Aptamers have a promising role in the field of life science and have been extensively researched for application as analytical tools, therapeutic agents and as vehicles for targeted drug delivery. ...Compared with RNA aptamers, DNA aptamers have inherent advantages in stability and facility of generation and synthesis. To better understand the specific potential of DNA aptamers, an overview of the progress in the generation and application of DNA aptamers in human disease diagnosis and therapy are presented in this review. Special attention is given to researches that are relatively close to practical application. DNA aptamers are expected to have great potential in the diagnosis and treatment of human diseases.
Targeted delivery is a promising way to improve the safety and efficiency of siRNA delivery. We show that a DNA aptamer could be used to deliver siRNA into CD4+ T cells specifically. The DNA aptamer ...was obtained from the conversion of a reported RNA aptamer that binds to CD4 protein on the surface of T cells. It was covalently conjugated to the sense strand of the siRNA targeting HIV-1 protease (HIV-PR). The resulting DNA aptamer-siRNA chimera could specifically enter into CD4+ T cells and efficiently knock down the expression of exogenous HIV-PR gene. This study provides the first evidence that the DNA aptamer with intrinsic stability has a greater potential to be used for siRNA delivery.
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► DNA aptamer was used to deliver siRNA specifically. ► A stable DNA aptamer targeting CD4 protein on the surface of T cells was reported. ► The DNA aptamer was converted from an RNA aptamer that selected by SELEX. ► The expression of HIV protease in CD4+ T cells was knocked down by RNA interference.
One of the conventional strategies for treating osteoporosis is to eliminate the multinucleated osteoclasts that are responsible for bone resorption. Our previous study revealed that ursolic acid, ...isolated from leaves of loquat that is used as tasty tea in Japan, suppressed osteoclastogenesis. We confirmed that ursolic acid exhibited osteoclast differentiation inhibitory activity with an 50% inhibitory concentration (IC
) value of 5.4 ± 0.96 μM. To disclose its mechanism of action, this study first uses polymer-coated magnetic nanobeads to identify potential target proteins. As a result, we identified a nuclear exporter protein named exportin 5 (XPO5). Further studies demonstrated that knockdown of XPO5 significantly blocks osteoclast differentiation ( P < 0.01). Expression profiling of mature microRNAs in the cells revealed that downregulation of XPO5 by small interfering RNA or by ursolic acid could downregulate the expression of mature microRNA let-7g-5p during osteoclast differentiation ( P < 0.01). Collectively, our findings suggest that ursolic acid inhibits osteoclast differentiation through targeting XPO5, which provides further evidence for the healthy function of the tea. This study also provides new insights into the role of XPO5 and its mediated microRNAs in treatment for bone resorption diseases.
Nanomedicine has become one of the most promising technologies to modernize the traditional food. However, not only the public perception of the new technology is uncertain, but also the regulators ...have not yet to agree on rules that apply globally. The gastrointestinal tract microbiota and its genes (the microbiome) are considered a fundamental part of the human body. The gut microbiota is a major part of the host microbiota and contains approximately 3 × 1013 bacterial cells in a commensal relationship with the host. However, once the gastric ecosystem is altered, various bacterial species (e.g., antibiotic-resistant Enterococcus and Clostridium difficile) can increase and develop pathogenic phenotypes. Recent evidence suggests that the gut microbiota is involved in carcinogenesis and can enhance the activity, efficacy, and toxicity of anticancer therapies. Recently, there is fast-growing concern regarding the effect of nanoparticles on the human gut microbiota. Nanomaterials can enter the human body via skin contact, ingestion, and inhalation.
In the present review, the recent advances on the roles of microbiota and nanomaterials in cancer therapy, the microbiota and their metabolic interventions via nanomaterials, microbial inspiration via nanomaterials, and the challenges associated with using nanomaterials in humans and animals is discussed. In short, this review will focus on the current status and future perspectives of gut microbiota targeted nanotechnology for cancer therapy and cancer-related metabolic diseases.
The changes in the gut microbiota or microbiome play vital roles in human diseases such as cancer. Traditional microbiome treatments have led to improved cancer treatments in some cases; however, problems such as collateral injury to the symbiotic microbiome and reliability of these treatment methods have led to new technological developments designed specifically for cancer microbiota crossing point. Hence, the prosperousness of nanomaterials in cancer prevention has led to the idea that nanomaterials can alter the cancer-causing microbiome/microbiota and their metabolites as well as alter the cancer microenvironment. Therefore, nanomaterials can be used as novel strategies to treat cancer. However, this emerging research area requires further in vivo clinical trials to determine the exact mechanisms of action involved in treating cancer via nanomaterials. Further studies should explore the connection between nanomaterials, the microbiota, microbial metabolites, cancer and cancer-related microenvironments in animals and humans.
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•Increasing evidence suggested that the gut microbiota dysbiosis influence cancer.•Interaction between nanomaterials and gut microbiota are largely unexplored.•The concept of nanomedicine based approached to alter gut microbiota for cancer therapy has been proposed.•The gut microbiota and nanomedicine might provide new specific biomarkers for cancer therapy.•Future perceptive toward the development of novel nanomedicine for cancer therapy are discussed.
Neuraminidase (NA) inhibitors are the dominant antiviral drugs for treating influenza in the clinic. Increasing prevalence of drug resistance makes the discovery of new NA inhibitors a high priority. ...Thirty-one triterpenoids from the medicinal mushroom Ganoderma lingzhi were analyzed in an in vitro NA inhibition assay, leading to the discovery of ganoderic acid T-Q and TR as two inhibitors of H5N1 and H1N1 NAs. Structure-activity relationship studies revealed that the corresponding triterpenoid structure is a potential scaffold for the design of NA inhibitors. Using these triterpenoids as probes we found, through further in silico docking and interaction analysis, that interactions with the amino-acid residues Arg292 and/or Glu119 of NA are critical for the inhibition of H5N1 and H1N1. These findings should prove valuable for the design and development of NA inhibitors.
As evidence has mounted that virus-infected cells, such as cancer cells, negatively regulate the function of T-cells via immune checkpoints, it has become increasingly clear that viral infections ...similarly exploit immune checkpoints as an immune system escape mechanism. Although immune checkpoint therapy has been successfully used in cancer treatment, numerous studies have suggested that such therapy may also be highly relevant for treating viral infection, especially chronic viral infections. However, it has not yet been applied in this manner. Here, we reviewed recent findings regarding immune checkpoints in viral infections, including COVID-19, and discussed the role of immune checkpoints in different viral infections, as well as the potential for applying immune checkpoint blockades as antiviral therapy.
Hand, foot, and mouth disease (HFMD) is a highly contagious disease in children caused by a group of enteroviruses. HFMD currently presents a major threat to infants and young children because of a ...lack of antiviral drugs in clinical practice. Drug repositioning is an attractive drug discovery strategy aimed at identifying and developing new drugs for diseases. Notably, repositioning of well-characterized therapeutics, including either approved or investigational drugs, is becoming a potential strategy to identify new treatments for virus infections. Various types of drugs, including antibacterial, cardiovascular, and anticancer agents, have been studied in relation to their therapeutic potential to treat HFMD. In this review, we summarize the major outbreaks of HFMD and the progress in drug repositioning to treat this disease. We also discuss the structural features and mode of action of these repositioned drugs and highlight the opportunities and challenges of drug repositioning for HFMD.
Previous studies have reported that recombinant tumor necrosis factor (TNF)-α has powerful antiviral activity but severe systematic side effects. Jasminin is a common bioactive component found in ...Chinese herbal medicine beverage "Jasmine Tea". Here, we report that jasminin-induced endogenous TNF-α showed antiviral activity in vitro. The underlying TNF-α-inducing action of jasminin was also investigated in RAW264.7 cells. The level of endogenous TNF-α stimulated by jasminin was first analyzed by an enzyme-linked immunosorbent assay (ELISA) from the cell culture supernatant of RAW264.7 cells. The supernatants were then collected to investigate the potential antiviral effect against herpes simplex virus 1 (HSV-1). The antiviral effects of jasminin alone or its supernatants were evaluated by a plaque reduction assay. The potential activation of the PI3K-Akt pathway, three main mitogen-activated protein kinases (MAPKs), and nuclear factor (NF)-κB signaling pathways that induce TNF-α production were also investigated. Jasminin induces TNF-α protein expression in RAW264.7 cells without additional stimuli 10-fold more than the control. No significant up-expression of type I, II, and III interferons; interleukins 2 and 10; nor TNF-β were observed by the jasminin stimuli. The supernatants, containing jasminin-induced-TNF-α, showed antiviral activity against HSV-1. The jasminin-stimulated cells caused the simultaneous activation of the Akt, MAPKs, and NF-κB signal pathways. Furthermore, the pretreatment of the cells with the Akt, MAPKs, and NF-κB inhibitors effectively suppressed jasminin-induced TNF-α production. Our research provides evidence that endogenous TNF-α can be used as a strategy to encounter viral infections. Additionally, the Akt, MAPKs, and NF-κB signaling pathways are involved in the TNF-α synthesis that induced by jasminin.
Ganoderma lingzhi
is a traditional medicinal mushroom, and its extract contains many bioactive compounds. Triterpenoids and polysaccharides are the primary bioactive components that contribute to its ...medicinal properties. In this study, we quantified 18 triterpenoids, total triterpenoid content and total polysaccharide content in the ethanol and water extracts of
G. lingzhi
at different growth stages. Triterpenoids were quantified by liquid chromatograph–tandem mass spectrometry in the multiple-reaction-monitoring mode. Total triterpenoid and total polysaccharide content were determined by colorimetric analysis. The results indicated that the fruit bodies at an early growth stage had a higher content of ganoderic acid A, C2, I and LM2, as well as of ganoderenic acid C and D, than those at a later growth stage. In contrast, ganoderic acid K, TN and T–Q contents were higher in mature fruit bodies (maturation stage). The highest total triterpenoid and total polysaccharide contents were found in fruit bodies before maturity (stipe elongation stage or early stage of pileus formation). Our results provide information which will contribute to the establishment of an efficient cultivation system for
G. lingzhi
with a higher content of triterpenoids.
•Besides antioxidant activity, three other bioactivities were investigated.•The fruits as well as nine other parts of strawberry were comparatively studied.•The phytochemical profiles of each parts ...of strawberry were determined.•The strawberry fruits possess potential anti-obesity and skin-lightening effects.•The parts of crown, stolon leaf and flower showed extraordinary activities.
The in vitro antioxidant, anti-obesity, anti-allergy and skin-lightening effects of extracts from strawberry fruits (ripe and unripe) and nine other plant parts of Amaou strawberry (Fragaria × ananassa var. Amaou) were comparatively investigated by using the antioxidant assay and inhibition assays of lipase, adipocyte differentiation, β-hexosaminidase release, melanogenesis and tyrosinase. Their total phenolic content and the main phenolic compounds were also determined. The ripe strawberry fruits were found to possess potential anti-obesity and skin-lightening effects. The ethanol extracts from unripe strawberry fruits and several other parts like the crown, stolon leaf and flower showed more strong activities in the bioactivity assays conducted. The phytochemical profile varied among extracts from various parts of the plant. Ellagic acid was found in every part of the strawberry plant except the root. Our study provides valuable evidence that strawberry fruit is a food with potential anti-obesity and skin-lightening functions. The findings also support that several inedible parts of the strawberry plant have great potential to be used as the ingredients of functional food products.
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