Engineering nanotheranostic strategies for liver cancer

The incidence and mortality of hepatocellular carcinoma have continued to increase over the last few years,and the medicine-based outlook of patients is poor.Given great ideas from the development of nanotechnology in medicine,especially the advantages in the treatments of liver cancer.Some engineering nanoparticles with active targeting,ligand modification,and passive targeting capacity achieve efficient drug delivery to tumor cells.In addition,the behavior of drug release is also applied to the drug loading nanosystem based on the tumor microenvironment.Considering clinical use of local treatment of liver cancer,in situ drug delivery of nanogels is also fully studied in orthotopic chemotherapy,radiotherapy,and ablation therapy.Furthermore,novel therapies including gene therapy,phototherapy,and immunotherapy are also applied as combined therapy for liver cancer.Engineering nonviral polymers to function as gene delivery vectors with increased efficiency and specificity,and strategies of co-delivery of therapeutic genes and drugs show great therapeutic effect against liver tumors,including drug-resistant tumors.Phototherapy is also applied in surgical procedures,chemotherapy,and immunotherapy.Combination strategies significantly enhance therapeutic effects and decrease side effects.Overall,the application of nanotechnology could bring a revolutionary change to the current treatment of liver cancer.

Fas/FasL and Complement Activation are Associated with Chronic Active Epstein-Barr Virus Hepatitis

Background and Aims:Chronic active Epstein-Barr virus hepatitis(CAEBVH)is a rare and highly lethal disease char-acterized by hepatitis and hepatomegaly.This study aimed to investigate the clinicopathological features and pathogenic mechanisms of CAEBVH.Methods:Ten patients with con-firmed Epstein-Barr virus hepatitis infection were enrolled.The clinicopathological characteristics of these patients were summarized and analyzed.Flow cytometry was utilized to detect peripheral blood immune cell phenotypes and whole exome sequencing was used to explore pathogenic genetic mechanisms.Lastly,immunohistochemical staining was em-ployed to verify pathogenic mechanisms.Results:Clinical features observed in all Epstein-Barr virus hepatitis patients included fever(7/10),splenomegaly(10/10),hepatomeg-aly(9/10),abnormal liver function(8/10),and CD8+T cell lymphopenia(6/7).Hematoxylin and eosin staining revealed lymphocytic infiltration in the liver.Positive Epstein-Barr vi-rus-encoded small RNA in-situ hybridization(EBER-ISH)of lymphocytes of liver tissues was noted.Whole exome se-quencing indicated that cytotoxic T lymphocytes and the complement system were involved.The expression of CD8,Fas,FasL,and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls(p<0.05).Lastly,Complement 1q and complement 3d expression,were higher in CAEBVH patients relative to controls(p<0.05).Conclusions:CAE-BVH patients developed fever,hepatosplenomegaly,and lymphadenopathy.Histopathological changes were a diffuse lymphocytic sinusoidal infiltrate with EBER-ISH positivity.Fas/FasL and complement activation were involved in CAE-BVH patients.

The synergy of Helicobacter pylori and lipid metabolic disorders in induction of Th17-related cytokines in human gastric cancer

Aim:To study the impact of Helicobacter pylori(H.pylori)and lipid metabolic disorder on the expression of Th17-related cytokines in gastric cancer(GC).Methods:GC specimens were randomly collected from 42 patients,of whom 15 had H.pylori infection and 27 were without.Tumor RNA was extracted for reverse transcription quantitative polymerase chain reaction quantification of gene expression.Results:The mRNA levels of interleukin(IL)-6 and leptin,which are known to regulate Th17 differentiation,were upregulated by 20 and 6 folds,respectively,in H.pylori-infected compared to uninfected patients.IL-17A and granulocyte-macrophage colony-stimulating factor,two cytokines produced by Th17 cells,were 5-and 6-fold higher in tumors with H.pylori infection,respectively.Consistently,RORγt,a transcription factor regulating Th17 differentiation,was increased 6-fold in H.pylori-positive vs.negative tumors.Further elevation of RORγt was seen in advanced H.pylori-associated tumors.In addition,H.pylori infection was also associated with enhanced expression of CXCL1(5 folds),chemotactic factor capable of driving bone marrow-derived immature myeloid cells.Interestingly,we observed that H.pylori-associated increase of IL-17A was enhanced in the group with higher plasma triglycerides.Conclusion:The findings demonstrate a cross-talk and synergistic role of H.pylori infection and abnormal lipid metabolism in GC development,at least partly via cooperative induction of Th17 differentiation and activation.