The effects of cannabidiol via TRPV2 channel in chronic myeloid leukemia cells and its combination with imatinib

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by accumulation of immature cells in bone marrow and peripheral blood. Although successful results were obtained with tyrosine kinase inhibitors, several patients show resistance. For this reason, the identification of new strategies and therapeutic biomarkers represents an attractive goal. The role of Transient Receptor Potential (TRP) ion channels as possible drug targets has been elucidated in different types of cancer. Among natural compounds known to activate TRPs, cannabidiol (CBD) displays anti-cancer properties. By using FACS analysis, confocal microscopy, gene silencing and cell growth assay, we demonstrated that CBD, through TRPV2, inhibits cell proliferation and cell cycle in CML cells. It promoted mitochondria dysfunction and mitophagy as shown by mitochondrial mass reduction and up-regulation of several mitophagy markers. These effects were associated with changes in the expression of OCT-4 and PU.1 markers regulated during cellular differentiation. Interestingly, a synergistic effect by combining CBD with the standard drug imatinib was found and imatinib-resistant cells remain susceptible to CBD effects. Therefore, the targeting of TRPV2 by using CBD, through the activation of mitophagy and the reduction in stemness, could be a promising strategy to enhance conventional therapy and improve the prognosis of CML patients

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Underwater Mediterranean image analysis based on the compute continuum paradigm

Human activity depends on the oceans for food, transportation, leisure, and many more purposes. Oceans cover 70% of the Earth’s surface, but most of them are unknown to humankind. This is the reason why underwater imaging is a valuable resource asset to Marine Science. Images are acquired with observing systems, e.g. autonomous underwater vehicles or underwater observatories, that presently transmit all the raw data to land stations. However, the transfer of such an amount of data could be challenging, considering the limited power supply and transmission bandwidth of these systems. In this paper, we discuss these aspects, and in particular how it is possible to couple Edge and Cloud computing for effective management of the full processing pipeline according to the Compute Continuum paradigm

Laparoscopic versus open appendectomy for the treatment of complicated appendicitis

Aim. Laparoscopic Appendectomy (LA) is widely performed for the treatment of acute appendicitis. However the use of laparoscopic approach for complicated appendicitis is controversial, in particular because it has been reported an increased risk of postoperative IntraAbdominal Abscess (IAA). The aim of this study was to compare the outcomes of LA versus Open Appendectomy (OA) in the treatment of complicated appendicitis, especially with regard to the incidence of postoperative IAA. Patients and Methods. A retrospective study of all patients treated at our institution for complicated appendicitis, from May 2004 to June 2009, was performed. Data collection included demographic characteristics, postoperative complications, conversion rate, and length of hospital stay. Results. Thirty-eight patients with complicated appendicitis were analysed. Among these, 18 (47,3%) had LA and 20 (52,7%) had OA. There were no statistical differences in characteristics between the two groups. The incidence of postoperative IAA was higher (16,6%), although not statistically significant, in the LA compared with OA group (5%). On the other hand the rate of wound infection was lower (5%) in the LA versus OA (20%). Conclusion. Our study indicated that LA should be utilised with caution in case of perforated appendicitis, because it is associated with an increased risk of postoperative IAA compared with OA

Patient-blood management for COVID19 convalescent plasma therapy: relevance of affinity and donor–recipient differences in concentration of neutralizing antibodies

Background: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is being extensively investigated as a treatment, with mixed results to date. Overall, there has been a generalized lack of appropriateness in prescriptions, which, in the field of transfusion medicine, is termed patient-blood management. Objectives: We aimed to separate study design variables that could affect clinical outcome after CCP therapy. We focus here on variables such as pretransfusion antibody testing in recipients, dose adjustments and antibody affinity measurements. Sources: We searched PubMed and preprint servers for relevant preclinical and clinical studies discussing each of these variables in the field of CCP therapy. Content: We show evidence that neglecting those variables has affected the outcomes of the vast majority of CCP clinical trials to date. Implications: A better understanding of such variables will improve the design of the next generation of CCP clinical trials. This will likely lead to better clinical outcomes and will minimize risks of immune evasion from subneutralizing doses of neutralizing antibodies. Keywords: Convalescent plasma; Coronavirus disease 2019; Neutralizing antibodies; Pharmacodynamics; Stoichiometry

NEREA, the Naples Ecological REsearch for Augmented observatories: Towards an end-to-end transdisciplinary approach for the study of marine ecosystems

2019 IMEKO TC-19 International Workshop on Metrology for the Sea (MetroSea 2019), 3-5 October 2019, Genova, Italy.-- 5 pages, 2 figuresHere we present the concept of NEREA, the Naples Ecological REsearch for Augmented observatories, an integrated observatory with a modular, adaptive structure, characterised by two main modules, NEREA-mob and NEREA-fix. NEREA-mob is conceived as monthly sampling at a coastal station in the Gulf of Naples where the whole water column is sampled for end-to-end (from microbes to fish) biological parameters coupling traditional with “omic” approaches (metagenomics, metatranscriptomics and metabolomics). NEREA-fix will be deployed in 2020 in the Dohrn canyon at ca. 600 m, and will integrate a seabed platform and a mooring line equipped with a set of different chemicalphysical and bio-ecological sensors. Ecological information from the two modules will be integrated by ad-hoc additional samplings in key moments and experimental activities aimed at contextualizing the sites at a larger scale. NEREA therefore aims at representing a first step towards the establishment of a network of augment observatories, end-to-end approaches under the multidisciplinary framework required for ocean health assessmen

Unveiling the Molecular Mechanisms Driving the Capsaicin-Induced Immunomodulatory Effects on PD-L1 Expression in Bladder and Renal Cancer Cell Lines

The blockade of the PD-L1/PD-1 immune checkpoint has promising efficacy in cancer treatment. However, few patients with bladder cancer (BC) or renal cell carcinoma (RCC) respond to this approach. Thus, it is important to implement a strategy to stimulate the immune anti-tumor response. In this scenario, our study evaluated the effects of a low capsaicin (CPS) dose in BC and RCC cell lines. Western blot, qRT-PCR and confocal microscopy were used to assess PD-L1 mRNA and protein expression. Alterations to the cellular oxidative status and changes to the antioxidant NME4 levels, mRNA modulation of cytokines, growth factors, transcriptional factors and oncogene, and the activation of Stat1/Stat3 pathways were examined using Western blot, cytofluorimetry and qRT-PCR profiling assays. In BC, CPS triggers an altered stress oxidative-mediated DNA double-strand break response and increases the PD-L1 expression. On the contrary, in RCC, CPS, by stimulating an efficient DNA damage repair response, thus triggering protein carbonylation, reduces the PD-L1 expression. Overall, our results show that CPS mediates a multi-faceted approach. In modulating PD-L1 expression, there is a rationale for CPS exploitation as a stimulus that increases BC cells’ response to immunotherapy or as an immune adjuvant to improve the efficacy of the conventional therapy in RCC patients