Small noncoding RNAs, as post-translational regulators of many target genes, are not only markers of neoplastic disease initiation and progression, but also markers of response to anticancer therapy. ...Hundreds of miRNAs have been identified as biomarkers of drug resistance, and many have demonstrated the potential to sensitize cancer cells to therapy. Their properties of modulating the response of cells to therapy have made them a promising target for overcoming drug resistance. Several methods have been developed for the delivery of miRNAs to cancer cells, including introducing synthetic miRNA mimics, DNA plasmids containing miRNAs, and small molecules that epigenetically alter endogenous miRNA expression. The results of studies in animal models and preclinical studies for solid cancers and hematological malignancies have confirmed the effectiveness of treatment protocols using microRNA. Nevertheless, the use of miRNAs in anticancer therapy is not without limitations, including the development of a stable nanoconstruct, delivery method choices, and biodistribution. The aim of this review was to summarize the role of miRNAs in cancer treatment and to present new therapeutic concepts for these molecules. Supporting anticancer therapy with microRNA molecules has been verified in numerous clinical trials, which shows great potential in the treatment of cancer.
Knee osteoarthritis (KOA) represents a clinical challenge due to poor potential for spontaneous healing of cartilage lesions. Several treatment options are available for KOA, including oral ...nonsteroidal anti-inflammatory drugs, physical therapy, braces, activity modification, and finally operative treatment. Intra-articular (IA) injections are usually used when the non-operative treatment is not effective, and when the surgery is not yet indicated. More and more studies suggesting that IA injections are as or even more efficient and safe than NSAIDs. Recently, research to improve intra-articular homeostasis has focused on biologic adjuncts, such as platelet-rich plasma (PRP). The catabolic and inflammatory intra-articular processes that exists in knee osteoarthritis (KOA) may be influenced by the administration of PRP and its derivatives. PRP can induce a regenerative response and lead to the improvement of metabolic functions of damaged structures. However, the positive effect on chondrogenesis and proliferation of mesenchymal stem cells (MSC) is still highly controversial. Recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, significant progress has been made in understanding the mechanism of PRP action. In this review, we will discuss mechanisms related to inflammation and chondrogenesis in cartilage repair and regenerative processes after PRP administration in in vitro and animal studies. Furthermore, we review clinical trials of PRP efficiency in changing the OA biomarkers in knee joint.
Breast cancer exhibits various epigenetic abnormalities that regulate gene expression and contribute to tumor characteristics. Epigenetic alterations play a significant role in cancer development and ...progression, and epigenetic-targeting drugs such as DNA methyltransferase inhibitors, histone-modifying enzymes, and mRNA regulators (such as miRNA mimics and antagomiRs) can reverse these alterations. Therefore, these epigenetic-targeting drugs are promising candidates for cancer treatment. However, there is currently no effective epi-drug monotherapy for breast cancer. Combining epigenetic drugs with conventional therapies has yielded positive outcomes and may be a promising strategy for breast cancer therapy. DNA methyltransferase inhibitors, such as azacitidine, and histone deacetylase inhibitors, such as vorinostat, have been used in combination with chemotherapy to treat breast cancer. miRNA regulators, such as miRNA mimics and antagomiRs, can alter the expression of specific genes involved in cancer development. miRNA mimics, such as miR-34, have been used to inhibit tumor growth, while antagomiRs, such as anti-miR-10b, have been used to inhibit metastasis. The development of epi-drugs that target specific epigenetic changes may lead to more effective monotherapy options in the future.
In the past decade, significant advances in molecular research have provided a deeper understanding of the intricate regulatory mechanisms involved in carcinogenesis. MicroRNAs, short non-coding RNA ...sequences, exert substantial influence on gene expression by repressing translation or inducing mRNA degradation. In the context of cancer, miRNA dysregulation is prevalent and closely associated with various stages of carcinogenesis, including initiation, progression, and metastasis. One crucial aspect of the cancer phenotype is the activity of histone-modifying enzymes that govern chromatin accessibility for transcription factors, thus impacting gene expression. Recent studies have revealed that miRNAs play a significant role in modulating these histone-modifying enzymes, leading to significant implications for genes related to proliferation, differentiation, and apoptosis in cancer cells. This article provides an overview of current research on the mechanisms by which miRNAs regulate the activity of histone-modifying enzymes in the context of cancer. Both direct and indirect mechanisms through which miRNAs influence enzyme expression are discussed. Additionally, potential therapeutic implications arising from miRNA manipulation to selectively impact histone-modifying enzyme activity are presented. The insights from this analysis hold significant therapeutic promise, suggesting the utility of miRNAs as tools for the precise regulation of chromatin-related processes and gene expression. A contemporary focus on molecular regulatory mechanisms opens therapeutic pathways that can effectively influence the control of tumor cell growth and dissemination.
Here we determined the impact of salt shock and salt stress on the level of DNA methylation in selected CpG islands localized in promoters or first exons of sixteen salt-responsive genes in beets. ...Two subspecies differing in salt tolerance were subjected for analysis, a moderately salt-tolerant sugar beet Beta vulgaris ssp. vulgaris cv. Huzar and a halophytic beet, Beta vulgaris ssp. maritima. The CpG island methylation status was determined. All target sequences were hyper- or hypomethylated under salt shock and/or salt stress in one or both beet subspecies. It was revealed that the genomic regions analyzed were highly methylated in both, the salt treated plants and untreated controls. Methylation of the target sequences changed in a salt-dependent manner, being affected by either one or both treatments. Under both shock and stress, the hypomethylation was a predominant response in sugar beet. In Beta vulgaris ssp. maritima, the hypermethylation occurred with higher frequency than hypomethylation, especially under salt stress and in the promoter-located CpG sites. Conversely, the hypomethylation of the promoter-located CpG sites predominated in sugar beet plants subjected to salt stress. This findings suggest that DNA methylation may be involved in salt-tolerance and transcriptomic response to salinity in beets.
Ascorbate oxidase, which is known to play a key role in regulating the redox state in the apoplast, cell wall metabolism, cell expansion and abiotic stress response in plants, oxidizes apo-plastic ...ascorbic acid (AA) to dehydroascorbic acid (DHA). However, there is little information about the AAO genes and their functions in beets under abiotic stress. The term salt or drought stress refers to the treatment of plants with slow and gradual salinity/drought. Contrastingly, salt shock consists of exposing plants to high salt levels instantaneously and drought shock occurs under fast drought progression. In the present work, we have subjected plants to salinity or drought treatments to elicit either stress or shock and carried out a genome-wide analysis of ascorbate oxidase (AAO) genes in sugar beet (B. vulgaris cv. Huzar) and its halophytic ancestor (B. maritima). Here, conserved domain analyses showed the existence of twelve BvAAO gene family members in the genome of sugar beet. The BvAAO_1–12 genes are located on chromosomes 4, 5, 6, 8 and 9. The phylogenetic tree exhibited the close relationships between BvAAO_1-12 and AAO genes of Spinacia oleracea and Chenopodium quinoa. In both beet genotypes, downregulation of AAO gene expression with the duration of salt stress or drought treatment was observed. This correlated with a decrease in AAO enzyme activity under defined experimental setup. Under salinity, the key downregulated gene was BvAAO_10 in Beta maritima and under drought the BvAAO_3 gene in both beets. This phenomenon may be involved in determining the high tolerance of beet to salinity and drought.
At the end of 2020, population-based vaccination programs with new generation mRNA-based vaccines began almost all over the world. The aim of the study was to evaluate the titer of anti-SARS-CoV-2 ...IgG antibodies against the S1 subunit of the virus’s spike protein as a marker of the humoral response in 477 patients and the concentration of interferon-gamma as an indicator of cellular response in 28 individuals. In our studies, we used serological enzyme-linked immunosorbent assays. IgG was measured in weeks 2 and 3 after the first dose and 1–5 weeks after the second dose of an mRNA vaccine in seropositive and seronegative individuals as well as in symptomatic and asymptomatic convalescents. High levels of antibodies were observed in 98% of our vaccinated cohort, and the presence of protective T cells was confirmed in the blood samples of all participants. The humoral immune response is diversified and is visible as early as 2–3 weeks after the first dose of the mRNA vaccine. The level of protection increased significantly after the second dose, with the increase being much greater in pre-vaccine healthy subjects and less in convalescents. In the second and third weeks after the second dose, the concentration of IgG antibodies was the highest, and in the following weeks, it decreased gradually. Regular serological measurements on eight subjects show that antibody titers are lower four months after vaccination than before the second dose.
Cartilage lesions have a multifactorial nature, and genetic factors are their strongest determinants. As biochemical and genetic studies have dramatically progressed over the past decade, the ...molecular basis of cartilage pathologies has become clearer. Several homeostasis abnormalities within cartilaginous tissue have been found, including various structural changes, differential gene expression patterns, as well as altered epigenetic regulation. However, the efficient treatment of cartilage pathologies represents a substantial challenge. Understanding the complex genetic background pertaining to cartilage pathologies is useful primarily in the context of seeking new pathways leading to disease progression as well as in developing new targeted therapies. A technology utilizing gene transfer to deliver therapeutic genes to the site of injury is quickly becoming an emerging approach in cartilage renewal. The goal of this work is to provide an overview of the genetic basis of chondral lesions and the different approaches of the most recent systems exploiting therapeutic gene transfer in cartilage repair. The integration of tissue engineering with viral gene vectors is a novel and active area of research. However, despite promising preclinical data, this therapeutic concept needs to be supported by the growing body of clinical trials.
This study aimed to evaluate the long-term effectiveness of COVID-19 vaccination in healthcare workers by analyzing the population's response to the vaccine after two years, based on anti-SARS-CoV-2 ...protein S antibody levels. Additionally, the study aimed to assess the impact of basic factors on antibody levels.
A total of 4,090 healthcare workers were included in the study, and their antibody levels were measured using ELISA to detect anti-SARS-CoV-2 immunoglobulin G (IgG). Statistical analysis was conducted to examine the influence of COVID-19 infection, vaccination status, and number of vaccine doses on antibody concentrations.
The majority of participants (85.1%) received the Pfizer/BioNTech vaccine, while a smaller percentage chose vector vaccines such as AstraZeneca and Johnson & Johnson. The incidence of COVID-19 among vaccinated individuals was relatively low for all vaccines, confirming their effectiveness in preventing symptomatic SARS-CoV-2 infection. The study observed variations in IgG antibody levels within the study population, with only 0.46% of individuals testing negative for the presence of antibodies. The average anti-SARS-CoV-2 IgG values showed significant differences across consecutive 3-month periods following infection or vaccination, with a gradual decrease over time. Notably, the most significant changes in antibody levels were observed within the first 6 months (mean values ranged from 3647.11 BAU/ml to 2601.49 BAU/ml). Subsequently, minor fluctuations were observed, with mean antibody values hovering around 2000 BAU/ml. The differences between average anti-SARS-CoV-2 IgG values between consecutive 3-month periods from disease onset were statistically significant.
In the recent years, significant development of molecular genetics has contributed to the better understanding of leukemogenesis and classification of the different leukemia subtypes. Patients ...diagnosed with acute leukemia usually undergo chemotherapy, which involves the induction of remission, consolidation of remission and maintenance therapy. Patients are still vulnerable to relapse due to differences in the sensitivity of leukemia cells to the chemotherapeutic agent, because of the active drugs removal from the cells, improving the repair of DNA damage or abnormalities in the apoptotic pathway. Cell adhesion and miRNA expression level also affect the drug resistance. New candidate genes and genes correlated with the disease have been sought to increase the survival of patients with leukemia. Candidate gene is usually a loci located in a certain chromosomal region suspected of involvement to the disease course or its expression product regulates disease progression. There are classic and digital methods of finding candidate genes. These techniques are inexpensive, quick and easy to carry out. Unfortunately, due to insufficient knowledge of the disease etiology and low accuracy, researchers cannot detect all genes, involved in leukemogenesis and cell resistance. Currently, scientists have many tools used for selecting genes, such as expression microarrays, comparative genomic hybridization and next generation sequencing. Among the validation techniques for candidate genes, the mostly used ones are fluorescent in situ hybridization and real-time PCR. In our review we present 18 candidate genes of resistance to therapy in childhood leukemia.
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