In the recent few decades, the increase in multidrug-resistant (MDR) bacteria has reached an alarming rate and caused serious health problems. The incidence of infections due to MDR bacteria has been accompanied by morbidity and mortality; therefore, tackling bacterial resistance has become an urgent and unmet challenge to be properly addressed. The field of nanomedicine has the potential to design and develop efficient antimicrobials for MDR bacteria using its innovative and alternative approaches. The uniquely constructed nano-sized antimicrobials have a predominance over traditional antibiotics because their small size helps them in better interaction with bacterial cells. Moreover, surface engineering of nanocarriers offers significant advantages of targeting and modulating various resistance mechanisms, thus owe superior qualities for overcoming bacterial resistance. This review covers different mechanisms of antibiotic resistance, application of nanocarrier systems in drug delivery, functionalization of nanocarriers, application of functionalized nanocarriers for overcoming bacterial resistance, possible limitations of nanocarrier-based approach for antibacterial delivery, and future of surface-functionalized antimicrobial delivery systems.
Bladder cancer is one of the most common types of urothelial carcinoma with a rising incidence rate worldwide. Circular RNAs (circRNAs) are involved in the development of numerous cancers, including bladder cancer. We aimed to uncover the role and associated mechanism of circMYLK in bladder cancer. The expression levels of cir-cMYLK, miRNA-34a (miR-34a) and Cyclin D3 (CCND3) mRNA were investigated using real-time quantitative polymerase chain reaction. The protein level of CCND3 was investigated using western blot. In functional assays, flow cytometry assays were utilized for cell cycle analysis and cell apoptosis analysis. Transwell assays were used for cell migration and invasion analysis. Caspase-3 activity was examined to monitor cell apoptosis. The putative relationship between miR-34a and circMYLK or CCND3 was validated by dual-luciferase reporter assay and RNA immunoprecipitation assay.CircMYLK was highly expressed in bladder cancer tissues and cells. CircMYLK downregulation inhibited bladder cancer cell migration and invasion, and promoted cancer cell apoptosis and cell cycle arrest. MiR-34a, a target of circMYLK, was downregulated in bladder cancer tissues and cells. MiR-34a inhibition reversed the effects of circMYLK downregulation and then recovered bladder cell malignant behaviors.Further analysis showed that CCND3 was a downstream target of miR-34a, and CCND3 was upregulated in bladder cancer tissues and cells. MiR-34a overexpression blocked bladder cancer cell migration and invasion, and induced cell apoptosis and cycle arrest, while these effects were abolished by CCND3 overexpression. Cir-cMYLK contributed to the malignant development of bladder cancer cells partly through the miR-34a/CCND3 regulatory network, showing the significance of cir-cMYLK in bladder cancer pathogenesis.
As a conserved microRNA (miRNA) family in plants, miR408 is known to be involved in different abiotic stress responses, including drought. Interestingly, some studies indicated a species-and/or cultivar-specific drought-responsive characteristic of miR408 in plant drought stress. Moreover, the functions of miR408 in perennial grass species are unknown. In this study, we investigated the role of miR408 in perennial ryegrass (Lolium perenne L.) by withholding water for 10 days for both wild type and transgenic plants with heterologous expression of rice (Oryza sativa L.) miR408 gene, Os-miR408. The results showed that transgenic perennial ryegrass plants displayed morphological changes under normal growth conditions, such as curl leaves and sunken stomata, which could be related to decreased leaf water loss. Moreover, transgenic perennial ryegrass exhibited improved drought tolerance, as demonstrated by maintaining higher leaf relative water content (RWC), lower electrolyte leakage (EL), and less lipid peroxidation compared to WT plants under drought stress. Furthermore, the transgenic plants showed higher antioxidative capacity under drought.These results showed that the improved drought tolerance in Os-miR408 transgenic plants could be due to leaf morphological changes favoring the maintenance of water status and to increased antioxidative capacity protecting against the reactive oxygen species damages under stress. These findings implied that miR408 could serve as a potential target for genetic manipulations to engineer perennial grass plants for improved water stress tolerance. | INTRODUCTIONAs sessile organisms living in constantly changing environment, plants are often exposed to abiotic stress, such as drought, salt, and temperature stresses (Zhu, 2016), which leads to more than 50% yield loss in major crops worldwide each year (Boyer, 1982;Lobell et al., 2011).Meanwhile, due to global climate change and world population growth, water scarcity is already a critical concern in many parts of the world, and drought has become one of the most adverse factors of plant growth and productivity (Shao et al., 2009). Therefore, it is critical to breed drought-tolerant crops and study plants' mechanism in response to drought stress.Plants can perceive abiotic stress signals and elicit appropriate responses by altering metabolism, growth, and development (Bartels & Sunkar, 2005). The primary signal caused by drought is hyperosmotic stress, which causes the accumulation of reactive oxygen species (ROS), damage to cellular components such as membrane lipids, proteins, nucleic acids, and metabolic dysfunction (Zhu, 2016).
With global warming, high temperature stress has become a main threat to the growth of cool-season turfgrasses, including perennial ryegrass. As one of the conserved plant microRNA families, miR408s are known to play roles in various abiotic stresses, including cold, drought, salinity, and oxidative stress, but no report, thus far, was found for heat. Here, perennial ryegrass plants overexpressing rice Os-miR408 were used to investigate the role of miR408 in plant heat tolerance. Both wild type (WT) and miR408 transgenic perennial ryegrass plants (TG) were subjected to short-term heat stress at 38 °C for 72 h (experiment 1) or at 42 °C for 48 h (experiment 2), and then let recover for 7 days at optimum temperature. Morphological changes and physiological parameters, including antioxidative responses of TG and WT plants, were compared. The results showed that miR408 downregulated the expression of two putative target genes, PLASTOCYANIN and LAC3. Additionally, overexpression of Os-miR408 improved thermo-tolerance of perennial ryegrass, demonstrated by lower leaf lipid peroxidation and electrolyte leakage, and higher relative water content after both 38 and 42 °C heat stresses. In addition, the enhanced thermotolerance of TG plants could be associated with its morphological changes (e.g., narrower leaves, smaller tiller angles) and elevated antioxidative capacity. This study is the first that experimentally reported a positive role of miR408 in plant tolerance to heat stress, which provided useful information for further understanding the mechanism by which miR408 improved plant high-temperature tolerance, and offered a potential genetic resource for breeding heat-resistant cool-season turfgrass in the future.
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