Decreased Glutathione Peroxidase Research Articles

METTL3 mediated ferroptosis in chondrocytes and promoted pain in KOA via HMGB1 m6A modification.

Methyltransferase-like 3 (METTL3) plays a role in the development of knee osteoarthritis (KOA). However, the mechanism underlying the role of METTL3 in KOA is unclear. This work investigated the effects of MELLT3 on ferroptosis and pain relief in in vitro and in vivo KOA models. Chondrocytes were treated with 10 ng/mL interleukin-1β (IL-1β) or 5 μM Erastin (ferroptosis inducer). IL-1β or Erastin treatment inhibited cell viability and glutathione levels; increased Fe2+, lipid reactive oxygen species and malondialdehyde production; and decreased glutathione peroxidase 4, ferritin light chain and solute carrier family 7 member 11 levels. The overexpression of METTL3 facilitated the N6-methyladenosine methylation of high mobility group box 1 (HMGB1). HMGB1 overexpression reversed the effect of sh-METTL3 on IL-1β-treated chondrocytes. A KOA rat model was established by the injection of monosodium iodoacetate into the joints and successful model establishment was confirmed by haematoxylin and eosin staining and Safranin O/Fast Green staining. METTL3 depletion alleviated cartilage damage, the inflammatory response, ferroptosis and knee pain in KOA model rats, and these effects were reversed by the addition of HMGB1. In conclusion, METTL3 depletion inhibited ferroptosis and the inflammatory response, and ameliorated cartilage damage and knee pain during KOA progression by regulating HMGB1.

The Impact of Diabetes on Male Silkworm Reproductive Health.

The increasing prevalence of diabetic reproductive complications has prompted the development of innovative animal models. The use of the silkworm Bombyx mori as a model for diabetic reproductive damage shows potential as a valuable research tool. This study employed silkworms as a novel model to investigate diabetic reproductive damage. The silkworms were fed a high-glucose diet containing 10% glucose to induce a diabetic model. Subsequently, the study concentrated on assessing the influence of diabetes on the reproductive system of male silkworms. The results indicate that diabetes resulted in reduced luteinizing hormone (LH) and testosterone (T) levels, as well as elevated triglyceride (TG) levels in male silkworms. Moreover, diabetes mellitus was associated with pathological testicular damage in male silkworms, accompanied by decreased glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels, along with increased malondialdehyde (MDA) levels in the testis. Additionally, diabetes mellitus reduced the expression of siwi1 and siwi2 genes in the testis of male silkworms. Overall, these results support using silkworms as a valuable model for studying diabetic reproductive damage.

Carrageenan-ferrocene-eicosapentaenoic acid composite hydrogel induce ferroptosis and apoptosis for anti-tumor recurrence and metastasis

The immune-suppressive microenvironment of solid tumors is a key factor limiting the effectiveness of immunotherapy, which seriously threatens human life and health. Ferroptosis and apoptosis are key cell-death pathways implicated in cancers, which can synergistically activate tumor immune responses. Here, we developed a multifunctional composite hydrogel (CE-Fc-Gel) based on the self-assembly of poloxamer 407, cystamine-linked ιota-carrageenan (CA)-eicosapentaenoic acid (EPA), and ferrocene (Fc). CE-Fc-Gel improved targeting in tumor microenvironment due to its disulfide bonds. Moreover, CE-Fc-Gel promoted lipid peroxidation, enhanced reactive oxygen species (ROS) production, and decreased glutathione peroxidase 4 (GPX4), inducing ferroptosis by the synergistic effect of Fc and EPA. CE-Fc-Gel induced apoptosis and immunogenic cell death (ICD), thereby promoting dendritic cells (DCs) maturation and T cell infiltration. As a result, CE-Fc-Gel significantly inhibited primary and metastatic tumors in vivo. Our findings provide a novel strategy for enhancing tumor immunotherapy by combining apoptosis, ferroptosis, and ICD.

Boswellia carterii n-hexane extract suppresses breast cancer growth via induction of ferroptosis by downregulated GPX4 and upregulated transferrin

Breast cancer (BC) remains a significant health concern for women globally, prompting the relentless pursuit of novel therapeutic modalities. As a traditional Chinese medicine, Boswellia carterii has been extensively used to treat various cancers, such as BC. However, the anti-BC effect and underlying mechanism of Boswellia carterii remain largely unclear. The aim of this study is to explore the therapeutic effect of Boswellia carterii n-hexane extract (BCHE) against BC as well as its underlying mechanism. The present study showed that BCHE significantly suppressed the viability of human BC cells. Moreover, BCHE exhibited potent anti-BC activity in vivo with no significant toxic effects. Additionally, BCHE induced ferroptosis via increased Transferrin expression and the intracellular accumulation of Fe2+, as well as decreased glutathione peroxidase 4 (GPX4) expression and the upregulation of reactive oxygen species (ROS)-induced lipid peroxidation in BC cells. In vivo experimental results also demonstrated that BCHE effectively induced ferroptosis through GPX4 downregulation and Transferrin upregulation in tumor-bearing mice. Overall, BCHE inhibited the growth of BC cells by inducing ferroptosis mediated by modulating the iron accumulation pathway and the lipid peroxidation pathway. Therefore, BCHE could serve as a potential ferroptosis-targeting drug for treating BC.

Memory enhancing and neuroprotective effects of apomorphine in a rat model of dementia.

Oxidative stress from generation of increased reactive oxygen species or has been reported to play an important role in dementia. Oxidative stress due to free radicals of oxygen or reactive oxygen species could be precipitating factors in the etiology of dementia. Apomorphine has been reported to have neuroprotective effects. To monitor memory enhancing and neuroprotective effects of apomorphine, we determined the antioxidant enzymes activities, lipid peroxidation, acetylcholine esterase (AChE) activity in brain and plasma, following repetitive administration of apomorphine in rat model of dementia. Biogenic amine levels were also monitored in hippocampus. Repeated administration of scopolamine was taken as an animal model of dementia. Decreased glutathione peroxidase, superoxide dismutase and catalase activities were observed in these animal models of dementia. While increased lipid peroxidation was also observed in the brain and plasma samples. The results showed significant effects of apomorphine. The activities of antioxidant enzymes displayed increased activities in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly higher in brain and plasma of apomorphine treated rats. Superoxide dismutase (SOD) was significantly decreased in plasma of scopolamine injected rats; and a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in scopolamine treated rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM). Short-term memory and long-term memory was impaired significantly in scopolamine treated rats, which was prevented by apomorphine. Moreover, a marked decrease in biogenic amines was also found in the brain of scopolamine treated rats and was reverted in apomorphine treated rats. Results showed that scopolamine-treatment induced memory impairment and induced oxidative stress in rats as compared to saline-treated controls. These impairments were significantly restored by apomorphine administration. In conclusion, our data suggests that apomorphine at the dose of 1mg/kg could be a potential therapeutic agent to treat dementia and related disorders.

Effect of vitamin blend supplementation on the oxidative stability and beef quality parameters of Nellore cattle

This study was conducted to investigate the effects of supplementation of B vitamins, fat-soluble vitamins (ADE), and combination of B+ADE on beef quality parameters and antioxidant status. Forty young Nellore bulls were allocated randomly across four treatments: no vitamin supplementation (Control); B vitamins supplementation (B); fat-soluble vitamins supplementation (ADE); and ADE + B supplementation. At the end of a 140-day trial, samples were collected to perform analysis of meat quality parameters and status activity of antioxidant enzymes at 1 h, 24 h, 192 h and 360 h post mortem. Treatments had no significant on pH24h, sarcomere length, meat color (L*, b*, chroma) or fat color (L*, a*, b*) of the longissimus lumborum muscle at 24 h, 192 h and 360 h post mortem between treatments B, ADE or ADE+B in relation to the control treatment. Furthermore, no significant changes were observed in the redox form of myoglobin (OMb, DMb, MMb) 24 h post mortem. However, the ADE and ADE+B treatments resulted in a higher percentage of intramuscular fat in the longissimus lumborum muscle when compared to the control treatment. Greater myofibrillar fragmentation index at 24 h, 192 h and 360 h, higher levels of oxymyoglobin at 192 h and 360 h, lower levels of metmyoglobin at 360 h were detected in the ADE and ADE+B treatments when compared to the control treatment. Furthermore, ADE increased superoxide dismutase (SOD) at 192 h and ferric reducing antioxidant power (FRAP) at 360 h compared to the control treatment, while ADE and ADE+B treatments increased FRAP at 24 h and 192 h, and catalase (CAT) at 192 h Moreover, ADE and ADE+B treatments decreased glutathione peroxidase (GPx) at 24 h and decreased malondialdehyde (MDA) content at 24 h and 360 h when compared to the control treatment. The use of ADE and ADE+B favored the formation of oxymyoglobin, prevented the oxidation of myoglobin, increased the ferric reducing antioxidant power and impaired lipid oxidation at different periods of ageing.

Integration of single-cell RNA sequencing of endothelial cells and proteomics to unravel the role of ICAM1-PTGS2 communication in apical periodontitis: A laboratory investigation.

Endothelial cells (EDs) play a key role in angiogenesis and are associated with granulomatous lesions in patients with chronic apical periodontitis (CAP). This study aimed to investigate the diversity of EDs using single-cell ribonucleic acid sequencing (scRNA-seq) and to evaluate the regulation of intercellular adhesion molecule 1 (ICAM1) on the ferroptosis-related protein, prostaglandin-endoperoxide synthase 2 (PTGS2), in CAP. EDs from the uploaded scRNA-seq data of five CAP samples (GSE181688 and GSE197680) were categorized using distinct marker genes. The interactions between vein EDs (veinEndo) and other cell types were analysed using CellPhoneDB. Differentially expressed proteins in the proteomics of human umbilical vein EDs (HUVECs) and THP-1-derived macrophages infected with Porphyromonas gingivalis were compared with the differentially expressed genes (DEGs) of VeinEndo in scRNA-seq of CAP versus healthy control periodontal tissues. The protein-protein interaction of ICAM1-PTGS2 in macrophages and HUVECs was validated by adding recombinant ICAM1, ICAM1 inhibitor and PTGS2 inhibitor using real-time polymerase chain reaction (PCR), western blotting, and immunofluorescence staining. EDs in patients with CAP were divided into eight subclusters: five vein ED, capillaries, arterials and EC (PLA). There were 29 mutually upregulated DEGs and two mutually downregulated DEGs in vein cells in the scRNA-seq data, as well as differentially expressed proteins in the proteomics of HUVECs. Real-time PCR and immunofluorescence staining showed that ICAM1 and PTGS2 were highly expressed in CAP, infected HUVECs, and macrophages. Recombinant protein ICAM1 may improve PTGS2 expression, reactive oxygen species (ROS), and Fe2+ levels and decrease glutathione peroxidase 4 (GPX4) and SLC7A11 protein levels. ICAM1 inhibitor may inverse the above changes. scRNA-seq revealed the diversity of EDs in CAP and identified the possible regulation of ICAM1 by the ferroptosis-related protein, PTGS2, in infected HUVECs and macrophages, thus providing a basis for therapeutic approaches that target the inflammatory microenvironment of CAP.

Phenylhydrazine-induced haemolysis disturbed iron pool homeostasis and activated expression pattern of FPN1 in the intestine of grass carp (Ctenopharyngodon idella)

As the only molecule that can transport iron to the cell exterior, the ferroportin 1 (FPN1) plays a key role in regulating the homeostasis of the iron ion. However, the function of FPN1 in teleost is remains unclear. In this study, the fpn1 gene was cloned from grass carp and its characteristics were studied. The results showed that grass carp Fpn1 protein contains eight transmembrane domains, which are similar to the amino acid sequences of different species. The tissue distribution of fpn1 was investigated by quantitative real-time PCR (qRT-PCR), which showed that the expression of fpn1 was the highest in the liver, followed by the spleen and muscle. Secondly, the haemolysis model of grass carp was established by the injection of phenylhydrazine (PHZ), and the effect of Fpn1 on the intestine in during haemolysis was explored. The determination data revealed that the PHZ-induced haemolysis increased the number of goblet cells in intestinal, as well as malondialdehyde (Mda), decreased glutathione peroxidase 4 (Gpx4) content in foregut. The result of tissue immunofluorescence assay showed that the PHZ-induced haemolysis modulated the expression of iron metabolism related genes, including Fpn1 and Tfr1 (transferrin receptor 1) in the intestine. Further determination data suggested that the iron deposition and apoptosis were higher in PHZ treatment group than that of the group. Taken together, the PHZ-induced haemolysis destroyed the iron homeostasis in intestinal and caused oxidative damage, the data of this study lays a foundation for the study of the mechanisms of intestinal iron homeostasis and provides a theoretical basis for understanding intestinal healthy.

Ochratoxin A induces hepatic and renal toxicity in mice through increased oxidative stress, mitochondrial damage, and multiple cell death mechanisms.

Ochratoxin A (OTA) is a widespread food toxin produced by Aspergillus ochraceus and other molds. In this study, we developed and established acute OTA toxicity conditions in mice, which received daily oral doses of OTA between 0.5 up to 8mg/kg body weight up to 7days and were subjected to histological and biochemical analysis to characterize renal and hepatic damage. Oral administration of OTA for 7days resulted in loss of body weight in a dose-dependent manner and increased the levels of serum biomarkers of hepatic and renal damage. The kidney was more sensitive to OTA-induced damage than the liver. In addition to necrosis, OTA induced hepatic and renal apoptosis in dose- and time-dependent manners. Especially, a high dose of OTA (8mg/kg body weight) administered for 7days led to necroptosis in both liver and kidney tissues. OTA dose-dependently increased the oxidative stress levels, including lipid peroxidation, in the liver and kidneys. OTA disrupted mitochondrial dynamics and structure in hepatic and renal cells, leading to the dysregulation of mitochondrial homeostasis. OTA increased transferrin receptor 1 and decreased glutathione peroxidase 4 levels in a dose- and time-dependent manner. These results suggest the induction of ferroptosis. Collectively, this study highlighted the characteristics of acute OTA-induced hepatic and renal toxicity in mice in terms of oxidative stress, mitochondrial damage, and multiple cell death mechanisms, including necroptosis and ferroptosis.

Protective effect of thymoquinone nanoemulsion in reducing the cardiotoxic effect of 5-fluorouracil in rats.

5-Fluorouracil (5-FU), which is one of the most widely used chemotherapy drugs, has various side effects on the heart. Thymoquinone (TMQ), the main bioactive component of Nigella sativa, has antioxidant and protective effects against toxicity. In this study, we investigated the protective effect of thymoquinone against cardiotoxicity caused by 5-FU in vitro and in vivo models. H9C2 cells were exposed to 5-FU and TMQ, and cell viability was evaluated in their presence. Also, 25 male Wistar rats were divided into five control groups, 5-FU, 2.5, and 5 mg TMQ in nanoemulsion form (NTMQ) + 5-FU and 5 mg NTMQ. Cardiotoxicity was assessed through electrocardiography, cardiac enzymes, oxidative stress markers, and histopathology. 5-FU induced cytotoxicity in H9c2 cells, which improved dose-dependently with NTMQ cotreatment. 5-FU caused body weight loss, ECG changes (increased ST segment, prolonged QRS, and QTc), increased cardiac enzymes (aspartate aminotransferase [AST], creatine kinase-myocardial band [CK-MB], and lactate dehydrogenase [LDH]), oxidative stress (increased malondialdehyde, myeloperoxidase, nitric acid; decreased glutathione peroxidase enzyme activity), and histological damage such as necrosis, hyperemia, and tissue hyalinization in rats. NTMQ ameliorated these 5-FU-induced effects. Higher NTMQ dose showed greater protective effects. Thus, the results of our study indicate that NTMQ protects against 5-FU cardiotoxicity likely through antioxidant mechanisms. TMQ warrants further research as an adjuvant to alleviate 5-FU chemotherapy side effects.

Tetramethylpyrazine attenuates renal tubular epithelial cell ferroptosis in contrast-induced nephropathy by inhibiting transferrin receptor and intracellular reactive oxygen species.

Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury (AKI). Recently, ferroptosis was reported to be crucial for AKI pathogenesis. Our previous studies indicated antioxidant tetramethylpyrazine (TMP) prevent CIN in vivo. However, whether ferroptosis is involved in TMP nephroprotective mechanism against CIN is unclear. In the present study, we investigated the role of renal tubular epithelial cell ferroptosis in TMP reno-protective effect against CIN and the molecular mechanisms by which TMP regulates ferroptosis. Classical contrast-medium, Iohexol, was used to construct CIN models in rats and HK-2 cells. Results showed that tubular cell injury was accompanied by ferroptosis both in vivo and in vitro, including the typical features of ferroptosis, Fe2+ accumulation, lipid peroxidation and decreased glutathione peroxidase 4 (GPX4). Ferroptosis inhibition by classic inhibitors Fer-1 and DFO promoted cell viability and reduced intracellular ROS production. Additionally, TMP significantly inhibited renal dysfunction, reduced AKI biomarkers, prevented ROS production, inhibited renal Fe2+ accumulation and increased GPX4 expression. Expressions of various proteins associated with iron ion metabolism, including transferrin receptor (TFRC), divalent metal transporter 1, iron-responsive element binding protein 2, ferritin heavy chain 1, ferroportin 1, and heat shock factor binding protein 1, were examined using mechanistic analyses. Among these, TFRC changes were the most significant after TMP pretreatment. Results of siRNA knockdown and plasmid overexpression of TFRC indicated that TFRC is essential for TMP to alleviate ferroptosis and reduce LDH release, Fe2+ accumulation and intracellular ROS. Our findings provide crucial insights about the potential of TMP in treating AKI associated with ferroptosis.

Sodium aescinate induces renal toxicity by promoting Nrf2/GPX4-mediated ferroptosis

Sodium aescinate (SA) is extracted from Aesculus wilsonii Rehd seeds and was first marketed as a medicament in German. With the wide application of SA in clinical practice, reports of adverse drug reactions and adverse events have gradually increased, including renal impairment. However, the pathogenic mechanisms of SA have not yet been fully elucidated. The toxic effects and underlying mechanisms of SA were explored in this study. Our data showed that SA significantly elevated the levels of blood urea nitrogen (BUN), serum creatinine (Scr) and Kidney injury molecule 1 (Kim-1), accompanied by pathologically significant changes in renal tissue. SA induced NRK-52E cell death and disrupted the integrity of the cell membrane. Moreover, SA caused significant reductions in FTH, Nrf2, xCT, GPX4, and FSP1 levels, but increased TFR1 and ACSL4 levels. SA decreased glutathione peroxidase (GPx), glutathione (GSH) and cysteine (Cys) levels, but improved Fe2+, malondialdehyde (MDA), reactive oxygen species (ROS) and lipid peroxidation levels, ultimately leading to the induction of ferroptosis. Importantly, inhibition of ferroptosis or activation of the Nrf2/GPX4 pathway prevented SA-induced nephrotoxicity. These findings indicated that SA induced oxidative damage and ferroptosis-mediated kidney injury by suppressing the Nrf2/GPX4 axis activity.

Effect and Mechanism of LIN28 on Ferroptosis in Mg2+-free Rat Hippocampal Neuron Model of Epilepsy.

Studies have demonstrated that LIN28 is expressed in the CNS and may exert protective effects on neurons. However, it remains unknown whether LIN28 regulates ferroptosis in the context of epilepsy. In this study, we established an epilepsy model by culturing hippocampal neurons from rats in a magnesium-free (Mg2+-free) medium. In Mg2+-depleted conditions, hippocampal neurons exhibited reduced LIN28 expression, heightened miR-142-5p expression, decreased glutathione peroxidase (GPX) activity and expression, elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), resulting in a significant decline in cell viability and an increase in ferroptosis. Conversely, overexpression of LIN28 reversed these trends in the mentioned indices. Altogether, this study reveals that LIN28 may exert neuroprotective effects by inhibiting the miR-142-5p expression and suppressing ferroptosis in hippocampal neurons induced by Mg2+-free via increasing GPX4 expression.

Ferroptosis and metabolic syndrome and complications: association, mechanism, and translational applications.

Metabolic syndrome is a medical condition characterized by several metabolic disorders in the body. Long-term metabolic disorders raise the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Therefore, it is essential to actively explore the aetiology of metabolic syndrome (MetS) and its comorbidities to provide effective treatment options. Ferroptosis is a new form of cell death that is characterized by iron overload, lipid peroxide accumulation, and decreased glutathione peroxidase 4(GPX4) activity, and it involves the pathological processes of a variety of diseases. Lipid deposition caused by lipid diseases and iron overload is significant in metabolic syndrome, providing the theoretical conditions for developing ferroptosis. Recent studies have found that the major molecules of ferroptosis are linked to common metabolic syndrome consequences, such as T2DM and atherosclerosis. In this review, we first discussed the mechanics of ferroptosis, the regulatory function of inducers and inhibitors of ferroptosis, and the significance of iron loading in MetS. Next, we summarized the role of ferroptosis in the pathogenesis of MetS, such as obesity, type 2 diabetes, and atherosclerosis. Finally, we discussed relevant ferroptosis-targeted therapies and raised some crucial issues of concern to provide directions for future Mets-related treatments and research.

Radioprotective effects of linden honey in rat peripheral blood

Radiotherapy affects not only malignant, but also a healthy tissue adjacent to tumor by increasing reactive oxygen species generation, with consequent damage to biomolecules, such as the oxidation of membrane lipids, known as lipid peroxidation. The end product of lipid peroxidation is malondialdehyde. Radioprotectors are compounds that could significantly protect normal cells from radiation, without changing the tumor cell radiosensitivity. Synthetic radioprotectors usually have side effects and are toxic. Natural radioprotectors exert protection without adverse effects. In this study, we examined the radioprotective ability of linden honey in rat blood, by detecting alterations in the activities of antioxidant enzymes catalase and glutathione peroxidase and malondialdehyde concentration after the exposure to a therapeutic dose of gamma rays. Sixteen rats were randomly divided into Control and Honey groups. Honey group received honey (1.5 mL(kgd-1)) orally for four weeks, while at the same time Control group were given distilled water. After four weeks, blood was sampled from all animals. Samples were halved, and one series of samples were gamma irradiated (2 Gy). Radiation induced decreased glutathione peroxidase activity and increased malondialdehyde level, while honey treatment attenuated those alterations, keeping glutathione peroxidase and malondialdehyde at physiological levels. These findings confirm radioprotective properties of linden honey.

Autophagy of OTUD5 destabilizes GPX4 to confer ferroptosis-dependent kidney injury

Ferroptosis is an iron-dependent programmed cell death associated with severe kidney diseases, linked to decreased glutathione peroxidase 4 (GPX4). However, the spatial distribution of renal GPX4-mediated ferroptosis and the molecular events causing GPX4 reduction during ischemia-reperfusion (I/R) remain largely unknown. Using spatial transcriptomics, we identify that GPX4 is situated at the interface of the inner cortex and outer medulla, a hyperactive ferroptosis site post-I/R injury. We further discover OTU deubiquitinase 5 (OTUD5) as a GPX4-binding protein that confers ferroptosis resistance by stabilizing GPX4. During I/R, ferroptosis is induced by mTORC1-mediated autophagy, causing OTUD5 degradation and subsequent GPX4 decay. Functionally, OTUD5 deletion intensifies renal tubular cell ferroptosis and exacerbates acute kidney injury, while AAV-mediated OTUD5 delivery mitigates ferroptosis and promotes renal function recovery from I/R injury. Overall, this study highlights a new autophagy-dependent ferroptosis module: hypoxia/ischemia-induced OTUD5 autophagy triggers GPX4 degradation, offering a potential therapeutic avenue for I/R-related kidney diseases.

Serum glutathione peroxidase 4 as a novel biomarker for nontraumatic osteonecrosis of the femoral head: A retrospective case-control study.

There are no serum biomarkers available in nontraumatic osteonecrosis of the femoral head in clinical practice. This study aimed to evaluate the clinical value of serum glutathione peroxidase 4 in nontraumatic osteonecrosis of the femoral head. This retrospective study analyzed serum glutathione peroxidase 4 levels and clinical data of 80 patients with nontraumatic osteonecrosis of the femoral head and 80 healthy controls between August 2021 and May 2022. Serum glutathione peroxidase 4 levels were analyzed using an enzyme-linked immunosorbent assay. The Association Research Circulation Osseous classification system determined disease progression. Clinical severity was assessed by Harris hip score and visual analogue scale. Correlations between serum glutathione peroxidase 4 and disease progression as well as clinical severity were evaluated statistically. The diagnostic accuracy of serum glutathione peroxidase 4 in nontraumatic osteonecrosis of the femoral head was determined using receiver operating characteristic analysis. The baseline characteristics of participants between 2 groups were comparable. Patients with nontraumatic osteonecrosis of the femoral head displayed a decreased glutathione peroxidase 4 level compared with healthy controls (11.87 ± 2.76 μU/mL vs 16.54 ± 4.89 μU/mL, P < .01). The levels of glutathione peroxidase 4 were inversely correlated with Association Research Circulation Osseous stage (P < .01) and visual analogue scale scores (P < .01), and positively correlated with Harris score (P < .01). Receiver operating characteristic analyses showed that area under curves of glutathione peroxidase 4 was 0.808 (95% CI 0.721-0.858) and 0.847 (95% CI 0.743-0.951) with regard to diagnosis and collapse prediction in nontraumatic osteonecrosis of the femoral head, respectively. Serum glutathione peroxidase 4 could serve as a novel biomarker for diagnosing nontraumatic osteonecrosis of the femoral head and predicting collapse of the femoral head.

Valproic Acid Treatment Improves Organ Function, Survival Rate, and Lipid Peroxidation in Fatally Scalded Rats

Background After hypovolemic shock caused by severe burns, lipid peroxidation is an important factor in tissue edema and multiorgan dysfunction syndrome (MODS). Many studies have shown that valproic acid (VPA) inhibits lipid peroxidation and reduces tissue and organ injury. Objectives This study investigated whether the VPA treatment of scalded rats reduced tissue edema by inhibiting lipid peroxidation, thereby improving organ function and survival rate. Materials and Methods A total of 60 male Sprague-Dawley rats (weighing: 280–300 g) with a 50% total body surface area (TBSA) full-thickness dermal burn were randomly assigned to the following 3 groups (with 20 rats per group): (I) the no infusion resuscitation (NR) group; (II) the sodium lactate Ringer’s solution (LR) group; and (III) the sodium valproate Ringer’s solution (VR) group. After scalding, the following hemodynamic parameters were measured: Copper2+-Zinc2+-superoxide dismutase (Cu2+-Zn2+-SOD) activity, thiobarbituric acid reactive substances (TBARSs), oxidized glutathione (GSSG), reduced glutathione (GSH), and antioxidant enzyme activities. Organ function parameters and water content were also measured. Another 60 male Sprague-Dawley rats were used to observe the 24-h survival rate of the rats using the same scald model and fluid resuscitation. Results VPA significantly increased the mean arterial pressure (MAP) and cardiac output (CO), and significantly decreased the pulmonary vascular permeability index (PVPI) and extravascular lung water index (ELWI). VPA also increased plasma Cu2+-Zn2+-SOD activity and decreased the plasma TBARS level. VPA reduced the TBARS level and GSSG in various tissues and increased the concentration of GSH. VPA decreased glutathione peroxidase (GPx) and catalase (CAT) activity, but significantly increased glutathione reductase (GR) activity in various tissues. VPA significantly improved organ functions and decreased water content. VPA significantly improved the survival rate, and the 24-h survival rate of the VR group was double that of the LR group. Conclusion Resuscitation with VPA reduced tissue edema, protected visceral functions, and improved the survival rate of rats with severe burn shock (BS) by alleviating lipid peroxidation.

Gut microbiota contribution to selenium deficiency-induced gut-liver inflammation.

There is limited knowledge about the factors that drive gut-liver axis changes after selenium (Se) deficiency-induced gut or liver injuries. Thus, we tested Se deficiency in mice to determine its effects on intestinal bacterial balance and whether it induced liver injury. Serum Se concentration, lipopolysaccharide (LPS) level, and liver injury biomarkers were tested using a biochemical method, while pathological changes in the liver and jejunum were observed via hematoxylin and eosin stain, and a fluorescence spectrophotometer was used to evaluate intestinal permeability. Tight junction (TJ)-related and toll-like receptor (TLR) signaling-related pathway genes and proteins were tested using quantitative polymerase chain reaction, western blotting, immunohistochemistry, and 16S ribosomal ribonucleic acid gene-targeted sequencing of jejunum microorganisms. Se deficiency significantly decreased glutathione peroxidase activity and disrupted the intestinal flora, with the most significant effect being a decrease in Lactobacillus reuteri. The expression of TJ-related genes and proteins decreased significantly with increased treatment time, whereas supplementation with Se, fecal microbiota transplantation, or L. reuteri reversed these decreases. Signs of liver injury and LPS content were significantly increased after intestinal flora imbalance or jejunum injury, and the levels of TLR signaling-related genes were significantly increased. The results indicated that Se deficiency disrupted the microbiota balance, decreased the expression of intestinal TJ factors, and increased intestinal permeability. By contrast, LPS increased due to a bacterial imbalance, which may induce inflammatory liver injury via the TLR4 signaling pathway.

Chronic Thermal Acclimation Effects on Critical Thermal Maxima (CTmax) and Oxidative Stress Differences in White Epaxial Muscle between Surface and Cave Morphotypes of the Mexican Cavefish (Astyanax mexicanus).

AbstractIn the face of increasing environmental temperatures, operative differences between mitochondrial function and whole-animal phenotypic response to the environment are underrepresented in research, especially in subtemperate ectothermic vertebrates. A novel approach to exploring this connection is to examine model species that are genetically similar but that have different whole-animal phenotypes, each of which inhabits different environments. The blind Mexican cavefish (Astyanax mexicanus) has the following two morphotypes: a surface form found in aboveground rivers and an obligate cave-dwelling form. Each morphotype inhabits vastly different thermal and oxygen environments. Whole-animal and mitochondrial responses to thermal acclimation and oxidative stress, with respect to increasing temperatures, have not been previously determined in either morphotype of this species. Here, we chronically acclimated both morphotypes to three temperatures (14°C, 25°C, and 31°C) to establish potential for acclimation and critical thermal maxima (CTmax) for each morphotype of this species. After measuring CTmax in six cohorts, we additionally measured enzymatic antioxidant capacity (catalase, superoxide dismutase, and glutathione peroxidase activities), peroxyl scavenging capacity, and lipid peroxidation damage in white epaxial muscle for each individual. We found a significant effect of acclimation temperature on CTmax (, ) but no effect of morphotype on CTmax (, ). Additionally, we found that morphotype had a significant effect on glutathione peroxidase activity, with the surface morphotype having increased glutathione peroxidase activity compared with the cave morphotype (, ). No other oxidative stress variable demonstrated significant differences. Increases in CTmax with chronic thermal acclimation to higher temperatures suggests that there is some degree of phenotypic plasticity in this species that nominally occupies thermally stable environments. The decreased glutathione peroxidase activity in the cave morphotype may be related to decreased environmental oxygen concentration and decreased metabolic rate in this environmentally constrained morphotype compared to in its surface-living counterparts.