ACS Applied Nano Materials最新文献

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis and lack of effective treatments. In recent years, peptide vaccines that use sequences based on tumor-specific or tumor-associated antigens to activate immune responses against tumor cells have emerged as a new therapeutic strategy. In this study, we developed a novel therapeutic polypeptide vaccine targeting the tumor-associated antigen Fibrinogen-Like Protein 2 (FGL2), whose dominant epitope peptide was tandemly linked to the C-terminus of HCMV-IE1mut via a linker. We used this vaccine to compare the therapeutic efficacy of HCMV-IE1mut alone versus HCMV-IE1mut-FGL2_172-220 and investigate the potential mechanism of action of HCMV-IE1mut-FGL2_172-220 in glioma treatment. An in situ GBM model (GL261-IE1-luc cells) was used to determine the efficacy of the vaccine. Treatment with HCMV-IE1mut-FGL2_172-220 exerted antitumor effects and extended the survival of the GL261 animal model. We observed reduced proportions of microglia, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) in the tumor microenvironment (TME) by immunofluorescence. Flow cytometry showed that compared to HCMV-IE1mut alone, treatment with HCMV-IE1mut-FGL2_172-220 increased the proportion of CD8+ T cells and tissue-resident memory T cells (TRM). ELISA analysis showed that it improved the secretion of tumor-specific IFN-γ and TNF-α by these cells and downregulated the expression of IL-6 and IL-10. Our study demonstrates that the long-peptide FGL2_172-220 improves the antitumor efficacy of HCMV-IE1mut, possibly by reshaping immune cells in the glioma microenvironment. These findings lay the groundwork for the development of therapeutic antigenic peptide vaccines to improve antitumor effects for cancer.

Neoantigen-reactive CD4⁺ T cells play a key role in the anti-tumor immune response. However, the majority of epithelial tumors are negative for HLA class II (HLA-II) surface expression, and less is known about the processing of HLA-II antigens. Here, we directly identified naturally presented HLA-II neoantigens in HLA-II negative colorectal cancer (CRC) tissue using a proteogenomic approach. The neoantigens were immunogenic and induced patient CD4⁺ T cells with a Th1-like memory phenotype that produced IFN-γ, IL2 and TNF-α. Multiplex immunohistochemistry (IHC) demonstrated an interaction between Th cells and HLA-II-positive antigen-presenting cells (APCs) at the invasive margin and within the tertiary lymphoid structures (TLS). In our CRC cohort, the density of stromal APCs was associated with HLA-II antigen presentation in the tumor microenvironment (TME), and the number of TLS was positively correlated with the number of somatic mutations in the tumors. These results demonstrate the presence of neoantigen-specific CD4⁺ surveillance in HLA-II-negative CRC and suggest a potential role for macrophages and dendritic cells (DCs) at the invasive margin and in TLS for antigen presentation. Stromal APCs in the TME can potentially be used as a source for HLA-II neoantigen identification.

Successful bone fragment fixation is a crucial factor in bone fracture healing, the fixation of crushed bone fragments could hinder bone fracture healing. Thus, ideal bone glues to effectively adhere and splice comminuted bone fragments are needed in clinical. Herein, an osteoinductive and biodegradable double cross-linked bone glue (GelMA-oDex-AMBGN) was constructed through Schiff's base reaction between commercial GelMA (with different substitution degrees of amino groups) and Odex mixed with amine-modified mesoporous bioactive glass nanoparticles (AMBGN), followed by crosslink with blue light irradiation. The GelMA-oDex-AMBGN bone glue successfully adhered and spliced the comminuted bone fragments of isolated rat skulls. GelMA-oDex-AMBGN promoted the proliferation of 3T3 cells and enhanced the expression of osteogenic proteins Runx2 and OCN in vitro. In rat cranial critical-sized defect models, GelMA-oDex-AMBGNs with different substitution degrees significantly increased the new bone contents at the fracture defect sites and promoted bone tissue regeneration in vivo. In conclusion, the double cross-linked bone glue (GelMA-oDex-AMBGN) was successfully constructed and can induce bone regeneration. Additionally, there was no significant difference in osteogenic activity among GelMA-oDex-AMBGNs with different substitution degrees and the equal content of AMBGN.

Colorectal cancer is a type of cancer that affects the colon or rectum, which are part of the digestive system. It usually develops from small growths called polyps that can turn cancerous over time. This study aimed to investigate the effects of Jianpi Yiqi prescription on clinical symptoms, inflammation, oxidative stress, efficacy, and adverse reactions in colorectal cancer (CRC) patients. A total of 84 CRC patients treated at a hospital from January 2020 to December 2021 were randomly divided into two groups: the conventional chemotherapy group and the Jianpi Yiqi prescription group. Patients in the Jianpi Yiqi group received traditional Chinese medicine on top of conventional chemotherapy. Clinical symptoms and plasma biomarkers were analyzed and compared between the two groups. Results showed that there were significant differences between the two groups before therapy. After therapy, the Jianpi Yiqi group had lower TCM symptom scores, inflammatory factor indices, MDA and SOD levels, and incidence of adverse reactions than the conventional group. Moreover, the total effective rate and tumor stability rate of the Jianpi Yiqi group were higher than those of the conventional group. The study concluded that Jianpi Yiqi prescription had better clinical efficacy in treating CRC patients compared to conventional chemotherapy, with fewer adverse reactions and better inhibition of inflammatory factors and oxidative stress. Overall, this study suggests that Jianpi Yiqi prescription could be a promising complementary therapy for CRC patients, but more research is needed to confirm these findings.

Objective: hsa_circ_0057104 (circPDK1) has been elucidated to regulate malignant behavior in pancreatic and renal cell carcinoma. The study functionally aimed at how circPDK1 modifies colorectal cancer (CRC) progression, along with its potential molecular mechanism.

Methods: circPDK1 expression patterns in CRC tissues and cell lines were analyzed by RT-qPCR. circPDK1/miR-627-5p/CCND2 expression levels were changed by transient transfection. CCK-8 assay, flow cytometry, Transwell, immunoblotting, and commercial kits were utilized to measure CRC cell proliferation, apoptosis, invasion/migration, and glycolysis processes. Dual luciferase reporting assay and RIP assay were employed to evaluate the targeting relationship between circPDK1/miR-627-5p/CCND2.

Results: circPDK1 was highly expressed in CRC. circPDK1 knockdown inhibited CRC cell proliferation, invasion/migration, and warburg effect and forced apoptosis. Overexpressing circPDK1 had the opposite effect. The effects of circPDK1 knockdown or circPDK1 overexpression on CRC cells were mitigated by downregulating miR-627-5p or CCND2, respectively. CircPDK1, by competitive adsorption of miR-627-5p, mediated CCND2 expression.

Conclusion: CircPDK1 induces the malignant behavior of CRC by competitive adsorption of miR-627-5p mediating CCND2 expression, offering new insights into the future development of CRC-targeted drugs.

This study analyzed records of 200 patients who underwent hepatobiliary surgery to identify factors that contribute to lower extremity venous thromboembolism (VTE). 19 patients (9.50%) developed lower extremity deep vein thrombosis. Univariate analysis revealed significant differences between the study group and the control group in terms of age, body mass index, previous thromboembolic history, hypertension, type 2 diabetes, hyperlipidemia, smoking history, times of lower extremity venipuncture, operation time, postoperative bedrest time, postoperative platelet count, postoperative D-dimer level, and postoperative C-reactive protein level (P<0.05). Multivariable logistic regression analysis identified age ≥60 years, body mass index ≥24 kg/m2, previous history of thromboembolism, hypertension, type 2 diabetes mellitus, hyperlipidemia, smoking history, number of lower extremity venipunctures ≥5, operation time ≥2 hours, postoperative bedrest time ≥48 hours, postoperative blood platelet count ≥300×109/L, postoperative D-dimer level ≥200 g/L, and postoperative C-reactive protein ≥8.0 mg/L as significant predisposing factors for lower extremity VTE. The study concludes that patients undergoing hepatobiliary surgery are at an increased risk of developing lower extremity VTE, and prevention strategies must be tailored to each patient's unique set of risk factors. This includes careful management of postoperative bed rest, monitoring of platelet count, D-dimer and C-reactive protein levels, controlling hypertension, type 2 diabetes mellitus, hyperlipidemia, and cessation of smoking. This study highlights the importance of early identification of patients at high risk of lower extremity VTE following hepatobiliary surgery and comprehensive prevention measures.

Monitoring changes in serum tumor marker concentrations can help in the early diagnosis of non-small cell lung cancer (NSCLC). However, there are few methods to monitor the efficacy and prognosis of radiotherapy in NSCLC patients. The present research aimed to explore the correlation between radiotherapy efficacy and squamous cell carcinoma antigen (SCCA) and cytokeratin 19 soluble fragment (CYFRA21-1) levels in NSCLC patients. Serum CYFRA21-1 and SCCA were detected with an automatic chemiluminescence immunoassay analyzer. Patients with NSCLC were followed up by telephone at regular intervals for 35 months. The χ² test was used to compare clinical characteristics such as age, gender, smoking history and other count data between groups. Predictive value of serum SCCA and CYFRA21-1 on the efficacy of radiotherapy was analyzed by Receiver Operating Characteristic (ROC) curves. The survival of the patients was analyzed by Kaplan-Meier method. The serum SCCA and CYFRA21-1 levels in the NSCLC group were apparently higher by comparison with control group. The SCCA and CYFRA21-1 concentration were both positive relevant to Tumor Node Metastasis (TNM) stage. The Area Under Curve (AUC) of serum SCCA and CYFRA21-1 were 0.732 and 0.721, respectively. In addition, high serum SCCA and CYFRA21-1 levels could predict poor radiotherapy outcomes. Patients with high serum concentration of SCCA and CYFRA21-1 have shorter survival times. High serum SCCA and CYFRA21-1 levels could predict poor prognosis and unfavorable efficacy of radiotherapy in invalids with NSCLC.

This study aimed to identify factors that affect the prognosis of children with pulmonary valve atresia and intact ventricular septum treated with transthoracic balloon dilation of the pulmonary valve. The study included 148 participants who were followed up for 5 years. Of these, 10 died, while 138 survived. Independent sample t-test and χ2 test were used to analyze clinical data of children in the death and survival groups. It was found that height, weight, body surface area, arterial oxygen saturation, degree of tricuspid regurgitation, pulmonary valve cross valve pressure difference, ICU length of stay, length of stay, reoperation intervention, and complications were statistically significant (P<0.05). ROC curve analysis of the measurement indicators with statistically significant differences showed that height, weight, body surface area, arterial oxygen saturation, ICU length of stay, and length of stay had AUCs ranging from 0.723 to 0.870. Logistic regression analysis revealed that the degree of tricuspid regurgitation, pulmonary valve cross valvular pressure difference, ICU length of stay, reoperation intervention, and complications were independent risk factors that affect the prognosis of patients with PA/IVS undergoing transthoracic balloon dilation of pulmonary valve. The study proposed a nomogram prediction model using R language software 4.0 "rms" package, which was validated using calibration curve and decision curve. The model had a C-index of 0.667 (95% CI: 0.643-0.786) and high degree of fit. This study provides clinicians with a prediction model to identify children with poor prognosis after treatment with transpulmonary valve balloon dilatation.           .

This study aimed to evaluate the effects of soybean, selenium and spirulina on bone metabolic factors in rats with combined fluoride and aluminum poisoning.Methods:Sixty SD rats were allocated to five groups: A control group, a high-fluoride aluminum group, a high-fluoride aluminum plus soybean group, a high-fluoride aluminum plus selenium group, and a high-fluoride aluminum plus spirulina group. Serum samples were collected and radioimmunoassay (RIA) was used to measure osteocalcin (BGP), calcitonin (CT), parathyroid hormone (PHT) and insulin growth factor I (IGF-1) levels after 90 and 165 days of intervention. 1. When comparing the serum BGP level in the high-fluorine aluminum plus selenium group with the high-fluorine aluminum group, suggesting that the addition of selenium intervention was beneficial in reducing the effect of high-fluorine aluminum on bone homeostasis. 2. After 90 days and 165 days, the difference in serum CT levels between the intervention group and the control group was not statistically significant, suggesting an effect of the intervention factors.3. After 90 days of exposure, the three intervention groups had lower serum PTH levels (p < 0.00), inferring the efficacy of the interventions.4. After 90 days, serum IGF-1 levels were elevated in the Spirulina group compared with the high-fluorinated aluminum group, and the difference was statistically significant, suggesting that the addition of Spirulina intervention may counteract the inhibition of bone growth by high-fluorinated aluminum. The intervention of soybean, selenium, and spirulina can counterbalance the effects of fluoride and aluminum on bone metabolism and slow down the process of bone turnover.

To investigate the correlation between the coefficient of variation of blood pressure and cognitive dysfunction in patients with hypertension complicated by cerebral small vessel disease. 415 patients with hypertension complicated by cerebral small vessel disease who received treatment in our hospital from January 2019 to June 2022 were retrospectively included in this study. These patients were divided into a cognitive dysfunction group (n = 74) and a non-cognitive dysfunction group (n = 341) according to whether they had cognitive dysfunction. Blood pressure and general data were recorded for each patient. The logistic regression coefficient was used to analyze the correlation between coefficient of variation of blood pressure and cognitive dysfunction in patients with hypertension complicated by cerebral small vessel disease. Multivariate logistic regression analysis showed that age, the weighted standard deviation of 24-hour systolic blood pressure (24hSBP-wSD), cholesterol level, and triglyceride level were risk factors for cognitive dysfunction in patients with hypertension complicated by cerebral small vessel disease (P < 0.05). The risk for cognitive dysfunction was increased by 3.532-fold in patients aged>65 years, increased by 1.203-fold in patients with a 24hSBP-wSD of 14.9-15.9%, and increased by 3.033-fold in patients with a 24hSBP-wSD>16.0% (P < 0.05). The coefficient of variation of blood pressure is markedly correlated with the risk for cognitive dysfunction; and a higher coefficient of variation of blood pressure leads to a higher risk for cognitive dysfunction in patients with hypertension complicated by cerebral small vessel disease.