SIRT1 inhibits apoptosis of human lens epithelial cells through suppressing endoplasmic reticulum stress in vitro and in vivo

AIM:To explore the effect of silent information regulator factor 2-related enzyme 1(SIRT1)on modulating apoptosis of human lens epithelial cells(HLECs)and alleviating lens opacification of rats through suppressing endoplasmic reticulum(ER)stress.METHODS:HLECs(SRA01/04)were treated with varying concentrations of tunicamycin(TM)for 24h,and the expression of SIRT1 and C/EBP homologous protein(CHOP)was assessed using real-time quantitative polymerase chain reaction(RT-PCR),Western blotting,and immunofluorescence.Cell morphology and proliferation was evaluated using an inverted microscope and cell counting kit-8(CCK-8)assay,respectively.In the SRA01/04 cell apoptosis model,which underwent siRNA transfection for SIRT1 knockdown and SRT1720 treatment for its activation,the expression levels of SIRT1,CHOP,glucose regulated protein 78(GRP78),and activating transcription factor 4(ATF4)were examined.The potential reversal of SIRT1 knockdown effects by 4-phenyl butyric acid(4-PBA;an ER stress inhibitor)was investigated.In vivo,age-related cataract(ARC)rat models were induced by sodium selenite injection,and the protective role of SIRT1,activated by SRT1720 intraperitoneal injections,was evaluated through morphology observation,hematoxylin and eosin(H&E)staining,Western blotting,and RT-PCR.RESULTS:SIRT1 expression was downregulated in TMinduced SRA01/04 cells.Besides,in SRA01/04 cells,both cell apoptosis and CHOP expression increased with the rising doses of TM.ER stress was stimulated by TM,as evidenced by the increased GRP78 and ATF4 in the SRA01/04 cell apoptosis model.Inhibition of SIRT1 by siRNA knockdown increased ER stress activation,whereas SRT1720 treatment had opposite results.4-PBA partly reverse the adverse effect of SIRT1 knockdown on apoptosis.In vivo,SRT1720 attenuated the lens opacification and weakened the ER stress activation in ARC rat models.CONCLUSION:SIRT1 plays a protective role against TM-induced apoptosis in HLECs and slows the progression of cataract in rats by inhibiting ER stress.These findings suggest a novel strategy for cataract treatment focused on targeting ER stress,highlighting the therapeutic potential of SIRT1 modulation in ARC development.

Research Progress on Self-Efficacy Level of Patients with Type 2 Diabetes Mellitus and Its Influencing Factors

Self-efficacy plays an important role in the management of type 2 diabetes mellitus (T2DM) patients, and it runs through the whole process of diabetes treatment, which is conducive to controlling and delaying the occurrence and development of complications, as well as improving the quality of life of patients. This paper mainly describes the concept of self-efficacy, the current situation of self-efficacy of diabetic patients at home and abroad, the functional aspects and their influencing factors, so as to take relevant measures on how to improve self-efficacy. It aims to provide a theoretical basis for the development of self-efficacy interventions for patients with type 2 diabetes mellitus.

Study on the Influencing Factors of L2 Reading Ability and Its Regulation Strategies

This paper takes college students as research subjects to investigate the factors affecting L2 Reading ability and their regulation strategies through scale surveys.The findings are as follows:(1)Linguistic factors have significant impacts on L2 Reading ability,and the influence of non-linguistic factors,such as non-intellectual factors and cultural background knowledge,is also important;and(2)flexible use of reading regulation strategies according to the learning conditions(such as the information extraction strategy,the metacognitive reading regulation strategy,and the interactive reading strategy)can effectively improve learners’L2 Reading ability.The findings of this study have important theoretical and practical value for improving L2 learners’Reading ability.

Relationship Between Diurnal Changes of Net Photosynthetic Rate and Influencing Factors in Rice under Saline Sodic Stress

The net photosynthetic rate of flag leaves and influencing factors under saline sodic soil conditions were investigated at the full heading stage of rice. The net photosynthetic rate of rice leaves showed a double-peak curve in a day in both non-saline sodic and saline sodic soil treatments. The first peak of the net photosynthetic rate appeared at 9：00-10：00 and 9：00 in the saline sodic and non-saline sodic soil treatments, respectively, whereas the second peak both at 14：00. The midday depression of the net photosynthetic rate always appeared regardless of non-saline sodic or saline sodic soil conditions. In addition, the net photosynthetic rate significantly decreased in all day under saline sodic conditions compared with that under non-saline sodic conditions. Some differences were observed in correlation characters between the net photosynthetic rate and all influencing factors during 9：00-13：00. Under non-saline sodic conditions, the diurnal changes of the net photosynthetic rate in a day were mainly caused by stomatal conductance, and the limitation value and the stomatal factors served as determinants; whereas under saline sodic stress, the diurnal changes of the net photosynthetic rate in a day were mainly caused by non stomatal factors including light intensity and air temperature.

Biochanin A attenuates spinal cord injury in rats during early stages by inhibiting oxidative stress and inflammasome activation

Previous studies have shown that Biochanin A,a flavonoid compound with estrogenic effects,can serve as a neuroprotective agent in the context of cerebral ischemia/reperfusion injury;howeve r,its effect on spinal cord injury is still unclea r. In this study,a rat model of spinal cord injury was established using the heavy o bject impact method,and the rats were then treated with Biochanin A(40 mg/kg) via intrape ritoneal injection for 14 consecutive days.The res ults showed that Biochanin A effectively alleviated spinal cord neuronal injury and spinal co rd tissue injury,reduced inflammation and oxidative stress in spinal cord neuro ns,and reduced apoptosis and pyroptosis.In addition,Biochanin A inhibited the expression of inflammasome-related proteins(ASC,NLRP3,and GSDMD)and the Toll-like receptor 4/nuclear factor-κB pathway,activated the Nrf2/heme oxygenase 1 signaling pathway,and increased the expression of the autophagy markers LC3 Ⅱ,Beclin-1,and P62.Moreove r,the therapeutic effects of Biochanin A on early post-s pinal cord injury were similar to those of methylprednisolone.These findings suggest that Biochanin A protected neurons in the injured spinal cord through the Toll-like receptor 4/nuclear factor κB and Nrf2/heme oxygenase 1 signaling pathways.These findings suggest that Biochanin A can alleviate post-spinal cord injury at an early stage.

Analysis of influencing factors and interaction of body weight and disease outcome in patients with prediabetes

BACKGROUND The trend of prediabetes progressing to type 2 diabetes mellitus(T2DM)is prominent,and effective intervention can lead to a return to prediabetes.Exploring the factors influencing the outcome of prediabetes is helpful to guide clinical intervention.The weight change in patients with prediabetes has not attracted much attention.AIM To explore the interaction between body weight and the factors affecting the progression of prediabetes to T2DM.METHODS We performed a retrospective analysis of 236 patients with prediabetes and 50 with normal glucose tolerance(NGT),and collected clinical data and follow-up results of all patients.Based on natural blood glucose outcomes,we classified 66 patients with progression to T2DM into the disease progression(DP)group,and 170 patients without progression to T2DM into the disease outcome(DO)group.We analyzed the factors that influenced prediabetes outcome and the influence of body weight on prediabetes blood glucose outcome by unconditional logistic regression.A general linear model(univariate)was used to analyze the interaction between body weight and independent influencing factors.RESULTS There were 98 cases of impaired fasting glucose(IFG),90 cases of impaired glucose tolerance(IGT),and 48 cases of coexistent IFG and IGT.The body weight,waist circumference,body mass index,fasting blood glucose,and 2 h plasma glucose of patients with IFG,IGT,and coexistent IFG and IGT were higher than those in patients with NGT(P<0.05).Logistic regression analysis showed that body weight,glycosylated hemoglobin,uric acid,fasting insulin,and homeostatic model assessment for insulin resistance were independent factors affecting progression of prediabetes to T2DM(P<0.05).Receiver operating characteristic curve analysis showed that the area under the curve predicted by the above indicators combined was 0.905[95%confidence interval(CI):0.863-0.948],which was greater than that predicted by each indicator alone.Logistic regression analysis with baseline body weight as an independent variable showed that compared with body weight 1,the odds ratio(95%CI)of body weight 3 was 1.399(1.142-2.126)(P=0.033).There was a multiplicative interaction between body weight and uric acid(β=1.953,P=0.005).CONCLUSION High body weight in patients with prediabetes is an independent risk factor for progression to T2DM,and the risk of progression is increased when coexisting with high uric acid level.

Responses of leaf stomatal and mesophyll conductance to abiotic stress factors

Plant photosynthesis assimilates CO_(2)from the atmosphere,and CO_(2)diffusion efficiency is mainly constrained by stomatal and mesophyll resistance.The stomatal and mesophyll conductance of plants are sensitive to abiotic stress factors,which affect the CO_(2)concentrations at carboxylation sites to control photosynthetic rates.Early studies conducted relevant reviews on the responses of stomatal conductance to the environment and the limitations of mesophyll conductance by internal structure and biochemical factors.However,reviews on the abiotic stress factors that systematically regulate plant CO_(2)diffusion are rare.Therefore,in this review,the rapid and long-term responses of stomatal and mesophyll conductance to abiotic stress factors(such as light intensity,drought,CO_(2)concentration and temperature)and their physiological mechanisms are summarized.Finally,future research trends are also investigated.

Stability influence factors analysis and construction of a deep beam anchorage structure in roadway roof

Deep beam anchorage structures based on spatial distribution analysis of the cable prestressed field have been proposed for roadway roof support. Stability and other factors that influence deep beam structures are studied in this paper using mechanical calculations, numerical analysis and field measurements. A mechanical model of deep beam structure subjected to multiple loading is established, including analysis of roof support in the return airway of S1203 working face in the Yuwu coal mine, China. The expression of maximum shear stress in the deep beam structure is deduced according to the stress superposition criterion. It is found that the primary factors affecting deep beam structure stability are deep beam thickness, cable pre-tension and cable spacing. The variation of maximum shear stress distribution and prestressed field diffusion effects according to various factors are analyzed using Matlabòand FLAC3D^(TM) software, and practical support parameters of the S1203 return airway roof are determined.According to the observations of rock pressure, there is no evidence of roof separation, and the maximum values of roof subsidence and convergence of wall rock are 72 and 48 mm, respectively. The results show that the proposed roof support design with a deep beam structure is feasible and achieves effective control of the roadway roof.

Contact Stress Reliability Analysis Model for Cylindrical Gear with Circular Arc Tooth Trace Based on an Improved Metamodel

Although there is currently no unified standard theoretical formula for calculating the contact stress of cylindrical gears with a circular arc tooth trace(referred to as CATT gear),a mathematical model for determining the contact stress of CATT gear is essential for studying how parameters affect its contact stress and building the contact stress limit state equation for contact stress reliability analysis.In this study,a mathematical relationship between design parameters and contact stress is formulated using the KrigingMetamodel.To enhance the model’s accuracy,we propose a new hybrid algorithm that merges the genetic algorithm with the Quantum Particle Swarm optimization algorithm,leveraging the strengths of each.Additionally,the“parental inheritance+self-learning”optimization model is used to fine-tune the KrigingMetamodel’s parameters.Following this,amathematicalmodel for calculating the contact stress of Variable Hyperbolic Circular-Arc-Tooth-Trace(VH-CATT)gears using the optimized Kriging model was developed.We then examined how different gear parameters affect the VH-CATT gears’contact stress.Our simulation results show:(1)Improvements in R2,RMSE,and RMAE.R2 rose from0.9852 to 0.9974(a 1.22%increase),nearing 1,suggesting the optimized Kriging Metamodel’s global error is minimized.Meanwhile,RMSE dropped from3.9210 to 1.6492,a decline of 57.94%.The global error of the GA-IQPSO-Kriging algorithm was also reduced,with RMAE decreasing by 58.69%from 0.1823 to 0.0753,showing the algorithm’s enhanced precision.In a comparison of ten experimental groups selected randomly,the GA-IQPSO-Kriging and FEM-based contact analysis methods were used to measure contact stress.Results revealed a maximum error of 12.11667 MPA,which represents 2.85%of the real value.(2)Several factors,including the pressure angle,tooth width,modulus,and tooth line radius,are inversely related to contact stress.The descending order of their impact on the contact stress is:tooth line radius>modulus>pressure angle>tooth width.(3)Complex interactions are noted among various parameters.Specifically,when the tooth line radius interacts with parameters such as pressure angle,tooth width,and modulus,the resulting stress contour is nonlinear,showcasing amultifaceted contour plane.However,when tooth width,modulus,and pressure angle interact,the stress contour is nearly linear,and the contour plane is simpler,indicating a weaker coupling among these factors.

Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

JA-mediated MYC2/LOX/AOS feedback loop regulates osmotic stress response in tea plant

Osmotic stress caused by low-temperature,drought and salinity was a prevalent abiotic stress in plant that severely inhibited plant development and agricultural yield,particularly in tea plant.Jasmonic acid(JA)is an important phytohormone involving in plant stress.However,underlying molecular mechanisms of JA modulated osmotic stress response remains unclear.In this study,high concentration of mannitol induced JA accumulation and increase of peroxidase activity in tea plant.Integrated transcriptome mined a JA signaling master,MYC2 transcription factor is shown as a hub regulator that induced by mannitol,expression of which positively correlated with JA biosynthetic genes(LOX and AOS)and peroxidase genes(PER).CsMYC2 was determined as a nuclei-localized transcription activator,furthermore,ProteinDNA interaction analysis indicated that CsMYC2 was positive regulator that activated the transcription of CsLOX7,CsAOS2,CsPER1 and CsPER3via bound with their promoters,respectively.Suppression of CsMYC2 expression resulted in a reduced JA content and peroxidase activity and osmotic stress tolerance of tea plant.Overexpression of CsMYC2 in Arabidopsis improved JA content,peroxidase activity and plants tolerance against mannitol stress.Together,we proposed a positive feedback loop mediated by CsMYC2,CsLOX7 and CsAOS2 which constituted to increase the tolerance of osmotic stress through fine-tuning the accumulation of JA levels and increase of POD activity in tea plant.

Research Review of Principles and Methods for Ultrasonic Measurement of Axial Stress in Bolts

Bolts are important fasteners indispensable in the manufacturing field for their advantages, which include convenient assembly and disassembly, easy maintenance, refastenability to prevent looseness, and the avoidance of a phase change in the connected material composition. The precise control of the tightening force in bolts is closely related to the safety and reliability of the connected equipment or structure. Although there are many methods for estimating the tightening force applied to a bolt during assembly, poor accuracy in controlling the preload during the tightening process and a lack of monitoring to determine the residual axial force in service remain issues in evaluating the safety of bolted assemblies. As a nondestructive testing technology, ultrasonic measurement can be applied to successfully address these issues. In order to help researchers understand the theoretical basis and technological development in this field and to equip them to conduct further in-depth research, in this review, the basic knowledge describing the state of stress and deformation of bolts, as well as conventional testing methods are summarized and analyzed. Then, through a review of recent research of the ultrasonic measurement of the axial stress in bolts, the influence of the e ective stressed length and temperature are analyzed and proposed methods of calibration and compensation are reviewed. In order to avoid coupling errors caused by traditional piezoelectric transducers, two newly proposed ultrasonic coupling technologies, the electromagnetic acoustic transducer(EMAT) and the permanent mounted transducer system(PMTS), are reviewed. Finally, the new direction of research of the detection of residual axial stress in in-service bolts that have been assembled to yield is discussed.

Stress distribution and surrounding rock control of mining near to the overlying coal pillar in the working face

The occurrence of overlying coal pillar(OCP)exerts a strong effect on the stress and strain distribution of the surrounding rock in the stope.In this paper,the stress distribution characteristics are analyzed via the numerical calculation with the account of OCP presence or absence.In addition,this study revealed the joint effect of side pressure relief area of the goaf and stress concentration in OCP on the final stress distribution.Furthermore,the rules of abutment stress distribution affected by three influencing factors,namely horizontal-vertical distances between OCP and working face and buried depth of OCP,are analyzed.The functional model linking the peak stress of surrounding rock with the above influencing factors is developed.The field application of the above results proved that the rib spalling and deformation of a 2.95 m-high and 5.66 m-wide roadway could be efficiently controlled by rationally adjusting working states of the support,and adopting the hydraulic prop coordinated with the p type metal beam and anchor cable to strengthen the surrounding rock of working face and roadway,respectively.The proposed measures are considered appropriate to satisfy the safe operation requirements.

Predicting the present-day in situ stress distribution within the Yanchang Formation Chang 7 shale oil reservoir of Ordos Basin, central China

The Yanchang Formation Chang 7 oil-bearing layer of the Ordos Basin is important in China for producing shale oil.The present-day in situ stress state is of practical implications for the exploration and development of shale oil;however,few studies are focused on stress distributions within the Chang 7 reservoir.In this study,the present-day in situ stress distribution within the Chang 7 reservoir was predicted using the combined spring model based on well logs and measured stress data.The results indicate that stress magnitudes increase with burial depth within the Chang 7 reservoir.Overall,the horizontal maximum principal stress(SHmax),horizontal minimum principal stress(Shmin) and vertical stress(Sv) follow the relationship of Sv≥SHmax>Shmin,indicating a dominant normal faulting stress regime within the Chang 7 reservoir of Ordos Basin.Laterally,high stress values are mainly distributed in the northwestern parts of the studied region,while low stress values are found in the southeastern parts.Factors influencing stress distributions are also analyzed.Stress magnitudes within the Chang 7 reservoir show a positive linear relationship with burial depth.A larger value of Young's modulus results in higher stress magnitudes,and the differential horizontal stress becomes higher when the rock Young's modulus grows larger.

Cloning and Expression Analysis of an AP2/ERF Gene and Its Responses to Phytohormones and Abiotic Stresses in Rice

Ethylene response factors （ERFs） play important roles in response to plant biotic and abiotic stresses. In this study, a gene encoding a putative AP2/ERF domain-containing protein was isolated by screening a SSH cDNA library from rice and designated as Oryza sativa AP2/ERF-like protein （OsAP2LP） gene. OsAP2LP is 1491 bp in length, interrupted by seven introns, and encodes a putative protein of 348 amino acids. Temporal and spatial expression analysis showed that the OsAP2LP gene was preferentially expressed in roots, panicles, mature embryos and seeds in rice. Real-time quantitative PCR analysis indicated that the expression levels of the OsAP2LP gene were increased under the treatments of drought and gibberellin but decreased under the treatments of low temperature, salt, abscisic acid （ABA） and zeatin. Taken together, these results suggest that OsAP2LP might be involved in stress responses, and probably plays roles as a transcription regulator when plants response to cold, salt and drought stresses through ABA and gibberellin pathways.

A sensitivity analysis of factors affecting in geologic CO_(2) storage in the Ordos Basin and its contribution to carbon neutrality

To accelerate the achievement of China’s carbon neutrality goal and to study the factors affecting the geologic CO_(2)storage in the Ordos Basin,China’s National Key R&D Programs propose to select the Chang 6 oil reservoir of the Yanchang Formation in the Ordos Basin as the target reservoir to conduct the geologic carbon capture and storage(CCS)of 100000 t per year.By applying the basic theories of disciplines such as seepage mechanics,multiphase fluid mechanics,and computational fluid mechanics and quantifying the amounts of CO_(2)captured in gas and dissolved forms,this study investigated the effects of seven factors that influence the CO_(2)storage capacity of reservoirs,namely reservoir porosity,horizontal permeability,temperature,formation stress,the ratio of vertical to horizontal permeability,capillary pressure,and residual gas saturation.The results show that the sensitivity of the factors affecting the gas capture capacity of CO_(2)decreases in the order of formation stress,temperature,residual gas saturation,horizontal permeability,and porosity.Meanwhile,the sensitivity of the factors affecting the dissolution capture capacity of CO_(2)decreases in the order of formation stress,residual gas saturation,temperature,horizontal permeability,and porosity.The sensitivity of the influencing factors can serve as the basis for carrying out a reasonable assessment of sites for future CO_(2)storage areas and for optimizing the design of existing CO_(2)storage areas.The sensitivity analysis of the influencing factors will provide basic data and technical support for implementing geologic CO_(2)storage and will assist in improving geologic CO_(2)storage technologies to achieve China’s carbon neutralization goal.

Dynamic characteristics and influencing factors of CO_(2) huff and puff in tight oil reservoirs

CO_(2)huff and puff experiments of different injection parameters,production parameters and soaking time were carried out on large-scale cubic and long columnar outcrop samples to analyze dynamic characteristics and influencing factors of CO_(2)huff and puff and the contribution of sweeping mode to recovery.The experimental results show that the development process of CO_(2)huff and puff can be divided into four stages,namely,CO_(2)backflow,production of gas with some oil,high-speed oil production,and oil production rate decline stages.The production of gas with some oil stage is dominated by free gas displacement,and the high-speed oil production stage is dominated by dissolved gas displacement.CO_(2)injection volume and development speed are the major factors affecting the oil recovery.The larger the injected CO_(2)volume and the lower the development speed,the higher the oil recovery will be.The reasonable CO_(2)injection volume and development speed should be worked out according to oilfield demand and economic evaluation.There is a reasonable soaking time in CO_(2)huff and puff.Longer soaking time than the optimum time makes little contribution to oil recovery.In field applications,the stability of bottom hole pressure is important to judge whether the soaking time is sufficient during the huff period.The oil recovery of CO_(2)huff and puff mainly comes from the contribution of flow sweep and diffusion sweep,and diffusion sweep contributes more to the oil recovery when the soaking time is sufficient.

Why do we not reverse the path?Stress can cause depression,reduction of brain-derived neurotrophic factor and increased inflammation

The aim of this paper is to describe the direction of the link between stress,depression,increased inflammation and brain-derived neurotrophic factor(BDNF)reduction.We hypothesize that severe stress or prolonged stress can be the driving factor that promote the onset of depression.Both stress and depression,if not resolved over time,activate the production of transcription factors that will switch on pro-inflammatory genes and translate them into cytokines.This cascade fosters systemic chronic inflammation and reduced plasma BDNF levels.Since people with depression have a 60%increased risk of developing type 2diabetes(T2D)and show high levels of inflammation and low levels of BDNF,we hypothesize possible reasons that might explain why T2D,depression and dementia are often associated in the same patient.

Neuroprotective effects of atorvastatin against cerebral ischemia/reperfusion injury through the inhibition of endoplasmic reticulum stress

Cerebral ischemia triggers secondary ischemia/reperfusion injury and endoplasmic reticulum stress initiates cell apoptosis. However, the regulatory mechanism of the signaling pathway remains unclear. We hypothesize that the regulatory mechanisms are mediated by the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α in the endoplasmic reticulum stress signaling pathway. To verify this hypothesis, we occluded the middle cerebral artery in rats to establish focal cerebral ischemia/reperfusion model. Results showed that the expression levels of protein kinase-like endoplasmic reticulum kinase and caspase-3, as well as the phosphorylation of eukaryotic initiation factor 2α, were increased after ischemia/reperfusion. Administration of atorvastatin decreased the expression of protein kinase-like endoplasmic reticulum kinase, caspase-3 and phosphorylated eukaryotic initiation factor 2α, reduced the infarct volume and improved ultrastructure in the rat brain. After salubrinal, the specific inhibitor of phosphorylated eukaryotic initiation factor 2α was given into the rats intragastrically, the expression levels of caspase-3 and phosphorylated eukaryotic initiation factor 2α in the were decreased, a reduction of the infarct volume and less ultrastructural damage were observed than the untreated, ischemic brain. However, salubrinal had no impact on the expression of protein kinase-like endoplasmic reticulum kinase. Experimental findings indicate that atorvastatin inhibits endoplasmic reticulum stress and exerts neuroprotective effects. The underlying mechanisms of attenuating ischemia/reperfusion injury are associated with the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/caspase-3 pathway.

Oxidative stress in retinal pigment epithelium degeneration:from pathogenesis to therapeutic targets in dry age-related macular degeneration

Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascular endothelial growth factor therapies against neovascular age-related macular degeneration;however, effective treatment is not yet available for geographical atrophy in dry agerelated macular degeneration or for preventing the progression from early or mid to the late stage of age-related macular degeneration. Both clinical and experimental investigations involving human agerelated macular degeneration retinas and animal models point towards the atrophic alterations in retinal pigment epithelium as a key feature in age-related macular degeneration progression. Retinal pigment epithelium cells are primarily responsible for cellular-structural maintenance and nutrition supply to keep photoreceptors healthy and functional. The retinal pigment epithelium constantly endures a highly oxidative environment that is balanced with a cascade of antioxidant enzyme systems regulated by nuclear factor erythroid-2-related factor 2 as a main redox sensing transcription factor. Aging and accumulated oxidative stress triggers retinal pigment epithelium dysfunction and eventually death. Exposure to both environmental and genetic factors aggravates oxidative stress damage in aging retinal pigment epithelium and accelerates retinal pigment epithelium degeneration in age-related macular degeneration pathophysiology. The present review summarizes the role of oxidative stress in retinal pigment epithelium degeneration, with potential impacts from both genetic and environmental factors in age-related macular degeneration development and progression. Potential strategies to counter retinal pigment epithelium damage and protect the retinal pigment epithelium through enhancing its antioxidant capacity are also discussed, focusing on existing antioxidant nutritional supplementation, and exploring nuclear factor erythroid-2-related factor 2 and its regulators including REV-ERBα as therapeutic targets to protect against age-related macular degeneration development and progression.