β-caryophyllene and low-doses of doxorubicin against liver cancer cells: a “metronomic chemotherapy”

Cholangiocarcinoma and hepatocellular carcinoma are primary liver cancers, both representing a growing challenge due to their increasing morbidity and mortality. A “metronomic chemotherapy”, consisting of the repeated administration of low and/or continuous doses of anti-neoplastic drugs, represents an alternative approach to the standard chemotherapy [1]. Numerous natural substances exhibited in vitro chemosensitizing features: in particular, the natural sesquiterpene β-caryophyllene (CRY) has been proved to increase the cytotoxicity of doxorubicin (DOXO) in leukemic cells [2]. Hence, our aim has been to evaluate the ability of CRY to enhance the efficacy of low-dose DOXO in human liver cancer cells, by applying a metronomic protocol. To this end, human liver HepG2 and CCA cells have been used as models of hepatocellular carcinoma and cholangiocarcinoma. The metronomic protocol was based on a 2h low-time exposition to the test substances, followed by 72h incubation for restoring. This scheduling has been applied 3 times and cytotoxicity was measured by MTT assay. Both the substances alone (CRY 1-100 μg/ml; DOXO 1-500 μg/ml) and the combination of DOXO with a nontoxic concentration of CRY were assessed. We found that the repeated treatments with low concentrations produced a significant potentiation (about 30 %) of DOXO cytotoxicity in HepG2. The combination with CRY increased the DOXO activity, reaching a 70 % inhibition of cell viability at 50 μg/ml after 2 repeated treatments. Similar effects were found in CCA, although repeated treatments induced no additional potentiation. These results highlight a possible role of CRY as a chemosensitizing agent for DOXO-based chemotherapy of liver cancer

β-caryophyllene and low-doses of doxorubicin against liver cancer cells: a “metronomic chemotherapy”

Cholangiocarcinoma and hepatocellular carcinoma are primary liver cancers, both representing a growing challenge due to their increasing morbidity and mortality. A “metronomic chemotherapy”, consisting of the repeated administration of low and/or continuous doses of anti-neoplastic drugs, represents an alternative approach to the standard chemotherapy [1]. Numerous natural substances exhibited in vitro chemosensitizing features: in particular, the natural sesquiterpene β-caryophyllene (CRY) has been proved to increase the cytotoxicity of doxorubicin (DOXO) in leukemic cells [2]. Hence, our aim has been to evaluate the ability of CRY to enhance the efficacy of low-dose DOXO in human liver cancer cells, by applying a metronomic protocol. To this end, human liver HepG2 and CCA cells have been used as models of hepatocellular carcinoma and cholangiocarcinoma. The metronomic protocol was based on a 2h low-time exposition to the test substances, followed by 72h incubation for restoring. This scheduling has been applied 3 times and cytotoxicity was measured by MTT assay. Both the substances alone (CRY 1-100 μg/ml; DOXO 1-500 μg/ml) and the combination of DOXO with a nontoxic concentration of CRY were assessed. We found that the repeated treatments with low concentrations produced a significant potentiation (about 30 %) of DOXO cytotoxicity in HepG2. The combination with CRY increased the DOXO activity, reaching a 70 % inhibition of cell viability at 50 μg/ml after 2 repeated treatments. Similar effects were found in CCA, although repeated treatments induced no additional potentiation. These results highlight a possible role of CRY as a chemosensitizing agent for DOXO-based chemotherapy of liver cancer

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

Gluten-sensitive enteropathy of the Irish Setter and similarities with human celiac disease

Gluten-sensitive enteropathy of the Irish Setter is an immune-mediated intolerance to gluten, the protein found in wheat, barley, rye, and oats, reminiscent of human celiac disease. Intestinal histological lesions include partial villous atrophy, infiltration of the lamina propria by lymphocytes and plasma cells, and an increased intraepithelial lymphocyte count. Gluten-sensitive enteropathy is transmitted via autosomal recessive inheritance and its pathogenesis appears to involve cell-mediated immunity but not humoral immunity. In comparison to healthy dogs, levels of anti-gliadin antibodies in diseased Irish Setters are lower, although the significance of this finding is unclear. Irish Setters affected by gluten-sensitive enteropathy present with chronic intermittent diarrhea and weight loss. The use of a gluten-free diet is indispensable both for diagnosis of the disease and for therapy. In this review we discuss the similarities between gluten-sensitive enteropathy of the Irish Setter and human celiac disease

An integrated system for monitoring the quality of sample transportation.

OBJECTIVES: Due to the consolidation of laboratory testing facilities, there is an increasing need for systems able to assure quality and safety in biological sample transportation, although little evidence on this aspect is available in literature. DESIGN AND METHODS: An integrated system for sample transportation, implemented and monitored over a five-year period by our team, consists of secondary and tertiary containers, a device for temperature and time recording, and a system manager allowing the acceptance or rejection of biological samples through the immediate visualization and validation of registered data. RESULTS: Data collected between 2009 and October 2011, after a preliminary phase for optimizing the temperature inside the containers, demonstrated the frequency of transportations at an acceptable temperature (25 \ub0C) had decreased by ~80%. CONCLUSIONS: The integrated system and related operating instructions allow improvement in the quality of sample transportation over time

Fragrance materials (FMs) affect the larval development of the copepod Acartia tonsa: An emerging issue for marine ecosystems

Fragrance materials (FMs) are used in a variety of detergents and cosmetics, including household and personal care products. Despite their widespread use and the growing evidence of their occurrence in surface waters worldwide, very little is known about their toxicity towards marine species, including a key component of the marine food webs such as copepods. Thus, we investigated the toxicity of six of the more long-lasting and stable commercial fragrances, including Amyl Salicylate (AMY), Oranger Crystals (ORA), Hexyl Salicylate (HEX), Ambrofix (AMB), Peonile (PEO), and Benzyl Salicylate (BZS), to assess their ability to impair the larval development of the calanoid copepod Acartia tonsa. FMs inhibited the development of A. tonsa significantly at concentrations by far lower than the effect-concentrations reported in the literature for aquatic species. The more toxic FMs were HEX (EC50 = 57 ng L−1), AMY (EC50 = 131 ng L−1) and ORA (EC50 = 766 ng L−1), while the other three compounds exerted toxic effects at concentrations higher than 1000 ng L−1 (LOEC at 1000 ng L−1 for PEO and BZS, and at 10,000 ng L−1 for AMB). Early life-stage mortality was unaffected by FMs at all the tested concentrations. A comparison with water concentrations of FMs reported in the literature confirmed that FMs, especially HEX and AMY, may act as contaminants of potential concern in many aquatic habitats, including urban areas and remote and polar environments

Capsicum annuum L. var. Cornetto di Pontecorvo PDO. Polyphenolic profile and in vitro biological activities

In present study, the potential functional properties of the ethanolic extracts from peel, pulp, edible part and seeds of Capsicum annuum L. var. Cornetto di Pontecorvo were studied. The antimutagenicity against environmental pollutants and oxidative mutagens, the digestive enzyme inhibition, and the antioxidant properties were evaluated in relation to phenolic content. All the samples produced antimutagenic effects against 1-nitropyrene, 2-aminoantracene and tert-butyl-hydroperoxide, and inhibited α-amylase, without affecting α-glucosidase. Also, radical scavenging effects, inhibition of ROS-mediated lipoperoxidation and chelating activity were highlighted. The peel and seed extracts were in general the most effective samples. The phytochemical analysis highlighted a high amount of polyphenols, with a very low carotenoid content. Among phenolics, rutin, gallic acid, carvacrol, chlorogenic acid, 4-OH benzoic acid, and traces of quercetin and epicatechin were determined. Present results highlight a functional role of this pepper ecotype and suggest a possible use of its derived products as food supplements

Potential Cost Savings for the Healthcare System by Physical Activity in Different Chronic Diseases: A Pilot Study in the Veneto Region of Italy

Background: Sedentary behaviour (SB) and physical inactivity (PI) are associated with an increased risk of chronic diseases and a significant economic burden. This pilot study aims to estimate the possible cost savings for the Veneto Regional Health Service (Italy) due to a population-based physical activity (PA) intervention. Methods: The PA-related cost-savings were assessed for four chronic diseases in the whole and sedentary populations of the Veneto region. The SB and PA epidemiological data, regarding an additional percutaneous coronary intervention in coronary artery disease, hospitalizations in chronic obstructive pulmonary disease, surgery for colorectal cancer, and femur fracture, were obtained from national and regional administrative sources. A relative risk reduction, due to PA, was obtained from the recent literature. The annual healthcare costs were estimated using the regional diagnosis-related group tariffs. Results: The annual estimated cost-savings for the regional healthcare service related to these four outcomes: an amount between EUR 5,310,179 (if a conservative analysis was performed) and EUR 17,411,317. Conclusion: By a downward estimate, regarding the direct healthcare costs, PA interventions could lead to important cost-savings in the Veneto region. The savings would be greater when considering the cross-sectional impact on other healthcare costs, comorbidities, and indirect costs