Hydrazone-functionalized nanoscale covalent organic frameworks as a nanocarrier for pH-responsive drug delivery enhanced anticancer activity.

Nanoscale covalent organic frameworks (NCOFs) as emerging drug-delivery nanocarriers have received much attention in biomedicine in recent years. However, there are few reports on the application of pH-responsive NCOFs for drug delivery nanosystems. In this work, hydrazone-decorated NCOFs as pH-triggered molecular switches are designed for efficient cancer therapy. These functionalized NCOFs with hydrazone groups on the channel walls (named NCOFs-NHNH2) are obtained via a post-synthetic modification strategy. Subsequently, the anticancer drug doxorubicin (DOX) as the model molecule is loaded through covalent linkage to yield NCOFs-NN-DOX. Finally, soybean phospholipid (SP) is coated on the surface of HNTs-NN-DOX, named NCOFs-NN-DOX@SP, to further enhance the dispersibility, stability and biocompatibility of HNTs in physiological solution. NCOFs-NN-DOX@SP showed an excellent and intelligent sustained-release effect with an almost sixfold increase at pH = 5.2 than at pH = 7.4. In vitro cell toxicity and imaging assays of NCOFs-NN-DOX@SP exhibited an enhanced therapeutic effect on Lewis lung carcinoma (LLC) cells, demonstrating that the fabricated NCOFs have a great potential in cancer therapy. Thus, this work provides a new way toward designing stimulus-responsive functionalized NCOFs and promotes their potential application as an on-demand drug delivery system in the field of cancer treatment.

Efficacy of sequential TACE on primary hepatocellular carcinoma with microvascular invasion after radical resection: a systematic review and meta-analysis.

OBJECTIVES: The purpose of this study is to examine the impact of sequential transcatheter arterial chemoembolization (TACE) on the prognosis of patients with hepatocellular carcinoma (HCC) and microvascular invasion (MVI) following radical resection. METHODS: Five databases were searched for studies on the efficacy of TACE after radical hepatectomy resection (HR) for treating HCC with MVI. Depending on the heterogeneity between included studies, the relative risk (RR) and 95% confidence interval (CI) were computed using a random or fixed effect model. RESULTS: Thirteen articles were included in this study. There were 1378 cases in the HR-TACE group (cases undergoing TACE after HR) and 1636 cases in the HR group (cases only undergoing HR). The recurrence-free survival (RFS) at 1 year, 2 years, 3 years, and 5 years after radical HCC resection was statistically significantly greater in the HR-TACE group than in the HR group. The HR-TACE group exhibited statistically significant advantages at 1-year, 2-year, 3-year, and 5-year overall survival (OS) after radical HCC resection when compared with the HR group. CONCLUSION: Postoperative sequential TACE treatment can improve the RFS and OS rates at 1 year, 2 years, 3 years, and 5 years following radical HR in patients with HCC and MVI. These findings will guide clinicians in selecting appropriate cases for adjuvant TACE treatment during clinical diagnosis and treatment to maximize patient benefit. TRIAL REGISTRATION: PROSPERO CRD42023449238.

Association of a tgf-b1-509c/t polymorphism with gastric cancer risk: a meta-analysis.

Published data on the association between the transforming growth factor B1 (TGF-B1) gene 509C/T polymorphism and gastric cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis of the TGFB1-509C/T polymorphism (with 2130 cases and 2374 controls) from seven published case-control studies was performed. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the codominant model, the dominant model, and the recessive model. In the overall analysis, the T allele was significantly associated with susceptibility to gastric cancer in the recessive model (TT vs. CC+CT) (TT vs. CC+CT: OR = 1.35, 95% CI: 1.10-1.66, P = 0.10 for heterogeneity) when all the included studies were pooled into the meta-analysis. In the stratified analysis by country, the T allele was also found to be significantly associated with increased gastric cancer risk in the recessive model (TT vs. CC+CT) in Chinese studies and in T versus C in the Indian study. In conclusion, this meta-analysis supports the TGFB1-509T polymorphism as a susceptibility factor for gastric cancer.

Protection against acute radiation-induced lung injury: a novel role for the anti-angiogenic agent Endostar.

Radiotherapy is commonly used to treat thoracic malignancies, but often causes severe lung injury. Currently there are no effective protective strategies against radiation-induced lung injury (RILI). This study aimed to evaluate the ability of an angiogenesis antagonist, Endostar, against RILI, and the underlying mechanism in a mouse model. A total of 108 C57BL/6 female mice were randomized into 4 groups (n=27): i) control group; ii) Endostar group, animals were administered 7.75 ml/kg Endostar through intraperitoneal injection; iii) irradiation group, RILI was induced by exposing the animals to a single external irradiation on the thoraces (6 MV X-ray, 12 Gy); and iv) irradiation plus Endostar group, animals were subjected to Endostar treatment and irradiation as in groups 2 and 3. A total of 3 animals from each of the 4 groups were sacrificed at 1, 6, 12, 24 and 72 h and at 2, 4, 8 and 24 weeks following treatment. Clinical signs and pathology of RILI were examined. The expression of transforming growth factor-ß 1 (TGF-ß1) in lungs was analyzed by real-time quantitative polymerase chain reaction (RT-QPCR) and immunohistochemistry. Compared with the control group, irradiation induced evident interstitial edema and a significant increase in inflammatory cells in the lungs (P<0.05). Correlated with these changes, a notable increase in TGF-ß1 mRNA level and a robust increase in TGF-ß1 immunoreactivity were observed in lung tissues in a time-dependent manner following irradiation (P<0.05). Endostar administration effectively attenuated the magnitude of the increase in inflammatory cells as well as the elevation of TGF-ß1 expression in lung tissues after RILI (P<0.05). In conclusion, radiation induced an increased expression of the inflammatory mediator TGF-ß1 and the associated pathogenesis in the lung, while Endostar was able to at least partially attenuate RILI through downregulating the expression of TGF-ß1 in mice. Our findings suggest that Endostar may be a novel protective agent against RILI.