Tanshinone IIA Liposomes Treat Doxorubicin-Induced Glomerulonephritis by Modulating the Microenvironment of Fibrotic Kidneys.

Renal fibrosis plays a key role in the pathogenesis of chronic kidney disease (CKD), in which the persistent high expression of transforming growth factor ß1 (TGF-ß1) and α-smooth muscle actin (α-SMA) contributes to the progression of CKD to renal failure. In order to improve the solubility, bioavailability, and targeting of tanshinone IIA (Tan IIA), a novel targeting material, aminoethyl anisamide-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphate ethanolamine (AEAA-PEG-DSPE, APD) modified Tan IIA liposomes (APD-Tan IIA-L) was constructed. An animal model of glomerulonephritis induced by doxorubicin in BALB/c mice was established. APD-Tan IIA-L significantly decreased blood urea nitrogen and serum creatinine (SCr), and the consequences of renal tissue oxidative stress indicators showed that APD-Tan IIA-L downregulated malondialdehyde, upregulated superoxide dismutase, catalase, and glutathione peroxidase. Masson's trichrome staining showed that the deposition of collagen in the APD-Tan IIA-L group decreased significantly. The pro-fibrotic factors (fibronectin, collagen I, TGF-ß1, and α-SMA) and epithelial-mesenchymal transition marker (N-cadherin) were significantly inhibited by APD-Tan IIA-L. By improving the microenvironment of fibrotic kidneys, APD-Tan IIA-L attenuated TGF-ß1-induced excessive proliferation of fibroblasts and alleviated oxidative stress damage to the kidney, providing a new strategy for the clinical treatment of renal fibrosis.

Development of a single-chain variable antibody fragment against a conserved region of the SARS-CoV-2 spike protein.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prolonged the duration of the pandemic because of the continuous emergence of new variant strains. The emergence of these mutant strains makes it difficult to detect the virus with the existing antibodies; thus, the development of novel antibodies that can target both the variants as well as the original strain is necessary. In this study, we generated a high-affinity monoclonal antibody (5G2) against the highly conserved region of the SARS-CoV-2 spike protein to detect the protein variants. Moreover, we generated its single-chain variable antibody fragment (sc5G2). The sc5G2 expressed in mammalian and bacterial cells detected the spike protein of the original SARS-CoV-2 and variant strains. The resulting sc5G2 will be a useful tool to detect the original SARS-CoV-2 and variant strains.

Ginsenoside Rg3 liposomes regulate tumor microenvironment for the treatment of triple negative breast cancer.

OBJECTIVE: To improve the solubility and targeting of Ginsenoside Rg3 (G-Rg3), in the current study, we constructed a novel targeting functional material folic acid -poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (FA-PEOz-CHMC, FPC) modified G-Rg3 liposomes (FPC-Rg3-L). METHODS: FPC was synthesized by using folic acid (FA) as a targeted head coupling with acid-activated poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate. The inhibitory effects of the G-Rg3 preparations on mouse breast cancer cells (4T1) were investigated by CCK-8 assay. Paraffin sections of female BALB/c mice viscera were taken for hematoxylin-eosin (H&E) staining after continuous tail vein injection of G-Rg3 preparations. BALB/c mice bearing triple-negative breast cancer (TNBC) were used as animal models to investigate the inhibition of G-Rg3 preparations on tumor growth and improving quality of life. Transforming growth factor-ß1 (TGF-ß1) and α-smooth muscular actin (α-SMA) were used to investigate the expression of two fibrosis factors in tumor tissues by western blotting. RESULTS: Compared with G-Rg3 solution (Rg3-S) and Rg3-L, FPC-Rg3-L had a significant inhibitory effect on 4T1 cells (p < .01), and the half maximal inhibitory concentration (IC50) of FPC-Rg3-L was significantly lower (p < .01). The H&E results showed that the injection of FPC-Rg3-L and Rg3-S did not cause damage to the organs of mice. Compared with the control group, tumor growth was significantly inhibited in mice treated with FPC-Rg3-L and G-Rg3 solutions (p < .01). CONCLUSIONS: This study presents a new and safe treatment for TNBC, reduces the toxic and side effects of the drug, and provides a reference for the efficient use of Chinese herbal medicine components.

Photoresponsive Shape Memory Hydrogels for Complex Deformation and Solvent-Driven Actuation.

A new design for photoresponsive shape memory hydrogels and their possible applications are demonstrated in the present study. We show that the photodissociable Fe3+-carboxylate coordination can be utilized as a molecular switch to realize photocontrol of shape memory on both macroscopic and microscopic scales and enable a number of functions. Indeed, Fe3+-carboxylate coordination can fix a large tensile strain (up to 680%) of the sodium alginate/polyacrylamide hydrogel through cross-linking of sodium alginate chains, and subsequent UV irradiation allows strain energy release in spatially selected regions through reduction of Fe3+ to Fe2+. By manipulating light irradiation, complex 3D structures are obtained from 2D hydrogel sheets, and they exhibit complex solvent-driven actuation behaviors due to a light-changeable modulus and cross-linking density in the hydrogel. Based on the same approach, micropatterns can be inscribed on the hydrogel surface using mask-assisted irradiation, and they exhibit chain orientation-mediated anisotropic topography change upon solvent exchange. Moreover, light-controlled strain energy release also enables changing hydrogel surface wettability by solvent replacement. The demonstrated mechanism for photoresponsive hydrogels is highly efficient and applicable to many systems, which offers new perspectives in developing hydrogels with multiple photoresponsive functions.

CuCl-Catalyzed direct C-H alkenylation of benzoxazoles with allyl halides.

An efficient and concise CuCl-catalyzed C2-alkenylation reaction of benzoxazoles with allyl halides has been established. The distinctive features of this protocol include the use of an inexpensive copper salt as a catalyst, simple and readily available starting materials, and ligand-free conditions. An important application of this method to the synthesis of 1,3-diene substituted benzoxazoles has also been achieved.