SAIF plays anti-angiogenesis via blocking VEGF-VEGFR2-ERK signal in tumor treatment.

Shark cartilage was created as a cancer-fighting diet because it was believed to have an element that may suppress tumor growth. Due to overfishing, sharks have become endangered recently, making it impossible to harvest natural components from shark cartilage for therapeutic development research. Previously, we identified a peptide SAIF from shark cartilage with an-tiangiogenic and anti-tumor effects, successfully expressed it in Escherichia coli by using genetic engineering techniques. However, we did not elucidate the specific target of SAIF and its antiangiogenic molecular mechanism, which hindered its further drug development. Therefore, in this work, the exact mechanism of action was studied using various techniques, including cellular and in vivo animal models, computer-aided simulation, molecular target capture, and transcriptome sequencing analysis. With VEGF-VEGFR2 interaction and preventing the activation of VEGFR2/ERK signaling pathways, SAIF was discovered to decrease angiogenesis and hence significantly limit tumor development. The findings further demonstrated SAIF's strong safety and pharmaceutically potential. The evidence showed that SAIF, which is expressed by, is a potent and safe angiogenesis inhibitor and might be developed as a candidate peptide drug for the treatment of solid tumors such as hepatocellular carcinoma and other conditions linked with angiogenic overgrowth.

Discovery and Characteristics of a Novel Antitumor Cyclopeptide Derived from Shark.

Peptides pose a challenge in drug development due to their short half-lives in vivo. In this study, we conducted in vitro degradation experiments on SAIF, which is a shark-derived peptide that we previously studied. The degradation fragments were sequenced and a truncated peptide sequence was identified. The truncated peptide was then cloned and expressed via the E. coli system with traceless cloning to form a novel cyclic peptide in vitro oxidation condition via the formation of a disulfide bond between the N- and C-termini, which was named ctSAIF. ctSAIF exhibited high anti-HCC activity and enhanced enzymatic stability in vitro, and retained antitumor activity and good biocompatibility in systemic circulation in a HCC xenograft model. Our study discovered and characterized a novel shark-derived cyclic peptide with antitumor activity, laying a foundation for its further development as an antitumor drug candidate. The study also provided a new solution for peptide drug development.

Inhibition of FGFR2 Signaling by Cynaroside Attenuates Liver Fibrosis.

Liver fibrosis represents a significant health hazard with a high morbidity rate and an increased risk of liver cancer. Targeting overactivated Fibroblast growth factor receptor 2 (FGFR2) is a promising strategy to counteract collagen accumulation during liver fibrosis. However, there is a shortage of drugs to specifically block the activation of FGFR2 in liver fibrosis patients. Data mining, cell validation, and animal studies showed a positive correlation between FGFR2 overexpression and liver fibrosis development. Novel FGFR2 inhibitors were screened using a microarray-based high-throughput binding analysis. The effectiveness of each candidate was validated through simulated docking, binding affinity verification, single-point mutation validation, and in vitro kinase inhibition measurements to demonstrate the ability of each inhibitor to block the catalytic pocket and reverse FGFR2 overactivation. A specific FGFR2 inhibitor, cynaroside (CYN, also known as luteoloside), was screened based on the finding that FGFR2 promotes hepatic stellate cell (HSC) activation and collagen secretion in hepatocytes. The results from cellular assays showed that CYN can inhibit FGFR2 hyperactivation resulting from its overexpression and excessive basic fibroblast growth factor (bFGF), reducing HSC activation and collagen secretion in hepatocytes. Animal experiments on a carbon tetrachloride (CCl4) mouse model and a nonalcoholic steatohepatitis mouse model indicate that CYN treatment reduces liver fibrosis during fibrosis formation. These findings suggest that CYN prevents liver fibrosis formation at the cell level and in mouse models.

Preparation of amphiphilic cationic polyacrylamide (CPAM) with cationic microblock structure to enhance printing and dyeing sludge dewatering and condition performance.

Flocculation is an important pretreatment technology for sludge dewatering, and the flocculant's performance is the key factor to determine the flocculation effect. Cationic polyacrylamide (CPAM) is commonly used in dewatering and conditioning of printing and dyeing sludge (PD sludge), and the research of high-efficiency flocculant is a hot spot in the field of PD sludge dewatering. Hydrophobic butylacrylate (BA) and (2-(Methacryloyloxy)ethyl) trimethylammonium chloride (DMC) were introduced into the copolymer, and amphiphilic (hydrophilic/lipophilic) CPAM, namely TP-ADB, with microblock structure was synthesized by ultrasonic initiated template copolymerization in this study. The functional group composition of TP-ADB was determined by FTIR and 1H NMR. Thermogravimetric analysis (TGA) showed that TP-ADB had good thermal stability. The amphiphilic rheological properties of the copolymer were measured according to the apparent viscosity. In addition, 1H NMR and TGA results confirmed the existence of microblock structure in the copolymer chain. The polymerization mechanism was discussed by association coefficient (KM) measurement. The results showed that the template copolymerization initiated by ultrasonic followed the law of free radical copolymerization. The pre-adsorption of DMC with sodium polyacrylate template (NaPAA) before the reaction confirmed that the template polymerization accorded with ZIP I mechanism. The cationic microblock structure and hydrophobic association of TP-ADB promoted the dewatering performance of PD sludge (FCMC = 72.9%, turbidity removal rate = 98.9%, SRF = 4.2 × 1012 m·kg-1). Hydrophobic association enhanced the bridging, sweeping, and net catching effect, and promoted the growth of floc size and fractal dimension. Cationic microblock structure can produce compact floc with higher mechanical strength by enhancing electrical neutralization and electrical patching. As a skeleton, the compressibility of filter cake was reduced and the permeability was enhanced, and the PD sludge dewatering effect was significantly improved.