Expression and functional role of formyl peptide receptor in human bone marrow-derived mesenchymal stem cells

AbstractWe investigated the expression of formyl peptide receptor (FPR) and its functional role in human bone marrow-derived mesenchymal stem cells (MSCs). We analyzed the expression of FPR by using ligand-binding assay with radio-labeled N-formyl-met-leu-phe (fMLF), and found that MSCs express FPR. FMLF stimulated intracellular calcium increase, mitogen-activated protein kinases activation, and Akt activation, which were mediated by Gi proteins. MSCs were chemotactically migrated to fMLF. FMLF-induced MSC chemotaxis was also completely inhibited by pertussis toxin, LY294002, and PD98059, indicating the role of Gi proteins, phosphoinositide 3-kinase, and extracellular signal regulated protein kinase. N-terminal fragment of annexin-1, Anx-1(2–26), an endogenous agonist for FPR, also induced chemotactic migration of MSCs. Thus MSCs express functional FPR, suggesting a new (patho)physiological role of FPR and its ligands in regulating MSC trafficking during induction of injured tissue repair

Inhibitory Potencies of Several Iridoids on Cyclooxygenase-1, Cyclooxygnase-2 Enzymes Activities, Tumor Necrosis factor-α and Nitric Oxide Production In Vitro

To verify the anti-inflammatory potency of iridoids, seven iridoid glucosides (aucubin, catalpol, gentiopicroside, swertiamarin, geniposide, geniposidic acid and loganin) and an iridoid aglycone (genipin) were investigated with in vitro testing model systems based on inhibition of cyclooxygenase (COX)-1/-2 enzymes, the tumor necrosis factor-α (TNF-α) formation and nitric oxide (NO) production. The hydrolyzed-iridoid products (H-iridoid) with β-gludosidase treatment only showed inhibitory activities, and revealed different potencies, depending on their chemical structures. Without the β-gludosidase treatment, no single iridoid glycoside exhibited any activities. The aglycone form (genipin) also did not show inhibitory activities. To compare anti-inflammatory potency, the inhibitory concentrations (IC50) in each testing system were measured. The hydrolyzed-aucubin product (H-aucubin) with β-gludosidase treatment showed a moderate inhibition on COX-2 with IC50 of 8.83 μM, but much less inhibition (IC50, 68.9 μM) on COX-1 was noted. Of the other H-iridoid products, the H-loganin and the H-geniposide exhibited higher inhibitory effects on COX-1, revealing IC50 values of 3.55 and 5.37 μM, respectively. In the case of TNF-α assay, four H-iridoid products: H-aucubin, H-catalpol, H-geniposide and H-loganin suppressed the TNF-α formation with IC50 values of 11.2, 33.3, 58.2 and 154.6 μM, respectively. But other H-iridoid products manifested no significant activity. Additional experiments on NO production were conducted. We observed that only the H-aucubin exhibited a significant suppression with IC50 value of 14.1 μM. Genipin, an agycone form, showed no inhibitory effects on all testing models, implying the hydrolysis of the glycosidic bond of iridoid glycoside is a pre-requisite step to produce various biological activities

The development of a web-based app employing machine learning for delirium prevention in long-term care facilities in South Korea

Background Long-term care facilities (LCFs) in South Korea have limited knowledge of and capability to care for patients with delirium. They also often lack an electronic medical record system. These barriers hinder systematic approaches to delirium monitoring and intervention. Therefore, this study aims to develop a web-based app for delirium prevention in LCFs and analyse its feasibility and usability. Methods The app was developed based on the validity of the AI prediction model algorithm. A total of 173 participants were selected from LCFs to participate in a study to determine the predictive risk factors for delerium. The app was developed in five phases: (1) the identification of risk factors and preventive intervention strategies from a review of evidence-based literature, (2) the iterative design of the app and components of delirium prevention, (3) the development of a delirium prediction algorithm and cloud platform, (4) a pilot test and validation conducted with 33 patients living in a LCF, and (5) an evaluation of the usability and feasibility of the app, completed by nurses (Main users). Results A web-based app was developed to predict high risk of delirium and apply preventive interventions accordingly. Moreover, its validity, usability, and feasibility were confirmed after app development. By employing machine learning, the app can predict the degree of delirium risk and issue a warning alarm. Therefore, it can be used to support clinical decision-making, help initiate the assessment of delirium, and assist in applying preventive interventions. Conclusions This web-based app is evidence-based and can be easily mobilised to support care for patients with delirium in LCFs. This app can improve the recognition of delirium and predict the degree of delirium risk, thereby helping develop initiatives for delirium prevention and providing interventions. Moreover, this app can be extended to predict various risk factors of LCF and apply preventive interventions. Its use can ultimately improve patient safety and quality of care. © 2022, The Author(s).1

Comparison of postoperative changes in the distal and proximal segments between conventional and sliding mini-plate fixation following mandibular setback

The purpose of the present study was to evaluate the postoperative three-dimensional (3D) changes in the proximal segments after mandibular setback sagittal split ramus osteotomy and to compare the changes between the conventional mini-plate fixation and semi-rigid sliding plate fixation

Multiomics analysis reveals that GLS and GLS2 differentially modulate the clinical outcomes of cancer

Acknowledgements: This work was supported by the Deanship of Scientific Research at King Saud University through Research Group Grant RGP-1438-044.Peer reviewe

Human Plasmablast Migration Toward CXCL12 Requires Glucose Oxidation by Enhanced Pyruvate Dehydrogenase Activity via AKT

Migration of human plasmablast to the bone marrow is essential for the final differentiation of plasma cells and maintenance of effective humoral immunity. This migration is controlled by CXCL12/CXCR4-mediated activation of the protein kinase AKT. Herein, we show that the CXCL12-induced migration of human plasmablasts is dependent on glucose oxidation. Glucose depletion markedly inhibited plasmablast migration by 67%, and the glucose analog 2-deoxyglucose (2-DG) reduced the migration by 53%; conversely, glutamine depletion did not reduce the migration. CXCL12 boosted the oxygen consumption rate (OCR), and 2-DG treatment significantly reduced the levels of all measured tricarboxylic acid (TCA) cycle intermediates. AKT inhibitors blocked the CXCL12-mediated increase of OCR. CXCL12 enhanced the pyruvate dehydrogenase (PDH) activity by 13.5-fold in an AKT-dependent manner to promote mitochondrial oxidative phosphorylation. The knockdown and inhibition of PDH confirmed its indispensable role in CXCL12-induced migration. Cellular ATP levels fell by 91% upon exposure to 2-DG, and the mitochondrial ATP synthase inhibitor oligomycin inhibited CXCL12-induced migration by 85%. Low ATP levels inhibited the CXCL12-induced activation of AKT and phosphorylation of myosin light chains by 42%, which are required for cell migration. Thus, we have identified a mechanism that controls glucose oxidation via AKT signaling and PDH activation, which supports the migration of plasmablasts. This mechanism can provide insights into the proper development of long-lived plasma cells and is, therefore, essential for optimal humoral immunity. To our knowledge, this study is the first to investigate metabolic mechanisms underlying human plasmablast migration toward CXCL12

Detection of Single Nanoparticles inside a Single Terahertz Resonator

With the rapid advancement of 5G/6G communications using millimeter wavelengths, the concomitant usage of these long wavelength radiation for remote sensing and monitoring of biological and chemical agents is anticipated. However, the ability to detect and identify these agents with sizes ranging from nanometers to microns is hampered by its millimeter wavelength, which drastically reduces the interaction cross-section. Herein, it is reported that single gold nanoparticles (NPs) drop-casted on the nanoresonator can be observed by monitoring the far-field transmitting spectra of individual terahertz (THz) nanoresonators, which enhance the electric field hundreds of times on the nanoscale. Despite the enormous mismatch in length scales, full-wave 3D numerical modeling of the single THz nanoresonator is also performed to interpret the experimental results, indicating the possibility to turn off the resonance using only one NP embedded in the hotspot of the nanoresonator. Such NP detection becomes the most sensitive when the particle, whose size is comparable to the gap width, is tightly fitted into the nanoresonator. This work unveils the potential associated with refractive index sensing and hyperspectral absorption spectroscopy for detecting and fingerprinting ultra-low density of bio/chemical molecules such as viruses, lipid vesicles, and explosives

The Traditional Herbal Medicine, Dangkwisoo-San, Prevents Cerebral Ischemic Injury through Nitric Oxide-Dependent Mechanisms

Dangkwisoo-San (DS) is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO) production in human brain microvascular endothelial cells (HBMECs). DS (10–300 μg/mL) produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS) inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF), although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS) inhibitor, N5-(1-iminoethyl)-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation

Refractory Duodenal Crohn's Disease Successfully Treated with Infliximab

Crohn's disease (CD) may involve any part of the gastrointestinal tract, from the mouth to the anus. Approximately >90% of cases occur in the small bowel and colon. Upper gastrointestinal involvement, especially duodenal manifestation, is relatively rare. Therefore, adequate medical treatment for duodenal CD has not yet been established. We report a case of CD with duodenal involvement. A 46-year-old man with Crohn's ileocolitis presented to our hospital with right upper quadrant pain. An endoscopy showed a deep excavated ulcer with deformity at the duodenal bulb, and he was initially treated with azathioprine (1 mg/kg), Pentasa (3.0 g/day), and a proton pump inhibitor for 1 year. However, the deep ulcer did not heal. Therefore, infliximab infusion therapy was initiated, and the duodenal lesion completely resolved on follow-up esophagogastroduodenoscopy. We report a case of duodenal CD that completely resolved following infliximab infusion, with a review of the literature