Role and prospect of ferroptosis in ischemia-reperfusion injury during organ transplantation / 器官移植

Ferroptosis is a newly-emerged pattern of programmed cell death discovered in recent years, which is defined as iron-dependent programmed necrosis mediated by lipid peroxidation damage. As a conservative procedure, ferroptosis plays a vital role in the development and diseases of multiple organisms including plants and animals. Since ferroptosis was first reported in 2012, growing interests have been diverted to the process of ferroptosis and its role in disease treatment. Ischemia-reperfusion injury is a common pathological process during organ transplantation, and ferroptosis is considered as one of the main patterns inducing ischemia-reperfusion injury. Consequently, the definition, regulatory mechanism and the mechanisms of ferroptosis in ischemia-reperfusion injury after kidney, liver, heart and lung transplantations were reviewed, aiming to provide theoretical basis for the prevention and treatment of ischemia-reperfusion injury in organ transplantation.

Zooming in and out of ferroptosis in human disease / 医学前沿

Ferroptosis is defined as an iron-dependent regulated form of cell death driven by lipid peroxidation. In the past decade, it has been implicated in the pathogenesis of various diseases that together involve almost every organ of the body, including various cancers, neurodegenerative diseases, cardiovascular diseases, lung diseases, liver diseases, kidney diseases, endocrine metabolic diseases, iron-overload-related diseases, orthopedic diseases and autoimmune diseases. Understanding the underlying molecular mechanisms of ferroptosis and its regulatory pathways could provide additional strategies for the management of these disease conditions. Indeed, there are an expanding number of studies suggesting that ferroptosis serves as a bona-fide target for the prevention and treatment of these diseases in relevant pre-clinical models. In this review, we summarize the progress in the research into ferroptosis and its regulatory mechanisms in human disease, while providing evidence in support of ferroptosis as a target for the treatment of these diseases. We also discuss our perspectives on the future directions in the targeting of ferroptosis in human disease.

Novel perspective in transplantation therapy of mesenchymal stem cells: targeting the ferroptosis pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.

Role of Ferroptosis in Cardiovascular Diseases and Chinese Medicine Treatment Based on Iron Homeostasis： A Review / 中国实验方剂学杂志

Cardiovascular diseases are a class of circulatory system diseases involving the heart and vessels， including arrhythmia， hypertension， coronary heart disease， myocardial infarction， heart failure and so on. Due to the complicated pathogenesis， diverse disease types， and difficult treatment， cardiovascular diseases pose serious threatens to the human health. Therefore， it is urgent to develop effective therapies. Ferroptosis， a new type of cell death different from autophagy and apoptosis， is iron-dependent and accompanied by lipid peroxide accumulation. The mechanism of ferroptosis is complex. Recent studies have shown that iron homeostasis plays a role in the occurrence of ferroptosis， which may be induced by iron intake， utilization， and output and iron-related protein synthesis. In addition， iron homeostasis and ferroptosis have been confirmed to be involved in the pathological process of cardiovascular diseases， so regulating iron homeostasis and ferroptosis in cardiomyocytes may be a focus of the future research on cardiovascular diseases. Traditional Chinese medicine （TCM） provides a unique treatment method， and the unique syndrome differentiation system and treatment methods have been widely used in the clinical diagnosis， prevention， and treatment of cardiovascular diseases. Studies have demonstrated that TCM compound prescriptions and the active components in Chinese medicinal materials can regulate iron homeostasis and ferroptosis to protect cardiomyocytes. This paper introduces the mechanism of iron homeostasis in regulating ferroptosis and summarizes the effects of iron homeostasis-mediated ferroptosis on cardiovascular diseases. Furthermore， the research progress of TCM in regulating iron homeostasis-mediated ferroptosis in cardiovascular diseases is reviewed to provide new ideas for TCM prevention and treatment of cardiovascular diseases.

Research advances in ferroptosis in the pathogenesis and treatment of nonalcoholic fatty liver disease / 临床肝胆病杂志

Ferroptosis is a pattern of non-apoptotic cell death characterized by iron dependence and lipid peroxidation. Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease with fat infiltration as its main pathological feature, and it is closely associated with insulin resistance and genetic susceptibility. The mechanism of transition from hepatic steatosis alone to steatohepatitis remains unclear, and studies have shown that ferroptosis in hepatocytes may be the trigger for the inflammatory initiation of steatohepatitis. This article reviews the role of abnormal iron metabolism and lipid peroxidation in promoting the development and progression of NAFLD and summarizes the application prospect of ferroptosis-related inhibitors in the treatment of NAFLD.

Research advances in the function of ferroptosis in ocular disease / 国际眼科杂志(Guoji Yanke Zazhi)

Ferroptosis is a novel form of cell death that has been discovered in recent years and differs markedly from previously known cell death. The mechanism of ferroptosis is the inactivation of glutathione peroxidase(GPX)and the accumulation of lethal intracellular lipid peroxides that occur on the basis of cellular iron overload. Changes such as cell membrane rupture, mitochondrial crest reduction, and outer mitochondrial membrane shrinkage rupture can be observed under electron microscopy. Current studies have found that many diseases in ophthalmology involve ferroptosis-related processes such as iron overload, the imbalance of redox homeostasis, the inactivation of GPX, and accumulation of lethal levels of lipid hydroperoxides, which identified the important role of ferroptosis in ocular disease. This review focuses on the mechanism of ferroptosis and its role in corneal injury, cataract, glaucoma, age-related macular degeneration and diabetic retinopathy, which helps to sort out the pathological mechanisms of common ocular diseases and provide new ideas for the prevention and treatment of ocular diseases.

Improvement effect and mechanism of matrine on experimental autoimmune encephalomyelitis mice / 中国药房

OBJECTIVE To investigate whether matrine exerts improvement effect on experimental autoimmune encephalomyelitis （EAE） mice by regulating ferroptosis pathway. METHODS Totally 30 female C57BL/6 mice were randomly assigned into normal group， model group and matrine group， with 10 mice in each group. Model group and matrine group were given antigen emulsion containing inactivated Mycobacterium tuberculosis and MOG35-55 to induce EAE model. Matrine group was injected with Matrine injection （50 mg/kg） intraperitoneally since the 7th day after immunization； normal group and model group were given constant volume of normal saline intraperitoneally， once a day， since 18th day after immunization. The neurofunctional score of mice was recorded， and hematoxylin and eosin staining and Luxol fast blue staining were used to observe inflammatory cell infiltration and demyelination in spinal cord tissue. The quantitative reverse transcription PCR and Western blot assay were performed to determine the mRNA expressions of transferrin receptor 1 （TFR1）， nuclear receptor coactivator 4 （NCOA4） and hephaestin （Heph）， and the protein expressions of system Xc－ （xCT） and glutathione peroxidase 4 （GPx4）. RESULTS Compared with normal group， accumulative neurofunctional score was significantly increased in model group （P＜0.01）； inflammatory cell infiltration and demyelination were obvious in spinal cord tissue， and related scores were increased significantly （P＜0.01）. The mRNA expressions of TFR1 and NCOA4 in myelin tissue were up-regulated significantly， while the mRNA expression of Heph and the protein expressions of xCT and GPx4 were down-regulated significantly （P＜0.05 or P＜0.01）. Compared with model group， above indexes of matrine group were all improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Matrine can improve EAE mice， the mechanism of which may be associated with regulating iron metabolism pathway and xCT/GPx4 pathway in ferroptosis.

Research progress on iron nutritional status of plateletpheresis donors / 中国输血杂志

Apheresis platelets are extensively utilized in clinical practice due to high purity and minimal side effects. These platelets are primarily obtained from regular blood donors. However, there is no consensus on whether plateletpheresis leads to iron deficiency among blood donors. In recent years, increasing attention has been given to the impact of plateletpheresis on the iron nutritional status of these donors. Numerous studies have indicated a prevalence of iron deficiency among plateletpheresis donors. The process of plateletpheresis involves the loss of red blood cells, which can accumulate over time and disrupt iron metabolism, ultimately resulting in iron deficiency anemia. This condition not only affects the physical well-being of the donors but also leads to a decline in their willingness to donate blood. Blood collection and supply institutions should enhance their focus on the iron nutritional status of plateletpheresis donors and implement various measures, such as intensifying health education regarding the significance of iron supplementation, implementing programs for testing iron deficiency, considering the provision of iron supplements and extending blood donation intervals. It is crucial to prevent iron deficiency in plateletpheresis donors. These institutions should explore calculation models that can predict personalized blood donation intervals and iron supplementation strategies, and seek a balanced approach that is optimal for maintaining adequate collections while safeguarding donor health. The article comprehensively reviews literature at home and abroad on the etiology and hazards of iron deficiency in plateletpheresis donors, as well as detection methods and response measures. It serves as a foundation for developing scientific and reasonable care measures for blood donation, while also achieving personalized and scientific management and recruitment strategies for blood donors.

Analysis of hematological parameters in male plateletpheresis donors / 中国输血杂志

【Objective】 To investigate the variation of hematological parameters in male plateletpheresis donors. 【Methods】 A total of 194 male plateletpheresis donors from Fujian Blood Center were divided into two groups according to the frequency of blood donation: Group 1 (n=107), with the number of plateletpheresis donation less than or equal to 12 per year; Group 2 (n=87), with the number of plateletpheresis donation more than 12 per year. Serum ferritin (SF) and related iron metabolism indexes, red blood cell count (RBC), hemoglobin (Hb), hematocrit(Hct), platelet count (Plt) and other blood routine indexes, as well as percentage of reticulocyte counts (RET%), immature reticulocyte fraction(IRF) and other reticulocyte indexes were measured before blood donation and analyzed by statistical methods. 【Results】 Compared with Group 2, the RBC, Hb, Hct, SF in Group 1 were significantly higher, while Plt, RET%and IRF were significantly lower(P<0.05), and the probability of ferritin decrease in Group 1 was lower, with significant difference(P<0.05). 【Conclusion】 As the number of donation increased, male plateletpheresis donors were prone to iron deficiency, and the bone marrow hematopoiesis were obviously enhanced. We should be more concerned about male plateletpheresis donors who donated more than 12 times per year, further more, SF monitoring should be conducted and the blood donation interval should be appropriately extended.

Transcranial sonography image characteristics of substantia nigra in different Parkinson′s disease subtypes and their correlation with iron metabolism / 中华超声影像学杂志

Objective:To explore the pathological mechanism of SN hyperechogenicity by investigating the characteristics of substantia nigra (SN) hyperechogenicity on transcranial sonography (TCS) and serum iron metabolism parameters in the postural instability gait difficulty and tremor dominant subtypes of Parkinson′s disease (PD), and the correlation between them.Methods:A total of 155 PD patients recruited in Parkinson′s Disease Specialty in the Second Affiliated Hospital of Soochow University from January 2019 to December 2021 were divided into postural instability gait difficulty group( n=95) and tremor dominant group( n=60). Meanwhile, 49 healthy gender- and age-matched healthy individuals who sought for physical examination during the same period were included as the control group. All subjects underwent TCS and blood test, and the echo of SN between the postural instability gait difficulty group and tremor dominant group, serum iron metabolism parameters among the three groups were compared. The postural instability gait difficulty group and tremor dominant group were subdivided into with SN hyperechogenicity (SN+ )subgroup and without SN hyperechogenicity (SN-) subgroup respectively according to TCS results, and the differences in serum iron metabolism parameters between the subgroups were further compared. The association between SN hyperechogenicity and serum iron metabolism parameters of the postural instability gait difficulty group and tremor dominant group were further analyzed. Results:The total area of bilateral SN+ , the area of SN+ on the larger side, and the ratio of the total area of SN+ to the midbrain area (S/M) in postural instability gait difficulty group were larger than those in tremor dominant group (all P<0.001). The value of serum ceruloplasmin and transferrin in both postural instability gait difficulty group and tremor dominant group were lower than those in control group (all P<0.001), and compared with tremor dominant group and control group, the postural instability gait difficulty group had lower serum ferritin(all P<0.01). In both postural instability gait difficulty group and tremor dominant group, serum ceruloplasmin in SN+ subgroup was lower than that in SN-subgroup ( P=0.001, 0.032). Moreover, there was a negative correlation between serum transferrin and the area of SN hyperechogenicity in two subgroups(postural instability gait difficulty group: rs=-0.454, P<0.001; tremor dominant group: rs=-0.494, P<0.001). Conclusions:Compared with the tremor dominant patients, the postural instability gait difficulty patients have larger area of SN hyperechogenicity and lower serum ferritin level. The area of SN hyperechogenicity is significantly negatively correlated with serum transferrin level, indicating that the production of this imaging characteristics is related to iron metabolism.

Effects of continuous renal replacement therapy on inflammation-related anemia, iron metabolism and prognosis in sepsis patients with acute kidney injury / 世界急诊医学杂志（英文）

@#BACKGROUND: This study aims to evaluate the effect of continuous renal replacement therapy (CRRT) on inflammation-related anemia, iron metabolism, and the prognosis in sepsis patients with acute kidney injury (AKI). METHODS: Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups. The clinical and laboratory data on days 1, 3 and 7 after intensive care unit (ICU) admission were collected. The serum interleukin (IL)-6, hepcidin, erythropoietin, ferritin, and soluble transferrin receptor (sTfR) were determined by enzyme-linked immunosorbent assay. The Sequential Organ Failure Assessment (SOFA) score and 28-day mortality were recorded. Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test (categorical variables), and Mann-Whitney U-test or t-test (continuous variables). RESULTS: The hemoglobin and serum erythropoietin levels did not significantly differ between the CRRT and control groups though gradually decreased within the first week of ICU admission. On days 3 and 7, the serum IL-6, hepcidin, ferritin, and red blood cell distribution width significantly decreased in the CRRT group compared to the control group (all P<0.05). On day 7, the serum iron was significantly elevated in the CRRT group compared to the control group (P<0.05). However, the serum sTfR did not significantly differ between the groups over time. In addition, the SOFA scores were significantly lower in the CRRT group compared to the control group on day 7. The 28-day mortality did not significantly differ between the control and CRRT groups (38.0% vs. 28.2%, P=0.332). CONCLUSION: CRRT might have beneficial effects on the improvement in inflammation-related iron metabolism and disease severity during the first week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.

HFE hemochromatosis: an overview about therapeutic recommendations

Abstract Hemochromatosis is currently characterized by the iron overload caused by hepcidin deficiency. Large advances in the knowledge on the hemochromatosis pathophysiology have occurred due to a better understanding of the protein of the iron metabolism, the genetic basis of hemochromatosis and of other iron overload diseases or conditions which can lead to this phenotype. In the present review, the main aims are to show updates on hemochromatosis and to report a practical set of therapeutic recommendations for the human factors engineering protein (HFE) hemochromatosis for the p.Cys282Tyr (C282Y/C282Y) homozygous genotype, elaborated by the Haemochromatosis International Taskforce.

The strategy change of targeting iron homeostasis for leukemia therapy: from iron chelation to iron overload as a therapeutic strategy to induce ferroptosis / 白血病·淋巴瘤

Iron, an indispensable element for life, is involved in all kinds of vital physiological activities. Due to its potential toxicity, the body has a strict regulation mechanism of iron metabolism to maintain the "iron homeostasis". Dysregulation of iron metabolism and subsequent accumulation of excess iron are closely associated with the development and progression of leukemia. Specifically, due to the pro-oxidative nature of iron and its damaging effects on DNA, excess iron promotes the progression of leukemia; on the other hand, leukemia cells need to obtain more iron than normal cells to maintain rapid growth and proliferation, which is known as "iron addiction". Iron chelators can remove iron in leukemia cells and induce differentiation and apoptosis of leukemia cells. However, "iron addiction" makes leukemia cells more susceptible to iron overload, and is more sensitive to a new form of iron-catalyzed cell death which was named ferroptosis. According to the different needs of leukemia cells and normal cells for iron, the method of selectively killing leukemia cells through iron overload may become a new strategy for leukemia treatment. This paper reviews the strategy of targeting iron homeostasis for leukemia therapy.

Effect of Toxoplasma gondii Chinese 1 genotype infections on brain iron metabolism in mice / 中国血吸虫病防治杂志

Objective To investigate the effect of Toxoplasma gondii Chinese 1 genotype infections on host brain iron metabolism and brain damages. Methods Twenty C57BL/6 mice, each weighing 15 to 17 g, were randomly divided into the control and infection groups, of 10 mice in each group. Each mouse in the infection group was injected intraperitoneally with 4 000 tachyzoites of the TgCtwh3 isolate with Chinese 1 genotype, while each mouse in the control group was injected with an equal amount of sterile phosphate-buffered saline (PBS). All mice were sacrificed 6 day post-infection and brain tissues were sampled. The iron levels were measured in mouse brain specimens using inductively coupled plasma mass spectrometry (ICP-MS). The differentially expressed genes were determined between the experimental and control groups using RNA chips and Gene Ontology (GO) term enrichment analysis of differentially expressed genes was performed. The mRNA expression of Toxoplasma gondii surface antigen 1 (TgSAG1) gene and some Zrt- and Irt-like protein (ZIP) family member coding genes was detected by quantitative real-time PCR (qPCR) assay. The ultrastructure of the hippocampus dentate gyrus in mouse brain specimens was observed using optical and electronic microscopy. The glutathione peroxidase 4 (GPx4) expression was determined using Western blotting, and malondialdehyde (MDA) level was measured using thiobarbituric acid (TBA) test. In addition, the optical density (OD) of vascular endothelial growth factor (VEGF) protein was measured using immunohistochemistry. Results Optical microscopy showed cell necrosis in the hippocampus dentate gyrus of mouse brain specimens in the infection group, and electronic microscopy cytoplasmic vacuolization, nuclear atrophy and necrosis, disruption of cristae mitochondriales and increased autophagosome levels in the mouse brain hippocampus specimens in the infection group. The iron level was significantly greater in mouse brain specimens in the infection group than in the control group [(32.92 ± 0.90) μg/g vs. (37.72 ± 1.10) μg/g; t = 3.397, P < 0.01]. RNA chips revealed 721 up-regulated genes and 276 down-regulated genes in mouse brain specimens between the infection and control groups, and the differentially expressed genes were significantly enriched in metal ion binding ability (molecular function). Elevated expression of metal element transporter ZIP2 mRNA (t = 8.659, P < 0.05), reduced GPx4 expression [(1.046 ± 0.025) vs. (0.720 ± 0.101); t = 3.129, P < 0.01], increased MDA level [(4.37 ± 0.33) nmol/mgprot vs. (5.93 ± 0.54) nmol/mgprot; t = 2.451, P < 0.05], and up-regulated mean OD of VEGF protein [(0.348 3 ± 0.017 8) vs. (0.490 6 ± 0.010 5); t = 6.641, P < 0.01] were found in mouse brain specimens in the infection group than in the control group. Conclusions Chinese 1 genotype T. gondii infection results in iron accumulation in brain tissues, reduced antioxidant ability and elevated levels of oxidative stress in mice, suggesting that T. gondii infection may cause brain damages through affecting iron metabolism in host brain tissues.

Recombinant Expression and Purification of F-box and Leucine-rich Repeat Protein 5 (FBXL5) using a Prokaryotic Expression System

Background@#The F-box and Leucine-rich Repeat Protein 5 (FBXL5), a member of the E3 ligases, is considered to be the central iron sensor in mammals. The cryo-EM structure of FBXL5 in complex with IRP2 and SKP1 was reported by Wang et.al. in 2020. Surprisingly, a 2Fe-2S cluster seemed to be responsible for the iron-sensing capability of FBXL5. @*Objectives@#To further explore the mechanism of its regulation, it is important to study the interaction of FBXL5 with other proteins under regulated conditions so we attempted to express FBXL5 in the hopes of studying its interaction with IRPs in vitro. @*Methodology@#Plasmids were constructed to express FBXL5 in Escherichia coli expression hosts. Purification of an MBP-fused FBXL5 and GST-fused FBXL5 were performed using affinity chromatography. Peptide Mass Fingerprinting, Circular Dichroism spectroscopy, and SEC-MALS were employed to analyze the purified MBP-FBXL5. GST-FBXL5 was also used in a pull-down assay with Iron Regulatory Protein 1 (IRP1). @*Results@#We are successful in expressing and partially purifying full-length FBXL5 using E. coli with the aid of a protein tag, the maltose binding protein (MBP) tag. However, cleavage of the protein tag resulted in decreased stability of FBXL5 as shown in SEC-MALS data. CD spectroscopy showed consistent secondary structure of FBXL5. A preliminary pull-down assay of GST-FBXL5 with IRP1 showed that IRP1 displayed interaction with the recombinant GST-FBXL5. @*Conclusion@#FBXL5, a 78-kDa mammalian protein was overexpressed in a prokaryotic expression system made stable by a fusion protein. The interaction of GST-FBXL5 with IRP1 also shows that it is possible to study their interaction in vitro.

Role and Mechanism of BDH2 Gene in Metabolism, Tumorigenesis and Progression of Cancer / 肿瘤防治研究

Cellular metabolism in tumor is an important biological process to promote the occurrence and development of tumor, and the genes related to cellular metabolism are gradually becoming the targets of tumor treatment. However, more researches are still needed to explore the abnormal metabolism in tumor progression and its prognostic value. BDH2 gene is a multifunctional gene, participates in a variety of metabolic pathways, plays an important catalytic role in iron metabolism, participates in ketone metabolism and is related to lipid metabolism. In recent years, researchers have found that BDH2 plays distinct roles in various types of tumors. The occurrence and development of a variety of tumors are closely related to BDH2. This paper analyzes, summarizes and prospects the role and mechanism of BDH2 in metabolism and tumorigenesis.

Brazilian family with hyperferritinemia-cataract syndrome: case report

ABSTRACT Hereditary hyperferritinemia-cataract syndrome is a rare autosomal dominant disease caused by a genetic mutation in the iron responsive element in the 5' untranslated region of the ferritin light chain gene. Hereditary hyperferritinemia-cataract syndrome is characterized by elevated serum ferritin levels and bilateral cataract development early in life and may be misdiagnosed as hemochromatosis. This case report describes a Brazilian family with a clinical diagnosis of hereditary hyperferritinemia-cataract syndrome, which was submitted to ferritin light chain gene sequencing. The genetic mutation c.-164C>G was identified in the 5' untranslated region. In conclusion, genetic testing can be used for accurate diagnosis of hereditary hyperferritinemia-cataract syndrome to avoid misdiagnosis of hemochromatosis, other diseases associated with iron overload or ophthalmic diseases.

Stress response and virulence factors in bacterial pathogens relevant for Chilean aquaculture: current status and outlook of our knowledge

The study of the stress responses in bacteria has given us a wealth of information regarding the mechanisms employed by these bacteria in aggressive or even non-optimal living conditions. This information has been applied by several researchers to identify molecular targets related to pathogeny, virulence, and survival, among others, and to design new prophylactic or therapeutic strategies against them. In this study, our knowledge of these mechanisms has been summarized with emphasis on some aquatic pathogenic bacteria of relevance to the health and productive aspects of Chilean salmon farming (Piscirickettsia salmonis, Tenacibaculum spp., Renibacterium salmoninarum, and Yersinia ruckeri). This study will aid further investigations aimed at shedding more light on possible lines of action for these pathogens in the coming years.

A case of mitochondrial membrane protein-associated neurodegeneration caused by C19orf12 p.Gly58Ser mutation / 中华神经科杂志

Neurodegeneration with brain iron accumulation (NBIA) is a group of rare genetic diseases of nervous system. NBIA is characterized by varying degrees of abnormal iron metabolism and excessive iron deposition in brain tissue. The most common symptoms of NBIA are extrapyramidal symptoms. NBIA can also be associated with varying degrees of dysfunction of the pyramidal tract, cerebellum, peripheral nervous system, autonomic nervous system, mental cognition and vision functions. A patient with NBIA admitted to the Department of Neurology of Xijing Hospital in December 2020 was collected and analyzed for clinical features. Whole exome sequencing (WES) was employed to gene mutation screening, and pathogenicity analysis was performed according to the American College of Medical Genetics and Genomics (ACMG) guideline. The patient was a 13-year-old male with a chronic course of disease that began at the age of 4. The first symptom was spastic gait. With the progress of the disease, the patient developed mental retardation, arrhythmia, coughing from drinking water and loss of vision. Magnetic resonance imaging of the head showed atrophy of the optic nerve and hypointensity signal in bilateral substantia nigra and globus pallidus on T 2WI, fluid attenuated inversion recovery sequency, diffusion weighted imaging and susceptibility weighted imaging without "tiger eye sign" which was commonly found in pantothenate kinase associated neurodegeneration. The homozygous mutation c.172G>A (p.Gly58Ser) was found through WES. The proband′s father and mother are cousins (inbreeding), carried heterozygous variation of this locus. This novel mutation was not reported in mutation database. According to ACMG guideline, C19orf12 gene c.172G>A (p.Gly58Ser) was identified for possible pathogenic mutations. The conservative prediction of this locus suggests high conservatism. The final diagnosis of the patient was mitochondrial membrane protein-associated neurodegeneration (MPAN,NBIA type 4). This finding enriched the known mutation database of MPAN and provided a basis for further study of the disease.

Effects of iron metabolism and oxidative stress level on blood glucose control during pregnancy in patients with gestational diabetes mellitus / 中国基层医药

Objective:To investigate the effects of iron metabolism and oxidative stress level on blood glucose control during pregnancy in patients with gestational diabetes mellitus (GDM).Methods:A total of 139 pregnant women who received prenatal examination between January 2020 and June 2021 in Wenzhou Central Hospital were included in this study. They were divided into GDM group ( n = 68) and control group ( n = 71) according to oral glucose tolerance test results at 24-48 weeks of gestation. Clinical data were collected. Iron metabolism, oxidative stress and blood glucose levels were measured. The relationships between iron metabolism and oxidative stress levels and blood glucose control in GDM were analyzed. Results:There was no significant difference in age between the GDM and control groups ( P > 0.05). Body mass index, fasting blood glucose, fasting insulin, glycosylated hemoglobin, nuclear factor-κB (NF-κB), malondialdehyde (MDA), ferritin (SF), serum iron, transferrin (TRF) and insulin resistance index (IRI) in the GDM group were (24.11 ± 3.05) kg/m 2, (4.92 ± 0.67) mmol/L, (10.56 ± 2.21) pmol/mL, (6.15 ± 0.62)%, (20.50 ± 1.72) μg/L, (20.34 ± 2.92) μmol/L, (70.77 ± 7.01) μg/L, (30.18 ± 4.25) μmol/L, (3.93 ± 0.69) g/L and (2.50 ± 1.03), respectively, which were significantly higher than those in the control group [(21.41 ± 2.86) kg/m 2, (4.69 ± 0.62) mmol/L, (5.76 ± 2.09) pmol/mL, (5.37 ± 0.58)%, (15.43 ± 1.55) μg/L, (12.93 ± 2.17) μmol/L, (42.53 ± 8.86) μg/L, (18.81 ± 3.85) μmol/L, (2.89 ± 0.53) g/L and (1.74 ± 0.89)] ( t = 5.39, 2.10, 13.16, 7.66, 18.27, 17.03, 20.78, 16.54, 9.99, 4.66, all P < 0.05). Superoxide dismutase (SOD), total antioxidant capacity (TAOC) and insulin sensitivity index in the GDM group were (21.49 ± 3.52) U/L, (10.87 ± 1.34) kU/L and (3.28 ± 0.46), respectively, which were significantly lower than those in the control group [(26.28 ± 3.95) U/L, (13.28 ± 1.52) kU/L, (3.86 ± 0.53), t = 7.54, 9.90, 6.88, all P < 0.05]. Multivariate logistic regression analysis revealed that SOD, TAOC, NF-κB, MDA, SF and TRF were independent influential factors of GDM occurrence [ OR (95% CI) = 1.57 (1.09-2.26), 3.15 (1.71-5.80), 2.18 (1.32-3.61), 3.27 (1.58-6.76), 2.12 (1.29-3.50), 1.23 (0.99-1.53), 3.65 (1.89-7.04), all P < 0.05]. SOD and TAOC levels were negatively correlated with IRI ( r = -0.75, -0.84, both P < 0.05), while NF-κB, MDA, SF, serum iron and TRF were positively correlated with IRI ( r = 0.93, 0.96, 0.98, 0.07, 0.92, all P < 0.05). Conclusion:Increased levels of iron metabolism and oxidative stress are risk factors for the occurrence of GDM, and they are closely related to the degree of insulin resistance. GDM screening should be carried out in advance in pregnant women with increased levels of iron metabolism and oxidative stress indicators, which plays a positive role in clinical diagnosis and treatment of GDM.