Cannabinoid Receptor Subtype 2 (Cb2R) Agonist Gw405833 Reduces Agonist-Induced Ca2+ Oscillations In Mouse Pancreatic Acinar Cells

Emerging evidence demonstrates that the blockade of intracellular Ca 2+ signals may protect pancreatic acinar cells against Ca 2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB 2 R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB 2 Rs modulate intracellular Ca 2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB 2 R agonist, GW405833 (GW) in agonist-induced Ca 2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB 1 R-knockout (KO), and CB 2 R-KO mice. Immunohistochemical labeling revealed that CB 2 R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB 2 Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca 2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB 2 R antagonist, AM630, or was absent in CB 2 R-KO but not CB 1 R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca 2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB 2 Rs eliminates ACh-induced Ca 2+ oscillations and L-arginine-induced enhancement of Ca 2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB 2 R-mediated protection in acute pancreatitis

Simultaneous arthroscopic cystectomy and unicompartmental knee arthroplasty for the management of partial knee osteoarthritis with a popliteal cyst: A case report

IntroductionPopliteal cysts are secondary to degenerative changes in the knee joint. After total knee arthroplasty (TKA), 56.7% of patients with popliteal cysts at 4.9 years follow-up remained symptomatic in the popliteal area. However, the result of simultaneous arthroscopic cystectomy and unicompartmental knee arthroplasty (UKA) was uncertain.Case presentationA 57-year-old man was admitted to our hospital with severe pain and swelling in his left knee and the popliteal area. He was diagnosed with severe medial unicompartmental knee osteoarthritis (KOA) with a symptomatic popliteal cyst. Subsequently, arthroscopic cystectomy and unicompartmental knee arthroplasty (UKA) were performed simultaneously. A month after the operation, he returned to his normal life. There was no progression in the lateral compartment of the left knee and no recurrence of the popliteal cyst at the 1-year follow-up.ConclusionFor KOA patients with a popliteal cyst seeking UKA, simultaneous arthroscopic cystectomy and UKA are feasible with great success if managed appropriately

Research progress on and molecular mechanism of vacuum sealing drainage in the treatment of diabetic foot ulcers

Diabetic foot ulcers (DFUs) are common chronic wounds and a common complication of diabetes. The foot is the main site of diabetic ulcers, which involve small and medium-sized arteries, peripheral nerves, and microcirculation, among others. DFUs are prone to coinfections and affect many diabetic patients. In recent years, interdisciplinary research combining medicine and material science has been increasing and has achieved significant clinical therapeutic effects, and the application of vacuum sealing drainage (VSD) in the treatment of DFUs is a typical representative of this progress, but the mechanism of action remains unclear. In this review, we integrated bioinformatics and literature and found that ferroptosis is an important signaling pathway through which VSD promotes the healing of DFUs and that System Xc-GSH-GPX4 and NAD(P)H-CoQ10-FSP1 are important axes in this signaling pathway, and we speculate that VSD is most likely to inhibit ferroptosis to promote DFU healing through the above axes. In addition, we found that some classical pathways, such as the TNF, NF-κB, and Wnt/β-catenin pathways, are also involved in the VSD-mediated promotion of DFU healing. We also compiled and reviewed the progress from clinical studies on VSD, and this information provides a reference for the study of VSD in the treatment of DFUs

Research on sensing characteristics of diamond multilayer waveguide structure racetrack micro-ring resonator

A racetrack micro-ring resonant cavity sensor based on the diamond's material is proposed in this paper. In the model, the vertical-section of the waveguide adopts a five-layer ridge-type waveguide structure based on CH3NH3PbI3, SiO2 and diamond, i.e. CH3NH3PbI3-SiO2-Diamond-SiO2-CH3NH3PbI3. First, on the basis of the resonant principle and coupled mode theory, this study investigated the light field intensity distribution characteristics of the integral resonant cavity, the longitudinal section of a single straight waveguide, the racetrack micro-ring, and the longitudinal section of the straight waveguide by using the finite element method in COMSOL. The analysis shows that the introduction of CH3NH3PbI3 as an isolation layer can avoid the light scattering loss and leakage loss, and significantly enhance the filtering performance. In addition the sensing characteristics of the Add-drop racetrack resonator were further studied. Results showed that the structure could achieve a quality factor of 105, and the sensitivity could reach 14833.33 dB/RIU. In the detection system with a signal-to-noise ratio of 30 dB, the detection limit was 2.02 × 10−7 RIU. Compared with the traditional All-pass single micro-ring resonator, the proposed structure shows advantages of high tenability, high sensitivity and low detection limit

Exploring the association between COVID-19 and male genital cancer risk in European population: evidence from mendelian randomization analysis

Abstract Background Recently accumulated evidence indicates a potential association between COVID-19 and elevated susceptibility to cancer, including male genital cancer. However, the causal nature of this relationship remains unclear. Methods In this Mendelian randomization (MR) study, we investigated the potential causal relationship between COVID-19 and male genital cancer using genetic variants as instrumental variables. We utilized summary statistics from two large-scale genome-wide association studies of COVID-19 hospitalized Vs. controls, as well as data from a population-based male genital cancer database based on European ancestry. We applied stringent quality control measures to select instrumental variables, including checking for linkage disequilibrium, removing low-quality variants, and assessing the strength of the instruments using the F-statistic. We conducted the MR  analysis using the inverse-variance weighted method and several sensitivity analyses (including MR Egger and Weighted Median MR analysis) to test the robustness of our results. Results Our MR analysis revealed no causal associations between COVID-19 hospitalization and the incidence of male genital cancer. In the inverse-variance weighted analysis, no causal associations were observed between patients with COVID-19 hospitalization and the incidence of male genital cancer (odds ratio = 1.000 and 95% confidence interval = 0.998-1.001, p = 0.668). The estimated causal effect was consistent across all sensitivity analyses (including the Weighted Median, the MR Egger analysis, and the MR PROSSO analysis). The leave-one-out analysis showed that there was no any sing Single-nucleotide polymorphism significantly influencing our results. Conclusions Our study provides evidence that there is no causal association between COVID-19 hospitalization and male genital cancer

Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells

Emerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB(2)Rs modulate intracellular Ca2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB(2)Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB(2)Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis.Seed Fund of Shangtou University Medical College; Guangdong Science and Technology FoundationOpen Access JournalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]