Efficacy and Safety of In-Office Transnasal Oesophagoscopy and Balloon Dilatation for Patients Presenting With High Dysphagia: A 6-Year Retrospective Analysis.

BACKGROUND: The primary objective of this study was to assess the efficacy and safety of in-office transnasal oesophagoscopy (TNO) and balloon dilatation for patients presenting with symptoms of high dysphagia. The secondary objective was to conduct a subgroup analysis to better understand patient selection. METHODS: Retrospective observational study from a single university hospital. RESULTS: Two-hundred four TNO and balloon dilatations were performed for 146 patients (median age 73 years; range 12-94 years). Indications included cricopharyngeal hypertrophy ± pouch (n = 70), hypopharyngeal/upper oesophageal web/stenosis (n = 18), head and neck cancer treatment-related (n = 41), multi-level obstruction (n = 13) and symptom-based (n = 4). The mean EAT-10 score improved from 21.2 (SD ± 8.92) pre-dilatation to 12.6 (SD ± 10.7) post-dilatation overall (median follow-up 4.4 months; range 1.5 months-6.21 years). Cricopharyngeal hypertrophy and/or web without dysmotility cohort responded the best with the mean EAT-10 score improvement from 20.4 (SD ± 8.21) to 4.4 (SD ± 6.71). Head and neck cancer patient group showed three types of responses: good response although effect transient requiring repeat dilatations; initial good response however stops responding over time and no response. The overall complication rate was 0.98% (n = 2/204; both failed in-clinic attempts) with 0% perforation rate. CONCLUSION: TNO and balloon dilatation is a safe and effective treatment modality for managing high dysphagia in patients with identifiable non-malignant obstructive pathologies at and around the level of the upper oesophageal sphincter, including head and neck cancer treatment-related patients, both short-term and long-term. Barium swallow is an excellent screening tool for assessing the swallow as a whole.

Central Mechanisms and Pathophysiology of Laryngeal Dystonia: An Up-to-Date Review.

OBJECTIVE: Laryngeal dystonia (LD), previously termed spasmodic dysphonia, is an isolated focal dystonia that involves involuntary, uncontrolled contractions of the laryngeal muscles during speech. It is a severely disabling condition affecting patients' work and social lives through prevention of normal speech production. Our understanding of the pathophysiology of LD and available therapeutic options are currently limited. The aim of this short review is to provide an up-to-date summary of what is known about the central mechanisms and the pathophysiology of LD. METHODS: A systematic review of the literature was performed searching Embase, CINHAL, Medline, and Cochrane with the cover period January 1990-October 2023 with a search strategy (("Laryngeal dystonia" OR "Spasmodic dysphonia") AND ("Central Mechanism" OR "Pathophysiology")). Original studies involving LD patients that discussed central mechanisms and/or pathophysiology of LD were chosen. RESULTS: Two hundred twenty-six articles were identified of which 27 articles were included to formulate this systematic review following the screening inclusion and exclusion criteria. LD is a central neurological disorder involving a multiregional altered neural network. Affected neural circuits not only involve the motor control circuit, but also the feedforward, and the feedback circuits of the normal speech production neural network, involving higher-order planning, somatosensory perception and integration regions of the brain. CONCLUSION: Speech production is a complex process, and LD is a central neurological disorder involving multiregional neural network connectivity alteration reflecting this. Neuromodulation targeting the central nervous system could therefore be considered and explored as a new potential therapeutic option for LD in the future, and should assist in elucidating the underlying central mechanisms responsible for causing the condition.

UAV telephotography elucidates floristic variability and beta diversity of island cliffs under grazing interventions.

Cliffs contain one of the least known plant communities, which has been overlooked in biodiversity assessments due to the inherent inaccessibility. Our study adopted the unmanned aerial vehicle (UAV) with the telephoto camera to remotely clarify floristic variability across unreachable cliffs. Studied cliffs comprised 17 coastal and 13 inland cliffs in Gageodo of South Korea, among which 9 and 5 cliffs were grazed by the introduced cliff-dwelling goats. The UAV telephotography showed 154 and 166 plant species from coastal and inland cliffs, respectively. Inland cliffs contained more vascular plant species (P < 0.001), increased proportions of fern and woody species (P < 0.05), and decreased proportion of herbaceous species (P < 0.001) than coastal cliffs. It was also found that coastal and inland cliffs differed in the species composition (P < 0.001) rather than taxonomic beta diversity (P = 0.29). Furthermore, grazed coastal cliffs featured the elevated proportions of alien and annual herb species than ungrazed coastal cliffs (P < 0.05). This suggests that coastal cliffs might not be totally immune to grazing if the introduced herbivores are able to access cliff microhabitats; therefore, such anthropogenic introduction of cliff-dwelling herbivores should be excluded to conserve the native cliff plant communities.

Biomass-Derived Carbon Utilization for Electrochemical Energy Enhancement in Lithium-Ion Batteries.

Cathodes made of LiFePO4 (LFP) offer numerous benefits including being non-toxic, eco-friendly, and affordable. The distinctive olivine structure of LFP cathodes contributes to their electrochemical stability. Nonetheless, this structure is also the cause of their low ionic and electronic conductivity. To enhance these limitations, an uncomplicated approach has been effectively employed. A straightforward solid-state synthesis technique is used to apply a coating of biomass from potato peels to the LFP cathode, boosting its electrochemical capabilities. Potato peels contain pyridinic and pyrrolic nitrogen, which are conducive to ionic and electronic movement and facilitate pathways for lithium-ion and electron transfer, thus elevating electrochemical performance. When coated with nitrogen-doped carbon derived from potato peel biomass (PPNC@LFP), the LFP cathode demonstrates an improved discharge capacity of 150.39 mAh g-1 at a 0.1 C-rate and 112.83 mAh g-1 at a 1.0 C-rate, in contrast to the uncoated LFP which shows capacities of 141.34 mAh g-1 and 97.72 mAh g-1 at the same rates, respectively.

Loss of hepatic Sirt7 accelerates diethylnitrosamine (DEN)-induced formation of hepatocellular carcinoma by impairing DNA damage repair.

The mammalian sirtuin family (SIRT1-SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor [BMB Reports 2024; 57(2): 98-103].

Inhibition of SIRT7 overcomes sorafenib acquired resistance by suppressing ERK1/2 phosphorylation via the DDX3X-mediated NLRP3 inflammasome in hepatocellular carcinoma.

AIMS: Sirtuin 7 (SIRT7) plays an important role in tumor development, and has been characterized as a potent regulator of cellular stress. However, the effect of SIRT7 on sorafenib acquired resistance remains unclear and a possible anti-tumor mechanism beyond this process in HCC has not been clarified. We examined the therapeutic potential of SIRT7 and determined whether it functions synergistically with sorafenib to overcome chemoresistance. METHODS: Cancer Genome Atlas-liver HCC data and unbiased gene set enrichment analyses were used to identify SIRT7 as a potential effector molecule in sorafenib acquired resistance. Two types of SIRT7 chemical inhibitors were developed to evaluate its therapeutic properties when synergized with sorafenib. Mass spectrometry was performed to discover a direct target of SIRT7, DDX3X, and DDX3X deacetylation levels and protein stability were explored. Moreover, an in vivo xenograft model was used to confirm anti-tumor effect of SIRT7 and DDX3X chemical inhibitors combined with sorafenib. RESULTS: SIRT7 inhibition mediated DDX3X depletion can re-sensitize acquired sorafenib resistance by disrupting NLRP3 inflammasome assembly, finally suppressing hyperactive ERK1/2 signaling in response to NLRP3 inflammasome-mediated IL-1ß inhibition. CONCLUSIONS: SIRT7 is responsible for sorafenib acquired resistance, and its inhibition would be beneficial when combined with sorafenib by suppressing hyperactive pro-cell survival ERK1/2 signaling.

Tumoural Pellino-1 expression and Pellino-1-expressive cytotoxic T-cells are associated with poor prognosis in diffuse large B-cell lymphoma.

Pellino-1 plays a role in regulating inflammation and immune responses, and its effects on tumours are complex, with different outcomes reported in various studies. Additionally, the role of Pellino-1 in diffuse large B-cell lymphoma (DLBCL) has not been thoroughly investigated. We aimed to examine the expression of Pellino-1 in tumour cells and tumour-infiltrating lymphocytes (TILs) separately and identify the clinicopathological significance of Pellino-1 expression in DLBCL. We evaluated Pellino-1 expression in 104 patients with DLBCL. The density of specific cell types was quantitatively analysed using digital image analysis after a multiplex immunofluorescence staining with Pellino-1, CD20, CD8, FOXP3, and PD-1. Pellino-1 expression was mostly observed in CD20+ tumour cells and CD8+ TILs. The high CD8+/Pellino-1+ group was significantly associated with the non-GCB subtype and higher numbers of Foxp3+ T-cells. Patients with high CD20+/Pellino-1+ and high CD8+/Pellino-1+ cell densities had significantly shorter event-free survival (EFS) rates. The multivariate Cox-regression analysis showed that CD20+/Pellino-1+ cell density and CD8+/Pellino-1+ cell density were independent poor prognostic factors for EFS. Furthermore, patients with low densities of both CD20+/Pellino-1+ and CD8+/Pellino-1+ cells demonstrated a prognosis superior to that of patients with high Pellino-1+ cell densities, either alone or in combination. Additionally, the multivariate analysis demonstrated that the combination of CD20+/Pellino-1+ and CD8+/Pellino-1+ cell densities was an independent prognostic factor for EFS and overall survival. Pellino-1 expression was observed in both tumour cells and TILs, particularly in cytotoxic T-cells, and was correlated with poor outcomes in DLBCL. Thus, Pellino-1 might have an oncogenic effect on DLBCL and might be a potential target for improving cytotoxic T-cell activity.

Soluble receptors in cancer: mechanisms, clinical significance, and therapeutic strategies.

Soluble receptors are soluble forms of receptors found in the extracellular space. They have emerged as pivotal regulators of cellular signaling and disease pathogenesis. This review emphasizes their significance in cancer as diagnostic/prognostic markers and potential therapeutic targets. We provide an overview of the mechanisms by which soluble receptors are generated along with their functions. By exploring their involvement in cancer progression, metastasis, and immune evasion, we highlight the importance of soluble receptors, particularly soluble cytokine receptors and immune checkpoints, in the tumor microenvironment. Although current research has illustrated the emerging clinical relevance of soluble receptors, their therapeutic applications remain underexplored. As the landscape of cancer treatment evolves, understanding and targeting soluble receptors might pave the way for novel strategies for cancer diagnosis, prognosis, and therapy.

Continuous Biopotential Monitoring via Carbon Nanotubes Paper Composites (CPC) for Sustainable Health Analysis.

Skin-based wearable devices have gained significant attention due to advancements in soft materials and thin-film technologies. Nevertheless, traditional wearable electronics often entail expensive and intricate manufacturing processes and rely on metal-based substrates that are susceptible to corrosion and lack flexibility. In response to these challenges, this paper has emerged with an alternative substrate for wearable electrodes due to its cost-effectiveness and scalability in manufacturing. Paper-based electrodes offer an attractive solution with their inherent properties of high breathability, flexibility, biocompatibility, and tunability. In this study, we introduce carbon nanotube-based paper composites (CPC) electrodes designed for the continuous detection of biopotential signals, such as electrooculography (EOG), electrocardiogram (ECG), and electroencephalogram (EEG). To prevent direct skin contact with carbon nanotubes, we apply various packaging materials, including polydimethylsiloxane (PDMS), Eco-flex, polyimide (PI), and polyurethane (PU). We conduct a comparative analysis of their signal-to-noise ratios in comparison to conventional gel electrodes. Our system demonstrates real-time biopotential monitoring for continuous health tracking, utilizing CPC in conjunction with a portable data acquisition system. The collected data are analyzed to provide accurate heart rates, respiratory rates, and heart rate variability metrics. Additionally, we explore the feasibility using CPC for sleep monitoring by collecting EEG signals.

Conversion of Natural Biowaste into Energy Storage Materials and Estimation of Discharge Capacity through Transfer Learning in Li-Ion Batteries.

To simultaneously reduce the cost of environmental treatment of discarded food waste and the cost of energy storage materials, research on biowaste conversion into energy materials is ongoing. This work employs a solid-state thermally assisted synthesis method, transforming natural eggshell membranes (NEM) into nitrogen-doped carbon. The resulting NEM-coated LFP (NEM@LFP) exhibits enhanced electrical and ionic conductivity that can promote the mobility of electrons and Li-ions on the surface of LFP. To identify the optimal synthesis temperature, the synthesis temperature is set to 600, 700, and 800 °C. The NEM@LFP synthesized at 700 °C (NEM 700@LFP) contains the most pyrrolic nitrogen and has the highest ionic and electrical conductivity. When compared to bare LFP, the specific discharge capacity of the material is increased by approximately 16.6% at a current rate of 0.1 C for 50 cycles. In addition, we introduce innovative data-driven experiments to observe trends and estimate the discharge capacity under various temperatures and cycles. These data-driven results corroborate and support our experimental analysis, highlighting the accuracy of our approach. Our work not only contributes to reducing environmental waste but also advances the development of efficient and eco-friendly energy storage materials.

Asymbiotic Seed Germination and In Vitro Seedling Development of the Endangered Orchid Species Cypripedium guttatum.

Cypripedium guttatum is a highly restricted terrestrial orchid that faces increasing endangerment owing to its habitat destruction and illegal collection. Compared to epiphytic orchids, terrestrial orchids such as C. guttatum have harder seed coats and more demanding in vitro germination conditions. This study aimed to develop an effective in vitro propagation system for C. guttatum to aid in its conservation. Seeds from mature capsules were subjected to various conditions, including sterilization using 1% sodium hypochlorite (NaOCl) and different light conditions, culture media, hormones, and organic supplements, to assess germination and early seedling development in vitro. Sterilization with 1% NaOCl significantly improved the germination rate, especially under dark conditions. Germination initiation occurred at 2 and 3 months in orchid seed sowing medium (OSM) and Murashige and Skoog (MS) medium, respectively. The addition of 1 mg/L naphthaleneacetic acid (NAA) further enhanced germination. However, the inclusion of organic supplements, such as apple and banana homogenates, in the culture medium led to substantial growth inhibition after 12 months. Notably, orchid maintenance medium (OMM) without organic additives proved to be the most suitable for seedling growth. The results of this study show that sterilization, appropriate light, and optimal NAA concentrations are beneficial for seed germination.

Feruloyl Esterase (LaFae) from Lactobacillus acidophilus: Structural Insights and Functional Characterization for Application in Ferulic Acid Production.

Ferulic acid and related hydroxycinnamic acids, used as antioxidants and preservatives in the food, cosmetic, pharmaceutical and biotechnology industries, are among the most abundant phenolic compounds present in plant biomass. Identification of novel compounds that can produce ferulic acid and hydroxycinnamic acids, that are safe and can be mass-produced, is critical for the sustainability of these industries. In this study, we aimed to obtain and characterize a feruloyl esterase (LaFae) from Lactobacillus acidophilus. Our results demonstrated that LaFae reacts with ethyl ferulate and can be used to effectively produce ferulic acid from wheat bran, rice bran and corn stalks. In addition, xylanase supplementation was found to enhance LaFae enzymatic hydrolysis, thereby augmenting ferulic acid production. To further investigate the active site configuration of LaFae, crystal structures of unliganded and ethyl ferulate-bound LaFae were determined at 2.3 and 2.19 Å resolutions, respectively. Structural analysis shows that a Phe34 residue, located at the active site entrance, acts as a gatekeeper residue and controls substrate binding. Mutating this Phe34 to Ala produced an approximately 1.6-fold increase in LaFae activity against p-nitrophenyl butyrate. Our results highlight the considerable application potential of LaFae to produce ferulic acid from plant biomass and agricultural by-products.

Pellino-1 expression is associated with epidermal proliferation and enhanced Th17 cell infiltration in psoriatic lesions.

Pellino-1 plays a crucial role in cellular proliferation and regulates inflammatory processes. This study investigated Pellino-1 expression patterns and their relationship with CD4+ T-cell subsets in psoriasis patients. Group 1 comprised primarily biopsied psoriasis lesions from 378 patients, multiplex-immunostained for Pellino-1, CD4 and representative T helper (Th) cells (T-bet [Th1], GATA3 [Th2], and RORγt [Th17] and regulatory T cell [FoxP3] markers). Ki-67 labeling was evaluated in the epidermis. Group 2 comprised 43 Pellino-1-positive cases immunostained for Pellino-1 in both lesion and non-lesion skin biopsy samples. Five normal skin biopsies served as controls. Among 378 psoriasis cases, 293 (77.5%) were positive for Pellino-1 in the epidermis. Pellino-1-positivity was higher in psoriasis lesions than in non-lesions and normal skin (52.55% vs. 40.43% vs. 3.48%, p < 0.001; H-score, 72.08 vs. 47.55 vs. 4.40, p < 0.001, respectively). Pellino-1-positive cases also had a significantly higher Ki-67 labeling index (p < 0.001). Epidermal Pellino1-positivity was significantly associated with higher RORγt+ (p = 0.001) and FoxP3+ (p < 0.001) CD4+ T cell ratios but not T-bet+ and GATA3+ CD4+ T cell ratios. Among the CD4+ Pellino-1+ T-cell subsets, the CD4+ Pellino-1+ RORγt+ ratio was significantly associated with epidermal Pellinio-1 expression (p < 0.001). Pellino-1 expression is thus increased in psoriasis lesions and associated with increased epidermal proliferation and CD4+ T-cell subset infiltration, especially Th17 cells. This suggests that Pellino-1 could be a therapeutic target that simultaneously regulates psoriasis epidermal proliferation and immune interactions.

Phosphatase Ssu72 Is Essential for Homeostatic Balance Between CD4+ T Cell Lineages.

Ssu72, a dual-specificity protein phosphatase, not only participates in transcription biogenesis, but also affects pathophysiological functions in a tissue-specific manner. Recently, it has been shown that Ssu72 is required for T cell differentiation and function by controlling multiple immune receptor-mediated signals, including TCR and several cytokine receptor signaling pathways. Ssu72 deficiency in T cells is associated with impaired fine-tuning of receptor-mediated signaling and a defect in CD4+ T cell homeostasis, resulting in immune-mediated diseases. However, the mechanism by which Ssu72 in T cells integrates the pathophysiology of multiple immune-mediated diseases is still poorly elucidated. In this review, we will focus on the immunoregulatory mechanism of Ssu72 phosphatase in CD4+ T cell differentiation, activation, and phenotypic function. We will also discuss the current understanding of the correlation between Ssu72 in T cells and pathological functions which suggests that Ssu72 might be a therapeutic target in autoimmune disorders and other diseases.

Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism.

Changes in the DNA damage response (DDR) and cellular metabolism are two important factors that allow cancer cells to proliferate. DDR is a set of events in which DNA damage is recognized, DNA repair factors are recruited to the site of damage, the lesion is repaired, and cellular responses associated with the damage are processed. In cancer, DDR is commonly dysregulated, and the enzymes associated with DDR are prone to changes in ubiquitination. Additionally, cellular metabolism, especially glycolysis, is upregulated in cancer cells, and enzymes in this metabolic pathway are modulated by ubiquitination. The ubiquitin-proteasome system (UPS), particularly E3 ligases, act as a bridge between cellular metabolism and DDR since they regulate the enzymes associated with the two processes. Hence, the E3 ligases with high substrate specificity are considered potential therapeutic targets for treating cancer. A number of small molecule inhibitors designed to target different components of the UPS have been developed, and several have been tested in clinical trials for human use. In this review, we discuss the role of ubiquitination on overall cellular metabolism and DDR and confirm the link between them through the E3 ligases NEDD4, APC/CCDH1, FBXW7, and Pellino1. In addition, we present an overview of the clinically important small molecule inhibitors and implications for their practical use.

Ssu72 phosphatase is essential for thermogenic adaptation by regulating cytosolic translation.

Brown adipose tissue (BAT) plays a pivotal role in maintaining body temperature and energy homeostasis. BAT dysfunction is associated with impaired metabolic health. Here, we show that Ssu72 phosphatase is essential for mRNA translation of genes required for thermogenesis in BAT. Ssu72 is found to be highly expressed in BAT among adipose tissue depots, and the expression level of Ssu72 is increased upon acute cold exposure. Mice lacking adipocyte Ssu72 exhibit cold intolerance during acute cold exposure. Mechanistically, Ssu72 deficiency alters cytosolic mRNA translation program through hyperphosphorylation of eIF2α and reduces translation of mitochondrial oxidative phosphorylation (OXPHOS) subunits, resulting in mitochondrial dysfunction and defective thermogenesis in BAT. In addition, metabolic dysfunction in Ssu72-deficient BAT returns to almost normal after restoring Ssu72 expression. In summary, our findings demonstrate that cold-responsive Ssu72 phosphatase is involved in cytosolic translation of key thermogenic effectors via dephosphorylation of eIF2α in brown adipocytes, providing insights into metabolic benefits of Ssu72.

Crystal Structure and Biochemical Analysis of a Cytochrome P450 Steroid Hydroxylase (BaCYP106A6) from Bacillus Species.

Cytochrome P450 (CYP) is a heme-containing enzyme that catalyzes hydroxylation reactions with various substrate molecules. Steroid hydroxylases are particularly useful for effectively introducing hydroxyl groups into a wide range of steroids in the pharmaceutical industry. This study reports a newly identified CYP steroid hydroxylase (BaCYP106A6) from the bacterium Bacillus sp. and characterizes it using an in vitro enzyme assay and structural investigation. Bioconversion assays indicated that BaCYP106A1 catalyzes the hydroxylation of progesterone and androstenedione, whereas no or low conversion was observed with 11ß-hydroxysteroids such as cortisol, corticosterone, dexamethasone, and prednisolone. In addition, the crystal structure of BaCYP106A6 was determined at a resolution of 2.8 Å to investigate the configuration of the substrate-binding site and understand substrate preference. This structural characterization and comparison with other bacterial steroid hydroxylase CYPs allowed us to identify a unique Arg295 residue that may serve as the key residue for substrate specificity and regioselectivity in BaCYP106A6. This observation provides valuable background for further protein engineering to design commercially useful CYP steroid hydroxylases with different substrate specificities.

3D-Printed Silicone Substrates as Highly Deformable Electrodes for Stretchable Li-Ion Batteries.

Stretchable energy storage devices receive a considerable attention at present due to their growing demand for powering wearable electronics. A vital component in stretchable energy storage devices is its electrode which should endure a large and repeated number of mechanical deformations during its prolonged use. It is crucial to develop a technology to fabricate highly deformable electrode in an easy and an economic manner. Here, the fabrication of stretchable electrode substrates using 3D-printing technology is reported. The ink for fabricating it contains a mixture of sacrificial sugar particles and polydimethylsiloxane resin which solidifies upon thermal curing. The printed stretchable substrate attains a porous structure after leaching the sugar particles in water. The resulting printed porous stretchable substrates are then utilized as electrodes for Li-ion batteries (LIBs) after loading them with electrode materials. The batteries with stretchable electrodes exhibit a decent electrochemical performance comparable to that of the conventional electrodes. The stretchable electrodes also exhibit a stable electrochemical performance under various mechanical deformations and even after several hundreds of stretch/release cycles. This work provides a feasible route for constructing LIBs with high stretchability and enhanced electrochemical performance thereby providing a platform for realizing stretchable batteries for next generation wearable electronics.

Protection against Lipopolysaccharide-Induced Endotoxemia by Terrein Is Mediated by Blocking Interleukin-1ß and Interleukin-6 Production.

Terrein is a fungal metabolite and has been known to exert anti-melanogenesis, anti-cancer, and anti-bacterial activities. However, its role in endotoxemia has never been investigated until now. In the present study, we examined the effect of terrein on lipopolysaccharide (LPS)-induced endotoxemia in mice and characterized the potential mechanisms of action. Treatment with terrein increased the survival of mice and decreased the production of inflammatory cytokines, including interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in an LPS-induced endotoxemia model. In addition, terrein suppressed the LPS-induced production of IL-1ß and IL-6 in RAW 264.7 cells, a murine macrophage-like cell line, and the mRNA expression of IL-1ß and IL-6 was also inhibited by terrein in LPS-stimulated RAW 264.7 cells. Further study demonstrated that terrein blocked LPS-induced phosphorylation of p65 subunit of nuclear factor (NF)/κB and the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) was also suppressed by terrein treatment. Collectively, these results suggest that terrein exerts a protective effect again LPS-induced endotoxemia in mice by blocking the production of inflammatory cytokines. Our results also suggest that the anti-inflammatory effect of terrein might be mediated, at least in part, by blocking the activation of NF-κB, JNK, and p38 MAPK signaling pathways.