Notes

Deep-learning-based graphic enrollment for nano-resolution tomographic reconstruction.
Coronavirus 2019 (COVID-19) is a pandemic with substantial mortality and no accepted therapy. We report here on four consecutive outpatients with clinical characteristics (CDC case definition) of and/or laboratory-confirmed COVID-19 who were treated with high dose zinc salt oral lozenges. All four patients experienced significant improvement in objective and symptomatic disease measures after one day of high dose therapy suggesting that zinc therapy was playing a role in clinical recovery. A mechanism for zinc's effects is proposed based on previously published studies on SARS- CoV-1, and randomized controlled trials assessing zinc shortening of common cold duration. The limited sample size and study design preclude a definitive statement about the effectiveness of zinc as a treatment for COVID-19 but suggest the variables to be addressed to confirm these initial findings in future trials.Polyphenols are phytochemical compounds found mostly in plants with several biological properties. Many of the benefits attributed to fruits and vegetables have been linked to their content in these molecules. As a result, the last decade has witnessed an increase in polyphenol-derived compounds claiming diverse therapeutic properties. Although the mechanism of action of such compounds is yet to be fully disclosed, one of the components that recently has been proposed to participate significantly in the health properties of polyphenols is the type 2 taste receptors (T2Rs). These receptors are responsible for the detection of bitter taste and represent the first line of defence against potentially harmful components in food. The recent discovery of extra-oral T2Rs in several metabolically active tissues has generated intense interest in the potential health impact. Given that most phenolic molecules taste bitter, exploring the T2Rs as a putative pharmacological target for the development of plant-based drug therapies is a promising field of research. Some T2Rs are involved in the control of cilia beat frequency and smooth muscle relaxation in the air tract together with leukocyte homeostasis, important events disrupted in the high prevalence of respiratory diseases. Furthermore, T2Rs are involved in nutrient-gut interactions to modulate gut hormones that influence gastrointestinal motility, appetite and glycemia. Thus, this commentary focuses on the latest novelty advances in relation to the peripheral expression of T2Rs, and polyphenols and T2Rs relationship from a therapeutic point of view.The therapeutic effect of gemcitabine (GEM) in pancreatic ductal adenocarcinoma (PDAC) is limited due to low drug sensitivity and high drug resistance. Tissue inhibitor of matrix metalloprotease 1 (TIMP1) is reportedly associated with GEM resistance in PDAC. However, the effect of TIMP1 down-regulation in combination with GEM treatment is unknown. We analyzed the expression of TIMP1 in human PDAC tissue using western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry. TIMP1 was highly expressed in PDAC specimens. Kaplan-Meier survival analysis suggested that a higher level of TIMP1 was correlated with poorer overall survival in 103 PDAC patients. The mRNA and protein expression profiles of TIMP1 were explored in the HTERT-HPNE human pancreatic ductal epithelium cell line, five PDAC cell lines (MIA PaCa-2, PANC-1, BxPC-3, Capan2, and SW1990), and two GEM-resistant PDAC cell lines (MIA PaCa-2R and PANC-1R). Compared with HTERT-HPNE, TIMP1 was highly expressed in the PDAC cell lines. In addition, TIMP1 was upregulated in GEM-resistant PDAC cell lines compared with their parental cells. When TIMP1 was knocked-down using short hairpin RNA, GEM-induced cytotoxicity and apoptosis were increased, while colony formation was repressed in MIA PaCa-2, PANC-1, and their GEM-resistant cells. When Bax was activated by BAM7 or Bcl-2 was inhibited by venetoclax, CCK-8 assays demonstrated that GEM sensitivity was restored in GEM-resistant cells. When Bax was down-regulated by siRNA, CCK-8 assays verified that GEM sensitivity was decreased in PDAC cells. The observations that TIMP1 knockdown enhanced GEM sensitivity and reversed chemoresistance by inducing cells apoptosis indicated cooperative antitumor effects of shTIMP1 and GEM therapy on PDAC cells. The combination may be a potential strategy for PDAC therapy.Methotrexate (MTX) induces the formation of reactive oxygen species (ROS) and leads to neurotoxicity. The drug also negatively impacts neurogenesis and memory. Hesperidin (Hsd) is a major flavanoid with multiple beneficial pharmacological effects such as anti-oxidation, anti-inflammation, and neuroprotective effects. The aim of our study was to investigate the neuroprotective effects of Hsd against MTX-induced alterations in oxidative stress and neurogenesis. Sprague Dawley rats were divided into four groups 1) a vehicle group, which received saline and propylene glycol, 2) an Hsd group, which was orally administered with Hsd (100 mg/kg) for 21 days, 3) an MTX group, which received MTX (75 mg/kg) by intravenous injection on days 8 and 15, and 4) an MTX + Hsd group, which received both MTX and Hsd. After treatment with MTX, p21-positive cells had increased significantly and doublecortin (DCX) expression in the hippocampus had decreased significantly. AZD8186 datasheet Treatment with MTX also increased malondialdehyde (MDA) in both the hippocampus and prefrontal cortex and decreased levels of brain-derived neurotropic factor (BDNF) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the hippocampus and prefrontal cortex. Additionally, there were significant decreases in superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the hippocampus and prefrontal cortex in the MTX group. However, co-treatment with Hsd ameliorated the negative effects of MTX on neurogenesis, oxidative stress, and antioxidant enzymes. These findings suggest that Hsd may be able to prevent neurotoxic effects of MTX by reducing oxidative stress and enhancing hippocampal neurogenesis.Food crops produced by new technologies such as genetic engineering are widely opposed (Gaskell, Bauer, Durant, & Allum, 1999; Scott, Inbar, Wirz, Brossard, & Rozin, 2018). Here, we examine one reason for this opposition recency. More recently-developed crops are evaluated less favorably, whether they are produced by artificial selection (i.e., conventional breeding), natural or man-made irradiation, or genetic engineering. Negative effects of recency persist in a within-subjects design where people are able to explicitly compare crops developed at different times, and an internal meta-analysis shows that the negative effect of recency is robust across measures and stimuli. These results have implications for the evaluation of crops produced using new modification techniques, including the widespread opposition to genetic engineering.
Homepage: https://www.selleckchem.com/products/azd8186.html