Unusual cytotoxic sulfated cadinene-type sesquiterpene glycosides from cottonseed (Gossypium hirsutum).

Two new sulfated cadinene-type sesquiterpene glycosides, 13-hydroxy-7-O-(60-O-sulfate-b-D-glucopyranosyl)-desoxyhemigossypol (1) and 13,15-dihydroxy-7-O-(60-O-sulfate-b-D-glucopyranosyl)-desoxyhemigossypol (2), have been isolated from whole cottonseed (Gossypium hirsutum). Their structures, which possess an unusual 6-O-sulfate-glucopyranosyl moiety, were determined through the interpretation of 2D NMR spectral data and H/D exchange ESI-MS experiments. Compounds 1 and 2 were screened for their toxicity on Jurkat cells. Both compounds inhibited cellular proliferation with IC50 values of 8.1 and 4.2 mg, respectively

Continuous two-step anaerobic digestion (TSAD) of organic market waste: rationalising process parameters

Experimental tests on continuous two-stage anaerobic digestion (TSAD) were conducted, to assess its energetic performance, using organic market waste as a substrate. The systems were tested to ascertain the effects of external stressors, which allow the separation into two different microorganism consortia, that is, hydrogen-producing bacteria and hydrogen-consuming bacteria, to be maintained. Two bioreactors were run in series under different operational conditions, including pH, mixing rate, and initial inoculum, and three different decreasing hydraulic retention times were considered, with a fixed ratio of 1:10 in volume between the first bioreactor (hydrogen) and the second one (methane). The performance of the whole system was assessed over > 140 days to monitor the stability of the process, in terms of the reduction of the volatile solids and the energy productivity for each step. Each tested condition was scored using two parameters: efficiency and efficacy. The first corresponds to the fraction of recovered energy of the available (η) and the second (ξ) was used to compare the energy produced by the TSAD with that of one-step anaerobic digestion. The efficiency resulted to be (24–32)%, while the efficacy proved to be around 1.20. The share of energy, under the form of hydrogen, compared to the total energy recovery, was in the (8–12) % range. Finally, the oscillation behaviour of the quasi-steady-state condition was analysed in terms of the Fano factor to establish the most stable conditions

An Italian expert consensus on the use of opioids for the management of chronic non-oncological pain in clinical practice: focus on buprenorphine

Purpose: The aim of the present work was to evaluate the knowledge and prescriptive habits of clinicians involved in the management of chronic non cancer pain (CNCP), with a special focus on the use of opioids. Methods: A Delphi method was used. A Board of specialists elaborated and discussed a series of statements, based on available literature and personal clinical expertise, about particularly controversial topics on pain pathophysiology and treatment. A Panel of experts in the field of pain management, selected by the Board, was invited to vote the proposed statements, indicating the level of agreement on a 5-point Likert scale (1: strongly disagree; 2: disagree; 3: partially agree; 4: agree; 5: strongly agree). The threshold for consensus was set at minimum 66.6% of the number of respondents with a level of agreement ≥4 (Agree or Strongly agree). Results: The Board included 5 pain therapists, 1 pharmacologist and 1 methodology expert and drew up a total of 36 statements (for a total of 40 requested answers)”. A total of 100 clinicians were included in the Expert Panel. Respondents were 89 (89%). Consensus was achieved for 32 out of 40 answers. Most of the lack of consensus was recorded for statements regarding opioids use, and resulted from a low level of agreement (3 on the Likert scale), suggesting a neutral position deriving from a lack of knowledge rather than a strong contrary opinion. Conclusion: Most of the proposed items reached consensus, suggesting a generally homogeneous approach to CNCP management. However, the lack of consensus recorded for several items regarding opioid use confirms the need to fill important gaps in the knowledge of available agents. A clear explanation of the peculiar pharmacological properties of drugs associated with potential clinical advantages (such as buprenorphine) will help optimize pain treatment in both primary care and hospital settings and improving pain control in CNCP patients

Cannabidiol and oxygen-ozone combination induce cytotoxicity in human pancreatic ductal adenocarcinoma cell lines

Pancreatic cancer (PC) is related to lifestyle risks, chronic inflammation, and germline mutations in BRCA1/2, ATM, MLH1, TP53, or CDKN2A. Surgical resection and adjuvant chemotherapy are the main therapeutic strategies but are less effective in patients with high-grade tumors. Oxygen-ozone (O2/O3) therapy is an emerging alternative tool for the treatment of several clinical disorders. O2/O3 therapy has been found to ameliorate mechanisms promoting chronic pain and inflammation, including hypoxia, inflammatory mediators, and infection. The advantages of using cannabinoids have been evaluated in vitro and in vivo models of several human cancers. Regarding PDAC, activation of cannabinoid receptors was found to induce pancreatic cancer cell apoptosis without affecting the normal pancreas cells. In a murine model of PDAC, a combination of cannabidiol (CBD) and gemcitabine increased survival length by nearly three times. Herein, we evaluate the anticancer effect of CBD and O2/O3, alone or in combination, on two human PDAC cell lines, PANC-1 and MiaPaCa-2, examining expression profiles of 92 pancreatic adenocarcinoma associated genes, cytotoxicity, migration properties, and cell death. Finally, we assess the combination effects with gemcitabine and paclitaxel. Summarizing, for the first time the antitumoral effect of combined therapy with CBD and oxygen-ozone therapy in PDAC is evidenced

RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction

Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in young children. The factors that contribute to the increased propensity of RSV-induced distal airway disease compared with other commonly encountered respiratory viruses remain unclear. Here, we identified the RSV-encoded nonstructural 2 (NS2) protein as a viral genetic determinant for initiating RSV-induced distal airway obstruction. Infection of human cartilaginous airway epithelium (HAE) and a hamster model of disease with recombinant respiratory viruses revealed that NS2 promotes shedding of infected epithelial cells, resulting in two consequences of virus infection. First, epithelial cell shedding accelerated the reduction of virus titers, presumably by clearing virus-infected cells from airway mucosa. Second, epithelial cells shedding into the narrow-diameter bronchiolar airway lumens resulted in rapid accumulation of detached, pleomorphic epithelial cells, leading to acute distal airway obstruction. Together, these data indicate that RSV infection of the airway epithelium, via the action of NS2, promotes epithelial cell shedding, which not only accelerates viral clearance but also contributes to acute obstruction of the distal airways. Our results identify RSV NS2 as a contributing factor for the enhanced propensity of RSV to cause severe airway disease in young children and suggest NS2 as a potential therapeutic target for reducing the severity of distal airway disease