Sunflower Pollen-Derived Microspheres Selectively Absorb DNA for microRNA Detection.

Herein, we report the finding that a naturally sunflower pollen-derived microspheres (HSECs) with hierarchical structures can selectively absorb polyC and polyA with high efficiency and affinity. HSECs exhibit the capability to selectively absorb polyC and polyA ssDNA under neutral and acidic conditions. It has been observed that the presence of metal cations, specifically Ca2+, enhances the absorption efficiency of HSECs. Mechanically, this absorption phenomenon can be attributed to both electrostatic interactions and cation-π interactions. Such an appealing property enables the functionalization of HSECs for broad potential biomedical applications, such as microRNA detection.

Sunflower pollen-derived microcapsules adsorb light and bacteria for enhanced antimicrobial photothermal therapy.

Bacterial infection is one of the most serious clinical complications, with life-threatening outcomes. Nature-inspired biomaterials offer appealing microscale and nanoscale architectures that are often hard to fabricate by traditional technologies. Inspired by the light-harvesting nature, we engineered sulfuric acid-treated sunflower sporopollenin exine-derived microcapsules (HSECs) to capture light and bacteria for antimicrobial photothermal therapy. Sulfuric acid-treated HSECs show a greatly enhanced photothermal performance and a strong bacteria-capturing ability against Gram-positive bacteria. This is attributed to the hierarchical micro/nanostructure and surface chemistry alteration of HSECs. To test the potential for clinical application, an in situ bacteria-capturing, near-infrared (NIR) light-triggered hydrogel made of HSECs and curdlan is applied in photothermal therapy for infected skin wounds. HSECs and curdlan suspension that spread on bacteria-infected skin wounds of mice first capture the local bacteria and then form hydrogels on the wound upon NIR light stimulation. The combination shows a superior antibacterial efficiency of 98.4% compared to NIR therapy alone and achieved a wound healing ratio of 89.4%. The current study suggests that the bacteria-capturing ability and photothermal properties make HSECs an excellent platform for the phototherapy of bacteria-infected diseases. Future work that can fully take advantage of the hierarchical micro/nanostructure of HSECs for multiple biomedical applications is highly promising and desirable.

Effect of Bariatric Surgery on Metabolic Syndrome in Chinese Patients with Low Body Mass Index: a Propensity Score Matching Study.

BACKGROUND: Bariatric surgery (BS) is known to improve the components of metabolic syndrome (MS) in patients with obesity. However, few studies have evaluated the effect of BS on patients with MS at low BMI levels. The study aims to assess the effect of BS on MS in patients with low BMI by comparing BS with medical therapy (MT). METHODS: A total of 271 patients with MS who underwent BS and MT at a single institution were reviewed in this retrospective cohort study. A 1:1 propensity score matching was performed for the BS and MT groups with BMI<35 kg/m2. We analyzed the 5 years effect of BS versus MT on the remission of MS, its components, atherosclerotic cardiovascular disease (ASCVD) risk, and medication used. RESULTS: Patients in the MT group showed a decrease in the prevalence of MS to 62% at the 1st year and 10% at the 5th year. In the BS group, MS prevalence in patients with BMI<35 kg/m2 decreased to 30% and 9% at the 1st and 5th year, whereas in patients with BMI≥35 kg/m2 was 26% and 7%, respectively. The 10-year ASCVD risk and the lifetime ASCVD were significantly decreased 5 years after BS in patients with BMI<35 kg/m2. The number and daily drug dose of hypoglycemic drugs, antihypertensive medications, and lipid-lowering drugs were reduced from baseline in both BS and MT groups. CONCLUSION: Bariatric surgery significantly improves MS remission rates and long-term cardiovascular risk in Chinese patients with metabolic syndrome and a BMI <35 kg/m2.

Framework Nucleic Acids Enabled Pulmonary Artery Endothelial Cell Growth Inhibition by Targeting microRNA-152.

Pulmonary artery vascular endothelial dysfunction plays a pivotal role in the occurrence and progression of pulmonary vascular remodeling (PVR). To address this, aberrantly expressed non-coding microRNAs (miRNAs) are excellent therapeutic targets in human pulmonary artery endothelial cells (HPAECs). Here, we discovered and validated the overexpression of miRNA-152 in HPAECs under hypoxia and its role in endothelial cell dysfunction. We constructed a framework nucleic acid nanostructure that harbors six protruding single-stranded DNA segments that can fully hybridize with miRNA-152 (DNT-152). DNT-152 was efficiently taken up by HPAECs with increasing time and concentration; it markedly induced apoptosis, and inhibited HPAEC growth under hypoxic conditions. Mechanistically, DNT-152 silenced miRNA-152 expression and upregulated its target gene Meox2, which subsequently inhibited the AKT/mTOR signaling pathway. These results indicate that miRNA-152 in HPAECs may be an excellent therapeutic target against PVR, and that framework nucleic acids with carefully designed sequences are promising nanomedicines for noncancerous cells and diseases.

Extracellular CIRP-Impaired Rab26 Restrains EPOR-Mediated Macrophage Polarization in Acute Lung Injury.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a condition with an imbalanced inflammatory response and delayed resolution of inflammation. Macrophage polarization plays an important role in inflammation and resolution. However, the mechanism of macrophage polarization in ALI/ARDS is not fully understood. We found that mice with lipopolysaccharide administration developed lung injury with the accumulation of extracellular cold-inducible RNA-binding protein (eCIRP) in the lungs. eCIRP, as a damage-associated molecular pattern (DAMP), inhibited M2 macrophage polarization, thereby tipping the balance toward inflammation rather than resolution. Anti-CIRP antibodies reversed such phenotypes. The levels of macrophage erythropoietin (EPO) receptor (EPOR) were reduced after eCIRP treatment. Myeloid-specific EPOR-deficient mice displayed restrained M2 macrophage polarization and impaired inflammation resolution. Mechanistically, eCIRP impaired Rab26, a member of Ras superfamilies of small G proteins, and reduced the transportation of surface EPOR, which resulted in macrophage polarization toward the M1 phenotype. Moreover, EPO treatment hardly promotes M2 polarization in Rab26 knockout (KO) macrophages through EPOR. Collectively, macrophage EPOR signaling is impaired by eCIRP through Rab26 during ALI/ARDS, leading to the restrained M2 macrophage polarization and delayed inflammation resolution. These findings identify a mechanism of persistent inflammation and a potential therapy during ALI/ARDS.

Clinical characteristics and a decision tree model to predict death outcome in severe COVID-19 patients.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) spreads rapidly among people and causes a pandemic. It is of great clinical significance to identify COVID-19 patients with high risk of death. METHODS: A total of 2169 adult COVID-19 patients were enrolled from Wuhan, China, from February 10th to April 15th, 2020. Difference analyses of medical records were performed between severe and non-severe groups, as well as between survivors and non-survivors. In addition, we developed a decision tree model to predict death outcome in severe patients. RESULTS: Of the 2169 COVID-19 patients, the median age was 61 years and male patients accounted for 48%. A total of 646 patients were diagnosed as severe illness, and 75 patients died. An older median age and a higher proportion of male patients were found in severe group or non-survivors compared to their counterparts. Significant differences in clinical characteristics and laboratory examinations were found between severe and non-severe groups, as well as between survivors and non-survivors. A decision tree, including three biomarkers, neutrophil-to-lymphocyte ratio, C-reactive protein and lactic dehydrogenase, was developed to predict death outcome in severe patients. This model performed well both in training and test datasets. The accuracy of this model were 0.98 in both datasets. CONCLUSION: We performed a comprehensive analysis of COVID-19 patients from the outbreak in Wuhan, China, and proposed a simple and clinically operable decision tree to help clinicians rapidly identify COVID-19 patients at high risk of death, to whom priority treatment and intensive care should be given.

Self-assembled triangular DNA nanoparticles are an efficient system for gene delivery.

Developing an advanced nucleic acid drug delivery system is of great significance in order to achieve optimal gene delivery. Self-assembled nucleic acid nanoparticles are an excellent platform for the delivery of nucleic acids and other small molecular drugs. In this study, we developed the efficient, three-stranded, RNA/DNA hybrid triangular self-assembled nanoparticles, namely, mTOR single-stranded siRNA-loaded triangular DNA nanoparticles (ssRNA-TNP). The ssRNA-TNP is formed by the complementary association of the above mentioned three components and is more stable in complete medium than standard duplex siRNA. It could be efficiently transfected into NCI-H292 cells in a dose- and time-dependent manner, resulting in high transfection efficiency. Furthermore, ssRNA-TNP uptake is dependent on macropinocytosis and clathrin-mediated endocytosis pathways. Interestingly, ssRNA-TNP is more efficient to inhibit the expression of mTOR. This ssRNA-TNP has a simpler structure, better stability, and higher transfection efficiency; therefore it may become a novel nonviral nanosystem for gene delivery.

Inhibition of DNA nanotube-conjugated mTOR siRNA on the growth of pulmonary arterial smooth muscle cells.

Here we provide raw and processed data and methods behind mTOR siRNA loaded DNA nanotubes (siRNA-DNA-NTs) in the growth of pulmonary arterial smooth muscle cells (PASMCs) under both normoxic and hypoxic condition, and also related to (You et al., Biomaterials, 2015, 67:137-150, [1]). The MTT analysis, Semi-quantitative RT-PCR data presented here were used to probe cytotoxicity of mTOR siRNA-DNA-NT complex in its TAE-Mg(2+) buffer. siRNA-DNA-NTs have a lower cytotoxicity and higher transfection efficiency and can, based on inhibition of mTOR expression, decrease PASMCs growth both hypoxic and normal condition.

Regulation of vascular smooth muscle cell autophagy by DNA nanotube-conjugated mTOR siRNA.

The efficient delivery of short interfering RNA (siRNA) is an enormous challenge in the field of gene therapy. Herein, we report a delivery nanosystem based on programmed DNA self-assembly mammalian target of rapamycin (mTOR) siRNA-loaded DNA nanotubes (DNA-NTs). We demonstrate that these siRNA-DNA-NTs can be effectively transfected into pulmonary arterial smooth muscle cells (PASMCs) via endocytosis; and that the loaded mTOR siRNA can induce obvious autophagy and inhibit cell growth under both normal and hypoxic conditions. Moreover, we found that mTOR siRNA can control the autophagy and proliferation of PASMCs under hypoxic condition, suggesting a potential therapeutic application for mTOR siRNA in diseases involving abnormal autophagy in PASMCs.

Inhibition of hypoxia-induced proliferation of pulmonary arterial smooth muscle cells by a mTOR siRNA-loaded cyclodextrin nanovector.

The proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a key pathophysiological component of vascular remodeling in pulmonary arterial hypertension (PAH), an intractable disease, for which pharmacotherapy is limited and only slight improvement in survival outcomes have achieved over the past few decades. RNA interference provides a highly promising strategy to the treatment of this chronic lung disease, while efficient delivery of small interfering RNA (siRNA) remains a key challenge for the development of clinically acceptable siRNA therapeutics. With the aim to construct useful nanomedicines, the mammalian target of rapamycin (mTOR) siRNA was loaded into hybrid nanoparticles based on low molecular weight (Mw) polyethylenimine (PEI) and a pH-responsive cyclodextrin material (Ac-aCD) or poly(lactic-co-glycolic acid) (PLGA). This hybrid nanoplatform gave rise to desirable siRNA loading, and the payload release could be modulated by the hydrolysis characteristics of carrier materials. Fluorescence observation and flow cytometry quantification suggested that both Ac-aCD and PLGA nanovectors (NVs) may enter PASMCs under either normoxia or hypoxia conditions as well as in the presence of serum, with uptake and transfection efficiency significantly higher than those of cationic vectors such as PEI with Mw of 25 kDa (PEI25k) and Lipofectamine 2000 (Lipo 2k). Hybrid Ac-aCD or PLGA NV containing siRNA remarkably inhibited proliferation and activated apoptosis of hypoxic PASMCs, largely resulting from effective suppression of mTOR signaling as evidenced by significantly lowered expression of mTOR mRNA and phosphorylated protein. Moreover, these hybrid nanomedicines were more effective than commonly used cationic vectors like PEI25k and Lipo 2k, with respect to cell growth inhibition, apoptosis activation, and expression attenuation of mTOR mRNA and protein. Therefore, mTOR siRNA nanomedicines based on hybrid Ac-aCD or PLGA NV may be promising therapeutics for diseases related to hypoxic abnormal growth of PASMCs.