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Drew Ellegaard posted an update 1 week ago
Copyright 2020 The Author(s).The lymph node metastasis of colorectal cancer (LMN-CRC) seriously threatens the prognosis of patients. Chemotherapy, as the most common treatment, results in severe bone marrow suppression. 20(S)-ginsenoside Rh2 (SGRh2), a major effective constituent of ginseng, has demonstrated therapeutic effects on a variety of diseases, including some tumours. SGRh2 treatment had no effect on other organs. Therefore, ginsenosides are considered a safe and effective antineoplastic drug. However, the effects of SGRh2 on LMN-CRC remain unknown. The current study investigated the potential effect of SGRh2 on LMN-CRC in vitro and in vivo. SW480 and CoLo205 cell lines were treated with SGRh2. SGRh2 dose-dependently decreased CRC cell proliferation by CCK-8, colony formation and Edu assays. The Transwell and scratch assays revealed that SGRh2 inhibits the migratory and invasive abilities of CRC cells in a dose-dependent manner. Furthermore, the results of western blotting revealed that SGRh2 decreased the expression of matrix metalloproteinase (MMP)-2 and MMP9. In terms of the underlying mechanisms, SGRh2 regulates CRC metastasis by affecting epithelial-mesenchymal transition (EMT), which significantly upregulated epithelial biomarkers (E-cadherin) and downregulated mesenchymal biomarkers (N-cadherin and vimentin) and EMT transcriptional factors (Smad-3, Snail-1, and Twist-1). SCR7 chemical structure In vivo, SGRh2 significantly inhibited LMN-CRC without affecting other normal organs. Immunohistochemical results showed that SGRh2 treats LMN-CRC by regulating EMT. These results demonstrate that SGRh2 has therapeutic potential for LMN-CRC. Copyright 2020 The Author(s).Bacterial heme nitric oxide/oxygen (H-NOX) domains are nitric oxide (NO) or oxygen sensors. This activity is mediated through binding of the ligand to a heme cofactor. However, H-NOX from Vibrio cholerae (Vc H-NOX) can be easily purified in a heme-free state that is capable of reversibly responding to oxidation, suggesting a heme-independent function as a redox sensor. This occurs by oxidation of Cys residues at a zinc-binding site conserved in a subset of H-NOX homologs. Remarkably, zinc is not lost from the protein upon oxidation, although its ligation environment is significantly altered. Using a combination of computational and experimental approaches, we have characterized localized structural changes that accompany the formation of specific disulfide bonds between Cys residues upon oxidation. Furthermore, the larger-scale structural changes accompanying oxidation appear to mimic those changes observed upon NO binding to the heme-bound form. Thus, Vc H-NOX and its homologs may act as both redox and NO sensors by completely separate mechanisms. © 2020 The Author(s).BACKGROUND Data on safety and efficacy of second-line tuberculosis drugs in pregnant women and their infants are severely limited due to exclusion from clinical trials and expanded access programmes. METHODS Pregnant women starting treatment for multidrug/rifampicin-resistant (MDR/RR)-tuberculosis at King Dinuzulu Hospital in KwaZulu-Natal, South Africa from 1 January 2013 – 31 December 2017 were included. We conducted a record review to describe maternal treatment and pregnancy outcomes, and a clinical assessment to describe infant outcomes. RESULTS Of 108 pregnant women treated for MDR/RR-tuberculosis, 88 (81%) were HIV-infected. Favourable MDR/RR-tuberculosis treatment outcomes were reported in 72 (67%) women. Ninety-nine (91%) of the 109 babies were born alive but, overall, 52 (48%) women had unfavourable pregnancy outcomes. Fifty-eight (54%) women received bedaquiline and 49 (45%) babies were exposed to bedaquiline in utero. Low birthweight was reported in more babies exposed to bedaquiline compared to babies not exposed (45% vs 26%; p=0.034). In multivariate analyses, bedaquiline and levofloxacin, drugs often used in combination, were both independently associated with increased risk of low birthweight. Of the 86 children evaluated at 12 months, 72 (84%) had favourable outcomes; 88% of babies exposed to bedaquiline were thriving and developing normally compared to 82% of the babies not exposed. CONCLUSIONS MDR/RR-tuberculosis treatment outcomes among pregnant women were comparable to non-pregnant adults. Although more babies exposed to bedaquiline were of low birthweight, over 80% had gained weight and were developing normally at one year. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.Breast cancer is one of the most human malignant diseases and the leading cause of cancer-related death in the world. However, the prognostic and therapeutic benefits of breast cancer patients cannot be predicted accurately by the current stratifying system. In this study, an immune-related prognostic score was established in 22 breast cancer cohorts with a total of 6415 samples. An extensive immunogenomic analysis was conducted to explore the relationships between immune score, prognostic significance, infiltrating immune cells, cancer genotypes and potential immune escape mechanisms. Our analysis revealed that this immune score was a promising biomarker for estimating overall survival in breast cancer. This immune score was associated with important immunophenotypic factors, such as immune escape and mutation load. Further analysis revealed that patients with high immune scores exhibited therapeutic benefits from chemotherapy and immunotherapy. Based on these results, we can conclude that this immune score may be a useful tool for overall survival prediction and treatment guidance for patients with breast cancer. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.n-3 polyunsaturated fatty acids (PUFAs) express anti-inflammatory properties and prevent tumor progression. Conversely, n-6 PUFAs exhibit carcinogenic properties. Recent epidemiologic studies have examined the association of fish with upper gastrointestinal cancer risk, but the associations with n-3 and n-6 PUFA subtypes remain unclear. Utilizing the NIH-AARP Diet and Health Study (1995-2011), we prospectively investigated the associations of PUFA subtypes, ratios, and fish with the incidence of head and neck (HNC, n=2,453), esophageal (n=855 adenocarcinoma, EA, and n=267 squamous cell carcinoma, ESCC), and gastric (n=603 cardia, GCA, and n=631 non-cardia, NCGA) cancers among 468,952 participants (median follow-up 15.5 years). A food frequency questionnaire assessed diet. Multivariable-adjusted HRs and 95% CIs were estimated using Cox proportional hazards regression. A Benjamini-Hochberg (BH) procedure was used for false-discovery control. Long-chain n-3 PUFAs were associated with a 20% decreased HNC and EA risk (quintile5vs.