Research upon Cu-Doping Contents in TiO2 Nanoparticles Incorporated onto Cellulose Nanofibers for Dye Removal and Self-Cleaning Applications.

Cu-doping contents in the TiO2 lattice structure were studied to show the effects on the crystal structure, morphology, and photocatalytic activity of TiO2 nanoparticles and thus composite cellulosic nanofibrous membranes. Pristine and copper-doped TiO2 nanoparticles were synthesized using the sol-gel technique, a wet chemical method with the advantages of low synthesizing temperature, uniform nanosize distribution, and purity. The as-synthesized semiconductor nanoparticles were first tested with the dye removal process and then impregnated onto electrospun cellulose nanofibers (CL nanofibers) to acquire modified nanofibers with self-cleaning properties. The as-prepared composite CL nanofibers consisting of doped and undoped TiO2 nanoparticles were characterized by various techniques, such as field emission scanning electron microscopy, transmission electron microscopy, UV-vis, X-ray diffraction, Fourier transform infrared spectroscopy, and tensile tests. The copper-doped TiO2 molar ratio in the nanocomposite was found to possess a pronounced impact on the dye removal and self-cleaning effects under the visible light spectrum, whereas TiO2 is highly effective under specific UV-light irradiation. Optical measurements and dye decomposition showed that the Cu-doped TiO2 nanocomposite was optimized at a 1% molar ratio by the copper-doping concentration regarding dye removal and self-cleaning applications under the visible light range.

Critical contributions of protein cargos to the functions of macrophage-derived extracellular vesicles.

BACKGROUND: Macrophages are highly plastic innate immune cells that play key roles in host defense, tissue repair, and homeostasis maintenance. In response to divergent stimuli, macrophages rapidly alter their functions and manifest a wide polarization spectrum with two extremes: M1 or classical activation and M2 or alternative activation. Extracellular vesicles (EVs) secreted from differentially activated macrophages have been shown to have diverse functions, which are primarily attributed to their microRNA cargos. The role of protein cargos in these EVs remains largely unexplored. Therefore, in this study, we focused on the protein cargos in macrophage-derived EVs. RESULTS: Naïve murine bone marrow-derived macrophages were treated with lipopolysaccharide or interlukin-4 to induce M1 or M2 macrophages, respectively. The proteins of EVs and their parental macrophages were subjected to quantitative proteomics analyses, followed by bioinformatic analyses. The enriched proteins of M1-EVs were involved in proinflammatory pathways and those of M2-EVs were associated with immunomodulation and tissue remodeling. The signature proteins of EVs shared a limited subset of the proteins of their respective progenitor macrophages, but they covered many of the typical pathways and functions of their parental cells, suggesting their respective M1-like and M2-like phenotypes and functions. Experimental examination validated that protein cargos in M1- or M2-EVs induced M1 or M2 polarization, respectively. More importantly, proteins in M1-EVs promoted viability, proliferation, and activation of T lymphocytes, whereas proteins in M2-EVs potently protected the tight junction structure and barrier integrity of epithelial cells from disruption. Intravenous administration of M2-EVs in colitis mice led to their accumulation in the colon, alleviation of colonic inflammation, promotion of M2 macrophage polarization, and improvement of gut barrier functions. Protein cargos in M2-EVs played a key role in their protective function in colitis. CONCLUSION: This study has yielded a comprehensive unbiased dataset of protein cargos in macrophage-derived EVs, provided a systemic view of their potential functions, and highlighted the important engagement of protein cargos in the pathophysiological functions of these EVs.

Development of Activity Rules and Chemical Fragment Design for In Silico Discovery of AChE and BACE1 Dual Inhibitors against Alzheimer's Disease.

Multi-target drug development has become an attractive strategy in the discovery of drugs to treat of Alzheimer's disease (AzD). In this study, for the first time, a rule-based machine learning (ML) approach with classification trees (CT) was applied for the rational design of novel dual-target acetylcholinesterase (AChE) and ß-site amyloid-protein precursor cleaving enzyme 1 (BACE1) inhibitors. Updated data from 3524 compounds with AChE and BACE1 measurements were curated from the ChEMBL database. The best global accuracies of training/external validation for AChE and BACE1 were 0.85/0.80 and 0.83/0.81, respectively. The rules were then applied to screen dual inhibitors from the original databases. Based on the best rules obtained from each classification tree, a set of potential AChE and BACE1 inhibitors were identified, and active fragments were extracted using Murcko-type decomposition analysis. More than 250 novel inhibitors were designed in silico based on active fragments and predicted AChE and BACE1 inhibitory activity using consensus QSAR models and docking validations. The rule-based and ML approach applied in this study may be useful for the in silico design and screening of new AChE and BACE1 dual inhibitors against AzD.

Corrigendum to' Anxiolytic effect of Korean Red Ginseng through upregulation of serotonin and GABA transmission and BDNF expression in immobilized mice' [Journal of Ginseng Research Volume 46, Issue 6, November 2022, Pages 819-829].

[This corrects the article DOI: 10.1016/j.jgr.2022.07.007.].

Four types of change and self-other agreement on change in personality traits during college years: A multi-informant longitudinal study.

Research in personality trait change has largely relied on mean-level and rank-order change across the lifespan. The current research expanded the literature in several ways: analyzing four types of change and correlated change patterns, obtaining multi-informant reports, including lower-order personality traits, and collecting multiple assessments during a short yet important time for college-attending emerging adults (baseline N = 259, Mage  = 18.79). There was little evidence for mean-level change, yet participants showed significant individual differences such that rank-ordering and ipsative profiles were much more dynamic than mean score patterns. Informant-reports from close others demonstrated largely similar patterns: little to no mean-level change, significant increase in rank-ordering, and about half of participants reporting configural change mostly in elevation and scatter rather than in profile shapes. Interestingly, there was no correlated change between self and other-reports. This indicated that close others do not share individuals' perception of their own personality trait change, at least not in the demographic group studied. By examining individual-level, sample-level, and multi-informant perspectives, our thorough investigation provided useful benchmarks for future research to examine the source of variability in change trajectories.

NVL-520 Is a Selective, TRK-Sparing, and Brain-Penetrant Inhibitor of ROS1 Fusions and Secondary Resistance Mutations.

SIGNIFICANCE: The combined preclinical features of NVL-520 that include potent targeting of ROS1 and diverse ROS1 resistance mutations, high selectivity for ROS1 G2032R over TRK, and brain penetration mark the development of a distinct ROS1 TKI with the potential to surpass the limitations of earlier-generation TKIs for ROS1 fusion-positive patients. This article is highlighted in the In This Issue feature, p. 517.

Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain.

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates the transcription of many genes that are responsible for the adaptation and survival of tumor cells in hypoxic environments. Over the past few decades, tremendous efforts have been made to comprehensively understand the role of HIF-1 in tumor progression. Based on the pivotal roles of HIF-1 in tumor biology, many HIF-1 inhibitors interrupting expression, stabilization, DNA binding properties, or transcriptional activity have been identified as potential therapeutic agents for various cancers, yet none of these inhibitors have yet been successfully translated into clinically available cancer treatments. In this review, we briefly introduce the regulation of the HIF-1 pathway and summarize its roles in tumor cell proliferation, angiogenesis, and metastasis. In addition, we explore the implications of HIF-1 in the development of drug resistance and cancer-related pain: the most commonly encountered obstacles during conventional anticancer therapies. Finally, the current status of HIF-1 inhibitors in clinical trials and their perspectives are highlighted, along with their modes of action. This review provides new insights into novel anticancer drug development targeting HIF-1. HIF-1 inhibitors may be promising combinational therapeutic interventions to improve the efficacy of current cancer treatments and reduce drug resistance and cancer-related pain.

Anxiolytic effect of Korean Red Ginseng through upregulation of serotonin and GABA transmission and BDNF expression in immobilized mice.

Background: Anxiolytic properties of Korean Red Ginseng (KRG) have been previously reported. However, the exact mechanism(s) of action remains to be elucidated. The present study investigated the effect of KRG on immobilization-induced anxiety-like behaviors in mice and explored the involvement of the serotonin and GABA systems and BDNF in the anxiolytic action. Methods: Mice were orally administered with KRG (200 mg/kg/day) for 4 weeks and immobilized once daily for 2 h. p-Chlorophenylalanine (p-CPA) was intraperitoneally injected on day 22-28, and flumazenil or bicuculline was injected on day 25-28. After behavioral evaluations, brains were dissected for biochemical analyses. Results: KRG improved immobilization-induced anxiety-like behaviors in mice, as assessed by the elevated plus maze (EPM) and marble burying tests (MBT). The anxiolytic effect of KRG was comparable to that of fluoxetine, a reference drug clinically used for anxiety disorders. A serotonin synthesis inhibitor, p-CPA, blocked the effect of KRG in the EPM and MBT, indicating the requirement of serotonin synthesis for anxiolytic action. In addition, the anxiolytic effect of KRG was inhibited by bicuculline (a GABAA antagonist) in MBT, implying the involvement of GABA transmission. Western blotting analyses revealed that KRG upregulated the expression of tryptophan hydroxylase and GABAA receptor in the brain, which was blocked by p-CPA. Enhanced BDNF expression by KRG in the hippocampus was also indicated to mediate the anxiolytic action of KRG in immobilized mice. Conclusion: KRG exhibited the anxiolytic effect in immobilized mice by multiple mechanisms of action, involving enhanced serotonin and GABA transmissions and BDNF expression.

A cultural evolutionary behavior genetics will need a more sophisticated conceptualization of cultural traits.

A framework that brings together cultural perspectives and behavior genetics has long been needed. To be successful, however, we need sophistication in the conceptualization of culture. Here, we highlight three imperatives to this end: the need for a clear definition of cultural traits, inclusion of the role of societal power, and recognizing the distinction between traits and characteristic adaptations.

Suppression of Tumor Growth and Cell Migration by Indole-Based Benzenesulfonamides and Their Synergistic Effects in Combination with Doxorubicin.

Pharmacological inhibition of the enzyme activity targeting carbonic anhydrases (CAs) demonstrated antiglaucoma and anticancer effects through pH control. Recently, we reported a series of indole-based benzenesulfonamides as potent CA inhibitors. The present study aimed to evaluate the antitumor effects of these compounds against various cancer cell lines, including breast cancer (MDA-MB-231, MCF-7, and SK-BR-3), lung cancer (A549), and pancreatic cancer (Panc1) cells. Overall, more potent cytotoxicity was observed on MCF-7 and SK-BR-3 cells than on lung or pancreatic cancer cells. Among the 15 compounds tested, A6 and A15 exhibited potent cytotoxic and antimigratory activities against MCF-7 and SK-BR-3 cells in the CoCl2-induced hypoxic condition. While A6 and A15 markedly reduced the viability of control siRNA-treated cells, these compounds could not significantly reduce the viability of CA IX-knockdown cells, suggesting the role of CA IX in their anticancer activities. To assess whether these compounds exerted synergism with a conventional anticancer drug doxorubicin (DOX), the cytotoxic effects of A6 or A15 combined with DOX were analyzed using Chou-Talalay and Bliss independence methods. Our data revealed that both A6 and A15 significantly enhanced the anticancer activity of DOX. Among the tested pairs, the combination of DOX with A15 showed the strongest synergism on SK-BR-3 cells. Moreover, this combination further attenuated cell migration compared to the respective drug. Collectively, our results demonstrated that A6 and A15 suppressed tumor growth and cell migration of MCF-7 and SK-BR-3 cells through inhibition of CA IX, and the combination of these compounds with DOX exhibited synergistic cytotoxic effects on these breast cancer cells. Therefore, A6 and A15 may serve as potential anticancer agents alone or in combination with DOX against breast cancer.

Sonidegib Suppresses Production of Inflammatory Mediators and Cell Migration in BV2 Microglial Cells and Mice Treated with Lipopolysaccharide via JNK and NF-κB Inhibition.

Our structure-based virtual screening of the FDA-approved drug library has revealed that sonidegib, a smoothened antagonist clinically used to treat basal cell carcinoma, is a potential c-Jun N-terminal kinase 3 (JNK3) inhibitor. This study investigated the binding of sonidegib to JNK3 via 19F NMR and its inhibitory effect on JNK phosphorylation in BV2 cells. Pharmacological properties of sonidegib to exert anti-inflammatory and anti-migratory effects were also characterized. We found that sonidegib bound to the ATP binding site of JNK3 and inhibited JNK phosphorylation in BV2 cells, confirming our virtual screening results. Sonidegib also inhibited the phosphorylation of MKK4 and c-Jun, the upstream and downstream signals of JNK, respectively. It reduced the lipopolysaccharide (LPS)-induced production of pro-inflammatory factors, including interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), and nitric oxide (NO), and the expression of inducible NO synthase and cyclooxygenase-2. The LPS-induced cell migration was suppressed by sonidegib. Sonidegib inhibited the LPS-induced IκBα phosphorylation, thereby blocking NF-κB nuclear translocation. Consistent with these findings, orally administered sonidegib attenuated IL-6 and TNF-α levels in the brains of LPS-treated mice. Collectively, our results indicate that sonidegib suppresses inflammation and cell migration in LPS-treated BV2 cells and mice by inhibiting JNK and NF-κB signaling. Therefore, sonidegib may be implicated for drug repurposing to alleviate neuroinflammation associated with microglial activation.

Efonidipine Inhibits JNK and NF-κB Pathway to Attenuate Inflammation and Cell Migration Induced by Lipopolysaccharide in Microglial Cells.

Efonidipine, a calcium channel blocker, is widely used for the treatment of hypertension and cardiovascular diseases. In our preliminary study using structure-based virtual screening, efonidipine was identified as a potential inhibitor of c-Jun N-terminal kinase 3 (JNK3). Although its antihypertensive effect is widely known, the role of efonidipine in the central nervous system has remained elusive. The present study investigated the effects of efonidipine on the inflammation and cell migration induced by lipopolysaccharide (LPS) using murine BV2 and human HMC3 microglial cell lines and elucidated signaling molecules mediating its effects. We found that the phosphorylations of JNK and its downstream molecule c-Jun in LPS-treated BV2 cells were declined by efonidipine, confirming the finding from virtual screening. In addition, efonidipine inhibited the LPS-induced production of pro-inflammatory factors, including interleukin-1ß (IL-1ß) and nitric oxide. Similarly, the IL-1ß production in LPS-treated HMC3 cells was also inhibited by efonidipine. Efonidipine markedly impeded cell migration stimulated by LPS in both cells. Furthermore, it inhibited the phosphorylation of inhibitor kappa B, thereby suppressing nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated BV2 cells. Taken together, efonidipine exerts anti-inflammatory and anti-migratory effects in LPS-treated microglial cells through inhibition of the JNK/NF-κB pathway. These findings imply that efonidipine may be a potential candidate for drug repositioning, with beneficial impacts on brain disorders associated with neuroinflammation.

The moderating and mediating roles of mindfulness and rumination on COVID-19 stress and depression: A longitudinal study of young adults.

The COVID-19 pandemic has not only accounted for a substantial number of deaths in the United States but also deleterious mental health outcomes. We integrated multiple lines of previous research to better understand psychological strengths and difficulties in the face of the pandemic by testing a moderated mediation model that posited that rumination mediates the relationship between COVID-related stress and depression, and mindfulness moderates the relationship between COVID-related stress and rumination. The participants were 196 young adults (79.6% female, 53.1% persons of color), who ranged in age between 18 and 33 years (M = 21.21; SD = 3.62). The participants completed measures of COVID-19 stress, rumination, mindfulness, and depressive symptoms at four time points spanning 1 month. Cross-sectional moderated mediation analysis of the data showed that COVID-related stress predicted rumination, which in turn, predicted depressive symptoms. In addition, mindfulness buffered the relationship between COVID-related stress and rumination. Later, we ran exploratory analyses to examine the robustness of the main models at each wave, linear mixed-effects models to investigate change over time, and conducted a cross-lagged model to test for directional effects. Notably, the longitudinal findings suggested that COVID-related stress and rumination tended to decrease over time and mindfulness remained temporally stable. Additionally, increases in rumination predicted increases in depression. Some longitudinal findings did not consistently congrue with cross-sectional results. Overall, the findings highlight the diverse ways in which individuals cope with stress and the promise of mindfulness as a protective factor against the negative effects of pandemic-related stressors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Analysis of lorlatinib analogs reveals a roadmap for targeting diverse compound resistance mutations in ALK-positive lung cancer.

Lorlatinib is currently the most advanced, potent and selective anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor for the treatment of ALK-positive non-small cell lung cancer in the clinic; however, diverse compound ALK mutations driving therapy resistance emerge. Here, we determine the spectrum of lorlatinib-resistant compound ALK mutations in patients, following treatment with lorlatinib, the majority of which involve ALK G1202R or I1171N/S/T. We further identify structurally diverse lorlatinib analogs that harbor differential selective profiles against G1202R versus I1171N/S/T compound ALK mutations. Structural analysis revealed increased potency against compound mutations through improved inhibition of either G1202R or I1171N/S/T mutant kinases. Overall, we propose a classification of heterogenous ALK compound mutations enabling the development of distinct therapeutic strategies for precision targeting following sequential tyrosine kinase inhibitors.

Induction of Paraptotic Cell Death in Breast Cancer Cells by a Novel Pyrazolo[3,4-h]quinoline Derivative through ROS Production and Endoplasmic Reticulum Stress.

Chemotherapy has been a standard intervention for a variety of cancers to impede tumor growth, mainly by inducing apoptosis. However, development of resistance to this regimen has led to a growing interest and demand for drugs targeting alternative cell death modes, such as paraptosis. Here, we designed and synthesized a novel derivative of a pyrazolo[3,4-h]quinoline scaffold (YRL1091), evaluated its cytotoxic effect, and elucidated the underlying molecular mechanisms of cell death in MDA-MB-231 and MCF-7 breast cancer (BC) cells. We found that YRL1091 induced cytotoxicity in these cells with numerous cytoplasmic vacuoles, one of the distinct characteristics of paraptosis. YRL1091-treated BC cells displayed several other distinguishing features of paraptosis, excluding autophagy or apoptosis. Briefly, YRL1091-induced cell death was associated with upregulation of microtubule-associated protein 1 light chain 3B, downregulation of multifunctional adapter protein Alix, and activation of extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase. Furthermore, the production of reactive oxygen species (ROS) and newly synthesized proteins were also observed, subsequently causing ubiquitinated protein accumulation and endoplasmic reticulum (ER) stress. Collectively, these results indicate that YRL1091 induces paraptosis in BC cells through ROS generation and ER stress. Therefore, YRL1091 can serve as a potential candidate for the development of a novel anticancer drug triggering paraptosis, which may provide benefit for the treatment of cancers resistant to conventional chemotherapy.

We are not all the same: The importance of perceived difference in racial ideology and Afrocentricity for African American relationships.

A large body of existing research on African American relationships perpetuates a deficit model that assumes Eurocentric norms and emphasizes between-group differences (e.g., cross-racial comparisons with the majority group-European Americans). The current study examined within-group variability and the influence of culturally unique factors, Afrocentricity, racial ideology, and perceived discrepancy between self and partner on African American relationship processes. Data were collected from 137 self-identified African American adults in same-race, cross-gender relationships. Consistent with the literature on protective values of Afrocentricity, there was an association between reported relationship quality and high levels of one's own and perceived partner's Afrocentricity. Discrepancies between self and partner Afrocentricity were not associated with relationship processes, but higher perceived discrepancies across all four subscales of racial ideology were associated with lower relationship dedication. Higher perceived discrepancies on the humanist and assimilationist subscales were also related to higher levels of conflict. These findings have important clinical implications and demonstrate a need for further research into the nuances of individual factors and dyadic processes that are unique to African American couples.

Un gran número de investigaciones existentes sobre las relaciones afroestadounidenses perpetúa un modelo deficitario que supone normas eurocéntricas y enfatiza las diferencias entre grupos (p. ej.: las comparaciones interraciales con el grupo mayoritario: los estadounidenses de ascendencia europea). El presente estudio analizó la variabilidad intragrupal y la influencia de los factores culturalmente únicos, la afrocentricidad, la ideología racial y la discrepancia percibida entre el yo y el otro integrante de la pareja en los procesos relacionales afroestadounidenses. Se recolectaron datos de 137 adultos autoidentificados como afroestadounidenses que estaban en relaciones con personas de la misma raza y de diferente género. De acuerdo con las publicaciones sobre los valores protectores de la afrocentricidad, hubo una asociación entre la calidad de la relación informada y los niveles altos de la afrocentricidad propia y de la percibida por el otro integrante de la pareja. Las discrepancias entre la afrocentricidad propia y la del otro integrante de la pareja no estuvieron asociadas con los procesos relacionales, pero las discrepancias mayores percibidas entre las cuatro subescalas de la ideología racial estuvieron asociadas con una menor dedicación a la relación. Las discrepancias mayores percibidas en las subescalas humanista y asimilacionista también estuvieron relacionadas con niveles más altos de conflicto. Estos resultados tienen consecuencias clínicas importantes e indican una necesidad de investigar más profundamente los matices de los factores individuales y los procesos diádicos que son exclusivos de las parejas afroestadounidenses.

Pathophysiological Roles of Histamine Receptors in Cancer Progression: Implications and Perspectives as Potential Molecular Targets.

High levels of histamine and histamine receptors (HRs), including H1R~H4R, are found in many different types of tumor cells and cells in the tumor microenvironment, suggesting their involvement in tumor progression. This review summarizes the latest evidence demonstrating the pathophysiological roles of histamine and its cognate receptors in cancer biology. We also discuss the novel therapeutic approaches of selective HR ligands and their potential prognostic values in cancer treatment. Briefly, histamine is highly implicated in cancer development, growth, and metastasis through interactions with distinct HRs. It also regulates the infiltration of immune cells into the tumor sites, exerting an immunomodulatory function. Moreover, the effects of various HR ligands, including H1R antagonists, H2R antagonists, and H4R agonists, on tumor progression in many different cancer types are described. Interestingly, the expression levels of HR subtypes may serve as prognostic biomarkers in several cancers. Taken together, HRs are promising targets for cancer treatment, and HR ligands may offer novel therapeutic potential, alone or in combination with conventional therapy. However, due to the complexity of the pathophysiological roles of histamine and HRs in cancer biology, further studies are warranted before HR ligands can be introduced into clinical settings.

Suppression of LPS-Induced Inflammation and Cell Migration by Azelastine through Inhibition of JNK/NF-κB Pathway in BV2 Microglial Cells.

The c-Jun N-terminal kinases (JNKs) are implicated in many neuropathological conditions, including neurodegenerative diseases. To explore potential JNK3 inhibitors from the U.S. Food and Drug Administration-approved drug library, we performed structure-based virtual screening and identified azelastine (Aze) as one of the candidates. NMR spectroscopy indicated its direct binding to the ATP-binding site of JNK3, validating our observations. Although the antihistamine effect of Aze is well documented, the involvement of the JNK pathway in its action remains to be elucidated. This study investigated the effects of Aze on lipopolysaccharide (LPS)-induced JNK phosphorylation, pro-inflammatory mediators, and cell migration in BV2 microglial cells. Aze was found to inhibit the LPS-induced phosphorylation of JNK and c-Jun. It also inhibited the LPS-induced production of pro-inflammatory mediators, including interleukin-6, tumor necrosis factor-α, and nitric oxide. Wound healing and transwell migration assays indicated that Aze attenuated LPS-induced BV2 cell migration. Furthermore, Aze inhibited LPS-induced IκB phosphorylation, thereby suppressing nuclear translocation of NF-κB. Collectively, our data demonstrate that Aze exerts anti-inflammatory and anti-migratory effects through inhibition of the JNK/NF-κB pathway in BV2 cells. Based on our findings, Aze may be a potential candidate for drug repurposing to mitigate neuroinflammation in various neurodegenerative disorders, including Alzheimer's and Parkinson's diseases.

A Novel 1,8-Naphthyridine-2-Carboxamide Derivative Attenuates Inflammatory Responses and Cell Migration in LPS-Treated BV2 Cells via the Suppression of ROS Generation and TLR4/Myd88/NF-κB Signaling Pathway.

Novel 1,8-naphthyridine-2-carboxamide derivatives with various substituents (HSR2101-HSR2113) were synthesized and evaluated for their effects on the production of pro-inflammatory mediators and cell migration in lipopolysaccharide (LPS)-treated BV2 microglial cells. Among the tested compounds, HSR2104 exhibited the most potent inhibitory effects on the LPS-stimulated production of inflammatory mediators, including nitric oxide (NO), tumor necrosis factor-α, and interleukin-6. Therefore, this compound was chosen for further investigation. We found that HSR2104 attenuated levels of inducible NO synthase and cyclooxygenase 2 in LPS-treated BV2 cells. In addition, it markedly suppressed LPS-induced cell migration as well as the generation of intracellular reactive oxygen species (ROS). Moreover, HSR2104 abated the LPS-triggered nuclear translocation of nuclear factor-κB (NF-κB) through inhibition of inhibitor kappa Bα phosphorylation. Furthermore, it reduced the expressions of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) in LPS-treated BV2 cells. Similar results were observed with TAK242, a specific inhibitor of TLR4, suggesting that TLR4 is an upstream regulator of NF-κB signaling in BV2 cells. Collectively, our findings demonstrate that HSR2104 exhibits anti-inflammatory and anti-migratory activities in LPS-treated BV2 cells via the suppression of ROS and TLR4/MyD88/NF-κB signaling pathway. Based on our observations, HSR2104 may have a beneficial impact on inflammatory responses and microglial cell migration involved in the pathogenesis of various neurodegenerative disorders.

Hepatitis B Testing Among Vietnamese in Metropolitan Atlanta: The Role of Healthcare-Related and Acculturation-Related Factors.

BACKGROUND: Compared to other racial/ethnic groups, U.S. Vietnamese have higher Hepatitis B infection prevalence, which is a major liver cancer risk factor. Increased testing could reduce this disparity. It is critical to understand subgroups of U.S. Vietnamese least likely to have been tested for Hepatitis B and design appropriate interventions. We examined healthcare- and acculturation-related factors influencing Hepatitis B testing among U.S. Vietnamese. METHODS: Survey data of 100 U.S. Vietnamese attending health fairs/programs hosted by community-based organizations (2017-2018) were analyzed. Healthcare-related predictors included insurance and past 2-year checkup. Acculturation-related predictors included Vancouver Acculturation Index, percentage of lifetime in the U.S., and Vietnamese and English fluency. We conducted a multiple logistic regression controlling for age, sex, education, and household income. RESULTS: The sample was an average 37.5 years old and 61.6% female. Insurance coverage was reported by 83.0%. Average percentage of lifetime in the U.S. was 56.8%. Seventy percent reported having received Hepatitis B testing. Hepatitis B testing was associated with health insurance (aOR = 2.61, 95% CI = [1.05-6.47], p = .04) but not any acculturation-related predictors CONCLUSION: Improving insurance coverage and options can be a strategy to increase Hepatitis B testing among U.S. Vietnamese. More education regarding Hepatitis B (e.g., via community-based, culturally-appropriate, lay health worker-led programs) is needed to ensure that individuals are aware of their testing status and pursue appropriate healthcare decisions.