Dietary Flavonoid and Subclass Intakes are not Associated with Markers of Bone Health in U.S. Adults Age 50+ Years.

BACKGROUND: Dietary flavonoid intakes have been associated with improved markers of bone health in Chinese and Scottish cohorts, but little data exist in middle aged to older adults in the United States. OBJECTIVES: The objective of our research was to assess if dietary flavonoid intakes are associated with bone mineral density (BMD), bone mineral content (BMC), and bone area of the lumbar spine and femoral neck in a nationally representative population of middle aged to older U.S. adults. We further sought to investigate if relationships of the main flavonoid subgroups (i.e., anthocyanins, flavan-3-ols, flavanones, flavones, flavonols, and isoflavones) exist, as a secondary objective. METHODS: Cross-sectional data from individuals aged 50+ years enrolled in the 2017-2018 National Health and Nutrition Examination Survey (NHANES) were used in our analyses (N = 2590). Weighted multivariate logistic regression models were used to investigate the relationship between quartiles of flavonoid intake and BMD, BMC, and bone area of the lumbar spine and femoral neck of participants. RESULTS: Mean age of participants was 63.4 ± 0.52 years and 64.1 ± 0.52 years for men and women, respectively. Average total flavonoid intake was 217 ± 19.4 mg/day and 306 ± 26.9 mg/day for men and women, respectively. Total flavonoid intakes were not significantly associated with BMD, BMC, or bone area of the femoral neck or lumbar spine in male or female participants. Flavonoid subclass intakes were also not consistently associated with improved markers of bone health. CONCLUSION: Although several limitations exist, this cross-sectional analysis of U.S. adults aged 50+ years provides contradictory evidence to the hypothesis that higher flavonoid and flavonoid subclass intakes beneficially impacts markers of bone health. Large prospective cohort investigations that better capture long-term dietary flavonoid intake and ascertain fractures the primary outcome, as well as randomized controlled trials, are needed to fully elucidate the effects flavonoids on bone health.

Curcumin can improve spinal cord injury by inhibiting DNA methylation.

Spinal cord injury (SCI) is a serious central nervous system disease. Traumatic SCI often causes persistent neurological deficits below the injury level. Epigenetic changes occur after SCI. Studies have shown DNA methylation to be a key player in nerve regeneration and remodeling, and in regulating some pathophysiological characteristics of SCI. Curcumin is a natural polyphenol from turmeric. It has anti-inflammatory, antioxidant, and neuroprotective effects, and can mitigate the cell and tissue damage caused by SCI. This report analyzed the specific functions of DNA methylation in central nervous system diseases, especially traumatic brain injury and SCI. DNA methylation can regulate the level of gene expressions in the central nervous system. Therefore, pharmacological interventions regulating DNA methylation may be promising for SCI.

Primary neuroendocrine carcinoma of the breast with markedly elevated alpha-fetoprotein: a case report.

Primary neuroendocrine carcinoma of the breast (PNECB) is a relatively rare subtype of breast cancer that has seldom been studied since its initial description. At present, the pathogenesis of the disease remains unknown, and there exit no specific clinical guidelines or specifications for its diagnosis and treatment. In addition, alpha-fetoprotein (AFP)-despite being a tumor marker-plays a small role in the diagnosis of breast cancer. Here, we explain the diagnosis and treatment of primary neuroendocrine (NE) breast carcinoma in a patient with a markedly elevated level of AFP. A 52-year-old woman visited our hospital, reporting she had palpated a nodule in her left breast 1 day before admission. After ultrasonographic detection of the hypoechoic lesion in her left breast-which was classified according to the Breast Imaging Reporting and Data System (BI-RADS) as grade 4C-and the abnormal enlargement of her left axillary lymph nodes, the patient was referred to our department as a case of malignant breast tumor. Meanwhile, the level of the tumor marker AFP was found to be over 1,210 ng/mL (0-7 ng/mL). And the patient had no past medical history of increased AFP, abnormal liver function, or gastrointestinal tumor. Analysis of the surgical specimens obtained from the left breast showed grade II invasive ductal carcinoma with NE differentiation. After discussion with a multidisciplinary team (MDT), according to the results of pathological and immunohistochemical examinations, the patient was diagnosed with PNECB. Due to axillary lymph node metastasis, she received combined chemotherapy with cyclophosphamide, epirubicin, and paclitaxel on postoperative day 13. Up to now, six cycles of chemotherapy have been successfully administered, with no evidence of adverse reactions. AFP levels were all above 1,210 ng/mL during chemotherapy. At the time of submission, the patient has been followed up for 10 months and there has been axillary lymph node metastasis, but no tumors in other parts have been found. Therefore, we think that the increase in AFP levels is related to the occurrence and poor prognosis of PNECB.

Association of STMN1 with survival in solid tumors: A systematic review and meta-analysis.

BACKGROUND: The prognostic value of Stathmin 1 (STMN1) in malignant solid tumors remains controversial. Thus, we conducted this meta-analysis to summarize the potential value of STMN1 as a biomarker for predicting overall survival in patients with solid tumor. METHODS: We systematically searched eligible studies in PubMed, Web of Science, and EMBASE from the establishment date of these databases to September 2018. Hazard ratio (HR) and its 95% confidence interval (CI) was used to assess the association between STMN1 expression and overall survival. RESULTS: A total of 25 studies with 4625 patients were included in this meta-analysis. Our combined results showed that high STMN1 expression was associated with poor overall survival in solid tumors (HR = 1.85, 95% CI 1.55, 2.21). In general, our subgroup and sensitivity analyses demonstrated that our combined results were stable and reliable. However, from the results of the subgroups we found that high STMN1 expression was not related to overall survival in colorectal cancer and endometrial cancer anymore, suggesting that much caution should be taken to interpret our combined result, and more studies with large sample sizes are required to further explore the prognostic value of STMN1 expression in the specific type of tumors, especially colorectal cancer and endometrial cancer. CONCLUSIONS: STMN1 could serve as a prognostic biomarker and could be developed as a valuable therapeutic target for patients with solid tumors. However, due to the limitations of the present meta-analysis, this conclusion should be taken with caution. Further studies adequately designed are required to confirm our findings.

Prognostic significance of NEK2 in human solid tumors: a systematic review and meta-analysis.

A consensus about the prognostic role of NIMA-related kinase 2 (NEK2) expression in various solid tumors has not been made yet. Thus, this meta-analysis aimed to systematically assess the prognostic role of NEK2 expression in patients with solid tumors. The eligible studies were identified through searching PubMed, Web of Science, and EMBASE. The hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were used to evaluate the link between NEK2 overexpression and overall survival (OS) and disease-free survival/recurrence-free survival (DFS/RFS) of patients with solid tumors. A total of 17 studies with 4897 patients were included in this meta-analysis. Among these studies, all of them explored the association between NEK2 expression and OS of patients with solid tumors. Our pooled analysis indicated that NEK2 overexpression was significantly related to adverse OS (HR = 1.66; 95% CI: 1.38-2.00; P = 0.001). Additionally, there were six studies with 854 patients that investigated the association between NEK2 expression and DFS/RFS. Our pooled result indicated that there was a substantial relationship between NEK2 overexpression and poorer DFS/RFS (HR = 2.00; 95% CI: 1.61-2.48; P = 0.003). In conclusion, our meta-analysis indicated that NEK2 may be a useful predictor of prognosis and an effective therapeutic target in solid tumors. Nevertheless, more high-quality studies are warranted to further support our conclusions because of several limitations in our meta-analysis.

RETRACTED: Preoperative chlorhexidine versus povidone-iodine antisepsis for preventing surgical site infection: A meta-analysis and trial sequential analysis of randomized controlled trials.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor of the Journal. The retraction has been made because the Editor has been informed that a similar article containing the same research was submitted to another journal by other authors. The authors have admitted errors in drafting and submitting the paper and apologise for the mistakes.

Mesh reinforcement for the prevention of incisional hernia formation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: European Hernia Society guidelines suggested that the evidence of mesh augmentation for the prevention of incisional hernia (IH) was weak. In addition, previous systematic reviews seldom focused on quality of life and cost-effectiveness related to mesh placement. Therefore, an updated meta-analysis was performed to clarify quality of life, cost-effectiveness, the safety, and effectiveness of mesh reinforcement in preventing the incidence of IH. METHODS: Embase, Pubmed, and the Cochrane library were searched from the inception to May 2016 without language limitation for randomized controlled trials (RCTs) which explored mesh reinforcement for the prevention of IH in patients undergoing abdominal surgeries. RESULTS: Twelve RCTs totaling 1661 patients (958 in mesh, 703 in nonmesh) were included in our study. Compared with nonmesh, mesh reinforcement can effectively decrease the incidence of IH (relative risk: 0.19; 95% CI: 0.09-0.42). Besides, mesh placement was associated with improved quality of life, a higher rate of seroma (relative risk: 1.64; 95% CI: 1.13-2.37), and longer operating time (mean difference: 17.62; 95% CI: 1.44-33.80). No difference can be found between both groups in postoperative overall morbidity, systemic postoperative morbidity, wound-related morbidity, surgical site infection, hematoma, wound disruption, postoperative mortality, and length of hospital stay. CONCLUSIONS: Prophylactic mesh reinforcement may be effective and safe to prevent the formation of IH after abdominal surgery, without impairing quality of life. Thus, preventive mesh should be routinely recommended in high-risk patients.

Glucagon like peptide-1 attenuates bleomycin-induced pulmonary fibrosis, involving the inactivation of NF-κB in mice.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high mortality and poor prognosis. Previous studies confirmed that NF-κB plays a critical role in the pathogenesis of pulmonary fibrosis and glucagon like peptide-1 (GLP-1) has a property of anti-inflammation by inactivation of NF-κB. Furthermore, the GLP-1 receptor was detected in the lung tissues. Our aim was to investigate the potential value and mechanisms of GLP-1 on BLM-induced pulmonary fibrosis in mice. Mice with BLM-induced pulmonary fibrosis were treated with or without GLP-1 administration. 28 days after BLM infusion, the number of total cells, macrophages, neutrophils, lymphocytes, and the content of TGF-ß1 in BALF were measured. Hematoxylin-eosin (HE) staining and Masson's trichrome (MT) staining were performed. The Ashcroft score and hydroxyproline content were analyzed. RT-qPCR and western blot were used to evaluate the expression of α-SMA and VCAM-1. The phosphorylation of NF-κB p65 was also assessed by western blot. DNA binding of NF-κB p65 was measured through Trans(AM) p65 transcription factor ELISA kit. GLP-1 reduced inflammatory cell infiltration and the content of TGF-ß1 in BLAF in mice with BLM injection. The Ashcroft score and hydroxyproline content were decreased by GLP-1 administration. Meanwhile, BLM-induced overexpression of α-SMA and VCAM-1 were blocked by GLP-1 treatment in mice. GLP-1 also reduced the ratio of phosphor-NF-κB p65/total-NF-κB p65 and NF-κB p65 DNA binding activity in BLM-induced pulmonary fibrosis in mice. Our data found that BLM-induced lung inflammation and pulmonary fibrosis were significantly alleviated by GLP-1 treatment in mice, possibly through inactivation of NF-κB.

Cytochrome P450 2A13 mediates the neoplastic transformation of human bronchial epithelial cells at a low concentration of aflatoxin B1.

Cytochrome P450 2A13 (CYP2A13), mainly expressed in human respiratory tract, is highly efficient in the metabolic activation of aflatoxin (AF) B1 (AFB1) and is assumed to play a role in human lung tumorigenesis in airborne AFB1 exposure. To validate the assumption, we exposed human bronchial epithelial (BEAS-2B) cells stably expressing CYP2A13 (B-2A13), CYP1A2 (B-1A2) and CYP2A6 (B-2A6) to 0.1-10 nM AFB1 for 30-50 passages. B-2A13 cells showed increased sensitivity to 0.1 nM AFB1-induced neoplastic transformation and the formation of tumors in nude mice were observed at passage 30 (P30) while it occurred at P50 B-1A2 cells. B-2A6, similar to vector control, showed no neoplastic transformation in this condition. Additionally, AFB1-DNA adducts and 8-OHdG significantly increased in transformed P40 B-2A13, in parallel with the upregulation of p-ATR, p-BRCA1, Mre11, Rad50 and Rad51. However, the apoptosis of P40 cells was near normal, while the expression of Bax, C-Caspase 3 and C-PARP increased passage-dependently. Inhibition of ATR (ATR siRNA or NU6027) reversely increased the apoptosis of P40 B-2A13 cells in parallel with the upregulation of Bax, C-Caspase 3 and C-PARP, suggesting that ATR plays an important role in maintaining cell survival via antiapoptosis. Additionally, activation of ATR was necessary to neoplastic transformation since blockage of ATR in P40 cells inhibited DNA damage repair response and anchorage-independent growth. Our data demonstrated that CYP2A13 played a critical role in AFB1-induced neoplastic transformation. ATR-mediated the dysfunction of apoptosis and DNA damage repair might be involved. These results help establish a linkage between airborne AFB1 and human respiratory carcinoma.

Cytochrome P450 2A13 is an efficient enzyme in metabolic activation of aflatoxin G1 in human bronchial epithelial cells.

Cytochrome P450 2A13 (CYP2A13) is an extrahepatic enzyme that mainly expresses in human respiratory system, and it is reported to mediate the metabolic activation of aflatoxin B1. Due to the structural similarity, AFG1 is predicted to be metabolized by CYP2A13. However, the role of CYP2A13 in metabolic activation of AFG1 is unclear. In present study, human bronchial epithelial cells that stably express CYP2A13 (B-2A13) were used to conduct the effects of AFG1 on cytotoxicity, apoptosis, DNA damages, and their response protein expression. Low concentrations of AFG1 induced significant cytotoxicity and apoptosis, which was consistent with the increased expressions of pro-apoptotic proteins, such as C-PARP and C-caspase-3. In addition, AFG1 increased 8-OHdG and γH2AX in the nuclies and induced S phase arrest and DNA damage in B-2A13 cells, and the proteins related to DNA damage responses, such as ATM, ATR, Chk2, p53, BRCA1, and γH2AX, were activated. All the above effects were inhibited by nicotine (a substrate of CYP2A13) or 8-MOP (an inhibitor of CYP enzymes), confirming that CYP2A13 mediated the AFG1-induced cytotoxicity and DNA damages. Collectively, our findings first demonstrate that CYP2A13 might be an efficient enzyme in metabolic activation of AFG1 and helps provide a new insight into adverse effects of AFG1 in human respiratory system.

Mechanism of BDE209-induced impaired glucose homeostasis based on gene microarray analysis of adult rat liver.

Several persistent organic pollutants are reported to be potentially associated with the risk of human diabetes that has become rapidly epidemic in China currently. 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE209) is commercially most important both in the production and in the use of polybrominated diphenyl ethers (PBDEs). It might bioaccumulate in wildlife and human and is the only PBDEs mixture still used today. In the present study, male adult rats treated with BDE209 (0, 0.05, 1, and 20 mg/kg) for 8 weeks were used to explore the effects of BDE209 on glucose homeostasis and possible mechanisms; 0.05 mg/kg of BDE209 induced dose-related hyperglycemia. Then, we performed the full-genome gene expression microarrays, gene ontology analysis, and pathway analysis in this group and control. BDE209 induced 1,257 liver gene transcript changes, and 18 canonical pathways were significantly enriched. Four of them were involved in immune diseases, including autoimmune thyroid disease, graft-versus-host disease, allograft rejection, and type I diabetes mellitus (T1MD), which was confirmed by the decrease in serum insulin. Subsequently, gene act network and gene co-expression network found that some MHC molecules and TNF-α were involved in T1DM pathway, which was then confirmed by the increase in serum TNF-α. Additionally, reduced glutathione and superoxide dismutase in plasma indicated that oxidative damage might partly contribute to BDE209-induced hyperglycemia. The results of this study provide some new experimental evidence that the exposure to high levels of BDE209 may contribute to the onset of diabetes in human populations. Further work needs to be done to confirm this link.

Cytochrome P450 2A13 enhances the sensitivity of human bronchial epithelial cells to aflatoxin B1-induced DNA damage.

Cytochrome P450 2A13 (CYP2A13) mainly expresses in human respiratory system and mediates the metabolic activation of aflatoxin B1 (AFB1). Our previous study suggested that CYP2A13 could increase the cytotoxic and apoptotic effects of AFB1 in immortalized human bronchial epithelial cells (BEAS-2B). However, the role of CYP2A13 in AFB1-induced DNA damage is unclear. Using BEAS-2B cells that stably express CYP2A13 (B-2A13), CYP1A2 (B-1A2), and CYP2A6 (B-2A6), we compared their effects in AFB1-induced DNA adducts, DNA damage, and cell cycle changes. BEAS-2B cells that were transfected with vector (B-vector) were used as a control. The results showed that AFB1 (5-80 nM) dose- and time-dependently induced DNA damage in B-2A13 cells. AFB1 at 10 and 80nM significantly augmented this effect in B-2A13 and B-1A2 cells, respectively. B-2A6 cells showed no obvious DNA damage, similar to B-vector cells and the vehicle control. Similarly, compared with B-vector, B-1A2 or B-2A6 cells, B-2A13 cells showed more sensitivity in AFB1-induced γH2AX expression, DNA adduct 8-hydroxy-deoxyguanosine formation, and S-phase cell-cycle arrest. Furthermore, AFB1 activated the proteins related to DNA damage responses, such as ATM, ATR, Chk2, p53, BRCA1, and H2AX, rather than the proteins related to DNA repair. These effects could be almost completely inhibited by 100 µM nicotine (a substrate of CYP2A13) or 1 µM 8-methoxypsoralen (8-MOP; an inhibitor of CYP enzyme). Collectively, these findings suggest that CYP2A13 plays an important role in low-concentration AFB1-induced DNA damage, possibly linking environmental airborne AFB1 to genetic injury in human respiratory system.

[Construction and expression characterization of transgenic chicken bioreactor vector].

We constructed transgenic chicken bioreactor vector, driven by chicken ovalbumin promoter, lentiviral vector and cytomegalovirus (CMV) promoter control vector encoding green fluorescent protein (GFP) and luciferase (Luc) as reporter genes. The three vectors were used to transfect or infect chicken primary oviduct epithelial cells, embryo fibroblasts cells, mouse 3T3-L1 preadipocytes cells and bovine mammary epithelial cells. High efficient and specific expression vector for transgenic chicken bioreactor was determined by detecting fluorescence and luciferase activity. Reporter gene analysis showed that chicken ovalbumin promoter expression vector was not cell type-specific in these four different cells. Additionally, luciferase reporter analysis illustrated that the chicken ovalbumin promoter activity was over 100 times lower than that of the CMV promoter in four different cells. Both of these two reporter genes were expressed in those four different cells infected by lentiviral expression vectors. Similarly, the GFP reached the similar expression level in cells infected by lentivirus and cells transfected with CMV promoter plasmid vectors when the multiplicity of infection was 20. In conclusion, the transgenic chicken bioreactor vector under the control of chicken ovalbumin promoter was not highly efficient and cell type-specific. However, the efficient expression and extensiveness oflentiviral vector could be used for studying chicken oviduct bioreactor.