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Abstract MicroRNA expression in breast cancer (BC) is explored both as a potential biomarker and for therapeutic purposes. Recent studies have revealed that miR-203a-3p is involved in BC, and importantly contributes to BC chemotherapy responses; however, the regulatory pathways of miR-203a in BC remain elusive. Hence, we aimed to investigate the miR-203a regulatory mechanisms and their potential functions in the progress of BC. To this end, the miR-203a potential involving pathways was predicted by databases analyzing its target genes. The relations between miR-203a, the phosphatidylinositol 3′-kinase (PI3K)–Akt, and Wnt signaling pathways were mechanistically investigated. Our results revealed that miR-203a inhibited the activation of the PI3K/Akt and Wnt pathways and reduced its downstream cell cycle signals, including Cyclin D1 and c-Myc. Moreover, the overexpression of miR-203a drastically arrested the cell cycle at subG1 and G1 phases, decreased the viability, proliferation, and migration, and increased apoptosis of BC cells. Therefore, miR-203a-3p may be considered a tumor suppressor factor and a potential biomarker or therapeutic target for BC.

Abstract HER-2/neu (HER2) is a member of the epidermal growth factor receptors family, encoding a protein with tyrosine kinase activity. Following the gene amplification or increased HER2 transcription, carcinogenesis has been observed in some cancers. Genetic and epigenetic changes occurring in enhancer sequences can deeply affect the expression and transcriptional regulation of downstream genes, which can cause some physiological and pathological changes, including tumor progression. A therapeutic approach that directly targets the genomic sequence alterations is of high importance, with low side effects on healthy cells. Here, we employed the CRISPR/Cas9 method to genetically knockout an expressed putative enhancer (GH17J039694; we coined it as Her2-Enhancer1) located within the HER2 gene, 17q12: 39,694,339–39,697,219 (UCSC-hg38). We then investigated the potential regulatory effect of Her2-Enhancer1 on HER2 and HER2-interacting genes. To evaluate the cis and trans effects of Her2-Enhancer1, genetic manipulation of this region was performed in HER2-positive and -negative breast cancer cells. Our bioinformatics and real-time PCR data revealed that this putative enhancer region is indeed expressed, and acts as an expressed enhancer. Further functional analysis on edited and unedited cells revealed a significant alteration in the expression of HER2 variants, as well as some other target genes of HER2. Moreover, the apoptosis rate was considerably elevated within the edited cells. As we expected, Western blot analysis confirmed a reduction in protein levels of HER2, GRB7, the gene interacting with HER2, and P-AKT in the PI3K/AKT pathway. Altogether, our findings revealed an enhancer regulatory role for Her2-Enhancer1 on HER2 and HER2-interacting genes; and that this region has a potential for targeted therapy of HER2-positive cancers.

Abstract Melatonin is a pleiotropic molecule that can influence various aspects of plant performance. Recent studies have exhibited that it mediates plant defensive responses, probably through managing redox homeostasis. We tried to track the regulatory effects of melatonin on the antioxidant machinery of Linum album cell culture. To this, different concentrations of melatonin were applied, and the oxidative status of cells was investigated by measuring the levels of oxidative molecules and antioxidant agents. The results showed that H2O2 content did not change at the low melatonin levels, while it increased at the high concentrations. It can be correlated with the low melatonin dosages capacity to remove excessive amounts of H2O2, while the high melatonin dosages exhibit toxicity effects. In contrast, the NO enhancement occurred at 50 μM melatonin, proposing its role in triggering melatonin-induced defensive responses. The MDA results stated that NO led to oxidative stress in melatonin-treated cells at 50 μM melatonin. Antioxidant enzyme POD was activated by melatonin treatment, while SOD enzyme behaved reversely which can explain the changes in the H2O2 level. In addition, the analysis of the phenolics profile showed that the contents of phenolic acids, flavonoids, and lignans enhanced following an increase in PAL enzyme activity. The increased level of phenolic hormone SA can indicate that melatonin affects the defensive responses in L. album cells through a SA-dependent pathway. In general, it seems that melatonin, by modulating NO and SA levels, can induce the activity of antioxidant enzymes and the production of phenolics, especially lignans, in L. album cells.

Abstract Cardiac fibrosis in the failing heart is modulated by activated myofibroblasts, and is a pathology marked by their deposition of extracellular matrix proteins. The TGFβ signaling pathway is important in stimulating fibrosis and therefore seems an attractive new target for anti-fibrotic therapy. The relationship between ncRNAs and TGFβ signaling pathway has been extensively studied. Here, we have provided several lines of evidence to prove that the fibrosis process could be regulated by miR-331 through targeting TGFβ signaling. First, bioinformatics analysis and dual luciferase assay validated a direct interaction between the miR-331 and TGFβ-R1 3′UTR sequence which results in the downregulation of TGFβ signaling pathway. Second, miR-331 expression was inversely related to the expression of a number of genes which are involved in extracellular matrix (ECM) production and deposition processes, both in the in vivo and in vitro fibrosis models. Third, in cultured mouse and human cardiac myofibroblasts (CMyoFbs) under ISO treatment, overexpression of miR-331 decreased the expression level of fibrosis-related genes. Consistently, western blot analysis confirmed that miR-331 overexpression ended in both Smad3 and Col1A1 protein level reduction in mouse cardiac myofibroblasts. Finally, flow cytometry analysis, cyclin D1 and D2 gene expression analysis, and wound-healing assay confirmed the inhibitory effect of miR-331 against cell proliferation and migration in ISO-treated cardiac myofibroblasts. Taken together, accumulative results showed that miR-331 reduced the level of fibrosis-related proteins in cardiac myofibroblasts culture via regulating TGFβ signaling pathway.

Nowadays, the use of natural wastes and adsorbents along with their modification by simple and new methods based on metal oxides to remove dye pollutants has been the focus of many researchers. In this study, for the first time, simple and low-cost modification of eggshell (EGS) with tungsten oxide (WO 3 ) based on the photochemical modification method as a green, ultra-fast, cost-effective, and biodegradable adsorbent is reported to remove of methylene blue (MB) dye pollutant. The EGS modified by WO 3 was investigated by EDX, EDX mapping, XRD, FE-SEM, and UV-Vis Diffuse Reflectance (DRS) analyses. The obtained results show that the modified EGS by WO 3 has more than ten times (78.5%) the ability to remove MB dye pollutant within 3 min compared to bare EGS (11%). Various parameters including dye pollutant pH, dye concentration, adsorbent dosage, and reusability of the WO 3 /EGS adsorbent for removal of MB dye pollutant were investigated and the result show that the adsorbent capacity of WO 3 /EGS is 1.64 mg g -1 . EGS adsorbent The synthesis of WO 3 /EGS adsorbent with a novel photochemical method as a fast and very cheap adsorbent with excellent efficiency can be a promising alternative adsorbent for various purposes in removing dye pollutants from water environments., (© 2024. The Author(s).)

In this study, a polymeric adsorbent based on carboxymethyl tragacanth (CMT) grafted by poly acrylic acid-co-acrylamide (AAc-co-AAm) synthesized by radical polymerization for the first time was used to remove the fungicide penconazole (PEN) or Topas 20% from surface water. The parameters of solution pH, adsorption isotherm, and adsorption kinetics of PEN were studied by the synthetic adsorbent. The surface morphology and functional groups of CMT-g-poly (AAc-co-AAm) were confirmed by XRD, SEM and FT-IR techniques. Adsorption of PEN on CMT-g-poly (AAc-co-AAm) follows the Freundlich and pseudo-second-order models. The significant maximum adsorption capacity of the synthesized polymer was found to be 196.08 mg/g. The synthetic adsorbent had good reproducibility in PEN removal for up to 5 cycles. CMT-g-poly (AAc-co-AAm) is a cost-effective and non-toxic adsorbent for the decontamination of surface water from pesticides., (© 2023. Springer Nature Limited.)

Ectomycorrhiza (ECM) is a symbiotic relation between plant and fungi that is essential for nutrient uptake of many stand forming trees. There are two conflicting views about the evolution of ECM in fungi suggesting (1) relatively few transitions to ECM followed by reversals to non-ECM, or (2) many independent origins of ECM and no reversals. In this study, we compare these, and other, hypotheses and test the impact of different models on inference. We assembled a dataset of five marker gene sequences (nuc58, nucLSU, nucSSU, rpb1, and rpb2) and 2,174 fungal taxa covering the three subphyla: Agaricomycotina, Mucoromycotina and Pezizomycotina. The fit of different models, including models with variable rates in clades or through time, to the pattern of ECM fungal taxa was tested in a Bayesian framework, and using AIC and simulations. We find that models implementing variable rates are a better fit than models without rate shift, and that the conclusion about the relative rate between ECM and non-ECM depend largely on whether rate shifts are allowed or not. We conclude that standard constant-rate ancestral state reconstruction models are not adequate for the analysis of the evolution of ECM fungi, and may give contradictory results to more extensive analyses., (© 2022. The Author(s).)