👤 Marina Panek

Molecular biomarkers are valuable tools to predict the disease and determine its course. Several markers have been associated with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS); however, none is sufficiently reliable to enable accurate diagnosis. We characterized a broad panel of serum proteins to assess disease-specific biomarker profiles and associate these findings with faecal microbiota composition in newly diagnosed IBD and IBS patients and healthy individuals. The study cohort consisted of 49 newly diagnosed treatment-naïve adult patients (13 Crohn's disease (CD), 13 ulcerative colitis (UC), and 23 IBS) and 12 healthy individuals. Inflammatory and metabolism-related serum proteins were assessed using PEA multiplex panels, while gut microbiota composition was determined by 16 s rRNA gene amplicon sequencing. Serum proteins AXIN1, TNFSF14, RNASE3, EN-RAGE, OSM, ST1A1, CA13 and NADK were identified as markers with the most promising specificity/sensitivity and predictivity between healthy and disease groups, while IL-17A and TNFRSF9 enabled differentiation between IBD and IBS patients. Increased abundance of Enterobacteriaceae was associated with protein markers significantly elevated in IBD/IBS. In contrast, depletion of beneficial taxa like Ruminococcaceae and Verucomicrobiaceae (i.e. Akkermansia muciniphila) was associated with decrease of a set of markers in diseased groups. Differences in the abundance of Turicibacteriaceae were more predictive to discern CD from UC than any of the serum proteins investigated. By using a broad panel of inflammation and metabolism-related proteins, we determined serum markers with significantly different levels in treatment-naïve IBD and IBS patients compared to healthy individuals, as well as between IBD and IBS. KEY MESSAGES : Significant changes in the levels of several serum proteins and abundances of faecal bacterial taxa between study groups were found. Increased levels of AXIN1, TNFSF14, RNASE3, EN-RAGE, OSM, ST1A1, CA13 and NADK characterize both IBD and IBS, while IL-17A and TNFRSF9 differentiate IBD from IBS. Increase of Enterobacteriaceae and depletion of beneficial taxa Ruminococcaceae and Verucomicrobiaceae (i.e. Akkermansia muciniphila) was found in IBD and IBS. Differences in Turicibacteriaceae were more predictive to discern CD from UC than any of the serum proteins investigated. Show less

As Alzheimer's disease (AD) is a neurodegenerative disease with a complex pathogenesis, the exploration of multi-target drugs may be an effective strategy for AD treatment. Multifunctional small molecular agents can be obtained by connecting two or more active drugs or privileged pharmacophores by multicomponent reactions (MCRs). In this paper, two series of polysubstituted pyrazine derivatives with multifunctional moieties were designed as anti-AD agents and synthesized by Passerini-3CR and Ugi-4CR. Since the oxidative stress plays an important role in the pathological process of AD, the antioxidant activities of the newly synthesized compounds were first evaluated. Subsequently, selected active compounds were further screened in a series of AD-related bioassays, including Aβ Show less

Alzheimer's disease (AD) is a global health problem in the medical sector that will increase over time. The limited treatment of AD leads to the search for a new clinical candidate. Considering the multifactorial nature of AD, a strategy targeting number of regulatory proteins involved in the development of the disease is an effective approach. Here, we present a discovery of new multi-target-directed ligands (MTDLs), purposely designed as GABA transporter (GAT) inhibitors, that successfully provide the inhibitory activity against butyrylcholinesterase (BuChE), β-secretase (BACE1), amyloid β aggregation and calcium channel blockade activity. The selected GAT inhibitors, 19c and 22a - N-benzylamide derivatives of 4-aminobutyric acid, displayed the most prominent multifunctional profile. Compound 19c (mGAT1 IC Show less

Molecular alterations in tumor-adjacent tissues have recently been recognized in some types of cancer. This phenomenon has not been studied in endometrial cancer. We aimed to analyze the expression of genes associated with cancer progression and metabolism in primary endometrial cancer samples and the matched tumor-adjacent tissues and in the samples of endometria from cancer-free patients with uterine leiomyomas. Paired samples of tumor-adjacent tissues and primary tumors from 49 patients with endometrial cancer (EC), samples of endometrium from 25 patients with leiomyomas of the uterus, and 4 endometrial cancer cell lines were examined by the RT-qPCR, for Show less

The main goal of this study was the formation of bone tissue using dexamethasone (DEX)-loaded [COCH₃]-RADARADARADARADA-[CONH₂] (RADA 16-I) scaffold that has the ability to release optimal DEX concentration under perfusion force. Bone-marrow samples were collected from three patients during a hip arthroplasty. Human mesenchymal stem cells (hMSCs) were isolated and propagated in vitro in order to be seeded on scaffolds made of DEX-loaded RADA 16-I hydrogel in a perfusion bioreactor. DEX concentrations were as follows: 4 × 10 Show less