Modulation of the oxidative stress and lipid peroxidation by endocannabinoids and their lipid analogues

Growing evidence supports the pivotal role played by oxidative stress in tissue injury development, thus resulting in several pathologies including cardiovascular, renal, neuropsychiatric, and neurodegenerative disorders, all characterized by an altered oxidative status. Reactive oxygen and nitrogen species and lipid peroxidation-derived reactive aldehydes including acrolein, malondialdehyde, and 4-hydroxy-2-nonenal, among others, are the main responsible for cellular and tissue damages occurring in redox-dependent processes. In this scenario, a link between the endocannabinoid system (ECS) and redox homeostasis impairment appears to be crucial. Anandamide and 2-arachidonoylglycerol, the best characterized endocannabinoids, are able to modulate the activity of several antioxidant enzymes through targeting the cannabinoid receptors type 1 and 2 as well as additional receptors such as the transient receptor potential vanilloid 1, the peroxisome proliferator-activated receptor alpha, and the orphan G protein-coupled receptors 18 and 55. Moreover, the endocannabinoids lipid analogues N-acylethanolamines showed to protect cell damage and death from reactive aldehydes-induced oxidative stress by restoring the intracellular oxidants-antioxidants balance. In this review, we will provide a better understanding of the main mechanisms triggered by the cross-talk between the oxidative stress and the ECS, focusing also on the enzymatic and non-enzymatic antioxidants as scavengers of reactive aldehydes and their toxic bioactive adducts

Alterations of clock gene RNA expression in brain Regions of a triple transgenic model of Alzheimer's Disease

A disruption to circadian rhythmicity and the sleep/wake cycle constitutes a major feature of Alzheimer's disease (AD). The maintenance of circadian rhythmicity is regulated by endogenous clock genes and a number of external Zeitgebers, including light. This study investigated the light induced changes in the expression of clock genes in a triple transgenic model of AD (3×Tg-AD) and their wild type littermates (Non-Tg). Changes in gene expression were evaluated in four brain areas¾suprachiasmatic nucleus (SCN), hippocampus, frontal cortex and brainstem¾of 6- and 18-month-old Non-Tg and 3×Tg-AD mice after 12 h exposure to light or darkness. Light exposure exerted significant effects on clock gene expression in the SCN, the site of the major circadian pacemaker. These patterns of expression were disrupted in 3×Tg-AD and in 18-month-old compared with 6-month-old Non-Tg mice. In other brain areas, age rather than genotype affected gene expression; the effect of genotype was observed on hippocampal Sirt1 expression, while it modified the expression of genes regulating the negative feedback loop as well as Rorα, Csnk1ɛ and Sirt1 in the brainstem. In conclusion, during the early development of AD, there is a disruption to the normal expression of genes regulating circadian function after exposure to light, particularly in the SCN but also in extra-hypothalamic brain areas supporting circadian regulation, suggesting a severe impairment of functioning of the clock gene pathway. Even though this study did not demonstrate a direct association between these alterations in clock gene expression among brain areas with the cognitive impairments and chrono-disruption that characterize the early onset of AD, our novel results encourage further investigation aimed at testing this hypothesis

Dysphagia in non-intubated patients affected by COVID-19 infection

Purpose Patients affected by COVID-19 are assumed to be at high risk of developing swallowing disorders. However, to our best knowledge, data on the characteristics and incidence of dysphagia associated with COVID-19 are lacking, especially in non-intubated patients. Therefore, we investigated the onset of swallowing disorders in patients with laboratory-confirmed COVID-19 infection who have not been treated with invasive ventilation, in order to evaluate how the virus affected swallowing function regardless of orotracheal intubation. Methods We evaluated 41 patients admitted to the COVID department of our Hospital when they had already passed the acute phase of the disease and were therefore asymptomatic but still positive for SARS-CoV-2 RNA by RT-PCR. We examined patients' clinical history and performed the Volume-Viscosity Swallow Test (VVST). Each patient also answered the Swallowing Disturbance Questionnaire (SDQ). After 6 months, we performed a follow-up in patients with swallowing disorders. Results Eight of 41 patients (20%) presented with dysphagia symptoms during hospitalization and 2 of them (25%) still presented a SDQ high score and swallowing disorders with liquid consistency after 6 months. Conclusion Non-intubated patients can experience various grades of swallowing impairment that probably directly related to pulmonary respiratory function alterations and viral direct neuronal lesive activity. Although these symptoms show natural tendency to spontaneous resolution, their impact on a general physical impaired situation should not be underestimated, since it can adversely affect patients' recovery from COVID-19 worsening health outcomes

Optical discrimination between malignant and benign breast lesions

Time domain multi-wavelength (635 to 1060 nm) optical mammography was performed on 82 subjects with breast lesions (45 malignant and 38 benign lesions). A perturbative approach based on the high-order calculation of the pathlength of photons inside the lesion was applied to estimate differences between lesion and average healthy breast tissue in terms of: i) absorption properties, and ii) concentration of the major tissue constituents (oxy- and deoxy-hemoglobin, water, lipid and collagen). The absorption difference a between lesion and healthy tissue is significantly different for malignant vs. benign lesions at all wavelengths. Logistic regression fitted to the absorption data identifies 975 nm as the key wavelength to discriminate malignant from benign lesions. When the difference in tissue composition between lesion and healthy tissue is considered, malignant lesions are characterized by significantly higher collagen content than benign lesions. Also the best model for the discrimination of malignant lesions obtained applying regression logistic to tissue composition is based only on collagen

Non-invasive optical estimate of tissue composition to differentiate malignant from benign breast lesions: A pilot study

Several techniques are being investigated as a complement to screening mammography, to reduce its false-positive rate, but results are still insufficient to draw conclusions. This initial study explores time domain diffuse optical imaging as an adjunct method to classify non-invasively malignant vs benign breast lesions. We estimated differences in tissue composition (oxy-and deoxyhemoglobin, lipid, water, collagen) and absorption properties between lesion and average healthy tissue in the same breast applying a perturbative approach to optical images collected at 7 red-near infrared wavelengths (635-1060 nm) from subjects bearing breast lesions. The Discrete AdaBoost procedure, a machine-learning algorithm, was then exploited to classify lesions based on optically derived information (either tissue composition or absorption) and risk factors obtained from patient's anamnesis (age, body mass index, familiarity, parity, use of oral contraceptives, and use of Tamoxifen). Collagen content, in particular, turned out to be the most important parameter for discrimination. Based on the initial results of this study the proposed method deserves further investigation

Immunological backbone of uveal melanoma: is there a rationale for immunotherapy?

No standard treatment has been established for metastatic uveal melanoma (mUM). Immunotherapy is commonly used for this disease even though UM has not been included in phase III clinical trials with checkpoint inhibitors. Unfortunately, only a minority of patients obtain a clinical benefit with immunotherapy. The immunological features of mUM were reviewed in order to understand if immunotherapy could still play a role for this disease

Time domain diffuse optical spectroscopy: In vivo quantification of collagen in breast tissue

Time-resolved diffuse optical spectroscopy provides non-invasively the optical characterization of highly diffusive media, such as biological tissues. Light pulses are injected into the tissue and the effects of light propagation on re-emitted pulses are interpreted with the diffusion theory to assess simultaneously tissue absorption and reduced scattering coefficients. Performing spectral measurements, information on tissue composition and structure is derived applying the Beer law to the measured absorption and an empiric approximation to Mie theory to the reduced scattering. The absorption properties of collagen powder were preliminarily measured in the range of 600-1100 nm using a laboratory set-up for broadband time-resolved diffuse optical spectroscopy. Optical projection images were subsequently acquired in compressed breast geometry on 218 subjects, either healthy or bearing breast lesions, using a portable instrument for optical mammography that operates at 7 wavelengths selected in the range 635-1060 nm. For all subjects, tissue composition was estimated in terms of oxy- and deoxy-hemoglobin, water, lipids, and collagen. Information on tissue microscopic structure was also derived. Good correlation was obtained between mammographic breast density (a strong risk factor for breast cancer) and an optical index based on collagen content and scattering power (that accounts mostly for tissue collagen). Logistic regression applied to all optically derived parameters showed that subjects at high risk for developing breast cancer for their high breast density can effectively be identified based on collagen content and scattering parameters. Tissue composition assessed in breast lesions with a perturbative approach indicated that collagen and hemoglobin content are significantly higher in malignant lesions than in benign ones

Measles Outbreak Among Healthcare Professionals: Operational Response and Remedial Measures

Given the numerous cases recorded in 2017, a descriptive epidemiological study was conducted in the Viterbo Local Health Unit (LHU) area, Italy. Hospital Discharge Sheets (HDSs) and the notifications of infectious diseases (NOIDs) were used.We were able to trace the distribution of the disease both in the general population and, in particular, among the staff of Belcolle Hospital in Viterbo. In 2017, 50 cases of measles were detected among the population in the area of Viterbo. Of these, 10 concerned healthcare professionals and 3 employees of the Viterbo LHU.Due to the education and information campaign on the measles, mumps, and rubella (MMR) vaccine and the close monitoring of the vaccination coverage among the employees of the hospital (performed for the first time), only 4 cases were registered from January 1, 2018 to December 31, 2018 in the same area, and no healthcare workers were involved

Is collagen an independent risk factor for breast cancer?

Collagen content was estimated on 109 subjects (53 healthy and 56 with malignant breast lesions) performing time domain 7-wavelength (635-1060 nm) optical mammography. Subjects with higher age-matched collagen content (top 15%) show higher cancer occurrence. Collagen correlates with mammographic density (recognized risk factor for breast cancer). However, top 15% clustering based on percentage mammographic density identifies a different set of patients, potentially indicating collagen as an independent breast cancer risk factor. If confirmed on a wider population, these initial results could have huge impact on personalized diagnostics and health care systems

Optical Quantification of Collagen and Breast Cancer: Lesion Classification and Risk Estimate

Collagen content quantified through 7-wavelength (635-1060 nm) time domain diffuse optical mammography in 200 women proved key to discriminate malignant from benign breast lesions, to measure breast density, and to estimate breast cancer risk