TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration.

Triggering receptor expressed on myeloid cells 2 (TREM2) is strongly linked to Alzheimer's disease (AD) risk, but its functions are not fully understood. Here, we found that TREM2 specifically attenuated the activation of classical complement cascade via high-affinity binding to its initiator C1q. In the human AD brains, the formation of TREM2-C1q complexes was detected, and the increased density of the complexes was associated with lower deposition of C3 but higher amounts of synaptic proteins. In mice expressing mutant human tau, Trem2 haploinsufficiency increased complement-mediated microglial engulfment of synapses and accelerated synaptic loss. Administration of a 41-amino-acid TREM2 peptide, which we identified to be responsible for TREM2 binding to C1q, rescued synaptic impairments in AD mouse models. We thus demonstrate a critical role for microglial TREM2 in restricting complement-mediated synaptic elimination during neurodegeneration, providing mechanistic insights into the protective roles of TREM2 against AD pathogenesis.

Association of lipid-modifying therapy with risk of obstructive sleep apnea: A drug-target mendelian randomization study.

BACKGROUND: Obstructive sleep apnea (OSA) is considered to be an important contributor of dyslipidemia. However, there lacks observational studies focusing on the potential effect of lipid management on OSA risk. Thus, we aimed to investigate the genetic association of lipid-modifying therapy with risk of OSA. METHODS: A drug-target mendelian randomization (MR) study using both cis-variants and cis-expression quantitative trait loci (eQTLs) of lipid-modifying drug targets was performed. The MR analyses used summary-level data of genome wide association studies (GWAS). Primary MR analysis was conducted using inverse-variance-weighted (IVW) method. Sensitivity analysis was performed using weighted median (WM) and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. RESULTS: Genetically proxied low-density lipoprotein cholesterol (LDL-C)-lowering effect of cholesteryl ester transfer protein (CETP) was associated with reduced risk of OSA (odds ratio [OR] =0.75, 95% confidence interval [CI]: 0.60-0.94, false discovery rate [FDR] q value = 0.046). A significant MR association with risk of OSA was observed for CETP expression in subcutaneous adipose tissue (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049), lung (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049) and small intestine (OR = 0.96, 95%CI: 0.93-1.00, FDR q value = 0.049). No significant effects of high-density lipoprotein cholesterol (HDL-C)-raising effect of CETP inhibition, LDL-C-lowering and triglycerides-lowering effect of other drug targets on OSA risk were observed. CONCLUSIONS: The present study presented genetic evidence supporting the association of LDL-C-lowering therapy by CETP inhibition with reduced risk of OSA. These findings provided novel insights into the role of lipid management in patients with OSA and encouraged further clinical validations and mechanistic investigations.

Comparative transcriptome analysis provides insights into the resistance regulation mechanism and inhibitory effect of fungicide phenamacril in Fusarium asiaticum.

Fusarium asiaticum is a destructive phytopathogenic fungus that causes Fusarium head blight of wheat (FHB), leading to serious yield and economic losses to cereal crops worldwide. Our previous studies indicated that target-site mutations (K216R/E, S217P/L, or E420K/G/D) of Type I myosin FaMyo5 conferred high resistance to phenamacril. Here, we first constructed one sensitive strain H1S and three point mutation resistant strains HA, HC and H1R. Then we conducted comparative transcriptome analysis of these F. asiaticum strains after 1 and 10 µg·mL-1 phenamacril treatment. Results indicated that 2135 genes were differentially expressed (DEGs) among the sensitive and resistant strains. The DEGs encoding ammonium transporter MEP1/MEP2, nitrate reductase, copper amine oxidase 1, 4-aminobutyrate aminotransferase, amino-acid permease inda1, succinate-semialdehyde dehydrogenase, 2, 3-dihydroxybenzoic acid decarboxylase, etc., were significantly up-regulated in all the phenamacril-resistant strains. Compared to the control group, a total of 1778 and 2097 DEGs were identified in these strains after 1 and 10 µg·mL-1 phenamacril treatment, respectively. These DEGs involved in 4-aminobutyrate aminotransferase, chitin synthase 1, multiprotein-bridging factor 1, transcriptional regulatory protein pro-1, amino-acid permease inda1, ATP-dependent RNA helicase DED1, acetyl-coenzyme A synthetase, sarcoplasmic/endoplasmic reticulum calcium ATPase 2, etc., showed significantly down-regulated expression in phenamacril-sensitive strain but not in resistant strains after phenamacril treatment. In addition, cyanide hydratase, mating-type protein MAT-1, putative purine nucleoside permease, plasma membrane protein yro2, etc., showed significantly co-down-regulated expression in all the strains after phenamacril treatment. Taken together, This study provides deep insights into the resistance regulation mechanism and the inhibitory effect of fungicide phenamacril and these new annotated proteins or enzymes are worth for the discovery of new fungicide targets.

Microglial repopulation reverses cognitive and synaptic deficits in an Alzheimer's disease model by restoring BDNF signaling.

Over the past decade, compelling genetic evidence has highlighted the crucial role of microglial dysregulation in the development of Alzheimer's disease (AD). As resident immune cells in the brain, microglia undergo dystrophy and senescence during the chronic progression of AD. To explore the potential therapeutic benefits of replenishing the brain with new microglia in AD, we utilized the CSF1R inhibitor PLX3397 to deplete existing microglia and induce repopulation after inhibitor withdrawal in 5xFAD transgenic mice. Our findings revealed the remarkable benefits of microglial repopulation in ameliorating AD-associated cognitive deficits, accompanied by a notable elevation in synaptic proteins and an enhancement of hippocampal long-term potentiation (LTP). Additionally, we observed the profound restoration of microglial morphology and synaptic engulfment following their self-renewal. The impact of microglial repopulation on amyloid pathology is dependent on the duration of repopulation. Transcriptome analysis revealed a high resemblance between the gene expression profiles of repopulated microglia from 5xFAD mice and those of microglia from WT mice. Importantly, the dysregulated neurotrophic signaling pathway and hippocampal neurogenesis in the AD brain are restored following microglial replenishment. Lastly, we demonstrated that the repopulation restores the expression of brain-derived neurotrophic factor (BDNF) in microglia, thereby contributing to synaptic plasticity. In conclusion, our findings provide compelling evidence to support the notion that microglial self-renewal confers substantial benefits to the AD brain by restoring the BDNF neurotrophic signaling pathway. Thus, targeted microglial repopulation emerges as a highly promising and novel therapeutic strategy for alleviating cognitive impairment in AD.

Silver-Mediated [2 + 2 + 1] Cyclization of ortho-Propioloylbenzonitriles with Elemental Selenium: Synthesis of 4H-indeno[1,2-c][1,2]selenazol-4-ones.

An efficient silver-mediated [2 + 2 + 1] cyclization protocol of ortho-propioloylbenzonitriles with elemental selenium for the synthesis of 4H-indeno[1,2-c][1,2]selenazol-4-ones has been developed. One C-Se bond, one N-Se bond, and one C-C bond were rapidly constructed in one step. The reaction might proceed via the formation of a highly reactive selenoketene intermediate, followed by intramolecular cyclization.

Silver-Mediated Intermolecular [2 + 2 + 1] Cyclization of Terminal Alkynones with Elemental Selenium: Regioselective Synthesis of 2,4- or 3,4-Dicarbonylselenophenes.

An efficient and atom-economical silver-mediated [2 + 2 + 1] cyclization protocol for the selective synthesis of 2,4- or 3,4-dicarbonylselenophenes has been developed. Readily accessible substrates, commercially available elemental selenium, and good functional group tolerance make this procedure attractive for the selective synthesis of dicarbonylselenophenes. Preliminary mechanistic investigations indicated that silver acetylene species are possible intermediates for the formation of 3,4-dicarbonylselenophenes.

Alternaria gansuense, a Plant Systematic Fungal Pathogen Producing Swainsonine in Vivo and in Vitro.

Astragalus adsurgens (A. adsurgens), which is considered a forage in China, grows widely in Eurasia and North America. However, Alternaria gansuense (A. gansuense) (synonym: Embellisia astragali) systematically infects A. adsurgens, producing swainsonine (SW), which poisons domesticated animals. In this study, we hypothesized that the A. gansuense SW-producing fungus is morphologically and molecularly related to the locoweed endophyte, Alternaria oxytropis (A. oxytropis), which systematically grows in host plants. Therefore, pure cultures of the fungi from diseased plants or endophytic interactions were collected from fields and assayed for SW via high-performance liquid chromatography linked to mass spectroscopy (HPLC-MS). The production of SW was also detected in A. adsurgens, A. oxytropis and diseased plants by assaying for the presence of the ß-ketoacyl synthase (KS) gene, which is required for SW synthesis. Diseased A. adsurgens and pure cultures of A. gansuense have SW and the healthy-looking A. adsurgens plants also contained SW, probably because they were infected with A. gansuense. Therefore, A. adsurgens-infected A. gansuense are not safe for livestock consumption.

Comparison of the upper airway morphology between Dutch and Chinese adults with obstructive sleep apnea.

PURPOSE: The pathogenesis of obstructive sleep apnea (OSA) is complex and may vary between different races. It has been suggested that the anatomical balance between skeletal tissues and soft tissues around the upper airway is a key pathophysiologic factor of OSA. Therefore, the aim of this study was to compare the anatomical balance of the upper airway between Dutch and Chinese patients with OSA based on cone beam computed tomography (CBCT) images. METHODS: This was a cross-sectional study performed in two centers and included Dutch and Chinese adults with OSA. CBCT scans in the supine position were obtained for both Dutch and Chinese OSA groups. The primary outcome variable was the anatomical balance of the upper airway, defined as the ratio of the tongue area and the maxillomandibular enclosure area. RESULTS: A total of 28 Dutch adults (mean age ± SD of 46.6 ± 14.1 years, body mass index [BMI] of 26.8 ± 3.5 kg/m2, and apnea-hypopnea index [AHI] of 15.7 ± 7.1 events/h) and 24 Chinese adults (age 41.0 ± 12.4 years, BMI 26.5 ± 3.3 kg/m2, and AHI 16.5 ± 7.8 events/h). There were no significant differences in AHI, age, BMI, and sex between the two groups (P = 0.14-0.76). The Dutch group had a significantly larger tongue area and tongue length compared to the Chinese group (P = 0.01 and P < 0.01). On the other hand, the Chinese group had a smaller maxilla length compared to the Dutch group (P < 0.01). However, the anatomical balance of the upper airway of both groups was not significantly different (P = 0.16). CONCLUSION: Within the limitations of this study, no significant difference was found in the anatomical balance of the upper airway between Dutch and Chinese patients with mild to moderate OSA. TRIAL REGISTRATION: The present study was registered at the ClinicalTrials.gov identifier NCT03463785.

Long noncoding RNA HOXA-AS2 ameliorates chronic intermittent hypoxia-induced lung inflammation by regulating miR-17-5p/tipe2 axis.

PURPOSE: The purpose is to confirm whether long noncoding RNA HOXA-AS2 relieves chronic intermittent hypoxia (CIH)-induced lung inflammation. METHODS: Male Sprague Dawley rats were used to establisha CIH rat model. Hematoxylin and Eosin staining was used on the lung tissue injury to determine the successful construction of CIH animal model. Arterial partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2) were measured. HOXA-AS2 was overexpressed to evaluate its role in the progression and development of CIH. T cell differentiation and cytokine production were determined using flow cytometry. Cell apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labelling assay kit. The target of HOXA-AS2 and miR-17-5p was predicted by the Encyclopedia of RNA Interactomes (ENCORI) and confirmed using luciferase assay. RESULTS: HOXA-AS2 was downregulated in CIH rat models. Lung tissue injury was observed in CIH rats, and the injury was attenuated by the overexpression of HOXA-AS2. PaO2 was reduced and PaCO2 was induced in CIH rats, which was reversed by the overexpression of HOXA-AS2. The overexpression of HOXA-AS2 inhibited CIH-induced cell apoptosis. It also reversed alterations in the levels of interferon gamma (IFNγ), interleukin (IL)-2, IL-6, IL-1ß, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta1 (TGF-ß1) in rats caused by CIH. The overexpression of HOXA-AS2 prevented the induction in CD4+ IFN-γ+ T cells and reduction in CD4+TGF-ß1+ T cells. The overexpression of HOXA-AS2 upregulated tumor necrosis factor-alpha-induced protein 8-like 2 (tipe2) key regulator through directly targeting miR-17-5p. Further experiments proved that tipe2 was the direct target of miR-17-5p. CONCLUSION: This study manifested that HOXA-AS2 acted as an anti-inflammatory regulator and protected lung tissue injury from CIH in the rat model; this was mediated by upregulation of tipe2 through directly targeting miR-17-5p. HOXA-AS2 upregulated the expression of tipe2, providing new understanding and therapeutic target for CIH.

Reliability and accuracy of a semi-automatic segmentation protocol of the nasal cavity using cone beam computed tomography in patients with sleep apnea.

OBJECTIVES: The objectives of this study included using the cone beam computed tomography (CBCT) technology to assess: (1) intra- and inter-observer reliability of the volume measurement of the nasal cavity; (2) the accuracy of the segmentation protocol for evaluation of the nasal cavity. MATERIALS AND METHODS: This study used test-retest reliability and accuracy methods within two different population sample groups, from Eastern Asia and North America. Thirty obstructive sleep apnea (OSA) patients were randomly selected from administrative and research oral health data archived at two dental faculties in China and Canada. To assess the reliability of the protocol, two observers performed nasal cavity volume measurement twice with a 10-day interval, using Amira software (v4.1, Visage Imaging Inc., Carlsbad, CA). The accuracy study used a computerized tomography (CT) scan of an OSA patient, who was not included in the study sample, to fabricate an anthropomorphic phantom of the nasal cavity volume with known dimensions (18.9 ml, gold standard). This phantom was scanned using one NewTom 5G (QR systems, Verona, Italy) CBCT scanner. The nasal cavity was segmented based on CBCT images and converted into standard tessellation language (STL) models. The volume of the nasal cavity was measured on the acquired STL models (18.99 ± 0.066 ml). RESULTS: The intra-observer and inter-observer intraclass correlation coefficients for the volume measurement of the nasal cavity were 0.980-0.997 and 0.948-0.992 consecutively. The nasal cavity volume measurement was overestimated by 1.1%-3.1%, compared to the gold standard. CONCLUSIONS: The semi-automatic segmentation protocol of the nasal cavity in patients with sleep apnea and by using cone beam computed tomography is reliable and accurate. CLINICAL RELEVANCE: This study provides a reliable and accurate protocol for segmentation of nasal cavity, which will facilitate the clinician to analyze the images within nasoethmoidal region.

Effect of Alfalfa Cultivars and Ages on the Occurrence of Verticillium Wilt Caused by Verticillium alfalfae.

In August 2019, Verticillium wilt was observed in commercial alfalfa fields in Jinta County, Jiuquan, located to the west of Gansu, China, where Verticillium wilt of alfalfa was first observed in this region. This study was conducted to evaluate the effect of alfalfa cultivars (Galaxie Max, Liangmu No. 2, and Danon VNS, planted in 2017) and ages (cultivar Adrenalin, planted in 2014, 2015, and 2016) on the occurrence of Verticillium wilt caused by Verticillium alfalfae. The results showed that V. alfalfae was successfully isolated from both symptomatic and asymptomatic plants. The percentage of V. alfalfae colonization ranged from 22 to 83% in symptomatic plants and 19 to 31% in asymptomatic plants. Among the three cultivars tested, the lowest incidence of disease symptoms was observed in the plants of cultivar Galaxie Max, In addition, the plants of Galaxie Max had a lower rate of infection with V. alfalfae in the field than the cultivar Danon VNS. Moreover, the diseased plants of Galaxie Max had a higher shoot dry weight and levels of nitrogen (N), phosphorus (P), starch, sucrose, and chlorophyll than the diseased plants of Liangmu No. 2 and Danon VNS. This demonstrated that Galaxie Max has higher resistance/tolerance to Verticillium wilt than Danon VNS. An examination of the different ages of Adrenalin indicated that the plants in 2014 had a higher incidence of disease and rate of infection in the field than the plants in 2016. In addition, the diseased plants in 2016 had a higher shoot dry weight and contents of N, P, sucrose, and starch than the diseased plants in 2014 and 2015. This result indicated that an increase in the age of alfalfa plants contributes to the occurrence and development of Verticillium wilt. The infection of V. alfalfae significantly decreased the shoot dry weights and the contents of chlorophyll, N, P, and starch of alfalfa plants. These results provide a better understanding of the physiological mechanisms of the response of alfalfa plants to Verticillium wilt caused by V. alfalfae.

Nuclear factor Y participates in alcoholic liver disease by activating SREBP1 expression in mice.

Chronic and excessive alcohol consumption leads to alcoholic liver disease (ALD). However, the molecular mechanisms in the regulation of ALD have not been fully deciphered. Liver lipid accumulation is an important research direction in ALD. In this study, the physiological role of nuclear factor Y (NF-Y) in ALD and the related mechanisms were investigated using murine hepatocytes and an ethanol-induced liver injury mouse model. In this study, ethanol promoted hepatic NF-Y expression in a mouse model and Hepa1-6 mouse hepatocytes. Lentivirus-mediated NF-Y overexpression in Hepa1-6 cells markedly increased sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN) expression compared with empty vector control cells. Conversely, CRISPR/Cas9-mediated knockdown of NF-Y subunit A (NF-YA) attenuated FASN and SREBP1 expression. Mechanistically, luciferase reporter gene assays and chromatin immunoprecipitation (ChIP) analysis indicated that NF-Y activates the transcription of SREBP1 by directly binding to the CCAAT regulatory sequence motif in the promoter. Overall, our results reveal a previously unrecognized physiological function of NF-Y in ALD by activating sterol regulatory element-binding protein 1 (SREBP1). Modulation of hepatic NF-Y expression may therefore offer an attractive therapeutic approach to manage ALD.

Selective Synthesis of Pyrano[3,2-b]indoles or Cyclopenta[b]indoles Tethered with Medium-Sized Rings via Cascade C-C σ-Bond Cleavage and C-H Functionalization.

Highly atom-economical tandem reactions have been developed for the synthesis of pyrano[3,2-b]indoles or cyclopenta[b]indoles tethered with 7-, 8-, or 9-membered rings. These reactions first undergo a carbon-carbon σ-bond cleavage reaction of cyclic ß-ketoesters. Next, in the presence of CuCl2 and Ag2CO3, intramolecular O-H/C-H coupling occurs to give pyrano[3,2-b]indoles. This is the first example for capture of the enoloxyl radical of the intramolecular C-O bond formation reaction, whereas C3 nucleophilic addition afforded cyclopenta[b]indoles using TsOH·H2O.

Straightforward Stereoselective Synthesis of Seven-Membered Oxa-Bridged Rings through In Situ Generated Cycloheptenol Derivatives.

An iodine-mediated stereoselective synthesis of seven-membered oxa-bridged rings via in situ generated cycloheptenols was reported. This process was realized through the combination of C-C σ-bond cleavage and C-O bond-forming reactions in a one-pot fashion from simple and easily accessible raw materials. The formation of carbon radicals initiated by I2 was the key to the reaction.

Atom-Economic Synthesis of Highly Functionalized Bridged Ring Systems Initiated by Ring Expansion of Indene-1,3-dione.

An atom economic procedure for the regioselective synthesis of bridged seven-membered-ring compounds from simple reactants such as ynones and indene-1,3-dione has been developed. This process was realized through the one-pot reactions of ring-expansion of indene-1,3-dione with alkynyl ketones and successive formal [4+2] cycloaddition. The Michael addition reaction is the key for the regioselectivity of the formal [4+2] cycloaddition.

Regioselective Synthesis of Tetrasubstituted Benzenes via Co-Catalyzed Cycloaddition of Alkynyl Ketones and 2-Acetylpyridines.

A Co(II)-catalyzed cycloaddition reaction of alkynyl ketones and 2-acetylpyridines using 2,2'-bipyridine as the ligand has been developed. These reactions have been realized through Co-catalyzed reductive coupling of two molecules of 2-acetylpyridine followed by regioselective insertion of the alkynone. It is the first example of regioselective cyclotrimerization of one molecule of alkyne and two molecules of monoketone to polysubstituted benzene derivatives in good to excellent yields. A mechanism involving the formation of a cobaltacyclopentane via homocoupling of 2-acetylpyridines is proposed, and it is supported by the DFT calculations.

Biocontrol Potential of Bacillus amyloliquefaciens LYZ69 Against Anthracnose of Alfalfa (Medicago sativa).

Anthracnose is a destructive disease of alfalfa (Medicago sativa) that causes severe yield losses. Biological control can be an effective and eco-friendly approach to control this alfalfa disease. In the present study, Bacillus amyloliquefaciens LYZ69, previously isolated from healthy alfalfa roots, showed a strong in vitro antifungal activity against Colletotrichum truncatum, an important causal agent of anthracnose of alfalfa. The strain LYZ69 protected alfalfa plants (biocontrol efficacy of 82.59%) from anthracnose under greenhouse conditions. The cell-free culture (CFC) of LYZ69 (20%, vol/vol) caused 60 and 100% inhibition of mycelial growth and conidial germination, respectively. High-performance liquid chromatography tandem mass spectrometry separated and identified cyclic lipopeptides (LPs) such as bacillomycin D and fengycin in the CFC of LYZ69. Light microscopy and scanning electron microscopy revealed that the mixture of cyclic LPs produced by LYZ69 caused drastic changes in mycelial morphology. Fluorescence microscopy showed that the LPs induced reactive oxygen species accumulation and caused apoptosis-like cell death in C. truncatum hyphae. In summary, our findings provide evidence to support B. amyloliquefaciens LYZ69 as a promising candidate for the biological control of anthracnose in alfalfa.

mTOR/NF-κB signaling pathway protects hippocampal neurons from injury induced by intermittent hypoxia in rats.

OBJECTIVE: To expound the roles of mTOR and NF-kB signaling pathway in intermittent hypoxia (IH)-induced damage of hippocampal neurons. METHODS: For rat experiments, mTOR inhibitor (Rapamycin, Rapa) and NF-κB signaling inhibitor (ammonium pyrrolidine dithiocarbamate, PDTC) were applied to inhibit mTOR and NF-κB signaling, respectively. For neuron experiments, hippocampal neurons from rat were successfully cultured. Different concentrations of Rapa and PDTC were added to the cultured hippocampal neurons. Rat or primary hippocampal neurons were exposed to normoxic or IH conditions after administration of Rapa and PDTC. The effects of Rapa and PDTC administration on learning and memory ability of rats and hippocampal injury after IH exposure were assayed by Morris water maze and H&E staining. Electron microscope was utilized to examine primary hippocampal neuron ultrastructure changes after IH exposure and Rapa or PDTC administration. The expressions of NF-κB-p65, IκBα, IKKß, BDNF, TNF-α, IL-1ß, PSD-95 and SYN in hippocampal neurons were examined. RESULTS: Compared with normal control rats or neurons, IH-treated group had elevated expression levels of NF-kB, TNF-α and IL-1ß and suppressed expression level of BDNF, PSD-95 and SYN. These results were reversed upon pre-treatment with Rapa and PDTC. Furthermore, IκBα and IKKß expressions were down-regulated in IH group. No notable difference was manifested in PDTC pre-treatment group, while a prominent increase was shown after Rapa pre-administration. CONCLUSION: The administration of PDTC and Rapa could prevent IH-induced hippocampal neuron impairment, indicating that inhibition of the mTOR and NF-κB pathway may likely act as a therapeutic target for obstructive sleep apnea.

Synthesis of indoline-fused eight-membered azaheterocycles through Zn-catalyzed dearomatization of indoles and subsequent base-promoted C-C activation.

A cascade reaction involving the Zn-catalyzed dearomatization of indoles, base-promoted ring-expansion and intramolecular SNAr reaction has been developed. This process realized a novel, atom economical and efficient synthesis of indoline-fused eight-membered azaheterocycles in a one pot manner.

Vitamin D Attenuates Hypoxia-Induced Injury in Rat Primary Neuron Cells through Downregulation of the Dual Oxidase 1 (DUOX1) Gene.

BACKGROUND This study aimed to investigate the mechanisms underlying the neuroprotective effects of vitamin D. MATERIAL AND METHODS Rat primary neuron cells were incubated under a hypoxia condition [a hypoxic chamber mixed with anaerobic gas (90% N2, 5% CO2) and 5% O2] to induce cell injury. Cell transfection was performed to overexpress or suppress the expression of dual oxidase 1 (DUOX1). The malondialdehyde (MDA) and superoxide dismutase (SOD) levels were detected using a MDA (A003-2) or SOD (A001-1) kit. DUOX1 mRNA levels were detected using RT-PCR. Hypoxia-inducible factor-1alpha (HIF-1alpha), DUOX1, vitamin D receptor (VDR), NF-kappaB protein expressions were determined by western blotting. Cell apoptosis and reactive oxygen species (ROS) were evaluated by flow cytometry. RESULTS ROS increased significantly after hypoxic treatment. The expressions of HIF-1alpha and DUOX1 were significantly increased after hypoxic treatment. Vitamin D could decrease ROS level, apoptotic neuron cells and DUOX1 expression, and increase VDR expression. Downregulation of DUOX1 significantly decreased MDA level and apoptotic percentages of neuron cells, increased SOD level, and counteracted the hypoxia-induced increase of NF-kappaB signal. Further study showed that overexpression of DUOX1 significantly increased MDA level, ROS level, apoptotic percentages of neuron cells, and NF-kappaB nuclear signaling, while decreased SOD level. Vitamin D significantly counteracted the effects of DUOX1 overexpression induced injury in rat primary neuron cells. CONCLUSIONS Our study indicated that vitamin D may protect neuron cells from hypoxia-induced injury by regulating DUOX1 via the NF-kappaB signaling pathway.