Ganoderic acid A mitigates dopaminergic neuron ferroptosis via inhibiting NCOA4-mediated ferritinophagy in Parkinson's disease mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum, a renowned tonic traditional Chinese medicine, is widely recognized for the exceptional activity in soothing nerves and nourishing the brain. It has been extensively employed to alleviate various neurological disorders, notably Parkinson's disease (PD). AIM OF THE STUDY: To appraise the antiparkinsonian effect of GAA, the main bioactive constituent of G. lucidum, and clarify the molecular mechanism through the perspective of ferritinophagy-mediated dopaminergic neuron ferroptosis. MATERIALS AND METHODS: PD mouse and cell models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+), respectively. Cell viability, behavioral tests and immunofluorescence analysis were performed to evaluate the neurotoxicity, motor dysfunction and dopaminergic loss, respectively. Biochemical assay kits were used to determine the levels of iron, lipid reactive oxygen species (ROS), malondialdehyde (MDA), total ROS and glutathione (GSH). Western blot and immunofluorescence were applied to detect the expressions of nuclear receptor co-activator 4 (NCOA4), ferritin heavy chain 1 (FTH1), p62 and LC3B. Additionally, NCOA4-overexpressing plasmid vector was constructed to verify the inhibitory effect of GAA on the neurotoxicity and ferroptosis-related parameters in PD models. RESULTS: GAA significantly mitigated MPP+/MPTP-induced neurotoxicity, motor dysfunction and dopaminergic neuron loss (p＜0.01 or p＜0.05). In contrast to MPP+/MPTP treatment, GAA treatment decreased the levels of iron, MDA, lipid and total ROS, while increasing the GSH level. GAA also reduced the levels of NCOA4 and LC3B, and enhanced the expressions of FTH1 and p62 in PD models (p＜0.01 or p＜0.05). However, the protective effect of GAA against the neurotoxicity, NCOA4-mediated ferritinophagy and ferroptosis in PD model was abolished by the overexpression of NCOA4 (p＜0.01). CONCLUSION: GAA exerted a protective effect on PD, and this effect was achieved by suppressing dopaminergic neuron ferroptosis through the inhibition of NCOA4-mediated ferritinophagy.

Prognostic Value of Inflammatory Cytokines in Predicting Hospital Readmissions in Heart Failure with Preserved Ejection Fraction.

Purpose: The aim of this study was to explore the relationship between inflammatory cytokines and the risk of heart failure (HF) readmission in patients with heart failure with preserved ejection fraction (HFpEF). Patients and Methods: We enrolled 429 patients with HFpEF admitted to the cardiology department in our hospital from January 2020 to July 2022. The patients were divided into the readmission or non-readmission groups according to whether they were readmitted for heart failure within 1 year of discharge. The clinical features and laboratory date of the subjects were collected and analyzed. Multivariate cox regression analysis was used to identify predictors of HF readmission. In addition, receiver operating characteristic (ROC) curves were used to determine the prognostic value of each factor. Results: The levels of IL-1ß, IL-6, IL-10, IL-17, TNF-α, NT-proBNP, heart rate, total cholesterol and NYHA class were significantly higher in the readmission group than in the non-readmission group (p < 0.05). IL-1ß, IL-6, IL-17, TNF-α, NT-proBNP, heart rate and NYHA class were identified as independent predictors of HF readmission. Conclusion: Inflammatory markers, including IL-1ß, IL-6, IL-17 and TNF-α were related to the HF readmission in patients with HFpEF.

Rapid Discovery of Aß42 Fibril Disintegrators from Ganoderma lucidum via Ligand Fishing and Their Neuroprotective Effects on Alzheimer's Disease.

An amyloid-ß (Aß) fibril is a vital pathogenic factor of Alzheimer's disease (AD). Aß fibril disintegrators possess great potential to be developed into novel anti-AD agents. Here, a ligand fishing method was employed to rapidly discover Aß42 fibril disintegrators from Ganoderma lucidum using Aß42 fibril-immobilized magnetic beads, which led to the isolation of six Aß42 fibril disintegrators including ganodermanontriol, ganoderic acid DM, ganoderiol F, ganoderol B, ganodermenonol, and ergosterol. Neuroprotective evaluation in vitro exhibited that these Aß42 fibril disintegrators could significantly mitigate Aß42-induced neurotoxicity. Among these six disintegrators, ergosterol and ganoderic acid DM with stronger protecting activity were further selected to evaluate their neuroprotective effect on AD in vivo. Results showed that ergosterol and ganoderic acid DM could significantly alleviate Aß42-induced cognitive dysfunction and hippocampus neuron loss in vivo. Moreover, ergosterol and ganoderic acid DM could significantly inhibit Aß42-induced neuron apoptosis and Nrf2-mediated neuron oxidative stress in vitro and in vivo.

An effective framework for predicting drug-drug interactions based on molecular substructures and knowledge graph neural network.

Drug-drug interactions (DDIs) play a central role in drug research, as the simultaneous administration of multiple drugs can have harmful or beneficial effects. Harmful interactions lead to adverse reactions, some of which can be life-threatening, while beneficial interactions can promote efficacy. Therefore, it is crucial for physicians, patients, and the research community to identify potential DDIs. Although many AI-based techniques have been proposed for predicting DDIs, most existing computational models primarily focus on integrating multiple data sources or combining popular embedding methods. Researchers often overlook the valuable information within the molecular structure of drugs or only consider the structural information of drugs, neglecting the relationship or topological information between drugs and other biological objects. In this study, we propose MSKG-DDI - a two-component framework that incorporates the Drug Chemical Structure Graph-based component and the Drug Knowledge Graph-based component to capture multimodal characteristics of drugs. Subsequently, a multimodal fusion neural layer is utilized to explore the complementarity between multimodal representations of drugs. Extensive experiments were conducted using two real-world datasets, and the results demonstrate that MSKG-DDI outperforms other state-of-the-art models in binary-class, multi-class, and multi-label prediction tasks under both transductive and inductive settings. Furthermore, the ablation analysis further confirms the practical usefulness of MSKG-DDI.

Prediction of cancer recurrence based on compact graphs of whole slide images.

Cancer recurrence is one of the primary causes of patient mortality following treatment, indicating increased aggressiveness of cancer cells and difficulties in achieving a cure. A critical step to improve patients' survival is accurately predicting recurrence status and giving appropriate treatment. Whole Slide Images (WSIs) are a common type of image data in the field of digital pathology, containing high-resolution tissue information. Furthermore, WSIs of primary tumors contain microenvironmental information directly associated with the growth of tumor cells. To effectively utilize this microenvironmental information. Firstly, we represented microenvironmental features of histopathological images as compact graphs. Secondly, this work aims to develop an enhanced lightweight graph neural network called the Adaptive Graph Clustering Network (AGCNet) for predicting cancer recurrence. Experiments are conducted on three cancer datasets from The Cancer Genome Atlas (TCGA), and AGCNet achieved an accuracy of 81.81% in BLCA, 69.66% in PAAD, and 81.96% in STAD. These results indicated that AGCNet is an effective model for predicting cancer recurrence and is expected to be applied in clinical applications.

Integrated network pharmacology and metabolomics analyses of the mechanism underlying the efficacy of Ma-Mu-Ran Antidiarrheal Capsules against dextran sulfate sodium-induced ulcerative colitis.

The current study utilizes a comprehensive network pharmacology and metabolomics analysis to investigate the mechanism of action of Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) for the treatment of ulcerative colitis (UC). In this study, we established a mouse model of UC using dextran sulfate sodium. Colonic tissues were collected from mice and then subjected to hematoxylin and eosin staining, as well as histopathological analysis, to assess the therapeutic effect of MMRAC. Furthermore, we assessed the mechanisms through which MMRAC combats UC by employing integrated metabolomics and network pharmacology strategies. Lastly, we validated the key targets identified through western blot and molecular docking. An integrated network of metabolomics and network pharmacology was constructed using Cytoscape to identify eight endogenous metabolites involved in the therapeutic action of MMRAC on UC. Further comprehensive analyses were focused on four key targets and their associated core metabolites and pathways. The results of western blot and molecular docking demonstrated that MMRAC could modulate key targets and their expression levels. The cumulative results indicated that MMRAC restored intestinal function in UC, reduced inflammatory responses, and alleviated oxidative stress by influencing the methionine and cysteine metabolic pathways, as well as the urea cycle. In addition, it had an impact on arginine, proline, glutamate, aspartate, and asparagine metabolic pathways and their associated targets.

Association between the systemic immune-inflammation index and outcomes among atrial fibrillation patients with diabetes undergoing radiofrequency catheter ablation.

PURPOSE: To investigate the relationship between the incidence of atrial fibrillation (AF) recurrence and the levels of the systemic immune-inflammatory index (SII, platelet × neutrophil/lymphocyte ratio) in patients with AF and diabetes mellitus (DM) undergoing after radiofrequency catheter ablation (RFCA). PATIENTS AND METHODS: Preoperative SII levels were determined in AF patients with DM undergoing RFCA. Restricted cubic splines were used to determine the correlation between SII and the risk of AF recurrence. Multivariate-adjusted logistic regression models were constructed to determine the relationship between SII levels and AF recurrence. The predictive value of the clinical model and combined with the SII index was estimated by the area under the receiver-operating characteristic curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: A total of 204 patients with AF and DM who underwent RFCA in our hospital were included. Seventy-seven patients had AF recurred during a mean follow-up of 20 months. Restricted cubic spline analysis showed that when SII ≥ 444.77 × 109 /L, there was a positive correlation with the incidence of AF recurrence. In addition, adding the SII to the predictive model for AF recurrence after RFCA in patients with DM and AF could contribute to an increase in C-statistics (0.798 vs. 0.749, p = .034). After SII was incorporated into the clinical model, the comprehensive discrimination and net reclassification tended to improve (IDI and NRI > 0, p < .05). CONCLUSION: SII was independently and positively associated with recurrence after the first catheter ablation in patients with DM and AF.

Pattern of lifestyle behaviors and associated risk of being bullied at schools: A latent class analysis of 25,379 adolescents in Jiangsu Province of China.

School bullying is a worldwide problem. Although previous studies examined the association between different lifestyle behaviors and bullying victimization, the complex co-occurrence of these behaviors was not identified, and their association with the risk of being bullied remains unclear. We aimed to identify the behavioral patterns of adolescents and to explore their association with bullying victimization. This cross-sectional study employed data from the "Surveillance for Common Diseases and Health Risk Factors among Students" project implemented in Jiangsu Province of China in 2019, and a total of 25,379 school-enrolled students were included. We used a latent class analysis to identify behavioral patterns and a regression mixture model to explore various demographic characteristics, such as age, sex, and family structure in relation to bullying victimization across different patterns. We considered respondents having targeted behaviors, including smoking, alcohol consumption, illicit drug use, sugar consumption, no fruit consumption, low physical activity, electronic media use, and insufficient sleep. Four behavioral patterns were identified, including the "adolescents without apparent targeted behaviors" (19.65%), "substance and electronic media users" (12.76%), "typical electronic media users" (54.49%), and "typical substance users" (8.10%). The risk of being bullied was the highest in the "substance and electronic media users" (probability: 0.33), tripled that in "adolescents without apparent targeted behaviors" (odds ratio: 3.60, 95% confidence interval: 3.01-4.30). Risk of being bullied was reduced for those "substance and electronic media users" living with a nuclear family. Behavioral patterns and their association with being bullied differ between groups of school-aged adolescents. To better inform decision-making based on the current real-world findings, the implementation of bullying prevention programs could target specific behavioral patterns.

Biosorption and bioreduction of aqueous chromium (VI) by different Spirulina strains.

Spirulina has emerged as a promising microorganism for the treatment of industrial heavy metal ions in wastewater due to their simplicity of cultivation and harvesting, rich functional binding groups, and high bioreductive activity during the uptake process. While the capacities of biosorption and bioreduction for heavy metal ions differ significantly among various algal strains. Therefore, the physiological characteristics were investigated to identify the different Spirulina strains, and the chromium (VI) adsorption capacities of the algal strains were also evaluated. In this study, it was found that algal strains YCX2643 and CLQ1848 performed higher removal efficiency (86.5% and 83.7%) than the other four Spirulina strains (59.4%, 56.3%, 65.6%, and 66.5%, respectively). Moreover, the mechanisms of chromium (VI) ions binding and biotransformation in the Spirulina cell were scrutinized by FTIR (Fourier transform infrared) spectroscopy and scanning electron microscopy (SEM), and it indicated that the varieties of cellular components involved in high binding affinity may cause the higher biosorption and bioreduction of aqueous chromium (VI) in algal strains YCX2643 and CLQ1848, which could be used as promising biosorbents in the removing heavy metal pollutants from wastewaters.

A novel prognostic signature contributes to precision treatment in colon adenocarcinoma with KRAS mutation.

BACKGROUND: Approximately 40% of colon cancer harbor Kirsten rat sarcoma viral oncogene ( KRAS ) mutations, but the prognostic value of KRAS mutations in colon cancer is still controversial. METHODS: We enrolled 412 colon adenocarcinoma (COAD) patients with KRAS mutations, 644 COAD patients with KRAS wild-type and 357 COAD patients lacking information on KRAS status from five independent cohorts. A random forest model was developed to estimate the KRAS status. The prognostic signature was established using least absolute shrinkage and selection operator-Cox regression and evaluated by Kaplan-Meier survival analysis, multivariate-Cox analysis, receiver operating characteristic curve and nomogram. The expression data of KRAS -mutant COAD cell lines from the Cancer Cell Line Encyclopedia database and the corresponding drug sensitivity data from the Genomics of Drug Sensitivity in Cancer database were used for potential target and agent exploration. RESULTS: We established a 36-gene prognostic signature classifying the KRAS -mutant COAD as high and low risk. High risk patients had inferior prognoses compared to those with low risk, while the signature failed to distinguish the prognosis of COAD with KRAS wild-type. The risk score was the independent prognostic factor for KRAS -mutant COAD and we further fabricated the nomograms with good predictive efficiency. Moreover, we suggested FMNL1 as a potential drug target and three drugs as potential therapeutic agents for KRAS -mutant COAD with high risk. CONCLUSION: We established a precise 36-gene prognostic signature with great performance in prognosis prediction of KRAS -mutant COAD providing a new strategy for personalized prognosis management and precision treatment for KRAS -mutant COAD.

Joint Contributions of Depression and Insufficient Sleep to Self-Harm Behaviors in Chinese College Students: A Population-Based Study in Jiangsu, China.

Self-harm in young people is common, and previous studies have shown that insufficient sleep or depression was associated with self-harm. However, the joint association of insufficient sleep and depression with self-harm is unknown. We employed representative population-based data from the "Surveillance for Common Disease and Health Risk Factors Among Students in Jiangsu Province 2019" project. College students reported their self-harm behavior over the past year. Rate ratios (RRs) and corresponding 95% confidence intervals (CIs) for self-harm in relation to sleep and depression were modeled using negative binomial regression with a sample population as an offset, adjusting for age, gender, and region. The instrumental variable approach was used for the sensitivity analyses. Of the study population, approximately 3.8% reported self-harm behaviors. Students with sufficient sleep experienced a lower risk of self-harm than those with insufficient sleep. Compared with students with sufficient sleep and the absence of depression, the adjusted risk of self-harm was elevated 3-fold (1.46-4.51) in those reporting insufficient sleep in the absence of depression, 11-fold (6.26-17.77) in those with sufficient sleep and definite depression, and 15-fold (8.54-25.17) in those with both insufficient sleep and definite depression. The sensitivity analyses indicate that insufficient sleep remained a contributing risk factor for self-harm. Lack of sleep in young people is significantly associated with self-harm, particularly in the presence of depression. The provision of mental health care and attention to sleep deprivation are particularly important for college students.

Design, methodology, and baseline of eastern China student health and wellbeing cohort study.

Purpose: To describe the study design, methodology, and cohort profile of the Eastern China Student Health and Wellbeing Cohort Study. The cohort baseline includes (1) targeted disease (myopia, obesity, elevated blood pressure, and mental health) and (2) exposures (individual behaviors, environment, metabolomics, and gene and epigenetics). Participants: Annual physical examination, questionnaire-based survey, and bio-sampling have been carried out in the study population. In the first stage (2019-2021), a total of 6,506 students in primary schools are enrolled in the cohort study. Findings to date: Of all the cohort participants, the ratio of male to female is 1.16 among a total of 6,506 student participants, of which 2,728 (41.9%) students are from developed regions and 3,778 (58.1%) students are from developing regions. The initial age of observation is 6-10 years, and they will be observed until they graduate from high school (>18 years of age). (1) Targeted diseases: The growth rates of myopia, obesity, and high blood pressure vary by regions, and for developed regions, the prevalence of myopia, obesity, and elevated blood pressure is 29.2%, 17.4%, and 12.6% in the first year, respectively. For developing regions, the prevalence of myopia, obesity, and elevated blood pressure is 22.3%, 20.7%, and 17.1% in the first year, respectively. The average score of CES-D is 12.9 ± 9.8 in developing regions/11.6 ± 9.0 in developed regions. (2) Exposures: ① The first aspect of individual behaviors: the questionnaire topics include diet, physical exercise, bullying, and family. ② The second aspect of environment and metabolomics: the average desk illumination is 430.78 (355.84-611.56) LX, and the average blackboard illumination is 365.33 (286.83-516.84) LX. Metabolomics like bisphenol A in the urine is 0.734 ng/ml. ③ The third aspect of gene and epigenetics: SNPs (rs524952, rs524952, rs2969180, rs2908972, rs10880855, rs1939008, rs9928731, rs72621438, rs9939609, rs8050136 and so on) are detected. Future plans: Eastern China Student Health and Wellbeing Cohort Study is aiming to focus on the development of student-targeted diseases. For children with student common diseases, this study will focus on targeted disease-related indicators. For children without targeted disease, this study aims to explore the longitudinal relationship between exposure factors and outcomes, excluding baseline confounding factors. Exposure factors include three aspects: (1) individual behaviors, (2) environment and metabolomics, and (3) gene and epigenetics. The cohort study will continue until 2035.

Transcriptomics and metabolomics revealed the pulmonary protective mechanism of Xixin-Ganjiang Herb Pair for warming the lungs to dissolve phlegm in COPD rats.

Xixin-Ganjiang Herb Pair (XGHP), a classic combination treatment to warm the lungs and dissolve phlegm, is widely used in the treatment of various pulmonary diseases. Chronic obstructive pulmonary disease (COPD) refers to a group of chronic obstructive airway diseases that can seriously harm human health. However, the effective components, targets, and pathways that underlie XGHP in the treatment of COPD remain unclear. Therefore, this study initially identified the effective components of XGHP through the use of UPLC-MS/MS and pharmacologic methods of traditional Chinese medicine. Secondly, transcriptomic analysis of the lung tissues of rats revealed the pharmacodynamic transcripts of each group, and metabolomics analysis revealed the differential metabolites associated with XGHP treatment. Finally, molecular docking of effective components with transcriptome genes was performed and western blotting was performed in order to determine the expression of related proteins in rat lung tissue. Overall, 30 effective components of XGHP were identified, including L-asarinin, 6-gingerol, sesamin, kaempferol, and quercetin. Transcriptomic studies demonstrated that expression of 386 genes recovered after XGHP treatment, and that they were mainly enriched in the oxidative phosphorylation and AMPK signaling pathways. According to the metabolomics studies, expression of eight metabolites differed between the COPD and the XGHP groups. These metabolites were mainly involved the biosynthesis of unsaturated fatty acids. Finally, the transcriptomic and metabolomics data were integrated. FASN and SCD in AMPK signaling pathway were directly linked to certain metabolites, including linoleic acid, palmitic acid, and oleic acid. These results indicate that XGHP can inhibit pAMPK expression and negatively regulate FASN and SCD expression during treatment of COPD in order to enhance the biosynthesis of unsaturated fatty acids and maintain energy homeostasis.

Metabolomics integrated network pharmacology reveals the mechanism of Ma-Mu-Ran Antidiarrheal Capsules on acute enteritis mice.

Acute enteritis (AE) is a type of digestive disease caused by biochemical factors that irritate the intestinal tract or pathogenic bacteria that infect it. In China, Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) have been applied against diarrhea caused by AE and bacillary dysentery for many years, but the underlying mechanisms of their beneficial effects are not known. In the present study, network pharmacology and metabolomics were performed to clarify the active ingredients of MMRAC and explore the specific mechanism of MMRAC on AE mice. A total of 43 active components of MMRAC with 87 anti-AE target genes were identified, and these target genes were enriched in IL-17 and HIF-1 signaling pathways. Integration analysis revealed that purine metabolism was the critical metabolic pathway by which MMRAC exerted its therapeutic effect against AE. Specifically, MAPK14, MMP9, PTGS2, HIF1A, EGLN1, NOS2 were the pivotal targets of MMRAC for the treatment of AE, and Western blot analysis revealed MMRAC to decrease protein levels of these pro-inflammatory signaling molecules. According to molecular docking, these key targets have a strong affinity with the MMRAC compounds. Collectively, MMRAC relieved the colon inflammation of AE mice via regulating inflammatory signaling pathways to reduce hypoxia and improved energy metabolism.

Dendrobium huoshanense stem polysaccharide ameliorates alcohol-induced gastric ulcer in rats through Nrf2-mediated strengthening of gastric mucosal barrier.

This study aimed to explore whether Dendrobium huoshanense stem polysaccharide (cDHPS) ameliorates alcohol-induced gastric ulcer (GU) through the strengthening effect of the gastric mucosal barrier in rats and its potential mechanism. In normal rats, the pretreatment of cDHPS effectively strengthened gastric mucosal barrier by increasing mucus secretion and tight junction protein expression. In GU rats, cDHPS supplementation effectively alleviated alcohol-induced gastric mucosal injury and nuclear factor κB (NF-κB)-driven inflammation by strengthening gastric mucosal barrier. Moreover, cDHPS significantly activated nuclear factor E2-related factor 2 (Nrf2) signaling and promoted antioxidant enzymes activities in both normal and GU rats. These results suggested that the pretreatment of cDHPS could strengthen gastric mucosal barrier to inhibit oxidative stress and NF-κB-driven inflammation induced gastric mucosal injury, which was likely related to the activation of Nrf2 signaling.

The complexing of cationic copolymer MPC30-DEA70 with TGF-ß1 antisense oligodeoxynucleotide and transfection into cardiomyocytes in vitro.

Although gene therapy is an attractive option for the treatment of cardiovascular diseases, the ideal gene delivery systems are still under investigation and must meet the following criteria: safety, adequate gene transfer efficiency, and stable expression of the transgene for a duration appropriate for treating the disease. In this study, we developed a cationic phosphorylcholine-containing diblock copolymer, namely MPC30-DEA70, as carrier systems to deliver a chemically synthesized transforming growth factor-beta 1(TGF-ß1) antisense oligonucleotide (AS-ODN) into cardiomyocytes (CMs) to observe the cell transfection efficiency of MPC30-DEA70 and the inhibition effect on the expression of TGF-ß1. MPC30-DEA70/TGF-ß1 AS-ODN complexes were formed through complexation between copolymer MPC30-DEA70 (N) and AS-ODN (P) at different N/P ratios and were characterized by DNA electrophoresis. Notably, the cytotoxicity and cell growth inhibition assay showed that the MPC30-DEA70 had low cytotoxicity to CMs within the effective transfection dosage range (<20 µL/mL). CLSM/TEM images displayed that most of the AS-ODN molecules engulfed by cells were located around the cell nuclei, and a few entered into the cell nuclei without harming the organelles in the cell. Transfection studies from CMs indicated a steady increase of transfection efficiency with increasing N/P ratios. The expression levels of TGF-ß1 mRNA and protein in CMs were significantly inhibited at high N/P ratios. This study shows that MPC30-DEA70 can function as an effective transgenic vector into CMs and that TGF-ß1 AS-ODN delivered by MPC30-DEA70 can silence the expression of the TGF-ß1 gene efficiently and specifically and thereafter antagonize TGF-ß1-mediated biological function in cardiomyocytes.

RAB27A promotes the proliferation and invasion of colorectal cancer cells.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancer types worldwide. Despite significant advances in prevention and diagnosis, CRC is still one of the leading causes of cancer-related mortality globally. RAB27A, the member of RAB27 family of small GTPases, is the critical protein for intracellular secretion and has been reported to promote tumor progression. However, it is controversial for the role of RAB27A in CRC progression, so we explored the exact function of RAB27A in CRC development in this study. Based on the stable colon cancer cell lines of RAB27A knockdown and ectopic expression, we found that RAB27A knockdown inhibited proliferation and clone formation of SW480 colon cancer cells, whereas ectopic expression of RAB27A in RKO colon cancer cells facilitated cell proliferation and clone formation, indicating that RAB27A is critical for colon cancer cell growth. In addition, our data demonstrated that the migration and invasion of colon cancer cells were suppressed by RAB27A knockdown, but promoted by RAB27A ectopic expression. Therefore, RAB27A is identified as an onco-protein in mediating CRC development, which may be a valuable prognostic indicator and potential therapeutic target for CRC.

Exosomal microRNA panel as a diagnostic biomarker in patients with hepatocellular carcinoma.

Background: Diagnostic tools for hepatocellular carcinoma (HCC) are critical for patient treatment and prognosis. Thus, this study explored the diagnostic value of the exosomal microRNA panel for HCC. Methods: Expression profiles of microRNAs in exosomes and plasma of HCC and control groups were assessed using microRNA microarray analysis. Reverse transcription-quantitative PCR was applied to evaluate the expression of candidate microRNAs in blood samples from 50 HCC patients, 50 hepatic cirrhosis patients, and 50 healthy subjects. The area calculated the diagnostic accuracy of the microRNAs and microRNA panel under the receiver operating characteristic curve (AUC). Results: MicroRNA microarray analysis revealed that there were more differentially expressed microRNAs in the exosome HCC group than plasma HCC group. Among the 43 differentially expressed microRNAs contained in both exosomes and plasma, we finally decided to testify the expression and diagnostic significance of microRNA-26a, microRNA-29c, and microRNA-199a. The results indicated that expression of the microRNA-26a, microRNA-29c, and microRNA-199a in both exosomes and plasma was significantly lower in HCC patients compared with hepatic cirrhosis and healthy group. Interestingly, exosomal microRNAs were substantially more accurate in diagnosing HCC than microRNAs and alpha-fetoprotein in plasma. Moreover, the exosomal microRNA panel containing microRNA-26a, microRNA-29c, and microRNA-199a showed high accuracy in discriminating HCC from healthy (AUC = 0.994; sensitivity 100%; specificity 96%) and hepatic cirrhosis group (AUC = 0.965; sensitivity 92%; specificity 90%). Conclusion: This study revealed that the exosomal microRNA panel has high accuracy in diagnosing HCC and has important clinical significance.