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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Plant peroxidases have strong potential utility for decontamination of phenol-polluted wastewater. However, large-scale use of these enzymes for phenol depollution requires a source of cheap, ...abundant, and easily accessible peroxidase-containing material. In this study, we show that potato pulp, a waste product of the starch industry, contains large amounts of active peroxidases. We demonstrate that potato pulp may serve as a tool for peroxidase-based remediation of phenol pollution. The phenol removal efficiency of potato pulp was over 95 % for optimized phenol concentrations. The potato pulp enzymes maintained their activity at pH 4 to 8 and were stable over a wide temperature range. Phenol solutions treated with potato pulp showed a significant reduction in toxicity compared with untreated phenol solutions. Finally we determined that this method may be employed to remove phenol from industrial effluent with over 90 % removal efficiency under optimal conditions.
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.
Guanosine 3',5'-cyclic monophosphate (cGMP) is an important signaling molecule in plants. cGMP and guanylyl cyclases (GCs), enzymes that catalyze the synthesis of cGMP from GTP, are involved in ...several physiological processes and responses to environmental factors, including pathogen infections. Using in vitro analysis, we demonstrated that recombinant BdGUCD1 is a protein with high guanylyl cyclase activity and lower adenylyl cyclase activity. In
, infection by
leads to changes in
mRNA levels, as well as differences in endogenous cGMP levels. These observed changes may be related to alarm reactions induced by pathogen infection. As fluctuations in stress phytohormones after infection have been previously described, we performed experiments to determine the relationship between cyclic nucleotides and phytohormones. The results revealed that inhibition of cellular cGMP changes disrupts stress phytohormone content and responses to pathogen. The observations made here allow us to conclude that cGMP is an important element involved in the processes triggered as a result of infection and changes in its levels affect jasmonic acid. Therefore, stimuli-induced transient elevation of cGMP in plants may play beneficial roles in priming an optimized response, likely by triggering the mechanisms of feedback control.
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.
Sugar beet is a highly salt-tolerant crop. However, its ability to withstand high salinity is reduced compared to sea beet, a wild ancestor of all beet crops. The aim of this study was to investigate ...transcriptional patterns associated with physiological, cytological and biochemical mechanisms involved in salt response in these closely related subspecies. Salt acclimation strategies were assessed in plants subjected to either gradually increasing salt levels (salt-stress) or in excised leaves, exposed instantly to salinity (salt-shock).
The majority of DEGs was down-regulated under stress, which may lead to certain aspects of metabolism being reduced in this treatment, as exemplified by lowered transpiration and photosynthesis. This effect was more pronounced in sugar beet. Additionally, sugar beet, but not sea beet, growth was restricted. Silencing of genes encoding numerous transcription factors and signaling proteins was observed, concomitantly with the up-regulation of lipid transfer protein-encoding genes and those coding for NRTs. Bark storage protein genes were up-regulated in sugar beet to the level observed in unstressed sea beet. Osmotic adjustment, manifested by increased water and proline content, occurred in salt-shocked leaves of both genotypes, due to the concerted activation of genes encoding aquaporins, ion channels and osmoprotectants synthesizing enzymes. bHLH137 was the only TF-encoding gene induced by salt in a dose-dependent manner irrespective of the mode of salt treatment. Moreover, the incidence of bHLH-binding motives in promoter regions of salinity-regulated genes was significantly greater than in non-regulated ones.
Maintaining homeostasis under salt stress requires deeper transcriptomic changes in the sugar beet than in the sea beet. In both genotypes salt shock elicits greater transcriptomic changes than stress and it results in greater number of up-regulated genes compared to the latter. NRTs and bark storage protein may play a yet undefined role in salt stress-acclimation in beet. bHLH is a putative regulator of salt response in beet leaves and a promising candidate for further studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Salicornia europaea, a succulent obligatory halophyte is the most salt-tolerant plant species in the world. It survives salt concentrations of more than 1 M. Therefore, it is a suitable model plant ...to identify genes involved in salt tolerance mechanisms that can be used for the improvement of crops. The changes in a plant's gene expression in response to abiotic stresses may depend on factors like soil conditions at the site, seasonality, etc. To date, experiments were performed to study the gene expression of S. europaea only under controlled conditions. Conversely, the present study investigates the transcriptome and physicochemical parameters of S. europaea shoots and roots from two different types of saline ecosystems growing under natural conditions.
The level of soil salinity was higher at the naturally saline site than at the anthropogenic saline site. The parameters such as EC
, Na
, Cl
, Ca
, SO
and HCO
of the soils and plant organs significantly varied according to sites and seasons. We found that Na
mainly accumulated in shoots, whereas K
and Ca
levels were higher in roots throughout the growing period. Moreover, changes in S. europaea gene expression were more prominent in seasons, than sites and plant organs. The 30 differentially expressed genes included enzymes for synthesis of S-adenosyl methionine, CP47 of light-harvesting complex II, photosystem I proteins, Hsp70 gene, ATP-dependent Clp proteases, ribulose bisphosphate carboxylase/oxygenase (Rubisco), phenylalanine ammonia-lyase (PAL), cytochrome c oxidase (COX) and ATP synthase.
The comparisons made based on two seasons, plant organs and two different sites suggest the importance of seasonal variations in gene expression of S. europaea. We identify the genes that may play an important role in acclimation to season-dependent changes of salinity. The genes were involved in processes such as osmotic adjustment, energy metabolism and photosynthesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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