Localization of nuclear actin in nuclear lipid microdomains of liver and hepatoma cells: Possible involvement of sphingomyelin metabolism

Nuclear actin has been implicated in different nuclear functions. In this work, its localization in nuclear membrane, chromatin and nuclear lipid microdomains was investigated. The implication of sphingomyelin metabolism was studied. Nuclear membrane, chromatin and nuclear lipid microdomains were purified from hepatocyte nuclei and H35 human hepatoma cell nuclei. The presence of \u3b2-actin was analyzed with immunoblotting by using specific antibodies. Sphingomyelinase, sphingomyelin-synthase, and phosphatidylcholine-specific phospholipase C activities were assayed by using radioactivity sphingomyelin and phosphatidylcholine as substrate. The results showed that \u3b2-actin is localized in nuclear lipid microdomains and it increases in cancer cells. Evidence is provided to the difference of phosphatidylcholine and sphingomyelin metabolism in various subnuclear fractions of cancer cell nuclei compared with normal cells. Our findings show increase of sphingomyelin-synthase and inhibition of sphingomyelinase activity only in nuclear lipid microdomains. Nuclear lipid microdomains, constituted by phosphatidylcholine, sphingomyelin and cholesterol, play a role as platform for \u3b2-actin anchoring. Possible role of sphingomyelin metabolism in cancer cells is discussed

Patients' preferences for chronic lymphocytic leukemia treatment: The CHOICE study

Chronic lymphocytic leukemia (CLL) therapies differ in efficacy, side effects, route, frequency, and duration of administration. We assessed patient preferences for treatment attributes and evaluated associations with disease stage, treatment line, and socio-demographic characteristics in a cross sectional, observational study conducted at 16 Italian hematology centers. Study visits occurred between February and July 2020; 401 adult patients with CLL (201 Watch and Wait (W & W), 200 treated) participated in a discrete choice experiment (DCE), composed of 8 choices between pairs of treatment profiles with different levels of 5 attributes of currently available CLL treatments (length of response, route and duration of administration, risk of side effects including diarrhea, infections, or organ damage). Health-related quality of life was assessed with the EQ-5D-5L, EORTC QLQ-C30 and QLQ CLL-16. Previously treated patients had longer disease duration (7 vs. 5 years), higher prevalence of serious comorbidities (45.5% vs. 36.2%) and high-risk molecular markers (unmutated IGHV 55.6% vs. 17.1%; TP53 mutation 15.2% vs. 4.0%). Health-related quality of life scores were similar between groups. In the DCE, W & W patients rated "possible occurrence of infections" highest (relative importance [RI] = 36.2%), followed by "treatment and relevant duration" (RI = 28.0%) and "progression-free survival (PFS)" (RI = 16.9%). Previously treated patients rated "treatment and relevant duration" highest (RI = 33.3%), followed by "possible occurrence of infections" (RI = 28.8%), "possible occurrence of organ damage" (RI = 19.4%), and "PFS" (RI = 9.8%). Concern over infection was rated highest overall; unexpectedly PFS was not among the most important criteria in either group, suggesting that the first COVID-19 pandemic wave may have influenced patient preferences and concerns about CLL therapy options

NOTCH1 Aberrations in Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is an incurable B-cell neoplasm characterized by highly variable clinical outcomes. In recent years, genomic and molecular studies revealed a remarkable heterogeneity in CLL, which mirrored the clinical diversity of this disease. These studies profoundly enhanced our understanding of leukemia cell biology and led to the identification of new biomarkers with potential prognostic and therapeutic significance. Accumulating evidence indicates a key role of deregulated NOTCH1 signaling and NOTCH1 mutations in CLL. This review highlights recent discoveries that improve our understanding of the pathophysiological NOTCH1 signaling in CLL and the clinical impact of NOTCH1 mutations in retrospective and prospective trials. In addition, we discuss the rationale for a therapeutic strategy aiming at inhibiting NOTCH1 signaling in CLL, along with an overview on the currently available NOTCH1-directed approaches

Exponential integrators for a mean-field selective optimal control problem

In this paper we consider a mean-field optimal control problem with selective action of the control, where the constraint is a continuity equation involving a non-local term and diffusion. First order optimality conditions are formally derived in a general framework, accounting for boundary conditions. Hence, the optimality system is used to construct a reduced gradient method, where we introduce a novel algorithm for the numerical realization of the forward and the backward equations, based on exponential integrators. We illustrate extensive numerical experiments on different control problems for collective motion in the context of opinion formation, pedestrian dynamics, and mass transfer

Possible Stress–Neuroendocrine System–Psychological Symptoms Relationship in Pregnant Women during the COVID-19 Pandemic

The COVID-19 pandemic induced long-term damages that weigh on the national health systems of various countries in terms of support and care. This review aimed to highlight the mental health impact of the COVID-19 pandemic in pregnant women. We first report data on the immune system physiopathology and the main viral infections in pregnancy, including COVID-19. Then, the attention is focused on the main factors that affect the mental health of pregnant women during the COVID-19 pandemic, such as (1) the fear of being infected and transmitting the infection to the fetus, (2) the cancellation of checkups and pre-child courses, and (3) confinement and the inability to have close friends or a partner at the time of delivery or in the first days after delivery, as well as family tensions. Because of all this, pregnant women find themselves in a stressful condition independent of the pregnancy, and thus experience anxiety, depression, insomnia, hostility, delirium, and an alteration of the mother–baby relationship. Several studies have shown an involvement of the hypothalamic–pituitary–adrenal axis and the hypothalamic–pituitary–thyroid axis in response to the pandemic. We propose a possible involvement of the neuroendocrine system as a mediator of the psychological symptoms of pregnant women induced by COVID-19-related stress

ibrutinib treatment of a patient with relapsing chronic lymphocytic leukemia and sustained remission of richter syndrome

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Hypercholesterolemia in Cancer and in Anorexia Nervosa: A Hypothesis for a Crosstalk

The relationship between cholesterol and cancer has been widely demonstrated. Clinical studies have shown changes in blood cholesterol levels in cancer patients. In parallel, basic research studies have shown that cholesterol is involved in the mechanisms of onset and progression of the disease. On the other hand, anorexic patients have high cholesterol levels and a high susceptibility to cancer. In this review, we first present a brief background on the relations among nutrition, eating disorders and cancer. Using several notable examples, we then illustrate the changes in cholesterol in cancer and in anorexia nervosa, providing evidence for their important relationship. Finally, we show a new possible link between cholesterol disorder in cancer and in anorexia nervosa

Brain and gut microbiota disorders in the psychopathology of anorexia nervosa

Studies of pathophysiological mechanisms involved in eating disorders (EDs) have intensified over the past several years, revealing their unprecedented and unanticipated complexity. Results from many articles highlight critical aspects in each member of ED family. Notably, anorexia nervosa (AN) is a disorder due to undefined etiology, frequently associated with symptoms of depression, anxiety, obsessive-compulsiveness, accompanied by endocrine alterations, altered immune response, increased inflammation, and dysbiosis of the gut microbiota. Hence, an advanced knowledge of how and why a multisystem involvement exists is of paramount importance to understand the pathogenetic mechanisms of AN. In this review, we describe the change in the brain structure/function focusing on hypothalamic endocrine disorders and the disequilibrium of gut microbiota in AN that might be responsible for the psychopathological complication