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  1. Abu-Bakar A, Hu H, Lang MA
    Basic Clin Pharmacol Toxicol, 2018 Sep;123 Suppl 5:72-80.
    PMID: 29788535 DOI: 10.1111/bcpt.13046
    The murine cytochrome P450 2a5 (Cyp2a5) gene is regulated by complex interactions of various stress-activated transcription factors (TFs). Elevated Cyp2a5 transcription under chemical-induced stress conditions is achieved by interplay between the various TFs - including as aryl hydrocarbon receptor (AhR) and nuclear factor (erythroid-derived 2)-like 2 wild-type (Nrf2) - at the 'stress-responding' cluster of response elements on the Cyp2a5 promoter, as well as through mRNA stabilization mediated by interaction of the stress-activated heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) with the 3'-UTR of the CYP2A5 mRNA. We designed a unique toxicity pathway-based reporter assay to include regulatory regions from both the 5' and the 3' untranslated regions of Cyp2a5 in a luciferase reporter plasmid to reflect in vivo responses to chemical insult. Human breast cancer MCF-7 cells were stably transfected with pGL4.38-Cyp2a5_Wt3k (wild-type) or mutant - pGL4.38-Cyp2a5_StREMut and pGL4.38-Cyp2a5_XREMut - reporter gene to monitor chemical-induced cellular response mediated by AhR and Nrf2 signalling. The recombinant cells were treated with representative of AhR agonist, polycyclic aromatic hydrocarbons, brominated flame retardant, fluorosurfactant, aromatic organic compound and metal, to determine the sensitivity of the Cyp2a5 promoter-based gene reporter assays to chemical insults by measuring the LC50 and EC50 of the respective chemicals. The three assays are sensitive to sublethal cellular responses of chemicals, which is an ideal feature for toxicity pathway-based bioassay for toxicity prediction. The wild-type reporter responded well to chemicals that activate crosstalk between the AhR and Nrf2, whilst the mutant reporters effectively gauge cellular response driven by either Nrf2/StRE or AhR/XRE signalling. Thus, the three gene reporter assays could be used tandemly to determine the predominant toxicity pathway of a given compound.
  2. Xue J, Chen K, Hu H, Gopinath SCB
    PMID: 33988271 DOI: 10.1002/bab.2193
    Prostate cancer is one of the predominant cancers affecting men and has been widely reported. In the past, various therapies and drugs have been proposed to treat prostate cancer. Among these treatments, gene therapy has been considered to be an optimal and widely applicable treatment. Furthermore, due to the increased specificity of gene sequence complementation, the targeted delivery of complementary gene sequences may represent a useful treatment in certain instances. Various gene therapies, including tumor-suppressor gene therapy, suicide gene therapy, immunomodulation gene therapy and anti-oncogene therapies, have been established to treat a wide range of diseases, such as cardiac disease, cystic fibrosis, HIV/AIDS, diabetes, hemophilia, and cancers. To this end, several gene therapy clinical trials at various phases are underway. This overview describes the developments and progress in gene therapy, with a special focus being placed on prostate cancer.
  3. Yu M, Xu S, Hu H, Li S, Yang G
    Behav Brain Res, 2023 Apr 12;443:114209.
    PMID: 36368444 DOI: 10.1016/j.bbr.2022.114209
    OBJECTIVE: We investigated brain activity associated with executive control attention network in elite, expert, and novice female ice hockey athletes during the revised lateralized attention network tast to determine whether the neural correlates of performance differ by skill level.

    METHODS: We collected and analyzed functional near-infrared spectroscopy data of 38 participants while performing the revised lateralized attention network tast.

    RESULTS: Elite players were significantly faster than novices (p = .005), and the experts' overall accuracy rate (ACC) was higher than that of novices (p = .001). The effect of the executive network on reaction time was higher in novices than in elite players (p = .008) and experts (p = .004). The effect of the executive network on the ACC was lower in elite players than in experts (p = .009) and novices (p = .010). Finally, elite player had higher flanker conflict effects on RT (p = .005) under the invalid cue condition. the effect of the alertness network and orientation on the ACC was lower in elite players than in novices (p = .000) and experts (p = .022). Changes in the blood oxygen level-dependent signal related to the flanker effect were significantly different in the right dorsolateral prefrontal cortex (F=3.980, p = .028) and right inferior frontal gyrus (F=3.703, p = .035) among the three groups. Elit players showed more efficient executive control (reduced conflict effect on ACC) (p = .006)in the RH.The changes related to the effect of blood oxygen level on orienting were significantly different in the right frontal eye fields (F=3.883, p = .030) among the three groups, Accompanied by significant activation of the right dorsolateral prefrontal cortex(p = .026).

    CONCLUSION: Our findings provide partial evidence of the superior cognitive performance and high neural efficiency of elite ice hockey players during cognitive tasks. These results demonstrate the right hemisphere superiority for executive control.We also found that specific brain activation in hockey players does not show a clear and linear relationship with skill level.

  4. Mei Y, Hu H, Deng L, Sun X, Tan W
    Sci Rep, 2022 Jul 27;12(1):12857.
    PMID: 35896572 DOI: 10.1038/s41598-022-16119-0
    Isosteviol sodium (STVNa) is a beyerane diterpene synthesized via acid hydrolysis of stevioside, which can improve glucose and lipid metabolism in animals with diabetes. However, it remains unknown whether STVNa can exhibit a therapeutic effect on nonalcoholic fatty liver disease (NAFLD) and its underlying mechanism. We hypothesize that autophagic initiation may play a key role in mediating the development of NAFLD. Herein, we assessed the effects of STVNa on NAFLD and its underlying mechanisms. The results demonstrated that STVNa treatment effectively ameliorated NAFLD in rats fed high-fat diet (HFD). Moreover, STVNa decreased the expression of inflammation-related genes and maintained a balance of pro-inflammatory cytokines in NAFLD rats. STVNa also reduced lipid accumulation in free fatty acid (FFA)-exposed LO2 cells. In addition, STVNa attenuated hepatic oxidative stress and fibrosis in NAFLD rats. Furthermore, STVNa enhanced autophagy and activated Sirtuin 1/adenosine monophosphate-activated protein kinase (Sirt1/AMPK) pathway both in vivo and in vitro, thus attenuating intracellular lipid accumulation. In summary, STVNa could improve lipid metabolism in NAFLD by initiating autophagy via Sirt1/AMPK pathway. Therefore, STVNa may be an alternative therapeutic agent for treatment of NAFLD.
  5. Wang G, Alias SB, Sun Z, Wang F, Fan A, Hu H
    Heliyon, 2023 May;9(5):e16112.
    PMID: 37215850 DOI: 10.1016/j.heliyon.2023.e16112
    Influential nodes identification technology is one of the important topics which has been widely applied to logistics node location, social information dissemination, transportation network carrying, biological virus dissemination, power network anti-destruction, etc. At present, a large number of influential nodes identification methods have been studied, but the algorithms that are simple to execute, have high accuracy and can be better applied to real networks are still the focus of research. Therefore, due to the advantages of simple to execute in voting mechanism, a novel algorithm based on adaptive adjustment of voting ability (AAVA) to identify the influential nodes is presented by considering the local attributes of node and the voting contribution of its neighbor nodes, to solve the problem of low accuracy and discrimination of the existing algorithms. This proposed algorithm uses the similarity between the voting node and the voted node to dynamically adjust its voting ability without setting any parameters, so that a node can contribute different voting abilities to different neighbor nodes. To verify the performance of AAVA algorithm, the running results of 13 algorithms are analyzed and compared on 10 different networks with the SIR model as a reference. The experimental results show that the influential nodes identified by AAVA have high consistency with SIR model in Top-10 nodes and Kendall correlation, and have better infection effect of the network. Therefore, it is proved that AAV algorithm has high accuracy and effectiveness, and can be applied to real complex networks of different types and sizes.
  6. Ma Q, Rejab MRM, Hassan SA, Hu H, Kumar AP
    J Mech Behav Biomed Mater, 2022 Dec;136:105514.
    PMID: 36215770 DOI: 10.1016/j.jmbbm.2022.105514
    Sandwich panel is increasingly used as lightweight energy absorbing components, which provides excellent crashworthiness performance with the three-dimensional periodic core. This paper investigates 3D-printed bio-inspired spherical-roof cubic cores with multi-walled carbon nanotubes (MWCNT) and foam-filled cores under quasi-static loading. The proposed bio-inspired spherical-roof cubic cores with 1.5 mm wall thickness were manufactured using the fused filament fabrication process, which used 70% polylactic acid (PLA) and 30% carbon fiber filament. Moreover, four groups of 3D-printed bio-inspired spherical-roof cubic cores were compared and analyzed on compressive properties and failure behavior. Experimental results were shown that foam-filled double bio-inspired spherical-roof cubic core with MWCNT was the maximum Fpeak with 1.92 kN, which provided a much more stable plateau load and better energy-absorbing characteristics. In addition, it is conducted that a double bio-inspired spherical-roof cubic core with four notches core is considered as the potential energy-absorbing core.
  7. Yi KH, Kim SB, Hu H, An HS, Hidajat IJ, Lim TS, et al.
    Dermatol Surg, 2024 Sep 01;50(9):834-837.
    PMID: 38712848 DOI: 10.1097/DSS.0000000000004208
    BACKGROUND: Hypertrophied submandibular glands provide a bulky contour to the lower face. Botulinum neurotoxin injection methods are commonly used for facial contouring; however, no studies have suggested injection points because of the lack of delicate anatomical information on the submandibular gland.

    OBJECTIVE: The aim of this study was to determine the optimal injection site for botulinum neurotoxin injections in the submandibular gland.

    MATERIALS AND METHODS: Anatomical considerations when injecting botulinum neurotoxin into the submandibular gland were determined using ultrasonography. The thickness of the submandibular gland, its depth from the skin surface, and the location of the vascular bundle were observed bilaterally in 42 participants. Two cadavers were dissected to measure the location of the submandibular gland corresponding to the ultrasonographic observation.

    RESULTS: The thickest part of the submandibular gland measured 11.12 ± 2.46 in width with a depth of 4.63 ± 0.76. At the point where it crosses the line of the lateral canthus, it measured 5.53 ± 1.83 in width and 8.73 ± 1.64 in depth.

    CONCLUSION: The authors suggest optimal injection sites based on external anatomical landmarks. These guidelines aim to maximize the effects of botulinum neurotoxin therapy by minimizing its deleterious effects, which can be useful in clinical settings.

  8. Wang Z, Wu T, Hu H, Alabed AAA, Cui G, Sun L, et al.
    J Psychiatry Neurosci, 2024;49(4):E265-E281.
    PMID: 39209459 DOI: 10.1503/jpn.230118
    BACKGROUND: Schizophrenia is characterized by a complex interplay of genetic and environmental factors, leading to alterations in various molecular pathways that may contribute to its pathogenesis. Recent studies have shown that exosomal microRNAs could play essential roles in various brain disorders; thus, we sought to explore the potential molecular mechanisms through which microRNAs in plasma exosomes are involved in schizophrenia.

    METHODS: We obtained sequencing data sets (SUB12404730, SUB12422862, and SUB12421357) and transcriptome sequencing data sets (GSE111708, GSE108925, and GSE18981) from mouse models of schizophrenia using the Sequence Read Archive and the Gene Expression Omnibus databases, respectively. We performed differential expression analysis on mRNA to identify differentially expressed genes. We conducted Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to determine differentially expressed genes. Subsequently, we determined the intersection of differentially expressed microRNAs in plasma exosomes and in prefrontal cortex tissue. We retrieved downstream target genes of mmu-miR-146a-5p from TargetScan and used Cytoscape to visualize and map the microRNA-target gene regulatory network. We conducted in vivo experiments using MK-801-induced mouse schizophrenia models and in vitro experiments using cultured mouse neurons. The role of plasma exosomal miR-146a-5p in schizophrenia was validated using a cell counting kit, detection of lactate dehydrogenase, dual-luciferase assay, quantitative reverse transcription polymerase chain reaction, and Western blot analysis.

    RESULTS: Differential genes were mainly enriched in synaptic regulation-related functions and pathways and were associated with neuronal degeneration. We found that mmu-miR-146a-5p was highly expressed in both prefrontal cortical tissue and plasma exosomes, which may be transferred to lobe cortical vertebral neurons, leading to the synergistic dysregulation of gene network functions and, therefore, promoting schizophrenia development. We found that mmu-miR-146a-5p may inhibit the Notch signalling pathway-mediated synaptic activity of mouse pyramidal neurons in the lobe cortex by targeting NOTCH1, which in turn could promote the onset and development of schizophrenia in mice.

    LIMITATIONS: The study's findings are based on animal models and in vitro experiments, which may not fully replicate the complexity of human schizophrenia.

    CONCLUSION: Our findings suggest that mmu-miR-146a-5p in plasma-derived exosomes may play an important role in the pathogenesis of schizophrenia. Our results provide new insights into the underlying molecular mechanisms of the disease.

  9. Jaisamrarn U, Esteban-Habana MA, Padolina CS, Decena DCD, Dee MT, Damodaran P, et al.
    SAGE Open Med, 2023;11:20503121231173377.
    PMID: 37223672 DOI: 10.1177/20503121231173377
    Addressing maternal malnutrition and its drivers is paramount in Southeast Asia. This article summarizes the key clinical learnings and evidence-based opinions from the experts to understand the need for vitamins and minerals supplementation, education, and self-care from preconception to the first 1000 days of life, which warranted further attention since COVID-19 pandemic. Evidence describing the importance of vitamins and minerals during preconception, pregnancy, and lactation stages was identified using literature databases. A pre-meeting survey was conducted to determine the current practices and challenges in Southeast Asia. Based on the literature review and clinical experience, experts defined the topics, and an online meeting was held on 13th July 2021. During the meeting, nine experts from Southeast Asia provided evidence-based opinion on the vitamins and minerals supplementation, education, and self-care need during preconception, pregnancy, and lactation stages. The expert opinions underpin maternal malnutrition as a prevalent issue and discuss appropriate interventions and prevention strategies for women in Southeast Asia. The recent pandemic further impacted nutrition status, pregnancy, and neonatal health outcomes. The expert panel emphasized a need to improve existing inadequacies in education, self-care, and social support, and discussed the role of policymakers in addressing the barriers to dietary changes. As inadequacies in regular vitamins and minerals supplementation, education, and self-care for women of reproductive age implicate maternal and child health outcomes, there is an urgent need for addressing malnutrition concerns in this population. Thus, a strong partnership between policymakers, healthcare professionals, and other relevant sectors is required.
  10. Gong Y, Hu H, Zhao X, Wei W, Zhang M, Tran NT, et al.
    J Virol, 2024 Nov 15.
    PMID: 39545727 DOI: 10.1128/jvi.01519-24
    As an enduring hot topic in the field of innate immunity, apoptosis is widely considered an effective approach to eliminate pathogenic microbes and plays a crucial role during host-pathogen interactions. Recently, researchers have found that the virus-containing host cells could transmit apoptotic signals to the surrounding uninfected cells during infection, but the mechanism remains unclear. Here, we found that exosomes secreted by WSSV-infected mud crab hemocytes contain viral nucleic acid wsv277, which could be transported to the recipient cells and further expressed viral protein with phosphokinase activity. Besides, by using transcriptome, proteome, ChIP-seq, and coIP techniques, the results revealed that wsv277 could activate the transcription and translation of apoptotic genes via interacting with CBF and EF-1α so as to suppress the spread of virus infection by inducing apoptosis of the surrounding cells. Therefore, for the first time, our study proved that the components of DNA virus could be encapsulated into exosomes and elucidated the mechanism of apoptotic signal transduction between cells from the perspective of exosomes.

    IMPORTANCE: Our study revealed that the components of DNA virus could be packaged and transmitted through the exosomes of lower invertebrates, which strongly demonstrated the diversity of exosome-mediated viral immunity and its universality in animals. Furthermore, we elucidated the mechanism of apoptotic signal transduction between cells from the perspective of exosomes and revealed a novel strategy for the host to cope with viral infection.

  11. Zheng H, Qin J, Chen H, Hu H, Zhang X, Yang C, et al.
    Microb Genom, 2021 11;7(11).
    PMID: 34762026 DOI: 10.1099/mgen.0.000659
    Burkholderia pseudomallei is a Gram-negative soil-dwelling bacillus that causes melioidosis, a frequently fatal infectious disease, in tropical and subtropical regions. Previous studies have identified the overall genetic and evolutionary characteristics of B. pseudomallei on a global scale, including its origin and transmission routes. However, beyond its known hyperendemicity foci in northern Australia and Southeast Asia, the distribution and genetic characteristics of B. pseudomallei in most tropical regions remain poorly understood, including in southern China. Here, we sequenced the genomes of 122 B. pseudomallei strains collected from Hainan, an island in southern China, in 2002-2018, to investigate the population structure, relationships with global strains, local epidemiology, and virulence and antimicrobial-resistance factors. A phylogenetic analysis and hierarchical clustering divided the Hainan strains into nine phylogenic groups (PGs), 80 % of which were concentrated within five major groups (group 1: corresponding to minor sequence types [STs], 12.3 %; group 3: ST46 and ST50, 31.1 %; group 9: ST58, 13.1 %; group 11: ST55, 8.2 %; group 15: mainly ST658, 15.6%). A phylogenetic analysis that included global strains suggested that B. pseudomallei in Hainan originated from Southeast Asian countries, transmitted in multiple historical importation events. We also identified several mutual transmission events between Hainan and Southeast Asian countries in recent years, including three importation events from Thailand and Singapore to Hainan and three exportation events from Hainan to Singapore, Malaysia, and Taiwan island. A statistical analysis of the temporal distribution showed that the Hainan strains of groups 3, 9, and 15 have dominated the disease epidemic locally in the last 5 years. The spatial distribution of the Hainan strains demonstrated that some PGs are distributed in different cities on Hainan island, and by combining phylogenic and geographic distribution information, we detected 21 between-city transmission events, indicating its frequent local transmission. The detection of virulence factor genes showed that 56 % of the Hainan strains in group 1 encode a B. pseudomallei-specific adherence factor, boaB, confirming the specific pathogenic characteristics of the Hainan strains in group 1. An analysis of the antimicrobial-resistance potential of B. pseudomallei showed that various kinds of alterations were identified in clinically relevant antibiotic resistance factors, such as AmrR, PenA and PBP3, etc. Our results clarify the population structure, local epidemiology, and pathogenic characteristics of B. pseudomallei in Hainan, providing further insight into its regional and global transmission networks and improving our knowledge of its global phylogeography.
  12. Zhao Z, Feng Y, Wang M, Wei J, Tan T, Li R, et al.
    Front Neuroinform, 2024;18:1392271.
    PMID: 39211912 DOI: 10.3389/fninf.2024.1392271
    BACKGROUND: The above studies indicate that the SCZ animal model has abnormal gamma oscillations and abnormal functional coupling ability of brain regions at the cortical level. However, few researchers have focused on the correlation between brain complexity and connectivity at the cortical level. In order to provide a more accurate representation of brain activity, we studied the complexity of electrocorticogram (ECoG) signals and the information interaction between brain regions in schizophrenic rats, and explored the correlation between brain complexity and connectivity.

    METHODS: We collected ECoG signal from SCZ rats. The frequency domain and time domain functional connectivity of SCZ rats were evaluated by magnitude square coherence and mutual information (MI). Permutation entropy (PE) and permutation Lempel-Ziv complexity (PLZC) were used to analyze the complexity of ECoG, and the relationship between them was evaluated. In addition, in order to further understand the causal structure of directional information flow among brain regions, we used phase transfer entropy (PTE) to analyze the effective connectivity of the brain.

    RESULTS: Firstly, in the high gamma band, the complexity of brain regions in SCZ rats is higher than that in normal rats, and the neuronal activity is irregularity. Secondly, the information integration ability of SCZ rats decreased and the communication of brain network information was hindered at the cortical level. Finally, compared with normal rats, the causal relationship between brain regions of SCZ rats was closer, but the information interaction center was not clear.

    CONCLUSION: The above findings suggest that at the cortical level, complexity and connectivity are valid biomarkers for identifying SCZ. This bridges the gap between peak potentials and EEG. This may help to understand the pathophysiological mechanisms at the cortical level in schizophrenics.

  13. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
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