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https://www.readbyqxmd.com/read/29045898/peptidoglycan-sensing-receptors-trigger-the-formation-of-functional-amyloids-of-the-adaptor-protein-imd-to-initiate-drosophila-nf-%C3%AE%C2%BAb-signaling
#1
Anni Kleino, Nancy F Ramia, Gunes Bozkurt, Yanfang Shen, Himani Nailwal, Jing Huang, Johanna Napetschnig, Monique Gangloff, Francis Ka-Ming Chan, Hao Wu, Jixi Li, Neal Silverman
In the Drosophila immune response, bacterial derived diaminopimelic acid-type peptidoglycan binds the receptors PGRP-LC and PGRP-LE, which through interaction with the adaptor protein Imd leads to activation of the NF-κB homolog Relish and robust antimicrobial peptide gene expression. PGRP-LC, PGRP-LE, and Imd each contain a motif with some resemblance to the RIP Homotypic Interaction Motif (RHIM), a domain found in mammalian RIPK proteins forming functional amyloids during necroptosis. Here we found that despite sequence divergence, these Drosophila cryptic RHIMs formed amyloid fibrils in vitro and in cells...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045658/exendin-4-a-glucagon-like-peptide-1-receptor-agonist-attenuates-breast-cancer-growth-by-inhibiting-nf-%C3%AE%C2%BAb-activation
#2
Chikayo Iwaya, Takashi Nomiyama, Shiho Komatsu, Takako Kawanami, Yoko Tsutsumi, Yuriko Hamaguchi, Tsuyoshi Horikawa, Yasuteru Yoshinaga, Shinichi Yamashita, Tomoko Tanaka, Yuichi Terawaki, Makito Tanabe, Kazuki Nabeshima, Akinori Iwasaki, Toshihiko Yanase
Incretin therapies have received significant attention because of their tissue-protective effects, which extend beyond those associated with glycemic control. Cancer is a primary cause of death in patients with diabetes mellitus. We previously reported anti-prostate cancer effects of the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonist exendin-4 (Ex-4). Breast cancer is one of the most common cancers in female patients with type 2 diabetes mellitus and obesity. Thus, we examined whether GLP-1 action could attenuate breast cancer...
October 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/29045271/rhabdomyosarcoma-cells-are-susceptible-to-cell-death-by-ldk378-alone-or-in-combination-with-sorafenib-independently-of-anaplastic-lymphoma-kinase-status
#3
Nadezda Dolgikh, Simone Fulda
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is often overexpressed in rhabdomyosarcoma (RMS). However, its oncogenic and functional role in RMS remains unclear. Therefore, we investigated the antitumor activity of LDK378 (ceritinib), a new second-generation ALK inhibitor approved for patients with ALK-positive non-small-cell lung cancers. Here, we report that LDK378 reduces cell viability and induces cell death in RMS cell lines at low micromolar IC50 concentrations irrespective of ALK expression levels or phosphorylation status...
November 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29045250/clinical-decision-making-for-immunotherapy-in-metastatic-renal-cell-carcinoma
#4
Manuela Schmidinger
PURPOSE OF REVIEW: To review the treatment options in metastatic renal cell carcinoma (mRCC) in the light of new immunotherapy results. RECENT FINDINGS: Second-line treatment strategies for treatment of mRCC after progression on first-line VEGF-targeted therapy have recently undergone a major change. Treatment guidelines currently recommend the use of either nivolumab, a programmed cell death 1 (PD-1) inhibitor, or cabozantinib, an inhibitor of multiple receptor tyrosine kinases, as preferred choices...
October 17, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/29044801/differential-physiological-responses-to-central-leptin-overexpression-in-male-and-female-rats
#5
Isabelle Côté, Sara M Green, Hale Z Toklu, Drake Morgan, Christy S Carter, Nihal Tümer, Philip J Scarpace
Brains of females are more sensitive to the acute catabolic actions of leptin. However, sex differences in the long-term physiological responses to central leptin receptor modulation are unknown. To this end, we centrally delivered a viral vector to overexpress leptin (Leptin), a neutral leptin receptor antagonist (Leptin-Antagonist), or a green fluorescence protein (Control). We examined chronic changes in body weight and composition in male and female rats. Females displayed greater and sustained responses to Leptin whereas males rapidly lost physiological effects and developed leptin resistance confirmed by lower acute leptin-mediated phosphorylation of STAT3 (P-STAT3)...
October 17, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29042976/anti-obesity-effect-of-robusta-fermented-with-leuconostoc-mesenteroides-in-high-fat-diet-induced-obese-mice
#6
Soo-Young Choi, Seung-Hyun Ryu, Jin-Il Park, Eui-Suk Jeong, Jong-Hyung Park, Seung-Hoon Ham, Hee-Yeon Jeon, Jun-Young Kim, Inn-Goo Kyeong, Dong-Goo Kim, Ji-Young Shin, Yang-Kyu Choi
Robusta beans cultivated with Monascus ruber (RMR) were successively fermented with Leuconostoc mesenteroides (LM) and the antiobesity effects were examined. To produce an obese mouse model to investigate the hypolipidemic effects, ICR mice were fed the same high-fat diet for 6 weeks. Treatment groups were given 10 or 20% RMR-LM. Body weight changes in the 20% RMR-LM group were lower compared with those in the control group. Visceral adipose tissue weight and adipose size were significantly lower in the 20% RMR-LM group compared with those in the control group...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29042674/knockout-of-maternal-cd163-protects-fetuses-from-infection-with-porcine-reproductive-and-respiratory-syndrome-virus-prrsv
#7
Randall S Prather, Kevin D Wells, Kristin M Whitworth, Maureen A Kerrigan, Melissa S Samuel, Alan Mileham, Luca N Popescu, Raymond R R Rowland
After infection of the porcine dam at about 90 days of gestation, porcine reproductive and respiratory syndrome virus (PRRSV) crosses the placenta and begins to infect fetuses. Outcomes of include abortion, fetal death and respiratory disease in newborn piglets. CD163 is the receptor for the virus. In this study, CD163-positive fetuses, recovered between 109 days of gestation or 20 days after maternal infection, were completely protected from PRRSV in dams possessing a complete knockout of the CD163 receptor...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042317/fentanyl-fentanyl-analogs-and-novel-synthetic-opioids-a-comprehensive-review
#8
REVIEW
Patil Armenian, Kathy T Vo, Jill Barr-Walker, Kara L Lynch
Deaths from opioid use are increasing in the US, with a growing proportion due to synthetic opioids. Until 2013, sporadic outbreaks of fentanyl and fentanyl analogs contaminating the heroin supply caused some deaths in heroin users. Since then, fentanyl has caused deaths in every state and fentanyl and its analogs have completely infiltrated the North American heroin supply. In 2014, the first illicit pills containing fentanyl, fentanyl analogs, and other novel synthetic opioids such as U-47700 were detected...
October 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29041905/clinicopathological-and-prognostic-significance-of-programmed-death-ligand-1-expression-in-breast-cancer-a-meta-analysis
#9
Hye Min Kim, Jinae Lee, Ja Seung Koo
BACKGROUND: Programmed cell death-ligand 1 (PD-L1) may be a useful molecule for targeted immunotherapy. Therefore, this meta-analysis aimed to investigate PD-L1 expression in breast cancer and its associations with clinicopathological factors and outcomes, which may help determine whether PD-L1 expression is a useful prognostic marker. METHODS: The Medline Ovid, Cochrane, PubMed, Google Scholar, and Web of Knowledge databases were searched for studies that evaluated the prognostic or clinicopathological significance of PD-L1 expression in patients with breast cancer, and reported at least one survival-related outcome...
October 17, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29040664/coumestrol-induces-mitochondrial-dysfunction-by-stimulating-ros-production-and-calcium-ion-influx-into-mitochondria-in-human-placental-choriocarcinoma-cells
#10
Whasun Lim, Changwon Yang, Muhah Jeong, Fuller W Bazer, Gwonhwa Song
STUDY QUESTION: Does coumestrol inhibit proliferation of human placental choriocarcinoma cells? SUMMARY ANSWER: Coumestrol promotes cell death in the choriocarcinoma cells by regulating ERK1/2 MAPK and JNK MAPK signaling pathways and through disruption of Ca2+ and ROS homeostasis. WHAT IS KNOWN ALREADY: A number of patients who suffer from choriocarcinomas fail to survive due to delayed diagnosis or a recurrent tumor and resistance to traditional chemotherapy using platinum-based agents and methotrexate...
October 11, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29039549/downregulation-of-caspase%C3%A2-3-alleviates-mycoplasma%C3%A2-pneumoniae%C3%A2-induced-apoptosis-in-alveolar-epithelial-cells
#11
Shan Shi, Xiaolei Liu, Haibo Li
Mycoplasma pneumoniae (M. pneumoniae) infection is closely associated with pneumonia in children. Apoptosis of alveolar epithelial cells is involved in the development of pneumonia in children. The present study aimed to examine how caspase‑3 influences apoptosis rates in M. pneumoniae‑infected alveolar epithelial cells. A549 alveolar epithelial cells were treated with M. pneumoniae, and cells and culture supernatant were collected at different time points. Alterations in apoptosis rates and caspase‑3 mRNA and protein levels were measured for each treatment group...
October 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29039543/oxidized-low-density-lipoprotein-facilitates-tumor-necrosis-factor%C3%A2-%C3%AE-mediated-chondrocyte-death-via-autophagy-pathway
#12
Pengcheng Shen, Yu Zhu, Lifan Zhu, Fengbiao Weng, Xiaolin Li, Yaozeng Xu
We aimed to investigate the role of oxidized low density lipoprotein (ox‑LDL) in tumor necrosis factor‑α (TNF‑α) mediated chondrocyte death and explore the mechanisms. Ten osteoarthritis (OA) and normal control cartilage tissue and synovial fluid (SF) samples were collected, and the expression of lectin‑like ox‑LDL receptor‑1 (LOX‑1) and ox‑LDL level was examined by real time quantitative PCR and enzyme‑linked immunosorbent assay (ELISA). An in vitro chondrocyte model was established by the introduction of TNF‑α and ox‑LDL, cell death was analyzed by trypan blue assay and the mechanisms were explored based on the apoptosis related pathway and autophagy pathway...
October 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29039470/effects-of-baicalein-on-proliferation-apoptosis-migration-and-invasion-of-ewing-s-sarcoma-cells
#13
Conglin Ye, Xiaolong Yu, Jin Zeng, Min Dai, Bin Zhang
Ewing's sarcoma (ES) is a rare tumor that is more frequent in pediatric and adolescent age groups. In the past few decades, long-term survival in affected patients has improved due to the success of multimodal therapy. However, long-term survival is inevitably restricted by the late side-effects of chemotherapy. Besides, early metastasis also contributes to the poor prognosis of ES. Recently, traditional Chinese medicines (TCMs) have increasingly attracted interest due to the promising clinical results and fewer side-effects for the treatment of cancers...
October 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29039467/insulin-like-growth-factor-binding-protein-6-released-from-human-mesenchymal-stem-cells-confers-neuronal-protection-through-igf-1r-mediated-signaling
#14
Hyo-Jin Jeon, Jihye Park, Joo-Hyun Shin, Mi-Sook Chang
Human bone marrow‑derived mesenchymal stem cells (hMSCs) are a desirable cell source for cell‑based therapy to treat nervous system injuries due to their ability to differentiate into specific cell types. In addition to their multipotency, hMSCs render the tissue microenvironment more favorable for tissue repair by secreting various growth factors. Our previous study demonstrated that hMSCs secrete several growth factors, including several insulin‑like growth factor binding proteins (IGFBPs). Among these, IGFBP‑6 binds with high affinity and inhibits insulin growth factor‑2 (IGF‑2) to inhibit the growth of IGF‑2‑dependent tumors...
October 5, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29039120/differential-presentation-and-survival-of-de-novo-and-recurrent-metastatic-breast-cancer-over-time-1990-2010
#15
Judith A Malmgren, Musa Mayer, Mary K Atwood, Henry G Kaplan
BACKGROUND: Differences in de novo (dnMBC) and recurrent metastatic breast cancer (rMBC) presentation and survival over time have not been adequately described. METHODS: A retrospective cohort study, 1990-2010, with follow up through 2015 of dnMBC patients (stage IV at diagnosis) and rMBC patients with subsequent distant metastatic recurrence (stage I-III initial diagnosis) [dnMBC = 247, rMBC = 911)]. Analysis included Chi squared tests of categorical variables, Kaplan-Meier survival estimates, and Cox proportional adjusted hazard ratios (HzR) and 95% confidence intervals (CI)...
October 16, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29037482/a-low-angiogenic-index-1-plgf-svegfr-1-ratio-at-24-28-weeks-of-gestation-is-a-biomarker-to-identify-the-patient-at-risk-for-subsequent-fetal-death
#16
Tinnakorn Chaiworapongsa, Roberto Romero, Offer Erez, Adi L Tarca, Agustin Conde-Agudelo, Piya Chaemsaithong, Chong Jai Kim, Yeon Mee Kim, Jung-Sun Kim, Bo Hyun Yoon, Sonia S Hassan, Lami Yeo, Steven J Korzeniewski
OBJECTIVE: To determine if maternal plasma concentrations of angiogenic and anti-angiogenic factors measured at 24-28 weeks of gestation can predict subsequent fetal death. METHODS: A case-cohort study was designed to include 1000 randomly selected subjects and all remaining fetal deaths (cases) from a cohort of 4006 women with a singleton pregnancy, enrolled at 6-22 weeks of gestation, in a pregnancy biomarker cohort study. The placentas of all fetal deaths were histologically examined by pathologists who used a standardized protocol and were blinded to patient outcomes...
October 13, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29035645/factors-that-contributed-to-black-white-disparities-in-survival-among-nonelderly-women-with-breast-cancer-between-2004-and-2013
#17
Ahmedin Jemal, Anthony S Robbins, Chun Chieh Lin, W Dana Flanders, Carol E DeSantis, Elizabeth M Ward, Rachel A Freedman
Purpose To estimate the contribution of differences in demographics, comorbidity, insurance, tumor characteristics, and treatment to the overall mortality disparity between nonelderly black and white women diagnosed with early-stage breast cancer. Patients and Methods Excess relative risk of all-cause death in black versus white women diagnosed with stage I to III breast cancer, expressed as a percentage and stratified by hormone receptor status for each variable (demographics, comorbidity, insurance, tumor characteristics, and treatment) in sequentially, propensity-scored, optimally matched patients by using multivariable hazard ratios (HRs)...
October 16, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29034589/involvement-of-local-renin-angiotensin-system-in-immunosuppression-of-tumor-microenvironment
#18
Kenta Nakamura, Tomonori Yaguchi, Gaku Ohmura, Asuka Kobayashi, Naoshi Kawamura, Takashi Iwata, Yukiko Kiniwa, Ryuhei Okuyama, Yutaka Kawakami
To improve the current cancer immunotherapies, strategies to modulate various immunosuppressive cells including myeloid derived suppressor cells (MDSCs) which were shown to be negative factors in the immune-checkpoint blockade therapy, need to be developed. In this study, we have evaluated the role of local renin-angiotensin system (RAS) in the tumor immune-microenvironment using murine models bearing tumor cell lines in which RAS was not involved in their proliferation and angiogenetic ability. Administration of angiotensin II receptor blockers (ARBs) to C57BL/6 mice bearing murine colon cancer cell line MC38 resulted in significant enhancement of tumor antigen gp70 specific T cells...
October 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/29034214/pathogenic-cd8-t-cells-cause-increased-levels-of-vegf-a-in-experimental-malaria-associated-acute-respiratory-distress-syndrome-but-therapeutic-vegfr-inhibition-is-not-effective
#19
Thao-Thy Pham, Melissa Verheijen, Leen Vandermosten, Katrien Deroost, Sofie Knoops, Kathleen Van den Eynde, Louis Boon, Chris J Janse, Ghislain Opdenakker, Philippe E Van den Steen
Malaria is a severe disease and kills over 400,000 people each year. Malarial complications are the main cause of death and include cerebral malaria and malaria-associated acute respiratory distress syndrome (MA-ARDS). Despite antimalarial treatment, lethality rates of MA-ARDS are still between 20 and 80%. Patients develop pulmonary edema with hemorrhages and leukocyte extravasation in the lungs. The vascular endothelial growth factor-A (VEGF-A) and the placental growth factor (PlGF) are vascular permeability factors and may be involved in the disruption of the alveolar-capillary membrane, leading to alveolar edema...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29033963/convergent-evolution-of-pathogen-effectors-toward-reactive-oxygen-species-signaling-networks-in-plants
#20
REVIEW
Nam-Soo Jwa, Byung Kook Hwang
Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants...
2017: Frontiers in Plant Science
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