Edible mushroom Morchella esculenta (L.) Pers. mycelium protects DNA and mitochondria from radiation induced damages

Mushrooms have gained great attraction not only for their nutritional and medicinal values but also for diversity of their bioactive components. Morchella esculenta, commonly called Morel, is an edible and nutritious mushroom. In the present study, we evaluated the radioprotective effect of cultured mycelium of M. esculenta against radiation induced damages in mouse spleen lymphocyte DNA and rat liver mitochondria. The mitochondria were exposed to 450 Gy g-radiation and lipid peroxidation caused by radiation was studied by LOOH assay and TBARS assay. M. esculenta extract at a concentration of 200 and 50 µg/mL significantly inhibited the formation of LOOH and TBARS formation in mitochondria. The protective effect of M. esculenta against radiation-induced damage to DNA in the spleen lymphocyte was measured using comet assay. Spleen lymphocytes were exposed to γ-radiation at a dose of 6 Gy in the presence and absence of the extract and the strand break were analyzed. The extract inhibited the strand break significantly. The study indicate that M. esculenta mycelia protect mitochondria form oxidative stress and DNA from deleterious effects induced by radiation and has potential for the development of safe and non-toxic radio protector with significant nutritional properties

Citostatsko i protuupalno djelovanje polisaharida biljke Ganoderma lucidum

In this study, polysaccharides were isolated from Ganoderma lucidum (Polyporaceae) and their antitumor and anti-inflammatory activities were investigated using in vivo models. Potential antitumor activity was shown by G. lucidum polysaccharides (GLP) against solid tumor induced by Ehrlich’s ascites carcinoma cells. GLP at 100 mg kg–1 body mass showed 80.8 and 77.6 % reduction in tumour volume and tumour mass, respectively, when administered 24 h after tumour implantation. Again, GLP at the same dose but when administered prior to tumour inoculation, showed 79.5 and 81.2 % inhibition of tumour volume and tumour mass, respectively. GLP showed significant dose-dependent activity in carrageenean-induced (acute) and formalin-induced (chronic) inflammation assays. At 100 mg kg–1, GLP exhibited 57.6 and 58.2 % inhibition in carrageenean-induced and formalin-induced assays, respectively.U radu je ispitano in vivo citostatsko i protuupalno djelovanje polisaharida (GLP) izoliranih iz biljke Ganoderma lucidum (Polyporaceae). Ispitivani polisaharidi pokazali su potencijalno antitumorsko djelovanje na Ehrlichov ascitesni tumor. GLP su u dozi od 100 mg kg1 tjelesne mase inhibirali volumen tumora za 80,8, a njegovu masu za 77,6 %, kada su primijenjeni 24 h nakon implantacije tumora. Ako se GLP daju u istoj dozi prije inokulacije tumora, inhibiraju volumen tumora za 79,5, a njegovu masu za 81,2 %. GLP pokazuju značajno, o dozi ovisno, protuupalno djelovanje u karagenan testu (akutna upala) i formalin testu (kronična upala). U dozi od 100 mg kg1, GLP inhibiraju upalne procese za 57,6 odnosno 58,2 % u testu s karagenanom, odnosno formalinom

Citostatsko i protuupalno djelovanje polisaharida biljke Ganoderma lucidum

In this study, polysaccharides were isolated from Ganoderma lucidum (Polyporaceae) and their antitumor and anti-inflammatory activities were investigated using in vivo models. Potential antitumor activity was shown by G. lucidum polysaccharides (GLP) against solid tumor induced by Ehrlich’s ascites carcinoma cells. GLP at 100 mg kg–1 body mass showed 80.8 and 77.6 % reduction in tumour volume and tumour mass, respectively, when administered 24 h after tumour implantation. Again, GLP at the same dose but when administered prior to tumour inoculation, showed 79.5 and 81.2 % inhibition of tumour volume and tumour mass, respectively. GLP showed significant dose-dependent activity in carrageenean-induced (acute) and formalin-induced (chronic) inflammation assays. At 100 mg kg–1, GLP exhibited 57.6 and 58.2 % inhibition in carrageenean-induced and formalin-induced assays, respectively.U radu je ispitano in vivo citostatsko i protuupalno djelovanje polisaharida (GLP) izoliranih iz biljke Ganoderma lucidum (Polyporaceae). Ispitivani polisaharidi pokazali su potencijalno antitumorsko djelovanje na Ehrlichov ascitesni tumor. GLP su u dozi od 100 mg kg1 tjelesne mase inhibirali volumen tumora za 80,8, a njegovu masu za 77,6 %, kada su primijenjeni 24 h nakon implantacije tumora. Ako se GLP daju u istoj dozi prije inokulacije tumora, inhibiraju volumen tumora za 79,5, a njegovu masu za 81,2 %. GLP pokazuju značajno, o dozi ovisno, protuupalno djelovanje u karagenan testu (akutna upala) i formalin testu (kronična upala). U dozi od 100 mg kg1, GLP inhibiraju upalne procese za 57,6 odnosno 58,2 % u testu s karagenanom, odnosno formalinom

Cre recombinase expression cooperates with homozygous FLT3 internal tandem duplication knockin mouse model to induce acute myeloid leukemia

Murine models offer a valuable tool to recapitulate genetically defined subtypes of AML, and to assess the potential of compound mutations and clonal evolution during disease progression. This is of particular importance for difficult to treat leukemias such as FLT3 internal tandem duplication (ITD) positive AML. While conditional gene targeting by Cre recombinase is a powerful technology that has revolutionized biomedical research, consequences of Cre expression such as lack of fidelity, toxicity or off-target effects need to be taken into consideration. We report on a transgenic murine model of FLT3-ITD induced disease, where Cre recombinase expression alone, and in the absence of a conditional allele, gives rise to an aggressive leukemia phenotype. Here, expression of various Cre recombinases leads to polyclonal expansion of FLT3(ITD/ITD) progenitor cells, induction of a differentiation block and activation of Myc-dependent gene expression programs. Our report is intended to alert the scientific community of potential risks associated with using this specific mouse model and of unexpected effects of Cre expression when investigating cooperative oncogenic mutations in murine models of cancer

Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative

Background Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2–3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. Methods We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. Discussion Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it

Ultrasound imaging versus morphopathology in cardiovascular diseases. Coronary collateral circulation and atherosclerotic plaque

This review article is aimed at comparing the results of histopathological and clinical imaging studies to assess coronary collateral circulation in humans. The role of collaterals, as emerging from morphological studies in both normal and atherosclerotic coronary vessels, is described; in addition, present role and future perpectives of echocardiographic techniques in assessing collateral circulation are briefly summarized

Imetelstat-mediated alterations in fatty acid metabolism to induce ferroptosis as a therapeutic strategy for acute myeloid leukemia

Telomerase enables replicative immortality in most cancers including acute myeloid leukemia (AML). Imetelstat is a first-in-class telomerase inhibitor with clinical efficacy in myelofibrosis and myelodysplastic syndromes. Here, we develop an AML patient-derived xenograft resource and perform integrated genomics, transcriptomics and lipidomics analyses combined with functional genetics to identify key mediators of imetelstat efficacy. In a randomized phase II-like preclinical trial in patient-derived xenografts, imetelstat effectively diminishes AML burden and preferentially targets subgroups containing mutant NRAS and oxidative stress-associated gene expression signatures. Unbiased, genome-wide CRISPR/Cas9 editing identifies ferroptosis regulators as key mediators of imetelstat efficacy. Imetelstat promotes the formation of polyunsaturated fatty acid-containing phospholipids, causing excessive levels of lipid peroxidation and oxidative stress. Pharmacological inhibition of ferroptosis diminishes imetelstat efficacy. We leverage these mechanistic insights to develop an optimized therapeutic strategy using oxidative stress-inducing chemotherapy to sensitize patient samples to imetelstat causing substantial disease control in AML

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders