Editors-in-Chief

Shu-Min DUAN

Zhi-Hong LIU

ISSN 1673-1581

CN 33-1356/Q

Published by

Zhejiang University Press

2022 JIF 4.7

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    Abstract：Patients with depression are more likely to have chronic gastrointestinal (GI) symptoms than the general population, but such symptoms are considered only somatic symptoms of depression and lack special attention. There is a chronic lack of appropriate diagnosis and effective treatment for patients with depression accompanied by GI symptoms, and studying the association between depression and GI disorders (GIDs) is extremely important for clinical management. There is growing evidence that depression is closely related to the microbiota present in the GI tract, and the microbiota-gut-brain axis (MGBA) is creating a new perspective on the association between depression and GIDs. Identifying and treating GIDs would provide a key opportunity to prevent episodes of depression and may also improve the outcome of refractory depression. Current studies on depression and the microbially related gut-brain axis (GBA) lack a focus on GI function. In this review, we combine preclinical and clinical evidence to summarize the roles of the microbially regulated GBA in emotions and GI function, and summarize potential therapeutic strategies to provide a reference for the study of the pathomechanism and treatment of depression in combination with GI symptoms.  

    Menglin LIU, Genhao FAN, Lingkai MENG, Kuo YANG, Huayi LIU

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  • Research Articles

    Abstract：ObjectiveWhether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial. This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.MethodsPatients with bipolar Ⅱ depression were enrolled in this prospective, two-center, randomized, 12-week pilot trial. The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale (MADRS) of ≥50%. All eligible patients initially received four weeks of lurasidone monotherapy. Patients who responded well continued to receive this kind of monotherapy. However, no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks. By comprehensively comparing the results of MADRS over a period of 4‍‒‍12 weeks, a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.ResultsThirty-seven patients responded to lurasidone monotherapy, and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks. After two weeks of combined valproate or vortioxetine treatment, the MADRS score in the vortioxetine group was significantly lower than that in the valproate group. There was no difference in the MADRS scores between the two groups at 8 and 12 weeks. The incidence of side effects did not significantly differ between the valproate and vortioxetine groups. Importantly, three patients in the vortioxetine group appeared to switch to mania or hypomania.ConclusionsThis study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage, while disease progression should be monitored closely for the risk of switching to mania.  

    Chunxiao DAI, Yaoyang FU, Xuanwei LI, Meihua LIN, Yinbo LI, Xiao LI, Keke HUANG, Chengcheng ZHOU, Jian XIE, Qingwei ZHAO, Shaohua HU

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  • Research Articles

    Abstract：White-matter tracts play a pivotal role in transmitting sensory and motor information, facilitating interhemispheric communication and integrating different brain regions. Meanwhile, sensorimotor disturbance is a common symptom in patients with major depressive disorder (MDD). However, the role of aberrant sensorimotor white-matter system in MDD remains largely unknown. Herein, we investigated the topological structure alterations of white-matter morphological brain networks in 233 MDD patients versus 257 matched healthy controls (HCs) from the DIRECT consortium. White-matter networks were derived from magnetic resonance imaging (MRI) data by combining voxel-based morphometry (VBM) and three-dimensional discrete wavelet transform (3D-DWT) approaches. Support vector machine (SVM) analysis was performed to discriminate MDD patients from HCs. The results indicated that the network topological changes in node degree, node efficiency, and node betweenness were mainly located in the sensorimotor superficial white-matter system in MDD. Using network nodal topological properties as classification features, the SVM model could effectively distinguish MDD patients from HCs. These findings provide new evidence to highlight the importance of the sensorimotor system in brain mechanisms underlying MDD from a new perspective of white-matter morphological network.  

    Peng WANG, Yanling BAI, Yang XIAO, Yuhong ZHENG, Li SUN, The DIRECT Consortium, Jinhui WANG, Shaowei XUE

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  • Correspondence

    Miaomiao ZHAO, Ying LI, Haoyang ZHAO, Chaonan JIANG, Manli HUANG

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  • Reviews

    Abstract：Adenosine triphosphate (ATP)-binding cassette (ABC) transporter systems are divided into importers and exporters that facilitate the movement of diverse substrate molecules across the lipid bilayer, against the concentration gradient. These transporters comprise two highly conserved nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). Unlike ABC exporters, prokaryotic ABC importers require an additional substrate-binding protein (SBP) as a recognition site for specific substrate translocation. The discovery of a large number of ABC systems in bacterial pathogens revealed that these transporters are crucial for the establishment of bacterial infections. The existing literature has highlighted the roles of ABC transporters in bacterial growth, pathogenesis, and virulence. These roles include importing essential nutrients required for a variety of cellular processes and exporting outer membrane-associated virulence factors and antimicrobial substances. This review outlines the general structures and classification of ABC systems to provide a comprehensive view of the activities and roles of ABC transporters associated with bacterial virulence and pathogenesis during infection.  

    Shu Sian HOW, Sheila NATHAN, Su Datt LAM, Sylvia CHIENG

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  • Research Article

    Abstract：Hexavalent chromium Cr(VI), as a well-established carcinogen, contributes to tumorigenesis for many human cancers, especially respiratory and digestive tumors. However, the potential function and relevant mechanism of Cr(VI) on the initiation of esophageal carcinogenesis are largely unknown. Here, immortalized human esophageal epithelial cells (HEECs) were induced to be malignantly transformed cells, termed HEEC-Cr(VI) cells, via chronic exposure to Cr(VI), which simulates the progress of esophageal tumorigenesis. In vitro and in vivo experiments demonstrated that HEEC-Cr(VI) cells obtain the ability of anchorage-independent growth, greater proliferative capacity, cancer stem cell properties, and the capacity to form subcutaneous xenografts in BALB/c nude mice when compared to their parental cells, HEECs. Additionally, HEEC-Cr(VI) cells exhibited weakened cell motility and enhanced cell adhesion. Interestingly, HEECs with acute exposure to Cr(VI) failed to display those malignant phenotypes of HEEC-Cr(VI) cells, suggesting that Cr(VI)‍-induced malignant transformation, but not Cr(VI) itself, is the cause for the tumor characteristics of HEEC-Cr(VI) cells. Mechanistically, chronic exposure to Cr(VI) induced abnormal activation of Notch signaling, which is crucial to maintaining the capacity for malignant proliferation and stemness of HEEC-Cr(VI) cells. As expected, N-‍[N-‍(3,5-difluorophenacetyl)‍-L-alanyl]‍-S-phenylglycine t-butyl ester (DAPT), an inhibitor for the Notch pathway, drastically attenuated cancerous phenotypes of HEEC-Cr(VI) cells. In conclusion, our study clarified the molecular mechanism underlying Cr(VI)‍-induced esophageal tumorigenesis, which provides novel insights for further basic research and clinical therapeutic strategies about Cr(VI)‍-associated esophageal cancer.  

    Yilin ZHU, Fanrong LIU, Lei LIU, Jinfu WANG, Fengyuan GAO, Lan YE, Honglei WU, Chengjun ZHOU, Guimei LIN, Xiaogang ZHAO, Peichao LI

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  • Research Article

    Abstract：Numerous studies have demonstrated that the high expression of CXC motif chemokine ligand 16 (CXCL16) in cancer correlates with poor prognosis, as well as tumor cell proliferation, migration, and invasion. While CXCL16 can serve as a tumor biomarker, the underlying mechanism in modulating head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, the aimed was to investigate the CXCL16 expression in HNSCC and to uncover the potential underlying mechanism. Hereby, we determined the high expression of CXCL16 in The Cancer Genome Atlas (TCGA) database, as well as in tissue samples from patients with HNSCC at our central hospital and from HNSCC cell lines. The results showed that CXCL16 knockdown inhibited the proliferation, migration, and invasion of HNSCC cells. Mechanistically, transcriptome sequencing revealed that CXCL16 may affect HNSCC cell growth by regulating the antioxidant pathway of glutathione peroxidase 1 (GPX1). The reactive oxygen species (ROS) levels were elevated in small interfering CXCL16 (si-CXCL16) cells, which may contribute to the inhibition of cell proliferation, migration, and invasion. Moreover, treatment of cells with the GPX1 inhibitor eldecalcitol (ED-71) revealed that HNSCC cell growth was significantly inhibited in the synergistic group of si-CXCL16 and GPX1 inhibitor compared to the si-CXCL16 group. In conclusion, CXCL16 contributed to the development of HNSCC cells by modulating the GPX1-mediated antioxidant pathway. Thus, targeting cellular CXCL16 expression seems to be a promising strategy for treating HNSCC.  

    Ru HE, Hongyi JIANG, Chengchi ZHANG, Yuan CHEN, Wenshun LIU, Xinyue DENG, Xiaozheng ZHU, Yunye LIU, Chuanming ZHENG, Yining ZHANG, Chengying SHAO, Yanting DUAN, Jiajie XU

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