Causal relationship between circulating lipid traits and periodontitis: univariable and multivariable Mendelian randomization.

Introduction: The correlation between dyslipidemia and periodontitis is revealed through epidemiological studies. However, the results are affected by several confounding factors. This study aims to elucidate the genetic causal association between circulating lipid traits and periodontitis by two-sample Mendelian randomization (MR) analysis. Methods: After the different screening processes, two cohorts of circulating lipid traits from the UK Biobank were used as exposure data, including five circulating lipid traits. The Periodontitis cohort was selected from the GeneLifestyle Interactions in Dental Endpoints (GLIDE) consortium as outcome data. In univariable MR, the inverse variance weighted (IVW) was used in conjunction with six additional analytical methods to assess causality. The Cochran Q test, IGX 2 statistic, MR-PRESSO, and MR-Egger intercept were used to quantify heterogeneity and pleiotropy. The multivariable MR-IVW (MVMR-IVW) and MVMR-robust were mainly used as analytical methods in the multiple MR analyses. Results: The IVW estimates showed that genetically predicted Apolipoprotein A1 (apo A1) [odds ratio (OR)=1.158, 95% confidence interval (CI)=1.007-1.331, P-value=0.040] was potentially associated with the risk of periodontitis, but the statistical power of the results was low. Multivariable MR analysis did not reveal any significant causal relationship between apo A1 and periodontitis (OR=0.72, 95% CI=0.36-1.41, P-value=0.34). In the validation cohort, there was also no significant causal relationship between apo A1 and periodontitis (OR=1.079, 95% CI=0.903-1.290, P-value=0.401). Meanwhile, genetically predicted Apolipoprotein B (apo B), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) (all P-values>0.05) were not significantly associated with the risk of periodontitis causal inference. Conclusion: This MR analysis was unable to provide genetic evidence for the influence of these five circulating lipid traits on periodontitis. However, a more extensive study with a more comprehensive circulating lipid profile and periodontitis data is needed due to study limitations.

Bias propagation in network meta-analysis models.

Network meta-analysis combines direct and indirect evidence to compare multiple treatments. As direct evidence for one treatment contrast may be indirect evidence for other treatment contrasts, biases in the direct evidence for one treatment contrast may affect not only the estimate for this particular treatment contrast but also estimates of other treatment contrasts. Because network structure determines how direct and indirect evidence are combined and weighted, the impact of biased evidence will be determined by the network geometry. Thus, this study's aim was to investigate how the impact of biased evidence spreads across the whole network and how the propagation of bias is influenced by the network structure. In addition to the popular Lu & Ades model, we also investigate bias propagation in the baseline model and arm-based model to compare the effects of bias in the different models. We undertook extensive simulations under different scenarios to explore how the impact of bias may be affected by the location of the bias, network geometry and the statistical model. Our results showed that the structure of a network has an important impact on how the bias spreads across the network, and this is especially true for the Lu & Ades model. The impact of bias is more likely to be diluted by other unbiased evidence in a well-connected network. We also used a real network meta-analysis to demonstrate how to use the new knowledge about bias propagation to explain questionable results from the original analysis.

A Light-Permeable Solar Evaporator with Three-Dimensional Photocatalytic Sites to Boost Volatile-Organic-Compound Rejection for Water Purification.

Solar-driven interfacial evaporation (SIE) is emerging as an energy-efficient technology to alleviate the global water shortages. However, there is a fatal disadvantage in using SIE, that is, the volatile organic compounds (VOCs) widely present in feedwater would concurrently evaporate and transport in distilled water, which threatens the water safety. Photocatalysis is a sustainable technology for pollution control, and after years of development, it has become a mature method. Considering the restriction by the insufficient reaction of the permeating VOCs on the two-dimensional (2D) light-available interface of conventional materials, a 3D photocatalytic approach can be established to boost VOC rejection for photothermal evaporation. In the present work, a light-permeable solar evaporator with 3D photocatalytic sites is constructed by a porous sponge decorated with BiOBrI nanosheets with oxygen-rich vacancies. The 3D microchannels in the evaporator provide a light-permeable path with the deepest irradiation depth of about 580 µm, and the reactive interface is increased by tens of times compared with the traditional 2D membrane, resulting in suppression of VOC remnants in distilled water by around four orders of magnitude. When evaporating river water containing 5 mg L-1 extra added phenol, no phenol residues (below 0.001 mg/L) were detected in the produced freshwater. This development is believed to provide a powerful strategy to resolve the VOC bottleneck of SIE.

Pharmacological inhibition of ALCAT1 mitigates amyotrophic lateral sclerosis by attenuating SOD1 protein aggregation.

OBJECTIVE: Mutations in the copper-zinc superoxide dismutase (SOD1) gene cause familial amyotrophic lateral sclerosis (ALS), a progressive fatal neuromuscular disease characterized by motor neurons death and severe skeletal muscle degeneration. However, there is no effective treatment for this debilitating disease, since the underlying cause for the pathogenesis remains poorly understood. Here, we investigated a role of acyl-CoA:lysocardiolipin acyltransferase 1 (ALCAT1), an acyltransferase that promotes mitochondrial dysfunction in age-related diseases by catalyzing pathological remodeling of cardiolipin, in promoting the development of ALS in the SOD1G93A transgenic mice. METHODS: Using SOD1G93A transgenic mice with targeted deletion of the ALCAT1 gene and treated with Dafaglitapin (Dafa), a very potent and highly selective ALCAT1 inhibitor, we determined whether ablation or pharmaceutical inhibition of ALCAT1 by Dafa would mitigate ALS and the underlying pathogenesis by preventing pathological remodeling of cardiolipin, oxidative stress, and mitochondrial dysfunction by multiple approaches, including lifespan analysis, behavioral tests, morphological and functional analysis of skeletal muscle, electron microscopic and Seahorse analysis of mitochondrial morphology and respiration, western blot analysis of the SOD1G93A protein aggregation, and lipidomic analysis of cardiolipin content and acyl composition in mice spinal cord. RESULTS: ALCAT1 protein expression is potently upregulated in the skeletal muscle of the SOD1G93A mice. Consequently, ablation or pharmacological inhibition of ALCAT1 by Dafa attenuates motor neuron dysfunction, neuronal inflammation, and skeletal muscle atrophy in SOD1G93A mice by preventing SOD1G93A protein aggregation, mitochondrial dysfunction, and pathological CL remodeling, leading to moderate extension of lifespan in the SOD1G93A transgenic mice. CONCLUSIONS: ALCAT1 promotes the development of ALS by linking SOD1G93A protein aggregation to mitochondrial dysfunction, implicating Dafa as a potential treatment for this debilitating disorder.

Autophagy-Related Genes Predict the Progression of Periodontitis Through the ceRNA Network.

Purpose: The goal of this study was to identify the crucial autophagy-related genes (ARGs) in periodontitis and construct mRNA-miRNA-lncRNA networks to further understand the pathogenesis of periodontitis. Methods: We used the Gene Expression Omnibus (GEO) database and Human Autophagy Database (HADb) to identify differentially expressed mRNAs, miRNAs, and ARGs. These ARGs were subjected to Gene Ontology (GO), KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, and PPI (protein-protein interaction) network analysis. Two databases (miRDB and StarBase v2.0) were used to reverse-predict miRNAs while the miRNA-lncRNA interaction was predicted using the StarBase v2.0 and LncBase Predicted v.2 databases. After excluding the lncRNAs only present in the nucleus, a competing endogenous RNA (ceRNA) network was built. Finally, we used quantitative real-time PCR (qRT-PCR) to confirm the levels of mRNA expression in the ceRNA network. Results: The differential expression analysis revealed 10 upregulated and 10 downregulated differentially expressed ARGs. After intersecting the reverse-predicted miRNAs with the differentially expressed miRNAs, a ceRNA network consisting of 4 mRNAs (LAMP2, NFE2L2, NCKAP1, and EGFR), 3 miRNAs (hsa-miR-140-3p, hsa-miR-142-5p, and hsa-miR-671-5p), and 30 lncRNAs was constructed. In addition, qRT-PCR results revealed that EGFR expression was downregulated in diseased gingival tissue of periodontitis patients. Conclusion: Four autophagy-related genes, especially EGFR, may play a key role in periodontitis progression. The novel ceRNA network may aid in elucidating the role and the mechanism of autophagy in periodontitis, which could be important in developing new therapeutic options.

Smarcd1 antagonizes the apoptosis of injured MES23.5 DA cells by enhancing the effect of Six2 on GDNF expression.

Glial cell line-derived neurotrophic factor (GDNF) played critical roles in the survival and repair of dopaminergic (DA) neurons. Transcription factor Six2 could repair injured DA cells by promoting the expression of GDNF, however, the underlying molecular mechanisms remain largely unknown. In this study, we screened forty-three proteins that interacted with Six2 in MES23.5 DA cells treated with 6-OHDA by liquid chromatography - electrospray - ionization tandem mass spectrometry (LC-ESI-ITMS/MS). Among these proteins, Smarcd1 is a member of SWI/SNF chromatin-remodeling complex family. Our results confirmed that Smarcd1 formed a transcription complex with Six2, and Smarcd1 mainly binded to the 2840 bp-2933 bp region of the GDNF promoter. Furthermore, knockdown of Smarcd1 inhibited the effect of Six2 on GDNF expression, and resulted in decreased cell viability and increased the apoptosis of injured DA neurons, and the result of overexpression of Smarcd1 is opposite to knockdown. Taken together, our results indicate that smarcd1 can be recruited to the promoter region of GDNF by transcription factor Six2 to promote the effect of Six2 on GDNF expression and protect injured MES23.5 DA cells, which could be useful in identifying potential drug targets for promoting endogenous GDNF expression.

Biomechanical Evaluation of Oblique Lumbar Interbody Fusion with Various Fixation Options: A Finite Element Analysis.

OBJECTIVE: The aim of the present study was to clarify the biomechanical properties of oblique lumbar interbody fusion (OLIF) using different fixation methods in normal and osteoporosis spines. METHODS: Normal and osteoporosis intact finite element models of L1 -S1 were established based on CT images of a healthy male volunteer. Group A was the normal models and group B was the osteoporosis model. Each group included four subgroups: (i) intact; (ii) stand-alone cage (Cage); (iii) cage with lateral plate and two lateral screws (LP); and (iv) cage with bilateral pedicle screws and rods (BPSR). The L3 -L4 level was defined as the surgical segment. After validating the normal intact model, compressive load of 400 N and torsional moment of 10 Nm were applied to the superior surface of L2 to simulate flexion, extension, left bending, right bending, left rotation, and right rotation motions. Surgical segmental range of motion (ROM), cage stress, endplate stress, supplemental fixation stress, and stress distribution were analyzed in each group. RESULTS: Cage provided the minimal reduction of ROM among all motions (normal, 82.30%-98.81%; osteoporosis, 92.04%-97.29% of intact model). BPSR demonstrated the maximum reduction of ROM (normal, 43.94%-61.13%; osteoporosis, 45.61%-62.27% of intact model). The ROM of LP was between that of Cage and BPSR (normal, 63.25%-79.72%; osteoporosis, 70%-87.15% of intact model). Cage had the minimal cage stress and endplate stress. With the help of LP and BPSR fixation, cage stress and endplate stress were significantly reduced in all motions, both in normal and osteoporosis finite element models. However, BPSR had more advantages. For cage stress, BPSR was at least 75.73% less than that of Cage in the normal model, and it was at least 80.10% less than that of Cage in the osteoporosis model. For endplate stress, BPSR was at least 75.98% less than that of Cage in the normal model, and it was at least 78.06% less than that of Cage in the osteoporosis model. For supplemental fixation stress, BPSR and LP were much less than the yield strength in all motions in the two groups. In addition, the comparison between the two groups showed that the ROM, cage stress, endplate stress, and supplemental fixation stress in the normal model were less than in the osteoporosis model when using the same fixation option of OLIF. CONCLUSION: Oblique lumbar interbody fusion with BPSR provided the best biomechanical stability both in normal and osteoporosis spines. The biomechanical properties of the normal spine were better than those of the osteoporosis spine when using the same fixation option of OLIF.

Volatile-Organic-Compound-Intercepting Solar Distillation Enabled by a Photothermal/Photocatalytic Nanofibrous Membrane with Dual-Scale Pores.

Solar distillation is emerging as a robust and energy-effective tool for water purification and freshwater production. However, many water sources contain harmful volatile organic compounds (VOCs), which can evaporate through the photothermal evaporators and be collected together with distilled water, or even be enriched in the distilled water. In view of the penetration of volatile organic compounds, herein, we rationally demonstrate a dual-scale porous, photothermal/photocatalytic, flexible membrane for intercepting volatile organic compounds during solar distillation, which is based on a mesoporous oxygen-vacancy-rich TiO2-x nanofibrous membrane (m-TiO2-x NFM). The dual-scale porous structure was constructed by micrometer-sized interconnected tortuous pores formed by the accumulation of m-TiO2-x nanofibers and nanometer-sized pores in the m-TiO2-x individual nanofibers. Consequently, the membrane can sustainably in situ intercept VOCs by providing more photocatalytic reactive sites for collision (mainly by mesopores) and longer tortuous channels for prolonging VOC retention (mainly by micrometer-sized pores); thus, it results in less than 5% of phenol residual in distilled water. As a proof of concept, when the m-TiO2-x NFM is employed to purify practical river water in an evaporation prototype under real solar irradiation, complex volatile natural organic contaminants can be effectively intercepted and the produced distilled water meets the drinking water standards of China. This development will promote the application prospects of solar distillation.

[Protective effect of edaravone on balance of mitochondrial fusion and fission in MPP+-treated PC12 cells].

The aim of this study was to investigate the effect of edaravone (Eda) on the balance of mitochondrial fusion and fission in Parkinson's disease (PD) cell model. A cell model of PD was established by treating PC12 cells with 500 µmol/L 1-methyl-4-phenylpyridinium (MPP+). Thiazole blue colorimetry (MTT) was used to detect the effect of different concentrations of Eda on the survival rate of PC12 cells exposed to MPP+. The mitochondrial morphology was determined by laser confocal microscope. Western blot was used to measure the protein expression levels of mitochondrial fusion- and fission-related proteins, including OPA1, MFN2, DRP1 and Fis1. The results showed that pretreatment with different concentrations of Eda antagonized MPP+-induced PC12 cell damage in a dose-dependent manner. The PC12 cells treated with MPP+ showed mitochondrial fragmentation, up-regulated DRP1 and Fis1 protein expression levels, and down-regulated MFN2 and OPA1 protein expression levels. Eda could reverse the above changes in the MPP+-treated PC12 cells, but did not affect Fis1 protein expression. These results suggest that Eda has a protective effect on the mitochondrial fusion disruption induced by MPP+ in PC12 cells. The mechanism may be related to the up-regulation of OPA1/MFN2 and down-regulation of DRP1.

Drainage after posterior single-level instrumented lumbar fusion: Natural pressure vs negative pressure.

Recent findings have shown a trend toward recommending against the routine use of drains in spinal surgery because it carries the risk for potential complications. However, most surgeons still use closed suction drainage to prevent hematoma formation. This study is to compare the clinical outcomes between natural pressure drainage and negative pressure drainage after posterior lumbar interbody fusion.Consecutive 132 patients who underwent spinal fusion in the Third Hospital of Hebei Medical University and met the inclusion criteria were reviewed from January 2018 to January 2019 and divided into negative pressure drainage group and natural pressure drainage group according to different pressure drainage. There were 64 patients who had a negative pressure drainage placed and 68 patients who had a natural pressure drainage placed. Demographics, intraoperative blood loss, operative room time, drainage volume at the 1st postoperative day, total volume of postoperative drainage, the total drainage days, postoperative temperature, and postoperative complications (wound infection, symptomatic hematoma) were compared between the 2 groups.The median drainage volume at the 1st postoperative day in negative pressure group was 204.89 ±â€Š95.19 mL, while in natural pressure group, it was 141.00 ±â€Š52.19 mL (P = .000). The median total volume of postoperative drainage in negative pressure group was 378.06 ±â€Š117.98 mL, while in natural pressure group, it was 249.32 ±â€Š70.74 mL (P = .000). The median total drainage days between natural pressure group and negative pressure group were obviously different (2.93 ±â€Š0.55 vs 3.51 ±â€Š0.71 days, P = .000). There was no difference in patient characteristics, operative data, postoperative temperature, and complications.Natural pressure drainage significantly reduced postoperative drainage volume and indwelling time, but did not increase postoperative complications. Therefore, it may offer an alternative to negative pressure drainage and is as safe and effective as negative pressure drainage.

MicroRNA-638 expression change in osteosarcoma patients via PLD1 and VEGF expression.

The present study aimed to investigate the function and mechanism of microRNA-638 (miR-638) in osteosarcoma. MiR-638 expression change in patients with osteosarcoma was detected by reverse transcription-quantitative polymerase chain reaction. Expression of miR-638 was observed to be downregulated in patients with osteosarcoma compared with the control group. In vitro, overexpression of miR-638 induced apoptosis, and inhibited cell proliferation and invasion of osteosarcoma cells. Overexpression of miR-638 induced Bcl-2 associated X and caspase-3 protein expression, and suppressed cyclin D1, phospholipase D1 (PLD1) and vascular endothelial growth factor (VEGF) protein expression in osteosarcoma. The promotion of PLD1 decreased the effects of miR-638 on osteosarcoma cell proliferation. In summary, it was demonstrated that miRNA-638 expression change in patients with osteosarcoma and an in vitro model via PLD1 and VEGF expression and miRNA-638 may be potential clinical indicators of osteosarcoma.

Cardiolipin remodeling by ALCAT1 links mitochondrial dysfunction to Parkinson's diseases.

Cardiolipin (CL) is a mitochondrial signature phospholipid that is required for membrane structure, respiration, dynamics, and mitophagy. Oxidative damage of CL by reactive oxygen species is implicated in the pathogenesis of Parkinson's disease (PD), but the underlying cause remains elusive. This work investigated the role of ALCAT1, an acyltransferase that catalyzes pathological remodeling of CL in various aging-related diseases, in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP). We show that MPTP treatment caused oxidative stress, mtDNA mutations, and mitochondrial dysfunction in the midbrain. In contrast, ablation of the ALCAT1 gene or pharmacological inhibition of ALCAT1 prevented MPTP-induced neurotoxicity, apoptosis, and motor deficits. ALCAT1 deficiency also mitigated mitochondrial dysfunction by modulating DRP1 translocation to the mitochondria. Moreover, pharmacological inhibition of ALCAT1 significantly improved mitophagy by promoting the recruitment of Parkin to dysfunctional mitochondria. Finally, ALCAT1 expression was upregulated by MPTP and by α-synucleinopathy, a key hallmark of PD, whereas ALCAT1 deficiency prevented α-synuclein oligomerization and S-129 phosphorylation, implicating a key role of ALCAT1 in the etiology of mouse models of PD. Together, these findings identify ALCAT1 as a novel drug target for the treatment of PD.

High-performance for hydrogen evolution and pollutant degradation of reduced graphene oxide/two-phase g-C3N4 heterojunction photocatalysts.

We have successfully synthesized the composites of two-phase g-C3N4 heterojunction photocatalysts by one-step method. And the reduced graphene oxide/two-phase g-C3N4 heterojunction photocatalyst was fabricated via a facile hydrothermal reduction method. The characterization results indicated that the two-phase g-C3N4 was integrated closely, and the common phenomenon of agglomeration for g-C3N4 was significantly reduced. Moreover, the oxidized graphene was reduced successfully in the composites and the graphene was overlaid on the surface or the interlayers of g-C3N4 heterojunction composite uniformly. In addition, we have carried out the photocatalytic activity experiments by H2 evolution and rhodamine B removal, tetracycline removal under the visible light irradiation. The results revealed that the composite has improved the separation efficiency a lot than the pure photocatalyst. The photocurrent test demonstrated that the recombination of electrons and holes were efficiently inhibited as well as enhanced the photocatalytic activity. The 0.4% rGO loaded samples, 0.4% rGOCN2, own the best performance. Its rate of H2 evolution was 15 times as high as that of the pure g-C3N4.

Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse.

Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. The expressions of P2X7R, NLRP3 inflammsome components, and cleaved caspase-3 were significantly enhanced in the ischemic brain tissue after stroke. However, the expression of cleaved caspase-3 was significantly attenuated after treatment of stroke with P2X7R antagonist (BBG) or NLRP3 inhibitor (MCC950). The treatment also significantly reduced the infarction volume, neuronal apoptosis, and neurological impairment. In addition, in vitro data also support the hypothesis that P2X7R/NLRP3 pathway plays a vital role in caspase-3 dependent neuronal apoptosis after ischemic stroke. Further investigation of effective regulation of P2X7R and NLRP3 in stroke is warranted.

Comparisons of periodontal regenerative therapies: A meta-analysis on the long-term efficacy.

AIM: We conducted a meta-analysis for the long-term differences in treatment outcomes between periodontal regeneration therapies and flap operation. METHODS: A systematic literature search was conducted using the EMBASE, PubMed and Cochrane databases up to June 2016. Treatment outcomes were changes in probing pocket depth and clinical attachment level. We extracted data reported at different time points after periodontal surgery and incorporated all data into the same model. The restricted cubic spline regression was used to estimate the non-linear trend in treatment outcomes. As some studies reported outcomes at multiple time points, we considered several correlation structures for data reported by the same study. RESULTS: A total of 52 randomized controlled trials were included in our longitudinal meta-analysis. The follow-up length ranged from 0.5 year to 10 years. The trends in the treatment outcomes were similar under different correlation structures. Enamel matrix derivatives (EMD) and guided tissue regeneration (GTR) achieved greater probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain than flap operation (FO) in the long-term follow up, but no differences were found between EMD and GTR. CONCLUSION: Compared with FO, periodontal regeneration surgeries achieved greater PPD reduction and gain in CAL after 1 year, and its effects may last for 5-10 years.

Fabrication, Characterization and Response Surface Method (RSM) Optimization for Tetracycline Photodegration by Bi3.84W0.16O6.24- graphene oxide (BWO-GO).

RSM is a powerful tool for optimizing photocatalytic processes. The BWO-GO photocatalysts have been successfully synthesized via inorganic-salt-assisted hydrothermal method. XRD, TEM, FESEM, HRTEM and STEM are used to characterize BWO-GO heterojunction. UV-vis, PL, ESR and radical scavenger experiments are used to explore the photocatalysis mechanism. The photocatalysts are evaluated by TC photodegradation under visible light irradiation. And the main active species in TC photodegradation is ·O2-. Response surface methodology is used to optimize three key independent operating parameters, namely photocatalyst dosage (X1), percentages of GO (X2) and reaction time (X3), for TC photodegradation. The central composite design (CCD) is used to conduct experiments. The results showed that TC removal is significantly affected by the synergistic effect of linear term of X1 and X3. However, the quadratic terms of X12 and X32 had an antagonistic effect on T removal. The obtained RSM model (R2 = 0.9206) shows a satisfactory correlation between experimental and predicted values of TC removal. The optimized conditions is of 0.3 g photocatalyst dosage, 1.49 wt% GO loaded percentage and 90 min reaction time. Under this condition, theoretical prediction removal is 80.22% and the actual removal is 78.43%.

Apelin-13 as a novel target for intervention in secondary injury after traumatic brain injury.

The adipocytokine, apelin-13, is an abundantly expressed peptide in the nervous system. Apelin-13 protects the brain against ischemia/reperfusion injury and attenuates traumatic brain injury by suppressing autophagy. However, secondary apelin-13 effects on traumatic brain injury-induced neural cell death and blood-brain barrier integrity are still not clear. Here, we found that apelin-13 significantly decreases cerebral water content, mitigates blood-brain barrier destruction, reduces aquaporin-4 expression, diminishes caspase-3 and Bax expression in the cerebral cortex and hippocampus, and reduces apoptosis. These results show that apelin-13 attenuates secondary injury after traumatic brain injury and exerts a neuroprotective effect.

Induction of HOXA9 expression in three-dimensional organotypic culture of the Claudin-low breast cancer cells.

The gene expression signatures of the molecular intrinsic subtypes of breast cancer are regulated by epigenetic mechanisms such as methylation of CpG islands in gene promoters. Epigenetic codes can be regulated by the tumor microenvironment. The Claudin-low subtype is associated with triple-negative invasive ductal carcinomas in patients. Herein we explored epigenetic regulation of gene expression in the Claudin-low breast cancer cells by extracellular matrix (ECM), a key component of the tumor microenvironment. We modeled attachment to ECM using laminin rich ECM three-dimensional organotypic culture (lrECM 3D). In 2D and lrECM 3D cultures we examined expression of the homeobox (HOX) genes that epigenetically regulated in development and cancer. We demonstrated induction of the selected HOX genes in lrECM 3D culture of the Claudin-low breast cancer cells MDA-MB-231 and Hs578T. In particular activation of HOXA9 expression in lrECM 3D culture required binding of bromodomain containing 4 to the HOXA9 promoter and involved CpG hypomethylation. Our findings warrant further investigation of the ECM-regulated epigenetic coding of gene expression in the Claudin-low breast cancer.

Comparative study of diethyl phthalate degradation by UV/H2O2 and UV/TiO2: kinetics, mechanism, and effects of operational parameters.

The photodegradation of diethyl phthalate (DEP) by UV/H2O2 and UV/TiO2 is studied. The DEP degradation kinetics and multiple crucial factors effecting the clearance of DEP are investigated, including initial DEP concentration ([DEP]0), initial pH values (pH0), UV light intensity, anions (Cl(-), NO(3-), SO4 (2-), HCO3 (-), and CO3 (2-)), cations (Mg(2+), Ca(2+), Mn(2+), and Fe(3+)), and humic acid (HA). Total organic carbon (TOC) removal is tested by two treatments. And, cytotoxicity evolution of DEP degradation intermediates is detected. The relationship between molar ratio ([H2O2]/[DEP] or [TiO2]/[DEP]) and degradation kinetic constant (K) is also studied. And, the cytotoxicity tests of DEP and its degradation intermediates in UV/H2O2 and UV/TiO2 treatments are researched. The DEP removal efficiency of UV/H2O2 treatment is higher than UV/TiO2 treatment. The DEP degradation fitted a pseudo-first-order kinetic pattern under experimental conditions. The K linearly related with molar ratio in UV/H2O2 treatment while nature exponential relationship is observed in the case of UV/TiO2. However, K fitted corresponding trends better in H2O2 treatment than in TiO2 treatment. The Cl(-) is in favor of the DEP degradation in UV/H2O2 treatment; in contrast, it is disadvantageous to the DEP degradation in UV/TiO2 treatment. Other anions are all disadvantageous to the DEP degradation in two treatments. Fe(3+) promotes the degradation rates significantly. And, all other cations in question inhibit the degradation of DEP. HA hinders DEP degradation in two treatments. The intermediates of DEP degradation in UV/TiO2 treatment are less toxic to biological cell than that in UV/H2O2 treatment.

Mangiferin regulates cognitive deficits and heme oxygenase-1 induced by lipopolysaccharide in mice.

Accumulating evidence reveals that lipopolysaccharide (LPS) can induce neuroinflammation, ultimately leading to cognitive deficits. Mangiferin, a natural glucoxilxanthone, is known to possess various biological activities. The present study aimed to investigate the effects of mangiferin on LPS-induced cognitive deficits and explore the underlying mechanisms. Brain injury was induced in mice via intraperitoneal LPS injection (1mg/kg) for five consecutive days. Mangiferin was orally pretreatmented (50mg/kg) for seven days and then treatmented (50mg/kg) for five days after LPS injection. The Morris water maze was used to detect changes in cognitive function. Immunohistochemical and immunoblotting were respectively performed to measure the expression of interleukin-6 (IL-6) and heme oxygenase-1 (HO-1) in the hippocampus. The results showed that mangiferin can ameliorate cognitive deficits. Moreover, mangiferin decreased LPS-induced IL-6 production and increase HO-1 in the hippocampus. Taken together, these results suggest that mangiferin attenuates LPS-induced cognitive deficits, which may be potentially linked to modulating HO-1 in the hippocampus.