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

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

Artificial insemination of all ejaculated sperm fractions accelerates embryo development and increases the uterine vascularity in the pig

© 2024 The Authors. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This document is the Published version of a Published Work that appeared in final form in Theriogenology. To access the final edited and published work see https://doi.org/10.1016/j.theriogenology.2024.02.017The semen of boar is characterized by ejaculation in well-differentiated fractions with specific concentration, composition, and volume. The ‘sperm-rich fraction' (SRF), the most concentrated seminal fraction, is habitually collected in insemination centers to make artificial insemination (AI) doses. The absence of the other fractions in AI doses could alter the uterine reaction to AI and not trigger essential responses that could maximize fertility. Thus, there is an urge to ascertain the impact of different ejaculate fractions on the uterus after AI to optimize the semen doses. This work analyzed specific parameters related to fertility in pregnant artificially inseminated sows (n = 15) with ac-cumulative fractions of the semen of boars (n = 6): F1, composed of the sperm-rich fraction (SRF); F2, composed of F1 plus the intermediate fraction; F3, composed of F2 plus the post-SRF. Non-inseminated sows (n = 5) were included as control (C). The different types of seminal dose did not affect the number of ovulated follicles (CL; corpora lutea, p > 0.05) but did affect the embryo development (p 0.05). Independently of the type of seminal dose (F1, F2, or F3), we observed by immunohistochemistry that AI significantly increased uterine vascularization, although with some anatomical differences. The cranial region of the uterine horns was significantly more vascularized in AI-F1 or AI-F2 sows (26.7 ± 2.3 and 28.6 ± 2.0%, respectively), and AI-F3 showed significantly less vascularization at that point (17.8 ± 1.6%, p < 0.05). To summarize, the synergistic effect of all ejaculate fractions accelerates embryo development, at least during the preimplantation period, and increases the uterine reaction to AI in certain parts of the uterus

Re-design of EU DEMO with a low aspect ratio

The design point that had been chosen for EU DEMO in 2016 is reviewed here and a modification is proposed with a lower aspect ratio. Previously the same aspect ratio, A, was chosen for EU DEMO as in major tokamak experiments including ITER (A = 3.1), and, to rely on mature technology, a peak magnetic field no greater than 13 T was considered. Here we do not consider these limitations recognizing the recent commissioning of JT60-SA with A = 2.5 and the successful recent operation of a model coil at a field of >20 T. EU DEMO must have a burning plasma and meet performance requirements relevant to a fusion power plant - at present, 2 GW fusion power and 2 h pulse length. The better plasma confinement at higher magnetic field allows reaching this condition in a smaller plasma. Thus, increasing the magnetic field appears as an obvious strategy to reduce the machine size. We confirmed though previous observations that the choice of a high magnetic field is associated with a large aspect ratio, mainly to generate space for the larger TF coils. In practice the magnetic field strength on DEMO-size TF coils is limited to ∼12 T by the high electromagnetic loads. Also, the extreme heat flux on the divertor increases further with the magnetic field. Hence the magnetic field on the plasma axis is limited in EU DEMO to ∼5.4 T, its aspect ratio to approximately 3. The limiting factor to lowering the aspect ratio is the space on the inboard side. This is primarily driven by the requirement to integrate the central solenoid to drive the plasma current inductively. Our literature review suggests that non-inductive plasma scenarios, as considered in most power plant studies in literature, are optimistic and not sufficiently supported by experimental results. Also, the space required for the superconducting toroidal field coils, the tritium breeding blanket, and the neutron shield is substantial. For a DEMO device the space on the inboard side becomes insufficient for aspect ratios below ∼2.6. We therefore conclude the aspect ratio of EU DEMO should be chosen within the range ∼2.6 - ∼3.0 trading-off lower magnetic field and lower divertor heat loads against machine compactness

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