Co-toxicity of Endotoxin and Indoxyl Sulfate, Gut-Derived Bacterial Metabolites, to Vascular Endothelial Cells in Coronary Arterial Disease Accompanied by Gut Dysbiosis

Gut dysbiosis, alongside a high-fat diet and cigarette smoking, is considered one of the factors promoting coronary arterial disease (CAD) development. The present study aimed to research whether gut dysbiosis can increase bacterial metabolites concentration in the blood of CAD patients and what impact these metabolites can exert on endothelial cells. The gut microbiomes of 15 age-matched CAD patients and healthy controls were analyzed by 16S rRNA sequencing analysis. The in vitro impact of LPS and indoxyl sulfate at concentrations present in patients’ sera on endothelial cells was investigated. 16S rRNA sequencing analysis revealed gut dysbiosis in CAD patients, further confirmed by elevated LPS and indoxyl sulfate levels in patients’ sera. CAD was associated with depletion of Bacteroidetes and Alistipes. LPS and indoxyl sulfate demonstrated co-toxicity to endothelial cells inducing reactive oxygen species, E-selectin, and monocyte chemoattractant protein-1 (MCP-1) production. Moreover, both of these metabolites promoted thrombogenicity of endothelial cells confirmed by monocyte adherence. The co-toxicity of LPS and indoxyl sulfate was associated with harmful effects on endothelial cells, strongly suggesting that gut dysbiosis-associated increased intestinal permeability can initiate or promote endothelial inflammation and atherosclerosis progression

Readiness and Willingness to Provide Immunization Services after Pilot Vaccination Training: A Survey among Community Pharmacists Trained and Not Trained in Immunization during the COVID-19 Pandemic in Poland

Background: Immunization rates among the adult population in Poland are below desired targets, urging the need to expand this service in the community. During the COVID-19 pandemic, the ultimate goals for limiting the spread of the infection are vaccines against SARS-CoV-2. Pharmaceutical companies are in a race for the fastest possible way to deliver vaccines. Community pharmacists in Poland are recognised as an accessible yet underutilised group of medical professionals. Therefore, involving pharmacists in vaccinations may have beneficial results for the healthcare system. Objectives: The objectives of this study were to assess the readiness and willingness of community pharmacists following the Pharmacist Without Borders project who had either been trained or not in providing immunization services, and to identify the factors that may support the implementation of such services in Poland. Methods: This study was conducted among pharmacists between February and August 2020 in Poland. A survey was developed to determine their readiness to provide vaccination services in their pharmacies, to recognise any barriers to vaccinations, as well as the factors necessary to implement vaccination services in Polish pharmacies. Results: A total of 1777 pharmacists participated in the study, comprising 127 (7.1%) pharmacists trained in vaccinations during the Pharmacists Without Borders project and 1650 (92.9%) pharmacists not participating in the workshops. Pharmacists participating in the workshops more often indicated that providing vaccinations in community pharmacies would improve the overall vaccination rate (p = 0.0001), and that pharmacists could play an important role in advertising and promoting vaccinations (p = 0.0001). For the pharmacists not participating in the workshops, they indicated to a much greater extent possible barriers affecting the readiness to provide vaccinations in pharmacies. They most often pointed out that vaccination services would result in a significant workload increase (p = 0.0001), that pharmacies were not adapted to immunization, and that there were not enough training courses for pharmacists (p = 0.0001). Conclusion: The pharmacists working in community pharmacies indicated many advantages of vaccinations in pharmacies. This study identified barriers to the introduction of vaccinations and factors necessary to implement these services in pharmacies. The pharmacists trained during the immunization programme of the Pharmacists Without Borders project showed a greater readiness to provide immunization services

Cornelian Cherry Iridoid-Polyphenolic Extract Improves Mucosal Epithelial Barrier Integrity in Rat Experimental Colitis and Exerts Antimicrobial and Antiadhesive Activities In Vitro

Background and Aims. Inflammatory bowel disease pharmacotherapy, despite substantial progress, is still not satisfactory for both patients and clinicians. In view of the chronic and relapsing disease course and not always effective treatment with adverse effects, attempts to search for new, more efficient, and safer substances are essential and reasonable. This study was designed to elucidate the impact of cornelian cherry iridoid-polyphenolic extract (CE) and loganic acid (LA) on adherent-invasive E. coli growth and adhesion in vitro and to assess the effect of pretreatment with CE or LA on the course of intestinal inflammation in rat experimental colitis compared with sulfasalazine. Methods. Antibacterial and antiadhesive activities of CE and LA were assessed using microdilution, Int407 cell adherence, and yeast agglutination assays. The colitis model was induced by 2,4,6-trinitrobenzenesulfonic acid. Studied substances were administered intragastrically for 16 days prior to colitis induction. Body weight loss; colon index; histological injuries; IL-23, IL-17, TNF-α, and chemerin levels; and STAT3, Muc2, and TFF3 mRNA expression were evaluated. Results. Only CE exerted antimicrobial and antiadhesive activities in vitro and alleviated colonic symptoms. CE coadministrated with sulfasalazine was more effective than single compounds in reversing increased concentrations of TNF-α, IL-17, and chemerin and decreased Muc2 mRNA expression. Conclusions. CE exerted a protective effect against experimental colitis via impaired mucosal epithelial barrier restoration and intestinal inflammatory response attenuation and given concomitantly with sulfasalazine counteracted colitis in a more effective way than sulfasalazine alone, which indicates their synergistic interaction. The beneficial effect of CE may also be due to its bacteriostatic and antiadhesive activities