Vangsgaarderiksen2083

The carnage wrought by systemic racism through social, judicial, and health injustices compels us to work towards a system that is fair and just for patients and colleagues. The evidence that change is necessary in medicine is hiding in plain sight in literature, oral histories, medical records, and news media. Notwithstanding this evidence, changing a system 400 years in the making will require a major paradigm shift. One of the many ways our department sought to catalyze such a shift was through media consumption, reflection, and discussion. Reading and studying literature and humanities in medicine can awaken our consciousness by making medicine an embodied practice that considers the totality of patients' lives in ways that a disembodied, purely scientific approach cannot. Thus, we started a Racial and Social Justice Book Club to normalize discussions about racial and social (in)justice and examine everything through an anti-racist lens. Herein, we describe our experiences in the inaugural year of the Book Club, a space to lend credence and dignity to the voices, experiences, and stories of folks who have long been marginalized by power structures in America, including medicine.We present the fabrication of three-dimensional inlets with gradually decreasing widths and depths and with nanopillars on the slope, all defined in just one lithography step. In addition, as an application, we show how these micro- and nanostructures can be used for micro- and nanofluidics and lab-on-a-chip devices to facilitate the flow and analyze single molecules of DNA. For the fabrication of 3D inlets in a single layer process, dose-modulated electron beam lithography was used, producing depths between 750 nm and 50 nm along a 30 μm long inlet, which is additionally structured with nanometer-scale pillars randomly distributed on top, as a result of incomplete exposure and underdevelopment of the resist. The fabrication conditions affect the slope of the inlet, the nanopillar density and coverage. The key parameters are the dose used for the electron beam exposure and the development conditions, like the developer's dilution, stirring and development time. The 3D inlets with nanostructured pillars were integrated into fluidic devices, acting as a transition between micro and nanofluidic structures for pre-stretching and unfolding DNA molecules, avoiding the intrusion of folded molecules and clogging the analysis channel. After patterning these structures in silicon, they can be replicated in polymer by UV nanoimprinting. We show here how the inlets with pillars slow down the molecules before they enter the nanochannels, resulting in a 3-fold decrease in speed, which would translate to an improvement in the resolution for DNA optical mapping.L-lysine (L-lys) had long been comprehended as an essential amino acid for humans. There were reports that the absence or inadequate availability of L-lys in the diet may lead to mental and physical impairments. The present study was designed to explore the effects of L-lys on body weight changes, cumulative food intake, anxiety-like behavior and pain perception in rats. 5-Hydroxytryptamine (5-HT, serotonin) metabolism, and tryptophan (Trp) levels in the midbrain (MB), hippocampus (HP), and prefrontal cortex (PFC) were also determined. Animals were treated with L-lys in doses of 0.5 g/kg and 1 g/kg for 20 days and behavioral studies were performed on day 1st and day 20th. After monitoring behaviors on day 20th, animals were killed to collect the serum and brain regions MB, HP and PFC. 5-HT metabolism and Trp levels were determined by HPLC-EC. The treatment produce no effect on food intakes but body weights were reduced. 20 days administration of L-lys produced an anxiolytic effect and increased exploratory activity on day 1st. Repeated administration of L-lys increased 5-HT levels in the PFC and HP. 5-Hydroxyindoleacetic acid (5-HIAA), the metabolite of 5-HT, decreased in the HP. Trp, the precourser of 5-HT, decreased in the PFC. Results suggested a decrease in 5-HT degredation in enhancing 5-HT levels. Results of in-silico analysis showed that lysine had a potential binding affinity for MAO (monoamine oxidase) A and B with an energy of (-4.8 kcal/mol and -5.3 kcal/mol) respectively. The molecular dynamic simulation study revealed the stability of L-lys after 10 ns for each protein. Conclusively, the present study showed that L-lys produced an anxiolytic effect and reduced body weight. These beneficial effects were associated with an increase in 5-HT levels in the PFC and HP. In-silico analysis suggested that 5-HT increase were due to the binding of L-lys with MAOs resulting in an inhibition of the degradation of monoamine.To evaluate the antinociceptive effect and the possible mechanism of action of two polar extracts of Mansoa alliacea, a medicinal plant used in Perú, Brazil, and Mexico to treat rheumatic pain, we used the formalin and hot-plate tests in mice. We found that ethanolic (MA-EtOH) and aqueous (MA-AQ) extracts of M. alliacea induced antinociceptive effects in both nociceptive tests. The antinociceptive efficacy of the highest dosage (300 mg/kg) of both extracts were also compared by using intraperitoneal and oral administration in the formalin test. Results showed that intraperitoneal injection of the two extracts produced better antinociceptive effects than that obtained by their oral administration. The mechanism of action involved in their antinociceptive activity was determined in the formalin test. Results showed that the presence of A784168 (TRPV1 antagonist) did not alter the antinociceptive effect induced by any of the M. alliacea extracts, whereas naltrexone (opioid antagonist) partially prevented the antinociceptive effect only of MA-EtOH in both phases of the formalin test. Furthermore, the effects of the extracts were diminished by L-NAME (inhibitor of nitric oxide synthase), but not by ODQ (inhibitor of the soluble guanylyl cyclase) or glibenclamide (blocker of K+ATP channels) in the neurogenic phase. SAR405 However, the effect of MA-AQ was diminished by all the inhibitors in the inflammatory phase. These results support the use of M. alliacea as a potential natural product with efficacy for pain relief depending on the form of preparation and the route of administration by involving opioid receptors and the production of nitric oxide.Cell therapy is one of the new treatment methods in which mesenchymal stem/stromal cell (MSCs) transplantation is one of the cells widely used in this field. The results of MSCs application in the clinic prove their therapeutic efficacy. For this reason, many clinical trials have been designed based on the application of MSCs for various diseases, especially inflammatory disease and regenerative medicine. These cells perform their therapeutic functions through multiple mechanisms, including the differentiative potential, immunomodulatory properties, production of therapeutic exosomes, production of growth factors and cytokines, and anti-apoptotic effects. Exosomes are nanosized extracellular vesicles (EVs) that change target cell functions by transferring different cargos. The therapeutic ability of MSCs-derived exosomes has been demonstrated in many studies. However, some limitations, such as the low production of exosomes by cells and the need for large amounts of them and also their limited therapeutic ability, have encouraged researchers to find methods that increase exosomes' therapeutic potential. One of these methods is the spheroid culture of MSCs. Studies show that the three-dimensional culture (3DCC) of MSCs in the form of multicellular spheroids increases the therapeutic efficacy of these cells in laboratory and animal applications. In addition, the spheroid culture of MSCs leads to enhanced therapeutic properties of their exosomes and production rate. Due to the novelty of the field of using 3DCC MSCs-derived exosomes, examination of their properties and the results of their therapeutic application can increase our view of this field. This review discussed MSCs and their exosomes enhanced properties in spheroid culture.Veronica persica is a flowering plant belonging to the family Scrophulariaceae. Here, we aimed to evaluate the pharmacological activity of the ethanol extract of Veronica persica (EEVP) in an airway inflammation model. We examined airway responsiveness to aerosolized methacholine, serum immunoglobulin (Ig)E levels, and total cell numbers in the lung and bronchoalveolar lavage fluid (BALF). Histological analysis of the lung tissue was performed using hematoxylin-eosin, Masson trichrome, or periodic acid-Schiff staining. Fluorescence-activated cell sorting analysis in the lung and BALF was applied to clarify the changes in immune cell types. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction were applied to investigate cytokine levels and gene expression related to airway inflammation. STAT-3/6 phosphorylation was examined in primary bronchial/tracheal epithelial cells using western blot analysis. EEVP significantly suppressed total IgE levels and methacholine-induced increase of Penh value in the HDM-challenged mouse model. EEVP also attenuated the severity of airway remodeling in lung tissues and decreased eosinophil and neutrophil infiltration in the lungs and BALF. EEVP significantly reduced the production of cytokines in BAL and splenocyte culture medium, and the expression of mRNAs related to airway inflammation in the lung tissue. EEVP suppressed IL-4/13-induced STAT-3/6 phosphorylation in the epithelial cells. We showed for the first time that EEVP effectively inhibits eosinophilic airway inflammation by suppressing the expression of inflammatory factors for T cell activation and polarization, and inhibits MCP-1 production of bronchial/tracheal epithelial cells by suppressing STAT-3/6 activation. EEVP may be a potential pharmacological agent to prevent inflammatory airway diseases.Chrysosplenium is the main component of a variety of Tibetan prescription preparations. Nevertheless, there are few chemical reports for different species of Chrysosplenium, which should be further explored. To this end, ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (UPLC-Q Exactive Orbitrap HRMS) and high-performance liquid chromatography-diode array detection (HPLC-DAD) were first integrated to qualitatively analyse the chemical characteristics of Chrysosplenium nudicaule, Chrysosplenium carnosum, Chrysosplenium sikangense, Chrysosplenium griffithii, Chrysosplenium absconditicapsulum, Chrysosplenium forrestii and Chrysosplenium axillare. As a result, a total of 40 compounds were identified or tentatively identified from these 7 species of Chrysosplenium, including 21 flavonoids, 3 triterpenoids and a variety of alkaloids, organic acids and anthraquinones, etc. Among them, 6 compounds were detected for the first time, and 8 compounds are common components in all 7 species of Chrysosplenium. In the specific chromatogram, 4 characteristic peaks, namely Riboflavin, 5,4'-dihydroxy-3,6,3'-trimethoxyflavin-7-O-β-D-glucoside, 5,7,3'-trihydroxy-6,4',5'-trimethoxyflavone and Chrysosplenetin, were selected to evaluate the similarities of 17 batches of Chrysosplenium samples, which ranged from 0.770 to 0.994. The established method is simple, feasible and accurate, and was proven to be suitable for characterizing the chemical compositions of Chrysosplenium from different species and evaluating their similarities by specific chromatogram analysis to clarify the rationality of using Chrysosplenium from different species in clinical medication, which provides experimental data for further quality evaluation of Chrysosplenium.