Breast cancer is one of the most common malignancies. However, the molecular mechanisms underlying its pathogenesis remain to be elucidated. The present study aimed to identify the potential prognostic marker genes associated with the progression of breast cancer. Weighted gene coexpression network analysis was used to construct free-scale gene coexpression networks, evaluate the associations between the gene sets and clinical features, and identify candidate biomarkers. The gene expression profiles of GSE48213 were selected from the Gene Expression Omnibus database. RNA-seq data and clinical information on breast cancer from The Cancer Genome Atlas were used for validation. Four modules were identified from the gene coexpression network, one of which was found to be significantly associated with patient survival time. The expression status of 28 genes formed the black module (basal); 18 genes, dark red module (claudin-low); nine genes, brown module (luminal), and seven genes, midnight blue module (nonmalignant). These modules were clustered into two groups according to significant difference in survival time between the groups. Therefore, based on betweenness centrality, we identified TXN and ANXA2 in the nonmalignant module, TPM4 and LOXL2 in the luminal module, TPRN and ADCY6 in the claudin-low module, and TUBA1C and CMIP in the basal module as the genes with the highest betweenness, suggesting that they play a central role in information transfer in the network. In the present study, eight candidate biomarkers were identified for further basic and advanced understanding of the molecular pathogenesis of breast cancer by using co-expression network analysis.

The Mediterranean diet is associated with a low incidence of physiologic and metabolic non-communicable diseases such as hypertension, obesity, and insulin resistance. These chronic diseases are closely related to oxidative status, which is determined by the balance between oxidant and antioxidant levels. The Mediterranean diet is rich in foods with important antioxidant properties, such as fruits and extra virgin olive oil. The aim of this work was to establish the relationship between dietary patterns, the total intake of polyphenols, and the levels of 8-isoprostanes in urine, as a marker of lipid peroxidation, in a group of healthy Spanish women. The main sources of dietary polyphenols were fruits, vegetables, pulses, nuts, and extra virgin olive oil. There was a significant and positive correlation between the estimated intake of polyphenols, total polyphenols excreted in urine, adherence to the Mediterranean diet, and the intake of specific food groups. A positive correlation was established between the total polyphenols in urine and the intake of raw extra virgin olive oil. However, a negative correlation was established between the amount of 8-isoprostanes in urine, total intake of polyphenols, adherence to the Mediterranean diet, and the intake of fruits and nuts. These results indicate an association between oxidative status and the intake of foods that are typical of the Mediterranean diet, in healthy women. Furthermore, the results demonstrate the use of urine 8-isoprostanes as a marker of adherence to the Mediterranean diet.

Background and objectives: This study aimed to assess the level of HIV disclosure to children in sub-Saharan Africa as it relates to prevalence of disclosure, barriers, merits and demerits, timing of disclosure, and factors that promote parents and caregivers' decisions to disclose the information. Materials and Methods: A systematic literature search was performed using the following online databases: PubMed, Google Scholar, Web of Science, Scopus, and Embase, to obtain relevant articles on HIV disclosure to children in sub-Saharan Africa. The following search terms were used: "HIV" AND "Disclosure" AND "Sub-Saharan Africa" AND "Children". Results: A total of 18 articles were included in this systematic review. The studies on HIV status disclosure to children in sub-Saharan Africa included a total of 1343 HIV-positive children and 1879 caregiver/child or healthcare worker-child dyads, from the following countries: Ethiopia, South Africa, Ghana, Kenya, Cote d'Ivoire, Burundi, Cameroon, Democratic Republic of Congo, Uganda, Burkina Faso, and Zambia. The prevalence of HIV disclosure ranged from as low as 9% to 72%. Age was a major factor associated with disclosure. Conclusions: HIV status disclosure to children is quite low in sub-Saharan Africa. This is a result of multiple factors such as parents'/caregivers' fear of the child disclosing status to others, a lack of knowledge on how the disclosure should be made, and the assertion that the children are young and cannot withstand the psychological impact of diagnosis.

The aim was to assess the level of physical activity and the quality of life of children undergoing cancer treatment, during and after the completion of the treatment. Eighty-eight children aged 11-15 were enrolled. Three groups of children were assessed, i.e., children undergoing cancer treatment (n = 30), children after cancer treatment (n = 28), and healthy children (n = 30). The level of physical activity in children was assessed using the questions from the Health Behavior in School-Aged Children (HBSC) questionnaire. The assessment of children's quality of life was conducted using the KIDSCREEN-10 Index. The chi-square test was used to assess the statistical significance of the differences in the results between the study groups in the case of both HBSC and KIDSCREEN-10 questionnaires. Children undergoing cancer treatment did not perform any physical activity of at least 60 min (in total) per day, during the week. Therefore, they did not meet the recommendations related to the appropriate level of daily physical activity (Moderate-to-Vigorous Physical Activity; MVPA). Children after cancer treatment and healthy children significantly more frequently undertook physical activity. The quality of life of children with cancer is significantly lower and different from the quality of life of healthy children.

Despite the widespread use of tetracycline antibiotics since the late 1940s, tetracycline hypersensitivity reactions have rarely been described in the literature. A comprehensive PubMed search was performed, including allergic and serious adverse reactions attributed to the tetracyclines class of antibiotics. Of the evaluated tetracycline analogs, minocycline was attributed to the greatest overall number and severity of serious adverse events reported in the literature, with notable reactions primarily reported as respiratory and dermatologic in nature. Reactions to tetracycline have also been well described in the literature, and although dermatologic reactions are typically less severe in comparison with minocycline and doxycycline, various reports of anaphylactic reactions exist. Although doxycycline has been noted to have had the fewest reports of severe allergic reactions, rare descriptions of life-threatening reactions are still reported in the literature. Allergic reactions regarding tetracyclines are rare; however, adverse reaction type, severity, and frequency among different tetracycline analogs is somewhat variable. A consideration of hypersensitivity and adverse reaction incidence should be performed prior to the selection of individual tetracycline entities.

Rheumatoid arthritis (RA) is a disease of the joints that causes decreased quality of life. Mesenchymal stromal cells (MSCs) have immunosuppressive properties, with possible use in the treatment of RA. Similarly, interleukin (IL)-4 has been shown as a potential RA treatment. However, their combination has not been explored before. Therefore, this study aimed to investigate the effect of a combination therapy of MSCs and IL-4 in the treatment of RA, using a murine collagen-induced arthritis (CIA) model. Arthritis was induced in Balb/c mice by two intradermal injections of type II collagen (CII), at days 0 and 21. CIA mice were randomly assigned to four groups; group I received an intravenous injection of mouse bone marrow-derived MSCs, while group II received an intraperitoneal injection of IL-4. Group III received a combined treatment of MSC and IL-4, while group IV served as a CIA diseased control group receiving phosphate buffer saline (PBS). A fifth group of healthy mice served as the normal healthy control. To assess changes induced by different treatments, levels of RA-associated inflammatory cytokines and biomarkers were measured in the serum, knee joints, and synovial tissue, using ELISA and Real Time-qPCR. Histopathological features of knee joints were analyzed for all groups. Results showed that combined MSC and IL-4 treatment alleviated signs of synovitis in CIA mice, reverting to the values of healthy controls. This was evident by the decrease in the levels of rheumatic factor (RF), C-reactive protein (CRP) and anti-nuclear antibodies (ANA) by 64, 80, and 71%, respectively, compared to the diseased group. Moreover, tumor necrosis factor-alpha (TNF- α) and monocyte chemoattractant protein-1 (MCP-1) levels decreased by 63 and 68%, respectively. Similarly, our gene expression data showed improvement in mice receiving combined therapy compared to other groups receiving single treatment, where cartilage oligomeric matrix protein (Comp), tissue inhibitor metalloproteinase-1 (Timp1), matrix metalloproteinase1 (Mmp-1), and IL-1 receptor (Il-1r) gene expression levels decreased by 75, 70, and 78%, respectively. Collectively, treatment with a combined therapy of MSC and IL-4 might have an efficient therapeutic effect on arthritis. Thus, further studies are needed to assess the potential of different MSC populations in conjugation with IL-4 in the treatment of experimental arthritis.

Oxidative stress is involved in different diseases, such as diabetes and neurodegenerative diseases. The genus Azorella includes about 70 species of flowering plant species; most of them are commonly used as food and in particular as a tea infusion in the Andean region of South America in folk medicine to treat various chronic diseases. Azorella glabra Wedd. aerial parts were firstly analyzed for their in vitro antioxidant activity using different complementary assays. In particular, radical scavenging activity was tested against biological neutral radical DPPH; ferric reducing power and lipid peroxidation inhibitory capacity (FRAP and Beta-Carotene Bleaching tests) were also determined. The Relative Antioxidant Capacity Index (RACI) was used to compare data obtained by different assays. Then, the inhibitory ability of samples was investigated against α-amylase and α-glucosidase enzymes involved in diabetes and against acetylcholinesterase and butyrylcholinesterase enzymes considered as strategy for the treatment of Parkinson's or Alzheimer's diseases. Moreover, the phytochemical profile of the sample showing the highest RACI (1.35) and interesting enzymatic activities (IC50 of 163.54 ± 9.72 and 215.29 ± 17.10 μg/mL in α-glucosidase and acetylcholinesterase inhibition, respectively) was subjected to characterization and quantification of its phenolic composition using LC-MS/MS analysis. In fact, the ethyl acetate fraction derived from ethanol extract by liquid/liquid extraction showed 29 compounds, most of them are cinnamic acid derivatives, flavonoid derivatives, and a terpene. To the best of our knowledge, this is the first report about the evaluation of significant biological activities and phytochemical profile of A. glabra, an important source of health-promoting phytochemicals.

Mitochondria evolved from free-living bacteria via endocytosis within eukaryotic host cells millions of year ago. We hypothesized that antibiotics cause mammalian mitochondrial damage while causing bacterial lethality. Mitochondrial toxicity of azithromycin in human mammary epithelia MCF-12A and fibroblasts were tested by fluorescent and transmission electron microscopy. Gene expression and DNA damage were tested by real-time polymerase chain reaction (qPCR) and ELISA. We found azithromycin suppressed the mitochondrial membrane potential gradient of MCF-12A cells and fibroblasts. Ultrastructure exams showed that the antibiotic caused vacuolated and swollen mitochondria with disrupted cristae in MCF-12A cells and fibroblasts compared to the morphology of mitochondria in the cells without antibiotic treatment. Fluorescent microscopy also showed azithromycin-induced mitochondrial reactive oxygen species (ROS), superoxide, after 3 h of culture. The DNA oxidative damage product, 8-hydroxy-2'-deoxyguanosine (8-OHdG, significantly increased in the media after MCF-12A cells and fibroblasts were cultured in the media containing azithromycin for 24 h. Azithromycin upregulated gene expression of hypoxia inducible factor 1 alpha (HIF1a), glycolytic enzymes including hexokinase 2 (HK2), phosphofructokinase 1 (PFKM), pyruvate kinase muscle isozyme M2 (PKM2), and glucose transporters in MCF-12A cells and fibroblasts. Lactate production also increased in the culture media. After treatment with azithromycin, healthy MCF-12A and fibroblast cells increased aerobic glycolysis-the "Warburg Effect"-to generate energy. In summary, azithromycin caused mitochondrial toxicity, ROS overproduction, DNA oxidative damage, upregulation of the HIF1a gene, and aerobic glycolysis in healthy mammalian cells. Over-usage of antibiotics could contribute to tumorigenesis and neurodegeneration and aggravate existing mitochondria-associated diseases.

Background This study investigated the relationships between children's friendship ties and their physical activity (PA) both before and after their transition to a new school year. Methods In 2011-2012, children in grades 5-8 attending a Canadian urban middle-school completed web-based health and friendship surveys two times before ("pre-transition") and three times after ("post-transition") they moved up in school grade. Cross-sectional associations between an average daily frequency of ≥60 min/day of moderate-to-vigorous intensity PA (MVPA) and characteristics of children's friendships were estimated for pre-transition (n = 191) and post-transition (n = 255) data. Sociodemographic-adjusted linear regression (β) estimated associations between a child's MVPA and friendship characteristics. Results We found positive associations between a child's MVPA and the average MVPA of their friends at post-transition only (β = 0.61, 95% CI 0.10 to 1.13) and the number of sent friendships at pre-transition (β = 0.03, 95% CI 0.01 to 0.05) and post-transition (β = 0.02, 95% CI 0.01 to 0.04). A statistically significant interaction between popularity and friends' average PA at pre-transition was also found. Conclusions The PA of friends and the number of school friends that a child identified are positively associated with MVPA. The estimated associations between MVPA and aspects of children's friendships are similar for boys and girls.

Protein consumption influences glucose homeostasis, but the effect depends on the type and origin of proteins ingested. The present study was designed to determine the effect of herring milt protein hydrolysate (HPH) on insulin function and glucose metabolism in a mouse model of diet-induced obesity. Male C57BL/6J mice were pretreated with a low-fat diet or a high-fat diet for 6 weeks. Mice on the high-fat diet were divided into four groups where one group continued on the high-fat diet and the other three groups were fed a modified high-fat diet where 15%, 35%, and 70%, respectively, of casein was replaced with an equal percentage of protein derived from HPH. After 10 weeks, mice that continued on the high-fat diet showed significant increases in body weight, blood glucose, insulin, and leptin levels and exhibited impaired oral glucose tolerance, insulin resistance, and pancreatic β-cell dysfunction. Compared to mice fed the high-fat diet, the 70% replacement of dietary casein with HPH protein reduced body weight, semi-fasting blood glucose, fasting blood glucose, insulin, leptin, and cholesterol levels and improved glucose tolerance, homeostasis model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of β-cell function (HOMA-β) indices. The 35% replacement of dietary casein with HPH protein showed moderate effects, while the 15% replacement of dietary casein with HPH protein had no effects. This is the first study demonstrating that replacing dietary casein with the same amount of protein derived from HPH can prevent high-fat-diet-induced obesity and insulin resistance.

The definition of neighborhoods as areas of exposure to the food environment is a challenge in food environment research. We aimed to test the association of density of restaurants with home cooking using four different definitions of residential neighborhoods. We also tested effect modification by age, length of residency, education, and income. This innovative cross-sectional study was conducted in the Netherlands (N = 1245 adults). We calculated geographic information system-based measures of restaurant density using residential administrative neighborhood boundaries, 800 m and 1600 m buffers around the home and respondents' self-defined boundaries (drawn by the respondents on a map of their residential area). We used adjusted Poisson regression to test associations of restaurant density (tertiles) and the outcome "weekly consumption of home-cooked meals" (six to seven as compared to five days per week (day/week) or fewer). Most respondents reported eating home-cooked meals for at least 6 day/week (74.2%). Regardless of the neighborhood definition used, no association between food environment and home cooking was observed. No effect modification was found. Although exposure in terms of density of restaurants was different according to the four different neighborhood definitions, we found no evidence that the area under study influences the association between density of restaurants and home cooking among Dutch adults.

Citrus flavonoids have well-documented protective effects on cardiovascular system, but the poor water solubility and reduced bioavailability restrict their therapeutic use. We aimed to overcome these limitations and encapsulated naringenin and hesperetin into lipid nanoemulsions (LNs), targeted to vascular cell adhesion molecule-1 (VCAM-1), which is expressed on activated endothelial cells (ECs). LNs were characterized by a hydrodynamic size of ~200 nm, negative zeta potential, an encapsulation efficiency of flavonoids higher than 80%, good in vitro stability and steady release of the cargo. The LNs were neither cytotoxic to human ECs line EA.hy926, nor provoked in vitro lysis of murine erithrocytes. Then, we tested whether these nanoformulations reduce tumor necrosis factor-alpha (TNF-α) induced EC-activation. We found that flavonoid-loaded LNs, either non-targeted or targeted to the endothelium, were taken up by the EA.hy926 cells in a dose-dependent manner, but dependent on TNF-α only in the case of endothelium-targeted LNs. Moreover, these nanoparticles inhibited both the adhesion and transmigration of THP-1 monocytes on/through activated ECs, by mechanisms involving a reduced expression of the pro-inflammatory chemokine monocyte chemotactic protein 1 (MCP-1) and diminished nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).

The nuclear factor (NF)-κB family of transcriptional factors plays a critical role in inflammation, immunoregulation, cell differentiation, and tumorigenesis. This study aims to investigate the role of methylation of genes encoding for the NF-κB family in breast cancer. We analyze the DNA methylation status of the NFKB1 gene and the RELA gene in breast cancer using pyrosequencing. The expression of NF-κB1 and RELA proteins is assessed and the level of RNA transcripts in frozen tissue is determined using RT-PCR. There is no statistically significant difference in the methylation status of the NFKB1 and the RELA genes between tumors and normal tissues. The methylation status of the NFKB1 gene and the RELA gene is not significantly associated with the levels of NF-κB1 transcripts in tumor tissues. However, the methylation level of the RELA gene is significantly associated with the level of tumor necrosis factor (TNF)-α. In addition, the level of NF-κB1 transcripts was associated with the levels of TNF-α and IL-4. In tumors with positive TNF-α, the increased methylation level of the RELA gene is significantly associated with the positive expression of NF-κB1 transcripts. These results demonstrate that the level of the RELA gene methylation is related to the levels of NF-κB1 transcripts under the influence of TNF-α. Further study is needed to determine how TNF-α is involved in the methylation of the RELA gene and the subsequent expression of NF-κB1.

A bark-like imitated polypr opylene (PP)/polycarbonate (PC) nanofibrous membrane was constructed by one-step meltblown technique for efficient particulate matter (PM) removal. The effects of PC content (0%, 1%, 3%, 5%, and 7%) on membrane thermal stability, microscopic characteristics, filtration performance, hydrophilicity, and water vapor transmission were investigated. The results demonstrated that using facile design of incompatibility and viscosity difference between PC and PP polymers decreases average fiber diameter, creating a bark-like groove appearance and increasing surface potential, making a new PP/PC membrane with high filtration performance. The resultant PP/PC membrane had finer average fiber diameter of 0.63 μm, which was nearly 89.41% lower than PP membranes (5.95 μm), and its quality factor (0.036 Pa-1) was nearly 2.12 times than that of PP membranes (0.017 Pa-1) with the die hole diameter of 0.5 mm. This fabrication technique of a special meltblown filter membrane saves the cost of die retrofitting and post-processing, which provides an innovative method for particulate efficient removal of high efficient filters.

Barley is a low phosphorus (P) demand cereal crop. Tibetan wild barley, as a progenitor of cultivated barley, has revealed outstanding ability of tolerance to low-P stress. However, the underlying mechanisms of low-P adaption and the relevant genetic controlling are still unclear.

The quest for novel sources of antibacterial compounds have necessitated the inclusion of ericoid mycorrhizal fungi (ERM) commonly found within the root of ericaceous plants. Agar-well diffusion method was used to detect antibacterial activity and was followed by the microbroth diffusion method [minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)].

Assessing the risk of bias (RoB) in included studies is one of the key methodological aspects of systematic reviews. Cochrane systematic reviews appraise RoB of randomised controlled trials (RCTs) with the Cochrane RoB tool. Detailed instructions for using the Cochrane RoB tool are provided in the Cochrane Handbook for Systematic Reviews of Interventions (The Cochrane Handbook). The purpose of this study was to analyse whether Cochrane authors use adequate judgments about the RoB for random sequence generation of RCTs included in Cochrane reviews.

Positron emission tomography (PET) and PET/computed tomography (PET/CT) imaging with 3,4-dihydroxy-6-[18F] fluoro-L-phenylalanine (18F-FDOPA) has been used in the evaluation of gliomas. We performed a meta-analysis to obtain the diagnostic and grading accuracy of 18F-FDOPA PET and PET/CT in patients with gliomas.

Astilbe rivularis L. is an indigenous medicinal plant growing in high altitude of Darjeeling Himalayan region of India and Nepal. The plant rhizome has been used traditionally as medicine by local tribes to treat various ailments including infectious and other diseases. The present study aims to evaluate the plant rhizome for chemical composition and in vitro antioxidant, antibacterial and cytotoxic bioactivities.

Bovine viral diarrhea virus (BVDV) causes severe economic losses and is one of the most important viral pathogens of ruminants worldwide. The infection manifests itself in a variety of clinical symptoms. Phylogenetic studies based mainly on 5'UTR of its genome, identified many different subtypes of BVDV. Previous study indicated the predominance of BVDV-1b and BVDV-1d in Poland. The aim of this study was to genotype BVDV isolates currently circulating in Polish dairy herds.