Sirtuin1-Mediated Deacetylation of Hypothalamic TTF-1 Contributes to the Energy Deficiency Response.

TTF-1 stimulates appetite by regulating the expression of agouti-related peptide (AgRP) and proopiomelanocortin (POMC) genes in the hypothalamus of starving animals. However, the mechanism underlying TTF-1's response to decreased energy levels remains elusive. Here, we provide evidence that the NAD+-dependent deacetylase, sirtuin1 (Sirt1), activates TTF-1 in response to energy deficiency. Energy deficiency leads to a twofold increase in the expression of both Sirt1 and TTF-1, leading to the deacetylation of TTF-1 through the interaction between the two proteins. The activation of Sirt1, induced by energy deficiency or resveratrol treatment, leads to a significant increase in the deacetylation of TTF-1 and promotes its nuclear translocation. Conversely, the inhibition of Sirt1 prevents these Sirt1 effects. Notably, a point mutation in a lysine residue of TTF-1 significantly disrupts its deacetylation and thus nearly completely hinders its ability to regulate AgRP and POMC gene expression. These findings highlight the importance of energy-deficiency-induced deacetylation of TTF-1 in the control of AgRP and POMC gene expression.

Bridging Energy Need and Feeding Behavior: The Impact of eIF2α Phosphorylation in AgRP Neurons.

Eukaryotic translation initiation factor 2α (eIF2α) is a key mediator of the endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR). In mammals, eIF2α is phosphorylated by overnutrition-induced ER stress and is related to the development of obesity. Here, we studied the function of phosphorylated eIF2α (p-eIF2α) in agouti-related peptide (AgRP) neurons using a mouse model (AgRPeIF2αA/A) with an AgRP neuron-specific substitution from Ser 51 to Ala in eIF2α, which impairs eIF2α phosphorylation in AgRP neurons. These AgRPeIF2αA/A mice had decreases in starvation-induced AgRP neuronal activity and food intake and an increased responsiveness to leptin. Intriguingly, impairment of eIF2α phosphorylation produced decreases in the starvation-induced expression of UPR and autophagy genes in AgRP neurons. Collectively, these findings suggest that eIF2α phosphorylation regulates AgRP neuronal activity by affecting intracellular responses such as the UPR and autophagy during starvation, thereby participating in the homeostatic control of whole-body energy metabolism. ARTICLE HIGHLIGHTS: This study examines the impact of eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, triggered by an energy deficit, on hypothalamic AgRP neurons and its subsequent influence on whole-body energy homeostasis. Impaired eIF2α phosphorylation diminishes the unfolded protein response and autophagy, both of which are crucial for energy deficit-induced activation of AgRP neurons. This study highlights the significance of eIF2α phosphorylation as a cellular marker indicating the availability of energy in AgRP neurons and as a molecular switch that regulates homeostatic feeding behavior.

Oncological and functional outcomes of transoral surgery compared with non-surgical management in small-volume oropharyngeal cancer: a systematic review protocol.

OBJECTIVE: The objective of this systematic review is to investigate oncological and functional outcomes following primary transoral surgery compared with non-surgical management in patients with small-volume (T1-2, N0-2) oropharyngeal cancer. INTRODUCTION: The incidence of oropharyngeal cancer is rising. Transoral surgery was introduced to provide a minimally invasive treatment option for patients with small-volume oropharyngeal cancer and to avoid the morbidity that results from open surgery and the potential acute and late toxicities of chemoradiotherapy. INCLUSION CRITERIA: The review will include all studies on adult patients with small-volume oropharyngeal cancer managed by transoral surgery or non-surgical management with radiotherapy and/or chemotherapy. All patients must have undergone treatment with curative intent. Participants who underwent palliative treatment will be excluded. METHODS: This review will follow the JBI methodology for systematic reviews of effectiveness. Eligible study designs will include randomized controlled trials, quasi-experimental studies, and prospective or retrospective cohort studies. Databases to be searched will include PubMed, Embase, CINAHL, Cochrane CENTRAL, and multiple trial registries from 1972. Titles and abstracts will be reviewed, and full-text articles will be retrieved if they meet the inclusion criteria. All eligible studies will be critically appraised by 2 independent reviewers using the appropriate JBI tools for experimental and observational designs. Where possible, outcome data from studies will be pooled with statistical meta-analysis to compare both oncological and functional outcomes between the two groups. All time to event to data will be converted to a common metric for oncological outcomes. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach will be followed to assess the certainty of findings. REVIEW REGISTRATION: PROSPERO CRD4202235209.

Recent trends in vanadium-based SCR catalysts for NOx reduction in industrial applications: stationary sources.

Vanadium-based catalysts have been used for several decades in ammonia-based selective catalytic reduction (NH3-SCR) processes for reducing NOx emissions from various stationary sources (power plants, chemical plants, incinerators, steel mills, etc.) and mobile sources (large ships, automobiles, etc.). Vanadium-based catalysts containing various vanadium species have a high NOx reduction efficiency at temperatures of 350-400 °C, even if the vanadium species are added in small amounts. However, the strengthening of NOx emission regulations has necessitated the development of catalysts with higher NOx reduction efficiencies. Furthermore, there are several different requirements for the catalysts depending on the target industry and application. In general, the composition of SCR catalyst is determined by the components of the fuel and flue gas for a particular application. It is necessary to optimize the catalyst with regard to the reaction temperature, thermal and chemical durability, shape, and other relevant factors. This review comprehensively analyzes the properties that are required for SCR catalysts in different industries and the development strategies of high-performance and low-temperature vanadium-based catalysts. To analyze the recent research trends, the catalysts employed in power plants, incinerators, as well as cement and steel industries, that emit the highest amount of nitrogen oxides, are presented in detail along with their limitations. The recent developments in catalyst composition, structure, dispersion, and side reaction suppression technology to develop a high-efficiency catalyst are also summarized. As the composition of the vanadium-based catalyst depends mostly on the usage in stationary sources, various promoters and supports that improve the catalyst activity and suppress side reactions, along with the studies on the oxidation state of vanadium, are presented. Furthermore, the research trends related to the nano-dispersion of catalytically active materials using various supports, and controlling the side reactions using the structure of shaped catalysts are summarized. The review concludes with a discussion of the development direction and future prospects for high-efficiency SCR catalysts in different industrial fields.

Hypothalamic TTF-1 orchestrates the sensitivity of leptin.

OBJECTIVE: Thyroid transcription factor-1 (TTF-1), a homeodomain-containing transcription factor, is predominantly expressed in discrete areas of the hypothalamus, which acts as the central unit for the regulation of whole-body energy homeostasis. Current study designed to identify the roles of TTF-1 on the responsiveness of the hypothalamic circuit activity to circulating leptin and the development of obesity linked to the insensitivity of leptin. METHODS: We generated conditional knock-out mice by crossing TTF-1flox/flox mice with leptin receptor (ObRb)Cre or proopiomelanocortin (POMC)Cre transgenic mice to interrogate the contributions of TTF-1 in leptin signaling and activity. Changes of food intake, body weight and energy expenditure were evaluated in standard or high fat diet-treated transgenic mice by using an indirect calorimetry instrument. Molecular mechanism was elucidated with immunohistochemistry, immunoblotting, quantitative PCR, and promoter assays. RESULTS: The selective deletion of TTF-1 gene expression in cells expressing the ObRb or POMC enhanced the anorexigenic effects of leptin as well as the leptin-induced phosphorylation of STAT3. We further determined that TTF-1 inhibited the transcriptional activity of the ObRb gene. In line with these findings, the selective deletion of the TTF-1 gene in ObRb-positive cells led to protective effects against diet-induced obesity via the amelioration of leptin resistance. CONCLUSIONS: Collectively, these results suggest that hypothalamic TTF-1 participates in the development of obesity as a molecular component involved in the regulation of cellular leptin signaling and activity. Thus, TTF-1 may represent a therapeutic target for the treatment, prevention, and control of obesity.

Determination of pharmacokinetics and tissue distribution of a novel lutetium-labeled PSMA-targeted ligand, 177Lu-DOTA-PSMA-GUL, in rats by using LC-MS/MS.

Prostate specific membrane antigen (PSMA) is known to be overexpressed in prostate cancer cells, providing as a diagnostic and therapeutic target for prostate cancer. A lutetium-labeled PSMA targeted ligand, 177Lu-DOTA-PSMA-GUL is a novel radiopharmaceutical, which has been developed for the treatment of prostate cancer. While the GUL domain of 177Lu-DOTA-PSMA-GUL binds to the antigen, the beta-emitting radioisotope, 177Lu-labeled DOTA, interacts with prostate cancer cells. However, the in vivo pharmacokinetics of intact 177Lu-DOTA-PSMA-GUL has never been characterized. This study aimed to evaluate the pharmacokinetics and tissue distribution of the radiopharmaceutical in rats by using its stable isotope-labeled analog, 175Lu-DOTA-PSMA-GUL. A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of 175Lu-DOTA-PSMA-GUL was developed and validated. Following intravenous injection, the plasma concentration-time profiles of 175Lu-DOTA-PSMA-GUL showed a multi-exponential decline with the average elimination half-life of 0.30 to 0.33 h. Systemic exposure increased with the dose and renal excretion is the major elimination route. Tissue distribution of 175Lu-DOTA-PSMA-GUL was most substantial in kidneys, followed by the prostate. The developed LC-MS/MS assay and the in vivo pharmacokinetic data of 175Lu-DOTA-PSMA-GUL would provide helpful information for further clinical studies to be developed as a novel therapeutic agent for prostate cancer.

High-Dispersed V2O5-CuOX Nanoparticles on h-BN in NH3-SCR and NH3-SCO Performance.

Typically, to meet emission regulations, the selective catalytic reduction of NOX with NH3 (NH3-SCR) technology cause NH3 emissions owing to high NH3/NOX ratios to meet emission regulations. In this study, V-Cu/BN-Ti was used to remove residual NOX and NH3. Catalysts were evaluated for selective catalytic oxidation of NH3 (NH3-SCO) in the NH3-SCR reaction at 200-300 °C. The addition of vanadium and copper increased the number of Brønsted and Lewis acid sites available for the reaction by increasing the ratio of V5+ and forming Cu+ species, respectively. Furthermore, h-BN was dispersed in the catalyst to improve the content of vanadium and copper species on the surface. NH3 and NOX conversion were 98% and 91% at 260 °C, respectively. Consequently, slipped NH3 (NH3-Slip) emitted only 2% of the injected ammonia. Under SO2 conditions, based on the NH3 oxidation reaction, catalytic deactivation was improved by addition of h-BN. This study suggests that h-BN is a potential catalyst that can help remove residual NOX and meet NH3 emission regulations when placed at the bottom of the SCR catalyst layer in coal-fired power plants.

Metabolic Profiling of the Hypothalamus of Mice during Short-Term Food Deprivation.

Nutrient availability and utilization in hypothalamic cells are directly associated with the regulation of whole-body energy homeostasis. Thus, establishing metabolic profiling in the hypothalamus in response to metabolic shift is valuable to better understand the underlying mechanism of appetite regulation. In the present study, we evaluate the alteration of lipophilic and hydrophilic metabolites in both the hypothalamus and serum of fasted mice. Fasted mice displayed an elevated ketone body and decreased lactate levels in the hypothalamus. In support of the metabolite data, we further confirmed that short-term food deprivation resulted in the altered expression of genes involved in cellular metabolic processes, including the shuttling of fuel sources and the production of monocarboxylates in hypothalamic astrocytes. Overall, the current study provides useful information to close the gap in our understanding of the molecular and cellular mechanisms underlying hypothalamic control of whole-body energy metabolism.

Spexin Regulates Hypothalamic Leptin Action on Feeding Behavior.

Spexin (SPX) is a recently identified neuropeptide that is believed to play an important role in the regulation of energy homeostasis. Here, we describe a mediating function of SPX in hypothalamic leptin action. Intracerebroventricular (icv) SPX administration induced a decrease in food intake and body weight gain. SPX was found to be expressed in cells expressing leptin receptor ObRb in the mouse hypothalamus. In line with this finding, icv leptin injection increased SPX mRNA in the ObRb-positive cells of the hypothalamus, which was blocked by treatment with a STAT3 inhibitor. Leptin also increased STAT3 binding to the SPX promoter, as measured by chromatin immunoprecipitation assays. In vivo blockade of hypothalamic SPX biosynthesis with an antisense oligodeoxynucleotide (AS ODN) resulted in a diminished leptin effect on food intake and body weight. AS ODN reversed leptin's effect on the proopiomelanocortin (POMC) mRNA expression and, moreover, decreased leptin-induced STAT3 binding to the POMC promoter sequence. These results suggest that SPX is involved in leptin's action on POMC gene expression in the hypothalamus and impacts the anorexigenic effects of leptin.

Does a failed DRIL mean the end for a fistula? A case report in the use of an Amplatzer plug post DRIL procedure for ongoing steal syndrome.

Dialysis access steal syndrome is a well-recognised complication, affecting 1%-8% of all patients who undergo arteriovenous fistula formation particularly those that are brachial based. We present a case of ongoing steal syndrome following a DRIL procedure via retrograde flow in the ulnar artery. This was managed via a hybrid procedure and the use of an Amplatzer plug. This case demonstrates a novel use for the Amplatzer occlusion device, it is also a reminder that failure to occlude the vessel close to the fistula anastomosis can result in continued steal despite a functioning DRIL bypass.

Ammonium Ion Enhanced V2O5-WO3/TiO2 Catalysts for Selective Catalytic Reduction with Ammonia.

Selective catalytic reduction (SCR) is the most efficient NOX removal technology, and the vanadium-based catalyst is mainly used in SCR technology. The vanadium-based catalyst showed higher NOX removal performance in the high-temperature range but catalytic efficiency decreased at lower temperatures, following exposure to SOX because of the generation of ammonium sulfate on the catalyst surface. To overcome these limitations, we coated an NH4+ layer on a vanadium-based catalyst. After silane coating the V2O5-WO3/TiO2 catalyst by vapor evaporation, the silanized catalyst was heat treated under NH3 gas. By decomposing the silane on the surface, an NH4+ layer was formed on the catalyst surface through a substitution reaction. We observed high NOX removal efficiency over a wide temperature range by coating an NH4+ layer on a vanadium-based catalyst. This layer shows high proton conductivity, which leads to the reduction of vanadium oxides and tungsten oxide; additionally, the NOX removal performance was improved over a wide temperature range. These findings provide a new mothed to develop SCR catalyst with high efficiency at a wide temperature range.

Selective Wettability Membrane for Continuous Oil-Water Separation and In Situ Visible Light-Driven Photocatalytic Purification of Water.

Membrane-based technologies are attractive for remediating oily wastewater because they are relatively energy-efficient and are applicable to a wide range of industrial effluents. For complete treatment of oily wastewater, removing dissolved contaminants from the water phase is typically followed by adsorption onto an adsorbent, which complicates the process. Here, an in-air superhydrophilic and underwater superoleophobic membrane-based continuous separation of surfactant-stabilized oil-in-water emulsions and in situ decontamination of water by visible-light-driven photocatalytic degradation of dissolved organic contaminants is reported. The membrane is fabricated by utilizing a thermally sensitized stainless steel mesh coated with visible light absorbing iron-doped titania nanoparticles. Post annealing of the membrane can enhance the adhesion of nanoparticles to the membrane surface by formation of a bridge between them. An apparatus that enables continuous separation of surfactant-stabilized oil-in-water emulsion and in situ photocatalytic degradation of dissolved organic matter in the water-rich permeate upon irradiation of visible light on the membrane surface with greater than 99% photocatalytic degradation is developed. The membrane demonstrates the recovery of its intrinsic water-rich permeate flux upon continuous irradiation of light after being contaminated with oil. Finally, continuous oil-water separation and in situ water decontamination is demonstrated by photocatalytically degrading model toxins in water-rich permeate.

Function of astrocyte MyD88 in high-fat-diet-induced hypothalamic inflammation.

BACKGROUND: A growing body of evidence shows that hypothalamic inflammation is an important factor in the initiation of obesity. In particular, reactive gliosis accompanied by inflammatory responses in the hypothalamus are pivotal cellular events that elicit metabolic abnormalities. In this study, we examined whether MyD88 signaling in hypothalamic astrocytes controls reactive gliosis and inflammatory responses, thereby contributing to the pathogenesis of obesity. METHODS: To analyze the role of astrocyte MyD88 in obesity pathogenesis, we used astrocyte-specific Myd88 knockout (KO) mice fed a high-fat diet (HFD) for 16 weeks or injected with saturated free fatty acids. Astrocyte-specific gene expression in the hypothalamus was determined using real-time PCR with mRNA purified by the Ribo-Tag system. Immunohistochemistry was used to detect the expression of glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, phosphorylated signal transducer and activator of transcription 3, and α-melanocyte-stimulating hormone in the hypothalamus. Animals' energy expenditure was measured using an indirect calorimetry system. RESULTS: The astrocyte-specific Myd88 KO mice displayed ameliorated hypothalamic reactive gliosis and inflammation induced by injections of saturated free fatty acids and a long-term HFD. Accordingly, the KO mice were resistant to long-term HFD-induced obesity and showed an improvement in HFD-induced leptin resistance. CONCLUSIONS: These results suggest that MyD88 in hypothalamic astrocytes is a critical molecular unit for obesity pathogenesis that acts by mediating HFD signals for reactive gliosis and inflammation.

Quasi-Solid-State Electrolyte Synthesized Using a Thiol-Ene Click Chemistry for Rechargeable Lithium Metal Batteries with Enhanced Safety.

Liquid electrolytes currently used in lithium-ion batteries have critical drawbacks such as high flammability, high reactivity toward electrode materials, and solvent leakage. To overcome these issues, most recent research has focused on synthesis and characterization of highly conductive gel-type polymer electrolytes containing large numbers of organic solvents in the polymer matrix. There are still many hurdles to overcome, however, before they can be applied to commercial-level lithium-ion batteries. Since a large amount of organic solvent is required to achieve high ionic conductivity, battery safety is not significantly enhanced. In our study, we synthesized highly conductive quasi-solid-state electrolytes (QSEs) containing an ionically conductive oligomer (polycaprolactone triacrylate) and a small amount of organic solvent by employing click chemistry. In the QSE, polycaprolactone participates in dissociation of lithium salt and migration of lithium ions, resulting in high ionic conductivity. The Li/LiNi0.6Co0.2Mn0.2O2 cell that used this QSE exhibited good cycling performance and enhanced thermal stability, and durability; no organic solvent leakage was observed even under high pressure.

Brain-specific chemokine FAM19A5 induces hypothalamic inflammation.

The cytokine-like protein FAM19A5 is highly expressed in the brain, but little is known about its functions there. Here, we found that FAM19A5 was expressed in mouse hypothalamic cells expressing proopiomelanocortin (POMC) and neuropeptide Y (NPY)/agouti-related peptide (AgRP), and in the microglia. Tumor necrosis factor-α (TNF-α), which induces inflammatory sickness responses, greatly increased hypothalamic expression of FAM19A5. Knockdown of FAM19A5 expression resulted in decreased TNF-α-induced anorexia, body weight loss and TNF-α-induced expression of inflammatory factors. In contrast, intracerebroventricular administration of FAM19A5 induced anorexia, body weight loss and hyperthermia, together with increased expression of inflammatory factors. FAM19A5 injection also induced increases in c-fos activation and POMC mRNA level in hypothalamic POMC neurons. Together, these results suggest that FAM19A5 plays an important role in hypothalamic inflammatory responses.

Tonicity-responsive enhancer binding protein (TonEBP) regulates TNF-α-induced hypothalamic inflammation.

Tonicity-responsive enhancer binding protein (TonEBP) is a widely expressed transcription factor and is important in the regulation of inflammatory cytokines. Here, we have identified TonEBP expression in the hypothalamus, which is particularly high in proopiomelanocortin (POMC) neurons. TonEBP overexpression stimulates POMC transcription, and TonEBP haploinsufficiency in TonEBP (+/-) mice results in a decrease in hypothalamic POMC expression. TonEBP (+/-) mice show reduced sickness responses, which include anorexia and hyperthermia, that are initially induced by tumor necrosis factor (TNF)-α. TonEBP (+/-) mice also show lower levels of TNF-α-induced hypothalamic expression of POMC and pro-inflammatory cytokines. These results suggest that TonEBP is an important molecular regulator in the development of inflammatory sickness responses through the control of POMC and pro-inflammatory cytokine expression in the hypothalamus.

Enhanced NOx removal efficiency for SCR catalyst of well-dispersed Mn-Ce nanoparticles on hexagonal boron nitride.

This research is conducted to improve the dispersion of MnOx-CeO2 catalyst because manganese is easily aggregated during continuous thermal environment at operating temperature. Aggregated MnOx particles on the support can be a major reason to degrade the catalyst performance. Therefore, the improved dispersion of MnOx particles leads to the enhancement of the catalyst performance by utilizing hexagonal boron nitride (h-BN) which is well known as thermally stable material. Due to the dispersion of MnOx-CeO2 with 5-20 nm particle size, h-BN-supported MnOx-CeO2 catalyst shows the 93% efficiency in NOx removal at 200 °C. The structure and properties of MnOx-CeO2/h-BN catalyst are characterized by X-ray diffraction, Fourier transform infrared spectroscopy spectra, and NH3-temperature programmed desorption. Then, NOx removal efficiency of catalyst is evaluated on a fixed bed reactor and h-BN-supported catalyst, (Mn0.2-Ce0.1)/BN, increases NOx removal efficiency up to 20% at 200 °C in spite of 2/3 reduced content of MnOx-CeO2 compared to no-supported catalyst (Mn0.3-Ce0.15).

FOXO1 functions in the regulation of nicotinamide phosphoribosyltransferase (Nampt) expression.

Here, we report that Forkhead Box O1 (FOXO1) protein, a tumor suppressor, regulates expression of nicotinamide phosphoribosyltransferase (Nampt) in human breast cancer MCF-7 cells. Nampt plays an important role in the regulation of cell growth, survival, DNA replication and repair, and angiogenesis in tumorigenesis. We revealed that FOXO1 directly inhibits Nampt expression via binding to FOXO1 binding domains in the 5'-flanking region of the nampt gene. Nampt expression was increased by insulin and downstream phosphatidylinositol 3-kinase (PI3K)/Akt signaling, which was inhibited by FOXO1 overexpression. Accordingly, we showed that FOXO1 is also involved in insulin signaling-induced cell survival and proliferation in MCF-7 cells. These results suggest that FOXO1 plays an important role in human breast cancer cells by regulating nampt gene expression.

Comparison of segmental analysis and sacral marker methods for determining the center of mass during level and slope walking.

BACKGROUND: A human's center of mass (COM) is a widely used parameter in both clinical and practical applications. The segmental analysis method for determining the COM is considered the gold standard but is difficult to apply in a real environment. RESEARCH QUESTION: The purpose of this study was to confirm the efficacy of an alternative COM determination method-the sacral marker method-by comparing segmental analysis and sacral marker method results in three dimensions during level or slope walking. METHODS: Ten healthy young subjects (age = 24.0 ±â€¯4.5 yr, height = 174.5 ±â€¯5.9 cm, and weight = 66.9 ±â€¯9.4 kg) participated in the study. Each participant was monitored using a Helen Hayes full-body marker set and asked to walk on level and sloped (7°) terrain. The markers' trajectories were subsequently recorded. Each participant's COM was determined using segmental analysis and sacral marker methods via calculation and direct measurement, respectively. RESULTS: Comparative results indicated no significant differences (p > 0.05) between the segmental analysis and sacral marker method results for the COM displacement, velocity, or acceleration in the fore-aft and vertical directions. Conversely, significant differences (p < 0.05) between the two methods were observed for the COM displacement and acceleration in the medial-lateral direction, suggesting kinematic differences. SIGNIFICANCE: Based on this latter finding, caution should be exercised when determining COM kinematics using the sacral marker method.

Role of thyroid transcription factor-1 in transcriptional regulation of heme oxygenase-1.

Here, we report thyroid transcription factor 1 (TTF-1) as an important transcription factor for the expression of heme oxygenase-1 (HO-1). HO-1 is a well-known cytoprotective enzyme against inflammation. We observed that HO-1 co-expressed with TTF-1 in mouse hypothalamic cells. Results from luciferase and chromatin immunoprecipitation assays revealed that TTF-1 directly activated HO-1 transcription by binding to binding domains in the 5'-flanking region of the HO-1 gene. A proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α), induced nuclear translocation of TTF-1 and increased binding affinity of TTF-1 to its binding sites on the HO-1 gene. HO-1 mRNA increased with TTF-1 overexpression but decreased with RNA interference of TTF-1 expression in rat astroglial C6 cells. Together with results showing involvement of TTF-1 in the TNF-α-induced increase in interleukin 1 beta and monocyte chemotactic protein 1 production, this study suggests that TTF-1 plays an important role in the mouse hypothalamus TNF-α-induced inflammatory response for regulating HO-1 gene expression.