Search results for "SIG"
showing 10 items of 19670 documents
Bone regeneration in the stem cell era: safe play for the patient?
2017
The past decade has seen outstanding scientific progress in the field of stem cell (SC) research and clinical application. SCs are convenient both technically and biologically: they are easy to find and to culture and they can differentiate in virtually all tissues and even in whole organs. Induced pluripotent stem cells (iPSs) are a type of pluripotent SC generated in vitro directly from mature cells through the introduction of key transcription factors. The use of iPSs, however tantalizing, poses serious safety concerns because of their genomic instability. Recently, it has been suggested that the main mechanism of SC action relies on paracrine signals. Therefore, the secretome would be p…
Models for preterm cortical development using non invasive clinical EEG
2017
AbstractThe objective of this study was to evaluate the piglet and the mouse as model systems for preterm cortical development. According to the clinical context, we used non invasive EEG recordings. As a prerequisite, we developed miniaturized Ag/AgCl electrodes for full band EEG recordings in mice and verified that Urethane had no effect on EEG band power. Since mice are born with a “preterm” brain, we evaluated three age groups: P0/P1, P3/P4 and P13/P14. Our aim was to identify EEG patterns in the somatosensory cortex which are distinguishable between developmental stages and represent a physiologic brain development. In mice, we were able to find clear differences between age groups wit…
Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology.
2018
Abstract Introduction Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. Adaptogens stimulate cellular and organismal defense systems by activating intracellular and extracellular signaling pathways and expression of stress-activated proteins and neuropeptides. The effects adaptogens on mediators of adaptive stress response and longevity signaling pathways have been reported, but their stress-protective mechanisms are still not fully understood. Aim of the study The aim of this study was to identify key molecular mechanisms of adaptogenic plants traditionally used to treat stress and aging-related disorders, i.e., Rhodiola r…
Critical Roles of EGFR family members in breast cancer and breast cancer stem cells: Targets for therapy
2016
The roles of the epidermal growth factor receptor (EGFR) signaling pathway in various cancers including breast, bladder, brain, colorectal, esophageal, gastric, head and neck, hepatocellular, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and other cancers have been keenly investigated since the 1980's. While the receptors and many downstream signaling molecules have been identified and characterized, there is still much to learn about this pathway and how its deregulation can lead to cancer and how it may be differentially regulated in various cell types. Multiple inhibitors to EGFR family members have been developed and many are in clinical use. Current research often focuses o…
Intervention of Inflammatory Monocyte Activity Limits Dermal Fibrosis
2019
Monocytes and monocyte-derived cells are important players in the initiation, progression, and resolution of inflammatory skin reactions. As inflammation is a prerequisite for fibrosis development, we focused on the role of monocytes in cutaneous fibrosis, the clinical hallmark of patients suffering from systemic sclerosis. Investigating the function of monocytes in reactive oxygen species–induced dermal fibrosis, we observed that early monocyte depletion partially reduced disease severity. Low numbers of inflammatory Ly6Chigh monocytes, as well as inhibition of CCR2 and CCL2 in wild type animals by a specific L-RNA aptamer, mitigated disease parameters, indicating a pivotal role for CCR2+ …
A cross-talk between fat and bitter taste modalities
2019
International audience; The choice of food is governed largely by the sense of taste. To date, five basic taste modalities have been described; however, there is an increasing agreement on the existence of a 6th fat taste. The taste modalities might interact with each other and also with other senses. The advancements in cellular and molecular biology have helped the characterization of taste signaling mechanisms, down to the receptor level and beyond. CD36 and GPR120 have been shown to be involved in the detection of fat taste while bitter taste is perceived by a number of receptors that belong to a family of taste-type 2 receptors (T2R or TAS2R). Hence, the most common role is played by T…
Activation of silent mating type information regulation 2 homolog 1 by human chorionic gonadotropin exerts a therapeutic effect on hepatic injury and…
2017
Incidence and prevalence of inflammatory liver diseases has increased over the last years, but therapeutic options are limited. Pregnancy induces a state of immune tolerance, which can result in spontaneous improvement of clinical symptoms of certain autoimmune diseases including autoimmune hepatitis (AIH). We investigated the immune-suppressive mechanisms of the human pregnancy hormone, chorionic gonadotropin (hCG), in the liver. hCG signaling activates silent mating type information regulation 2 homolog 1 (SIRT1), which deacetylates forkhead box o3 (FOXO3a), leading to repression of proapoptotic gene expression, because the immunosuppressive consequence attributed to the absence of caspas…
Extracellular vesicles as a novel source of biomarkers in liquid biopsies for monitoring cancer progression and drug resistance
2019
Cancer-derived extracellular vesicles (EVs) have been detected in the bloodstream and other biofluids of cancer patients. They carry various tumor-derived molecules such as mutated DNA and RNA fragments, oncoproteins as well as miRNA and protein signatures associated with various phenotypes. The molecular cargo of EVs partially reflects the intracellular status of their cellular origin, however various sorting mechanisms lead to the enrichment or depletion of EVs in specific nucleic acids, proteins or lipids. It is becoming increasingly clear that cancer-derived EVs act in a paracrine and systemic manner to promote cancer progression by transferring aggressive phenotypic traits and drug-res…
IL4 Primes the Dynamics of Breast Cancer Progression via DUSP4 Inhibition
2017
Abstract The tumor microenvironment supplies proinflammatory cytokines favoring a permissive milieu for cancer cell growth and invasive behavior. Here we show how breast cancer progression is facilitated by IL4 secreted by adipose tissue and estrogen receptor–positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL4 signaling with the IL4Rα antagonist IL4DM compromised breast cancer cell proliferation, invasion, and tumor growth by downregulating MAPK pathway activity. IL4DM reduced numbers of CD44+/CD24− cancer stem-like cells and elevated expression of the dual specificity phosphatase DUSP4 by inhibiting NF-κB. Enforced expression of DUSP4 drove conversio…
Down-Regulation of Cannabinoid Type 1 (CB1) Receptor and its Downstream Signaling Pathways in Metastatic Colorectal Cancer
2019
Changes in the regulation of endocannabinoid production, together with an altered expression of their receptors are hallmarks of cancer, including colorectal cancer (CRC). Although several studies have been conducted to understand the biological role of the CB1 receptor in cancer, little is known about its involvement in the metastatic process of CRC. The aim of this study was to investigate the possible link between CB1 receptor expression and the presence of metastasis in patients with CRC, investigating the main signaling pathways elicited downstream of CB1 receptor in colon cancer. Fifty-nine consecutive patients, with histologically proven colorectal cancer, were enrolled in the study,…