expHRD: an individualized, transcriptome-based prediction model for homologous recombination deficiency assessment in cancer.

BACKGROUND: Homologous recombination deficiency (HRD) stands as a clinical indicator for discerning responsive outcomes to platinum-based chemotherapy and poly ADP-ribose polymerase (PARP) inhibitors. One of the conventional approaches to HRD prognostication has generally centered on identifying deleterious mutations within the BRCA1/2 genes, along with quantifying the genomic scars, such as Genomic Instability Score (GIS) estimation with scarHRD. However, the scarHRD method has limitations in scenarios involving tumors bereft of corresponding germline data. Although several RNA-seq-based HRD prediction algorithms have been developed, they mainly support cohort-wise classification, thereby yielding HRD status without furnishing an analogous quantitative metric akin to scarHRD. This study introduces the expHRD method, which operates as a novel transcriptome-based framework tailored to n-of-1-style HRD scoring. RESULTS: The prediction model has been established using the elastic net regression method in the Cancer Genome Atlas (TCGA) pan-cancer training set. The bootstrap technique derived the HRD geneset for applying the expHRD calculation. The expHRD demonstrated a notable correlation with scarHRD and superior performance in predicting HRD-high samples. We also performed intra- and extra-cohort evaluations for clinical feasibility in the TCGA-OV and the Genomic Data Commons (GDC) ovarian cancer cohort, respectively. The innovative web service designed for ease of use is poised to extend the realms of HRD prediction across diverse malignancies, with ovarian cancer standing as an emblematic example. CONCLUSIONS: Our novel approach leverages the transcriptome data, enabling the prediction of HRD status with remarkable precision. This innovative method addresses the challenges associated with limited available data, opening new avenues for utilizing transcriptomics to inform clinical decisions.

Kushenol C Prevents Tert-Butyl Hydroperoxide and Acetaminophen-Induced Liver Injury.

Sophora flavescens, also known as Kushen, has traditionally been used as a herbal medicine. In the present study we evaluated the ameliorative effects of kushenol C (KC) from S. flavescens against tBHP (tert-Butyl hydroperoxide)-induced oxidative stress in hepatocellular carcinoma (HEPG2) cells and acetaminophen (APAP)-induced hepatotoxicity in mice. KC pretreatment protected the HEPG2 cells against oxidative stress by reducing cell death, apoptosis and reactive oxygen species (ROS) generation. KC pretreatment also upregulated pro-caspase 3 and GSH (glutathione) as well as expression of 8-Oxoguanine DNA Glycosylase (OGG1) in the HEPG2 cells. The mechanism of action was partly related by KC's activation of Akt (Protein kinase B (PKB)) and Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) in the HepG2 cells. In in vivo investigations, coadministration of mice with KC and APAP significantly attenuated APAP-induced hepatotoxicity and liver damage, as the serum enzymatic activity of aspartate aminotransferase and alanine aminotransferase, as well as liver lipid peroxidation and cleaved caspase 3 expression, were reduced in APAP-treated mice. Coadministration with KC also up-regulated antioxidant enzyme expression and prevented the production of proinflammatory mediators in APAP-treated mice. Taken together, these results showed that KC treatment has potential as a therapeutic agent against liver injury through the suppression of oxidative stress.

In vitro Anti-Inflammatory and Anti-Oxidative Stress Activities of Kushenol C Isolated from the Roots of Sophora flavescens.

Kushenol C (KC) is a prenylated flavonoid isolated from the roots of Sophora flavescens aiton. Little is known about its anti-inflammatory and anti-oxidative stress activities. Here, we investigated the anti-inflammatory and anti-oxidative stress effects of KC in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, and tert-butyl hydroperoxide (tBHP)-induced oxidative stress in HaCaT cells. The results demonstrated that KC dose-dependently suppressed the production of inflammatory mediators, including NO, PGE2, IL-6, IL1ß, MCP-1, and IFN-ß in LPS-stimulated RAW264.7 macrophages. The study demonstrated that the inhibition of STAT1, STAT6, and NF-κB activations by KC might have been responsible for the inhibition of NO, PGE2, IL-6, IL1ß, MCP-1, and IFN-ß in the LPS-stimulated RAW264.7 macrophages. KC also upregulated the expression of HO-1 and its activities in the LPS-stimulated RAW264.7 macrophages. The upregulation of Nrf2 transcription activities by KC in the LPS-stimulated RAW264.7 macrophages was demonstrated to be responsible for the upregulation of HO-1 expression and its activity in LPS-stimulated RAW264.7 macrophages. In HaCaT cells, KC prevented DNA damage and cell death by upregulating the endogenous antioxidant defense system involving glutathione, superoxide dismutase, and catalase, which prevented reactive oxygen species production from tert-butyl hydroperoxide (tBHP)-induced oxidative stress in HaCaT cells. The upregulated activation of Nrf2 and Akt in the PI3K-Akt signaling pathway by KC was demonstrated to be responsible for the anti-oxidative stress activity of KC in HaCaT cells. Collectively, the study suggests that KC can be further investigated as a potential anti-inflammatory candidate for the treatment of inflammatory diseases.

Apigenin Inhibits IL-31 Cytokine in Human Mast Cell and Mouse Skin Tissues.

IL-31 is a recently discovered cytokine that is produced not only in T-cells but also in mast cells. It is strongly implicated to play a key role in inflammatory diseases and in the pathogenesis of itch in atopic dermatitis. Apigenin, a flavonoid of plant origin has numerous biological applications. In this study, we showed that apigenin modulates IL-31 mRNA, protein expression, and release in stimulated human mast (HMC-1) by inhibiting the phosphorylation activation of MAPK and NF-κB. To determine whether apigenin has similar effects in vivo, using Compound 48/80, we developed an atopic dermatitis itch model in mice and found an increase in IL-31 expression in the skin. We also revealed that apigenin prevents the infiltration and degranulation of mast cells and suppressed mRNA and protein expression of IL-31 in the skin of mice. These results provide a new suggestion of the potential applicability of apigenin for treatment of various inflammatory diseases and itch mediated by IL-31.

Mapping of a major quantitative trait locus for bakanae disease resistance in rice by genome resequencing.

Bakanae disease (BD) has emerged as a serious threat in almost all rice cultivation regions worldwide. Nampyeong is a Korean japonica rice variety known to be resistant to BD. In this study, quantitative trait locus (QTL) mapping was performed with F2 and F3 plants derived from a cross between the Nampyeong variety and a susceptible Korean japonica line, DongjinAD. First, resequencing of Nampyeong and DongjinAD was performed, which identified 171,035 single nucleotide polymorphisms (SNPs) between the two parental varieties. Using these SNPs, 161 cleaved amplified polymorphic sequence (CAPS) markers and six derived CAPS markers were developed; then, a genetic map was constructed from the genotypes of 180 plants from the DongjinAD/Nampyeong F2 plants. The total length of the constructed genetic map was 1386 cM, with an average interval of 8.9 cM between markers. The BD mortality rates of each F3 family were measured by testing 40 F3 progenies using in vitro seedling screening method. QTL analysis based on the genetic map and mortality rate data revealed a major QTL, qFfR1, on rice chromosome 1. qFfR1 was located at 89.8 cM with a logarithm of the odds (LOD) score of 22.7. Further, there were three markers at this point: JNS01033, JNS01037, and JNS01041. A total of 15 genes were identified with annotations related to defense against plant diseases among the 179 genes in the qFfR1 interval at 95% probability, thereby providing potential candidate genes for qFfR1. qFfR1 and its closely linked markers will be useful in breeding rice varieties resistant to BD.

Communities of practice to improve employment outcomes: a needs assessment.

PURPOSE: Communities of practice (CoPs) offer a promising strategy to improve communication among various professionals committed to advancing employment outcomes for people with disabilities. CoPs also provide a tool for professionals to share knowledge and resources related to the Americans with Disabilities Act and job accommodations. METHODS: The current study conducted four focus groups with human resource (HR) professionals and vocational rehabilitation professionals to fully assess the need for this CoP. Coding and memoing were the two data analysis strategies employed in this study. RESULTS: Results indicate a strong interest in developing a CoP to assist with employment concerns for people with disabilities. CONCLUSIONS: HR professionals report a need for current, relevant information on this topic, and participants outline guidelines for developing the CoP and building useful content areas.

Anti-inflammatory and antipruritic effects of luteolin from Perilla (P. frutescens L.) leaves.

Perilla (Perilla frutescens L.) leaves have shown therapeutic efficacy in the treatment of inflammatory disorders, allergies, bronchial asthma, and systemic damage due to free radicals. In the present study we analyzed the active constituents in perilla leaves using high-performance liquid chromatography (HPLC) and isolated luteolin, a polyphenolic flavonoid. We investigated the anti-inflammatory and antipruritic properties of luteolin. Luteolin inhibited the secretion of inflammatory cytokines such as interleukin-1ß (IL-1 ß) and tumor necrosis factor-α (TNF-α) from human mast cells (HMC-1) stimulated with phorbol myristate acetate plus calcium ionophore A23187 in a dose-dependent manner. Luteolin also significantly reduced the histamine release from rat peritoneal mast cells stimulated by compound 48/80, a potent histamine liberator. Furthermore, the administration of luteolin markedly inhibited the scratching behavior and vascular permeability induced by pruritogens, such as compound 48/80 or serotonin, in ICR mice. These results suggested that luteolin has potential as a therapeutic agent against inflammation and itch-related skin diseases.

Empowering pancreatic tumor homing with augmented anti-tumor potency of CXCR2-tethered CAR-NK cells.

Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells are a promising immunotherapy for solid cancers; however, their effectiveness against pancreatic cancer is limited by the immunosuppressive tumor microenvironment. In particular, low NK cell infiltration poses a major obstacle that reduces cytotoxicity. The current study aimed to enhance the tumor-homing capacity of CAR-NK cells by targeting the chemokine-chemokine receptor axis between NK and pancreatic cancer cells. To this end, data from a chemokine array and The Cancer Genome Atlas pan-cancer cohort were analyzed. Pancreatic cancer cells were found to secrete high levels of ligands for C-X-C motif receptor 1 (CXCR1) and CXCR2. Subsequently, we generated anti-mesothelin CAR-NK cells incorporating CXCR1 or CXCR2 and evaluated their tumor-killing abilities in 2D cancer cell co-culture and 3D tumor-mimetic organoid models. CAR-NK cells engineered with CXCR2 demonstrated enhanced tumor killing and strong infiltration of tumor sites. Collectively, these findings highlight the potential of CXCR2-augmented CAR-NK cells as a clinically relevant modality for effective pancreatic cancer treatment. By improving their infiltration and tumor-killing capabilities, these CXCR2-augmented CAR-NK cells have the potential to overcome the challenges posed by the immunosuppressive tumor microenvironment, providing improved therapeutic outcomes.

High-throughput organo-on-pillar (high-TOP) array system for three-dimensional ex vivo drug testing.

The development of organoid culture technologies has triggered industrial interest in ex vivo drug test-guided clinical response prediction for precision cancer therapy. The three-dimensional culture encapsulated with basement membrane (BM) components is extremely important in establishing ex vivo organoids and drug sensitivity tests because the BM components confer essential structures resembling tumor histopathology. Although numerous studies have demonstrated three-dimensional culture-based drug screening methods, establishing a large-scale drug-screening platform with matrix-encapsulated tumor cells is challenging because the arrangement of microspots of a matrix-cell droplet onto each well of a microwell plate is inconsistent and difficult to standardize. In addition, relatively low scales and lack of reproducibility discourage the application of three-dimensional organoid-based drug screening data for precision treatment or drug discovery. To overcome these limitations, we manufactured an automated organospotter-integrated high-throughput organo-on-pillar (high-TOP) drug-screening platform. Our system is compatible with various extracellular matrices, including BM extract, Matrigel, collagen, and hydrogel. In addition, it can be readily utilized for high-content analyses by simply exchanging the bottom plates without disrupting the domes. Our system demonstrated considerable robustness, consistency, reproducibility, and biological relevancy in three-dimensional drug sensitivity analyses using Matrigel-encapsulated ovarian cancer cell lines. We also demonstrated proof-of-concept cases representing the clinical feasibility of high-TOP-assisted ex vivo drug tests linked to clinical chemo-response in ovarian cancer patients. In conclusion, our platform provides an automated and standardized method for ex vivo drug-sensitivity-guided clinical response prediction, suggesting effective chemotherapy regimens for patients with cancer.

Human transcriptome analysis of acute responses to glucose ingestion reveals the role of leukocytes in hyperglycemia-induced inflammation.

Glucose ingestion-induced hyperglycemia has been known to induce inflammation, which is related to the pathogenesis of diabetic complications. To examine acute gene expression responses to physiological oral glucose ingestion in human circulating leukocytes, we conducted a microarray study of human circulating leukocytes sampled before, 1 h after, and 2 h after glucose ingestion in community-based participants without previous histories of diabetes (n = 60). Ingestion of 75 g glucose successfully induced acute hyperglycemia (glucose concentration 91.6 ± 5.3 mg/dl for fasting and 180.7 ± 48.5 mg/dl for 1 h after glucose ingestion). Oral glucose ingestion significantly increased the expressions of 23 genes and decreased the expressions of 13 genes [false discovery rate (FDR) P value <0.05]. These genes are significantly involved in immunity by way of natural killer cell-mediated immunity, granulocyte-mediated immunity, and the cytokine-mediated signaling pathway (FDR P value <0.05). The present study demonstrated 36 genes that showed acute gene expression change in human leukocytes within 1 h after glucose ingestion, suggesting that leukocytes participate in the inflammatory process induced by acute hyperglycemia. We believe that these results will provide some basic insight into the role of leukocytes in hyperglycemia-induced inflammation and the pathogenesis of diabetic complications.

Noble polymeric surface conjugated with zwitterionic moieties and antibodies for the isolation of exosomes from human serum.

New zwitterionic polymer-coated immunoaffinity beads were developed to resist nonspecific protein adsorption from undiluted human serum for diagnostic applications of exosomes. A zwitterionic sulfobetaine monomer with an amine functional group was employed for simple surface chemistry and antifouling properties. An exosomal biomarker protein, epithelial cell adhesion molecule (EpCAM), was selected as a target molecule in this work. The beads were coated with polyacrylic acids (PAA) for increasing biorecognition sites, and protein G was then conjugated with carboxylic acid groups on the surfaces for controlling EpCAM antibody orientation. The remaining free carboxylic acid groups were modified with sulfobetaine moieties, and anti-EpCAM antibody was finally introduced. The amount of anti-EpCAM on the beads was increased by 40% when compared with PAA-uncoated beads. The surfaces of the beads exhibited near-net-zero charge, and nonspecific protein adsorption was effectively suppressed by sulfobetaine moieties. EpCAM was captured from undiluted human serum with almost the same degree of efficiency as from PBS buffer solution using the newly developed immunoaffinity beads.

A direct extraction method for microRNAs from exosomes captured by immunoaffinity beads.

A direct extraction method was developed for exosomal microRNAs. After isolation of exosomes from human serum by immunoaffinity magnetic beads, microRNAs were extracted by just mixing beads with a lysis solution and heating without further purification. The lysis solution was composed of a nonionic detergent and salt (NaCl). The concentration of each component was optimized to maximize lysis efficiency and to inhibit adsorption of extracted microRNAs on beads. MicroRNAs extracted by this method could be quantitatively analyzed by qRT-PCR, indicating that the method could replace conventional methods for extracting microRNAs from immunobead-captured exosomes.

Diphenylamino-fluorenylethylene derivatives for highly efficient blue organic light-emitting diodes.

Highly efficient blue organic light-emitting diodes (OLEDs) were developed using diphenylamino-fluorenylethylene derivatives. In particular, OLEDs using compound 3 as a dopant in the emitting layer showed a maximum luminance of 12940 cd/m2 at 10 V; a luminous efficiency of 12.68 cd/A at 20 mA/cm2; a power efficiency of 5.24 Im/W at 20 mA/cm2, and CIE(x,y) coordinates of 0.181, 0.295 at 10 V. Furthermore, a deep blue OLED using dopant 2 with CIE coordinates of (0.154, 0.129) exhibited a maximum luminance of 5315 cd/m2 at 10 V; a luminous efficiency of 4.11 cd/A at 20 mA/cm2, and a power efficiency of 1.66 Im/W at 20 mA/cm2.

Highly efficient red phosphorescent organic light-emitting devices using iridium(III) complexes based on 2-(biphenyl-3-yl)quinoline derived ligands.

Red phosphorescent emitters were synthesized based on Ir(III) phenylquinoline complexes for applications to OLEDs. Ir(III) complexes 1-3 were based on 2-(biphenyl-3-yl)-quinoline units connected to various phenyl groups such as 5-phenyl, 5-(4-fluorophenyl), and 6-phenyl groups. The EL efficiencies were quite sensitive to the structural features of the dopants in the emitting layers. In particular, a high-efficiency red OLED was fabricated using complex 1 as the dopant in the emitting layer. This OLED showed a maximum luminance, luminous efficiency, power efficiency, external quantum efficiency and CIE(x,y) coordinates of 21,600 cd/m2 at 16 V, 11.80 cd/A at 20 mA/cm2, 3.57 Im/W at 20 mA/cm2, 10.90% at 20 mA/cm2, and (x = 0.63, y = 0.32) at 12 V, respectively.

Orange-red phosphorescent OLEDs using iridium(III) complexes with benzoylphenylpyridine ligands containing fluorine and trifluoromethyl groups.

We have designed and synthesized four orange-red phosphorescent Ir(III) complexes based on the benzoylphenylpyridine ligand with fluorine and trifluoromethyl substitution. Multilayered OLEDs were fabricated using these complexes as dopant materials. Particularly, by using 1 as a dopant in the emitting layer, a highly efficient orange-red OLED was fabricated, showing a maximum luminance of 10410 cd/m2 at 10 V, a luminous efficiency of 17.47 cd/A, a power efficiency of 7.19 Im/W, an external quantum efficiency of 6.27% at 20 mA/cm2, respectively, and CIE(x,y) coordinates of (0.51, 0.48) at 10 V. Furthermore, a red OLED using dopant 2, with CIE(x,y) coordinates of (0.61, 0.39), exhibited a maximum luminance of 5797 cd/m2 at 10 V, a luminous efficiency of 11.43 cd/A at, a power efficiency of 4.12 Im/W, and an external quantum efficiency of 6.62% at 20 mA/cm2, respectively.

Unraveling the Transcriptomic Signatures of Homologous Recombination Deficiency in Ovarian Cancers.

Homologous recombination deficiency (HRD) is a crucial driver of tumorigenesis by inducing impaired repair of double-stranded DNA breaks. Although HRD possibly triggers the production of numerous tumor neoantigens that sufficiently stimulate and activate various tumor-immune responses, a comprehensive understanding of the HRD-associated tumor microenvironment is elusive. To investigate the effect of HRD on the selective enrichment of transcriptomic signatures, 294 cases from The Cancer Genome Atlas-Ovarian Cancer project with both RNA-sequencing and SNP array data are analyzed. Differentially expressed gene analysis and network analysis are performed to identify HRD-specific signatures. Gene-sets associated with mitochondrial activation, including enhanced oxidative phosphorylation (OxPhos), are significantly enriched in the HRD-high group. Furthermore, a wide range of immune cell activation signatures is enriched in HRD-high cases of high-grade serous ovarian cancer (HGSOC). On further cell-type-specific analysis, M1-like macrophage genes are significantly enriched in HRD-high HGSOC cases, whereas M2-macrophage-related genes are not. The immune-response-associated genomic features, including tumor mutation rate, neoantigens, and tumor mutation burdens, correlated with HRD scores. In conclusion, the results of this study highlight the biological properties of HRD, including enhanced energy metabolism, increased tumor neoantigens and tumor mutation burdens, and consequent exacerbation of immune responses, particularly the enrichment of M1-like macrophages in HGSOC cases.

Pyridine/isoquinoline-carbazole containing bipolar host materials for green phosphorescent organic light-emitting diodes.

We demonstrated the electroluminescent properties of bipolar host materials such as 9-(3-(6-methylpyridin-2-yl)phenyl)-9H-carbazole (Czpmpy), 9-(6-phenylpyridin-2-yl)-9H-carbazole (Czppy), and 9-(3-(isoquinolin-1-yl)phenyl)-9H-carbazole (Czpiq). Particularly, by using host (Czpiq) and dopant (bis[2-(1,1',2',1"-terphen-3-yl)pyridinato-C,N]iridium(III) (tphpy),2Ir(acac)) as the emitting layer, a green phosphorescent OLED was fabricated, showing a maximum luminance of 12780 cd/m2 at 10 V, maximum luminous efficiency of 45.0 cd/A, power efficiency of 47.1 Im/W, maximum external quantum efficiency of 12.3%, and CIE x, y coordinates of (0.34, 0.58) at 8 V.

Effects of Lavender on Anxiety, Depression, and Physiological Parameters: Systematic Review and Meta-Analysis.

PURPOSE: The recent evidence suggested substantial anxiolytic efficacy of lavender. The aim of this study was to examine the efficacy of lavender for anxiety, depression, and physiological parameters and to elucidate the differential effects of lavender on anxiety and depression by study characteristics. METHODS: A systematic review and meta-analysis was performed following the PRISMA guidelines. We searched PubMed, Embase, Cochrane Library, Web of Science, and Cumulative Index of Nursing and Allied Health Literature databases for randomized controlled trials investigating the efficacy of lavender on anxiety, depression, or physiological parameters in humans. We assessed the risk of bias within studies with the revised Cochrane risk of bias tool for randomized trials. We used random effect model to estimate the average effect and computed bias-corrected standardized mean difference as effect size metric, Hedges' g for all outcomes. RESULTS: Lavender was superior to placebo or no treatment in reducing anxiety (Hedges' g = -0.72, 95% confidence interval [CI] -0.90 to -0.55, p value <.001), depression (Hedges' g = -0.43, 95% CI, -0.59 to -0.27, p value <.001), and systolic blood pressure (Hedges' g = -0.23, 95% CI, -0.41to -0.05, p value = .01). The moderator analysis by meta-regression indicated that route of administration accounted 6.5% (p value = .187) for the heterogeneity in anxiolytic effects, sessions of treatment accounted 13.2% (p value = .055), and participants' health state accounted 8.9% (p value = .131) for the variance in anxiolytic effects. CONCLUSION: Lavender aromatherapy showed substantial effect in reducing anxiety and depression, and sessions of administration increased the anxiolytic effects. The effects on physiological parameters showed small with inconsistent significances and randomized controlled trials on the effect of lavender on depression were scarce. Future trials on depression and physiological parameters are recommended, and increasing the sessions of administration is recommended.

Protective effects of halophyte complex extract against UVB-induced damage in human keratinocytes and the skin of hairless mice.

Limonium tetragonum, Triglochin maritimum, Artemisia scoparia and red ginseng have been used as folk remedies for treating a variety of diseases. In the current study, the protective effects of halophyte and red ginseng against ultraviolet (UV)-induced skin damage were investigated. Halophyte red ginseng complex extract (HRCE) was prepared and its effects on UV-B irradiated human keratinocytes and mouse skin were studied through ELISA, Western blotting immunofluorescence and histological staining. HRCE inhibited peroxide-induced damage in human keratinocytes. HRCE also inhibited UVB-induced collagen and elastin degradation in human keratinocytes and mouse skin. In addition, HRCE inhibited mast cell infiltration in the skin of mice irradiated with UVB light. This effect was likely due to HRCE inhibiting the activation of MAPK and NF-κB. By protecting the skin from UVB-induced skin damage, HRCE has the potential to be used in the treatment and prevention of UV-induced skin damage and photoaging.

Anti­inflammatory effect of Chrysanthemum zawadskii, peppermint, Glycyrrhiza glabra herbal mixture in lipopolysaccharide­stimulated RAW264.7 macrophages.

The normal inflammatory reaction protects the body from harmful external factors, whereas abnormal chronic inflammation can cause various diseases, including cancer. The purpose of the present study was to investigate the anti­inflammatory activity of a mixture of Chrysanthemum zawadskii, peppermint and Glycyrrhiza glabra (CPG) by analyzing the expression levels of inflammatory mediators, cytokines and transcription factors in lipopolysaccharide (LPS)­stimulated Raw264.7 cells. A nitric oxide assay, ELISA, western blotting and immunofluorescence staining were performed to investigate the anti­inflammatory activity of the CPG mixture. Pretreatment of Raw264.7 cells with CPG inhibited the increase of inflammatory mediators (inducible nitric oxide synthase, cyclooxygenase­2 and IFN­ß) induced by LPS. Additionally, it inhibited the production of pro­inflammatory cytokines (TNF­α, IL­6 and IL­1ß). CPG suppressed LPS­induced phosphorylation of STAT1, AKT, Iκb and NF­κB. Furthermore, CPG inhibited the translocation of NF­κB into the nucleus. In summary, CPG could inhibit LPS­induced inflammation, which occurs primarily through the AKT/Iκb/NF­κB signaling pathway in RAW264.7 cells.