Johansenvilladsen4681

However, these compounds have the capacity to prevent signs of neuroinflammation such as the activation of astrocytes and glial cells, as well as MPTP-induced reduction of BDNF levels in key regions of the brain implicated in motor functions. These findings suggest that selective S1P1R modulation has the ability to provide neuroprotection in response to MPTP neurotoxicity. Targeting S1P1R in PD therapy may represent a prominent candidate for treatment of this neurodegenerative conditions. Copyright © 2020 Pépin, Jalinier, Lemieux, Massicotte and Cyr.Introduction Acoustic cluster therapy (ACT) comprises co-administration of a formulation containing microbubble/microdroplet clusters (PS101), together with a regular medicinal drug (e.g., a chemotherapeutic) and local ultrasound (US) insonation of the targeted pathological tissue (e.g., the tumor). PS101 is confined to the vascular compartment and, when the clusters are exposed to regular diagnostic imaging US fields, the microdroplets undergo a phase-shift to produce bubbles with a median diameter of 22 µm when unconstrained by the capillary wall. In vivo these bubbles transiently lodge in the tumor's microvasculature. Low frequency ultrasound (300 kHz) at a low mechanical index (MI = 0.15) is then applied to drive oscillations of the deposited ACT bubbles to induce a range of biomechanical effects that locally enhance extravasation, distribution, and uptake of the co-administered drug, significantly increasing its therapeutic efficacy. Methods In this study we investigated the therapeutic efficacy of ACT wesponse during clinical use. Copyright © 2020 Bush, Healey, Shah, Box, Kirkin, Eccles, Sontum, Kotopoulis, Kvåle, van Wamel, Davies and Bamber.Diabetic nephropathy is a common complication in diabetes, but still lack of effective therapeutic strategies. This study aimed to investigate the therapeutic effect of basic fibroblast growth factor (bFGF) in db/db mice with diabetic nephropathy and explore its possible metabolic mechanisms using a nuclear magnetic resonance-based metabolomic approach. We found that bFGF treatment significantly alleviate urinary albumin to creatinine ratio and renal fibrosis in db/db mice, suggesting a potential renal protective effect. Metabolomics results reveal that bFGF remodeled metabolic phenotypes of the kidney and urine in db/db mice, mainly involving energy metabolism, methylamine metabolism, osmoregulation, and oxidative stress. Furthermore, the results show that bFGF-induced reductions of oxidative stress and apoptosis in db/db mice might be mediated by NOX-ROS-Nrf2 signaling. Therefore, our study suggests that the protective effect of bFGF on diabetic nephropathy could be mediated by remodeling metabolic phenotype and suppressing oxidative stress. Copyright © 2020 Wei, Shu, Ning, Wang, Li, Zhao, Zheng and Gao.Ischemic stroke patients suffer from relatively limited treatment options. Studies have shown that in cerebral ischemia, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a key mediator in mediating inflammatory responses and results in activation of apoptosis signaling pathways. Here we assessed the in vivo and in vitro effects of Qingnao Dripping Pills (QNDP), a traditional Chinese prescription, on inflammatory responses and apoptosis. Our results showed that QNDP could significantly decrease cerebral ischemia injury, improve neurological function and inhibit apoptosis in rats impaired by middle cerebral artery occlusion (MCAO). Further, we found that QNDP inhibited NLRP3 inflammasome expression both in MCAO rats and in SH-SY5Y cells under OGD. Moreover, the levels of inflammatory cytokines including interleukin-1β (IL-1β) and IL-18, which mediated by NLRP3 inflammasome and increased in MCAO rats, could be reduced by QNDP, suggesting that QNDP could protect the neurons against inflammation through a mechanism mediated by NLRP3 inflammasome. Nuclear factor-kappa B (NF-κB) was also involved in the anti-inflammatory effect of QNDP. In conclusion, QNDP had neuroprotective effects against cerebral ischemia via inhibiting NLRP3 inflammasome signaling pathway, and was a potential candidate for the future treatment of ischemic stroke. Copyright © 2020 Fu, Zhang, Zeng, Tian, Jin, Wang, Xu, Chen, Zheng and Liu.Objective The study aimed to evaluate the association between disease knowledge and medication adherence in patients with type 2 diabetes mellitus. Methods A cross-sectional study was conducted for three months, in patients with type 2 diabetes who visited three community pharmacies located in Khobar, Saudi Arabia. Patients' disease knowledge and their adherence to medications were documented using Arabic versions of the Michigan Diabetes Knowledge Test and the General Medication Adherence Scale respectively. Data were analyzed through SPSS version 23. Chi-square test was used to report association of demographics with adherence. Spearman's rank correlation was employed to report the relationship among HbA1c values, disease knowledge and adherence. Logistic regression model was utilized to report the determinants of medication adherence and their corresponding adjusted odds ratio. Study was approved by concerned ethical committee (IRB-UGS-2019-05-001). Results A total of 318 patients consented to participate in the study. Mean HbA1c value was 8.1%. A third of patients (N = 105, 33%) had high adherence and half of patients (N = 162, 50.9%) had disease knowledge between 51% - 75%. selleck products A significantly weak-to-moderate and positive correlation (ρ = 0.221, p 50% correct answers in the diabetes knowledge test questionnaire were more likely to be adherent to their medications (AOR 4.46, p less then 0.01). Conclusion Disease knowledge in most patients was average and half of patients had high-to-good adherence. Patients with better knowledge were 4 to 5 times more likely to have high adherence. This highlights the importance of patient education and awareness regarding medication adherence in managing diabetes. Copyright © 2020 AlShayban, Naqvi, Alhumaid, AlQahtani, Islam, Ghori, Haseeb, Ali, Iqbal, Elrggal, Ishaqui, Mahmoud, Khan and Jamshed.We developed a highly stable recombinant human acidic fibroblast growth factor (rh-aFGF) carbomer 940 hydrogel for wound healing. This study aimed to reveal toxicity target organs and the toxicity dose-response in the long-term administration of rh-aFGF carbomer 940 hydrogel in a rabbit skin wound model. New Zealand rabbits were topically administrated rh-aFGF carbomer 940 hydrogel at a daily dose of 900 IU/cm2, 1,800 IU/cm2, and 3,600 IU/cm2 for 28 days. Lyophilized rh-aFGF agent was used as the positive control group. General behavior, serum chemistry, skin irritation, immunogenicity, immunotoxicity, and histopathology were analyzed at designated time points. Results revealed that food intake, body weight, body temperature, heart rate, and eye examinations were all normal, suggesting no obvious toxicity induced by the rh-aFGF hydrogel. Medium and high dose rh-aFGF hydrogel groups and the positive control group displayed increased cell numbers in the local lymph nodes near the site of administration, likely caused mesenteric lymph node follicular hyperplasia, and this observation was alleviated after 14 days of recovery. Immunogenicity studies demonstrated that the serum antibody titer against rh-aFGF increased with the duration and number of drug applications but were not neutralization antibodies. After administration stopped, antibody titer decreased and disappeared in some mice. In summary, the safe dose for long-term administration of rh-aFGF carbomer 940 hydrogel for persistently damaged skin was 900 IU/cm2, which is 10 times that of the proposed clinical dosing. Copyright © 2020 Zhang, Huang, Bi, Zheng, Lu, Hui, Wang and Lin.In the present study, a systematic effort has been made to predict the hemolytic potency of chemically modified peptides. All models have been trained, tested, and evaluated on a dataset that contains 583 modified hemolytic peptides and a balanced number of non-hemolytic peptides. Machine learning techniques have been used to build the classification models using an immense range of peptide features that include 2D, 3D descriptors, fingerprints, atom, and diatom compositions. Random Forest based model developed using fingerprints as an input feature achieved maximum accuracy of 78.33% with AUC of 0.86 on the main dataset and accuracy of 78.29% with AUC of 0.85 on the validation dataset. Models developed in this study have been incorporated in a web server "HemoPImod" to facilitate the scientific community (http//webs.iiitd.edu.in/raghava/hemopimod/). Copyright © 2020 Kumar, Kumar, Agrawal, Patiyal and Raghava.Seleno-polymannuronate (Se-PM) was prepared from alginate-derived polymannuronate (PM) through a sulfation followed by a selenylation replacement reaction. The organic selenium content of Se-PM was 437.25 μg/g and its average molecular weight was 2.36 kDa. The neuroprotection effect of Se-PM and corresponding molecular mechanisms were investigated. Our results showed that, comparing to both sulfated PM (S-PM) and PM, Se-PM remarkably inhibited the aggregation of Aβ1-42 oligomer in vitro and significantly reduced the APP and BACE1 protein expression in N2a-sw cells, highlighting the critical function of the selenium presented in Se-PM. Moreover, Se-PM decreased the expression of cytochrome c and the ratio of Bax to Bcl-2, and enhanced the mitochondrial membrane potential in N2a-sw cells. These results suggested that Se-PM treatment can markedly inhibit N2a-sw cell apoptosis and promote N2a-sw cell survival and that Se-PM might be a potential therapeutic agent for the prevention of neurodegeneration owing to its remarkable neuroprotection effect. Copyright © 2020 Bi, Li, Li, Li, Lin, Yao, Li, Xu, Hu, Zhang, Liu and Xu.Introduction Implementation of health technology assessment (HTA) is still in an early stage with some heterogeneity in the Middle East and North Africa (MENA). Our objective was to assess the current and future status of HTA implementation in the MENA region by focusing on regional commonalities. Methods Preparatory discussions for the first ISPOR conference in the MENA region indicated some potentially generalizable trends of HTA roadmaps. To widen the perspective, a policy survey was conducted among conference participants by applying an HTA implementation scorecard. Discussion group members helped to validate key conclusions during and after the conference. Results Health policy experts in MENA countries would like to facilitate HTA implementation and expect significant changes with some generalizable directions in 10 years compared to the current status according. HTA capacity building has to be strengthened by more graduate and postgraduate programs. Increased public budget and enhanced institutionalizaight © 2020 Fasseeh, Karam, Jameleddine, George, Kristensen, Al-Rabayah, Alsaggabi, El Rabbat, Alowayesh, Chamova, Ismail, Abaza and Kaló.Helicobacter pylori is one of the most widespread infections involved in the pathogenesis of chronic gastritis, peptic ulcer, and gastric cancer. Hence, there is an urgent need to develop medications against H. pylori. This study aimed to evaluate synergistic effect of Rubus crataegifolius (RF) and Ulmus macrocarpa Hance (UL) against H. pylori. Antibacterial susceptibility of each extract either separately or in combination was studied against two H. pylori standard strains and 11 clinical isolates using agar dilution method. The effect of the extracts on H. pylori inoculated Balb/c mice model was also studied using single dosing (100 mg/kg each) approach. The MIC50 of RF and UL were more than 100 and 200 µg/ml, respectively, against the tested strains. However, simultaneous treatment with RF and UL at 75 and 50 µg/ml, respectively, showed decreased viable cell number, MIC70, and at 75 µg/ml each showed synergic effect with MIC90. On H. pylori inoculated Balb/c mice model, RF and UL separately (100 mg/kg each) showed moderate anti-H.