Background: Melanoma is the most common symptom of aggressive skin cancer, and it has become a serious health concern worldwide in recent years. The metastasis rate of malignant melanoma remains high, and it is highly difficult to cure with the currently available treatment options. Effective yet safe therapeutic options are still lacking. Alternative treatment options are in great demand to improve the therapeutic outcome against advanced melanoma. This study aimed to develop albumin nanoparticles (ANPs) coated with macrophage plasma membranes (RANPs) loaded with paclitaxel (PTX) to achieve targeted therapy against malignant melanoma. Methods: Membrane derivations were achieved by using a combination of hypotonic lysis, mechanical membrane fragmentation, and differential centrifugation to empty the harvested cells of their intracellular contents. The collected membrane was then physically extruded through a 400 nm porous polycarbonate membrane to form macrophage cell membrane vesicles. Albumin nanoparticles were prepared through a well-studied nanoprecipitation process. At last, the two components were then coextruded through a 200 nm porous polycarbonate membrane. Results: Using paclitaxel as the model drug, PTX-loaded RANPs displayed significantly enhanced cytotoxicity and apoptosis rates compared to albumin nanoparticles without membrane coating in the murine melanoma cell line B16F10. RANPs also exhibited significantly higher internalization efficiency in B16F10 cells than albumin nanoparticles without a membrane coating. Next, a B16F10 tumor xenograft mouse model was established to explore the biodistribution profiles of RANPs, which showed prolonged blood circulation and selective accumulation at the tumor site. PTX-loaded RANPs also demonstrated greatly improved antitumor efficacy in B16F10 tumor-bearing mouse xenografts. Conclusion: Albumin-based nanoscale delivery systems coated with macrophage plasma membranes offer a highly promising approach to achieve tumor-targeted therapy following systemic administration.

We have previously reported that the CNDP1 (CTG)5 allele affords protection against diabetic nephropathy (DN) in patients with Type 2 diabetes (T2DM) of Caucasian origin. Because the incidence of ESRD attributable to both Type 1 diabetes (T1DM) and T2DM is higher among South Asian than Caucasian people, the present study assessed relevant CNDP1 polymorphisms and their association with metabolic parameters in the Chinese Han population. To this end, the (CTG)n allele distribution along with 5 relevant SNPs in the CNDP1 gene, previously reported to be associated with DN in non (CTG)5 carriers of Afro-American ethnicity, were determined in 663 healthy individuals. The (CTG)6 homozygous genotype was the most prevalent (84.5%) genotype in the Chinese Han population. The (CTG)5 and (CTG)4 alleles were present in a small minority of individuals accounting for 15.2% and 0.3% of genotypes with at least one (CTG)5 or one (CTG)4 allele, respectively. Only 0.5% of individuals carried the homozygous (CTG)5 genotype and individuals carrying the homozygous (CTG)4 genotype were not found. The minor allele frequencies (MAFs) of the 5 SNP were 0.197 (C allele for rs4892247), 0.0855 (C allele for rs62099905), 0.085 (G allele for rs62099906), 0.066 (T allele for rs62099907), and 0.18 (A allele for rs72979715). All the SNPs except rs4892247 genotypes were in the Hardy-Weinberg equilibrium. Neither the (CTG)n polymorphism nor the latter three SNPs reached significance when compared with different metabolic parameters. In contrast, individuals with the TT genotype of rs62099905 presented lower fasting blood glucose but higher HbA1c levels. In conclusion, the rs62099905 in the CNDP1 gene is associated with serum glucose levels in the healthy Chinese Han population, while for the CNDP1 (CTG)n polymorphism, no association with serological parameters was found.

Histone acetyltransferases are responsible for histone acetylation, while histone deacetylases (HdAcs) counteract histone acetylation. An unbalanced dynamic between histone acetylation and deacetylation may lead to aberrant chromatin landscape and chromosomal function. HdAc2, a member of class I HdAc family, serves a crucial role in the modulation of cell signaling, immune response and gene expression. HdAc2 has emerged as a promising therapeutic target for liver disease by regulating gene transcription, chromatin remodeling, signal transduction and nuclear reprogramming, thus receiving attention from researchers and clinicians. The present review introduces biological information of HdAc2 and its physiological and biochemical functions. Secondly, the functional roles of HdAc2 in liver disease are discussed in terms of hepatocyte apoptosis and proliferation, liver regeneration, hepatocellular carcinoma, liver fibrosis and non-alcoholic steatohepatitis. Moreover, abnormal expression of HdAc2 may be involved in the pathogenesis of liver disease, and its expression levels and pharmacological activity may represent potential biomarkers of liver disease. Finally, research on selective HdAc2 inhibitors and non-coding RNAs relevant to HdAc2 expression in liver disease is also reviewed. The aim of the present review was to improve understanding of the multifunctional role and potential regulatory mechanism of HdAc2 in liver disease.

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PurposeTo evaluate the long-term cost-effectiveness of dapagliflozin, in addition to standard treatment, for the treatment of adult patients with type 2 diabetes (T2DM) at high cardiovascular risk from the Chinese healthcare system perspective.MethodsA decision-analytic Markov model with one-year cycles was developed to evaluate the health and economic outcomes in patients with T2DM and high risk of cardiovascular disease (CVD) treated with standard treatment and dapagliflozin plus standard treatment for 30 years. Clinical data, cost, and utility data were extracted from databases or published literature. Quality-adjusted life-years (QALYs), costs (€/¥ 2021) as well as incremental cost-effectiveness ratios (ICERs) were calculated. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty in the results.ResultsCompared with standard treatment, dapagliflozin plus standard treatment was predicted to result in an additional 0.25 QALYs (12.26 QALYs vs. 12.01 QALYs) at an incremental cost of €4,435.81 (¥33,875.83) per patient. The ICER for dapagliflozin plus standard treatment vs. standard treatment was €17,742.07 (¥135,494.41) per QALY gained, which was considered cost-effective in China compared to three times the GDP per capita in 2021 (€31,809.77/¥242,928). The deterministic and probabilistic sensitivity analyses showed the base-case results to be robust.ConclusionsThe study suggests that, from the perspective of the Chinese health system, dapagliflozin plus standard treatment is a cost-effective option for patients with T2DM at high cardiovascular risk. These findings may help clinicians make the best treatment decisions for patients with T2DM at high cardiovascular risk.