Causal association of polyunsaturated fatty acids with biliary tract diseases: A Mendelian randomization study.

OBJECTIVES: The evidence connecting polyunsaturated fatty acids (PUFAs) to biliary problems is still highly contested and speculative despite the fact that biliary diseases are common and PUFAs have long been studied for their potential health benefits. This work used Mendelian randomization (MR) techniques in conjunction with genome-wide association study (GWAS) data to clarify the causal relationships between PUFAs and biliary tract diseases. METHODS: We compiled data on PUFAs, including Omega-3 fatty acids, Omega-6 fatty acids, and the ratio of Omega-6 to Omega-3 fatty acids (Omega-6:Omega-3), using GWAS. MR was used to examine biliary tract problems (cholecystitis, cholelithiasis, gallbladder cancer, primary biliary cholangitis, primary sclerosing cholangitis, and disorders of gallbladder, biliary tract and pancreas). Single nucleotide polymorphisms significantly associated with PUFAs were selected as instrumental variables to estimate causal effects on biliary tract diseases. The final results were analyzed using five MR analysis techniques. Inverse variance weighting (IVW) was used as the primary outcome. And IVW was utilized in conjunction with the other MR analysis techniques (MR-Egger, weighted median, simple mode, and weighted mode). Additionally, we evaluated heterogeneity and horizontal multiplicity using the MR-Egger intercept test and Cochrane's Q test, respectively. Finally, to increase the accuracy and precision of the study outcomes, we carried out a number of sensitivity analyses. RESULTS: We found that Omega-3 fatty acids reduced the risk of cholecystitis (OR: 0.851, P = 0.009), cholelithiasis (OR: 0.787, P = 8.76e-5), and disorders of gallbladder, biliary tract and pancreas (OR: 0.842, P = 1.828e-4) but increased the primary biliary cholangitis (OR: 2.220, P = 0.004). There was no significant association between Omega-3 fatty acids and risk of gallbladder cancer (OR: 3.127, P = 0.530) and primary sclerosing cholangitis (OR: 0.919, P = 0.294). Omega-6 fatty acids were associated with a reduced risk of cholecystitis (OR: 0.845, P = 0.040). However, they were not linked to an increased or decreased risk of cholelithiasis (OR: 0.878, P = 0.14), gallbladder cancer (OR: 4.670, P = 0.515), primary sclerosing cholangitis (OR: 0.993, P = 0.962), primary cholestatic biliary cholangitis (OR: 1.404, P = 0.509), or disorders of gallbladder, biliary tract and pancreas. Omega-6:Omega-3 fatty acids were linked to a greater risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas (OR:1.168, P = 0.009, OR:1.191, P = 1.60e-6, and OR:1.160, P = 4.11e-6, respectively). But (OR: 0.315, P = 0.010) was linked to a decreased risk of primary biliary cholangitis. Not linked to risk of primary sclerosing cholangitis (OR: 1.079, P = 0.078) or gallbladder cancer (OR: 0.046, P = 0.402). According to the MR-Egger intercept, our MR examination did not appear to be impacted by any pleiotropy (all P > 0.05). Additionally, sensitivity studies validated the accuracy of the calculated causation. CONCLUSION: Inconsistent causative relationships between PUFAs and biliary tract diseases were revealed in our investigation. However, Omega-3 fatty acids were found to causally lower the risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas. Omega-3 fatty acids increased the risk of primary biliary cholangitis in a causative way. Omega-3 fatty acids with the risk of gallbladder cancer and primary sclerosing cholangitis did not have any statistically significant relationships. Omega-6 fatty acids were not significantly causally connected with the risk of cholelithiasis, gallbladder cancer, primary sclerosing cholangitis, or disorders of gallbladder, biliary tract and pancreas. However, they did play a causative role in lowering the risk of cholecystitis. Omega-6:Omega-3 fatty acids decreased the risk of primary biliary cholangitis but increased the risk of cholecystitis, gallstone disease, and disorders of gallbladder, biliary tract and pancreas. They had no effect on the risk of gallbladder cancer or primary sclerosing cholangitis. Therefore, additional research should be done to examine the probable processes mediating the link between polyunsaturated fatty acids and the risk of biliary tract diseases.

Advances in Thyroid Organoids Research and Applications.

INTRODUCTION: Organoids are three-dimensional cellular aggregates derived from stem cells or primary tissues that can self-organize into organotypic structures and showcase the physiological functions of that organ. Organoids typically comprise multiple organ-specific cell types that are responsible for organ function in vivo. They may also incorporate various cellular and molecular stromal components to recapitulate the in vivo microenvironment of the target organ. METHODS: All articles related to thyroid-like organs were synthesized. Articles published between 1959 and 2023 were assessed, categorized, and analyzed using relevant keywords. RESULTS: As such, organoids provide a model of greater physiological relevance than 2D cell culture for basic and translational research. Murine and human organoids of the thyroid have been established from embryonic stem cells (ESCs), pluripotent stem cells (PSCs) and from various healthy or diseased thyroid tissues. These thyroid organoids have been used in basic and translation research on thyroid-related diseases including hyperthyroidism, Graves' disease, and Hashimoto's thyroiditis. In addition, organoids derived from patients with thyroid cancer retain histopathological features and mutational profile of the original tumor. These patient-derived organoids have been successfully used in in vitro evaluation of drug response of individual patients, demonstrating their potential application in personalized treatment of thyroid cancer. CONCLUSION: In this review article, we have discussed various techniques for establishing thyroid organoids and their applications in thyroid-related diseases as disease models, regenerative medicines, or a tool for drug testing.

Targeting hnRNPC suppresses thyroid follicular epithelial cell apoptosis and necroptosis through m6A-modified ATF4 in autoimmune thyroid disease.

Both environmental and genetic factors contribute to the etiology of autoimmune thyroid disease (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT). However, the exact pathogenesis and interactions that occur between environmental factors and genes remain unclear, and therapeutic targets require further investigation due to limited therapeutic options. To solve such problems, this study utilized single-cell transcriptome, whole transcriptome, full-length transcriptome (Oxford nanopore technology), and metabolome sequencing to examine thyroid lesion tissues from 2 HT patients and 2 GD patients as well as healthy thyroid tissue from 1 control subject. HT patients had increased ATF4-positive thyroid follicular epithelial (ThyFoEp) cells, which significantly increased endoplasmic reticulum stress. The enhanced sustained stress resulted in cell death mainly including apoptosis and necroptosis. The ATF4-based global gene regulatory network and experimental validation revealed that N6-methyladenosine (m6A) reader hnRNPC promoted the transcriptional activity, synthesis, and translation of ATF4 through mediating m6A modification of ATF4. Increased ATF4 expression initiated endoplasmic reticulum stress signaling, which when sustained, caused apoptosis and necroptosis in ThyFoEp cells, and mediated HT development. Targeting hnRNPC and ATF4 notably decreased ThyFoEp cell death, thus ameliorating disease progression. Collectively, this study reveals the mechanisms by which microenvironmental cells in HT and GD patients trigger and amplify the thyroid autoimmune cascade response. Furthermore, we identify new therapeutic targets for the treatment of autoimmune thyroid disease, hoping to provide a potential way for targeted therapy.

GTS-21, a selective alpha7 nicotinic acetylcholine receptor agonist, ameliorates diabetic nephropathy in Leprdb/db mice.

Diabetic nephropathy (DN) is a serious complicating factor in human type 2 diabetes mellitus (T2DM), and it commonly results in end-stage renal disease (ESRD) that requires kidney dialysis. Here, we report that the α7 nicotinic acetylcholine receptor (α7nAChR) agonist GTS-21 exerts a novel anti-inflammatory action to ameliorate DN, as studied using an inbred strain of Leprdb/db mice in which hyperglycemia and obesity co-exist owing to defective leptin receptor (Lepr) signaling. For this analysis, GTS-21 was administered to 10-12 week-old male and female mice as a 4 mg/kg intraperitoneal injection, twice-a-day, for 8 weeks. Kidney function and injury owing to DN were monitored by determination of plasma levels of BUN, creatinine, KIM-1 and NGAL. Histologic analysis of glomerular hypertrophy and mesangial matrix expansion were also used to assess DN in these mice. Concurrently, renal inflammation was assessed by measuring IL-6 and HMGB1, while also quantifying renal cell apoptosis, and apoptotic signaling pathways. We found that Leprdb/db mice exhibited increased markers of BUN, creatinine, NGAL, KIM-1, IL-6, cytochrome C, and HMGB-1. These abnormalities were also accompanied by histologic kidney injury (mesangial matrix expansion and apoptosis). Remarkably, all such pathologies were significantly reduced by GTS-21. Collectively, our results provide new evidence that the α7nAChR agonist GTS-21 has the ability to attenuate diabetes-induced kidney injury. Additional studies are warranted to further investigate the involvement of the vagal cholinergic anti-inflammatory reflex pathway (CAP) in ameliorating diabetic nephropathy.

Analysis of the Transmission of SARS-CoV-2 Delta VOC in Yantai, China, August 2021.

Objective: Starting 31 July 2021, a SARS-CoV-2 outbreak occurred in Yantai, Shandong Province. The investigation showed that this outbreak was closely related to the epidemic at Nanjing Lukou Airport. In view of the fact that there were many people involved in this outbreak and these people had a complex activity area, the transmission route cannot be analyzed by simple epidemiological investigation. Here we combined the SARS-COV-2 whole-genome sequencing with epidemiology to determine the epidemic transmission route of Yantai. Methods: Thirteen samples of SARS-CoV-2 outbreak cases from 31 July to 4 August 2021 were collected and identified by fluorescence quantitative PCR, then whole-genome deep sequencing based on NGS was performed, and the data were analyzed and processed by biological software. Results: All sequences were over 29,000 bases in length and all belonged to B.1.617.2, which was the Delta strain. All sequences shared two amino acid deletions and 9 amino acid mutations in Spike protein compared with reference sequence NC_045512.2 (Wuhan virus strain). Compared with the sequence of Lukou Airport Delta strain, the homology was 99.99%. In order to confirm the transmission relationship between patients, we performed a phylogenetic tree analysis. The results showed that patient 1, patient 2, and patient 9 belong to an independent branch, and other patients have a close relationship. Combined with the epidemiological investigation, we speculated that the epidemic of Yantai was transmitted by two routes at the same time. Based on this information, our prevention and control work was carried out in two ways and effectively prevented the further spread of this epidemic.

Circulating endothelial progenitor cells from septic patients are associated with different infectious organisms.

BACKGROUND: In sepsis, endothelial progenitor cells (EPCs) play a central role in the repair of endothelial injury by enhancing the processes of re-endothelialization and angiogenesis. However, the surface markers of EPCs have yet to be standardized, and Changes of EPCs in quantities and functions with different infectious organisms are still unclear. This study explored the relationship between the percentages of EPCs and various infectious organisms in patients with sepsis. METHODS: Thirty-nine septic patients and 20 healthy controls were enrolled in this study. The percentages of CD34+/KDR+, CD133+/KDR+, CD34+/CD133+/KDR+, CD34+, CD133+, and KDR+ cells in different groups of septic patients and the healthy controls were analyzed by flow cytometry. RESULTS: The peripheral blood of septic patients had higher percentages of EPCs than that of the healthy controls. There were no significant differences in the percentages of EPCs between the sepsis and septic shock groups, nor between the survival group and the non-survival group. Additionally, the percentages of CD34+/CD133+/KDR+ cells in the gram-positive bacteremia group were significantly higher than those in the gram-negative bacteremia group and the negative blood culture group. The percentage of KDR+ cells in both the gram-positive bacteremia group and the gram-negative bacteremia group was significantly higher than that in the negative blood culture group. CONCLUSIONS: The percentages of circulating EPCs in patients with sepsis are associated with different infectious organisms.

Analysis of Severe Fever With Thrombocytopenia Syndrome in Critical Ill Patients in Central China.

INTRODUCTION: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis infected by virus (SFTSV) in central and eastern China, which is associated with high mortality. However, limited clinical data have been reported about this critical illness. PATIENTS AND METHODS: Retrospective cohort study in intensive care unit (ICU) patients with SFTSV infection admitted in 2014 to 2019. Diagnosis was confirmed using reverse transcription polymerase chain reaction on serum samples. RESULTS: One hundred sixteen patients with SFTSV infection were included (mean age 63 ±â€Š9 years, 59 [51.3%] males). Non-survivors (43.1%) were older, and had lower Glasgow Coma Score, higher Acute Physiology and Chronic Health Evaluation II, and sequential organ failure assessment score at ICU admission. In addition, non-survivors had more severe respiratory failure (PaO2/FiO2: 208 ±â€Š14 mm Hg vs. 297 ±â€Š15 mm Hg), more frequent shock (25[50%] vs. 7[10.6%]), and required more frequently mechanical ventilation (78% vs. 19.7%; P < 0.001) and vasopressor support (56% vs. 9.1%; P < 0.001). Non-survivors experienced more obvious monocyte loss. After adjustment for potential confounding factors, older age, elevated lactate level, and elevated creatinine level were the independent risk factors for death. CONCLUSION: We provided knowledge about the clinical characteristics of SFTS admitted in ICU. Older age, elevated lactate level, and elevated creatinine level may be useful for identifying patients with poor outcome and intensive medical intervention can be provided for patients as soon as possible to reduce mortality.

Protective effects of glucocorticoid on liver injury in a rat sepsis model.

Sepsis is one of the leading causes of death with unsatisfactory current treatments. The present study assessed the liver protective effect of glucocorticoids on different levels of inflammation in septic shock rats. A rat septic shock model was established by lipopolysaccharide (LPS) injection. Rats were divided into control (Control), high-inflammation treated with hydrocortisone (HT), high-inflammation non-treatment (HNT), low-inflammation treated with hydrocortisone (LT) and low-inflammation non-treatment (LNT) groups according to the levels of serum C-reactive protein (CRP), interleukin (IL)-6 and interferon (IFN)-γ. The mean arterial pressure and heart rate changes were continuously monitored and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured by an automatic biochemical analyzer. Hematoxylin and eosin (H&E) staining was performed to observe the pathological changes of liver tissue. Western blot analysis was used to detect the expression of p38 mitogen-activated protein kinase (MAPK) and NF-κB protein. The results demonstrated that following 7 days of treatment, there were no obvious differences in the serum CRP, IL-6 and IFN-γ levels between the HT group and the control group, whilst the HNT group, LT group and LNT group were significantly different compared with the HT and control groups. H&E staining demonstrated that the liver cells in the HT group were homogeneous following 7 days of treatment. Western blot analysis determined that the phosphorylation levels of p38MAPK and NF-κB in HT group were reduced significantly compared with the LT group, while there was no obvious difference with the control group after 7 days treatment. The present results indicated that glucocorticoids have better therapeutic effect on septic shock rats with high-inflammation compared with low-inflammation rats. The present study provides a novel approach for glucocorticoid treatment of septic shock.

LINC00520 targeting miR-27b-3p regulates OSMR expression level to promote acute kidney injury development through the PI3K/AKT signaling pathway.

BACKGROUND: Acute kidney injury (AKI) shows several kinds of disorders, which acutely harm the kidney. However, the current medical methods have limited therapeutic effects. The present study aimed to find out the molecular mechanism of AKI pathogenesis, which may provide new insights for future therapy. METHODS: Bioinformatic analysis was conducted using the R language (AT&T BellLaboratories, University of Auckland, New Zealand) to acquire the differentially expressed long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in AKI. The expression levels of RNAs and related proteins in tissues and cells were detected by quantitative real-time PCR (qRT-PCR) and western blot. Dual-luciferase reporter gene assays were performed to verify the target relationship between microRNA (miRNA) and lncRNA as well as miRNA and mRNA. Flow cytometry and tunnel assay were used to detect the cell apoptotic rate in AKI. RESULTS: LINC00520, miR-27b-3p, and OSMR form an axis to regulate AKI. Knockdown of LINC00520 reduced acute renal injury both in vitro and in vivo. LINC00520 activated the PI3K/AKT pathway to aggravate renal ischemia/reperfusion injury, while upregulation of miR-27b-3p or downregulation of OSMR could accelerate the recovery of AKI. CONCLUSION: Overexpression of LINC00520 contributes to the aggravation of AKI by targeting miR-27b-3p/ OSMR.

Myricetin against ischemic cerebral injury in rat middle cerebral artery occlusion model.

The purpose of the present study was to examine the effects of myricetin on reducing cerebral ischemia injury in a rat model. A rat model of permanent middle cerebral artery occlusion (pMCAO) was used in the present study. Rats were randomized into the following five groups: Sham, model, low­myricetin (1 mg/kg), medium­myricetin (5 mg/kg) and high­myricetin (25 mg/kg) groups. Neurological deficit scores were evaluated by an examiner blinded to the experimental groups. Brain infarct size was estimated macroscopically using 2,3,5­triphenyltetrazolium chloride staining. The levels of inflammatory factors tumor necrosis factor (TNF)­α, interleukin (IL)­6 and IL­1ß, and oxidative stress index superoxide dismutase (SOD), malondiadehyde (MDA), and the glutathione/glutathione disulfide (GSH/GSSG) ratio were measured by ELISA. The degree of brain cell apoptosis was determined using a terminal deoxynucleotidyl transferase dUTP nick­end labeling assay. Protein expression levels of total or phosphorylated p38 mitogen activated protein kinase (MAPK), nuclear factor (NF)­κB/p65 and protein kinase B (AKT) were determined using a western blotting assay. The neurological deficit score and infarct area induced by pMCAO decreased in a dose­dependent manner following myricetin treatment. Furthermore, myricetin reduced the expression levels of IL­1ß, IL­6, TNF­α, and MDA, and increased GSH/GSSG ratio and SOD activity. A significant decrease in cell apoptosis was observed in response to myricetin. In addition, myricetin significantly increased the level of phosphorylated AKT protein, and decreased the phosphorylation of p38 MAPK and the level of NF­κB/p65. Overall, the results of the present study suggested that myricetin exhibits a therapeutic effect by reducing ischemic cerebral injury, and the protective effect of myricetin may be associated with the p38 MAPK, NF­κB/p65 and AKT signaling pathways.

Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial.

BACKGROUND: Studies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis. METHODS: First, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the association between platelet desialylation and thrombocytopenia in patients with sepsis, severe sepsis, and septic shock. Gender- and age-matched healthy adults were selected as normal controls in analysis of the platelet desialylation levels (study I). Next, we conducted an open-label randomized controlled trial (RCT) in which the patients who had severe sepsis with thrombocytopenia (platelet counts ≤50 × 109/L) were randomly assigned to receive antimicrobial therapy alone (control group) or antimicrobial therapy plus oseltamivir (oseltamivir group) in a 1:1 ratio (study II). The primary outcomes were platelet desialylation level at study entry, overall platelet response rate within 14 days post-randomization, and all-cause mortality within 28 days post-randomization. Secondary outcomes included platelet recovery time, the occurrence of bleeding events, and the amount of platelets transfused within 14 days post-randomization. RESULTS: The platelet desialylation levels increased significantly in the 127 septic patients with thrombocytopenia compared to the 134 patients without thrombocytopenia. A platelet response was achieved in 45 of the 54 patients in the oseltamivir group (83.3%) compared with 34 of the 52 patients in the control group (65.4%; P = 0.045). The median platelet recovery time was 5 days (interquartile range 4-6) in the oseltamivir group compared with 7 days (interquartile range 5-10) in the control group (P = 0.003). The amount of platelets transfused decreased significantly in the oseltamivir group compared to the control group (P = 0.044). There was no difference in the overall 28-day mortality regardless of whether oseltamivir was used. The Sequential Organ Failure Assessment score and platelet recovery time were independent indicators of oseltamivir therapy. The main reason for all of the mortalities was multiple-organ failure. CONCLUSIONS: Thrombocytopenia was associated with increased platelet desialylation in septic patients. The addition of oseltamivir could significantly increase the platelet response rate, shorten platelet recovery time, and reduce platelet transfusion. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-16008542 .

Cardioprotection provided by Echinatin against ischemia/reperfusion in isolated rat hearts.

BACKGROUND: This study evaluated the protective effect of Echinatin against myocardial ischemia/reperfusion (I/R) injury in rats. METHODS: The effect of Echinatin on cardiac function in rats subjected to I/R was demonstrated through improved Langendorff retrograde perfusion technology. Adult Sprague-Dawley rats were randomly divided into five groups, and myocardial infarct size was macroscopically estimated through 2,3,5-triphenyltetrazolium chloride staining. The coronary effluent was analyzed for the release of lactate dehydrogenase (LDH) and creatine kinase (CK) to assess the degree of cardiac injury. The concentrations of malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined along with superoxide dismutase (SOD) activity using ELISA. Finally, cardiomyocyte apoptosis analysis was conducted with POD, an in situ cell death detection kit. RESULTS: Echinatin (0.5 and 2.5 µg/mL) pretreatment enhanced the maximum up/down rate of the left ventricular pressure (±dp/dtmax), improved the heart rate, increased the left ventricular developed pressure (LVDP), enhanced the coronary flow, and reduced the CK and LDH levels in the coronary flow of the treated group compared with the I/R group. Echinatin limited the contents of CK and LDH, improved the LVDP, reduced the contents of MDA, IL-6, and TNF-α, and increased the SOD activity. The infarct size and cell apoptosis in the hearts of the rats in the Echinatin-treated group were smaller and lower, respectively, than those in the hearts of the rats in the I/R control group. CONCLUSION: Echinatin exerts a protective effect against I/R-induced myocardial injury on hearts. This effect may be attributed to the antioxidant and anti-inflammatory activities of this compound.

Protective effect of fasudil hydrochloride against acute renal injury in septicopyemia rats.

OBJECTIVE: To observe the protective effect of fasudil hydrochloride against acute renal injury in septicopyemia rats. METHODS: A total of 60 Wister rats were included in the study and divided into control group (n = 10), model group (n = 25) and treatment group (n = 25). Model group and treatment group received intraperitoneal injection of endotoxin (ET) to establish acute renal injury models while the control group only received daily intraperitoneal injection of normal saline 1 mL. Five rats were taken out of model group and treatment group respectively at 1 h (T1), 6 h (T2), 12 h (T3), 24 h (T4) and 48 h (T5), for intraperitoneal injection of ET 30 mg/kg. Treatment group received intraperitoneal injection of fasudil hydrochloride 30 mg/kg 1 h before injection of ET. For three groups, 5 mL blood samples were collected from postcava for determination of serum creatinine and urea nitrogen levels at different time points. Concentrations of serum tumor necrosis factor α and ET-1 were determined by using ELISA. The renal pathologic changes were observed under the microscope. RESULTS: Serum creatinine levels in both model group and treatment group were significantly higher than control group at T2-T5 (P < 0.05) while the levels in treatment group were significantly lower than control group at T3-T5 (P < 0.05). At T2-T5, blood urea nitrogen levels in model group and treatment group were significantly higher than control group (P < 0.05) while the levels in treatment group were significantly lower than model group at T3-T5 (P < 0.05). Concentrations of serum tumor necrosis factor α in model group and treatment group were significantly higher than control group at T1-T5 (P < 0.05) while the levels in treatment group were significantly lower than model group at T1-T5 (P < 0.05). Serum ET-1 concentrations in model group and treatment group were significantly higher than control group at T1-T5 (P < 0.05) while the levels in treatment group at T1-T4 were significantly lower than model group (P < 0.05). Rats in control group showed no swelling or hyperemia in kidney cells but normal structure and normally arranged renal tubular epithelial cells. Obvious injury was observed in model group at T3 and renal tubular epithelial cells in disorder and at swelling condition, hyperemia and angiectasis in glomerulus, degenerative opacities and vacuolar degeneration, and maximized injury were observed at T4. Injury in renal tissue in treatment group was significantly milder than model group. CONCLUSIONS: Fasudil hydrochloride has the significantly protective effect against acute renal injury in septicopyemia rats.

Luteolin-induced protection of H2O2-induced apoptosis in PC12 cells and the associated pathway.

Increasing evidence has indicated that the generation of reactive oxygen species (ROS) contributes to H2O2­induced nerve injury. This may result in oxidative stress that leads to cell damage or death. Dietary or pharmaceutical augmentation of the endogenous antioxidant defense capacity is a potential means by which to prevent ROS­induced damage. The aim of the current study was to investigate the effect of luteolin on H2O2­induced cell apoptosis in cultured rat pheochromocytoma cells (PC12 cells) and to investigate the role of the phosphatidylinositol­3­kinase (PI3K)/protein kinase B (Akt) pathway on H2O2­induced apoptosis. The results demonstrated that luteolin was able to inhibit the reduction in cell viability induced by H2O2. In addition, luteolin reduced ROS generation and lactate dehydrogenase release in H2O2­treated PC12 cells. The levels of superoxide dismutase and glutathione peroxidase activity were increased following treatment with luteolin, however malondialdehyde levels were observed to be reduced. Additionally, luteolin increased the Bcl­2/Bax ratio and enhanced Akt phosphorylation. However, these alterations were attenuated by pretreatment with an inhibitor of the PI3K/Akt pathway. In conclusion, luteolin inhibited H2O2­induced apoptosis via reducing ROS levels and activating the PI3K/Akt pathway.