Wen Li

The pathophysiology of autistic spectrum disorder (ASD) is not fully understood and there are no diagnostic or predictive biomarkers. Extracellular vesicles (EVs) are cell-derived nano-sized vesicles, carrying nucleic acids, proteins, lipids, and other bioactive substances. As reported, serum neural cell adhesion molecule L1 (L1CAM)-captured EVs (LCEVs) can provide reliable biomarkers for neurological diseases; however, little is known about the LCEVs in children with ASD. The study enrolled 100 children with ASD (2.5–6 years of age; 90 males) and 60 age-matched TD children (54 males) as control. The serum sample was collected and pooled into five ASD subgroups and three TD subgroups (n = 20). LCEVs were isolated and characterized meticulously. Whole-transcriptome of LCEVs was analyzed by lncRNA microarray and RNA-sequencing. All raw data was submitted on GEO Profiles, and GEO accession numbers is GSE186493. RNAs expressed differently in LCEVs from ASD sera vs. TD sera were screened, analyzed, and further validated. A total of 1418 mRNAs, 1745 lncRNAs, and 11 miRNAs were differentially expressed, and most of them were downregulated in ASD. Most RNAs were involved in neuron- and glycan-related networks implicated in ASD. The levels of EDNRA, SLC17A6, HTR3A, OSTC, TMEM165, PC-5p-139289_26, and hsa-miR-193a-5p were validated in at least 15 ASD and 15 TD individual serum samples, which were consistent with the results of transcriptome analysis. In conclusion, whole-transcriptome analysis of serum LCEVs reveals neural and glycosylation changes in ASD, which may help detect predictive biomarkers and molecular mechanisms of ASD, and provide reference for diagnoses and therapeutic management of the disease.

Significance: In many malignancies, resistance to targeted therapy emerges rapidly and leads to disease progression and mortality. Here, we show that trident cold atmospheric plasma (Tri-CAP), a reactive oxygen species–producing gas discharge, simultaneously blocks three cancer survival pathways, including deregulated redox balance, glycolysis, and proliferative signaling, in a mouse cell line model of therapy-resistant chronic myeloid leukemia (CML). This activity leads to high-rate apoptotic death in these CML cell lines and primary CD34 ⁺ hematopoietic stem and progenitor cells from CML patients, while minimally affecting nonmalignant control cells. Furthermore, Tri-CAP reduces tumor formation and prolongs the survival of tumor-bearing mice in mouse models of CML. Thus, treatment with Tri-CAP may be an effective strategy for overcoming therapy resistance in human cancers.

Background: Nm23‐H1 gene has been found to be an inhibitor of tumor metastasis in lung cancer. MicroRNAs (miRNAs) play key roles in tumor metastasis through multiple signaling pathways. This study explored whether the nm23‐H1 gene could inhibit invasion and metastasis of lung cancer cells by regulating miRNA‐660‐5p targets.Methods: Quantitative real‐time PCR (qRT‐PCR) and western blots were used to measure the expression of nm23‐H1 and miR‐660‐5p of various human lung cancer cell lines. Cell counting kit‐8 (CCK‐8), wound‐healing and transwell assay were carried out to assess cell proliferation, migration and invasion of each cell line. Xenograft were applied to determine in vivo effects of miR‐660‐5p among nude mice. Luciferase assay and western blot were performed to determine the target gene of miR‐660‐5p.Results: We found that high expression of nm23‐H1 correlated with decreased miRNA‐660‐5p expression. Inhibiting miR‐660‐5p suppressed lung cancer cells progression significantly in vitro, whereas overexpression of miR‐660‐5p facilitated tumor growth and bone metastasis in vivo. In addition, as the potential target gene of miR‐660‐5p, SMARCA5 overexpression in vitro suppressed tumor progression and osteolytic metastasis associated RANKL signaling, which is congruent with the effect of nm23‐H1 on the lung cancer cells.Conclusion: Nm23‐H1 inhibits tumor progression and bone‐specific metastasis of lung cancer by regulating miR‐660‐5p/SMARCA5/RANKL axis, which indicates the related genes may serve as potential targets for the treatment of human lung cancer.Key points: Significant findings of the studyHigh expression of nm23‐H1 correlated with decreased miRNA‐660‐5p expression. Further, downregulation of miR‐660‐5p significantly suppressed the tumor progression and bone‐specific metastasis of lung cancer cells.What this study addsThis is the first study to show an inverse association between nm23‐H1 and miR‐660‐5p, and confirm that nm23‐H1 inhibits tumor progression and bone‐specific metastasis of lung cancer by regulating miR‐660‐5p/SMARCA5/RANKL axis.

Adenoviruses (Ad) are commonly used as vectors for gene therapy and/or vaccine delivery. Recombinant Ad vectors are being tested as vaccines for many pathogens. We have made a surprising observation that peptides derived from various hepatitis C virus (HCV) antigens contain extensive regions of homology with multiple adenovirus proteins, and conclusively demonstrate that adenovirus vector can induce robust, heterologous cellular and humoral immune responses against multiple HCV antigens. Intriguingly, the induction of this cross-reactive immunity leads to significant reduction of viral loads in a recombinant vaccinia-HCV virus infected mouse model, supporting their role in antiviral immunity against HCV. Healthy human subjects with Ad-specific pre-existing immunity demonstrated cross-reactive cellular and humoral immune responses against multiple HCV antigens. These findings reveal the potential of a previously uncharacterized property of natural human adenovirus infection to dictate, modulate and/or alter the course of HCV infection upon exposure. This intrinsic property of adenovirus vectors to cross-prime HCV immunity can also be exploited to develop a prophylactic and/or therapeutic vaccine against HCV.