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Cancer stem cells (CSCs), also known as tumor-initiating cells, are a sub-population of tumor cells found in many human cancers that are endowed with self-renewal and pluripotency. CSCs may be more resistant to conventional anticancer therapies than average cancer cells, as they can easily escape the cytotoxic effects of standard chemotherapy, thereby resulting in tumor relapse. Despite significant progress in related research, effective elimination of CSCs remains an unmet clinical need. CSCs are localized in a specialized microenvironment termed the niche, which plays a pivotal role in cancer multidrug resistance. The niche components of CSCs, such as the extracellular matrix, also physically shelter CSCs from therapeutic agents. Colorectal cancer is the most common malignancy worldwide and presents a relatively transparent process of cancer initiation and development, making it an ideal model for CSC niche research. Here, we review recent advances in the field of CSCs using colorectal cancer as an example to illustrate the potential therapeutic value of targeting the CSC niche. These findings not only provide a novel theoretical basis for in-depth discussions on tumor occurrence, development, and prognosis evaluation, but also offer new strategies for the targeted treatment of cancer.

Although parental HIV disclosure has benefits for parents and children, the disclosure rate among parents remains low. This study aims to qualitatively examine parental concerns regarding disclosure of their HIV status to their children. Eighty parents were enrolled in a randomized controlled trial of a three-session disclosure-support intervention, with forty receiving the intervention and forty receiving treatment as usual. Intervention sessions were audio recorded, and transcriptions were qualitatively coded for content related to concerns of disclosure. Four themes emerged: Intention to disclose, disclosure approach, indicators for disclosure, and fears about disclosure. These themes reveal struggles that parents experience when considering HIV disclosure suggesting that an effective disclosure intervention must help parents assess pros and cons, discuss the emotions of the children after the disclosure, and monitor the impact on children’s lives after disclosure over time. Future research is needed to implement interventions supporting HIV-positive parents’ disclosure decision-making and actions.

Jie Wang,1 Huaxin Liang,2 Meiyan Sun,3 Lei Zhang,3 Huijing Xu,3 Wei Liu,3 Yan Li,3 Yue Zhou,4 Yingya Li,5 Miao Li2 1Department of Neurology, The China-Japan Union Hospital of Jilin University, Changchun 130033, China; 2Department of Neurosurgery, The China-Japan Union Hospital of Jilin University, Changchun 130033, China; 3College of Laboratory Medicine, Jilin Medical University, Jilin 132013, China; 4Department of Statistics, North Dakota State University, Fargo, ND 58108, USA; 5Department of Cereal Science, North Dakota State University, Fargo, ND 58108, USA Background: It has been reported that cell inflammation pathways contribute to the development of prostaglandin E2 (PGE2)-inhibitor of DNA-binding protein-1 (ID1)-dependent radioresistance in glioblastoma. Here, we proposed that inhibiting delta-6-desaturase (D6D) could block arachidonic acid synthesis and PGE2 production, thereby reversing PGE2-ID1-dependent radioresistance in glioblastoma cells and xenograft tumor models.Materials and methods: Two glioblastoma cell lines, namely, U-87 MG and LN-229, were used for the in vitro study. The combination effects of SC-26196 (a D6D inhibitor) and radiation were assessed by the MTS assay, colony formation assay, and cell apoptosis analysis. HPLC/MS analysis was performed to quantify the production of arachidonic acid and PGE2. For the in vivo study, 6-week-old nude mice, each bearing a U-87 MG xenograft tumor, were subjected to 4-week treatments of vehicle, SC-26196, radiation, or the combination of both. Tumor growth was monitored during the treatment, and the tumor tissues were collected at the end for further analysis.Results: Treatment with SC-26196 significantly improved radiosensitivity in both glioblastoma cell lines in vitro, and radiosensitivity was associated with inhibited synthesis of arachidonic acid and PGE2. The combination of SC-26196 and radiation synergistically inhibited U-87 MG xenograft tumor growth, in association with the induction of tumor apoptosis and suppressed tumor proliferation. SC-26196 also inhibited arachidonic acid and PGE2 production in vivo and limited expression of ID1.Conclusion: These data suggested that the D6D inhibitor could reverse PGE2-ID1-dependent radioresistance in glioblastoma cells and xenograft tumor models by blocking the synthesis of arachidonic acid and PGE2. Although further investigation is required, the outcomes from this study may guide us in developing a potentially novel combination strategy for current glioblastoma therapy. Keywords: delta-6-desaturase, glioblastoma, radiation therapy, inflammation pathway

Aim To understand COVID patients' experiences of and perspectives on disclosure of their illness and to explore and describe the factors affecting disclosure decisions among COVID patients in China. Background Disease disclosure is a critical component of prevention and control of a virus outbreak, and this is especially true during the COVID-19 pandemic. Understanding COVID patients' experiences and perspectives on disclosure could play a vital role in COVID management. Design A qualitative study. Methods A semi-structured interview guide was used to conduct qualitative in-depth interviews from April to June 2020. All the interviews were audio-recorded and transcribed, and then, a thematic analysis was conducted. The Standards for Reporting Qualitative Research (SRQR) were applied to this study. Results A total of 26 COVID-confirmed patients were recruited for the in-depth interviews. Four themes emerged from the thematic analysis on disclosure: persons disclosed to, reasons for disclosure, reasons for nondisclosure and impact of disclosure. The participants disclosed their COVID diagnosis to different groups, including family, close friends, community members and workplace contacts. The main reasons for disclosure included the following: government policy, social responsibility, gaining support and fear of being blamed for nondisclosure. However, some participants decided not to disclose to some groups for fear of facing stigma and discrimination or to protect family members from discrimination. Despite the potential benefits of obtaining support after disclosure, many participants did experience stigma and discrimination, privacy exposure, psychological distress and social isolation. Conclusions An individual's decision as to whether to disclose their COVID-positive status is affected by many factors. To prevent the spread of COVID-19 and reduce the potential risks of disclosure, such as discrimination and privacy exposure, a balanced intervention should be designed to protect COVID patients and to secure any contact tracing. Therefore, the chances of discrimination could be decreased and patients' confidentiality could be protected. Relevance to clinical practice As the number of COVID patients increases, disclosure of an individual's infectious status is encouraged by health departments. Despite the potential benefits of disclosure, discrimination and privacy exposure should not be ignored. A disclosure protocol is necessary to ensure patients' privacy regarding their COVID status.

KRAS is one of the most frequently mutated oncogenes in cancers. Currently no direct and effective anti-KRAS therapies are available. Using the powerful CRISPR-Cas9 technology to target the mutant KRAS promoter, we designed an epigenetic repressor to silence KRAS through epigenome editing. Catalytically dead Cas9 (dCas9) functioned as a DNA binding device, which was fused with a transcriptional repressor histone deacetylase 1 (HDAC1). We designed a panel of three CRISPR RNAs (crRNAs) covering 1500-bp range of the KRAS promoter and identified that crRNA1 and crRNA2 efficiently silenced KRAS. The suppression of K-Ras resulted in a significant inhibition of cell growth, suppression of colony formation in soft agar and induction of cell death in cancer cells with KRAS mutations. In addition, the chromatin immunoprecipitation (ChIP) assay demonstrated dCas9-HDAC1 modified histone acetylation on the KRAS promoter. Furthermore, transfection of dCas9-HDAC1 protein and gRNA ribonucleoprotein complex also inhibited K-Ras and suppressed cell proliferation. In summary, we have developed a new strategy that combines CRISPR-Cas9 technology with HDAC1 epigenetic silencing to target cancers driven by KRAS mutations.

People living with HIV/AIDS (PLWHA) in China experience significant psychological distress, due to high rates of stigma and low availability of mental health resources. Recently diagnosed Chinese PLWHA who are men who have sex with men (MSM) are particularly vulnerable to distress, facing both HIV and sexual orientation stigma. Reducing distress and enhancing psychological resilience is critical in promoting wellbeing. However, no research to date has examined evidence-based interventions to reduce psychological symptoms and improve resilience in this population. Based on qualitative research on their mental health needs, we developed a culturally tailored, brief 3-session CBT skills-based intervention for integration into primary care [Yang, J. P., Simoni, J., Cheryan, S., Shiu, C., Chen, W., Zhao, H., & Lu, H. (2018). The development of a brief distress reduction intervention for individuals recently diagnosed with HIV in China. Cognitive Behavioral Practice, 25(2), 319-334. doi: 10.1016/j.cbpra.2017.08.002 ]. The intervention includes cognitive restructuring to address depressive thought patterns, behavioral activation to decrease isolation, and paced breathing to reduce anxiety. We conducted a pilot Type 1 hybrid effectiveness-implementation trial assessing pre-post mental health outcomes as well as feasibility, acceptability, and appropriateness information. Ten recently diagnosed MSM completed the research protocol of three individual weekly sessions. Paired-samples t tests demonstrated significant reduction in HIV-related distress, depression, problems with adjustment, as well as improvements in resilience, and perceived social support. Participants and community advisory board members found the intervention highly acceptable, appropriate, and feasible. Preliminary data from the first known study examining a psychological intervention with evidence-based components for recently diagnosed Chinese MSM suggests that this brief intervention may be useful for reducing distress and promoting resilience.

Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for specific targeting and extracellular vesicles for efficient membrane fusion, the resulting ligand-displaying extracellular vesicles were capable of specific delivery of siRNA to cells, and efficiently blocked tumour growth in three cancer models. Extracellular vesicles displaying an aptamer that binds to prostate-specific membrane antigen, and loaded with survivin siRNA, inhibited prostate cancer xenograft. The same extracellular vesicle instead displaying epidermal growth-factor receptor aptamer inhibited orthotopic breast cancer models. Likewise, survivin siRNA-loaded and folate-displaying extracellular vesicles inhibited patient-derived colorectal cancer xenograft.

Anoctamin 7 (ANO7) is a member of the transmembrane protein TMEM16 family. It has a conservative topology similar to other members in this family, such as the typical eight-transmembrane domain, but it also has unique features. Although the ion channel role of ANO7 has been well accepted, evolutionary analyses and relevant studies suggest that ANO7 may be a multi-facet protein in function. Studies have shown that ANO7 may also function as a scramblase. ANO7 is highly expressed in prostate cancer as well as normal prostate tissues. A considerable amount of evidence has confirmed that ANO7 is associated with human physiology and pathology, particularly with the development of prostate cancer, which makes ANO7 a good candidate as a diagnostic and prognostic biomarker. In addition, ANO7 may be a potential target for prostate cancer immunotherapy. Antibody-based or T cell-mediated immunotherapies against prostate cancer by targeting ANO7 have been highly anticipated. ANO7 may also correlate with several other types of cancers or diseases, where further studies are warranted.

Vitamin D is an important hormone that regulates many physiological processes related to human health. Through its nuclear receptor, VDR, vitamin D controls gene expression through genetic and epigenetic mechanisms. Increasing data have demonstrated the anti-cancer activities of vitamin D in various cancers, including colon cancer. This review summarizes the recent progresses in our understanding of the molecular mechanisms of vitamin D and its interaction with the epigenetic machinery in colon cancer. Vitamin D changes the status of DNA methylation and histone modifications, resulting in the activation of tumor suppressors and inhibition of oncogenes. In addition, vitamin D activates the expression of tumor suppressing miRNAs, which contribute to the tumor suppressive activity. Further understanding of the epigenetic action of vitamin D will help the development of therapeutic strategies targeting the vitamin D signaling pathway without inducing the hypercalcemic side effects.

Gut microbiota dysbiosis, which has been linked to many neurological diseases, is common in HIV infection. However, its role in the pathogenesis of neurocognitive impairment is still not established. In this study, a total of 85 HIV infected subjects, naïve to antiretroviral therapy, were classified into two groups—those with HIV-associated neurological diseases (HAND) and those without, using the Montreal Cognitive Assessment (MoCA) test. Fecal samples were collected from all subjects and microbiota were analyzed by 16S rRNA amplicon sequencing. Subjects with HAND were older (P < 0.001), with lower levels of education (P = 0.002), lower CD4 T-cell counts (P = 0.032), and greater heterosexual preference (P < 0.001), than those without HAND. Gut microbiota from subjects with HAND showed significantly lower α-diversity compared to gut microbiota from subjects without HAND (Shannon index, P = 0.003). To exclude confounding bias, 25 subjects from each group, with comparable age, gender, CD4 T-cell count, educational level and sexual preference were further analyzed. The two groups showed comparable α-diversity (for SOB index, Shannon index, Simpson index, ACE index, and Chao index, all with P-value > 0.05) and β-diversity (ANOSIM statistic = 0.010, P = 0.231). There were no significant differences in microbiota composition between the two groups after the correction for a false discovery rate. Consistently, microbiota from the two groups presented similar predictive functional profiles. Gut microbiota dysbiosis is not independently associated with neurocognitive impairment in people living with HIV.

Both siRNA and miRNA can serve as powerful gene-silencing reagents but their specific delivery to cancer cells in vivo without collateral damage to healthy cells remains challenging. We report here the application of RNA nanotechnology for specific and efficient delivery of anti-miRNA seed-targeting sequence to block the growth of prostate cancer in mouse models. Utilizing the thermodynamically ultra-stable three-way junction of the pRNA of phi29 DNA packaging motor, RNA nanoparticles were constructed by bottom-up self-assembly containing the anti-prostate-specific membrane antigen (PSMA) RNA aptamer as a targeting ligand and anti-miR17 or anti-miR21 as therapeutic modules. The 16 nm RNase-resistant and thermodynamically stable RNA nanoparticles remained intact after systemic injection in mice and strongly bound to tumors with little or no accumulation in healthy organs 8 hours postinjection, and subsequently repressed tumor growth at low doses with high efficiency.

The purpose of this study was to identify fecal bacterial microbiome changes in patients with chronic human immunodeficiency virus (HIV) infection in China. Bacterial 16S rRNA genes were amplified, sequenced (454 pyrosequencing), and clustered into operational taxonomic units using the QIIME software. Relative abundance at the phylum and genus levels were calculated. Alpha diversity was determined by Chao 1 and observed-species indices, and beta diversity was determined by double principal component analysis using the estimated phylogeny-based unweighted Unifrac distance matrices. Fecal samples of the patients with chronic HIV-infection tended to be enriched with bacteria of the phyla Firmicutes (47.20% ± 0.43 relative abundance) and Proteobacteria (37.21% ± 0.36) compared with those of the non-HIV infected controls (17.95% ± 0.06 and 3.81% ± 0.02, respectively). Members of the genus Bilophila were exclusively detected in samples of the non-HIV infected controls. Bacteroides and arabacteroides were more abundant in the chronic HIV-infected patients. Our study indicated that chronic HIV-infected patients in China have a fecal bacterial microbiome composition that is largely different from that found in non-HIV infected controls, and further study is needed to evaluate whether microbiome changes play a role in disease complications in the distal gut, including opportunistic infections.

Colorectal cancer (CRC) is one of the most lethal malignancies worldwide and CRC therapy remains unsatisfactory. In recent decades, nitric oxide (NO)—a free-radical gas—plus its endogenous producer NO synthases (NOS), have attracted considerable attention. NO exerts dual effects (pro- and anti-tumor) in cancers. Endogenous levels of NO promote colon neoplasms, whereas exogenously sustained doses lead to cytotoxic functions. Importantly, NO has been implicated as an essential mediator in many signaling pathways in CRC, such as the Wnt/β-catenin and extracellular-signal-regulated kinase (ERK) pathways, which are closely associated with cancer initiation, metastasis, inflammation, and chemo-/radio-resistance. Therefore, NO/NOS have been proposed as promising targets in the regulation of CRC carcinogenesis. Clinically relevant NO-donating agents have been developed for CRC therapy to deliver a high level of NO to tumor sites. Notably, inducible NOS (iNOS) is ubiquitously over-expressed in inflammatory-associated colon cancer. The development of iNOS inhibitors contributes to targeted therapies for CRC with clinical benefits. In this review, we summarize the multifaceted mechanisms of NO-mediated networks in several hallmarks of CRC. We review the clinical manifestation and limitations of NO donors and NOS inhibitors in clinical trials. We also discuss the possible directions of NO/NOS therapies in the immediate future.

Background Mesenchymal stem cells (MSCs) are multipotent, genomic stable, self-renewable, and culturally expandable adult stem cells. MSCs facilitate tissue development, maintenance and repair, and produce secretory factors that support engraftment and trophic functions, marking them an attractive option in cell therapy, regenerative medicine and tissue engineering. Method In this review, we summarize the recent researches regarding the isolation and characterization of MSCs, therapeutic applications and advanced engineering techniques. We also discuss the advantages and limitations that remain to be overcome for MSCs based therapy. Results It has been demonstrated that MSCs are able to modulate endogenous tissue and immune cells. Preclinical studies and early phase clinical trials have shown their great potential for tissue engineering of bone, cartilage, marrow stroma, muscle, fat, and other connective tissues. Conclusions MSC-based therapy show considerable promise to rebuild damaged or diseased tissues, which could be a promising therapeutic method for regeneration medicine.

The dietary effect on gut health has long been recognized through the empirical practice of soothing gastric discomfort with certain types of food, and recently the correlation between specific diets with lower incidences of several gastrointestinal diseases has been revealed. Ingredients from those considered beneficial foods have been isolated and studied, and some of them have already been put into the supplement market. In this review, we focus on latest studies of these food-derived ingredients for their proposed preventive and therapeutic roles in gastrointestinal disorders, with the attempt of drawing evidence-based suggestions on consuming these products.

Aquaporin-8 (AQP8) is a water channel protein expressed exclusively in granulosa cells (GCs) in mouse ovary. Our previous studies of AQP8-deficient (AQP8-/-) mice demonstrated that AQP8 participates in folliculogenesis, including in the formation of follicles, ovulation, and atresia. However, its physiological function in formation of the antral follicle is still largely unknown. In the present study, we observed significantly increased numbers of antral follicles in AQP8-/- ovaries as well as significantly increased follicular antrum formation in in vitro 3D culture of AQP8-/- follicles. Functional detection of AQP8-/- GCs indicated that cell proliferation is impaired with FSH treatment, and wound healing and Transwell migration are also impaired with or without FSH treatment, compared with that in WT. However, the biosynthesis of estradiol and progesterone as well as the mRNA levels of key steroidogenic enzyme genes (CYP19A1 and StAR) in AQP8-/- GCs did not change, even with addition of FSH and/or testosterone. In order to estimate the influence of the impaired proliferation and migration on the density of GC mass, preantral follicles were injected with FITC-dextran, which distributes only in the intercellular space, and analyzed by confocal microscopy. The micrographs showed significantly higher transmission of fluorescence in AQP8-/- follicles, suggesting increased intercellular space of GCs. Based on this evidence, we concluded that AQP8 deficiency leads to increased formation of follicular antra in vivo and in vitro, and the mechanism may be associated with increased intercellular space of GCs, which may be caused by defective proliferation and migration of GCs. This study may offer new insight into the molecular mechanisms of the formation of follicular antrum.

For HIV-infected parents, deciding whether and how to disclose their illness to their children is a major stressor. In China, due to significant HIV stigma, disclosure distress is acute. Our objective was to understand HIV-infected parents' concerns regarding disclosure of their HIV status to their children. HIV-infected parents (N=10) were recruited to attend a three-session nursing intervention. In our post hoc analysis, progress notes from each session were analyzed for themes to illuminate parental decision-making processes. By the end of the intervention, all parents had considered the importance of HIV disclosure and stated that they felt somewhat prepared to disclose. Primary themes included (a) severe stigma experienced by fathers who were sexually active with men, (b) need for both parents to agree on plans for disclosure, and (c) parents' fears about the consequences of disclosure. Parents living with HIV can benefit from nurse-delivered interventions during parental HIV disclosure decision-making.

Background Understanding the mechanisms of drug resistance can facilitate better management of antiretroviral therapy, helping to prevent transmission and decrease the morbidity and mortality of people living with HIV/AIDS. However, there is little data about transmitted drug resistance and acquired drug resistance for HIV/AIDS patients in Shanghai. Methods A retrospective cohort study of HIV-infected patients who visited the Department of Infectious Disease from June 2008 to June 2015 was conducted in Shanghai, China. Logistic regression analysis was performed to analyze risk factors for drug resistance among HIV-infected people with virological failure. The related collected factors included patient age, gender, marital status, infection route, baseline CD4 count, antiretroviral therapy regimens, time between HIV diagnosis and initiating antiretroviral therapy. Factors with p

The class I selective inhibitor of the histone deacetylases, mocetinostat, has promising antitumor activities in both preclinical studies and the clinical trials. To understand how mocetinostat induces apoptosis, we examined the effects of mocetinostat on miR-31, a proapoptotic microRNA that was previously found to be epigenetically silenced in prostate cancer. We found that miR-31 was significantly upregulated by mocetinostat in prostate cancer cells. Antiapoptotic protein E2F6, the target of miR-31, was decreased by mocetinostat treatment. When miR-31 was blocked with an inhibitor, the ability of mocetinostat to induce apoptosis was reduced. We further demonstrated that mocetinostat enhanced the activity of docetaxel in apoptosis induction. While siRNA knockdown of E2F6 sensitized cancer cells to mocetinostat-induced apoptosis, overexpression of E2F6 blocked mocetinostat-induced apoptosis. In an orthotopic xenograft model, we demonstrated that mocetinostat activated miR-31, decreased E2F6, induced apoptosis, and significantly reduced prostate cancer growth. Importantly, we found that mocetinostat also increased miR-31 expression, decreased E2F6, and induced apoptosis in the primary prostate cancer stem cells. Thus, activation of miR-31 and downregulation of E2F6 constitute an important mechanism in mocetinostat-induced apoptosis in prostate cancer.

Cytochrome P450 enzyme CYP3A4 is an important drug-metabolizing enzyme, and high levels of tumoral expression of CYP3A4 are linked to drug resistance. We investigated the function of vitamin D–regulated miR-627 in intratumoral CYP3A4 suppression and its role in enhancing the efficacy of chemotherapy. We found that miR-627 targets CYP3A4 and suppresses CYP3A4 expression in colon cancer cell lines. Furthermore, calcitriol (the active form of vitamin D) suppressed CYP3A4 expression by activating miR-627. As a result, calcitriol inhibited CYP3A4-mediated metabolism of irinotecan (a topoisomerase I inhibitor) in cancer cells. We show that calcitriol enhanced the efficacy of irinotecan in growth inhibition and apoptosis induction. When miR-627 is inhibited, calcitriol fails to enhance the activity of irinotecan. In addition, overexpression of miR-627 or siRNA knockdown of CYP3A4 enhanced the efficacy of irinotecan in growth inhibition and apoptosis induction. In contrast, overexpression of CYP3A4 abolished the effects of calcitriol on the activity of irinotecan. Using a nude mouse xenograft model, we demonstrated that calcitriol inhibited CYP3A4 and enhanced the in vivo antitumor activity of irinotecan without causing side effects. Our study identified a novel target for improving cancer therapy, i.e., modulating the intratumoral CYP3A4-mediated drug metabolism with vitamin D. This strategy could enhance the therapeutic efficacy without eliciting the side effects. Mol Cancer Ther; 15(9); 2086–95. ©2016 AACR.

In conjunction with the classical functions of regulating intestinal, bone, and kidney calcium and phosphorus absorption, as well as bone mineralization of vitamin D, the population-based association between low vitamin D status and increased cancer risk is now generally accepted. Inflammation is causally related to oncogenesis. It is widely thought that vitamin D plays an important role in the modulation of the inflammation system by regulating the production of inflammatory cytokines and immune cells, which are crucial for the pathogenesis of many immune-related diseases. Mechanistic studies have shown that vitamin D influences inflammatory processes involved in cancer progression, including cytokines, prostaglandins, MAP kinase phosphatase 5 (MKP5), the nuclear factor kappa B (NF-κB) pathway, and immune cells. Multiple studies have shown that vitamin D has the potential to inhibit tumor development by interfering with the inflammation system. The present review summarizes recent studies of the mechanisms of vitamin D on regulating the inflammation system, which contributes to its potential for cancer prevention and therapy. This review helps answer whether inflammation mediates a causal relationship between vitamin D and tumorigenesis.

Objective: Neuromyelitis optica (NMO) is a severe neurological demyelinating autoimmune disease that affects the optic nerves and spinal cord with no cure and no FDA-approved therapy. Research over the last decade revealed that the binding of NMO-IgG to the water channel protein astrocyte aquaporin 4 (AQP4) might be the primary cause of NMO pathogenesis. The purpose of this study was to identify potential blockers of NMO-IgG and AQP4 binding. Methods: We developed a two-step screening platform consisting of a reporter cell-based high-throughput screen assay and a cell viability-based assay. Purified NMO-IgG from NMO patient serum and transfected Chinese hamster lung fibroblast V79 cells stably expressing human M23-AQP4 were used for primary screening of 40,000 small molecule fractions from 500 traditional Chinese herbs. Results: Thirty-six positive fractions were identified, of which 3 active fractions (at 50 μg/ml) were found to be from the same Chinese traditional herb Mahonia japonica (Thunb.). A bioactivity-guided method based on a primary screening assay for blocking activity led to the isolation of an active single natural compound, isotetrandrine, from the 3 fractions. Our immunofluorescence staining results showed that isotetrandrine can block NMO-IgG binding to AQP4 without affecting the expression and function of AQP4. It can also inhibit NMO-IgG binding to astrocyte AQP4 in NMO patient sera and block NMO-IgG-dependent complement-mediated cytotoxicity with the IC50 at ∼3 μM. Conclusions: The present study developed a cell-based high-throughput screen to identify small molecule inhibitors for NMO-IgG and AQP4 binding, and suggests a potential therapeutic value of isotetrandrine in NMO.