Postepy biochemii最新文献

For over 100 years, medicine has not developed an effective method for treating Alzheimer's disease (AD). Despite countless studies, successes have been rather modest. This situation requires a new approach. In the current article, the authors attempt to outline and propose, based on literature and their own research results, the directions of such an approach. We begin with the observation that the strongest risk factor for AD is the aging process of the body, organs, and cells. According to the Informational Theory of Aging, the process of amyloidogenesis, must be the result of earlier molecular events leading to epigenetic chaos. However, the use of anti-amyloid antibodies has shown some moderate successes. Economic considerations suggest, that use of antibodies will not solve the problem on a population-wide scale due to the very high cost. Therefore, small molecule inhibitors of amyloidogenesis are promising molecules for stopping AD dementia processes.

In order for a variety of biochemical processes to take place efficiently within the same cell, the existence of discrete areas within the cell is essential. In addition to encapsulated organelles, these include membraneless bio-molecular condensates, dynamically changing structures formed from proteins and nucleic acids. These condensates are often formed by liquid-liquid phase separation (LLPS). Numerous scientific reports in recent years have indicated that liquid-liquid phase separation (LLPS) is an important mechanism allowing plants to identify various biotic and abiotic stresses and respond to them. The following paper reviews the methods currently used to study macromolecular condensates and the function of proteins undergoing LLPS in plants.

During the September 2024 Science Festival in Warsaw, three unique events were organized in collaboration between the Nencki Institute of Experimental Biology PAS, the Academy of Fine Arts in Warsaw, and the Marceli Nencki Foundation for the Advancement of Biological Sciences. These events focused on exploring interactions between biological sciences and visual arts. As part of this collaboration, an exhibition titled “Vibration” was presented at the Hermitage in the Royal Łazienki Park. Additionally, lectures and an exhibition titled “Can Molecular Biology Inspire Visual Artists” were held at the Nencki Institute PAS. A unique event, the “Bio-Workshop”, was organized for high school students at the Graphic Arts Department of the Academy of Fine Arts in Warsaw. In addition to recounting and detailing these events, this article presents a broader context of the interplay between art and natural sciences. The benefits of creative interdisciplinary activities are discussed, highlighting the potential for mutual inspiration between these two fields, benefiting both artists and scientists.

In recent years, a progressive increase in the incidence of neurodegenerative diseases has been observed. The etiology and pathophysiology of Parkinson's, Alzheimer's, and Huntington's diseases are diverse; however, universal mechanisms occurring during neurodegeneration warrant attention. Among the best-characterized are chronic inflammation, oxidative stress, and altered autophagy processes resulting from abnormal protein aggregation. Neuronal loss of structure and function is accompanied by impaired repair mechanisms. Given the lack of therapies capable of halting neurodegeneration progression, studies aimed at identifying substances that activate natural cellular repair mechanisms or mitigate factors promoting neurodegeneration are of significant importance. Recently, spermidine has attracted considerable interest from research teams worldwide. This study aims to present evidence confirming the broad spectrum of spermidine’s effects in models replicating degenerative changes in the central nervous system, highlighting its influence on mechanisms of neuronal cell death associated with neurodegenerative diseases.

Glioblastoma multiforme (GBM) is a malignant and most agressive brain tumor. However, the current treatment standards and the progress that has been made over the last years in imaging methods and surgical techniques for glioma have not resulted in the extension of patients'live (the median is approximately 15 months). This situation has not been changed by the knowledge of unique changes at the molecular level of the tumor or the prospect of gene therapy, which has had grest hopes. These failures have created an urgent need to serach for new therapeutic strategies.Since in recent years there has been an interest in searching for new uses of drugs outside their main indication (co-called ,,drug repositioning'') supplementing the basic glioma therapy with antidepressants may be an example of such a strategy. These drugs, apart from their antidepressant properties, are used among others in the the treatment of neuropathic pain, anxiety, cicardian rhytm disorders and appetite. The results of experimental studies also indicate theit potential anticancer properties.

Clear cell renal cell carcinoma (ccRCC) is the most common renal tumor with a highly aggressive phenotype and poor prognosis. A key process in tumor progression is epithelial-mesenchymal transition (EMT), as a result of which cells acquire the ability to metastasize. An important inducer of the EMT process is inflammation. A negative regulator of inflammation is the Monocyte Chemoattractant Protein-1 Induced Protein 1 (MCPIP1), which by regulating the immune response may contribute to inhibiting tumor progression. A specific function of the MCPIP1 protein is RNase activity regulating the level of mRNA and miRNA expression. In our studies, we investigated how the MCPIP1 protein affects the EMT process, migratory activity and the level of tumor suppressor genes in clear cell renal cell carcinoma cell lines, tumor tissues of patients and an in vivo xenotransplantation model. We have shown that MCPIP1 regulates the EMT process by preventing cells from acquiring a mesenchymal phenotype. MCPIP1, due to its RNase activity, degrades miRNA-519a-3p, miRNA-519b-3p and miRNA-520c-3p, thereby actively affecting the levels of SFRP4, KREMEN1, ZNRF3, CXXC4 and CSNK1A1 inhibitors and inhibiting the Wnt pathway by inactivating β-catenin and, consequently, inhibiting the EMT process. Furthermore, MCPIP1 regulates the level of Rho proteins, phosphorylation of FAK and Src kinases, and consequently actin remodeling. The obtained results indicate that the lack of MCPIP1 RNase activity activates genes and processes associated with the migratory activity of cancer cells. In summary, the results obtained in this doctoral thesis indicated that MCPIP1 may regulate the progression of clear cell renal cancer at various levels of proangiogenic and prometastatic factors, as well as by influencing the EMT process.

Insulin resistance refers to the diminished response of insulin-sensitive tissues to insulin signaling. Recent observational studies increasingly indicate that insulin resistance may be one of the risk factors for the development of cardiovascular disease. The article focuses on the molecular basis of this phenomenon. In insulin resistance, hyperinsulinemia is observed, followed by impaired glucose metabolism, which subsequently leads to the development of inflammation due to triggering inflammatory signaling pathways and production of pro-inflammatory cytokines. Inflammation contributes to the formation of reactive oxygen species, which further exacerbate insulin resistance and promote the formation of atherosclerotic plaques. In turn reactive oxygen species indirectly contribute to reduced endothelial NO production, leading to vasoconstriction and increased blood pressure. Insulin resistance also stimulates vascular smooth muscle hypertrophy, a key contributor to hypertension and cardiovascular disease.

Colorectal cancer (RJG) is one of the most frequently diagnosed malignant neoplasms: approximately 1.9 million new cases are reported annually. Notwithstanding the advent of techniques for the early detection of RJG and the introduction of novel therapeutic modalities, this disease remains the second leading cause of cancer-related mortality. The results of recent studies highlight the role of fatty acid transporters, including fatty acid translocase/cluster of differentiation 36 (FAT/CD36), fatty acid transport proteins (FATPs), and fatty acid-binding proteins (FABPs), in the pathogenesis of RJG. Changes in serum concentrations and in expression levels in tumor tissue may serve as promising biomarkers for the early diagnosis of the disease and/or the monitoring of its progression and the efficacy of its treatment. Moreover, the fatty acid carriers present a promising avenue for the development of efficacious therapies against RJG.

Pancreatic cancer is a common cancer with a very poor prognosis and aggressive course. The main reason for the highly unfavorable prognosis of patients with pancreatic cancer is its long-term asymptomatic development, which results in the diagnosis being made at a stage when the cancer process is significantly advanced. Despite extensive research in the field of effective diagnosis and treatment of this cancer, patient survival rates are increasing slowly and insignificantly. Pancreatic cancer cells contain many mutations, the most frequently found of which concern the KRAS, TP53, CDKN2A, SMAD4, BRCA1 and BRCA2 genes. Each of these mutations is associated with specific consequences at the molecular level and translates into further cell functioning, including uncontrolled cell division. The occurrence of specific mutations influences the planning of therapeutic procedures and patient prognosis. Many mutations are associated with a hereditary predisposition to cancer, including pancreatic cancer.

Prostaglandins are hormones found in almost all mammalian tissues. As signaling molecules, they play a key role in the regulation of many physiological processes, including hair growth cycle. The article describes the history of the discovery of prostaglandins, including the work of Professor Ryszard Gryglewski – the discoverer of prostacyclin. Particular attention was paid to the synthetic analogue of prostaglandin F2α - latanoprost. Indicated for the treatment of glaucoma, the drug is known for inducing eyelash growth as a side effect. A prodrug, latanoprostis converted to its active metabolite, latanoprost acid. Recent research demonstrated that latanoprost acid has a chance to become an effective alternative to minoxidil and finasteride - the only drugs currently registered for the treatment of androgenetic alopecia. The development ofanti-alopecia drugs containing prostaglandin derivatives, including latanoprost acid, will be a much faster process compared to the traditional path of product development based on a new chemical compound.