Small but signifiant- the role of microRNAs in the formation, detection and treatment of cancer based on gastric cancer

W dobie intensywnego rozwoju chorób cywilizacyjnych, m.in. nowotworów żołądka, niezbędne jest zaprojektowanie markerów, które umożliwią wczesne ich wykrycie, pozwolą na szybkie podjęcie leczenia oraz zapobiegną zwiększeniu liczby zgonów. Taką potencjalną możliwością są mikroRNA, czyli krótkie cząsteczki RNA modulujące aktywność ściśle określonych fragmentów RNA i odgrywające szczególną rolę w wielu procesach fijologicznych i patologicznych. Wpływając na proliferację, cykl komórkowy oraz apoptozę komórek nowotworowych odgrywają znaczącą rolę również w nowotworzeniu. Wykrywalne w osoczu odstępstwa od ich normalnego poziomu, związane z każdym z etapów rozwojowych nowotworu mogą czynić je skutecznymi i nieinwazyjnymi biomarkerami, pozwalającymi nie tylko na detekcję i rozpoznawanie nowotworów, ale także na ich predykcję. Dalsze poznanie ich funkcji i właściwości może owocować odkryciem skutecznych leków do walki z nowotworami.In the era of intensive development of lifestyle diseases such as stomach cancer, it is crucial to design markers that enable their early detection, allow rapid introduction of treatment and prevent the increase in the number of deceases. Potential possibility is microRNAs, short RNA molecules which modulate the activity of specifi fragments of RNA and play an important role in many physiological and pathological processes. Affcting cell proliferation, cell cycle and apoptosis of cancer cells also play a significant role in neoplasia. Detectable levels of derogation from the regular level associated with each of the stages of tumor development may make them effctive and non-invasive biomarkers, allowing not only for early detection and identifiation of cancer’s type, but also on their prediction. Further understanding of their functions and properties can result in the discovery of effctive methods of cancer treatment

Does the Gut Microbial Metabolome Really Matter? The Connection between GUT Metabolome and Neurological Disorders

Herein we gathered updated knowledge regarding the alterations of gut microbiota (dysbiosis) and its correlation with human neurodegenerative and brain-related diseases, e.g., Alzheimer’s and Parkinson’s. This review underlines the importance of gut-derived metabolites and gut metabolic status as the main players in gut-brain crosstalk and their implications on the severity of neural conditions. Scientific evidence indicates that the administration of probiotic bacteria exerts beneficial and protective effects as reduced systemic inflammation, neuroinflammation, and inhibited neurodegeneration. The experimental results performed on animals, but also human clinical trials, show the importance of designing a novel microbiota-based probiotic dietary supplementation with the aim to prevent or ease the symptoms of Alzheimer’s and Parkinson’s diseases or other forms of dementia or neurodegeneration

Gold Nanoparticles Promote Oxidant-Mediated Activation of NF-κB and 53BP1 Recruitment-Based Adaptive Response in Human Astrocytes

Nanogold-based materials are promising candidate tools for nanobased medicine. Nevertheless, no conclusive information on their cytotoxicity is available. In the present study, we investigated the effects of gold nanoparticles (AuNPs) on human astrocytes in vitro. Nanogold treatment in a wide range of concentrations did not result in cytotoxicity. In contrast, nanogold provoked changes in the astrocyte cell cycle and induced senescence-associated β-galactosidase activity. AuNPs promoted oxidative stress and caused activation of NF-κB pathway. After nanogold treatment, an inverse correlation between the formation of 53BP1 foci and micronuclei generation was observed. The robust 53BP1 recruitment resulted in reduced micronuclei production. Thus, nanogold treatment stimulated an adaptive response in a human astrocyte cell

Focus on the Role of Klotho Protein in Neuro-Immune Interactions in HT-22 Cells Upon LPS Stimulation

Neuroinflammation is defined as the activation of the brain’s innate immune system in response to an inflammatory challenge and is considered to be a prominent feature of neurodegenerative diseases. The contribution of overactivated neuroglial cells to neuroinflammation and neurodegenerative disorders is well documented, however, the role of hippocampal neurons in the neuroinflammatory process remains fragmentary. In this study, we show for the first time, that klotho acts as a signal transducer between pro-survival and pro-apoptotic crosstalk mediated by ER stress in HT-22 hippocampal neuronal cells during LPS challenge. In control HT-22 cells, LPS treatment results in activation of the IRE1α-p38 MAPK pathway leading to increased secretion of anti-inflammatory IL-10, and thus, providing adaptation mechanism. On the other hand, in klotho-deficient HT-22 cells, LPS induces oxi-nitrosative stress and genomic instability associated with telomere dysfunctions leading to p53/p21-mediated cell cycle arrest and, in consequence, to ER stress, inflammation as well as of apoptotic cell death. Therefore, these results indicate that klotho serves as a part of the cellular defense mechanism engaged in the protection of neuronal cells against LPS-mediated neuroinflammation, emerging issues linked with neurodegenerative disorders

Cytotoxic and cytostatic side effects of chitosan nanoparticles as a non-viral gene carrier

Although chitosan nanoparticles (CNs) became a promising tool for several biological and medical applications owing to their inherent biocompatibility and biodegradability features, studies regarding their effects on cytotoxic and cytostatic properties still remain insufficient. Therefore, in the present study, we decided to perform comprehensive analysis of the interactions between CNs–pKindling-Red-Mito (pDNA) and different cell line models derived from blood system and human solid tissues cancers. The resulting CNs-pDNA was investigated in terms of their cellular uptake, transfection efficiency, and physico-chemical, cytotoxic and cytostatic properties. The nanoparticles showed high encapsulation efficiency and physical stability for various formulations even after two days time period. Moreover, high gene expression levels were observed after 96 h of transfection. CNs-pDNA treatment, despite the absence of oxidative stress induction, caused cell cycle arrest in G0/G1 phase and as a consequence led to premature senescence which turned out to be both p21-dependent and p21-independent. Also, observed DNMT2 upregulation may suggest the activation of different pathways protecting from the results of CNs-mediated stress. In conclusion, treatment of different cell lines with CNs-pDNA showed that their biocompatibility was limited and the effects were cell type-dependent

Seasonal expression of insulin-like growth factor 1 (IGF-1), its receptor IGF-1R and klotho in testis and epididymis of the European bison (Bison bonasus, Linnaeus 1758)

The European bisons are the largest mammals of Europe that are still in danger of extinction. The species conservation is associated with their continuous reproduction, and bisons are characterized by the well-pronounced seasonality of reproductive processes. However, the exact mechanisms regulating their reproduction still remain unknown. Our previous studies indicated the involvement of some of the growth factors in the regulation of male seasonal reproductive activities in bison, showing expression patterns that seemed to be regulated by the length of the daylight. In the present study, using RT-PCR and Western blot approaches, we verified the expression and possible relationship between the insulin-like growth factor (IGF-1), its receptor (IGF-1R), and klotho in testis and epididymis of the European bison in pre- and post-reproductive periods, i.e., in June and in December. The observed expression of IGF-1 and IGF-1R mRNA in testis and epididymis was higher in June than in December. At the same time, klotho mRNA expression in both testis and epididymis did not differ between the analyzed seasons. However, along with the higher levels of IGF-1R protein observed in June, klotho protein levels for the membrane form and for the secrete form were higher in December than in June. Finally, the messenger and protein expression profiles presented herein indicate the importance of both the IGF-system and klotho in reproductive processes in the European bison, implying their involvement in the regulation of seasonal testicular activity in males of this threatened species

Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes

Immunosenescence in monocytes has been shown to be associated with several biochemical and functional changes, including development of senescence-associated secretory phenotype (SASP), which may be inhibited by klotho protein. To date, it was believed that SASP activation is associated with accumulating DNA damage. However, some literature data suggest that endoplasmic reticulum and Golgi stress pathways may be involved in SASP development. Thus, the aim of this study was to investigate the role of klotho protein in the regulation of immunosenescence-associated Golgi apparatus and ER stress response induced by bacterial antigens in monocytes. We provide evidence that initiation of immunosenescent-like phenotype in monocytes is accompanied by activation of CREB34L and TFE3 Golgi stress response and ATF6 and IRE1 endoplasmic reticulum stress response, while klotho overexpression prevents these changes. Further, these changes are followed by upregulated secretion of proinflammatory cytokines, which final modification takes place exclusively in the Golgi apparatus. In conclusion, we provide for the first time evidence of klotho involvement in the crosstalk on the line ER-Golgi, which may, in turn, affect activation of SASP. This data may be useful for a novel potential target for therapy in age-related and chronic inflammatory conditions

The strain-dependent cytostatic activity of Lactococcus lactis on CRC cell lines is mediated through the release of arginine deiminase

Abstract Background Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, posing a serious public health challenge that necessitates the development of new therapeutics, therapies, and prevention methods. Among the various therapeutic approaches, interventions involving lactic acid bacteria (LAB) as probiotics and postbiotics have emerged as promising candidates for treating and preventing CRC. While human-isolated LAB strains are considered highly favorable, those sourced from environmental reservoirs such as dairy and fermented foods are also being recognized as potential sources for future therapeutics. Results In this study, we present a novel and therapeutically promising strain, Lactococcus lactis ssp. lactis Lc4, isolated from dairy sources. Lc4 demonstrated the ability to release the cytostatic agent - arginine deiminase (ADI) - into the post-cultivation supernatant when cultured under conditions mimicking the human gut environment. Released arginine deiminase was able to significantly reduce the growth of HT-29 and HCT116 cells due to the depletion of arginine, which led to decreased levels of c-Myc, reduced phosphorylation of p70-S6 kinase, and cell cycle arrest. The ADI release and cytostatic properties were strain-dependent, as was evident from comparison to other L. lactis ssp. lactis strains. Conclusion For the first time, we unveil the anti-proliferative properties of the L. lactis cell-free supernatant (CFS), which are independent of bacteriocins or other small molecules. We demonstrate that ADI, derived from a dairy- Generally Recognized As Safe (GRAS) strain of L. lactis, exhibits anti-proliferative activity on cell lines with different levels of argininosuccinate synthetase 1 (ASS1) expression. A unique feature of the Lc4 strain is also its capability to release ADI into the extracellular space. Taken togethe