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.

Neuroinflammation is considered to be one of the potential causes for the development of neurodegenerative diseases, including Alzheimer's disease. In this study, we evaluated the effect of four newly synthesized pyrrolo [3,4-d]pyridazinone derivatives on the neuron-like PC12 cells under simulated inflammation conditions by preincubation with lipopolysaccharide (LPS). Our novel derivatives are selective cyclooxygenase-2 (COX-2) inhibitors and have similar effects to nonsteroidal anti-inflammatory drugs (NSAIDs). We assessed viability (LDH assay), metabolic activity (MTT assay), DNA damage (number of double-strand breaks measured by fast halo assay), and the neuronal features of cells (average neurite length and neurite outgrowth measured spectrofluorimetrically). DCF-DA and Griess assays were also performed, which allowed determining the impact of the tested compounds on the level of oxygen free radicals and nitrites. LPS administration significantly negatively affected the results in all tests performed, and treatment with the tested derivatives in most cases significantly reduced this negative impact. Multiple-criteria decision analysis indicated that overall, the best results were observed for compounds 2a and 2b at a concentration of 10 µM. The new derivatives showed intense activity against free oxygen radicals and nitrites. Reduced reactive oxygen species level also correlated with a decrease in the number of DNA damage. The compounds improved neuronal features, such as neurite length and outgrowth, and they also increased cell viability and mitochondrial activity. Our results suggest that derivatives 2a and 2b may also act additionally on mechanisms other than 3a and 3b.

Despite the availability of the current drug arsenal for pain management, there is still a clinical need to identify new, more effective, and safer analgesics. Based on our earlier study, newly synthesized 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone, especially 10b and 13b, seem to be promising as potential analgesics. The current study was designed to investigate whether novel derivatives attenuate nociceptive response in animals subjected to thermal or chemical noxious stimulus, and to compare this effect to reference drugs. The antinociceptive effect of novel compounds was studied using the tail-flick and formalin test. Pretreatment with novel compounds at all studied doses increased the latency time in the tail-flick test and decreased the licking time during the early phase of the formalin test. New derivatives given at the medium and high doses also reduced the late phase of the formalin test. The achieved results indicate that new derivatives dose-dependently attenuate nociceptive response in both models of pain and exert a lack of gastrotoxicity. Both studied compounds act more efficiently than indomethacin, but not morphine. Compound 13b at the high dose exerts the greatest antinociceptive effect. It may be due to the reduction of nociceptor sensitization via prostaglandin E2 and myeloperoxidase levels decrease.

Recently, a growing body of research has linked gut microbiota dysbiosis to central nervous system diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and has suggested that AD and PD pathology may take its origin from chronic inflammation in the gastrointestinal tract. Thus, this study aimed to elucidate whether inflammatory bowel disease (IBD) is associated with a higher risk of developing AD and PD as compared to the non-IBD population by conducting a meta-analysis. A thorough search of Pubmed and Embase databases was performed to identify all relevant articles. The quality of included studies was assessed using the Newcastle-Ottawa Scale. The odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed using a fixed-effect model. To assess publication bias and heterogeneity among the studies, Egger’s test and L’Abbé plots were used, respectively. A total of eight eligible studies were included in this meta-analysis. No significant heterogeneity or significant publication bias was detected. The risk of developing AD in IBD patients was higher than in non-IBD patients (OR = 0.37; 95% CI = 0.14–1.00; p = 0.05), and there was a relationship between the occurrence of AD and Crohn’s disease or ulcerative colitis (OR = 0.11; 95% CI = 0.04–0.30; p < 0.0001, OR = 0.14; 95% CI = 0.04–0.49; p = 0.0024, respectively). The risk of developing both of the most common neurodegenerative diseases, AD and PD, was also significantly higher in patients diagnosed with Crohn’s disease or ulcerative colitis (OR = 0.21; 95% CI = 0.09–0.49; p = 0.0003, OR = 0.25; 95% CI = 0.13–0.51; p = 0.0001, respectively). This meta-analysis revealed a higher risk of AD and PD among CD and UC patients compared to the general population. It may suggest a key role for the gut microbiota in the pathogenesis of not only Crohn’s disease and ulcerative colitis but also AD and PD. The identification of this potential risk may provide earlier preventive measures to be implemented to reduce comorbidity and mortality rate.

No abstract

Cyclophosphamide (CPX) exerts toxicity in the urogenital system. The current study was designed to evaluate the effect of morin-5′-sulfonic acid sodium salt (NaMSA) on CPX-induced urogenital toxicity in rats. NaMSA (100 mg/kg/daily) and CPX (15 mg/kg/daily) alone or in combination and 0.9% NaCl (as a control) were given intragastrically for 10 days. Testes and epididymes from male and urinary bladders from male and female rats were evaluated histologically. In testes and epididymes, morphological changes and relative decrease in sperm count were assessed. In urinary bladders edema, hemorrhage and urothelium erosions were described by 0–2 points scoring system. Reproductive score (RS—in total 6 points) and urinary bladder score (BS—in total 6 points) were thereafter calculated. In CPX-receiving group RS (2.7) and BS (3.3) were significantly higher than in the control (0.5 and 0.25 for RS and BS, respectively). Co-administration of NaMSA reversed most of the morphological changes, which was reflected by lower RS and BS score (0.5 and 1.2 for RS and BS, respectively). The preliminary findings suggest that NaMSA may attenuate CPX-induced histological changes in rat urogenital tract.

Hydroxyapatite has been used in medicine for many years as a biomaterial or a cover for other biomaterials in orthopedics and dentistry. This study characterized the physicochemical properties (structure, particle size and morphology, surface properties) of Li+- and Li+/Eu3+-doped nanohydroxyapatite obtained using the wet chemistry method. The potential regenerative properties against neurite damage in cultures of neuron-like cells (SH-SY5Y and PC12 after differentiation) were also studied. The effect of nanohydroxyapatite (nHAp) on the induction of repair processes in cell cultures was assessed in tests of metabolic activity, the level of free oxygen radicals and nitric oxide, and the average length of neurites. The study showed that nanohydroxyapatite influences the increase in mitochondrial activity, which is correlated with the increase in the length of neurites. It has been shown that the doping of nanohydroxyapatite with Eu3+ ions enhances the antioxidant properties of the tested nanohydroxyapatite. These basic studies indicate its potential application in the treatment of neurite damage. These studies should be continued in primary neuronal cultures and then with in vivo models.

Background and aim: The use of dietary supplements (DS) and over-the-counter (OTC) drugs is increasing every year. The COVID-19 pandemic might additionally influence the use of such preparations. The study aimed to investigate factors influencing the use of dietary supplements (DS), including stress-relieving supplements, by the students. Methods: In the cross-sectional study, 624 students of the Wroclaw Medical University in Poland, from the second to the last year of studies, completed the anonymous questionnaire, consisting of 22 items, about the use of DS/OTC drugs during the academic year 2020/2021. Obtained data were analyzed using Pearson’s chi-square test, the U-Mann Whitney test, the Kruskal–Wallis test with the post-hoc analysis, and with logistic regression. Results: About 70% of students declared the use of any DS, 33% used DS for stress, anxiety, depression, or sleeping problems, and 59% used other DS. The most important factors influencing the decision to take any kind of DS were Division (p = 0.0001, odds ratio [OR]: 0.35, and confidence interval [CI]: 0.21–0.59), a self-estimated level of stress (p = 0.014, OR: 1.13, CI: 1.03–1.25), and self-estimated level of knowledge about DS (p = 0.0000, OR: 1.31, CI: 1.19–1.36). In the case of students taking DS for stress, anxiety, depression, or sleeping problems, the level of stress and the declared knowledge had the greatest impact on the decision for such a use of DS (p = 0.0001, OD: 1.24, CI: 1.11–1.39 and p = 0.0000, OD: 1.35, CI: 1.22–1.5, respectively). The COVID-19 pandemic did not change the pattern of DS/OTC drug usage in about 33% of students. Those who started taking DS during the pandemic accounted for 19% of all students. Conclusions: The use of DS is common among Wroclaw Medical University students with some differences between subgroups of respondents. Additionally, despite declared good knowledge about DS, most students declare the need to learn more about them.