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Ferraro, A.

Publications and source records attributed to Ferraro, A..

3 recordsLinked to original sources

Effects of chronic mild stress and CB1 receptor activation on hippocampal-dependent fear conditioning in female adolescent rats

Sex differences in responses to chronic stress are implicated in the higher prevalence of major depression and PTSD in females. Evidence of sex differences in endocannabinoid (eCB) physiology suggests that eCB signaling contributes to sexual disparities in fear conditioning and extinction. In adolescent male Sprague-Dawley rats, exposure to chronic-mild-unpredictable stress (CMS) resulted in enhanced trace-fear conditioning that was reversed by CB1 activation (Reich et al, 2013). In the present study, we assessed the effects of CMS and CB1 activation on hippocampal-dependent trace and contextual fear conditioning in adolescent female Sprague-Dawley rats. CMS exposure enhanced trace freezing behavior during memory recall compared to non-stress controls. This effect was not observed in contextually conditioned females. The CB1 receptor agonist, ACEA (0.1 mg/kg), administered prior to trace memory recall, but not prior to acquisition, significantly decreased freezing in both stress and non-stress females. ACEA significantly reduced baseline freezing behavior during trace memory recall in both stress and non-stress rats, however ACEA either 1) did not affect or 2) impaired short and long-term extinction in stress and non-stress females. In contextually conditioned females, ACEA decreased freezing during memory recall, although the effect was more robust in stress rats. ACEA impaired long-term contextual extinction in stress females while facilitating this in non-stress controls. However, ACEA had no effect or impaired short-term contextual extinction in both stress and non-stress groups. The results demonstrate that CMS enhances hippocampal-dependent episodic fear memories but has limited effects on contextual fear conditioning in female rats. These findings have implications in the use of medical cannabinoid treatment of disorders such as PTSD, as well as recreational cannabis use in adolescent/young adult females.

neuroscience↗

Nirmatrelvir treatment blunts the development of antiviral adaptive immune responses in SARS-CoV-2 infected mice

Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir - an orally available inhibitor of the 3-chymotrypsin-like cysteine protease - has been shown to reduce the risk of progression to severe COVID-19. However, the impact of nirmatrelvir treatment on the development of SARS-CoV-2-specific adaptive immune responses is unknown. Here, by using a mouse model of SARS-CoV-2 infection, we show that nirmatrelvir administration early after infection blunts the development of SARS-CoV-2-specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir-treated mice recruited significantly fewer memory T and B cells to the infected lungs and to mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals.

immunology↗

Nanoscale prognosis of colorectal cancer metastasis from AFM image processing of histological sections

Early ascertainment of metastatic tumour phases is crucial to improve cancer survival, formulate an accurate prognostic report of disease advancement and, most important, quantify the metastatic progression and malignancy state of primary cancer cells with a universal numerical indexing system. This work proposes an early improvement of cancer detection with 97 nm spatial resolution by indexing the metastatic cancer phases from the analysis of atomic force microscopy images of human colorectal cancer histological sections. The procedure applies variograms of residuals of Gaussian filtering and theta statistics of colorectal cancer tissue image settings. The methodology elucidates the early metastatic progression at the nanoscale level by setting metastatic indexes and critical thresholds from relatively large histological sections and categorising the malignancy state of a few suspicious cells not identified with optical image analysis. In addition, we sought to detect early tiny morphological differentiations indicating potential cell transition from epithelial cell phenotypes of low to high metastatic potential. The metastatic differentiation, also identified by higher moments of variograms, sets different hierarchical levels for the metastatic progression dynamic, potentially impacting therapeutic cancer protocols.

cancer biology↗