Reduced chemotherapeutic sensitivity in high glucose condition: implication of antioxidant response

Resistance to chemotherapy represents a major obstacle to successful treatment. The generation of reactive oxygen species (ROS) has been directly linked to the cytotoxic effects of several antitumor agents, including Adriamycin (ADR), and modulation of the oxidative balance has been implicated in the development and/or regulation of resistance to chemotherapeutic drugs. We recently showed that high glucose (HG) markedly diminished the cancer cell death induced by anticancer agents such as ADR. In the present study we attempted to evaluate the mechanism that impaired the cytotoxic effect of ADR in HG. We found that, in colon cancer cells, HG attenuated ADR-induced ROS production that consequently diminished ADR-induced H2AX phosphorylation and micronuclei (MN) formation. Mechanistically, HG attenuation of ADR-induced ROS production correlated with increased antioxidant response promoted by NRF2 activity. Thus, pharmacologic inhibition of NRF2 pathway by brusatol re-established the ADR cytotoxic effect impaired by HG. Together, the data provide new insights into chemotherapeutic-resistance mechanisms in HG condition dictated by increased NRF2-induced antioxidant response and how they may be overcome in order to restore chemosensitivity and ADR-induced cell death

Emotional Health and Mental Coaching: Safeguarding Oncological Patients' Mental Health in the COVID-19 Era

The new Coronavirus infection, called COVID-19, has appeared on the world stage with significant implications for patients suffering from cancer and their caregivers. Patients with oncological diseases are particularly at risk, both for morbidity and lethality related to respiratory virus infections and are exposed to a higher risk of severe events. The assistance to these types of patients had to deal with the consequences and damage that arise from a state of health emergency and has therefore undergone a remodeling. While the threat of slowdowns threatens patients and all people who risk being diagnosed late, many oncologists face severe occupational burnout. This situation has repercussions on an emotional level: a shared path is desirable to protect the patient himself and the health professionals who take responsibility for the therapeutic care process of such fragile patients. Our model of assistance is based on coaching pointed towards patients affected by cancer, their caregivers and healthcare professionals with the aim of addressing the crisis through an operational process aimed at helping to integrate the experience of illness in order to rebuild the continuity of the existence and give it an evolutionary sense

Better Understanding of Bipolar Disorder from Clinical Expression to Therapeutic Strategies

Bipolar disorder is a psychiatric disease that involves profound changes in mood accompanied by severe changes in feelings, thoughts and behaviors: emotions can move quickly from a deep depression to excessive excitement, without some apparent reason. BD is usually a chronic condition and may last for life with recurring episodes that often occur during adolescence or early adulthood, sometimes during childhood and usually requires treatment for life. In the manic phase the disorder typically occurs in forms of exasperated disinhibition and manic symptoms may include: an euphoric mood or irritable, angry and reactive state of mind; increased activity and feelings of strength and energy; ambitious and grandiose aspirations; poor self-criticism; greater interest in sexual activity and reduction in hours of sleep and need for sleep. On the other hand, depressive phases may be so serious that can also lead to episodes of self-harm. Depressive symptomatology may include: depressed or apathetic mood; reduced strength in activities, thinking and talking; feeling of being hopeless and helpless; pessimistic approach to reality, sometimes, with suicidal thoughts; alteration in the rhythm of appetite and in sleep patterns. Although it is not known a definitive cure, BD is a very treatable disease that can be kept under control. Drugs play a key role in the care of persons affected by BD, in particular medications commonly used to treat the manic episodes of bipolar disorder are mood stabilizers. During depressive episodes, people with bipolar disorder can be treated with antidepressants by evaluating administration and dosage with extreme caution because of the risk to switch to a manic phase. In addition to medications psychotherapy and psychoeducational approaches are essential for individuals suffering from bipolar disorder. At present BD is considered a multifactorial etiology condition in which many physiopathogenetic factors are involved, thus researchers have identified several causes such as biological differences, imbalance of neurotransmitters and hormones, genetic predisposition, traumatic life events, stress and environmental factors

Functional neuroimaging: points of intersection between biology and psychotherapy.

Objectives: In the evaluation of the biological basis of psychotherapeutic changes many researches have noticed potential effects of psychotherapeutic interventions on the neural correlates of mental illness. In a psychotherapeutic setting, modifications in individual thoughts and feelings can restore brain functioning at physiological levels. This paper gives an overview about neurobiological methods and their potential to support psychotherapy research and to examine psychotherapy effects across a number of psychiatric disorders. Methods: Relevant informations are identified through searches of MEDLINE and Current Contents/Clinical Medicine. Results: Studies demonstrate that it is important to consider putative neural mechanisms of psychotherapy, changes in the brain associated with psychotherapy on a global and molecular level, intervention-specific effects and prediction of outcome. Pharmacotherapy and psychotherapy converge in a common change of neuronal functions that might be detected by imaging techniques and might resemble correlates of clinical improvement. Conclusions: Neuroimaging techniques applied to psychotherapy research are relevant for further understanding neurobiological underpinnings of psychotherapy processes and predicting treatment outcome in order to improve clinical decision-making and treatment

Resveratrol affects DNA damage induced by ionizing radiation in human lymphocytes in vitro

Resveratrol (3,4',5-trihydroxystilbene; RSV) acts on cancer cells in several ways, inducing cell cycle delay and apoptotic death, and enhancing ionizing radiation (IR)-mediated responses. However, fewer studies have examined RSV effects on normal cells. We have treated human lymphocytes in vitro with RSV, either alone or combined with IR, to evaluate its potential use as a radioprotector. We measured the effects of RSV on induction of DNA damage, repair kinetics, and modulation of histone deacetylase activit

Resveratrol and its methoxy-derivatives as modulators of DNA damage induced by ionising radiation

Various naturally occurring stilbene-like compounds that are related to resveratrol (RSV) possess some of the beneficial effects of the parent molecule and provide even further benefits. Therefore, a series of methoxylated analogues of RSV were prepared with the aim of increasing antitumour and proapoptotic activity. In a previous article, we studied two methoxy-derivatives, pterostilbene (PTERO) and trimethoxystilbene (TRIMETHOXY), in which the first was formed by the substitution of two hydroxyl groups with two methoxy groups (trans-3,5-dimethoxy-4'-hydroxystilbene) and the second was formed by the replacement of all three OH groups with methoxy groups (trans-3,5,4'-trimethoxystilbene). Both methoxy-derivatives showed stronger antioxidant activity when compared with RSV. In the present article, we focused on the analysis of the ability of RSV and its two methoxylated derivatives to protect proliferating non-tumoural cells from the damage induced by ionising radiation (IR). First we showed that the methoxy derivatives, contrary to their parental compound, are unable to affect topoisomerase enzyme and consequently are not clastogenic per se. Second we showed that both PTERO and TRIMETHOXY more efficiently reduce the chromosome damage induced by IR. Furthermore, TRIMETHOXY, but not PTERO, causes a delay in cell proliferation, particularly in mitosis progression increasing the number of cells in metaphase at the expense of prophases and ana/telophases

Effect of p53 activation through targeting MDM2/MDM4 heterodimer on T regulatory and effector cells in the peripheral blood of Type 1 diabetes patients.

Various immunotherapies for the treatment of type 1 diabetes are currently under investigation. Some of these aim to rescue the remaining beta cells from autoimmune attack caused by the disease. Among the strategies employed, p53 has been envisaged as a possible target for immunomodulation. We studied the possible effect of p53 activation on Treg subsets and Treg/Teff balance in type 1 diabetes patients' PBMC. Upon p53 activation, we observed an increase in CD8+ Treg and activated CD8+ Teff whilst CD8+ Teff cells significantly decreased in healthy PBMC when stimulated with anti-CD3/CD28. No effect was detected on percentages of CD4+ Treg, while a reduction was seen in CD4+ Teff cells and an increase in activated CD4+ Teff cells. In patients' PBMC, upon p53 activation followed by 6 days of anti-CD3/CD28 stimulation, CD8+ Treg and activated CD8+ Teff were increased while CD8+ Teff were decreased. No differences were detected in the CD4+ counterparts. CD8+ Teff PD1+, CD8+ Teff PD1low were increased upon p53 activation in type 1 diabetics compared to controls while CD8+ Teff PD1high were increased in both groups. The same increased percentages were detected for CD4+ counterparts. CD4+ Treg PD1high cells were decreased in diabetics upon p53 activation at day 6 of anti-CD3/CD28 stimulation. In conclusion, a Teff dysregulation is observed upon p53 activation suggesting that molecules promoting p53 cannot be used for therapy in type 1 diabetics