Autism spectrum disorder (ASD) is characterized by stereotyped behavior and deficits in communication and social interactions. Gastrointestinal (GI) dysfunction is an ASD-associated comorbidity, implying a potential role of the gut microbiota in ASD GI pathophysiology. Several recent studies found that autistic individuals harbor an altered bacterial gut microbiota. In some cases, remodeling the gut microbiota by antibiotic administration and microbiota transfer therapy reportedly alleviated the symptoms of ASD. However, there is little consensus on specific bacterial species that are similarly altered across individual studies. The aim of this study is to summarize previously published data and analyze the alteration of the relative abundance of bacterial genera in the gut microbiota in controls and individuals with ASD using meta-analysis. We analyzed nine studies, including 254 patients with ASD, and found that children with ASD had lower percentages of Akkermansia , Bacteroides , Bifidobacterium , and Parabacteroides and a higher percentage of Faecalibacterium in the total detected microflora compared to controls. In contrast, children with ASD had lower abundance of Enterococcus , Escherichia coli , Bacteroides , and Bifidobacterium and higher abundance of Lactobacillus . This meta-analysis suggests an association between ASD and alteration of microbiota composition and warrants additional prospective cohort studies to evaluate the association of bacterial changes with ASD symptoms, which would provide further evidence for the precise microbiological treatment of ASD.

Bumetanide has been reported to alter synaptic excitation-inhibition (E-I) balance by potentiating the action of γ-aminobutyric acid (GABA), thereby attenuating the severity of autism spectrum disorder (ASD) in animal models. However, clinical evidence of its efficacy in young patients with ASD is limited. This was investigated in the present clinical trial of 83 patients, randomised to the bumetanide group (bumetanide treatment, 0.5 mg twice daily) or the control group (no bumetanide treatment). Primary [Children Autism Rating Scale (CARS)], secondary [Clinical Global Impressions (CGI)], and exploratory [inhibitory (γ-aminobutyric acid, GABA) and excitatory (glutamate, Glx) neurotransmitter concentrations measured in the insular cortex (IC) and visual cortex (VC) by magnetic resonance spectroscopy (MRS)] outcome measures were evaluated at baseline and at the 3-month follow-up. Side effects were monitored throughout the treatment course. Compared with the control group, the bumetanide group showed significant reduction in symptom severity, as indicated by both total CARS score and number of items assigned a score ≥ 3. The improvement in clinical symptoms was confirmed by CGI. GABA/Glx ratio in both the IC and VC decreased more rapidly over the 3-month period in the bumetanide group than that in the control group. This decrease in the IC was associated with the symptom improvement in the bumetanide group. Our study confirmed the clinical efficacy of bumetanide on alleviating the core symptoms of ASD in young children and it is the first demonstration that the improvement is associated with reduction in GABA/Glx ratios. This study suggests that the GABA/Glx ratio measured by MRS may provide a neuroimaging biomarker for assessing treatment efficacy for bumetanide.

Lung cancer is a malignancy with high morbidity and mortality worldwide. More evidences indicated that gut microbiome plays an important role in the carcinogenesis and progression of cancers by metabolism, inflammation and immune response. However, the study about the characterizations of gut microbiome in lung cancer is limited. In this study, the fecal samples were collected from 16 healthy individuals and 30 lung cancer patients who were divided into 3 groups based on different tumor biomarkers (cytokeratin 19 fragment, neuron specific enolase and carcinoembryonic antigen, respectively) and were analyzed using 16S rRNA gene amplicon sequencing. Each lung cancer group has characterized gut microbial community and presents an elimination, low-density, and loss of bacterial diversity microbial ecosystem compared to that of the healthy control. The microbiome structures in family and genera levels are more complex and significantly varied from each group presenting more different and special pathogen microbiome such as Enterobacteriaceae, Streptococcus, Prevotella, etc and fewer probiotic genera including Blautia, Coprococcus, Bifidobacterium and Lachnospiraceae. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and COG annotation demonstrated decreased abundance of some dominant metabolism-related pathways in the lung cancer. This study explores for the first time the features of gut microbiome in lung cancer patients and may provide new insight into the pathogenesis of lung cancer system, with the implication that gut microbiota may serve as a microbial marker and contribute to the derived metabolites, development and differentiation in lung cancer system.

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Endothelial dysfunction and excessively stimulated autophagy, often caused by oxidant injury or inflammation, will lead to atherosclerosis development and progression in diabetes. The aim of this study is to investigate the protective effect of glucagon-like peptide-1 (GLP-1) treatment on preventing oxidative stress-induced endothelial dysfunction and excessively stimulated autophagy. Treatment of endothelial cells with GLP-1 significantly attenuated oxidative stress-induced endothelial dysfunction and autophagy, which was associated with the reduction of intracellular reactive oxygen species (ROS) levels. These protective effects of GLP-1 were likely mediated by reducing phosphorylation of ERK1/2. We further demonstrated that GLP-1 treatment could reverse downregulation of epigenetic factor histone deacetylase 6 (HDAC6), a downstream molecular of the EKR1/2, induced by oxidant injury. In conclusion, our results suggest that GLP-1 produces a protective effect on endothelial cells from oxidant injury by preventing endothelial dysfunction and autophagy, which may be dependent on restoring HDAC6 through a GLP-1R-ERK1/2-dependent manner.

Clinical evidence suggests that there exists a strong correlation between Zika virus (ZIKV) infection and abnormal development of the nervous system. However, the underlying mechanisms remain to be elusive. In this study, recombinant lentiviral vectors coding for ZIKV structural proteins and truncations (prM-Env, M-Env and Env) were transduced into PC12 cells. Envelope (Env) overexpression induced significant inhibition of proliferation and triggered G2/M cell cycle arrest and apoptosis in PC12 cells. Flow cytometry and western blot analysis showed that the apoptosis was associated with up-regulation of both p53 and p21Cip1/Waf1 and down-regulation of cyclin B1. Presence of aberrant nuclei clusters were confirmed by immunofluorescence staining analysis. The data indicate that overexpression of prM-Env, M-Env or Env led to apoptosis via an intrinsic cell death signaling pathway that is dependent on the activation of caspase-9 and caspase-3 and accompanied by an increased ratio of Bax to Bcl-2 in transduced PC12 cells. In summary, our results suggest that ZIKV Env protein causes apoptosis in PC12 cells via an intrinsic cell death signaling pathway, which may contribute to ZIKV-induced abnormal development of the nervous system.

Objective: As two common neurodevelopmental disorders, autistic spectrum disorder and attention deficit hyperactivity disorder frequently occur together. Until now, only a few studies have investigated the co-occurrence of attention deficit hyperactivity disorder and autistic spectrum disorder, this is due to restrictions associated with previous Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Most previous research has focused on the developmental trajectories for autistic spectrum disorder and attention deficit hyperactivity disorder separately, while the neural mechanisms underpinning the co-occurrence of autistic spectrum disorder and attention deficit hyperactivity disorder remain largely unknown. Methods:We studied 162 autistic spectrum disorder individuals (including 79 co-attention deficit hyperactivity disorder and 83 non-attention deficit hyperactivity disorder patients) and 177 typical developing individuals using resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange II, an aggregated magnetic resonance imaging dataset from 19 centers. Independent component analysis was used to extract sub-networks from the classic resting-state networks. Functional connectivity values within (intra-iFC) and between (inter-iFC) these networks were then determined. Subsequently, we compared the ASD_coADHD group with the ASD_nonADHD group in relation to the abnormal intra-iFC and inter-iFC of autistic spectrum disorder group relative to the typical developing group. Results:The ASD_coADHD group showed more severe social impairment and decreased intra-iFC in the bilateral posterior cingulate cortex of the default mode network (independent component 17) and increased inter-iFC between the default mode network (independent component 8) and the somatomotor networks (independent component 2) compared to the ASD_nonADHD group. In addition, the strength of the intra-iFC in the default mode network was associated with the severity of autistic traits across the entire autistic spectrum disorder group and particularly the ASD_coADHD group. Conclusion:Our results showed that dysfunction of the default mode network is a central feature in the co-occurrence of autistic spectrum disorder and attention deficit hyperactivity disorder, including connectivity within the default mode network as well as between the default mode network and the somatomotor networks, thus supporting the existence of a clinically combined phenotype (autistic spectrum disorder + attention deficit hyperactivity disorder).

ObjectiveDuring the COVID-19 pandemic, face-to-face intervention services for families of children with autism spectrum disorder (ASD) were limited. This study aimed to evaluate the effectiveness of an 8-week, online-delivered Project ImPACT program for children with ASD and their parents in China during the COVID-19 pandemic.MethodsA pilot non-randomized study with a waitlist control group was conducted in 68 children with ASD and their parents in the Department of Developmental and Behavioral Pediatrics between April 15, 2020 and March 19, 2021. Participants were allocated to either the intervention (IG) or the waitlist group (WLG) according to their order of recruitment. Parents in the IG immediately received 8 weeks of the online-delivered Project ImPACT program, and the WLG received the same program with a delay when the IG had completed all sessions. Participants in both groups received treatment as usual during the research period.ResultsThe online-delivered Project ImPACT program significantly improved the parent-reported social communication skills of children with ASD. Furthermore, parent's involvement in the training program produced a collateral reduction in parenting stress and an increase in perceived competence in the parental role. Parents rated the program acceptable in terms of curriculum schedule, session content, homework assignments, and therapist feedback.ConclusionsThe 8-week, online-delivered Project ImPACT program is a feasible and effective social skill training program for families of children with ASD in China during the COVID-19 pandemic. Due to the methodological limitations, randomized controlled studies with larger sample sizes are suggested to provide more solid evidence.