y-90-radioembolization-pd-1-inhibitor-as-neoadjuvant-treatment

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma

This study showcases a comprehensive treatment protocol for high-risk hepatocellular carcinoma (HCC) patients, focusing on the combined use of Y-90 ...

jinan university

Previous investigation have indicated Silibinin induces apoptosis and JNK/SAPK in human pancreatic cancer cells. This study aims to evaluate the further mechanism of Silibinin in pancreatic cancer treatment.

Silibinin inhibited autophagy and mitochondrial apoptosis in pancreatic carcinoma by activating JNK/SAPK signaling.

Liver fibrosis currently represents a global health problem without effective pharmacotherapeutic strategies. The clinical translation of polydatin, a promising natural anti-fibrotic drug candidate with broad anti-inflammatory and antioxidant capabilities, remains a major challenge due to its limited water solubility and tissue absorption. Herein, a polydatin-loaded micelle (PD-MC) based on reactive oxygen species (ROS) and pH dual-sensitive block polymer PEG-P(PBEM--DPA) is developed. The micelle exerts great potential in improving the biocompatibility of polydatin and shows highly efficient liver-targeted drug release in response to the fibrotic microenvironment. Both in vitro and in vivo studies demonstrate that PD-MC can significantly suppress inflammatory response and oxidative stress, reduce hepatocyte apoptosis, and avert activation of macrophages and hepatic stellate cells. More excitingly, the blank micelle itself promotes the hepatic ROS consumption at the pathologic site to provide anti-inflammatory benefits. These favorable therapeutic virtues of targeting multiple cell types endow PD-MC with remarkable efficacy with minimal side effects in liver fibrosis treatment. Thus, PD-MC holds great potential to push forward the clinical application of polydatin in pharmacotherapeutic approaches against liver fibrosis.

Nanodrug with ROS and pH Dual-Sensitivity Ameliorates Liver Fibrosis via Multicellular Regulation.

Circular RNAs (circRNAs), a novel class of noncoding RNAs, have been shown to play critical regulatory roles in clear cell renal cell carcinoma (ccRCC). Metastasis is the main contributor to the poor prognosis of patients with ccRCC. However, the role of circRNAs in ccRCC metastasis has not been fully elucidated. In this study, microarray and RNA-seq analyses revealed that circPSD3 (hsa_circ_0002111) was dramatically downregulated in ccRCC tissues compared to adjacent nontumor tissues. A qRT-PCR analysis performed on our ccRCC cohorts confirmed the downregulation of circPSD3 in ccRCC tissues and further suggested that a low level of circPSD3 expression was associated with tumor metastasis in patients with ccRCC. Based on the results of functional studies, circPSD3 significantly inhibited cell migration, invasion, and the epithelial-mesenchymal transition (EMT) in vitro and blocked pulmonary metastasis in vivo. Mechanistically, circPSD3 functioned as a competing endogenous RNA for microRNA 25-3p (miR-25-3p) to regulate F-box and WD repeat domain-containing 7 (FBXW7) expression. Further verification indicated that circPSD3 overexpression restrained an EMT-like phenotype in cells, while miR-25-3p partially rescued these effects. In summary, circPSD3 inhibits tumor metastasis by repressing the miR-25-3p/FBXW7-EMT axis and might be developed as a potential diagnostic and therapeutic target for ccRCC.

Downregulation of Circular RNA circPSD3 Promotes Metastasis by Modulating FBXW7 Expression in Clear Cell Renal Cell Carcinoma.

The injective lyotropic liquid crystalline nanogels (LLCNs) were widely used in drug delivery systems. But when administered in vivo, LLCNs exposed to the biological environment interact with proteins. Recently, it has been shown that nanoparticles coated with zwitterions can inhibit their interaction with proteins. Thus, in this study, the interaction between proteins and LLCNs coated with the zwitterionic material sulfobetaine (GLLCNs@HDSB) was investigated using bovine serum albumin (BSA) as a model protein. Interestingly, it was found that GLLCNs@HDSB at higher concentrations (≥0.8 mg/mL) could block its interaction with BSA, but not at lower concentrations (<0.8 mg/mL), according to the results of ultraviolet, fluorescence, and circular dichroism spectra. In the ultraviolet spectra, the absorbance of GLLCNs@HDSB (0.8 mg/mL) was 1.9 times higher than that without the sulfobetaine coating (GLLCNs) after incubation with protein; the fluorescence quenching intensity of GLLCNs@HDSB was conversely larger than that of the GLLCNs; in circular dichroism spectra, the ellipticity value of GLLCNs@HDSB was significantly smaller than that of the GLLCNs, and the change in GLLCNs@HDSB was 10 times higher than that of the GLLCNs. Generally, nanoparticles coated with sulfobetaine can inhibit their interaction with proteins, but in this study, LLCNs showed a concentration-dependent inhibitory effect. It could be inferred that in contrast to the surface of nanoparticles covered with sulfobetaine in other cases, the sulfobetaine in this study interacted with the LLCNs and was partially inserted into the hydrophobic region of the LLCNs. In conclusion, this study suggests that coating-modified nanoparticles do not necessarily avoid interacting with proteins, and we should also study coating-modified nanoparticles interacting with proteins both in vitro and in vivo. In the future, finding a coating material to completely inhibit the interaction between LLCNs and proteins will generate a great impetus to promote the clinical transformation of LLCNs.

The Effect of Sulfobetaine Coating in Inhibiting the Interaction between Lyotropic Liquid Crystalline Nanogels and Proteins.

Recurrence represents a well-known poor prognostic factor for colorectal cancer (CRC) patients. This study aimed to establish an effective prognostic prediction model based on noninvasive circulating tumor DNA methylation markers for CRC patients receiving radical surgery.

Predicting disease-free survival in colorectal cancer by circulating tumor DNA methylation markers.

Phospholipid-based materials exhibit great application potential in the fields of chemistry, biology, and pharmaceutical sciences. In this study, an inside-out oriented choline phosphate molecule, 2-{2-(methacryloyloxy)ethyldimethylammonium}ethyl -butyl phosphate (MBP), was proposed and verified as a novel ligand of C-reactive protein (CRP) to enrich the functionality of these materials. Compared with phosphorylcholine (PC)-CRP interactions, the binding between MBP and CRP was not affected by the reverse position of phosphate and choline groups and even found more abundant binding sites. Thus, high-density MBP-grafted biomimetic magnetic nanomaterials (MBP-MNPs) were fabricated by reversible addition-fragmentation chain transfer polymerization based on thiol-ene click chemistry. The novel materials exhibited multifunctional applications for CRP including purification and ultrasensitive detection. On the one hand, higher specificity, recovery (90%), purity (95%), and static binding capacity (198.14 mg/g) for CRP were achieved on the novel materials in comparison with traditional PC-based materials, and the enriched CRP from patient serum can maintain its structural integrity and bioactivity. On the other hand, the CRP detection method combining G-quadruplex and thioflavin T developed with MBP-MNPs showed a lower detection limit (10 pM) and wider linear range (0.1-50 nM) than most PC-functionalized analytical platforms. Therefore, the inside-out oriented choline phosphate can not only precisely recognize CRP but also be combined with biomimetic nanomaterials to provide high application potential.

Inside-Out Oriented Choline Phosphate-Based Biomimetic Magnetic Nanomaterials for Precise Recognition and Analysis of C-Reactive Protein.

Selective enrichment and analysis of therapeutic antibodies in biological fluids are crucial for the development of biopharmaceuticals. Recently, peptide-based affinity chromatography has exhibited fascinating prospects for antibody enrichment due to the high affinity and specificity of small peptides. However, the post-modification approach of peptide ligands on the material surface is complicated and time-consuming. In this study, a methacrylate modified tetrapeptide (m-EDPW) was firstly demonstrated as the affinity ligand of trastuzumab (K = 1.91 ± 1.81 μM). Next, the m-EDPW based affinity monolith was prepared using a facile one-step polymerization method, which could overcome the drawbacks of traditional post-modification preparation strategies. Based on the monolith as described above, a simple enrichment approach was developed under the optimal washing and elution conditions. Based on the excellent properties, such as high porosity (53.09%), weak electrostatic interaction and suitable affinity (1.00 ± 2.14 μM for anti-HER2 ADC), this novel monolith exhibited good specificity and recovery for antibodies (91.6% for trastuzumab, 98.37% for anti-HER2 ADC), and low nonspecific adsorption for human serum albumin (DBC = 0.5 mg/g polymer). Particularly, this material was successfully applied to enrich trastuzumab and its related antibody-drug conjugate (ADC) from different cell culture medias. The dynamic tracking analysis of ADC in the critical quality attributes (e.g., charge variants, drug to antibody ratio and subunit conjugation ratio) was also achieved by combining the enrichment approach, capillary electrophoresis or reversed phase liquid chromatography. In summary, the exploited peptide-based mimotope affinity materials showed a great potential for the application in biopharmaceutical analysis.

Tetrapeptide-based mimotope affinity monolith for the enrichment and analysis of anti-HER2 antibody and antibody-drug conjugate.

Pterygium is a common ocular surface disease. Pterygium combined with corneal perforation is rare.

Pterygium combined with corneal perforation: a case report.

Esophageal cancer is a highly aggressive malignancy with limited treatment options and poor prognosis. The identification of novel molecular subtypes and therapeutic targets is crucial for improving clinical outcomes.

Zhiwei Chen

Department of Hepatobiliary Surgery,
The First Affiliated Hospital,
Department of Hepatobiliary Surgery, The First Affiliated Hospital

jinan university

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma

Zhiwei Chen

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Hepatobiliary Surgery,The First Affiliated Hospital,Department of Hepatobiliary Surgery, The First Affiliated Hospital

jinan university

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma

Department of Hepatobiliary Surgery,
The First Affiliated Hospital,
Department of Hepatobiliary Surgery, The First Affiliated Hospital