Importance of early detection of esophageal cancer before the tumor progresses too much for effective treatment

This editorial comments on an article by Qu et al published in the World Journal of Gastrointestinal Oncology.It focuses on the importance of early detection of esophageal cancer,including recurrence or secondary malignancy after chemoradiotherapy(CRT).Endoscopic resection is the first choice for treatment for esophageal cancer remaining within the mucous membrane,while surgery or radical CRT are treatment options for advanced stages depending on the patient’s general condition and desire.Although these treatments are potentially curative,they are more invasive than endoscopic resection.Early-stage esophageal cancer is often asymptomatic and difficult to detect.Uniform periodic endoscopy is unrealistic.Although less burdensome tests exist,including liquid biopsy and urinary biomarkers,these have not yet been widely used in clinical practice.Early detection is important after radical CRT because the local recurrence rate is higher than that after surgery.However,endoscopic resection or photodynamic therapy is indicated if detected in the early stages,and positive results have been reported.Early detection of esophageal cancer is crucial.Endoscopy is the main diagnostic method;however,new and less burdensome methods should be established to ensure early treatment for patients with esophageal cancer.

Comment on:Recurrence after spontaneous separation of epiretinal membrane in a young woman:a case report

Dear Editor,Herein,we provide a commentary on the recently published article by Zeng QZ and Yu WZ[1].This case report provides interesting novel insights into the recurrence of epiretinal membrane(ERM)following self-separation in a young patient.In addition to the study,we have been investigating spontaneous ERM release for many years and have recently published a related paper[2].

Radical radiotherapy without surgical tumor resection for rectal cancer

In this editorial,I would like to comment on the article,recently published in the World Journal of Clinical Oncology.The article focuses on non-surgical treatments for locally recurrent rectal cancer,including the watch-and-wait(WW)strategy after total neoadjuvant therapy(TNT)and particle beam therapy.As treatment options for rectal cancer continue to evolve,the high complete response rate achieved with TNT has led to the development of a new non-surgical approach:WW.Chemoradiotherapy followed by consolidation chemotherapy,in particular,has a low rate of tumor growth and is a treatment aimed at achieving a cure without surgery.However,the risk of recurrence within two years is significant,necessitating careful follow-up.Establishing standardized follow-up methods that can be implemented by many physicians is essential.Carbon ion radiotherapy has demonstrated high local control with a low incidence of severe late toxicities,even after previous pelvic radiotherapy.While these new non-surgical curative treatments for rectal cancer require further investigation,future advancements in this field are anticipated.

Correlation between dose-volume parameters and rectal bleeding after 12 fractions of carbon ion radiotherapy for prostate cancer

BACKGROUND Carbon ion radiotherapy(CIRT)is currently used to treat prostate cancer.Rectal bleeding is a major cause of toxicity even with CIRT.However,to date,a correlation between the dose and volume parameters of the 12 fractions of CIRT for prostate cancer and rectal bleeding has not been shown.Similarly,the clinical risk factors for rectal bleeding were absent after 12 fractions of CIRT.AIM To identify the risk factors for rectal bleeding in 12 fractions of CIRT for prostate cancer.METHODS Among 259 patients who received 51.6 Gy[relative biological effectiveness(RBE)],in 12 fractions of CIRT,15 had grade 1(5.8%)and nine had grade 2 rectal bleeding(3.5%).The dose-volume parameters included the volume(cc)of the rectum irradiated with at least x Gy(RBE)(Vx)and the minimum dose in the most irradiated x cc normal rectal volume(Dx).RESULTS The mean values of D6cc,D2cc,V10 Gy(RBE),V20 Gy(RBE),V30 Gy(RBE),and V40 Gy(RBE)were significantly higher in the patients with rectal bleeding than in those without.The cutoff values were D6cc=34.34 Gy(RBE),D2cc=46.46 Gy(RBE),V10 Gy(RBE)=9.85 cc,V20 Gy(RBE)=7.00 cc,V30 Gy(RBE)=6.91 cc,and V40 Gy(RBE)=4.26 cc.The D2cc,V10 Gy(RBE),and V20 Gy(RBE)cutoff values were significant predictors of grade 2 rectal bleeding.CONCLUSION The above dose-volume parameters may serve as guidelines for preventing rectal bleeding after 12 fractions of CIRT for prostate cancer.

Lithium Ion Transport Environment by Molecular Vibrations in Ion-Conducting Glasses

Controlling Li ion transport in glasses at atomic and molecular levels is key to realizing all-solid-state batteries,a promising technology for electric vehicles.In this context,Li_(3)PS_(4)glass,a promising solid electrolyte candidate,exhibits dynamic coupling between the Li^(+)cation mobility and the PS_(4)^(3-)anion libration,which is commonly referred to as the paddlewheel effect.In addition,it exhibits a concerted cation diffusion effect(i.e.,a cation-cation interaction),which is regarded as the essence of high Li ion transport.However,the correlation between the Li^(+)ions within the glass structure can only be vaguely determined,due to the limited experimental information that can be obtained.Here,this study reports that the Li ions present in glasses can be classified by evaluating their valence oscillations via Bader analysis to topologically analyze the chemical bonds.It is found that three types of Li ions are present in Li_(3)PS_(4)glass,and that the more mobile Li ions(i.e.,the Li3-type ions)exhibit a characteristic correlation at relatively long distances of 4.0-5.0A.Furthermore,reverse Monte Carlo simulations combined with deep learning potentials that reproduce X-ray,neutron,and electron diffraction pair distribution functions showed an increase in the number of Li3-type ions for partially crystallized glass structures with improved Li ion transport properties.Our results show order within the disorder of the Li ion distribution in the glass by a topological analysis of their valences.Thus,considering the molecular vibrations in the glass during the evaluation of the Li ion valences is expected to lead to the development of new solid electrolytes.

Impact of a Low Severity Fire on Soil Organic Carbon and Nitrogen Characteristics in Japanese Cedar Soil, Yamagata Prefecture, Japan

Slash and burn practices are widely used around the globe with different degrees of success which are mostly related to the impact of fire on soil properties. In Japan slash and burn practises, known as Yakihata, have a long history and are still used in Yamagata Prefecture today. The purpose of this study was to determine the impact of a low severity controlled fire underneath Japanese cedar (Cryptomeria japonica) on brown forest soil (Cambisol). Japanese Cedar is the dominant species among plantations in Japan. We measured organic carbon and nitrogen content as well as changes in carbon (δ13C) and nitrogen (δ15N) stable isotope composition in a steep west facing slope under heavy precipitation (~2600 mm/a) and heavy snowfall (~3 to 4 m/a). The accumulation of Ctotal and Ntotal at the bottom of the slopes was remarkably higher at the slash and burned site than in the control forest site. After slash and burn δ15N isotopes in the slope in general became significantly lighter than in the control forest while the δ13C did not show any significant difference between the two sites except at the bottom of the slopes where δ13C was heavier in the forest. The results show that Ctotal and Ntotal values as well as the isotopes ratios of C and N change with decreasing elevation in the forest as well as in the burned site being consistent with leaching and erosion. The changes in soil nitrogen and carbon isotopes at the bottom of the slope appear to be related to the transport of material with different isotopic composition from the upper slope. The effect of the low severity fire (as part of the slash and burn practice) on soil organic carbon and nitrogen movement was enhanced by the steepness of the slopes and the high precipitation of Shonai region.

Effects of docosahexaenoic acid or arachidonic acid supplementation on the behavior of cardiomyocytes derived from human pluripotent stem cells

Background:Human heart changes its energetic substrates from lactate and glucose to fatty acids during the neonatal period.Noticing the lack of fatty acids in media for the culture of cardiomyocytes derived from human pluripotent stem cells(hiPS-CM),researchers have supplemented mixtures of fatty acids to hiPS-CM and reported the enhancement in the maturation of hiPS-CM.In our previous studies,we separately supplemented two polyunsaturated fatty acids(PUFAs),docosahexaenoic acid(DHA)or arachidonic acid(AA),to rat fetal cardiomyocytes and found that the supplementations upregulated the expressions of mRNAs for cardiomyocyte differentiation,fatty acid metabolism,and cellular adhesion.The enhancement in cellular contractility was attributed to the improvement in intercellular connection rather than a direct enhancement of the contractile force.Methods:This study reports the successive results of the effects of DHA or AA supplementation on hiPS-CM.In addition to the contractile force and mRNA measurements used in the previous study,we further investigated the effect of different cellular aggregations on the contractile force output by means of finite element analysis,measured glucose and fatty acids metabolites,and assessed cTNT and MLC2v expressions through immunofluorecsence evaluation.Results:It showed that the sole supplementation of albumin-conjugated DHA or AA can be taken up by hiPS-CM without other uptake-enhancing factors,and the supplementations may activate the CD36_ERRγmetabolic pathway.DHA or AA supplementation increased the cellular contractile ratio on collagen gels and AA supplementation stimulated hiPS-CM aggregation to form cellular clusters.The enhancement effect on the hiPS-CM contractile force was modest since the increase in contractile force was not significant.AA supplementation was more effective than DHA supplementation because it significantly upregulated mRNA expressions of P300 and CD36.However,finite element analysis showed that the formation of clusters on a collagen gel attenuated the contractile force exerted by the gel on its surroundings.Conclusion:DHA and AA,as having been supplemented in infant formulas,have no direct and significant enhancement effect on the performance of the hiPS-CM when they were supplemented individually,although they were able to enter the cellular metabolic system.The AA supplementation showed some auxiliary effect on the maturation of hiPS-CM,which is worthy of further investigation under the consideration of membrane composition alteration and remodeling of membrane molecules.

Complete response to an anti-programmed cell death 1 antibody following a combination therapy of an anti-programmed cell death ligand 1 antibody and a tyrosine kinase inhibitor for metastatic renal cell carcinoma

Dear Editor,Several Phase 3 trials have demonstrated the efficacy of immune checkpoint inhibitor(ICI)-based combination therapies in the treatment of advanced clear cell renal cell carcinoma(RCC)[1-5].However,there is still no well-defined adequate treatment for patients who experience disease progression after initial ICI-based combination therapy.

A durable complete response resulting from treatment with nivolumab plus ipilimumab for metastatic collecting duct carcinoma of the kidney

Dear Editor,Collecting duct carcinoma(CDC)or Bellini carcinoma originates in the distal collecting ducts.CDC is a markedly aggressive subtype of renal cell carcinoma and accounts for less than 1%of all renal cell carcinomas[1].We described a patient with CDC and psoriasis,who showed complete response(CR)after being treated with combination therapy of nivolumab and ipilimumab(NI).The study was conducted in accordance with and approved by the Ethics Committee of Yamagata University Faculty of Medicine(approval no.2019-35).The need for patient consent was waived by the same institutional review board;all the patients provided written informed consents.

Purification and Characterization of Hyaluronate Lyases Produced by Two Types of Bacteria

Hyaluronate lyases were obtained from two types of naturally isolated bacterial strains Paenibacillus yunnanensis and Paennarthrobacter nicotinovorans.PyHL(form P.yunnanensis)in the culture supernatant of the bacteria was purified by two steps of column chromatography.The enzyme showed the molecular mass of 74 kDa by SDS-PAGE and the maximal activity at pH 5.0,35℃.PyHL maximally degraded hyaluronate by an endo-type manner,and showed low degradation activity toward chondroitin sulfates.Dermatan sulfate was not the substrate.PnHL(from P.nicotinovorans)in the culture supernatant of the bacteria was purified by two steps of column chromatography.The enzyme showed the molecular mass of 70 kDa by SDS-PAGE and the maximal activity at pH 6.0,30℃.Genomic analysis of P.nicotinovorans on the bases of the internal amino acid sequences of PnHL.

Not Follicular but Dermal Melanocyte Precursors Are Histopathologically Retained in Vitiligo

Although perifollicular repigmentation in the vitiligo lesions is owing to activation of follicular melanocyte stem cells and/or precursor cells followed by supplying matured melanocytes, the underlying mechanism of diffuse repigmentation on the whole vitiligo surface remains still unknown. In addition to the presence of remaining melanocytes, it is conceivable that dermal melanocyte precursor cells contribute to induce diffuse repigmentation after treatment. Therefore, we investigated here whether dermal and follicular melanocyte precursor cells were reduced or not in vitiligo lesions. We performed an immunostaining for Nestin and p75NGFR as dermal melanocyte precursor cells and MITF/Fzd4 as follicular melanocyte precursor cells and compared the positive cells number between lesions and non-lesions (n = 11). Although MITF+/Fzd4+ cells in the hair follicle were significantly decreased in number in the lesions, Nestin+ and p75NGFR+ cells were not. This result indicates that dermal precursor cells could be retained in the vitiligo lesions but be disturbed to differentiate into matured melanocytes.

Simulation of Crack Pattern Formation Due to Shrinkage in a Drying Material

Crack patterns observed in nature have attracted the interest of researchers in various fields, and the mechanism of the pattern formation has been investigated. However, the phenomenon is very complicated, and many factors affect the process. Therefore, we are motivated to construct a general simulation code with a simple algorithm. In this study, crack pattern formation due to shrinkage caused by the drying of a wet material was simulated. The process was simplified as follows: tensile force is generated in the model, and a crack is generated when the tension exceeds a critical value. The tensile forces in the x and y directions are independently evaluated. A crack propagates perpendicular to the tension until it reaches another crack or a boundary. Based on this modeling, simulations with a two-dimensional square domain were performed. Consequently, a cross-divided pattern was generated. Assuming zigzag crack propagation, more realistic patterns were obtained. The effects of the boundary and domain size were also considered, and various characteristic patterns were obtained. Furthermore, the orientation dependency was simulated, and 45&#730 declined patterns and rectangularly divided patterns were generated. The model presented in this study is very simplified and is expected to be applicable to various objects.

庚型肝炎病毒基因组RNA转录体恒河猴肝内注射感染的初步研究

GBV-C/HGV RNA transcripts were transcribed in vitro from a single GBV-C/HGV full-length cDNA clone pHGVqz, and injected directly into the liver of Macaca mulatta to test their infectivity. Serum samples from the experimental Macaca mulatta were collected weekly after injection to detect ALT, anti-GBV-C/HGV and GBV-C/HGV RNA. At week 6 post injection, the liver tissues of the infected Macaca mulatta were dissected through operation for histological examination. The results showed that ALT level of the Macaca mulatta remained normal and anti-GBV-C/HGV kept negative after infection. GBV-C/HGV RNA was detected positve from week 1 through week 14 post injection. The liver biopsy showed light viral-hepatitis like histological changes. From the preliminary results, we concluded that the in vitro transcripts of GBV-C/HGV may be infectious. Further studies are under way to confirm the conclusion.

森林土壤融化期异养呼吸和微生物碳变化特征

采用室内土柱培养的方法,研究在不同湿度(55%和80%WFPS,土壤充水孔隙度)和不同氮素供给(NH_4Cl和KNO_3,4.5 g N/m^2)条件下,外源碳添加(葡萄糖,6.4 g C/m^2)对温带成熟阔叶红松混交林和次生白桦林土壤融化过程微生物呼吸和微生物碳的激发效应。结果表明:在整个融化培养期间,次生白桦林土壤对照CO_2累积排放量显著高于阔叶红松混交林土壤。随着土壤湿度的增加,次生白桦林土壤对照CO_2累积排放量和微生物代谢熵(q_(CO_2))显著降低,而阔叶红松混交林土壤两者显著地增加(P<0.05)。两种林分土壤由葡萄糖(Glu)引起的CO_2累积排放量(9.61—13.49 g C/m^2)显著大于实验施加的葡萄糖含碳量(6.4g C/m^2),同时由Glu引起的土壤微生物碳增量为3.65—27.18 g C/m^2,而施加Glu对土壤DOC含量影响较小。因此,这种由施加Glu引起的额外碳释放可能来源于土壤固有有机碳分解。融化培养结束时,阔叶红松混交林土壤未施氮处理由Glu引起的CO_2累积排放量在两种湿度条件下均显著大于次生白桦林土壤(P<0.001);随着湿度的增加,两种林分土壤Glu引起的CO_2累积排放量显著增大(P<0.001)。单施KNO_3显著地增加两种湿度的次生白桦林土壤Glu引起的CO_2累积排放量(P<0.01)。单施KNO_3显著地增加了两种湿度次生白桦林土壤Glu引起的微生物碳(P<0.001),单施NH_4Cl显著地增加低湿度阔叶红松混交林土壤Glu引起的微生物碳(P<0.001)。结合前期报道的未冻结实验结果,发现冻结过程显著地影响外源Glu对温带森林土壤微生物呼吸和微生物碳的刺激效应(P<0.05),并且无论冻结与否,温带森林土壤微生物呼吸和微生物碳对外源Glu的响应均与植被类型、土壤湿度、外源氮供给及其形态存在显著的相关性。

Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer

The development and progression of gastric cancer involves a number of genetic and epigenetic alterations of tumor suppressor and tumor-related genes. The majority of differentiated carcinomas arise from intestinal metaplastic mucosa and exhibit structurally altered tumor suppressor genes, typified by p53, which is inactivated via the classic two-hit mechanism, i.e. loss of heterozygosity （LOH） and mutation of the remaining allele. LOH at certain chromosomal loci accumulates during tumor progression. Approximately 20% of differentiated carcinomas show evidence of mutator pathway tumorigenesis due to hMLH1 inactivation via hypermethylation of promoter CpG islands, and exhibit high-frequency microsatellite instability. In contrast, undifferentiated carcinomas rarely exhibit structurally altered tumor suppressor genes. For instance, while methylation of E-cadherin is often observed in undifferentiated carcinomas, mutation of this gene is generally associated with the progression from differentiated to undifferentiated carcinomas. Hypermethylation of tumor suppressor and tumor-related genes, including APC, CHFR, DAP- kinase, DCC, E-cadherin, GSTP1, hMLH1, p16, PTEN, RASSF1A, RUNX3, and TSLC1, can be detected in both differentiated and undifferentiated carcinomas at varying frequencies. However, the significance of the hypermethylation varies according to the analyzed genomic region, and hypermethylation of these genes can also be present in non-neoplastic gastric epithelia. Promoter demethylation of specific genes, such as MAGE and synudein y, can occur during the progressive stages of both histological types, and is associated with patient prognosis. Thus, while the molecular pathways of gastric carcinogenesis are dependent on histological background, specific genetic alterations can still be used for risk assessment, diagnosis, and prognosis.

Cooperative function of antioxidant and redox systems against oxidative stress in male reproductive tissues

Reactive oxygen species (ROS) are produced under oxidative stress, such as high oxygen concentration and during the metabolic consumption of oxygen molecules. Male reproductive tissues appear to be continuously exposed to ROS produced by active metabolism. In addition, spermatozoa must pass through a high oxygen environment during the mating process. Thus, to maintain viable reproductive ability, a protective mechanism against oxidative stress is of importance. Here, we overview our current understanding of the cooperative function of antioxidative and redox systems that are involved in male fertility. Superoxide dismutase and glutathione peroxidase are major enzymes that scavenge harmful ROS in male reproductive organs. In turn, glutathione and thioredoxin systems constitute the main redox systems that repair oxidized and damaged molecules and also play a role in regulating a variety of cellular functions. While glutathione functions as an antioxidant by donating electrons to glutathione peroxidase and thioredoxin donates electrons to peroxiredoxin as a counterpart of glutathione peroxidase. In addition, aldo-keto reductases, which detoxify carbonyl compounds produced by oxidative stress, are present at high levels in the epithelia of the genital tract and Sertoli cells of the testis. Since these systems are involved in cross-talk, a comprehensive understanding will be required to maintain the physiological functions of male reproductive system.

Decreased levels of plasma adiponectin associated with increased risk of colorectal cancer

AIM:To investigate the association between adiponectin levels and risk of colorectal adenoma and cancer (early and advanced).METHODS: A cross-sectional study in a cohort of hospital-based patients was conducted between January 2004 and March 2006 at Yamagata University Hospital. Male subjects, who had colorectal tumors detected by endoscopic examination, were enrolled according to inclusion and exclusion criteria. Based on the T factor of the TNM system, intraepithelial carcinoma and submucosally invasive carcinoma were def ined as early cancer, and invasion into the muscularis propria or deeper was defined as advanced cancer. The plasma levels of glucose, insulin, total cholesterol, triglyceride, high sensitivity C-reactive protein, insulin like growth factor (IGF)-1, IGF binding protein-3, adiponectin, leptin, and resistin were measured. Each factor level was designated low or high, and the risk of adenoma or cancer was estimated by univariate and multivariate logistic regression analysis.RESULTS: We enrolled 124 male subjects (47 with adenoma, 34 with early cancer, 17 with advanced cancer, and 26 without tumors as controls). In patients with adenoma, high triglyceride and low adiponectin were associated with a significant increase in the odds ratio (OR) by univariate analysis. Only a low adiponectin level was related to increased adenoma risk, with an adjusted OR for low level (<11 μg/mL) to high (≥11 μg/mL) of 5.762 (95% confidence interval (CI):1.683-19.739, P=0.005). In the patients with early cancer, high body mass index, high triglyceride, and low adiponectin were associated with a significant increase in OR in univariate analysis. Imultivariate analysis, only low adiponectin was significantly associated with early cancer, with an adjusted OR of 4.495 (95% CI:1.090-18.528, P=0.038). However, in patients with advanced cancer, low adiponectin was not recognized as a significant risk factor for advanced cancer.CONCLUSION: A decreased level of adiponectin is strongly associated with an increased risk of colorectal adenoma and early cancer. These data call for further investigation, including a controlled prospective study.

Spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein

PreservaUon of the spleen at distal pancreatectomy has recently attracted considerable attention. Since our first successful trial, spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein for tumors of the pancreas and chronic pancreatitis has been performed more frequently. The technique for spleenpreserving distal pancreatectomy with conservation of the splenic artery and vein are outlined. The splenic vein is identified behind the pancreas and within the thin connective tissue membrane. The connective tissue membrane is cut longitudinally above the splenic vein. An important issue is to remove the splenic vein from the body of the pancreas toward the spleen, since a different approach may be very difficult. The pancreas is preferably removed from the splenic artery toward the head of the pancreas itself. This procedure is much easier than removing the pancreas from the vein side. One patient had undergone distal gastrectomy for duodenal ulcer, with reconstruction by Billroth Ⅱ tehcnique. If distal pancreatectomy with splenectomy had been performed for the lesion of the distal pancreas at the time, the residual stomach would also have to be resected. The potential damage done to the patient by reconstruction of the gastrointestinal tract in combination with distal pancreatectomy and splenectomy would have been much greater than with distal pancreatectomy only with preservation of the spleen and residual stomach. Benign lesions as well as low-grade malignancy of the body and tail of the pancreas may be a possible indication for this procedure.

Pancreatic schwannoma:Case report and an updated 30-year review of the literature yielding 47 cases

Pancreatic schwannomas are rare neoplasms. Authors briefly describe a 64-year-old female patient with cystic pancreatic schwannoma mimicking other cystic tumors and review the literature. Databases for PubMed were searched for English-language articles from 1980 to 2010 using a list of keywords, as well as references from review articles. Only 41 articles, including 47 cases, have been reported in the English literature. The mean age was 55.7 years （range 20-87 years）, with 45% of patients being male. Mean tumor size was 6.2 cm （range 1-20 cm）. Tumor location was the head （40%）, head and body （6%）, body （21%）, body and tail （15%）, tail （4%）, and uncinate process （13%）. Thirty-four percent of patients exhibited solid tumors and 60% of patients exhibited cystic tumors. Treatment included pancreati- coduodenectomy （32%）, distal pancreatectomy （21%）, enucleation （15%）, unresectable （4%）, refused opera- tion （2%） and the detail of resection was not specified in 26% of patients. No patients died of disease with a mean follow-up of 15.7 mo （range 3-65 too）, although 5 （11%） patients had a malignancy. The tumor size was significantly related to malignant tumor （13.8 ＋ 6.2 cm for malignancy vs 5.5 ＋ 4.4 cm for benign, P = 0.001） and cystic formation （7.9 ~ 5.9 cm for cystic tumor vs 3.9 ＋ 2.4 cm for solid tumor, P = 0.005）. The preoperative diagnosis of pancreatic schwannoma remains difficult. Cystic pancreatic schwannomas should be considered in the differential diagnosis of cystic neoplasms and pseudocysts. In our caset intraoperative frozen sec- tion confirmed the diagnosis of a schwannoma. Simple enudeation may be adequate, if this is possible.

Mutual interaction between oxidative stress and endoplasmic reticulum stress in the pathogenesis of diseases specifically focusing on non-alcoholic fatty liver disease

Reactive oxygen species(ROS) are produced during normal physiologic processes with the consumption of oxygen. While ROS play signaling roles, when they are produced in excess beyond normal antioxidative capacity this can cause pathogenic damage to cells. The majority of such oxidation occurs in polyunsaturated fatty acids and sulfhydryl group in proteins, resulting in lipid peroxidation and protein misfolding, respectively. The accumulation of misfolded proteins in the endoplasmic reticulum(ER) is enhanced under conditions of oxidative stress and results in ER stress, which, together, leads to the malfunction of cellular homeostasis. Multiple types of defensive machinery are activated in unfolded protein response under ER stress to resolve this unfavorable situation. ER stress triggers the malfunction of protein secretion and is associated with a variety of pathogenic conditions including defective insulin secretion from pancreatic β-cells and accelerated lipid droplet formation in hepatocytes. Herein we use nonalcoholic fatty liver disease(NAFLD) as an illustration of such pathological liver conditions that result from ER stress in association with oxidative stress. Protecting the ER by eliminating excessive ROS viathe administration of antioxidants or by enhancing lipidmetabolizing capacity via the activation of peroxisome proliferator-activated receptors represent promising therapeutics for NAFLD.