Inhibition of MEK/ERK signalling pathway promotes erythroid differentiation and reduces HSCs engraftment in ex vivo expanded haematopoietic stem cells

The MEK/ERK pathway is found to be important in regulating different biological processes such as proliferation, differentiation and survival in a wide variety of cells. However, its role in self‐renewal of haematopoietic stem cells is controversial and remains to be clarified. The aim of this study was to understand the role of MEK/ERK pathway in ex vivo expansion of mononuclear cells (MNCs) and purified CD34⁺ cells, both derived from human umbilical cord blood (hUCB). Based on our results, culturing the cells in the presence of an inhibitor of MEK/ERK pathway—PD0325901 (PD)—significantly reduces the expansion of CD34⁺ and CD34⁺ CD38^? cells, while there is no change in the expression of stemness‐related genes (HOXB4, BMI1). Moreover, in vivo analysis demonstrates that PD reduces engraftment capacity of ex vivo expanded CD34⁺ cells. Notably, when ERK pathway is blocked in UCB‐MNCs, spontaneous erythroid differentiation is promoted, found in concomitant with increasing number of burst‐forming unit‐erythroid colony (BFU‐E) as well as enhancement of erythroid glycophorin‐A marker. These results are in total conformity with up‐regulation of some erythroid enhancer genes (TAL1, GATA2, LMO2) and down‐regulation of some erythroid repressor genes (JUN, PU1) as well. Taken together, our results support the idea that MEK/ERK pathway has a critical role in achieving the correct balance between self‐renewal and differentiation of UCB cells. Also, we suggest that inhibition of ERK signalling could likely be a new key for erythroid induction of UCB‐haematopoietic progenitor cells.     

Identification of SSR and retrotransposon-based molecular markers linked to morphological characters in oily sunflower ($$\textit{}$$ L.) under natural and water-limited states

Sunflower is an important source of edible oil. Drought is known as an important factor limiting the growth and productivity of field crops in most parts of the world. Agricultural biotechnology mainly aims at developing crops with higher tolerance to the challenging environmental conditions, such as drought. This study examined a number of morphological characters, along with relative water content (RWC) in 100 inbred sunflower lines. A 10 \(\times \) 10 simple lattice design with two replications was employed to measure the mentioned parameters under natural and water-limited states during two successive years. In molecular trial, 30 simple sequence repeat (SSR) primer pairs, as well as 14 inter-retrotransposon amplified polymorphism (IRAP) and 14 retrotransposon-microsatellite amplified polymorphism (REMAP) primer combinations were used for DNA fingerprinting of the lines. Most of the examined characters had lower average values under water-limited than natural states. Maximum and minimum reductions were observed in the cases of yield and oil percentage, respectively. The broad-sense heritabilities for all the examined characters were 0.20–0.73 and 0.10–0.34 under natural and water-limited states, respectively. In the studied samples, 8.97% of the 435 possible locus pairs of the SSRs represented significant linkage disequilibrium (LD) levels. In the association analysis using SSR markers, 22 and 21 markers were identified (\(P \le 0.05\)) for the studied characters under natural and water-limited states, respectively. The corresponding values were 50 and 37 using retrotransposon-based molecular markers. Some detected markers were communal between the characters under water-limited and natural states. This was in line with the phenotypic correlations detected between the characters. Communal markers facilitate the simultaneous selection of several characters and can thus improve the efficacy of selection based on markers in the plant-breeding activities.     

Exosomes and microRNAs: New potential therapeutic candidates in Alzheimer disease therapy

Exosomes are biological nanocarriers which could be involved in a variety of basic physiological events. They exert their effects via targeting their cargos (i.e., DNAs, messenger RNAs, microRNAs [miRNAs], and proteins) to host cells, which led to change behaviors of recipient cells. One of the important aspects of exosomes is the roles of them in disease conditions. Increasing evidence indicated that exosomes are one of the main players in Alzheimer’s disease (AD) pathogenesis. Hence, it seems that these nanocarriers could be used as diagnostic and therapeutic biomarkers in AD treatment. Another important player in AD pathogenesis is miRNA. MiRNAs are short noncoding RNAs which exert their effects as epigenetic regulators. These molecules involved in different stages of AD. Therefore, miRNAs could be used as prognostic, diagnostic, and therapeutic biomarkers in AD. Here, we summarized various roles of exosomes and application of them in AD pathogenesis. Moreover, we highlighted the utilization of miRNAs as a therapeutic option in AD therapy.     

The rhizosheath: a potential root trait helping plants to tolerate drought stress

Plant and Soil - Experimental data concerning possible trophic relationships between phorophytes and epiphytes are contradictory. Several studies have indirectly shown that epiphytes affect the...     

Using parthenogenesis‐inducing Wolbachia for the selection of optimal lines of the egg parasitoid Trichogramma pretiosum for use in biocontrol

Trichogramma wasps (Hymenoptera: Trichogrammatidae) are egg parasitoids commonly employed in augmentative biological control releases against a variety of mainly lepidopteran pests. By exploiting the mechanism by which the endosymbiotic bacterium Wolbachia induces parthenogenesis in this genus, we created a set of completely homozygous Wolbachia‐infected recombinant isofemale lines (RILs), each consisting of a different combination of the genome of two well‐characterized lines of Trichogramma pretiosum Riley. We subsequently use 16 of these RILs to investigate the effect of genetic variation on various measures associated with offspring production under laboratory conditions. Unsurprisingly, substantial differences were found between the RILs in their propensity to parasitize hosts, the number of hosts they parasitize, and the levels of mortality in their offspring. Such measures can be used to choose an optimal line for biological control purposes. A method was also developed to characterize the 16 RILs using their allelic state at five loci. Essentially, this binary system uses high‐resolution melt analysis to resolve identity at each locus, with alleles originating from either the grandmaternal or grandpaternal line, and is such that each RIL can be distinguished from each other RIL by their allelic state at one or more loci. The method facilitates the easy diagnosis of line origin when two or more lines are competing with each other in competition assays, allowing for the design of more complicated tests of parasitoid quality. Future field experiments will determine which genetic line performs best under more realistic biological control conditions. The fact that these lines are infected with parthenogenesis‐inducing Wolbachia will allow for prolonged rearing without appreciable change in their genetic makeup, which should lead to a predictable biological control performance.     

The role of inflammation and its related microRNAs in breast cancer: A narrative review

Breast cancer is recognized as the most common type of cancer among women with a high rate of mortality all over the world. Over the past years, growing attention has been regarded to realize more about the mechanisms underlying the disease process. It is revealed that the progression of breast cancer may be strongly linked to chronic inflammation owing to the role of inflammatory factors in genetic instability and subsequent cancer predisposition. Although the association between breast cancer and inflammatory pathways has been well-defined now, only recent evidence pointed towards the inflammation-related microRNAs (miRNAs) as potential biomarkers and therapeutic targets involved in the crosstalk of multiple pathways during breast cancer development. Moreover, the practical interactions between these miRNAs and inflammatory factors are also a little characterized. In this review, we intended to describe the effects of predominant inflammatory pathways such as cytokines, phosphoinositide 3-kinase/protein kinase B, and nuclear factor kappa B in association with tumor promoting and tumor suppressing miRNAs on breast cancer progression. Providing new studies in the field of combining biomarkers for early diagnosis, prognosis, and monitoring breast cancer are very important. Notably, understanding the underlying mechanisms of miRNAs as a possible link between inflammation and tumorigenesis may offer a novel insight for combating this epidemic.     

Epigenetic modulation of BRCA-1 and MGMT genes,and histones H4 and H3 are associated with breast tumors

Aberrant patterns in promoter methylation of tumor-suppressor genes and posttranslational modifications of histone proteins are considered as major features of malignancy. In this study, we aimed to investigate promoter methylation of three tumor-suppressor genes (BRCA-1, MGMT, and P16) and three histone marks (H3K9ac, H3K18ac, and H4K20me3) in patients with breast tumors. This case-control study included 27 patients with malignant breast tumors (MBT) and 31 patients with benign breast tumors (BBT). The methylation-specific PCR was used for determining promoter methylation of BRCA-1, MGMT, and P16 genes. Western blot analysis was performed to detect histone lysine acetylation (H3K9ac and H3K18ac) and lysine methylation (H4K20me3). BRCA-1 promoter methylation was detected in 44.4% of the MBT whereas this alteration was found in 9.7% of BBT (P = 0.005). The Kaplan-Meier analysis indicated that hypermethylation in BRCA-1 promoter was significantly associated with poor overall survival of patients with breast cancer (P = 0.039). MGMT promoter methylation was identified in 18.5% of MBT and 0.0% of the BBT (P = 0.01). The frequency of P16 promoter methylation was 25.8% in BBT and 11.1% in MBT (P = 0.12). As compared with BBT, MBT samples displayed the aberrant patterns of histones marks with hypomethylation of H4K20 and hypoacetylation of H3K18 (P = 0.03 and P = 0.04, respectively). There was a negative significant correlation between H3K9ac levels and tumor size in MBT group (r = −0.672; P = 0.008). The present findings suggest that promoter hypermethylation of MGMT and BRCA-1 genes along with alterations in H3K18ac and H4K20me3 levels may have prognostic values in patients with breast cancer. Moreover, the detection of these epigenetic modifications in breast tumors could be helpful in finding new methods for breast cancer therapy.     

Spatial analysis of urban material stock with clustering algorithms: A Northern European case study

A large share of construction material stock (MS) accumulates in urban built environments. To attain a more sustainable use of resources, knowledge about the spatial distribution of urban MS is needed. In this article, an innovative spatial analysis approach to urban MS is proposed. Within this scope, MS indicators are defined at neighborhood level and clustered with k‐mean algorithms. The MS is estimated bottom‐up with (a) material‐intensity coefficients and (b) spatial data for three built environment components: buildings, road transportation, and pipes, using seven material categories. The city of Gothenburg, Sweden is used as a case study. Moreover, being the first case study in Northern Europe, the results are explored through various aspects (material composition, age distribution, material density), and, finally, contrasted on a per capita basis with other studies worldwide. The stock is estimated at circa 84 million metric tons. Buildings account for 73% of the stock, road transport 26%, and pipes 1%. Mineral‐binding materials take the largest share of the stock, followed by aggregates, brick, asphalt, steel, and wood. Per capita, the MS is estimated at 153 metric tons; 62 metric tons are residential, which, in an international context, is a medium estimate. Denser neighborhoods with a mix of nonresidential and residential buildings have a lower proportion of MS in roads and pipes than low‐density single‐family residential neighborhoods. Furthermore, single‐family residential neighborhoods cluster in mixed‐age classes and show the largest content of wood. Multifamily buildings cluster in three distinct age classes, and each represent a specific material composition of brick, mineral binding, and steel. Future work should focus on megacities and contrasting multiple urban areas and, methodologically, should concentrate on algorithms, MS indicators, and spatial divisions of urban stock.     

The influence of the use of improved sanitation facilities and improved drinking-water sources on the diarrhea-associated deaths in children under 5 years

Diarrhea is one of the main causes of children's death. Due to the importance of health in children under 5 years, this study has been conducted to determine the influence of the use of improved sanitation facilities (UISF) and the use of improved drinking-water sources (UIDWS) on the diarrhea-associated deaths per 1000 live births in this age group. An ecologic study was conducted in 75 countries, and the data on UIDWS and UISF information have been collected by World Health Organization (WHO) under a program named “Global Analysis and Assessment of Sanitation and Drinking-Water” (GLAAS). To determine the correlation between UIDWS and UISF with the diarrhea-associated deaths in children, Pearson correlation was applied. Besides, a linear regression analysis was used to investigate the relationship between UIDWS and UISF with the diarrhea-associated deaths in children. According to the findings, there was a significant statistical relationship between UIDWS and UISF with the diarrhea-associated deaths in children (p < 0.001). The diarrhea-associated deaths in children under 5 years are influenced by factors such as UIDWS and UISF, and this rate can be reduced making UISF and UIDWS available for people and especially people of rural areas.     

AurH1: a new heptapeptide derived from Aurein1.2 antimicrobial peptide with specific and exclusive fungicidal activity

Due to the increasing incidence of fungal opportunistic infections and emergence of antibiotic‐resistant fungal strains, antimicrobial peptides (AMPs) are considered as ideal candidates for antifungal compounds. In silico methods can reduce the limitations of natural AMPs such as toxicity and instability and improve their antimicrobial properties and selectivity. In this study, we designed AurH1, a new truncated peptide, based on the six‐amino acid sequence of Aurein1.2. Further , the antimicrobial activities and toxicity effects of AurH1 on human skin fibroblast cells and red blood cells were investigated. Finally, field emission scanning electron microscopy (FE‐SEM) and flow cytometry were performed in order to study the mechanism of action of AurH1. The results indicated that AurH1 had only antifungal activity (at a minimal inhibitory concentration (MIC) of 7.3‐125 μg/mL) without any antibacterial effects on the selected bacteria, while Aurein1.2 had both antifungal and antibacterial activities as positive control. Furthermore, AurH1 did not show any toxicity on Hu02 cells and human red blood cells at its MIC range. In conclusion, it became clear that AurH1 is a selective peptide against fungi with no toxic effects on the selected bacteria and human cells.