Polydopamine-Based Nanoparticles for Synergistic Chemotherapy of Prostate Cancer.

Introduction: Immune regulatory small molecule JQ1 can block its downstream effector PD-L1 pathway and effectively reverse the PD-L1 upregulation induced by doxorubicin (DOX). So the synergistic administration of chemotherapeutic drug DOX and JQ1 is expected to increase the sensitivity of tumors to immune checkpoint therapy and jointly enhance the body's own immunity, thus effectively killing tumor cells. Therefore, a drug delivery system loaded with DOX and JQ1 was devised in this study. Methods: Polydopamine nanoparticles (PDA NPs) were synthesized through spontaneous polymerization. Under appropriate pH conditions, DOX and JQ1 were loaded onto the surface of PDA NPs, and the release of DOX and JQ1 were measured using UV-Vis or high performance liquid chromatography (HPLC). The mechanism of fabricated nanocomplex in vitro was investigated by cell uptake experiment, cell viability assays, apoptosis assays, and Western blot analysis. Finally, the tumor-bearing mouse model was used to evaluate the tumor-inhibiting efficacy and the biosafety in vivo. Results: JQ1 and DOX were successfully loaded onto PDA NPs. PDA-DOX/JQ1 NPs inhibited the growth of prostate cancer cells, reduced the expression of apoptosis related proteins and induced apoptosis in vitro. The in vivo biodistribution indicated that PDA-DOX/JQ1 NPs could accumulated at the tumor sites through the EPR effect. In tumor-bearing mice, JQ1 delivered with PDA-DOX/JQ1 NPs reduced PD-L1 expression at tumor sites, generating significant tumor suppression. Furthermore, PDA-DOX/JQ1 NPs could reduce the side effects, and produce good synergistic treatment effect in vivo. Conclusion: We have successfully prepared a multifunctional platform for synergistic prostate cancer therapy.

Research Progress of Disulfide Bond Based Tumor Microenvironment Targeted Drug Delivery System.

Cancer poses a significant threat to human life and health. Chemotherapy is currently one of the effective cancer treatments, but many chemotherapy drugs have cell toxicity, low solubility, poor stability, a narrow therapeutic window, and unfavorable pharmacokinetic properties. To solve the above problems, target drug delivery to tumor cells, and reduce the side effects of drugs, an anti-tumor drug delivery system based on tumor microenvironment has become a focus of research in recent years. The construction of a reduction-sensitive nanomedicine delivery system based on disulfide bonds has attracted much attention. Disulfide bonds have good reductive responsiveness and can effectively target the high glutathione (GSH) levels in the tumor environment, enabling precise drug delivery. To further enhance targeting and accelerate drug release, disulfide bonds are often combined with pH-responsive nanocarriers and highly expressed ligands in tumor cells to construct drug delivery systems. Disulfide bonds can connect drug molecules and polymer molecules in the drug delivery system, as well as between different drug molecules and carrier molecules. This article summarized the drug delivery systems (DDS) that researchers have constructed in recent years based on disulfide bond drug delivery systems targeting the tumor microenvironment, disulfide bond cleavage-triggering conditions, various drug loading strategies, and carrier design. In this review, we also discuss the controlled release mechanisms and effects of these DDS and further discuss the clinical applicability of delivery systems based on disulfide bonds and the challenges faced in clinical translation.

Response of exogenous melatonin on transcription and metabolism of soybean under drought stress.

Amino acid metabolism is an important factor in regulating nitrogen source assimilation and source/sink transport in soybean. Melatonin can improve plant stress resistance, but whether it affects amino acid metabolism is not known. Therefore, this study investigated whether exogenous melatonin had an effect on amino acid metabolism of soybean under drought conditions and explored its relationship with yield. The treatments were normal water supply treatment (WW), drought stress treatment (D), drought stress and melatonin treatment group (D + M), sprayed with 100 µmol/L melatonin. The effects of melatonin on amino acid metabolism and grain filling were studied by physiological and omics experiments using Kangxian 9 (drought-sensitive variety) and Suinong 26 (drought-resistant variety) soybean cultivars. The results showed that drought stress decreased the activity of carbon and nitrogen metabolizing enzymes, which inhibited the accumulation of dry matter and protein, and decreased the yield. In the drought-sensitive soybean variety, glycoenzymes and amino acid synthetases synthetic genes were upregulated in melatonin-treated soybeans, hence carbon and nitrogen metabolism enzyme activity increased, increasing the carbohydrate and amino acid contents simultaneously. This resulted in higher dry matter and yield than drought-stressed soybean not treated with melatonin. In the drought-resistant variety, the grain weight per plant increased by 7.98% and 6.57% in 2020 and 2021, respectively, while it increased by 23.20% and 14.07% in the drought-sensitive variety during the respective years. In conclusion, melatonin treatment can enhance the activity of nitrogen and carbon metabolism and amino acid content by upregulating the expression of soybean metabolic pathway and related genes, thus increasing the yield of soybean under drought stress.

[Influence of cytokine gene polymorphism on renal transplantation].

OBJECTIVE: To study the influence of cytokine gene polymorphism on the incidence of acute rejection in renal transplantation. METHODS: The cytokine genotypes of TNF-alpha, TGF-beta(1), IL-10 and IL-6 in 24 normal people and 115 consecutive renal transplant recipients were determined by PCR-SSP using sequence-specific oligonucleotide primer. The cytokine genotypes were then correlated with the incidence of acute rejection in renal transplantation. RESULTS: The frequency of TNF-alpha and IL-10 low producer genotype in the 115 kidney recipients and control group was 88.7%, 80% and 87.5%, 75% respectively, and the frequency of TGF-beta(1) and IL-6 high producer genotype was 79.1%, 100% and 66.7%, 100% respectively. The incidence of acute rejection was higher in the recipients with TNF-(high producer or IL-10 intermediate high producer genotype than in the recipients with low producer genotype [53.8%, 43.5% vs 18.6% (chi(2) = 8.17), 17.4% (chi(2) = 7.16), P < 0.01, respectively]. CONCLUSION: This study demonstrated that TNF-alpha and IL-10 gene polymorphism has significant influence on the incidence of acute rejection in renal transplantation.