Murine studies have shown that immunological targeting of fibroblast activation protein (FAP) can elicit protective immunity in the absence of significant pathology. Fibroblast activation protein is ...a product overexpressed by tumor‐associated fibroblasts (TAF) and is the predominant component of the stoma in most types of cancer. Tumor‐associated fibroblasts differ from normal adult tissue fibroblasts, and instead resemble transient fetal and wound healing‐associated fibroblasts. Tumor‐associated fibroblasts are critical regulators of tumorigenesis, but differ from tumor cells by being more genetically stable. Therefore, in comparison to tumor cells, TAF may represent more viable therapeutic targets for cancer immunotherapy. To specifically target TAF, we constructed a DNA vaccine directed against FAP. This vaccine significantly suppressed primary tumor and pulmonary metastases primarily through CD8+ T‐cell‐mediated killing in tumor‐bearing mice. Most importantly, tumor‐bearing mice vaccinated against FAP exhibited a 1.5‐fold increase in lifespan and no significant pathology. These results suggest that FAP, a product preferentially expressed by TAF, could function as an effective tumor rejection antigen. (Cancer Sci 2010; 101: 2325–2332)
Several studies have reported the effects of DJ-1 gene and miR-199a/b-3p on HCC development. However, whether miR-199a/b-3p regulates HCC progression through a novel compensatory signaling pathway ...involving DJ-1, Ras, and PI3K/AKT remains unknown. We used (TCGA, HPA, miRWalk and Target scan) databases, cancer and para-tissue HCC patients, dual-luciferase reporter gene analysis, proteomic imprinting, qPCR, cell proliferation, scratch, transport, and flow cytometry to detect the molecular mechanism of DJ-1 and miR-199a/b-3p co-expression in HCC cell lines. Bioinformatics analysis showed that DJ-1 was highly expressed in HCC ((P < 0.001) were closely associated with tumor stage (T), portal vein vascular invasion, OS, DSS, and PFI (P < 0.05); miR-199a/b-3p was lowly expressed in HCC (P < 0.001), which was the upstream regulator of DJ-1. Spearman coefficient r = -0.113, P = 0.031; Dual luciferase gene report verified the negative targeting relationship between them P< 0.001; Western blotting demonstrated that miR-199a/b-3p could inhibit the protein expression of DJ-1, Ras and AKT(P < 0.05); The results of CCK8, cell scratch, Transwell migration and flow cytometry showed that OE + DJ-1 increased the proliferation, migration and invasion ability of HepG2 cells, and decreased the apoptosis process, and the differences were statistically significant (P < 0.05), while miR-199a/b-3p had the opposite effect (P < 0.05).
Photodynamic therapy (PDT) is ineffective against deeply seated metastatic tumors due to poor penetration of the excitation light. Herein, we developed a biomimetic nanoreactor (bio-NR) to achieve ...synergistic chemiexcited photodynamic-starvation therapy against tumor metastasis. Photosensitizers on the hollow mesoporous silica nanoparticles (HMSNs) are excited by chemical energy in situ of the deep metastatic tumor to generate singlet oxygen (
O
) for PDT, and glucose oxidase (GOx) catalyzes glucose into hydrogen peroxide (H
O
). Remarkably, this process not only blocks the nutrient supply for starvation therapy but also provides H
O
to synergistically enhance PDT. Cancer cell membrane coating endows the nanoparticle with biological properties of homologous adhesion and immune escape. Thus, bio-NRs can effectively convert the glucose into
O
in metastatic tumors. The excellent therapeutic effects of bio-NRs in vitro and in vivo indicate their great potential for cancer metastasis therapy.
Effective control of oral biofilm infectious diseases represents a major global challenge. Microorganisms in biofilms exhibit increased drug tolerance compared with planktonic cells. The present ...review covers innovative antimicrobial strategies for controlling oral biofilm-related infections published predominantly over the past 5 years. Antimicrobial dental materials based on antimicrobial agent release, contact-killing and multi-functional strategies have been designed and synthesized for the prevention of initial bacterial attachment and subsequent biofilm formation on the tooth and material surface. Among the therapeutic approaches for managing biofilms in clinical practice, antimicrobial photodynamic therapy has emerged as an alternative to antimicrobial regimes and mechanical removal of biofilms, and cold atmospheric plasma shows significant advantages over conventional antimicrobial approaches. Nevertheless, more preclinical studies and appropriately designed and well-structured multi-center clinical trials are critically needed to obtain reliable comparative data. The acquired information will be helpful in identifying the most effective antibacterial solutions and the most optimal circumstances to utilize these strategies.
This paper lays forth a process for continuing Bayesian calibration of full-scale building energy simulation (BES) models by making use of data obtained from building information modeling (BIM) and ...building energy management systems (BEMS). According to a survey taken in China, it is possible that importing data from BIM and BEMS will dramatically cut down on the amount of time and effort required for the continuing calibration of BES models. After that, the continuous calibration approach that had been developed was examined with the use of a case study that was based on the actual calibration of a building. In China, Building Information Modeling (BIM) and data on the amount of electricity used each month over the course of the preceding three years were both incorporated into the case study. According to the findings, a non-continuous technique on the test dataset fared worse than a continuous Bayesian calibration method in terms of prediction accuracy and reduced uncertainty. The normalized mean biased error (NMBE) and the coefficient of variation of the root mean square error (CVRMSE) are both discussed in this research, and comparisons are drawn between the two.
ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are among the most common ...opportunistic pathogens in nosocomial infections. ESKAPE pathogens distinguish themselves from normal ones by developing a high level of antibiotic resistance that involves multiple mechanisms. Contemporary therapeutic strategies which are potential options in combating ESKAPE bacteria need further investigation. Herein, a broad overview of the antimicrobial research on ESKAPE pathogens over the past five years is provided with prospective clinical applications.
ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are among the most common opportunistic pathogens in nosocomial infections. Herein, contemporary therapeutic strategies against drug‐resistance ESKAPE and antimicrobial agents with prospective clinical applications are summarized, with a forecast on the future tendency of ESKAPE infection control.
Sensitive and reliable detection of DNA methyltransferase (MTase) is of great significance for both early tumor diagnosis and therapy. In this study, a simple, label-free and sensitive DNA ...MTase-sensing method was developed on the basis of a nicking endonuclease-mediated multiple primers-like rolling circle amplification (RCA) strategy. In this method, a dumbbell RCA template was prepared by blunt-end ligation of two molecules of hairpin DNA. In addition to the primer-binding sequence, the dumbbell template contained another three important parts: 5′-CCGG-3′ sequences in double-stranded stems, nicking endonuclease recognition sites and C-rich sequences in single-stranded loops. The introduction of 5′-CCGG-3′ sequences allows the dumbbell template to be destroyed by the restriction endonuclease, HpaII, but is not destroyed in the presence of the target MTase—M.SssI MTase. The introduction of nicking endonuclease recognition sites makes the M.SssI MTase-protected dumbbell template-mediated RCA proceed in a multiple primers-like exponential mode, thus providing the RCA with high amplification efficiency. The introduction of C-rich sequences may promote the folding of amplification products into a G-quadruplex structure, which is specifically recognized by the commercially available fluorescent probe thioflavin T. Improved RCA amplification efficiency and specific fluorescent recognition of RCA products provide the M.SssI MTase-sensing platform with high sensitivity. When a dumbbell template containing four nicking endonuclease sites is used, highly specific M.SssI MTase activity detection can be achieved in the range of 0.008–50U/mL with a detection limit as low as 0.0011U/mL. Simple experimental operation and mix-and-detection fluorescent sensing mode ensures that M.SssI MTase quantitation works well in a real-time RCA mode, thus further simplifying the sensing performance and making high throughput detection possible. The proposed MTase-sensing strategy was also demonstrated to be applicable for screening and evaluating the inhibitory activity of MTase inhibitors.
•A simple and sensitive DNA methyltransferase (MTase)-sensing method was reported.•High sensitivity is achieved by using a multiple primers-like RCA strategy.•The use of G-quadruplex probe provides a label-free and highly specific mode.•The proposed method can work well in high throughput real-time RCA mode.•The method can also be used for MTase inhibitor screening and evaluation.
An efficient transition-metal free C-C bond cleavage/borylation of cycloketone oxime esters has been described. In this reaction, the B
(OH)
reagent not only served as the boron source but also acted ...as an electron donor source through formation of a complex with a DMAc-like Lewis base. This complex could be used as an efficient single electron reductant in other ring-opening transformations of cycloketone oxime esters. Free-radical trapping, radical-clock, and DFT calculations all suggest a radical pathway for this transformation.
The gut microbiota, the largest symbiotic ecosystem with the host, has been shown to play important roles in maintaining intestinal homeostasis. Dysbiosis of the gut microbiome is caused by the ...imbalance between the commensal and pathogenic microbiomes. The commensal microbiome regulates the maturation of the mucosal immune system, while the pathogenic microbiome causes immunity dysfunction, resulting in disease development. The gut mucosal immune system, which consists of lymph nodes, lamina propria and epithelial cells, constitutes a protective barrier for the integrity of the intestinal tract. The composition of the gut microbiota is under the surveillance of the normal mucosal immune system. Inflammation, which is caused by abnormal immune responses, influences the balance of the gut microbiome, resulting in intestinal diseases. In this review, we briefly outlined the interaction between the gut microbiota and the immune system and provided a reference for future studies.
Accumulating evidence suggests that Ras GTPase‐activating protein SH3 domain‐binding protein 1 (G3BP1) is very crucial to regulate tumorigenesis and metastasis. Recently, many research works have ...suggested that G3BP1 is overexpressed in many human cancers including esophageal cancer. Nevertheless, the functional roles of G3BP1 in esophageal cancer are still unknown. Here, the results suggested that silencing of G3BP1 inhibited proliferation, migration, and invasion of esophageal cancer cells, whereas overexpression of G3BP1 led to opposite effects on the growth and metastasis. Surprisingly, G3BP1‐depletion had no effect on cell death but caused the arrest of cell cycle in the G0/G1 phase and increased the levels of p53 and p21. In addition, loss of G3BP1 led to a significant elevation of E‐cadherin and decrease of N‐cadherin, Vimentin, Snail, MMP‐9, and MMP‐2. Mechanistically, loss of G3BP1 dramatically suppressed Wnt‐stimulated T‐cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor activity and downregulated its target genes including c‐Myc, Axin2, and cyclin D1. Moreover, knockdown of G3BP1 downregulated the expression levels of p‐PI3K, p‐AKT, and p‐GSK‐3β, but the total PI3K, AKT, and GSK‐3β were not changed. Furthermore, our data proved that the promoting effects of G3BP1‐overexpression on cell proliferation, migration, and invasion could be rescued by PI3K inhibitor LY294002 treatment. Collectively, our results here elucidate that G3BP1‐depletion suppresses proliferation, migration, and invasion capabilities of esophageal cancer cells via the inactivation of Wnt/β‐catenin and PI3K/AKT signaling pathways. Furthermore, our findings imply that G3BP1 can participate in the regulation of esophageal cancer progression, and will be taken as a promising target to treat esophageal cancer.
In our study, we investigated the effects of GTPase‐activating protein SH3 domain‐binding protein 1‐depletion (G3BP1) on cell proliferation, cell cycle, cell death, migration, and invasion of esophageal cancer cells. Our results demonstrated that knockdown of G3BP1 gave rise to inhibition of esophageal cancer cell proliferation, migration, invasion, epithelial‐mesenchymal transition, and cell cycle arrest in the G0/G1 phase through suppressing Wnt/β‐catenin and PI3K/AKT signaling pathways, whereas overexpression of G3BP1 led to opposite the effects on proliferation, migration, and invasion. Our data suggest that G3BP1 plays a crucial role in esophageal cancer progression, and may be a novel prognostic marker and potential therapeutic target for esophageal cancer.
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