Colorectal cancer (CRC) is one of the most common cancers worldwide. MicroRNAs (miRNAs) play a vital role in a variety of biology processes. Our previous work identified miR-139-5p as a tumor suppressor gene overexpressed in CRC that assisted in inhibiting progression of cancer. The main challenge of miRNAs as therapeutic agents is their rapid degradation in plasma, poor uptake, and off-target effects. Therefore, the development of miRNA-based therapies is necessary. In this study, we developed a cationic liposome-based nanoparticle loaded with miR-139-5p (miR-139-5p-HSPC/DOTAP/Chol/DSPE-PEG2000-COOH nanoparticles, MNPs) and surface-decorated with epithelial cell adhesion molecule (EpCAM) aptamer (Apt) (miR-139-5p-EpCAM Apt-HSPC/DOTAP/Chol/DSPE-PEG2000-COOH nanoparticles, MANPs) for the targeted treatment of CRC. The size of MANPs was 150.3 ± 8.8 nm, which had a round-shaped appearance and functional dispersion capabilities. It also showed negligible hemolysis in the blood. MANPs markedly inhibited the proliferation, migration, and invasion of one or more CRC cell lines in vitro. Furthermore, we demonstrated the uptake and targeting ability of MANPs in vivo and in vitro. MANPs inhibit the growth of HCT8 cells in vitro and have a significant tumor suppressive effect on subcutaneous HCT8 colorectal tumor mice. Our results demonstrated that MANPs were an effective carrier approach to deliver therapeutic miRNAs to CRC.

S-propargyl-cysteine (SPRC; alternatively known as ZYZ-802) is a novel modulator of endogenous tissue H 2 S concentrations with known cardioprotective and antiinflammatory effects. However, its rapid metabolism and excretion have limited its clinical application. To overcome these issues, we have developed some novel liposomal carriers to deliver ZYZ-802 to cells and tissues and have characterized their physicochemical, morphological and pharmacological properties. Methods: Two liposomal formulations of ZYZ-802 were prepared by thin-layer hydration and the morphological characteristics of each liposome system were assessed using a laser particle size analyzer and transmission electron microscopy. The entrapment efficiency and ZYZ-802 release profiles were determined following ultrafiltration centrifugation, dialysis tube and HPLC measurements. LC-MS/MS was used to evaluate the pharmacokinetic parameters and tissue distribution profiles of each formulation via the measurements of plasma and tissues ZYZ-802 and H 2 S concentrations. Using an in vivo model of heart failure (HF), the cardio-protective effects of liposomal carrier were determined by echocardiography, histopathology, Western blot and the assessment of antioxidant and myocardial fibrosis markers. Results: Both liposomal formulations improved ZYZ-802 pharmacokinetics and optimized H 2 S concentrations in plasma and tissues. Liposomal ZYZ-802 showed enhanced cardioprotective effects in vivo. Importantly, liposomal ZYZ-802 could inhibit myocardial fibrosis via the inhibition of the TGF-β1/Smad signaling pathway. Conclusion: The liposomal formulations of ZYZ-802 have enhanced pharmacokinetic and pharmacological properties in vivo. This work is the first report to describe the development of liposomal formulations to improve the sustained release of H 2 S within tissues.

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Colon cancer stem cells (CCSCs) stand for a critical subpopulation of colon cancer cells that possess self-renewal and multilineage differentiation potentials and drive tumorigenicity. Due to their impact on treatment tolerance, CCSCs have been a hot research topic in the past few years. We have previously reported that miR-139-5p is a vital tumor repressive noncoding RNA whose level decreases in the clinical colon cancer samples with the increase of tumor malignancy. This research discovered that miR-139-5p targets the Wnt/β-catenin/TCF7L2 downstream effector E2-2 in CCSCs.E2-2 is a pivot molecule in the negative feedback loop of miR-139-5p/Wnt/β-catenin/ TCF7L2. Its small interfering RNA reverses the stemness maintenance and epithelialmesenchymal transition of colon cancer CSCs. This study provides a theoretical foundation for the clinical diagnosis and medical treatment of recurrent or metastatic colon cancer with miR-139-5p and its target E2-2.

Houttuynia cordata Thunb (H. Cordata), an aromatic medicinal herb belonging to family Saururaceae, is a plant that grows in moist habitats, well known for its medicinal properties and widely used worldwide. H. Cordata is an aromatic medicinal herb belonging to family Saururaceae and is restricted to specialized moist habitats. Three extracts, successively obtained from the leaves of H. cordata, namely the diethyl ether leaves extract (DELE), the ethanolic leaves extract (ELE) and the aqueous leaves extract (ALE), were used to determine the polyphenol and flavonoid content in the leaves. Phytochemical screening of plant extracts showed the presence of flavonoid, saponin, alkaloid, tannin, and steroid compounds. Quantitative determination of total phenolics, total flavonoids of methanolic extract were carried out using colorimetric methods. The result of quantitative determination showed that total polyphenol content of the DELE, ELE and ALE were 32.18 ± 2.64, 97.98 ± 1.77, and 22.22 ± 2.00 mg of gallic acid equivalents per gram dry extract, respectively. Meanwhile total flavonoid content of the DELE, ELE and ALE achieved 31.65 ± 1.07, 35.72 ± 1.23, and 4.06 ± 0.54 mg of quercetin equivalents per gram dry extract, respectively.