Search

There is increasing evidence that circular RNAs (circRNAs) can serve as microRNA (miRNA) sponges to regulate metastasis of multiple tumors, including pancreatic ductal adenocarcinoma (PDAC). However, the role of the circRNA/miRNA regulatory network in metastasis of PDAC has not been elucidated. The purpose of this study is to explore the role of circ_0047744/miR-21/SOCS5 in the metastasis of PDAC. We found that circRNA_0047744 was weakly expressed in PDAC tissues and cell lines. The expression of circ_0047744 was negatively correlated with lymph node metastasis and positively correlated with overall survival in PDAC patients. Functionally, the overexpression of circ_0047744 suppressed cell migration and invasion in vitro and in vivo. Mechanistically, circ_0047744 could regulate SOCS5 expression by acting as a sponge of miR-21 to inhibit migration and invasion of PDAC cells. Our study demonstrates that circ_0047744 acts as an anti-oncogene to inhibit PDAC metastasis by regulating the miR-21/SOCS5 axis, indicating that circ_0047744 may be a potential novel therapeutic target for PDAC patients. • circ_0047744 was downregulated in PDAC. • circ_0047744 suppressed metastasis of PDAC. • circ_0047744 served as a sponge for miR-21. • miR-21 promoted the metastasis of PDAC cells through targeting SOCS5. • circ_0047744 inhibited the metastasis of PDAC through the miR-21/SOCS5 axis. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs (lncRNAs) have been elucidated to participate in the development and progression of various cancers. In this study, we aimed to explore the underlying functions and mechanisms of LINC00958 in colorectal cancer. Methods: LINC00958 expression in colorectal cancer tissues was examined by qRT-PCR. The correlations between LINC00958 expression and clinical characteristics and prognosis were evaluated. The biological functions of LINC00958 were detected by CCK-8, MTT, colony formation and flow cytometric analyses. RNA pulldown, RIP and luciferase reporter assays were used to confirm the regulatory effects of LINC00958 on miR-422a. Rescue experiments were performed to detect the effects of miR-422a on the roles of LINC00958. Results: LINC00958 was upregulated in colorectal cancer tissues and cell lines. High LINC00958 levels were positively associated with T stage and predicted poor prognosis. Cell experiments showed that LINC00958 promoted cell proliferation and suppressed apoptosis and sensitivity to radiotherapy in vitro and promoted tumor growth in vivo. Bioinformatics analysis predicted the binding site of miR-422a on LINC00958. Mechanistically, RNA pulldown, RIP and luciferase reporter assays demonstrated that LINC00958 specifically targeted miR-422a. In addition, we found that miR-422a suppressed MAPK1 expression by directly binding to the 3'-UTR of MAPK1, thereby inhibiting cell proliferation and enhancing cell apoptosis and radiosensitivity. Furthermore, miR-422a rescued the roles of LINC00958 in promoting MAPK1 expression and cell proliferation and decreasing cell apoptosis and radiosensitivity. Conclusions: LINC00958 promoted MAPK1 expression and cell proliferation and suppressed cell apoptosis and radiosensitivity by targeting miR-422a, which suggests that it is a potential biomarker for the prognosis and treatment of colorectal cancer. [ABSTRACT FROM AUTHOR]

Chronic pancreatitis (CP) is a major risk factor for pancreatic cancer; however, little is known about the pathogenic mechanisms underlying the development of CP. Legumain (Lgmn) has been linked to some chronic inflammatory diseases. The present study investigated the role of legumain in pancreatic fibrogenesis. We induced CP in wild type C57BL6 (WT), Lgmn-deficient (Lgmn−/−), Lgmnflox/flox and Lgmnflox/flox × LysMCre mice by intraperitoneal injection of caerulein for 4 weeks. Pancreata were collected and analyzed by quantitative reverse transcription polymerase chain reaction, Western blotting, and histology. Pancreatic stellate cells and macrophages were isolated and studied using immunofluorescence, gelatin zymography, and enzyme-linked immunosorbent assay. The effects of inhibition of legumain were investigated in vivo by administration of the specific legumain inhibitor, RR-11a. Legumain was found to be upregulated in the serum and pancreatic tissues of mice with caerulein-induced CP. Mice with global and macrophage-specific legumain deficiency exhibited significantly reduced development of pancreatic fibrosis compared with control mice, based on pancreas size, histology, and expression of fibrosis-associated genes. Our results indicate that legumain promotes activation of pancreatic stellate cells and increases synthesis of extracellular matrix proteins via activation of matrix metalloproteinase-2(MMP-2), which hydrolyzes the transforming growth factor-β1 (TGF-β1) precursor to form active TGF-β1. Administration of RR-11a markedly attenuated pancreatic fibrosis in mice with CP. Deficiency or inhibition of legumain significantly reduces the severity of pancreatic fibrosis by suppressing activation of the TGF-β1 precursor. Our results highlight the potential of legumain as a novel therapeutic target for CP. Key messages: • Legumain expression was markedly upregulated in CP mice. • Deletion of legumain attenuated pancreatic fibrosis in CP mice. • Legumain promotes fibrosis via MMP-2 activation, which hydrolyzed the TGF-β1 precursor to the active form. • Legumain is a potential therapeutic target for the management of CP. [ABSTRACT FROM AUTHOR]

AbstractPurposeMaterials and MethodsResultsConclusionThis study aims to investigate the impact of specialized nursing care at fracture sites coordinated with disease progression monitoring in thoracolumbar spine fractures.Patients diagnosed with definitive thoracolumbar spine fractures and underwent surgical treatment at our hospital between February 2022 and August 2023 were selected. Patients were divided into a treatment group (specialized nursing care at fracture sites coordinated with disease progression monitoring) and a control group (conventional care) based on different nursing methods.A comparative assessment was conducted to evaluate the role and significance of specialized nursing care at fracture sites coordinated with disease progression monitoring in thoracolumbar spine fracture rehabilitation. The results showed that compared to conventional care, specialized nursing care at fracture sites coordinated with disease progression monitoring could better promote the recovery of patients’ neurological functions, alleviate pain, and effectively improve symptoms and functional recovery, thus enhancing patients’ quality of life and satisfaction.The study confirms the effectiveness of specialized nursing care at fracture sites coordinated with disease progression monitoring in clinical practice post thoracolumbar spine fractures. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) is a fatal tumor with grave prognosis. Pyroptosis, a programmed cell death, is involved in tumorigenesis. However, a few studies have elucidated the functions of pyroptosis in PDAC. Methods: The mRNA expression profiles were downloaded from the TCGA and GEO databases. Univariate and LASSO Cox regression analyses were used to screen out differentially expressed genes (DEGs) and construct the pyroptosis-related genes (PRGs) risk model. The efficiency of model was examined by Kaplan–Meier curve, ROC curve, and nomogram. Univariate and multivariate Cox regression analyses were utilized to assess whether the risk model could be used as an independent prognostic factor. The biological function was analyzed by GO, KEGG, and GSEA enrichment analysis. qRT-PCR and immunohistochemical staining detected gene expression. Results: Totally 9 PRGs with differential expression were identified between normal and PDAC tissues. Then, according to PRGs, we filtered out three key DEGs and constructed the prognostic risk model. Kaplan–Meier curve, ROC curve, and nomogram indicated that the prognostic risk model had high survival prediction efficiency. Meanwhile, the risk model had also shown to be an independent prognostic factor. Further functional enrichment analysis showed that cell adhesion, PI3K–AKT signaling pathway, and dysregulated immune status may be associated with PDAC development. External validation of the model was carried out in the GEO cohort, and the results were similar to that in the TCGA cohort. Finally, the expression of three genes was verified by qRT-PCR and immunohistochemical staining. Conclusion: The prognostic risk model established in this study can give a good prediction of the prognosis of PDAC patients, which might provide insights into clinical treatments and prognostic prediction of PDAC. [ABSTRACT FROM AUTHOR]

Carbon nanotube (CNT)-reinforced hydroxyapatite (HA) composites were successfully fabricated by a double in situ synthesis process, which combined the in situ synthesis of CNTs in HA powders by chemical vapor deposition (CVD) with the further encapsulation of CNTs using HA by a sol–gel method. This double in situ synthesis approach not only improves the homogeneous dispersion of CNTs within the HA matrix, but also enhances the interfacial bonding between the CNTs and HA, thus leading to enhanced mechanical properties. Flexural tests indicated that the flexural strength of the composite is 1.6 times higher than that of pure HA, and significantly higher than that of the commercial and in situ synthesized CNT/HA composites. Furthermore, the in vitro cell culture experiments indicated that the CNT/HA composites fabricated by this double in situ process significantly accelerate the proliferation of fibroblast cells (L-929), compared with those fabricated by traditional methods, confirming their biocompatibility. With this biocompatibility and excellent mechanical properties, the obtained CNT/HA composites have a high potential as biomaterials, particularly in bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

Purpose: To establish a new way for long-term vascular access for dialysis patient with vascular access exhaustion. Materials and Methods: A patient with diabetes was found with edema of right arm and high venous pressure of AVF during hemodialysis. Intervention operations were performed to establish a tunneled cuffed catheterization. Results: Occlusion of innominate vein was confirmed by MDCTV. Puncture to superior vena cava was successful 0.5 cm below the lateral head of sternocleidomastoid muscle directly via the right neck area. Conclusion: Direct puncture via superior vena cava might be the last choice for catheter insertion site. choice for catheter insertion site. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. We conducted this prospective, randomized, double-blind, placebo-controlled study to evaluate the effects of transcutaneous electric acupoint stimulation (TEAS) on the quality of recovery (QoR) and postoperative analgesia after gynecological laparoscopic surgery. Methods. 74 American Society of Anesthesiologists physical status (ASA) I or II patients undergoing gynecological laparoscopic surgery were randomly allocated to TEAS or control groups. The primary outcome was the quality of recovery, which was assessed on the day before surgery and 24 h after surgery using a 40-item questionnaire. Secondary outcomes included postoperative pain scores, the incidence of postoperative nausea and vomiting (PONV), duration of postanesthesia care unit (PACU) stay, and patient’s satisfaction. Results. The TEAS group had higher QoR scores than control group upon 24 h after surgery (177 versus 165; P<0.001). Compared with the control group, postoperative pain scores and the cumulative number of opioids administered were lower in the TEAS group patients (P=0.04). TEAS reduced the incidence of PONV and dizziness, as well as duration of PACU stay. Simultaneously, the patient’s satisfaction scores were higher in the TEAS group (P=0.002). Conclusion. Preoperative TEAS enhances QoR, improves postoperative analgesia and patient’s satisfaction, alleviates postoperative side effects, and accelerates discharge after general anesthesia for gynecological laparoscopic surgery. [ABSTRACT FROM AUTHOR]

The extracellular matrix (ECM) plays critical roles in cytoskeletal support, biomechanical transduction and biochemical signal transformation. Tumor-associated macrophage (TAM) function is regulated by matrix stiffness in solid tumors and is often associated with poor prognosis. ECM stiffness-induced mechanical cues can activate cell membrane mechanoreceptors and corresponding mechanotransducers in the cytoplasm, modulating the phenotype of TAMs. Currently, tuning TAM polarization through matrix stiffness-induced mechanical stimulation has received increasing attention, whereas its effect on TAM fate has rarely been summarized. A better understanding of the relationship between matrix stiffness and macrophage function will contribute to the development of new strategies for cancer therapy. In this review, we first introduced the overall relationship between macrophage polarization and matrix stiffness, analyzed the changes in mechanoreceptors and mechanotransducers mediated by matrix stiffness on macrophage function and tumor progression, and finally summarized the effects of targeting ECM stiffness on tumor prognosis to provide insight into this new field. [ABSTRACT FROM AUTHOR]

Background: A novel form of cell death termed cuproptosis was proposed recently. miRNAs play important roles in colorectal cancer (CRC). However, their relationships have not been reported. Methods: miRNAs that negatively regulate 16 cuproptosis regulators were predicted using Targetscan database. The univariate Cox, LASSO, and multivariate Cox regression analyses were performed to select cuproptosis‐related miRNAs. GSEA and ssGSEA analysis was carried out for functional enrichment analysis. The immune cell proportion score (IPS) and the efficiencies of multiple chemotherapy drugs were compared between different risk groups. The CCK8, cell colony, edu, and flow cytometry assays were performed to validate the roles of miRNA. Luciferase reporter assay confirmed the regulatory mechanism of miRNA on cuproptosis. Results: Six cuproptosis‐related miRNAs (hsa‐miR‐653, hsa‐miR‐216a, hsa‐miR‐3684, hsa‐miR‐4437, hsa‐miR‐641, and hsa‐miR‐552) were screened out for model construction. The risk score could act as an independent prognostic indicator in CRC (p < 0.001, 95% HR = 1.243 (1.129–1.369)). The nomogram could efficiently predict the overall survival rate (AUC = 0.836). Then, the level of immunosuppressive pathways, immunosuppressive cells, stromal‐activated genes, and stromal score was higher in the high‐risk group. The IPS analysis showed a better response to immunotherapy in the low‐risk group. Also, the risk score was closely correlated with efficiencies of multiple chemotherapy drugs. Furthermore, miR‐653 was highly expressed in CRC tissues (p < 0.001), closely correlated with T stage (p < 0.001), metastasis (p < 0.001), and tumor stage (p < 0.001). High expression of miR‐653 predicted a shorter overall survival (p = 0.0282) and disease‐free survival (p = 0.0056). In addition, miR‐653 promoted cell proliferation, inhibited apoptosis, and negatively regulated the expression of DLD through directly binding to the 3'‐UTR of DLD mRNA. Conclusion: We constructed a cuproptosis‐related miRNA signature for the prediction of CRC patient survival and immunotherapy sensitivity. miR‐653 was highly expressed in CRC tissues, promoted cell proliferation, and inhibited apoptosis by negatively regulating the expression of DLD. [ABSTRACT FROM AUTHOR]

Background/Aims: Although endoscopic metal biliary endoprosthesis (EMBE) is widely accepted as the most suitable drainage method for patients with unresectable malignant obstruction, uncontrolled post-procedural cholangitis is still a problem. We aimed to validate a new treatment modality to prevent post-ERCP cholangitis in patients with unresectable cholangiocarcinoma. Patients and Methods: A total of 378 patients who were diagnosed with unresectable malignant biliary obstruction and underwent EMBE or temporary endoscopic nasobiliary drainage (ENBD) following EMBE placement, from January 2010 to July 2016, were enrolled in this retrospective study. Incidence of cholangitis, related infectious indicators, success rate of biliary drainage, and occurrence of complications were evaluated. Results: The risk of overall cholangitis and related infectious indicators was significantly lower in EMBE plus ENBD group than that in EMBE group. The occurrence of cholangitis was 2.4% versus 11.9% (P = 0.004). On further analysis of subgroups, although no difference was detected in nonhilar cholangiocarcinoma subgroup, the incidence of cholangitis and related infectious indicators in hilar cholangiocarcinoma subgroup with EMBE modality were distinctly higher than that with EMBE plus ENBD modality (type I + II was 18.5% vs 0%, P < 0.05; type III + IV was 19.8% vs 3.8%, P < 0.05). No significant difference was found in successful biliary drainage rate and procedure-related complications when all subgroups were compared. Conclusions: The temporary placement of ENBD following EMBE is a simple and effective treatment modality to prevent post-ERCP cholangitis, especially in patients with hilar cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Increasing evidence shows that selenium and polyphenols are two types of the most reported compounds in tumor chemoprevention due to their remarkable antitumor activity and high safety profile. The cross-talk between polyphenols and selenium is a hot research topic, and the combination of polyphenols and selenium is a valuable strategy for fighting cancer. The current work investigated the combination anti-peritoneal carcinomatosis (PC) effect of selenium nanoparticles (SeNPs) and green tea (Camellia sinensis) polyphenol (-)-epigallocatechin-3-gallate (EGCG) in mice bearing murine hepatocarcinoma 22 (H22) cells. Results showed that SeNPs alone significantly inhibited cancer cell proliferation and extended the survival time of mice bearing H22 cells. Still, the potential therapeutic efficacy is accompanied by an approximately eighty percent diarrhea rate. When EGCG was combined with SeNPs, EGCG did not affect the tumor proliferation inhibition effect but eliminated diarrhea triggered by SeNPs. In addition, both the intracellular selectively accumulated EGCG without killing effect on cancer cells and the enhanced antioxidant enzyme levels in ascites after EGCG was delivered alone by intraperitoneal injection indicated that H22 cells were insensitive to EGCG. Moreover, EGCG could prevent SeNP-caused systemic oxidative damage by enhancing serum superoxide dismutase, glutathione, and glutathione peroxidase levels in healthy mice. Overall, we found that H22 cells are insensitive to EGCG, but combining EGCG with SeNPs could protect against SeNP-triggered diarrhea without compromising the suppressing efficacy of SeNPs on PC in mice bearing H22 cells and attenuate SeNP-caused systemic toxicity in healthy mice. These results suggest that EGCG could be employed as a promising candidate for preventing the adverse reactions of chemotherapy including chemotherapy-induced diarrhea and systemic toxicity in cancer individuals. [ABSTRACT FROM AUTHOR]

The present study focused on the RGM (repulsive guidance molecule) a and RGMb expression in cerebral cortex and hippocampus of newborn mice with maternal lead exposure. Lead exposure initiated from gestation to weaning. Lead acetate was dissolved in deionized water with concentrations of 0.1%, 0.2% and 0.5% groups respectively. On the 21st postnatal day, lead in blood and tissue levels was examined by GFAAS. The protein expressions of RGMa and RGMb in hippocampus and cerebral cortex tissues were tested by western blotting and immunohistochemistry. Comparing with the control group, the lead levels in blood, cerebral cortex and hippocampus of newborn mice in 0.1%, 0.2% and 0.5% lead exposure groups were remarkably higher (P < 0.05). Compared with the control group, the RGMa and RGMb expression in hippocampus were upregulated in lead exposed groups (P < 0.05), and the RGMa and RGMb expression in cerebral cortex were also higher (P < 0.05). The increased expression of RGMa and RGMb in hippocampus and cerebral cortex may lead to the neurotoxicity in the context of maternal lead exposure. [ABSTRACT FROM AUTHOR]

Synthetic oligodeoxyribonucleotides containing CpG dinucleotides exhibit potent immunostimulatory activity in vertebrates. Although the molecular mechanisms of recognition and interaction of CpG DNA sequences with receptors are not well understood, the current evidence suggests that the receptor shows considerable selectivity for CpG DNA sequences with different preferences in mouse (GACGTT) and human (GTCGTT) species. In our continued effort to understand the chemical and structural characteristics of CpG DNA required for the immunostimulatory activity and thereby for the recognition of receptors in the immunostimulatory pathway, we examined the requirement of nucleobases in the two adjacent nucleotide positions on the 5′- and the 3′-side to the CpG dinucleotide (P1P2CGP3P4) for the immunostimulatory activity. These studies, in which a natural nucleoside is substituted with an abasic nucleoside (X), suggest that a nucleobase is absolutely required in C, G, P3, and P4 positions for immunostimulatory activity. Surprisingly, an abasic nucleoside is permitted at either P1 or P2 depending on the neighboring base. It was found that ‘GXCGTT’ motif has an intermediate immunostimulatory activity between those of ‘GACGTT’ and ‘GTCGTT’ in the mouse cells. [Copyright &y& Elsevier]

Background. Esophageal cancer is one of the most deadly malignant tumors. Among the common malignant tumors in the world, esophageal cancer is ranked seventh, which has a high mortality rate. Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of various tumors. lncRNAs can competitively bind microRNAs (miRNAs) with mRNA, which can regulate the expression level of the encoded gene at the posttranscriptional level. This regulatory mechanism is called the competitive endogenous RNA (ceRNA) hypothesis, and ceRNA has important research value in tumor-related research. However, the regulation of lncRNAs is less studied in the study of esophageal cancer. Methods. The Cancer Genome Atlas (TCGA) database was used to download transcriptome profiling data of esophageal cancer. Gene expression quantification data contains 160 cancer samples and 11 normal samples. These data were used to identify differentially expressed lncRNAs and mRNAs. miRNA expression data includes 185 cancer samples and 13 normal samples. The differentially expressed RNAs were identified using the edgeR package in R software. Then, the miRcode database was used to predict miRNAs that bind to lncRNAs. MiRTarBase, miRDB, and TargetScan databases were used to predict the target genes of miRNAs. Cytoscape software was used to draw ceRNA network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using DAVID 6.8. Finally, multifactor cox regression was used to screen lncRNAs related to prognosis. Results. We have screened 1331 DElncRNAs, 3193 DEmRNAs, and 162 DEmiRNAs. Among them, the ceRNA network contains 111 lncRNAs, 11 miRNAs, and 63 DEmRNAs. Finally, we established a prediction model containing three lncRNAs through multifactor Cox regression analysis. Conclusions. Our research screened out three independent prognostic lncRNAs from the ceRNA network and constructed a risk assessment model. This is helpful to understand the regulatory role of lncRNAs in esophageal cancer. [ABSTRACT FROM AUTHOR]

Background. Esophageal cancer is one of the most deadly malignant tumors. Among the common malignant tumors in the world, esophageal cancer is ranked seventh, which has a high mortality rate. Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of various tumors. lncRNAs can competitively bind microRNAs (miRNAs) with mRNA, which can regulate the expression level of the encoded gene at the posttranscriptional level. This regulatory mechanism is called the competitive endogenous RNA (ceRNA) hypothesis, and ceRNA has important research value in tumor-related research. However, the regulation of lncRNAs is less studied in the study of esophageal cancer. Methods. The Cancer Genome Atlas (TCGA) database was used to download transcriptome profiling data of esophageal cancer. Gene expression quantification data contains 160 cancer samples and 11 normal samples. These data were used to identify differentially expressed lncRNAs and mRNAs. miRNA expression data includes 185 cancer samples and 13 normal samples. The differentially expressed RNAs were identified using the edgeR package in R software. Then, the miRcode database was used to predict miRNAs that bind to lncRNAs. MiRTarBase, miRDB, and TargetScan databases were used to predict the target genes of miRNAs. Cytoscape software was used to draw ceRNA network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using DAVID 6.8. Finally, multifactor cox regression was used to screen lncRNAs related to prognosis. Results. We have screened 1331 DElncRNAs, 3193 DEmRNAs, and 162 DEmiRNAs. Among them, the ceRNA network contains 111 lncRNAs, 11 miRNAs, and 63 DEmRNAs. Finally, we established a prediction model containing three lncRNAs through multifactor Cox regression analysis. Conclusions. Our research screened out three independent prognostic lncRNAs from the ceRNA network and constructed a risk assessment model. This is helpful to understand the regulatory role of lncRNAs in esophageal cancer. [ABSTRACT FROM AUTHOR]

Achieving ordered arrangement of gold nanoparticles (AuNPs) on an electrode can further improve the signal intensity of an electrochemical immunosensor. This ordered AuNPs self-assembly can be inspired by peptide amphiphile (PA). The rational design of hydrophobic chains in PA is a crucial step when the range of hydrophobic alkane chain from 14 to 18 carbons. As arginine (R) can combine specifically with Au surface plane (111), four PAs, i.e., C 15 H 23 CO-RR (C16R2), C 15 H 23 CO-RRR (C16R3), C 15 H 23 CO-RRRR (C16R4), and C 15 H 23 CO-RRRRR (C16R5), in this work are designed to investigate the extent of ordered AuNPs self-assembly. The results indicate that C16R4 presented a dominant electron donating ability and can inspire the self-assembly of AuNPs to form a mono-dispersed raspberry-like structure (C16R4-AuNPs) to obtain the largest ΔI (15.4 μA). In the detection system, C16R4-AuNPs firstly capture and immobilize anti-β-lactam receptor monoclonal antibodies (mAb) by electrostatic adsorption, and the anti-β-lactam receptor mAb possess antigen-antibody binding sites away from the active site of the receptors. Then, they capture β-lactam receptors through an antigen-antibody reaction to form a ternary complex (C16R4-AuNPs-mAb-β-lactam receptors). Based on this indirect-labeling process, the receptor active sites have been exposed completely, facilitating ligand recognition, which greatly further improves the sensitivity of the present method. Finally, a highly sensitive electrochemical immunosensor based on the ternary complex is developed to achieve the determination of 22 β-lactam antibiotics, which is more sensitive and applicable than other reported electrochemical sensors. [ABSTRACT FROM AUTHOR]

Although the patient's survival time in various cancers has significantly increased in recent decades, the overall 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) has remained virtually unchanged due to rapid progression and metastasis. While N -acetyltransferase 10 (NAT10) has been identified as a regulator of mRNA acetylation in many malignancies, its role in PDAC remains unclear. Here, we found that NAT10 mRNA and protein levels were upregulated in PDAC tissues. Increased NAT10 protein expression was significantly correlated with poor prognosis in PDAC patients. Through our experiments, we demonstrated that NAT10 acted as an oncogene to promote PDAC tumorigenesis and metastasis in vitro and in vivo. Mechanistically, NAT10 exerts its oncogenic effects by promoting mRNA stability of receptor tyrosine kinase AXL in an ac4C-dependent manner leading to increased AXL expression and further promoting PDAC cell proliferation and metastasis. Together, our findings highlight the critical of NAT10 in PDAC progression and reveal a novel epigenetic mechanism by which modified mRNA acetylation promotes PDAC metastasis. [ABSTRACT FROM AUTHOR]

Abstract: Alzheimer’s disease (AD), a chronic neurodegenerative disorder associated with the abnormal accumulations of amyloid β (Aβ) peptide and oxidative stress in the brain, is the most common form of dementia among the elderly. Crude caffeine (CC), a major by-product of the decaffeination of coffee, has potent hydrophilic antioxidant activity and may reduce inflammatory processes. Here, we showed that CC and pure caffeine intake had beneficial effects in a mouse model of AD. Administration of CC or pure caffeine for 2months partially prevented memory impairment in AD mice, with CC having greater effects than pure caffeine. Furthermore, consumption of CC, but not pure caffeine, reduced the Aβ1–42 levels and the number of amyloid plaques in the hippocampus. Moreover, CC and caffeine protected primary neurons from Aβ-induced cell death and suppressed Aβ-induced caspase-3 activity. Our data indicate that CC may contain prophylactic agents against the cell death and the memory impairment in AD. [Copyright &y& Elsevier]

Oligodeoxynucleotides containing CpG dinucleotides in specific sequence contexts activate the vertebrate immune system. Our previous studies showed that the 5′-end of a CpG oligonucleotide should be accessible for receptor recognition and subsequent immune stimulation. Activity is abrogated if this end is blocked by joining two CpG oligos through 5′–5′ linkage. It was not known whether a similar effect would arise from secondary structures at either end of a CpG oligo, such as hairpin loops or terminal dimers. In the present study we found that 5′-terminal secondary structures affect activity significantly more than those at the 3′-end. The need for an open 5′-end suggests that the receptor responsible for immune stimulation reads the DNA sequence from this end. These results may also provide insights to place CpG motifs appropriately in DNA vaccines to induce additional Th1 type responses. [Copyright &y& Elsevier]

The occurrence and development of silicosis is related to the interaction of multiple cells through signal transmission caused by silica dust. Including inflammatory changes reduced by macrophages and phenotypic transdifferentiation reduced by lung fibroblasts. As a communication medium between cells, exosomes have become a hot research topic. To explore the role of exosomal proteins in the occurrence and development of silicosis and the possible intervention targets, this study conducted proteomic analysis of macrophage-derived exosomes induced by silica, to identify specific proteins for intervention. In this study, we used proteomic analysis to screen exosomal protein profiles from the RAW264.7 macrophages exposed to silica. A total of 291 proteins were differentially expressed, of which 178 were upregulated and 113 were downregulated. By performing functional annotation and analysis of the differentially expressed proteins, we identified proteins SPP1, HMGB3, and HNRNPAB, which were consistent with the proteomics analysis. The involvement of SPP1 protein in fibrosis was studied further. Knocking down the expression of SPP1 in exosomes resulted in a decrease in fibrosis-related indicators. These results help to understand that exosomal protein can mediate cell communication and play a key role in the transition from fibroblasts to myofibroblasts. Further, this study also provided strategies and scientific basis for future studies on the intervention of silicosis • The exosomes of macrophages exposed to silica promoted fibroblasts transdifferentiation. • The expression profile of the exosomal protein of the silica-exposed macrophages changed. • Knockdown of SPP1 protein in exosomes can inhibit the process of fibroblasts transdifferentiation. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most frequent malignant bone cancer in teenagers. In this study, cell division cycle 6 (Cdc6) was upregulated in the tumor tissues from patients with osteosarcoma according to the results of RNA sequencing. Cdc6 has been considered as a candidate prognostic marker, which was associated with cell apoptosis and cell cycle. However, the mechanisms by which Cdc6 regulates the apoptosis and cell cycle arrest in osteosarcoma remain unclear. Firstly, 3 pairs of osteosarcoma and adjacent normal tissues were subjected to RNA sequencing. In addition, the levels of Cdc6 in 30 pairs of patients' tissues and in osteosarcoma cell lines were detected by western blotting and RT-qPCR. Moreover, the effects of Cdc6 on cell proliferation, apoptosis, cell cycle and invasion were evaluated by cell counting kit-8 (CCK-8), flow cytometric and transwell assay, respectively. Cdc6 was significantly upregulated in patients with osteosarcoma and in osteosarcoma cell lines. Downregulation of Cdc6 inhibited the proliferation and invasion of MG63 cells by promoting apoptosis. In addition, downregulation of Cdc6 induced G1 phase cell cycle arrest. Moreover, inhibition of Cdc6 downregulated the expression of Cyclin D1 and Cyclin A2, and upregulated the level of p21 in MG63 cells. In vivo study confirmed downregulation of Cdc6 inhibited osteosarcoma tumor growth by inducing apoptosis. Our findings indicated that Cdc6 may serve as an oncogene in osteosarcoma. Thus, inhibiting Cdc6 may be a therapeutic approach for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]