О Продавце
p-Synephrine (SN) is an alkaloid added to thermogenic formulations for weight loss that is predominantly absorbed in the human gastrointestinal tract (GI). As the adverse effects of SN on GI cells remain unclear, the aim of present study was to examine whether SN affected cell viability, cell cycle kinetics, genomic stability, redox status, and expression of cAMP/PKA pathway genes related to metabolism/energy homeostasis in stomach mucosa (MNP01) and colon adenocarcinoma (Caco-2) human cells. p-Synephrine at 25-5000 μM was not cytotoxic to both cell lines. At 2-200 μM, SN increased the formation of reactive oxygen species (ROS) but also enhanced levels of antioxidant defense molecules glutathione (GSH) and catalase (CAT) activity, which may account for the absence of cytotoxicity/mutagenicity in both cell lines. SN induced expression of the cAMP/PKA pathway genes ADCY3 and MAPK1 in MNP01 cells and MAPK1, GNAS, PRKACA, and PRKAR2A in Caco-2 cells, as well as modulated the transcription of genes related to cell proliferation (JUN; AKT1) and inflammation (RELA; TNF) in both cell lines. Therefore, the improved antioxidant state mitigated pro-oxidative effects attributed to SN. Evidence indicates that SN does not appear to exhibit adverse potential but modulated the cAMP/PKA pathway in human GI cell lines.While current clinical research generally employs complex computational methods to analyze large amounts of data, reproducible research is a growing movement within the scientific community. This methodology paper consists of five sections discussing the definitions of replicability, reproducibility, and reproducible research, the current status of reproducible research in nursing science, the introduction of a reproducible framework, and the challenges and recommendations for reproducible research. To ensure the data preprocessing process and data analysis of an original study at the minimum standard, it is necessary for the study's data investigative cycle to be transparent. Most arguments for reproducible research were driven by a critical review of journal articles and conference proceedings. The suggested methodological framework capturing how scientific research generates is expected to contribute to guiding nurse scientists to conduct reproducible research. To generate high-quality scientific evidence for evidence-based practice, the reproducible framework should be integrated into nursing research. To report our early experience using endografts with inner branches for the treatment of complex abdominal aortic aneurysms and thoracoabdominal aortic aneurysms (TAAAs). A retrospective analysis of all patients treated in our institution for complex abdominal aortic aneurysms and TAAAs with custom-made stent grafts consisting of one or more inner branches. Data collected included patients demographics, aortic aneurysm morphology, stent grafts features, perioperative morbidity and mortality and short-term reintervention and mortality rates. Twenty-seven patients (18 males, mean age 70 ± 7.1) were included. Indications for surgery included TAAAs (12, 41%) juxtarenal abdominal aortic aneurysms (10, 37%), type 1A endoleaks (4, 15%) and paraanastamotic aneurysms (1, 4%). A total of 90 inner branches were used. Twenty-one (78%) of the stent grafts consisted only of inner branches and six (22%) had a combination of inner branches with either fenestrations or outer branches. Technical success was achieved in 2Further follow-up is required to determine the long-term durability of this technology.A 27-y-old Anglo-Arabian gelding with bay coat color was presented with a swelling of the left maxillary region. Fenestration on the left maxilla revealed that the left maxillary sinus was filled with black-red tissue. A portion of the tissue was excised and diagnosed histologically as malignant melanoma. Genotyping of the STX17 gene for gray coat color revealed that the horse did not have the "gray" factor. TPOXX The horse was euthanized ~3 mo after first presentation. During autopsy, a black-to-gray mass extended from the left nasal cavity to the surrounding paranasal sinus and invaded the hard palate, cribriform plate, and the cranial portion of the left olfactory bulb. Moreover, identical black nodules were present in lymph nodes from the mandible to the larynx, and in the spleen, liver, kidney, and adrenal glands. However, masses were not found in the skin, perineal region, or pelvic cavity. All of the black-to-gray nodules were malignant melanomas that were histologically identical to the initial biopsy; tumor emboli were also found in the kidney. Sinonasal mucosal melanoma is a rare disease in horses.The pandemic disease COVID-19, caused by SARS CoV-2, has created a global crisis. Presently, researchers across the globe are in a quest to identify/develop drugs or vaccines by targeting different non-structural proteins (Nsps) of SARS CoV-2. One such important drug target is Nsp5/main protease (Mpro) which plays a critical role in the viral replication. This cysteine protease/Mpro of SARS CoV-2 has high sequence similarity with the same protease from SARS CoV-1. Previously, it has been shown experimentally that eight polyphenols derived from the root of Isatis indigotica show inhibitory effect on the cleavage/catalytic activity of the SARS CoV-1 Mpro. But whether these polyphenols exhibit any inhibitory effect on SARS CoV-2 Mpro is unclear. To explore this possibility, here, we have adopted various computational approaches. Polyphenols that qualified the pharmacological parameters (indigo, sinigrin, hesperetin and daidzein) and two well-known Mpro inhibitors (N3 and lopinavir) were subjected to molecular docking studies. Two of them (sinigrin and hesperetin) were selected by comparing their binding affinities with N3 and lopinavir. Sinigrin and hesperetin interacted with the two most important catalytic residues of Mpro (His41 and Cys145). Molecular dynamics studies further revealed that these two Mpro-polyphenol complexes are more stable and experience less conformational fluctuations than Mpro-N3/lopinavir complex. The Mpro-hesperetin complex was more compact and less expanded than Mpro-sinigrin complex. These findings were additionally validated by MM-GBSA analysis. As a whole, our study revealed that these two polyphenols may be potent SARS CoV-2 Mpro inhibitors and may possibly be considered for COVID-19 treatment.