical limitations to the industrial mass fabrication of cavities for large-scale particle accelerators. Key technologies remain hot topics due to continuously growing demands on cavity performance, particularly when in pursuit of high quality beams at higher beam currents or higher luminosities than currently achievable. This relates to higher order mode (HOM) damping requirements. Meeting the desired beam properties implies avoiding coupled multi-bunch or beam break-up instabilities depending on the machine and beam parameters that will set the acceptable cavity impedance thresholds. The use of cavity HOM-dampers is crucial to absorb the wakefields, comprised by all beam-induced cavity Eigenmodes, to beam-dynamically safe levels and to reduce the heat load at cryogenic temperature. Cavity damping concepts may vary, but are principally based on coaxial and waveguide couplers as well as beam line absorbers or any combination. Next generation energy recovery linacs and circular colliders call for cavities with strong HOM-damping that can exceed the state-of-the-art, while the operating mode efficiency shall not be significantly compromised concurrently. This imposes major challenges given the rather limited damping concepts. A detailed survey of established cavities is provided scrutinizing the achieved damping performance, shortcomings, and potential improvements. The scaling of the highest passband mode impedances is numerically evaluated in dependence on the number of cells for a single-cell up to a nine-cell cavity, which reveals the increased probability of trapped modes. This is followed by simulations for single-cell and five-cell cavities, which incorporate multiple damping schemes to assess the most efficient concepts. The usage and viability of on-cell dampers is elucidated for the single-cell cavity since it can push the envelope towards quasi HOM-free operation suited for next generation storage and collider rings. Geometrical end-cell shape alterations for the five-cell cavity with already efficient mode damping are discussed as a possibility to further lower specific high impedance modes. The findings are eventually put into relation with demanding impedance instability thresholds in future collider rings. [ABSTRACT FROM AUTHOR]

An overview of a theory of electromagnetic response of superconductors in strong radio-frequency (RF) electromagnetic fields is given with the emphasis on applications to superconducting resonant cavities for particle accelerators. The paper addresses fundamentals of the BCS surface resistance, the effect of subgap states and trapped vortices on the residual surface resistance at low RF fields, and a nonlinear surface resistance at strong fields, particularly the effect of the RF field suppression of the surface resistance. These issues are essential for the understanding of the field dependence of high quality factors achieved on the Nb cavities at 1.3–2 K in strong RF fields Ba close to the depairing limit, and the extended rise which has been observed on Ti and N-treated Nb cavities. Possible ways of further increase of and the breakdown field by optimizing impurity concentration at the surface and by multilayer nanostructuring with materials other than Nb are discussed. [ABSTRACT FROM AUTHOR]

In the present study the radio-frequency complex response of trapped vortices in superconductors is calculated and compared to experimental data previously published. The motion equation for a magnetic flux line is solved assuming a bi-dimensional and mean-free-path-dependent Lorentzian-shaped pinning potential. The resulting surface resistance shows the unprecedented bell-shaped trend as a function of the mean-free-path observed in our previous experimental work. We demonstrate that such bell-shaped trend of the surface resistance as a function of the mean-free-path may be described as the interplay of the two limiting regimes of the surface resistance, for low and large mean-free-path values: pinning and flux-flow regimes respectively. Since the possibility of defining the pinning potential at different locations from the surface and with different strengths, we discuss how the surface resistance is affected by different configurations of pinning sites. By tackling the frequency dependence of the surface resistance, we also demonstrate that the separation between pinning- and flux-flow-dominated regimes cannot be determined only by the depinning frequency. The dissipation regime can be tuned either by acting on the frequency or on the mean-free-path value. [ABSTRACT FROM AUTHOR]

Theoretical limits to the performance of superconductors in high magnetic fields parallel to their surfaces are of key relevance to current and future accelerating cavities, especially those made of new higher-Tc materials such as Nb3Sn, NbN, and MgB2. Indeed, beyond the so-called superheating field , flux will spontaneously penetrate even a perfect superconducting surface and ruin the performance. We present intuitive arguments and simple estimates for , and combine them with our previous rigorous calculations, which we summarize. We briefly discuss experimental measurements of the superheating field, comparing to our estimates. We explore the effects of materials anisotropy and the danger of disorder in nucleating vortex entry. Will we need to control surface orientation in the layered compound MgB2? Can we estimate theoretically whether dirt and defects make these new materials fundamentally more challenging to optimize than niobium? Finally, we discuss and analyze recent proposals to use thin superconducting layers or laminates to enhance the performance of superconducting cavities. Flux entering a laminate can lead to so-called pancake vortices; we consider the physics of the dislocation motion and potential re-annihilation or stabilization of these vortices after their entry. [ABSTRACT FROM AUTHOR]

The surface resistance Rs of superconducting materials can be obtained by measuring the quality factor of an elliptical cavity excited in a transverse magnetic mode (TM010). The value obtained has however to be taken as averaged over the whole surface. A more convenient way to obtain Rs, especially of materials which are not yet technologically ready for cavity production, is to measure small samples instead. These can be easily manufactured at low cost, duplicated and placed in film deposition and surface analytical tools. A commonly used design for a device to measure Rs consists of a cylindrical cavity excited in a transverse electric (TE110) mode with the sample under test serving as one replaceable endplate. Such a cavity has two drawbacks. For reasonably small samples the resonant frequency will be larger than frequencies of interest concerning SRF application and it requires a reference sample of known Rs. In this article we review several devices which have been designed to overcome these limitations, reaching sub-nΩ resolution in some cases. Some of these devices also comprise a parameter space in frequency and temperature which is inaccessible to standard cavity tests, making them ideal tools to test theoretical surface resistance models. [ABSTRACT FROM AUTHOR]