• MAFLD
• MASH
• MASLD
• NAFLD
• NASH
• cytokines
• diabetes
• immune cells
• inflammation
• liver fibrosis

• Humans
• Liver/immunology
• Liver/pathology
• Liver/metabolism
• Animals
• Cytokines/metabolism
• Diabetes Mellitus/immunology
• Diabetes Mellitus/pathology
• Liver Cirrhosis/immunology
• Liver Cirrhosis/pathology
• Signal Transduction

• Cancer
• CircRNA
• LncRNA
• MicroRNA
• Toll-like receptor (TLR)

• Humans
• Tumor Microenvironment/genetics
• Tumor Microenvironment/immunology
• Toll-Like Receptors/genetics
• Toll-Like Receptors/metabolism
• Inflammation/genetics
• Inflammation/pathology
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/immunology
• RNA, Untranslated/genetics
• Animals
• Signal Transduction
• RNA, Long Noncoding/genetics
• Gene Expression Regulation, Neoplastic
• MicroRNAs/genetics

• Cancer
• Diseases
• PRRs
• Prostate cancer
• Toll like receptor

• Humans
• Prostatic Neoplasms/drug therapy
• Prostatic Neoplasms/metabolism
• Prostatic Neoplasms/pathology
• Toll-Like Receptors/metabolism
• Toll-Like Receptors/antagonists & inhibitors
• Male
• Signal Transduction/drug effects
• Animals
• Molecular Targeted Therapy

• gut microbiota
• inflammation
• probiotics
• signaling pathways
• ulcerative colitis

• agonists
• antagonists
• chemotherapy
• human cancers
• immunotherapy
• therapeutic interventions
• toll-like receptors (TLRs)

• Humans
• Immunity, Innate
• Toll-Like Receptors/metabolism
• Neoplasms/drug therapy
• Signal Transduction
• Adaptive Immunity

• hepatocellular carcinoma
• toll-like receptor
• tumor immunotherapy
• tumor microenvironment

• MAPK
• MMPs
• Magnolia kobus
• NF-κB
• Porphyromonas gingivalis
• RAW 264.7
• inflammation
• magnolin
• periodontitis

• TLR2
• TLR4
• inflammation
• platelet
• thrombopoiesis
• toll-like receptors

• Humans
• Thrombopoiesis
• Toll-Like Receptor 2/metabolism
• Toll-Like Receptor 4/metabolism
• Toll-Like Receptors
• Thrombocytopenia/metabolism
• Inflammation

• 82074129 National Natural Science Foundation of China
• 22ZYZYTS0191 and 2022JDJQ0061 Sichuan Province Science and Technology Support Program

Probiotics have been used for the treatment of chronic metabolic diseases, including type 2 diabetes (T2D). However, the mechanisms of antidiabetic effects are not well understood. The object of this study is to assess the antidiabetic effect of Lactiplantibacillus plantarum Y15 isolated from Chinese traditional dairy products in vivo. Results revealed that L. plantarum Y15 administration improved the biochemical indexes related to diabetes, reduced pro-inflammatory cytokines, L. plantarum Y15 administration reshaped the structure of gut microbiota, decreased the abundance of LPS-producing, and increased short-chain fatty acids (SCFAs)-producing bacteria, which subsequently reduce the levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines. L. plantarum Y15 administration also regulated the expressions of the inflammation and insulin signaling pathway-related genes. These results suggest that L. plantarum Y15 may serve as a potential probiotic for developing food products to ameliorate T2D.

• Gut microbiota
• Inflammation
• Lactiplantibacillus plantarum
• Signaling pathway
• Type 2 diabetes

• PEAOXA
• apoptosis
• cytokines
• inflammation
• zebrafish

• chemotherapy
• inflammation
• pancreatic cancer
• toll-like receptor

• Animals
• Humans
• Inflammation/complications
• Inflammation/metabolism
• Pancreatic Neoplasms/etiology
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology
• Signal Transduction
• Toll-Like Receptors/metabolism

• glioma
• inflammatory mediators
• neuroinflammation
• signaling pathways
• tumor-associated macrophages
• tumor-associated neutrophils

As one of the most common neoplastic diseases, hepatocellular carcinoma (HCC) has a high morbidity and mortality, which seriously threatens human health and places a heavy burden on society and medical care. At present, effective early diagnosis, prognosis and treatment of HCC are limited. Altered gene expression patterns of lncRNA are associated with the occurrence, development and prognosis of various malignancies, including HCC. The aim of this study was to investigate the correlation between the expression of LINC01268 and HCC, and to elucidate the potential underlying molecular mechanism.

Expression level and localization of LINC01268 in human liver cancer cells and HCC tissues were investigated using RT-qPCR and fluorescent in situ hybridization (FISH), respectively. Correlation of expression levels of LINC01268 and MAP3K7 with differentiation and poor overall patient survival of HCC were analyzed using in house collected and publicly available HCC tissue data. RT-qPCR and Western blot were applied to inspect the effects of depletion and overexpression of LINC01268 on MAP3K7 expression. HCC cell proliferation and apoptosis were also investigated by simultaneous overexpression of LINC01268 and knockdown of MAP3K7, in order to delineate that MAP3K7 is a downstream effector of LINC01268.

In this study, we identified that LINC01268 was highly expressed in HCC cell lines and tissues. High LINC01268 expression level was associated with lower HCC nodule number, moderate/poor differentiation and poor overall survival. Knockdown of LINC01268 inhibited the proliferation of HCC cells, which was enhanced by overexpression of LINC01268. Co-expression analysis implied an interaction between LINC01268 and MAP3K7. Similar to LINC01268, MAP3K7 was highly expressed in HCC cells, and positively correlated with moderate/poor differentiation as well as poor prognosis. Knockdown of LINC01268 in HCC cell lines led to reduction of MAP3K7 at both mRNA and protein levels. Phenotypic effects due to LINC01268 overexpression in HCC cells were reversed by knockdown of MAP3K7.

Taken together, the abnormal high expression of LINC01268 is associated with HCC progression via regulating MAP3K7, suggesting LINC01268 as a novel marker for HCC prognosis and potentially a new therapeutic target.

• LINC01268
• MAP3K7
• hepatocellular carcinoma
• prognosis
• proliferation

• cancer
• immune escape
• inflammation
• metastasis
• targeted therapy
• toll-like receptor 4 (TLR4)

• TLR agonists
• TLR antagonists
• cancer
• inflammation
• toll-like receptors

Previous studies have suggested that the Lactobacillus plantarum bacteria strain could be effective in ulcerative colitis (UC) management. However, its effects are strain-specific and the related mechanisms for its attenuating effects on UC remain unclear. This study aimed to elucidate the underlying mechanisms for the protective effect of L. plantarum on UC. Firstly, 15 L. plantarum strains were screened for potential probiotic characteristics with good tolerance to simulated human gastrointestinal transit and adhesion. Secondly, the inflammatory response of selected strains to the Caco-2 cells induced by lipopolysaccharide (LPS) was measured. Finally, an in vivo mouse model induced by dextran sulfate sodium (DSS) was used to assess the beneficial effects and likely action mechanisms the successfully screened in vitro strain, L. plantarum L15. In vitro results showed that L. plantarum L15 possessed the highest gastrointestinal transit tolerance, adhesion and reduction of pro-inflammatory abilities compared to the other screened strains. In vivo, high dose of L. plantarum L15 supplementation increased the body weight, colon length and anti-inflammatory cytokine production. Pro-inflammatory cytokine production, disease activity index (DAI) levels and myeloperoxidase (MPO) parameters decreased using this strain. In addition, L. plantarum L15 alleviated the histopathological changes in colon, modulated the gut microbiota, and decreased LPS secretion. The activities of this strain down-regulated the expression of TLR4 and MyD88 genes as well as genes associated with NF-κB signaling pathway. Our findings present L. plantarum L15 as a new probiotic, with promising application for UC management.

• DSS-colitis
• Lactobacillus plantarum
• NF-κB signaling
• gut microbiota
• lipopolysaccharide (LPS)

Inflammation is considered as one of the hallmarks of cancer development and progression. Ursolic acid (UA) showed strong effects as an anti-inflammatory and antioxidant. However, the anti-cancer effects of ursolic acid require further study.

This study aimed to investigate the role of ursolic acid in a lipopolysaccharide (LPS)-treated gastric tumour mouse model and in a human gastric carcinoma cell line (BGC-823 cells). This study also aimed to confirm whether ursolic acid can protect against proliferation and the inflammatory response induced by LPS, by inhibiting the activation of the NLRP3 inflammasome via the NF-κB pathway.

The present study demonstrated that ursolic acid significantly attenuated LPS-treated proliferation in a gastric tumour mouse model and the human gastric carcinoma BGC-823 cell line, reduced the expression of the NLRP3 inflammasome and suppressed the release of pro-inflammatory cytokines. In addition, ursolic acid inhibited the LPS-induced activation of NF-κB. Furthermore, the NF-κB pathway regulated the activation of the NLRP3 inflammasome.

In conclusion, these results demonstrated that ursolic acid could suppress proliferation and the inflammatory response in an LPS-induced mouse gastric tumour model and human BGC-823 cells by inhibiting the activation of the NLRP3 inflammasome via the NF-κB pathway. This indicates that ursolic acid can be a potential therapeutic agent for the treatment of gastric cancer.

• NF-κB pathway
• NLRP3 inflammasome
• gastric carcinoma
• inflammatory
• proliferation
• ursolic acid

• CRISPR imaging
• CRISPR-Cas systems
• CRISPR-based genome-wide screening
• RNA editing
• base editor
• gene edting
• genome editing

• Archaea/genetics
• Bacteria/genetics
• CRISPR-Associated Protein 9/metabolism
• CRISPR-Cas Systems/genetics
• Clustered Regularly Interspaced Short Palindromic Repeats/genetics
• Endonucleases/genetics
• Gene Editing/methods
• Genome/genetics
• High-Throughput Nucleotide Sequencing/methods
• RNA, Guide, CRISPR-Cas Systems/genetics

• National Natural Science Foundation of China
• Research Grants Council, University Grants Committee

Juxtaposed with another zinc finger gene 1 (JAZF1) is involved in gluconeogenesis, insulin sensitivity, cell differentiation, lipid metabolism and inflammation, but its role in carcinoma remains inexplicit.

We explored the JAZF1 expression in human papillary thyroid cancer (PTC) tissues, adjacent normal thyroid tissues and nodular goitre tissues, as well as Ki67 expression in PTC tissues, using immunohistochemistry staining. Western blotting and RT-qPCR were performed to explore the JAZF1 expression levels in Nthy-ori 3–1, BCPAP and TPC-1 cells. BCPAP cells overexpressing JAZF1 were constructed using an Adv-JAZF1-GFP recombinant adenovirus vector. Next, the cell proliferation assay, colony formation assay, cell cycle analysis, apoptosis and immunofluorescence were performed. The mRNA expression level of nuclear factor-κB p65 (NF-κB p65) was examined using RT-qPCR. The expression of Bcl-2, Bax, transforming growth factor beta-activated kinase 1 (TAK1), NF-κB p65 and NF-κB p-p65 were examined using Western blotting.

The expression of JAZF1 in human PTC tissues was downregulated compared with adjacent thyroid tissues or nodular goitre. Additionally, JAZF1 expression was associated with the location and lymph node metastasis of PTC. The expression level of JAZF1 had a negative correlation with Ki67 labelling index (LI). Compared to Nthy-ori 3–1 cells and TPC-1 cells, BCPAP cells expressed the lowest JAZF1. JAZF1 overexpressed significantly inhibited proliferation, caused G0/G1 cell cycle arrest and promoted apoptosis in BCPAP cells. Furthermore, JAZF1 overexpressed in BCPAP cells clearly upregulated the expression level of Bax protein, whereas decreased the expression of Bcl-2, TAK1, NF-κB but did not affect the mRNA or protein expression level of NF-κB p65.

JAZF1 inhibits proliferation and induces apoptosis in BCPAP cells by suppressing the activation of TAK1/NF-κB signalling pathways, suggesting that JAZF1 may serve as a reliable molecular marker in PTC.

• Juxtaposed with another zinc finger gene 1
• NF-κB
• TAK1
• papillary thyroid cancer

• Lipopolysaccharide
• Myeloid differentiation factor 88
• NF-κB
• Osteoarthritis
• Tetramethylpyrazine
• p38MAPK

• Animals
• Apoptosis/drug effects
• Cells, Cultured
• Chondrocytes/drug effects
• Chondrocytes/metabolism
• Chondrocytes/pathology
• Inflammation/drug therapy
• Inflammation/metabolism
• Inflammation/pathology
• Lipopolysaccharides/toxicity
• Mice
• Myeloid Differentiation Factor 88/genetics
• Myeloid Differentiation Factor 88/metabolism
• NF-kappa B/genetics
• NF-kappa B/metabolism
• Pyrazines/pharmacology
• Signal Transduction
• Vasodilator Agents/pharmacology
• p38 Mitogen-Activated Protein Kinases/genetics
• p38 Mitogen-Activated Protein Kinases/metabolism

• Anti-inflammation
• Indolealkylamines
• LPS-Induced zebrafish model
• MyD88
• Sphingolipids

• Animals
• Animals, Genetically Modified
• Anti-Inflammatory Agents/chemistry
• Anti-Inflammatory Agents/pharmacology
• Bufonidae
• Cytokines/genetics
• Female
• Indoles/chemistry
• Indoles/pharmacology
• Inflammation/chemically induced
• Inflammation/drug therapy
• Inflammation/genetics
• Larva
• Lipid Metabolism/drug effects
• Lipopolysaccharides
• MAP Kinase Signaling System/drug effects
• Male
• Myeloid Differentiation Factor 88/genetics
• NF-kappa B/metabolism
• Skin
• Toll-Like Receptor 4/genetics
• Zebrafish

Purpose: The root of Cynanchum auriculatum Royle ex Wight, known as Baishouwu, has been widely used for a tonic supplement since ancient times. The current study was performed to explore the effect of Baishouwu extract on the development of experimental hepatocellular carcinoma (HCC) and the potential mechanism involved.

Methods: Rats were injected diethylnitrosamine (DEN) to initiate the multistep hepatocarcinogenesis. Animals were treated concurrently with Baishouwu extract given daily by oral gavage for 20 weeks to evaluate its protective effects. Time series sera and organ samples from each group were collected to evaluate the effect of Baishouwu extract on hepatic carcinogenesis.

Results: It was found that Baishouwu extract pretreatment successfully attenuated liver injury induced by DEN, as shown by decreased levels of serum biochemical indicators (AST, ALT, ALP, TP, and T-BIL). Administration of Baishouwu extract inhibited the fibrosis-related index in serum and live tissue, respectively from inflammation stage to HCC stage after DEN treatment. It significantly reduced the incidence and multiplicity of DEN-induced HCC development in a dose-dependent manner. Macroscopic and microscopic features suggested that pretreatment with Baishouwu extract for 20 weeks was effective in inhibiting DEN-induced inflammation, liver fibrosis, and HCC. Furthermore, TLR4 overexpression induced by DEN was decreased by Baishouwu extract, leading to the markedly down-regulated levels of MyD88, TRAF6, NF-κB p65, TGF-β1 and α-SMA in hepatitis, cirrhosis, and hepatocarcinoma.

Conclusion: In conclusion, Baishouwu extract exhibited potent effect on the development of HCC by altering TLR4/MyD88/ NF-κB signaling pathway in the sequence of hepatic inflammation-fibrosis-cancer, which provided novel insights into the mechanism of Baishouwu extract as a candidate for the pretreatment of HCC in the future.

• Baishouwu extract
• TLR4
• hepatocellular carcinoma
• inflammation-fibrosis-cancer axis
• pretreatment

• Foxo3a
• TRIM3
• cytokines, FLS
• proliferation

The changes in ratio of T helper 17 cells (Th17) to Treg cells in the transition of chronic hepatitis B (CHB) to liver cirrhosis, and the correlations with liver function and inflammation were investigated. A total of 20 normal subjects (control group), 35 CHB patients (CHB group) and 40 post-hepatitis liver cirrhosis patients (liver cirrhosis group) were enrolled into this study. Liver function was measured through the levels of alanine aminotransferase (ALT) and aspartic transaminase (AST), and the hematoxylin and eosin (H&E) staining method was used to detect the histopathological features. mRNA expression of inflammation-associated factors was detected using RT-PCR. The protein expression of nuclear factor κB (NF-κB) was measured in liver tissues using the immunofluorescent method and western blot assay. In the CHB and liver cirrhosis groups, the increases in Th17 cells were more evident than those in Treg cells. Moreover, an evident increase in levels of ALT and AST was identified in the two groups. Structures of liver tissues in the CHB and liver cirrhosis groups were destroyed with damage to the cell nuclei. The expression of inflammation-associated factors were significantly elevated compared to those in the control group. NF-κB expressed in the CHB and liver cirrhosis groups was significantly higher than that in control group. The results of analysis of variance indicated that differences in the expression of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and NF-κB in the three groups had statistical significance (P<0.01). In conclusion, transition from CHB to liver cirrhosis comes with significant changes in Th17/Treg ratio, which is correlated with a decrease in liver function, and also closely associated with the development and progression of inflammation.

• Th17/Treg
• chronic hepatitis B
• inflammation
• liver cirrhosis
• liver function

Microtubule associated serine/threonine kinase-like (MASTL) is the functional mammalian ortholog of Greatwall kinase (Gwl), which was originally discovered in Drosophila. Gwl is an essential kinase for accurate chromosome condensation and mitotic progression, and inhibits protein phosphatase 2A (PP2A), which subsequently dephosphorylates the substrates of cyclin B1-cyclin-dependent kinase 1, leading to mitotic exit. Previous studies have indicated that MASTL has a critical function in the regulation of mitosis in HeLa and U2OS cell lines, though there is currently limited evidence for the involvement of MASTL in hepatocarcinogenesis. The results of the present study revealed that MASTL was inducible by the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), which promoted the proliferation and mitotic entry of human liver cancer cells. It was also determined that MASTL was significantly overexpressed in cancerous liver tissues compared with non-tumor liver tissues. Mechanistically, stimulation by IL-6 and TNF-α induced the trimethylation of histone H3 lysine 4 (H3K4Me3) at the MASTL promoter to facilitate chromatin accessibility. Additionally, H3K4Me3 was associated with the activation of nuclear factor-κB, which subsequently upregulated MASTL expression. These findings suggested that MASTL may have pivotal functions in the development of hepatocarcinoma, and that it may be a potential target for treatment.

• hepatocarcinogenesis
• inflammatory cytokines
• microtubule associated serine/threonine kinase-like
• mitosis

• Castanea mollissima shells
• TLR4–NF-κB pathway
• anti-inflammatory activities
• anticancer activities
• hepatoma cells
• phenols

• Apoptosis/drug effects
• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Diterpenes/pharmacology
• Fagaceae/chemistry
• Hep G2 Cells
• Humans
• I-kappa B Proteins/metabolism
• Inflammation/chemically induced
• Inflammation/metabolism
• Interleukin-6/metabolism
• Lipopolysaccharides/toxicity
• NF-kappa B/metabolism
• Phenols/pharmacology
• Plant Extracts/pharmacology
• Toll-Like Receptor 4/metabolism
• Tumor Necrosis Factor-alpha/metabolism

• 16401901200 Shanghai Committee of Science and Technology, China
• A1-U17205010416 Xinglin Young Scholar of Shanghai University of Traditional Chinese Medicine

•

Both treatments inhibited cancer proliferation in a time and dose dependent manner.

In this study, anti-proliferative effects of C. calcitrans extract and its fucoxanthin rich fraction (FxRF) were assessed on human liver HepG2 cancer cell line. Efficacy from each extract was determined by cytotoxicity assay, morphological observation, and cell cycle analysis. Mechanisms of action observed were evaluated using multiplex gene expression analysis. Results showed that CME and FxRF induced cytotoxicity to HepG2 cells in a dose and time-dependent manner. FxRF (IC₅₀: 18.89 μg.mL⁻¹) was found to be significantly more potent than CME (IC₅₀: 87.5 μg.mL⁻¹) (p < 0.05). Gene expression studies revealed that anti-proliferative effects in treated cells by C. calcitrans extracts were mediated partly through the modulation of numerous genes involved in cell signaling (AKT1, ERK1/2, JNK), apoptosis (BAX, BID, Bcl-2, APAF, CYCS) and oxidative stress (SOD1, SOD2, CAT). Overall, C. calcitrans extracts demonstrated effective intervention against HepG2 cancer cells where enhanced apoptotic activities were observed with increased fucoxanthin content.

• Apoptosis
• CME, crude methanolic extract
• Chaetoceros calcitrans
• DMSO, dimethyl sulfoxide
• Fucoxanthin
• FxRF, fucoxanthin rich fraction
• Gene expression
• MTT, 3-(4,5-dimethylthizol-2-yl-2,5 diphenyltetrazolium bromide)
• Microalgae
• PBS, phosphate buffered saline
• RNA, ribonucleic acid
• Rich fraction
• mg FX.g−1 extract, milligram of fucoxanthin per gram of Chaetoceros calcitrans extract

Immune challenge of invading macrophages at sites of infection is associated with release of TNF, which triggers a local cytokine storm as part of the normal inflammatory response. Whereas this response maybe beneficial in fighting off infections, similar responses triggered in autoimmune diseases contribute significantly to the underlying damaging pathology associated with these diseases. Here we show that Takinib, a highly discriminatory inhibitor of transforming growth factor Beta- activated kinase 1 (TAK1), selectively and potently reduces TNF production in pro-inflammatory THP-1 macrophages. A complete survey of 110 cytokines, showed robust loss of proinflammatory cytokine responsiveness to lipopolysaccharide (LPS) and interferon gamma (IFNγ) challenge in response to Takinib. The mechanisms of action of Takinib was recapitulated in TAK1 KO macrophages. TAK1 KO cells showed significant loss of TNF production as well as release of IL-6 in response to LPS challenge. Furthermore, Takinib blocked the ability of exogenously added LPS to promote phosphorylation of, c-Jun, p38 protein kinases as well as downstream transcription factors regulated by nuclear factor κ-light-chain-enhancer of activated B cells (NFκB). In a mouse LPS challenge model, Takinib significantly reduced TNF serum levels. Our findings demonstrate that Takinib has utility in the treatment inflammatory disease by locally suppressing TNF production from invading macrophages.

Toll-like receptor 4 (TLR4)-mediated immune and inflammatory signaling serves a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Our previous study demonstrated that celastrol treatment was able to improve hepatic steatosis and inhibit the TLR4 signaling cascade pathway in type 2 diabetic rats. The present study aimed to investigate the effects of celastrol on triglyceride accumulation and inflammation in steatotic HepG2 cells, and the possible mechanisms responsible for the regulation of cellular responses following TLR4 gene knockdown by small interfering RNA (siRNA) in vitro. A cell model of hepatic steatosis was prepared by exposing the HepG2 cells to free fatty acid (FFA) in the absence or presence of celastrol. Intracellular triglycerides were visualized by Oil red O staining, and the TLR4/myeloid differentiation primary response 88 (MyD88)/nuclear factor-κB (NF-κB) signaling cascade pathway were investigated. To directly elucidate whether TLR4 was the blocking target of celastrol upon FFA exposure, the cellular response to inflammation was determined upon transfection with TLR4 siRNA. The results revealed that celastrol significantly reduced triglyceride accumulation in the steatotic HepG2 cells, and downregulated the expression levels of TLR4, MyD88 and phospho-NF-κBp65, as well as of the downstream inflammatory cytokines interleukin-1β and tumor necrosis factor α. Knockdown of TLR4 also alleviated FFA-induced inflammatory response. In addition, co-treatment with TLR4 siRNA and celastrol further attenuated the expression of inflammatory mediators. These results suggest that celastrol exerts its protective effect partly via inhibiting the TLR4-mediated immune and inflammatory response in steatotic HepG2 cells.

Non-small cell lung cancer (NSCLC) has a very poor prognosis even when treated with the best therapies available today often including radiation. NSCLC is frequently complicated by pulmonary infections which appear to impair prognosis as well as therapy, whereby the underlying mechanisms are still not known. It was investigated here, whether the bacterial lipopolysaccharides (LPS) might alter the tumor cell radiosensitivity. LPS were found to induce a radioresistance but solely in cells with an active TLR-4 pathway. Proteome profiling array revealed that LPS combined with irradiation resulted in a strong phosphorylation of cAMP response element-binding protein (CREB). Inhibition of CREB binding protein (CBP) by the specific inhibitor ICG-001 not only abrogated the LPS-induced radioresistance but even led to an increase in radiosensitivity. The sensitization caused by ICG-001 could be attributed to a reduction of DNA double-strand break (DSB) repair.

It is shown that in NSCLC cells LPS leads to a CREB dependent radioresistance which is, however, reversible through CBP inhibition by the specific inhibitor ICG-001. These findings indicate that the combined treatment with radiation and CBP inhibition may improve survival of NSCLC patients suffering from pulmonary infections.

• CREB
• LPS
• X-irradiation
• infection
• lung cancer

Bioavailable and less toxic synthetic retinoids, such as the atypical adamantyl retinoid ST1926, have been well developed and investigated in clinical trials for many diseases. The aim of our study was to explore the role of ST1926 in lipopolysaccharide (LPS)-induced acute lung injury (ALI) and to reveal the possible molecular mechanism. Mice were treated with LPS to induce acute lung injury followed by ST1926 administration. After LPS induction, mice administered with ST1926 showed lower inflammation infiltration in bronchoalveolar lavage (BAL) fluid, and pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-18, IL-6 and tumor necrosis factor-α (TNF-α) in serum and lung tissue samples obtained from mice. In addition, western blot assays suggested that ST1926 suppressed nuclear factor-κB (NF-κB), inhibitor-κB kinase-α (IκBα) and IκB kinase (IKKα), as well as Toll-like receptor 4 (TLR4) induced by LPS. In addition, reactive oxygen species (ROS) stimulated by LPS was also suppressed for ST1926 through inhibiting p38 and extracellular receptor kinase (ERK) signaling pathway. Taken together, the data here indicated that ST1926 may be of potential value in treating acute lung injury through inflammation and ROS suppression via inactivating TLR4/NF-κB and p38/ERK1/2 signaling pathways.

Agaricus bisporus is one of the most important edible and medicinal mushrooms in the world.

• AH7614 (PubChem CID 233085).
• COX-2
• FFA4
• Free-fatty acids
• GPR120
• Reactive oxygen species
• TUG-891 (Pubchem CID 57522038)

• CaMKIIα
• GABA
• MAPK/ErK
• TLR4
• VGLUT2
• sympathoexcitation
• β2R

• R03 MH104851 NIMH NIH HHS

• Hepatocellular carcinoma
• Inflammation
• TLR4

The pathogenesis of acute lung injury (ALI) induced by lipopolysaccharide (LPS) involves excessive pulmonary inflammation and oxidative stress. In turn, autophagy is associated with inflammatory diseases and organ dysfunction, and studies have demonstrated that LPS treatment may trigger autophagy. Thus, excessive autophagy may stimulate the strong inflammatory response observed in the development of LPS-induced ALI. Saturated hydrogen saline may alleviate LPS-induced ALI by inhibiting autophagy, however its underlying mechanisms of action remain unknown. It has been suggested that saturated hydrogen saline may downregulate expression of nuclear factor (NF)-κB, leading to a decrease in Beclin-1 transcription and inhibition of autophagy. Inhibition of autophagy also occurs via the phosphorylation of Unc-51-like autophagy activating kinase 1 and autophagy-related protein-13 by mechanistic target of rapamycin, which in turn may be upregulated by saturated hydrogen saline. In addition, signaling pathways involving heme oxygenase-1 and p38 mitogen-activated protein kinase are associated with the alleviative effects of saturated hydrogen saline on LPS-induced autophagy. The present review focuses on potential molecular mechanisms regarding the effects of saturated hydrogen saline in the reduction of autophagy during LPS-induced ALI.

• acute lung injury
• autophagy
• lipopolysaccharides
• saturated hydrogen saline

• Infection
• Interleukin-8
• Lipoteichoic acids
• Lung cancer
• Toll-like-receptor-2
• Tumor proliferation

• IFN-τ
• LPS
• MAPKs
• NF-κB
• anti-inflammation

• Acute injury
• Chicken
• Lipopolysaccharide
• Liver
• Toll-like receptor 4

• Alanine Transaminase/blood
• Animals
• Caspase 3/metabolism
• Chemical and Drug Induced Liver Injury/immunology
• Chickens/immunology
• Female
• Lipopolysaccharides/immunology
• Liver/immunology
• Myeloid Differentiation Factor 88/metabolism
• NF-kappa B/metabolism
• Proliferating Cell Nuclear Antigen/metabolism
• Salmonella/immunology
• Signal Transduction
• Toll-Like Receptor 4/metabolism
• Tumor Necrosis Factor-alpha/metabolism

• Fundamental Research Funds for the Central Universities
• Fundamental Research Funds for the Central Universities
• National Natural Science Foundation of China (CN)

• CD200Fc
• Cigarette smoke extract
• Inflammatory responses
• Mouse cardiac microvascular endothelial cells
• NF-κB pathway
• Vascular endothelial barrier

• Animals
• Cell Line
• Dose-Response Relationship, Drug
• Endothelial Cells/drug effects
• Endothelial Cells/metabolism
• Immunoglobulin G/pharmacology
• Immunoglobulin G/therapeutic use
• Inflammation/drug therapy
• Inflammation/metabolism
• Inflammation Mediators/antagonists & inhibitors
• Inflammation Mediators/metabolism
• Mice
• NF-kappa B/antagonists & inhibitors
• NF-kappa B/metabolism
• Signal Transduction/drug effects
• Signal Transduction/physiology
• Smoke/adverse effects
• Smoking/drug therapy
• Smoking/metabolism
• Nicotiana