Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

Cancer immunotherapy has great potential and is expected to become the mainstream method of cancer treatment.In the current application of cancer immunotherapy,immune checkpoint inhibitors(ICIs)have achieved remarkable results.The cur-rently widely used ICIs in clinical practice include inhibitors targeting cytotoxic T lymphocyte-associated antigen-4(CTLA-4),pro-grammed death-1(PD-1)and programmed death-ligand 1(PD-L1).In addition,new immunotherapies such as oncolytic viruses and chimeric antigen receptor T cells are gradually entering the clinical practice,and combination therapy related to ICIs has shown unique advantages.This article will focus on the current application status of ICIs,oncolytic viruses,and chimeric antigen receptor T cell ther-apies in solid tumors either their individual or combined forms.

BACKGROUND:Titanium and its alloys are widely used in orthopedic implants due to their excellent biocompatibility,corrosion resistance,and mechanical properties.However,it has biological inertia itself,cannot provide a good growth environment for osteoblasts,and it is difficult to form good osseointegration. OBJECTIVE:To construct a composite hydrogel material of gelatin methacryloyl and polyacrylamide on the surface of titanium alloy scaffold,and analyze its osteogenic ability in vitro. METHODS:Gelatin methacryloyl was mixed with acrylamide.Crosslinking agent and catalyst were added to synthesize gelatin methacryloyl and acrylamide(Gelma-PAAM)composite hydrogel.The titanium alloy scaffold modified by affinity silane was mixed with the Gelma hydrogel and Gelma-PAAM composite hydrogel to complete the loading(recorded as Ti-Gelma and Ti-Gelma-PAAM,respectively).The swelling ratio and degradation rate of the two hydrogels on the surface of the scaffold were compared.The bonding state between hydrogels and titanium alloy was observed by scanning electron microscope.Rat bone marrow mesenchymal stem cells were inoculated into Ti,Ti-Gelma and Ti-Gelma-PAAM scaffolds,separately.Cell proliferation,adhesion,and osteogenic differentiation were detected. RESULTS AND CONCLUSION:(1)Compared with Gelma hydrogel,Gelma-PAAM hydrogel had higher swelling rate and lower degradation rate.(2)Scanning electron microscope showed that the surface of the two kinds of hydrogels was honeycomb structure.After being combined with porous titanium alloy scaffold,the film was wrapped on the surface of scaffold and filled with pores.Among them,the Gelma-PAAM composite hydrogel coated the scaffold more fully.(3)CCK-8 assay and live/dead fluorescence staining showed that bone marrow mesenchymal stem cells proliferated well after coculture with Ti-Gelma and Ti-Gelma-PAAM scaffolds and maintained high activity.After osteogenic induction culture,alkaline phosphatase activity,calcium deposition,and osteogenic gene expression of cells of titanium alloy scaffold group were the lowest,and alkaline phosphatase activity,calcium deposition,and osteogenic gene expression of cells of Ti-Gelma-PAAM scaffold group were the highest.(4)Phalloidin cytoskeletal staining exhibited that the cells of pure titanium alloy scaffold group and Ti-Gelma scaffold group were sparse and insufficiently extended,while the cells of Ti-Gelatin-PAAM group had the most adequate stretching and the densest filamentous actin.(5)The results show that Gelma-PAAM hydrogel has good biocompatibility and osteogenic ability,and is more suitable for osteogenic modification on the surface of titanium alloy than Gelma hydrogel.

BACKGROUND:The low catalytic activity and lack of targeting of commonly used metal ions have severely limited the clinical application of chemodynamic therapy in tumor treatment.On the other hand,although the composite nanoplatforms are endowed with tumor-targeting functions by surface functionalization,the lack of tumor microenvironment acidity also severely weakens the efficacy of chemodynamic therapy. OBJECTIVE:To prepare novel composite nanoplatforms and assess their feasibility to enhance the effects of chemodynamic therapy at the cellular level. METHODS:SLC-0111-loaded zeolite imidazole framework-8 doped with divalent iron ions(Fe2+)and divalent cobalt ions(Co2+)(Fe-Co/ZIF-8@SLC-0111)was synthesized by ion-exchange reaction and self-assembly,and loaded with hyaluronic acid(HA)by electrostatic adsorption,followed by obtaining the target nanoparticles Fe-Co/ZIF-8@SLC-0111-HA(abbreviated as FC-S).Meanwhile,nanoparticles Fe-Co/ZIF-8-HA(abbreviated as FC)without SLC-0111 were synthesized by the same method.The nanocomposite platform was tested for particle size,zeta potential,surface morphology,in vitro reactive oxygen species generation,and ability to consume glutathione.Human osteosarcoma cell MG-63 and mouse fibroblast cell L929 were used as experimental subjects.The cytotoxicity of FC-S was detected by CCK-8 assay.Human osteosarcoma cell MG-63 was used as the experimental object to detect the cell internalization of FC-S.In addition to H2O2,the effects of FC-S and FC on intracellular pH,carbonic anhydrase 9 protein expression,cell viability and apoptosis,intracellular reactive oxygen species and glutathione content,and mitochondrial membrane potential were investigated. RESULTS AND CONCLUSION:(1)The FC-S composite nanoplatform was successfully prepared with a well-defined rhombic dodecahedral structure,uniform size and good dispersion.Its particle size was about 323 nm;zeta potential was about-11.1 mV,and the nanoplatform had a certain reactive oxygen species generation capacity in vitro.(2)FC-S nanoplatforms accumulated intracellularly in a time-dependent manner and could successfully escape from lysosomes.When the mass concentration of FC-S was≤20 μg/mL,there was no obvious cytotoxicity to MG-63 cells and L929 cells,and 20 μg/mL FC-S was selected to act on MG-63 cells in subsequent experiments.(3)Compared with FC group,the protein expression of carbonic anhydrase 9 in MG-63 cells in FC-S group was decreased(P<0.01);the intracellular acidic environment was enhanced;the content of reactive oxygen species was increased(P<0.001);the mitochondrial damage was aggravated;the number of dead cells was increased,and the apoptosis rate was increased(P<0.001).(4)The results indicate that FC-S,as a novel composite nanoplatform,can effectively improve the weakly acidic microenvironment in tumor cells and enhance the level of intracellular reactive oxygen species production,thus enhancing the efficacy of chemodynamic therapy.

Objective:To create AAPM TG 119 test plans for intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in order to evaluate the accuracy of the United Imaging Healthcare′s URT treatment planning system (URT-TPS). The plans were delivered to the phantom using the United Imaging Healthcare′s URT-Linac 506C.Methods:The overall accuracy of IMRT and VMAT planning, measurement, and analysis were evaluated for four test geometries provided by American Association of Physicists in Medicine (AAPM) Task Group Report 119(TG-119) on multi-target, prostate, head and neck and C-shape (easy). The dose distributions were measured in the coronal plane. The point measurements were measured by a Farmer type ion chamber and fluence measurements were completed with film and Delta4 phantom, respectively. Measured planar dose distributions were analyzed using gamma index with criteria 3%/3 mm.Results:For IMRT and VMAT plans, the planning results matched the TG-119 planning results. Measured point doses of IMRT and VMAT were within 2.62% and 3.90% of the planned doses, respectively. Measured film dosimetry gamma values of IMRT and VMAT were> 97.50% and> 93.27%, respectively.Conclusion:Based on these analyses which were performed in line with the TG119 recommendations, it is evident that the URT treatment planning system and URT-Linac 506C have commissioned IMRT and VMAT techniques with adequate accuracy.