AmyloGraph : a comprehensive database of amyloid-amyloid interactions

Information about the impact of interactions between amyloid proteins on their fibrillization propensity is scattered among many experimental articles and presented in unstructured form. We manually curated information located in almost 200 publications (selected out of 562 initially considered), obtaining details of 883 experimentally studied interactions between 46 amyloid proteins or peptides. We also proposed a novel standardized terminology for the description of amyloid-amyloid interactions, which is included in our database, covering all currently known types of such a cross-talk, including inhibition of fibrillization, cross-seeding and other phenomena. The new approach allows for more specific studies on amyloids and their interactions, by providing very well-defined data. AmyloGraph, an online database presenting information on amyloid-amyloid interactions, is available at (). Its functionalities are also accessible as the R package (). AmyloGraph is the only publicly available repository for experimentally determined amyloid-amyloid interactions

Preclinical Study of Immunological Isoxazole Derivatives as a Potential Support for Melanoma Chemotherapy

(1) Background: Melanoma is an aggressive neoplasm derived from melanocyte precursors with a high metastatic potential. Responses to chemotherapy and immunotherapy for melanoma remain weak, underlining the urgent need to develop new therapeutic strategies for the treatment of melanoma. (2) Methods: The viability of NHDF and A375 cell cultures after the administration of the tested isoxazole derivatives was assessed after 24-h and 48-h incubation periods with the test compounds in the MTT test. ROS and NO scavenging analyses, a glycoprotein-P activity analysis, a migration assay, a test of apoptosis, and a multiple-criteria decision analysis were also performed. (3) Results: All compounds that were tested resulted in a slower migration of melanoma neoplastic cells. The mechanism of the antitumor activity of the tested compounds was confirmed—i.e., the pro-apoptotic activity of the compounds in A375 cell cultures. Compound O7K qualified for further research. (4) Conclusions: All the tested compounds inhibited the formation of melanoma metastases and demonstrated the ability to reduce the risk of developing drug resistance in the tumor. The MCDA results showed that O7K showed the strongest antitumor activity

Investigation of the Properties of Linen Fibers and Dressings

In antiquity, flax was used as a dressing for healing wounds. Currently, work is underway on the genetic modification of flax fibers to improve their properties. Genetic modifications have resulted in an increased content of antioxidants and more favorable mechanical properties. The works published so far have presented independent tests of fibers and dressings after appropriate technological treatments in cell cultures. This study aimed to compare the properties of the fibers and the dressing produced in cell cultures—hamster fibroblasts—V79. The research material was traditional NIKE fibers; genetically modified M, B, and MB fibers; and linen dressings obtained from these fibers. The extract from 48-h incubation of 40 mg of fiber in the culture medium, which was desolved into 10, 20, and 30 mg, was administered to the cell culture. On the other hand, a linen dressing was placed on cells with an area of 0.5 cm2, 1 cm2, 1.5 cm2, and 2 cm2. Cells with fiber or dressing were incubated for 48 h, and then, biological tests were performed, including cell viability (in propidium iodide staining), cell proliferation (in the SRB assay), evaluation of the intracellular free radical level (in the DCF-DA assay), genotoxicity (in the comet assay), assessment of the apoptotic and necrotic cells (in staining anexin-V and iodide propidium), the course of the cell cycle, and the scratch test. The correlation between apoptosis and genotoxicity and the levels of free radicals and genotoxicity were determined for the tested linen fibers and fabrics. The tests presented that the fibers are characterized by the ability to eliminate damaged cells in the elimination phase. However, the obtained fabrics gain different properties during the technological processing of the fibers into linen dressings. Linen fabrics have better regenerative properties for cells than fibers. The linseed dressing made of MB fiber has the most favorable regenerative properties

Patients’ Habits and the Role of Pharmacists and Telemedicine as Elements of a Modern Health Care System during the COVID-19 Pandemic

Aims/Introduction: The Polish government introduced the epidemic on 20 March 2020, after The World Health Organization (WHO) announced the new coronavirus disease (COVID-19) in January 2020. Patients’ access to specialist clinics and family medicine clinics was limited. In this situation, pharmacists were likely the first option for patient’s health information. On 18 March 2020, the National Health Fund issued modifications that increased the accessibility to primary health care such as telemedicine. The development of e-health in Poland during the COVID-19 pandemic included the implementation of electronic medical records (EDM), telemedicine development, e-prescription, and e-referrals implementation. We investigated this emergency’s effect on patients’ health habits, access to healthcare, and attitude to vaccination. Materials and methods: An anonymous study in the form of an electronic and paper questionnaire was conducted in March 2021 among 926 pharmacies patients in Poland. The content of the questionnaire included access to medical care, performing preventive examinations, implementation of e-prescriptions, patient satisfaction with telepathing, pharmaceutical care, and COVID-19 vaccination. Results: During the COVID-19 pandemic, 456 (49.2%) patients experienced worse access to a doctor. On the other hand, 483 (52.2%) patients did not perform preventive examinations during the COVID-19 pandemic. Almost half of the patients (45.4% (n = 420)) were not satisfied with the teleconsultation visit to the doctor. A total of 90% (n = 833) of the respondents do not need help in making an appointment with a doctor and buying medications prescribed by a doctor in the form of an e-prescription. In the absence of access to medical consultation, 38.2% (n = 354) of respondents choose the Internet as a source of medical advice. However, in the absence of contact with a doctor, 229 persons (24.7%) who took part in the survey consulted a pharmacist. In addition, 239 persons (25.8%) used pharmacist advice more often during the COVID-19 pandemic than before its outbreak on 12 March 2020. Moreover, 457 (49.4%) respondents are satisfied with the advice provided by pharmacists, and even 439 patients of pharmacies (47.4%) expect an increase in the scope of pharmaceutical care in the future, including medical advice provided by pharmacists. Most of the respondents, 45.6% (n = 422), want to be vaccinated in a hospital or clinic, but at the same time, for a slightly smaller number of people, 44.6% (n = 413), it has no meaning where they are will be vaccinated against COVID-19. Conclusions: Telemedicine is appreciated by patients but also has some limitations. The COVID-19 pandemic is the chance for telemedicine to transform from implementations to a routine healthcare system structure. However, some patients still need face-to-face contact with the doctor or pharmacist. Pharmacists are essential contributors to public health and play an essential role during the COVID-19 pandemic. Integration of pharmaceutical care with public health care and strong growth in the professional group of pharmacists may have optimized patient care

The Incidence and Severity of Post-Vaccination Reactions after Vaccination against COVID-19

The pandemic of COVID-19 might be limited by vaccination. Society should be vaccinated to prevent the spread of coronavirus disease 2019 (COVID-19) and to protect persons who are at high risk for complications. In Poland, the National Vaccination Program has been introduced, which is a strategy for planning activities to ensure safe and effective vaccinations among Polish citizens. It includes not only the purchase of an appropriate number of vaccines, their distribution but also monitoring of the course and effectiveness of vaccination and the safety of Poles. The national COVID-19 immunization program has been divided into four stages. Stage 0 covers the healthcare workers to be vaccinated first, as they are most at risk of being infected with the coronavirus. The study aims to prove the thesis that GIS statistical data on the incidence of COVID-19 post-vaccination reactions should be verified, as patients do not report their occurrence through the procedure indicated by GIS. In March 2021, an anonymous questionnaire survey was conducted using an electronic questionnaire among persons belonging to group zero of the National Vaccination Program. The survey consisted of 19 short questions concerning, inter alia, getting COVID-19, post-vaccination reactions after receiving the first and second doses of the COVID-19 vaccine, and motivation to proceed with vaccination. A total of 1678 complete responses were received. It has been shown that only a small number of post-vaccination reactions are reported to the Sanitary Inspection, which makes GIS statistics on the incidence of post-vaccination reactions in COVID-19 unreliable. In addition, having earlier suffered from COVID-19 had an impact on the occurrence of more severe side effects after the first dose of the COVID-19 vaccine

Oils from Transgenic Flax Lines as Potential Chemopreventive Agents in Colorectal Cancer

Colorectal cancer is a major global health concern, and the need for effective chemopreventive agents is paramount. This study aimed to evaluate the potential of oils from transgenically modified flax for the prevention of colorectal cancer, in relation to the oil concertation. Flaxseed oils were obtained from traditional (Nike) and genetically modified flax lines (M and B). Cell viability assays were performed on various cancer cell lines, including colon adenocarcinoma cells. Flaxseed oil B exhibited the strongest anti-proliferative properties compared to the reference drugs and other oils. Additionally, M and B oils showed enhanced accumulation of Rhodamine 123 and increased apoptosis in colorectal cancer cells. M oil exhibited the highest levels of p53 protein. Notably, the tested transgenic oils did not induce metastasis and displayed stronger inhibition of COX-1 compared to COX-2. These data indicate the utility of flaxseed oils, especially from the M line, as adjuvants in colorectal cancer treatment, targeting the colon specifically

The Role of the Microbiota-Gut-Brain Axis in the Development of Alzheimer’s Disease

Along with the increase in life expectancy in the populations of developed and developing countries resulting from better access and improved health care, the number of patients with dementia, including Alzheimer’s disease (AD), is growing. The disease was first diagnosed and described at the beginning of the 20th century. However, to this day, there is no effective causal therapy, and symptomatic treatment often improves patients’ quality of life only for a short time. The current pharmacological therapies are based mainly on the oldest hypotheses of the disease—cholinergic (drugs affecting the cholinergic system are available), the hypothesis of amyloid-β aggregation (an anti-amyloid drug was conditionally approved by the FDA in 2020), and one drug is an N-methyl-D-aspartate receptor (NMDAR) antagonist (memantine). Hypotheses about AD pathogenesis focus on the nervous system and the brain. As research progresses, it has become known that AD can be caused by diseases that have been experienced over the course of a lifetime, which could also affect other organs. In this review, we focus on the potential association of AD with the digestive system, primarily the gut microbiota. The role of diet quality in preventing and alleviating Alzheimer’s disease is also discussed. The problem of neuroinflammation, which may be the result of microbiota disorders, is also described. An important aspect of the work is the chapter on the treatment strategies for changing the microbiota, potentially protecting against the disease and alleviating its course in the initial stages

The N’-Substituted Derivatives of 5-Chloro-3-Methylisothiazole-4-Carboxylic Acid Hydrazide with Antiproliferative Activity

Thanks to the progress in oncology, pharmacological treatment of cancer is gaining in importance and in the near future anti-cancer chemotherapeutics are expected to be the main method of treatment for cancer diseases. What is more, the search for new anti-cancer compounds with the desired application properties is constantly underway. As a result of designed syntheses, we obtained some new N’-substituted 5-chloro-3-methylisothiazole-4-carboxylic acid hydrazide derivatives with anticancer activity. The structure of new compounds was determined by mass spectrometry (MS), elemental analysis, proton nuclear magnetic resonance spectroscopy (1H-NMR), carbon nuclear magnetic resonance spectroscopy (13C-NMR), 1H-13C NMR correlations and infrared spectroscopy (IR). Moreover, the structures of the compounds were confirmed by crystallographic examination. The antiproliferative MTT tests for 11 prepared compounds was conducted towards human biphenotypic B cell myelomonocytic leukemia MV4-11. SRB test was used to examine their potential anticancer activity towards human colon adenocarcinoma cell lines sensitive LoVo, resistant to doxorubicin LoVo/DX, breast adenocarcinoma MCF-7 and normal non-tumorigenic epithelial cell line derived from mammary gland MCF-10A. The most active compound was 5-chloro-3-methyl-N′-[(1E,2E)-(3-phenyloprop-2-en-1-ylidene]isothiazole-4-carbohydrazide, which showed the highest antiproliferative activity against all tested cell lines

Design, Synthesis, Biological Evaluation, and Molecular Docking Study of 4,6-Dimethyl-5-aryl/alkyl-2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl]pyrrolo[3,4-<i>c</i>]pyrrole-1,3(2<i>H</i>,5<i>H</i>)-diones as Anti-Inflammatory Agents with Dual Inhibition of COX and LOX

In the present study, we characterize the biological activity of a newly designed and synthesized series of 15 compounds 2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl] derivatives of pyrrolo[3,4-c]pyrrole 3a–3o. The compounds were obtained with good yields of pyrrolo[3,4-c]pyrrole scaffold 2a–2c with secondary amines in C2H5OH. The chemical structures of the compounds were characterized by 1H-NMR, 13C-NMR, FT-IR, and MS. All the new compounds were investigated for their potencies to inhibit the activity of three enzymes, i.e., COX-1, COX-2, and LOX, by a colorimetric inhibitor screening assay. In order to analyze the structural basis of interactions between the ligands and cyclooxygenase/lipooxygenase, experimental data were supported by the results of molecular docking simulations. The data indicate that all of the tested compounds influence the activity of COX-1, COX-2, and LOX