161 research outputs found
The role of the cancer stem cell marker CD271 in DNA damage response and drug resistance of melanoma cells
Several lines of evidence have suggested that stemness and acquired resistance
to targeted inhibitors or chemotherapeutics are mechanistically linked. Here
we observed high cell surface and total levels of nerve growth factor
receptor/CD271, a marker of melanoma-initiating cells, in sub-populations of
chemoresistant cell lines. CD271 expression was increased in drug-sensitive
cells but not resistant cells in response to DNA-damaging chemotherapeutics
etoposide, fotemustine and cisplatin. Comparative analysis of melanoma cells
engineered to stably express CD271 or a targeting short hairpin RNA by
expression profiling provided numerous genes regulated in a CD271-dependent
manner. In-depth analysis of CD271-responsive genes uncovered the association
of CD271 with regulation of DNA repair components. In addition, gene set
enrichment analysis revealed enrichment of CD271-responsive genes in drug-
resistant cells, among them DNA repair components. Moreover, our comparative
screen identified the fibroblast growth factor 13 (FGF13) as a target of
CD271, highly expressed in chemoresistant cells. Further we show that levels
of CD271 determine drug response. Knock-down of CD271 in fotemustine-resistant
cells decreased expression of FGF13 and at least partly restored sensitivity
to fotemustine. Together, we demonstrate that expression of CD271 is
responsible for genes associated with DNA repair and drug response. Further,
we identified 110 CD271-responsive genes predominantly expressed in melanoma
metastases, among them were NEK2, TOP2A and RAD51AP1 as potential drivers of
melanoma metastasis. In addition, we provide mechanistic insight in the
regulation of CD271 in response to drugs. We found that CD271 is potentially
regulated by p53 and in turn is needed for a proper p53-dependent response to
DNA-damaging drugs. In summary, we provide for the first time insight in a
CD271-associated signaling network connecting CD271 with DNA repair, drug
response and metastasis
Essential oils of Origanum vulgare L. subsp glandulosum (Desf.) letswaart from Tunisia: chemical composition and antioxidant activity
BACKGROUND: Characterisation of the essential oils from O. glandulosum collected in three locations of Tunisia, chemical composition and the evaluation of their antioxidant activities were carried out.
RESULTS: The essential oils from Origanum vulgare L. subsp. glandulosum (Desf.) letswaart collected from three localities of north Tunisia - Krib, Bargou and Nefza - were obtained in yields of 2.5, 3.0 and 4.6% (v/w), respectively. The essential oils were analysed by GC and GC/MS and assayed for their total phenolics content, by the Folin-Ciocalteu method, and antioxidant effectiveness, using the 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging assay. The main components of these essential oils, from Nefza, Bargou and Krib, were p-cymene (36%, 40% and 46%), thymol (32%, 39% and 18%), gamma-terpinene (24%, 12% and 16%) and carvacrol (2%, 2% and 15%), respectively). The ability to scavenge the DPPH radicals, expressed by IC50, ranged from 59 to 80 mg L-1. The total phenolic content, expressed in gallic acid equivalent (GAE) g kg(-1) dry weight, varied from 9.37 to 17.70 g kg(-1) dw. CONCLUSIONS: A correlation was identified between the total phenolic content of the essential oils and DPPH radical scavenger capacity. The occurrence of a p-cymene chemotype of O. glandulosum in the northern region of Tunisia is demonstrated
The Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel
Unraveling the relationship between genetic variation and phenotypic traits remains a fundamental challenge in biology. Mapping variants underlying complex traits while controlling for confounding environmental factors is often problematic. To address this, we establish a vertebrate genetic resource specifically to allow for robust genotype-to-phenotype investigations. The teleost medaka (Oryzias latipes) is an established genetic model system with a long history of genetic research and a high tolerance to inbreeding from the wild
Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries
Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely
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