Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.

Dry Mix Slag—High-Calcium Fly Ash Binder. Part Two: Durability

This work investigates durability of cement-free mortars with a binder comprised of ground granulated blast furnace slag (GGBFS) activated by high-calcium fly ash (HCFA) and sodium carbonate (Na2CO3): the soundness, sulfate resistance, alkali-silica reactivity and efflorescence factors are considered. Results of tests show that such mortars are resistant to alkali-silica expansion. Mortars are also sulfate-resistant when the amount of HCFA in the complex binder is within a limit of 10 wt%. The fineness of fly ash determines its’ ability to activate GGBFS hydration, and influence soundness of the binder, early strength development, sulfate resistance and efflorescence behavior. The present article is a continuation of authors’ work, previously published in MSA, Vol. 14, 240-254.

Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage

BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.

Lowering ash slagging and fouling tendency of high-alkali coal by hydrothermal pretreatment

High-alkali species in coal are notorious for causing ash slagging and fouling incidents.In this paper,four high-alkali coals were individually subject to hydrothermal pretreatment(HTP),within a batch-type autoclave at 300 -C for 1 h,and the treated coals were analyzed,along with the oxygen-containing functional groups determined by Fourier transform infrared spectrometer(FT-IR).Then the alkali species and other components in the coal ash were quantified by X-ray fluorescence(XRF)for evaluating the ash slagging and fouling tendency.Apart from this,FactSage was adopted to simulate the occurrence and transformation of alkali species during coal thermal conversion ending at various temperatures.The findings indicate that the treated coals are superior to the parent ones in terms of certain remarkable changes via HTP.The moisture,oxygen and sulfur of the hydrothermally treated coals decline obviously,while the calorific value rises sharply.HTP could reduce the alkali species to less than 2%(%,by weight,equivalent to Na2O in dry ash),with a maximum removal ratio of 88.9%,lowering the ash slagging and fouling tendency.The proposed mechanism of HTP was that the alkali species in coal matrix became released due to the breakage of the coal functional groups and micropores during HTP.

Steam gasification reactivity of a high-sodium coal fly ash obtained from a pilot scale CFB gasifier

Circulating fluidized bed （CFB） gasification has several advantages for the utilization of low rank coals. However, the carbon content of fly ash is usually very high, which greatly infuences the gasification efficiency. The purpose of this research is to investigate the gasification reactivity of a high-sodium Zhundong （ZD） coal fly ash obtained from a pilot-scale 2.5 t/d CFB gasification system. The experiments were carried out in a thermogravimetric analyzer with steam as gasification agent, and fast pyrolyzed ZD char was also investigated as a reference sample. The results show that increasing temperature accelerates the gasification rate both for fly ash and ZD char. Fly ash has higher gasification rate at the initial gasification stage. On the contrary, ZD char has higher reaction rate even at higher carbon conversion stage. Via distributed activation energy model, the average activation energy of ZD char and fly ash is calculated to be 94.4 and 91.2 kJ/mol, respectively. The integrated model study reveals that the reaction order of ZD char is about 0.74, whereas the reaction order of fly ash decreases from 1 to 0.59 when temperature increases from 900 to 1050 ℃. The gasification reactivity of ZD coal fly ash is quite different with literature research on those fly ashes with rarely little catalytic elements in coal ashes. The interesting results are related with the unique properties of ZD coal fly ash and the transformation of sodium during gasification process.

Synthesis of Mullite from High-alumina Fly Ash:a Case from the Jungar Power Plant in Inner Mongolia, Northern China

In this paper, an experimental study was conducted in order to test the feasibility of sintering mullite directly from the high-alumina fly ash, without adding any extra material. The results show that the mullite contents in most sintered samples are over 70%. The samples sintered from the beneficiated fly ash have a higher content of mullite than those from the as-received fly ash under the same synthetic conditions. To obtain an equal amount of mullite, a higher sintering temperature is needed for the beneficiated fly ash than for the as-received fly ash. Considering the physical properties of sintered mullite, the favorable sintering temperature is 1400℃ for the as-received fly ash and 1500℃ for the beneficiated fly ash. A higher sintering temperature and a shorter holding time are profitable to sintering mullite. The orthogonal test confirmed that the dominant factor affecting mullite synthesis is sintering temperature, and that the most profitable matching conditions are 200 MPa-1500℃-3 h for the as-received fly ash and 200 MPa-1500 ℃-4 h for the beneficiated fly ash.

Combined use of fly ash and silica to prevent the long-term strength retrogression of oil well cement set and cured at HPHT conditions

The long-term strength retrogression of silica-enriched oil well cement poses a significant threat to wellbore integrity in deep and ultra-deep wells, which is a major obstacle for deep petroleum and geothermal energy development. Previous attempts to address this problem has been unsatisfactory because they can only reduce the strength decline rate. This study presents a new solution to this problem by incorporating fly ash to the traditional silica-cement systems. The influences of fly ash and silica on the strength retrogression behavior of oil well cement systems directly set and cured under the condition of 200°C and 50 MPa are investigated. Test results indicate that the slurries containing only silica or fly ash experience severe strength retrogression from 2 to 30 d curing, while the slurries containing both fly ash and silica experience strength enhancement from 2 to 90 d. The strength test results are corroborated by further evidences from permeability tests as well as microstructure analysis of set cement. Composition of set cement evaluated by quantitative X-ray diffraction analyses with partial or no known crystal structure(PONKCS) method and thermogravimetry analyses revealed that the conversion of amorphous C-(A)-S-H to crystalline phases is the primary cause of long-term strength retrogression.The addition of fly ash can reduce the initial amount of C-(A)-S-H in the set cement, and its combined use with silica can prevent the crystallization of C-(A)-S-H, which is believed to be the working mechanism of this new admixture in improving long-term strength stability of oil well cement systems.

Accelerated Carbonation Assessment of High-Volume Fly Ash Concrete

The issue of concrete carbonation has gained importance in recent years due to the increase use in supplementary cementing materials (SCMs) in concrete mixtures. While there is general agreement that concrete carbonation progresses at maximum at a relative humidity of about 60%, the rate may differ in the case of cements blended with SCMs, especially with high-volume fly ash replacements. In this study, the effect of high-volume fly ash concrete exposed to low ambient relative humidity (RH) conditions (57%) and accelerated carbonation (4% CO2) is investigated. Twenty-three concrete mixtures were produced varying in cementitious contents (310, 340, 370, and 400 kg/m3), water-to-cementitious materials ratio (0.45 and 0.50), and fly ash content (0%, 15%, 30%, and 50%) using a low and high-calcium fly ash. The specimens were allowed 1 and 7 days of moist curing and monitored for their carbonation rate and depth through phenolphthalein measurements up to 105 days of exposure. The accelerated carbonation test results indicated that increasing the addition of fly ash also led to increasing the depth of carbonation. Mixtures incorporating high-calcium fly ash were also observed to be more resistant against carbonation than low-calcium fly ash due to the higher calcium oxide (CaO) content. However, mixtures incorporating high-volume additions (50%) specimens were fully carbonated regardless of the type of fly ash used. It was evident that the increase in the duration of moist curing from 1 day to 7 days had a positive effect, reducing the carbonation depth for both plain and blended fly ash concrete mixes, however, this effect was minimal in high-volume fly ash mixtures. The results demonstrated that the water-to-cementitious ratio (W/CM) had a more dramatic impact on carbonation resistance than the curing age for mixtures incorporating 30% or less fly ash replacement, whereas those mixtures incorporating 50% showed minor differences regardless of curing age or W/CM. Based on the compressive strength results, carbonation depth appeared to decrease with increase in compressive strength, but this correlation was not significant.

Shrinkage, Strength of High and Ordinary Concrete Incorporating Kosovo and Japanese Fly-ash

Ordinary and high performance concrete （OC-C 25/30 and HPC C-50/60） made with fly ash has found numerous applications all over the world since 1970. In Kosovo, fly ash as cement substitution in concrete has not been utilized yet despite the large amount that is produced annually and the positive economical-environment aspects of such technique. This hesitance is due to the laek of experience in the concrete engineering field and because of the chemical composition of Kosovo fly ash, which is classified as non-standard high calcium fly ash （KF）. In light of this fact, this study intended to develop further. So, this paper reports the consistency, workability, shrinkage, high and ordinary compressive strength of concrete containing different percentage of non-class high calcium fly ash as Portland cement substitution （first case-Kosovo fly ash KF） comparing results with F class-low caleium fly ash content （second ease-Japanese fly ash JF） which is common used as cement replacement.

Dry Mix Slag—High-Calcium Fly Ash Binder. Part One: Hydration and Mechanical Properties

High-calcium fly ash (HCFA)—a residue of high-temperature coal combustion at thermal power plants, in combination with sodium carbonate presents an effective hardening activator of ground granulated blast-furnace slag (GGBFS). Substitution of 10% - 30% of GGBFS by HCFA and premixing of 1% - 3% Na2CO3 to this dry binary binder was discovered to give mortar compression strength of 10 - 30 to 30 - 45 MPa at 7 and 28 days when moist cured at ambient temperature. High-calcium fly ash produced from low-temperature combustion of fuel, like in circulating fluidized bed technology, reacts with water readily and is itself a good hardening activator for GGBFS, so introduction of Na2CO3 into such mix has no noticeable effect on the mortar strength. However, low-temperature HCFA has higher water demand, and the strength of mortar is compromised by this factor. As of today, our research is still ongoing, and we expect to publish more data on different aspects of durability of proposed GGBFS-HCFA binder later.

Reaction behaviour of Al_2O_3 and SiO_2 in high alumina coal fly ash during alkali hydrothermal process

The reaction behaviours of A1203 and SiO2 in high alumina coal fly ash under various alkali hydrothermal conditions were studied. The means of XRD, XRF, FTIR and SEM were used to measure the mineral phase and morphology of the solid samples obtained by different alkali hydrothermal treatments as well as the leaching ratio of SiO2 to A1203 in alkali solution. The results showed that with the increase of the hydrothermal treating temperature from 75 to 160 ~C, phillipsite-Na, zeolite A, zeolite P, and hydroxysodalite were produced sequentially while the mullite and corundum phase still remained. Zeolite P was massively formed at low-alkali concentration and the hydroxysodalite was predominantly obtained at high-alkali concentration. By the dissolution of aluminosilicate glass and the formation of zeolites together, the leaching efficiency of SiO2 can reach 42.13% with the mass ratio of A1203/SIO2 up to 2.19：1.

前列腺癌患者外周血中CD4^+CD25^(high)调节性T细胞及调节因子TGF-β1和COX-2的表达

目的:通过检测前列腺癌患者以及健康志愿者外周血中CD4+CD25high调节性T细胞、TGF-β1及COX-2的表达,初步探讨CD4+CD25high调节性T细胞在前列腺癌发病机制中的作用及其与TGF-β1和COX-2的相关性。方法:应用流式细胞术检测30例前列腺癌患者治疗前后(其中前列腺癌局限组11例,非局限组19例)及20例健康志愿者外周血单个核细胞(PBMC)中CD4+CD25high调节性T细胞占CD4+T细胞的比例;应用酶联免疫吸附试验(ELISA)检测其外周血清中TGF-β1和COX-2的表达。对前列腺癌患者上述指标进行术前术后对比分析,另对CD4+CD25high调节性T细胞与TGF-β1及COX-2的相关性进行分析;并探讨上述指标在前列腺癌患者局限组和非局限组间是否存在差异性。结果:流式细胞术检测显示,前列腺癌患者治疗前PBMC中CD4+CD25high调节性T细胞占CD4+T细胞的比例为(18.32±7.49)%,高于健康志愿者对照组(7.77±1.86)%(P<0.05)。前列腺癌患者治疗后其比值为(17.34±5.87)%,较治疗前稍减低,但两者相比无显著差异(P>0.05)。ELISA检测外周血清中TGF-β1和COX-2显示,前列腺癌组分别为(215.97±55.16)ng/ml和(6.88±5.14)ng/ml,对照组分别为(149.75±47.11)ng/ml和(5.65±2.69)ng/ml;前列腺癌患者外周血清中TGF-β1的表达水平高于健康志愿者对照组(P<0.05),COX-2的表达水平与对照组无显著差异(P>0.05)。通过多重线性回归分析表明,前列腺癌患者PBMC中CD4+CD25high调节性T细胞的表达与血清中TGF-β1和COX-2的表达无显著相关。前列腺癌局限组和非局限组外周血中CD4+CD25high调节性T细胞、TGF-β1及COX-2的表达均无显著性差异(P>0.05)。结论:前列腺癌患者PBMC中CD4+CD25high调节性T细胞可能参与前列腺癌的发生,其增殖机制与血清中TGF-β1和COX-2的表达无关,可能与肿瘤本身及肿瘤局部微环境相关。

高温后HVFA-SHCC材料弯曲性能试验研究

采用100 mm×100 mm×13 mm的板状试件,研究了HVFA-SHCC材料高温后的弯曲性能,探讨不同温度和不同冷却方式对其破坏模式、残余弯曲强度、弯曲应力挠度曲线和弯曲韧性的影响。采用扫描电镜观察HVFA-SHCC材料的微观结构,揭示其破坏机理。结果表明:当温度为100℃时,温度对HVFA-SHCC试件的弯曲性能及质量损失影响较小。随着温度的升高,HVFA-SHCC试件内部微结构不断劣化,质量损失率逐渐增大,破坏模式由延性破坏转变为脆性破坏,残余弯曲性能劣化严重。尤其是800℃时,试件的质量损失率达15.5%,残余弯曲强度仅为常温状态的30%,弯曲耗能为常温状态的0.74%;浸水冷却试件的残余弯曲强度和弯曲韧性有一定程度的提高。

Impact Properties of Engineered Cementitious Composites with High Volume Fly Ash Using SHPB Test

The split Hopkinson pressure bar （SHPB） testing with diameter 40 mm was used to investigate the dynamic mechanical properties of engineered cementitious composites （ECCs） with different fly ash content. The basic properties including deformation, energy absorption capacity, strain-stress relationship and failure patterns were discussed. The ECCs showed strain-rate dependency and kept better plastic flow during impact process compared with reactive powder concrete （RPC） and concrete, but the critical compressive strength was lower than that of RPC and concrete. The bridging effect of PVA fiber and addition of fly ash can significantly improve the deformation and energy absorption capacities of ECCs. With the increase of fly ash content in ECCs, the static and dynamic compressive strength lowered and the dynamic increase factor enhanced. Therefore, to meet different engineering needs, the content of fly ash can be an important index to control the static and dynamic mechanical properties of ECCs.

Static and Dynamic Leaching Experiments of Heavy Metals from Fly Ash-Based Geopolymers

The feasibility of high calcium fly ash （CFA）-based geopolymers to fix heavy metals were studied. The CFA-based geopolymers were prepared from CFA, flue gas desulfurization gypsum （FGDG）, and water treatment residual （WTR）. The static leaching showed that heavy metals concentrations from CFA- based geopolymers were lower than their maximum concentration limits according to the U.S. environmental protection law. And the encapsulated and fixed ratios of heavy metals by the CFA-based geopolymers were 96.02%-99.88%. The dynamic real-time leaching experiment showed that concentration of Pb （II） was less than 1.μg / L, Cr （VI） less than 3.25 mg / L, while Hg （II） less than 4.0 μg / L. Additionally, dynamic accumulated leaching concentrations were increased at the beginning of leaching process then kept stable. During the dynamic leaching process, heavy metals migrated and accumulated in an area near to the solid-solution interface. When small part of heavy metals in ＂the accumulated area＂ breached through the threshold value of physical encapsulation and chemical fixation they migrated into solution. The dynamic leaching ratios and effective diffusion coefficients of heavy metals from CFA-based geopolymer were very low and the long-term security of heavy metals in CFA-based geopolymer was safe.

Effect of Nano Silica on Hydration and Microstructure Characteristics of Cement High Volume Fly Ash System Under Steam Curing

The influences of nano silica (NS) on the hydration and microstructure development of steam cured cement high volume fly ash (40 wt%, CHVFA) system were investigated. The compressive strength of mortars was tested with different NS dosage from 0 to 4%. Results show that the compressive strength is dramatically improved with the increase of NS content up to 3%, and decreases with further increase of NS content (e g, at 4%). Then X?ray diffraction (XRD), differential scanning calorimetry-thermogravimetry (DSCTG), scanning electron microscope (SEM), energy disperse spectroscopy (EDS), mercury intrusion porosimeter (MIP) and nuclear magnetic resonance (NMR) were used to analyze the mechanism. The results reveal that the addition of NS accelerates the hydration of cement and fly ash, decreases the porosity and the content of calcium hydroxide (CH) and increases the polymerization degree of C-S-H thus enhancing the compressive strength of mortars. The interfacial transition zone (ITZ) of CHVFA mortars is also significantly improved by the addition ofNS, embodying in the decrease of Ca/Si ratio and CH enrichment of ITZ.

Adsorption properties of CFBC ash-cement pastes as compared with PCC fly ash-cement pastes

Circulating fluidized bed combustion （CFBC） ash can be potentially used as supplementary cementitious materials for concrete production due to its desirable pozzolanic activity. The adsorption properties of CFBC ash-cement pastes were studied, and ordinary pulverized coal combustion （PCC） fly ash-cement pastes were used as control. The water-adsorption and superplasticizer （SP）-adsorption properties of the pastes were evaluated by water demand and UV-visible absorption spectroscopy respectively. The results show that CFBC ash-cement system has greater compressive strength as compared with PCC fly ash-cement system at a given curing age, although the water demand of the former is significantly higher than that of the latter. CFBC ash-cement pastes possess higher adsorption ability of aliphatic SP than PCC fly ash-cement pastes and the adsorption amount increases with an increase in ash replacement ratio. CFBC ash- cement pastes exhibit lower workability with higher slump loss. It is concluded that CFBC ash can be potentially used as supplementary cementitious material in concrete production, but the mix design of CFBC ash concrete needs to be appropriately adjusted. It is suggested that CFBC ash is used for the production of the concrete needing low flowability.

Demineralization mechanism and influence of parameters on high ash Indian coal by chemical leaching of acid and alkali solution

The current research was investigated the mechanism of coal demineralization and the effect of leaching parameters on high ash coal and study the characterization of pre and post-treated coal. The two high ash Indian coal selected from Mahanadi Coalfield Limited, Odisha, pulverized to 375, 230 and 180 gm particle size were undergone simultaneous acid and alkali treatment at a different concentration, temperature and time. The percent demineralization was increased with decrease the size of the particle and rises with leaching parameters. The investigation suggested 180 μm particle size offers efficient demineralization for both coals at 30% NaOH and 30% H2SO4 concentration. The alkali leaching leads to obtaining the demineralization 46% and 42% whereas acid treatment resulted in 34% and 32% of the original coal samples. The extent of demineralization was improved the calorific value of coal. Besides, the degree of demineralization was proved from the FTIR, XRF and FESEM-EDX analysis results. FTIR analysis result showed that the peak intensity of mineral band decreased by the leaching effect and the degree of demineralization was significantly obtained to large extent by the X-ray Fluorescence spectrometer; which elucidates major minerals removed from coal by the leaching effect of acid and alkali solution.

Future Changes in Extreme High Temperature over China at 1.5℃-5℃ Global Warming Based on CMIP6 Simulations

Extreme high temperature(EHT)events are among the most impact-related consequences related to climate change,especially for China,a nation with a large population that is vulnerable to the climate warming.Based on the latest Coupled Model Intercomparison Project Phase 6(CMIP6),this study assesses future EHT changes across China at five specific global warming thresholds(1.5℃-5℃).The results indicate that global mean temperature will increase by 1.5℃/2℃ before 2030/2050 relative to pre-industrial levels(1861-1900)under three future scenarios(SSP1-2.6,SSP2-4.5,and SSP5-8.5),and warming will occur faster under SSP5-8.5 compared to SSP1-2.6 and SSP2-4.5.Under SSP5-8.5,global warming will eventually exceed 5℃ by 2100,while under SSP1-2.6,it will stabilize around 2℃ after 2050.In China,most of the areas where warming exceeds global average levels will be located in Tibet and northern China(Northwest China,North China and Northeast China),covering 50%-70%of the country.Furthermore,about 0.19-0.44 billion people(accounting for 16%-41%of the national population)will experience warming above the global average.Compared to present-day(1995-2014),the warmest day(TXx)will increase most notably in northern China,while the number of warm days(TX90p)and warm spell duration indicator(WSDI)will increase most profoundly in southern China.For example,relative to the present-day,TXx will increase by 1℃-5℃ in northern China,and TX90p(WSDI)will increase by 25-150(10-80)days in southern China at 1.5℃-5℃ global warming.Compared to 2℃-5℃,limiting global warming to 1.5℃ will help avoid about 36%-87%of the EHT increases in China.

High fat diet dysregulates microRNA-17-5p and triggers retinal inflammation:Role of endoplasmic-reticulum-stress

AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed either normal diet or 60% high fat diet for 4-8 wk. During the 4 wk study, mice received phenyl-butyric acid(PBA); endoplasmic reticulum-stress inhibitor; for 2 wk. Insulin resistance was assessed by oral glucose tolerance. Effects of palmitate-bovine serum albumin(BSA)(400 μmol/L) were examined in retinal Müller glial cell line and primary Müller cells isolated from wild type and thioredoxin interacting protein knock-out mice. Expression of thioredoxin interacting protein, endoplasmic reticulum-stress markers, mi R-17-5p m RNA, as well as nucleotide-binding oligomerization domain-like receptor protein(NLRP3) and IL1β protein was determined.RESULTS High fat diet for 8 wk induced obesity and insulin resistance evident by increases in body weight and impaired glucose tolerance. By performing quantitative real-time polymerase chain reaction, we found that high fat diet triggered the expression of retinal endoplasmic reticulum-stress markers(P < 0.05). These effects were associated with increased thioredoxin interacting protein and decreased mi R-17-5p expression, whichwere restored by inhibiting endoplasmic reticulumstress with PBA(P < 0.05). In vitro, palmitate-BSA triggered endoplasmic reticulum-stress markers, which was accompanied with reduced mi R-17-5p and induced thioredoxin interacting protein m RNA in retinal Müller glial cell line(P < 0.05). Palmitate upregulated NLRP3 and IL1β expression in primary Müller cells isolated from wild type. However, using primary Müller cells isolated from thioredoxin interacting protein knock-out mice abolished palmitate-mediated increase in NLRP3 and IL1β.CONCLUSION Our work suggests that targeting endoplasmic reticulumstress or thioredoxin interacting protein are potential therapeutic strategies for early intervention of obesityinduced retinal inflammation.