Transcriptomics combined with proteomics to analyze the signaling pathway of EGFL9 gene affecting the proliferation, invasion and migration of hepatocellular carcinoma / 中华肝胆外科杂志

Objective:Transcriptomics combined with proteomics was used to analyze the potential signaling pathways of epidermal growth factor-like domain 9 (EGFL9) affecting the proliferation, invasion and migration of hepatocellular carcinoma.Methods:RNA interference technique was used to build hepatocellular carcinoma cell line with EGFL9 Huh-7 gene knockdown, the control group (NC group) and experimental group (KD group), each group of three samples, were performed the transcriptome and proteomics analysis, screening differences genes and proteins, to express the correlation analysis, cluster analysis, and subsequently gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were used for gene function and pathway annotation enrichment analysis, respectively.Results:Based on omics analysis, there were 8 335 different genes in KD group compared with NC group, among which 4 207 were up-regulated and 4 128 were down-regulated. There were 298 different proteins, of which 188 were up-regulated and 110 down-regulated. Based on the combined analysis of the two omics, 213 differentially expressed genes were found. Among them, the top three common differentially expressed genes at the level of transcription and translation were transferrin receptor 2 (TFR2), annexin A1 (ANXA1) and solute carrier family 38 member 2(SLC38A2). The common differentially expressed genes were significantly enriched in cell cycle signaling pathway, amino acid biosynthesis pathway, p53 signaling pathway and glycolysis/gluconeogenesis signaling pathway.Conclusion:EGFL9 may participate in the regulation of cell function of hepatocellular carcinoma cells by regulating the expression of TFR2, ANXA1, LC38A2 and other genes, and may play a role through the regulation of cell cycle and other molecular signaling pathways.

Relationship between serum sTfR and FGF22 levels and clinical symptoms in first-episode schizophrenia patients and their diagnostic value / 国际检验医学杂志

Objective To investigate the expression of soluble transferrin receptor(sTfR)and fibroblast growth factor 22(FGF22)in serum of first-episode schizophrenia(FES)patients,analyze the relationship be-tween the two and the clinical symptoms of FES patients,and analyze their diagnostic value.Methods A total of 97 FES patients diagnosed in the hospital from March 2021 to February 2023 were regarded as the FES group,during the same period,96 healthy volunteers who came to this hospital for physical examination were regarded as the control group.Immunotransmission turbidimetry was applied to detect the level of sTfR,en-zyme linked immunosorbent assay(ELISA)was applied to detect the level of FGF22,Spearman method was applied to analyze the correlation between the levels of sTfR and FGF22 in the serum of FES patients and Pos-itive and Negative Syndrome Scale(PANSS)score and Wisconsin Card Sorting Test(WCST)results,and re-ceiver operating characteristic(ROC)curve was applied to analyze the clinical diagnostic value of levels of sTfR and FGF22 for FES.Results There were no obvious differences between the two groups in terms of gender,age,body mass index,years of education,history of alcohol consumption,and smoking history(P>0.05).Compared with the control group,the serum levels of sTfR and FGF22 in the FES group were obvious-ly lower(P<0.05).The area under the curve(AUC)of sTfR for diagnosing FES alone was 0.835,with the cut off value of 4.606 mg/L,the AUC of FGF22 for diagnosing FES alone was 0.772,with the cut off value of 208.333 μg/L,the AUC of the combination of the two(0.921)was obviously higher than that of sTfR alone(Z=2.613,P=0.009),and that of FGF22 alone(Z=5.140,P<0.001).The PANSS positive symptom score,negative symptom score,pathological symptom score,total score,WCST persistent errors,and incorrect responses in the high sTfR level group and high FGF22 group were lower than those in the low sTfR group and low FGF22 group(P<0.05),while the number of WCST completed classifications and WCST correct re-sponses were higher than those in the low sTfR group and low FGF22 group(P<0.05).The levels of sTfR and FGF22 in the FES group were negatively correlated with PANSS positive symptom score,negative symp-tom score,pathological symptom score,total score,WCST persistent errors,and WCST incorrect responses(P<0.05),and positively correlated with the number of WCST completed classifications and WCST correct responses(P<0.05).Conclusion The levels of sTfR and FGF22 in the serum of FES patients are obviously decreased.Combined detection of sTfR and FGF22 levels is of great significance for the clinical diagnosis of FES.

Changes and biological significance of ferroptosis in a mouse model of bloodstream infection induced by different bacteria / 中国组织工程研究

BACKGROUND:It is of great significance to find new diagnostic markers of the disease and molecular targets for the treatment of the disease and the alleviation of organ injury.Ferroptosis is a newly discovered form of cell death.Overactivation of ferroptosis in animal models of sepsis is associated with the activation of inflammatory response and the injury of the liver,heart,kidney and other important organs,but the relationship between ferroptosis and bloodstream infection is not very clear. OBJECTIVE:To study the changes and biological significance of ferroptosis in a mouse model of blood stream infection induced by different bacteria. METHODS:Blood stream infection models induced by gram negative bacteria Escherichia coli,Klebsiella pneumoniae and gram positive bacteria Staphylococcus aureus and Enterococcus faecalis were established in SPF-grade ICR male mice,with 42 mice in each group.The mRNA expression levels of ferroptosis marker genes transferrin receptor 1 and glutathione peroxidase 4 in the liver,myocardium and kidney were detected at 0.5,1,3,6,12,24 and 48 hours after modeling.Another 18 SPF-grade ICR male mice were selected and randomly divided into dimethyl sulfoxide(DMSO)control group,DMSO+Klebsiella pneumoniae group,and Ferrostatin-1+Klebsiella pneumoniae group,with 6 mice in each group.In the latter two groups,animal models of Klebsiella pneumoniae bloodstream infection were established by tail vein injection of Klebsiella pneumoniae suspension,and 5 mg/kg Ferrostatin-1 and an equal dose of DMSO were given intraperitoneally 1 hour prior to the modeling of bloodstream infection,respectively.Serum levels of alanine aminotransferase,aspartate aminotransferase,blood creatinine,blood urea nitrogen,phosphocreatine kinase isoenzyme,lactate dehydrogenase,and mRNA expression levels of ferroptosis marker genes in various tissues were assayed at 6 hours after modeling. RESULTS AND CONCLUSION:After bloodstream infection modeling,the mRNA expression levels of transferrin receptor 1 in the liver,myocardium and kidney of bloodstream infection mice with different bacteria increased first and then decreased;and the mRNA expression level of glutathione peroxidase 4 decreased first,then increased,and reached the peak at 6 hours after modeling.The changes in transferrin receptor 1 and glutathione peroxidase 4 mRNA levels in bloodstream infection mice induced by gram-negative bacteria were more significant than those in blood stream infection mice induced by gram-positive bacteria,especially in bloodstream infection mice induced by Klebsiella pneumoniae.At 6 hours after bloodstream infection induced by Klebsiella pneumoniae,the levels of alanine aminotransferase,aspartate aminotransferase,serum creatinine,blood urea nitrogen,creatine phosphate kinase isoenzyme,lactate dehydrogenase in mice were significantly increased.Before modeling,Ferrostatin-1 intervention significantly reduced the levels of alanine aminotransferase,aspartate aminotransferase,serum creatinine,blood urea nitrogen,creatine phosphate kinase isoenzyme,and lactate dehydrogenase.All these findings indicate that the activation of ferroptosis in bloodstream infection mice induced by different bacteria is obvious,and the activation of ferroptosis in bloodstream infection mice induced by gram-negative bacteria is more obvious.Inhibition of iron death significantly attenuates liver,myocardial,and kidney injury in the mouse model of bloodstream infection induced by Klebsiella pneumoniae.

Brain endothelial cell-derived extracellular vesicles with a mitochondria-targeting photosensitizer effectively treat glioblastoma by hijacking the blood‒brain barrier

Glioblastoma (GBM) is the most aggressive malignant brain tumor and has a high mortality rate. Photodynamic therapy (PDT) has emerged as a promising approach for the treatment of malignant brain tumors. However, the use of PDT for the treatment of GBM has been limited by its low blood‒brain barrier (BBB) permeability and lack of cancer-targeting ability. Herein, brain endothelial cell-derived extracellular vesicles (bEVs) were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB. To enhance PDT efficacy, the photosensitizer chlorin e6 (Ce6) was linked to mitochondria-targeting triphenylphosphonium (TPP) and entrapped into bEVs. TPP-conjugated Ce6 (TPP-Ce6) selectively accumulated in the mitochondria, which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation. Moreover, the encapsulation of TPP-Ce6 into bEVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6, leading to significantly enhanced PDT efficacy in U87MG GBM cells. An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that bEVs containing TPP-Ce6 [bEV(TPP-Ce6)] substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis. As such, bEV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity, suggesting that mitochondria are an effective target for photodynamic GBM therapy.

The role of transferrin receptor CD71 as a diagnostic and prognostic biomarker in sepsis / 中华危重病急救医学

Objective:To find new biomarkers for the diagnosis and prognosis of sepsis through analyzing the differential expression protein in sepsis by proteomics and bioinformatics analysis and enzyme linked immunosorbent assay (ELISA).Methods:Patients with sepsis admitted to the emergency department of the Affiliated Hospital of Southwest Medical University from January to December 2019 were enrolled. And meanwhile, healthy volunteers who had normal physical examinations were included as the control group. Blood samples from two groups were collected. The samples were randomly selected for the protein concentration by data independent acquisition (DIA). Bioinformatics method was used in differentially expressed proteins by gene ontology (GO) pathway, enrichment analyses, groups meta-analysis and survival curves construction. ELISA method was used to verified marker screened. Then the data of transferrin receptor CD71 and the clinical data of procalcitonin (PCT), C-reactive protein (CRP) and blood lactic acid (Lac) were collected to construct receiver operator characteristic curve (ROC curve), and biomarker was screened for diagnostic and prognostic of sepsis.Results:The result of DIA showed that 71 differentially expressed proteins were screened out from sepsis group, 6 proteins were down-regulated and 65 proteins were up-regulated. Those differentially expressed proteins were enriched in the inflammatory response, response to stress, leukocyte migration in the GO pathway and enrichment analyses. The meta-analysis showed that the expression level of CD71 was higher in sepsis group than normal control group [standardized mean difference ( SMD) = -0.47, 95% confidence interval (95% CI) was -0.93 to 0.00, P < 0.01], the expression level of CD71 was higher in non-survivor group than survivor group ( SMD = -0.44, 95% CI was -0.70 to -0.18, P = 0.63). Survival curve showed that the expression of CD71 was inversely correlated to survival rates, the patients with a lower expression had higher survival rates ( P = 0.000 34); the ELISA showed that the level of CD71 was higher in sepsis group than normal control group (nmol/L: 156.83±84.71 vs. 87.99±47.89, P < 0.05), the level of CD71 was higher in non-survivor group than survivor group (nmol/L: 219.63±125.59 vs. 130.97±40.45, P < 0.05). The area under the ROC curve (AUC) of CD71 in diagnostic performance of sepsis was 0.790 (sensitivity was 65.1%, specificity was 90.0%), the AUC of CD71 in prognostic performance of sepsis was 0.744 (sensitivity was 57.1%, specificity was 94.1%); CD71 had a better prognostic performance than PCT (AUC = 0.547, sensitivity was 64.3%, specificity was 55.9%), CRP (AUC = 0.594, sensitivity was 64.3%, specificity was 61.8%), Lac (AUC = 0.540, sensitivity was 42.9%, specificity was 82.4%). Conclusion:CD71 had a great value of diagnostic and prognostic performance in sepsis, and it was expected to be a potential biomarker for sepsis.

Role Of Serum Soluble Transferrin Receptors (STFR) To Differentiate Iron Deficiency Anaemia And Anaemia Of Chronic Disease

Background:Iron deficiency is a common condition that is usually diagnosed using conventional laboratory tests of iron status, such as serum ferritin and transferrin saturation. However, both ferritin and transferrin proteins are markedly influenced by inflammation, behaving as acute-phase reactants and making it difficult to differentiate between iron-deficiency anemia (IDA) and anemia of chronic disease (ACD). Objectives: To evaluate the roleof serum soluble transferrin receptors (STFR) to differentiate iron deficiency anaemia and anaemia of chronic disease.Material And Methods:A cross-sectional study was conducted in the Department of Medicine, Victoria hospital and Bowring and Lady Curzonhospital, Bangalore Medical College and Research institute, Bangalore. A total of 150 blood samples were evaluated, i.e., 50 samples from iron deficiency anaemia group and 50 samples from patients with anaemia of chronic disorders & 50 samples from healthy normal individual.Result:In present study, samples are age matched with mean age of control 45.66±10.23, ACD 50.68±18.03, IDA 48.14±18.47. Hb, MCV, MCHC & MCH were decreased in both the groups. However, the decrease in Hb & MCV was much more in IDA as compared to ACD. Microcytosis was seen in 92% cases of IDA while it was observed in only 11% cases of ACD. Serum soluble transferrin receptor levels is <3 ?gm/ml in 90% of ACD group whereas >3 ?gm/ml in 78% of IDA Group.STFR/ log ferritin index was >1.5 in 80% of IDA. 90% of ACD and control subjects had STFR/log ferritin index <1.5. STFRlevels were significantly higher in IDA (7.7± 5.8) as compared to the ACD cases (1.6 ±0.89) (p<0.001). STFR/Log ferritin index is significantly higher in patients with Iron deficiency anemia (9.34±10.25) as compared to ACD (0.76±0.52) (p<0.001).Conclusion:The STFRlevels along with the STFR/Log ferritin index indices is very useful in differentiating pure IDA, ACD and ACD with coexisting iron deficiency, thus pr oviding anon invasive alternative to bone marrow iron.

Body iron store and prevalence of iron deficiency In Mongolian children aged 6-59 months / Монголын Анагаах Ухаан

Background@#Iron is an essential mineral needed for physical and cognitive development with iron needs greatest during pregnancy, infancy, childhood, and adolescence. Iron is vital throughout the lifespan as it is a component of haemoglobin, the protein responsible for transporting oxygen from the lungs to body cells for energy production. Iron deficiency results from a depletion of body iron stores due to increased iron needs, inadequate dietary iron intake, reduced iron absorption, or loss of iron from infections caused by malaria, hookworms, and other intestinal parasites. In advanced stages, iron deficiency leads to iron deficiency anaemia, a condition of low red blood cells and reduced oxygen-carrying capacity.@*Goal@#This study aimed to determine body iron stores in Mongolian children aged 6-59 months, and estimate prevalence of iron deficiency among of studied children. @*Materials and Methods@#In this study were used materials that collected during the fifth national nutrition survey conducted in 21 provinces of 4 economic regions and 8 districts of Ulaanbaatar city of Mongolia. The fifth national nutrition survey was household based survey; therefore sampling unit was household with 5 year-old child. We had used demographic information collected by interview methods and laboratory examination results on ferritin, soluble transferrin (sTfR), C reactive protein (CRP) and α1-acid glycoprotein (AFP) in serum samples collected from 6 to 59 months old children, pregnant women and 15–49 year-old men living in child’s households. Serum Ferritin and soluble transferrin (sTfR) were used as a biomarker for iron store and iron deficiency and C reactive protein (CRP) and AFG were used as indicators for acute and chronic infection. The determination of iron status is challenging when concomitant infection and inflammation are present because of confounding effects of the acute-phase response on the interpretation of most iron indicators. Effects of C reactive protein (CRP) and AGP concentrations on estimates of ID according to serum ferritin (SF) and soluble transferrin receptor (sTfR) were considered in the study. @*Ethical considerations @#The survey protocol was discussed at the scientific committee of the Public health institute and approved by director of scientific committee of PHI on June 28, 2016. Ethical approval for conducting the survey, including obtaining biological samples was obtained from the Medical ethics committee under the Ministry of Health of Mongolia on July 7, 2016. Participation in the survey was voluntary, oral and written informed consent was obtained from each participants and adult caregivers of under 5 year-old children. @*Results@#Biomarkers of iron status were adjusted with inflammation indicators and estimated iron deficiency (ID) and total body iron store in 1732 children 6-59 month-olds. The study findings showed that adjusted mean concentration of serum ferritin and soluble transferrin receptor was 33.7 µg/l and 8.8 mg/l in children age of 6-59 months, respectively. The calculated total body iron store by using adjusted SF and soluble transferrin receptor was 2.8 mg/kg among surveyed children. Iron deficiency was estimated by using 2 different biomarkers among selected population group. The prevalence of iron deficiency estimated by using SF was 20.7% in children 6-59 months. Iron deficiency in children defined by using serum soluble transferrin receptor was 27.7%.@*Conclusions@#</br> 1. The average serum ferritin and soluble transferrin receptor concentrations was 33.7 µg/l and 8.8 mg/l in children age of 6-59 months, respectively. Total body iron store estimated by using SF and soluble transferrin was 2.8 mg/kg among surveyed children. </br>2. The prevalence of iron deficiency estimated by using SF and sTfR was 20.7% and 27.7% in children 6-59 months, respectively. According to the WHO recommendation, prevalence of iron deficiency among Mongolian children aged 6-59 months is classified as “prevalent”. </br>3. Overall proportion of children with low body iron store was 22.4%. The prevalence of iron depletion is relatively common in boys, young children aged 6–23 months, and rural children aged 6-59 months.

Soluble transferrin receptor levels among pregnant women in Port Harcourt, Nigeria

Background: Anaemia in pregnancy is one of the medical problems that affect pregnant women in developing countries. It contributes considerably to the morbidity and mortality in pregnancy especially in areas where malaria is endemic. The concentration of soluble transferrin receptor is a reflection of body iron status. It is therefore, a valuable tool for assessing bone marrow erythropoetic activity and can also be a marker of iron deficiency.Methods: This study evaluated the levels of soluble transferrin receptor in pregnant subjects. A total of 275 pregnant subjects of age 20 to 45 years and 88 age-matched apparently healthy control subjects were involved in this study. Individuals who had severe anaemia, HIV infection, sickle cell disease or Hookworm infestation were excluded from this study. Five millilitres (5ml) of blood were collected from each consenting subject for the analysis of soluble transferrin receptor, haematological parameters and iron parameters using appropriate methods.Results: The mean value of parameters for the study subjects were sTfR( 21.16±9.11 nmol/L), Hb(9.05±1.22 g/dl), TIBC(332.61±80.87 µg/dl), Serum Iron(97.91±39.44 µg/dl), LIBC(239.36±80.52 µg/dl), TS(30.24±11.00 %) while for control subjects were sTfR(18.21±3.77 nmol/L), Hb(12.19±0.66 g/dl), TIBC(261.94±52.49µg/dl), Serum Iron(107.10±34.77 µg/dl), LIBC(155.52±61.25 µg/dl), TS(42.81±18.03 %). The mean sTfR levels in pregnant women was significantly lower (p<0.001) than in control subjects. The pregnant women also had significantly lower values of Hb (p<0.001), serum iron (p=0.038) and TS( p<0.001) values, and significantly higher values of TIBC(p<0.0001) and LIBC(p<0.0001). There were also increases in soluble transferrin receptor levels from first to third trimesters. The sensitivity of sTfR as against Serum iron parameters from this study was 76% while the specificity was 50%. The positive predictive value was 60% while the negative predictive value was 50%.Conclusions: sTfR may be a useful supplementary diagnostic tool in the management of anaemia in pregnancy.

Cognitive function observation and clinical features of 100 cases of elderly patients with non-alcoholic fatty liver disease / 中华消化杂志

Objective To observe the changes of cognitive function,clinical characteristics and hippocampal structure in elderly patients with non-alcoholic fatty liver disease (NAFLD).Methods From December 2014 to June 2016,at Department of Geriatrics,Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School,169 elderly hospitalized patients who underwent health checkups were enrolled and divided into NAFLD group and non-NAFLD group.The clinical data of two groups were collected,and the Montreal cognitive assessment scale (MoCA) was used for cognitive function assessment.The serum level of soluble transferrin receptor (sTfR) was detected,the liver-spleen ratio was measured and hippocampal proton magnetic resonance spectroscopy (1H-MRS) was performed.T test and linear regression analysis were used for statistical analysis.Results Among the 169 elderly patients,100 were NAFLD and 69 were non-NAFLD.The body mass index(BMI) and waist-to-hip ratio(WHR) of patients in NAFLD group were (25.9 ± 3.4) kg/m2 and 1.03 ± 0.13,respectively,which were higher than those in non-NAFLD group ((24.2 ± 3.7) kg/m2 and 0.95 ± 0.06),and the differences were statistically significant (t =-2.714 and-3.605,both P ＜0.01).MoCA score of the patients in NAFLD group was 20.1 ± 5.8,which was lower than that in non-NAFLD group (22.1 ± 4.4),and the difference was statistically significant(t =2.154,P =0.033).The serum sTfR level and liver-spleen computed tomography(CT) ratio of NAFLD group were (8.78 ± 4.31) mg/L and 0.97 ± 0.12,respectively,which were lower than those of non-NAFLD group ((12.66 ± 3.93) mg/L and 1.19 ± 0.15),and the differences were statistically significant(t =3.765 and 6.142,both P ＜ 0.01).The CT ratio of liver to spleen (β=7.597,95％ confidence interval(CI):2.938 to 12.935) and sTfR (β =0.552,95％ CI:0.304 to 0.787) were positively correlated with cognitive function in elderly patients (both P ＜ 0.01).The height of right hippocampus of NAFLD group was (0.410 ± 0.074) mm,which was lower than that of non-NAFLD group ((0.453 ± 0.086) ram),and the difference was statistically significant (t =2.078,P =0.042).Conclusion Cognitive impairment in elderly NAFLD patients is closely related to iron load and liver fat.

Relationship between body iron and elevated blood glucose in mosuo people / 解剖学报

Objective To study the relationship between physiological iron reserve, anemia and elevated blood glucose in Mosuo population in Yunnan, China. Methods Blood samples were collected from 187 Mosuo people in Ninglang County, Yunnan Province, and their glycated hemoglobin (HbAlc), transferrin receptor (TfR) and hemoglobin levels (Hb) were measured. Logistic Regression analysed the relationship between iron status and elevated blood glucose in Mosuo data and Chinese national data (CHNS). Results Compared with the control group, Mosuo people were deficient in iron without anemia, ie iron deficiency erythropoiesis (IDE) corresponds to an increase in the risk of elevated blood glucose (OR = 2. 70) , which is consistent with national data for China. The results of the analysis are consistent. Conclusion Compared with healthy people, Mosuo people with iron deficiency anemia and non-iron deficiency anemia, Mosuo people who are deficient in iron without anemia are at risk of rising blood sugar. The body iron level of Mosuo people has reference significance for the risk and control of type 2 diabetes.

Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer

Recently, considerable attention in the field of cancer therapy has been focused on the mammalian rapamycin target (mTOR), inhibition of which could result in autophagic cell death (ACD). Though novel combination chemotherapy of autophagy inducers with chemotherapeutic agents is extensively investigated, nanomedicine-based combination therapy for ACD remains in infancy. In attempt to actively trigger ACD for synergistic chemotherapy, here we incorporated autophagy inducer rapamycin (RAP) into 7pep-modified PEG-DSPE polymer micelles (7pep-M-RAP) to specifically target and efficiently priming ACD of MCF-7 human breast cancer cells with high expression of transferrin receptor (TfR). Cytotoxic paclitaxel (PTX)-loaded micelle (7pep-M-PTX) was regarded as chemotherapeutic drug model. We discovered that with superior intracellular uptake and more tumor accumulation of micelles , 7pep-M-RAP exhibited excellent autophagy induction and synergistic antitumor efficacy with 7pep-M-PTX. Mechanism study further revealed that 7pep-M-RAP and 7pep-M-PTX used in combination provided enhanced efficacy through induction of both apoptosis- and mitochondria-associated autophagic cell death. Together, our findings suggested that the targeted excess autophagy may provide a rational strategy to improve therapeutic outcome of breast cancer, and simultaneous induction of ACD and apoptosis may be a promising anticancer modality.

Study on the association of transferrin receptor gene polymorphism with age related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To develop the correlation of patients in age-related macular degeneration and TFR2 gene polymorphism in the Han people of northeast China.<p>METHODS: Totally 200 patients with ARMD(dry-ARMD 100 individuals and wet-ARMD 100 individuals)and 100 healthy control people were chosen as the experiment team and control team. Peripheral venous blood were collected and anticoagulated dealed with EDTA. Then we extraced genome DNA and amplificate rs2075674, which was the polymorphic locus of TFR2 gene according to the primer sequences provided by references, for polymerase chain reaction(PCR). The group representativeness of samples is identified according to hardy Weinberg equilibrium principle. <p>RESULTS: We found that the difference between ARMD group and control group in the polymorphism of TFR2 gene rs2075674 is statistically significant(χ²=6.494, <i>P</i>=0.011). There was significant difference between the wet ARMD group and control group(χ²=11.054, <i>P</i>=0.001). There had no significant differences when it comes to the dry ARMD group and the control group(χ²=1.418, <i>P</i>=0.234).<p>CONCLUSION: The above findings indicate that polymorphism of TFR2 gene increases the risk of ARMD in the Han population of Northeast China. It is concluded that rs2075674 is significantly correlated with wet-ARMD.

Micro-325 inhibiting malignant biological characteristics of glioma cells via transferrin receptor pathway / 中华神经医学杂志

Objective To study the influence of micro (miR)-325 in progression of glioma and its molecular mechanism by regulating transferrin receptor (TFRC) gene expression in glioma cells. Methods (1) Thirty-five glioma tissues and paired adjacent normal tissues were collected during surgical excision performed in our hospital from January 2015 to January 2018. The miR-325 and TFRC mRNA expression levels in the glioma tissues and paired adjacent normal tissues were detected by inverse transcription-quantitative PCR (RT-qPCR); the expression of miR-325 in glioma tissues of patients with different clinical characteristics and the survival curves of patients with low or high miR-325 expressions were compared. (2) RT-qPCR was used to examine the miR-325 expression in HA, U251, and U87 cell lines in vitro; the regulatory relations between miR-325 and its potential target gene TFRC in U251, and U87 cell lines were measured by luciferase report assay; miR-325 mimic and its negative control were transfected into U251 and U87 cell lines for 48 h, and then, the mRNA and protein expressions of TFRC were detected by RT-qPCR and Western blotting, respectively; control small interfering RNA (siRNA)+nonsense inhibitor, TFRC siRNA+nonsense inhibitor, and siTFRC+miR-325 inhibitor were transfected into U251 and U87 cell lines for 48 h, respectively, Western blotting was employed to detect the TFRC protein expression, cell proliferation was detected by CCK-8 assay, and cell invasion was detected by Transwell assay; pcDNA3.1 empty vector+nonsense sequence, TFRC pcDNA3. 1+nonsense sequence, TFRC pcDNA3.1+miR-325 mimic were transfected into U251 and U87 cell lines for 48 h, respectively, TFRC protein expression was detected by Western blotting, cell proliferation was detected by CCK-8 assay, and cell invasion was detected by Transwell assay. Results (1) As compared with those in the adjacent tissues, the miR-325 expression was significantly decreased and the TFRC mRNA expression was statistically increased in glioma tissues (P<0.05); the TFRC mRNA expression and miR-325 expression were negatively correlated in glioma tissues (P<0.05); as compared with patients with Karnofsky functional status scores≥80, patients with scores<80 had significantly decreased miR-325 expression; as compared with glioma tissues of WHO grading I-II, glioma tissues of grading III-IV had significantly decreased miR-325 expression (P<0.05); the survival rate of patients with low miR-325 expression was statistically lower than that of patients with high miR-325 expression (P< 0.05). (2) As compared with that in HA cells, the miR-325 expression was statistically down-regulated in U87 and U251 cells (P<0.05); in TFRC wild-type (TFRC WT) transfected cells, the miR-325 mimic group had significantly lower luciferase activity than the nonsense sequence group, while the miR-325 inhibitor group had significantly higher luciferase activity than the nonsense inhibitor group (P<0.05); as compared with those in the nonsense sequence group, the TFRC mRNA and protein expressions were statistically decreased in U87 and U251 cells of miR-325 mimic group; as compared with those in the control siRNA+nonsense inhibitor group, the TFRC protein expression and absorbance value were significantly decreased, and number of invasive cells was significantly smaller in the siTFRC+nonsense inhibitor group; and as compared with those in the siTFRC+nonsense inhibitor group, the TFRC protein expression and absorbance value were significantly increased, and number of invasive cells was significantly larger in the siTFRC+miR-325 inhibitor group (P<0.05); as compared with the pcDNA3.1 empty vector+nonsense sequence group, the TFRC protein expression and absorbance value were significantly increased, and number of invasive cells was significantly larger in the TFRC pcDNA3.1 +nonsense sequence group, and as compared with the TFRC pcDNA3.1+nonsense sequence group, the TFRC protein expression and absorbance value were significantly decreased, and number of invasive cells was significantly smaller in the TFRC pcDNA3.1+miR-325 mimic group (P<0.05). Conclusion The miR-325 expression is decreased in glioma cells and has a tumor suppressor effect; patients with low miR-325 expression have poor prognosis; miR-325 inhibits cancer cell progression by inhibiting the expression of the target gene TFRC.

The diagnostic clinical value of sTFR and its compound parameters in the inflammatory bowel disease combined with iron deficiency anemia / 安徽医科大学学报

Objective To evaluate the value of serum soluble transferrin receptor ( sTFR) and sTFR-ferritin index (sTFR/LogSF) in diagnosing iron deficiency anemia ( IDA) with inflammatory bowel disease ( IBD) . Methods 161 patients with diagnosis of IBD was continuous collected, including 81 cases of Crohn's disease ( CD) and 80 cases of ulcerative colitis( UC) . Drawing venous blood to check complete blood count, iron metabolism, CRP, folic acid and vitamin B12 (VitB12) in the next morning with an empty stomach. According to the WHO anemia diag-nostic criterion, patients were divided into anemia group and non anemia group. The incidence and etiology of IBD were analysed. All patients with IBD were divided into iron deficiency anemia group and non iron deficiency group based on SF. Receiver-operating characteristic curve ( ROC curve) were applied to evaluate the value of sTFR and sTFR/LogSF in diagnosis of IDA with IBD. All the cases were followed till the endpoint of the study, lasted for 12 months at least. Results The incidence of IBD combined with anemia was 62. 1% (100/161), among which IDA and ACD hold up to 40. 0 % (40/100) and 14. 0% (14/100) respectively, while the mix of IDA and ACD ac-count for 26. 0% (26/100), and 10. 0% (10/100) was taken by lack of folic acid and VitB12. The level of sTFR and sTFR/LogSF in IDA group were obviously higher than those in non IDA group,and this difference was statisti-cally significant (U=655. 5,306. 0,P ＜0. 001). The AUC of sTFR/LogSF (0. 937) was higher than the AUC (0. 865) of sTFR. High sTfR levels ( ＞4. 7 mg/L) had a sensitivity of 77. 5% and a specificity of 86. 0%, whereas high sTfR/LogSF ( ＞2. 8) had a sensitivity of 87. 5% and a specificity of 90. 9% for the diagnosis of IDA. Both sTFR and sTFR/LogSF index were not correlated with CRP levels (r=0. 042,0. 958, P＞0. 05). Con-clusion The incidence of IBD combined anemia is high,among which IDA is common. By detecting serum sTFR/LogSF and sTfR,the diagnosis of IBD combined IDA may be more accurate.

Anemia microcítica-hipocrómica: anemia ferropénica versus b talasemia menor / Microcytic and hypochromic anemia: iron deficiency anemia versus b thalassemia trait / Anemia microcitica-hipocrômica: anemia ferropênica versus b talassemia menor

Las anemias microcíticas hipocrómicas (m-H) presentan VCM<80 fL y HCM<27 pg. Son producto de la baja biodisponibilidad del hierro (Fe), o del defecto de la síntesis de globinas o del HEMO. La más frecuente es la anemia por deficiencia de hierro (ADH), seguida por las talasemias y las anemias de procesos crónicos. Menos frecuentes son aquellas por defectos en el HEMO o por causas genéticas del metabolismo del Fe. El objetivo del trabajo es revisar, por medio de parámetros de distinta complejidad, diferencias entre ADH y b talasemia heterocigota (b-Tal-het), las m-H de mayor prevalencia en nuestro medio. Los recuentos de eritrocitos y reticulocitos, hemoglobina, ferremia, ferritina, saturación de la transferrina, HbA2, porcentaje de alteraciones morfológicas son menores en la ADH. El VCM, el HCM, la ADE, los índices de microcitosis, transferrina, y los receptores solubles de transferrina son menores en b-Tal-het. El estrés oxidativo está aumentado en ambas patologías. En el análisis de estos parámetros se discute el grado de deficiencia de Fe y/o la mutación de b-Tal-het. Se aplica un algoritmo para m-H a partir del Fe sérico. Una vez descartadas las m-H más comunes, se debe investigar a-Tal-het, la cual se considera la causa de la mayoría de m-H inexplicadas.

Microcytic hypochromic anemia (m-H) presents MCV<80 fL and MCH<27 pg. m-H can result from iron availability, defects in globin or HEMO synthesis. The most frequent m-H is iron deficiency anemia (IDA), followed by thalassemias and anemia chronic disease. Rare m-H are a consequence of HEME defects or iron metabolism genetic defects. The aim of this study is to review the differential diagnosis between IDA and b thalassemia trait (b thal trait), the most frequent in our environment. Results of laboratory tests are analysed. Erythrocytes, hemoglobin, reticulocytes, iron, ferritin, transferrin saturation, HbA2 and percentage of morphologic changes are lower in IDA compared with b Thal trait. MCV, MCH, RDW, microcytic index, transferrin and soluble transferrin receptor are higher in IDA compared with b Thal trait. Oxidative stress is increased in the two forms of microcytoses. Degree iron deficiency in IDA and b Thal trait mutation must be considered in the analysis of the parameters. A flowchart is proposed to evaluate m-H stemming from serum iron value. After excluding the most frequent causes of microcytic anemia, a thalassemia trait must be considered.

As anemias microcíticas hipocrômicas (m-H) apresentam VCM<80 fL e HCM<27 pg. São produto da baixa biodisponibilidade do ferro (Fe), ou do defeito da síntese de globinas ou do HEMO. A mais frequente é a anemia por deficiência de ferro (ADH), seguida pelas talassemias e as anemias de processos crônicos. Menos frequentes são aquelas por defeitos no HEMO ou por causas genéticas do metabolismo do Fe. O objetivo do trabalho é revisar, através de parâmetros de diversa complexidade, diferenças entre ADH e b talassemia heterocigota (b-Tal-het), as m-H de maior prevalência no nosso meio. As contagens de eritrócitos e reticulócitos, hemoglobina, ferremia, ferritina, saturação da transferrina, HbA2, percentagem de alterações morfológicas são menores em ADH. O VCM, o HCM, a ADE, os índices de microcitose, transferrina, receptores solúveis de transferrina são menores em b-Tal-het. O estresse oxidativo está aumentado em ambas as patologias. Na análise destes parâmetros é discutido o grau de deficiência de Fe e/ou a mutação de b-Tal-het. Aplica-se um algoritmo para m-H a partir do Fe sérico. Depois de serem descartadas as m-H mais comuns, deve investigar-se a-Tal-het, a qual é considerada a causa da maior parte de m-H inexplicadas.

¿Puede usarse el receptor soluble de transferrina para diagnosticar anemia ferropénica y evaluar la respuesta al hierro en lactantes con desnutrición aguda moderada? / Can soluble transferrin receptor be used in diagnosing iron deficiency anemia and assessing iron response in infants with moderate acute malnutrition?

Objetivo. Evaluar la eficacia del receptor soluble de transferrina (RST) en el diagnóstico de la anemia ferropénica (AF) y en la evaluación de la respuesta al hierro en los lactantes con desnutrición aguda moderada (DAM). Población y métodos. Se reclutó a lactantes con valores de hemoglobina (Hb) inferiores a los valores umbrales de anemia para su edad y con anemia hipocrómica/microcítica observada en el frotis de sangre periférica. La DAM se definió como un puntaje Z de peso/estatura de entre < -2 y -3. Se compararon los valores del hemograma, los parámetros férricos y el RST entre 41 lactantes con DAM y anemia (grupo DA), 32 lactantes con anemia sin DAM (grupo A) y controles saludables (n= 30). Una vez completado el tratamiento de la anemia y la desnutrición, se repitieron las evaluaciones. Resultados. Además de los índices hematológicos compatibles con AF, los valores de hierro sérico (Fe) y saturación de transferrina (ST) eran significativamente menores, mientras que el valor de transferrina era significativamente mayor en los grupos DA y A en comparación con los controles (p < 0,001). Los valores de ferritina y proteína C-reactiva (PCR) eran significativamente más elevados en el grupo DA (p < 0,05 para la ferritina, p < 0,01 para la PCR). El valor medio del RST fue similar en ambos grupos (DA y A) (p > 0,05) y significativamente mayor que en los controles (p < 0,001). Después del tratamiento con hierro, el RST disminuyó en los grupos DA y A (p < 0,001) a valores similares a los observados en los controles. El RST se correlacionó negativamente con la Hb durante todo el estudio (grupo DA: r= -0,350, p < 0,05; grupo A: r= -0,683, p < 0,01). Conclusiones. Dado que los valores del RST en los grupos DA y A disminuyeron después del tratamiento con hierro, consideramos que este parámetro no estuvo afectado por la DAM ni la inflamación y puede usarse, por sí solo, para detectar la AF y supervisar la respuesta al tratamiento en los lactantes con DAM.

Objective. To evaluate the efficacy of soluble transferrin receptor (sTfR) in diagnosing iron deficiency anemia (IDA) and evaluating iron response in infants with moderate acute malnutrition (MAM). Population and methods. Infants withhemoglobin (Hb) levels lower than threshold values for anemia for their ages and hypochromic/ microcytic anemia on peripheral smear were recruited. MAM was defined as weight/height z score < -2 to -3. Complete blood count (CBC), iron parameters and sTfR were compared among 41 infants with MAM and anemia (MA group), 32 infants with anemia without MAM (group A), and healthy controls (n= 30). Following anemia and malnutrition treatment, tests were repeated. Results. Besides hematological indices compatible with IDA, serum iron (Fe) and transferrin saturation (TS) were significantly lower, while transferrin was significantly higher in MA and A groups compared to controls (p <0.001). Ferritin and C-reactive protein (CRP) were significantly higher in MA group (p <0.05 ferritin, p <0.01 for CRP). Mean sTfR was similar in both MA and A groups (p >0.05) and significantly higher than controls (p <0.001). Following iron treatment, sTfR decreased inboth MA and A groups (p <0.001) to similar values as controls. sTfR was negatively correlated to Hb throughout the study (for MA group, r= -0.350, p <0.05; for A group, r= -0.683, p <0.01). Conclusions. As sTfR values in both MA and A groups decreased following iron treatment, we believe that this parameter was not influenced by MAM or inflammation; and it alone can be used to detect IDA and monitor treatment response in infants with MAM.

Effect of Artesunate on Transferrin Receptor in K562/ADM Cells / 现代生物医学进展

Objective:To investigate the effect of Artesunate (Art) on the expression of transferrin receptor (TtR)in K562/ADM cells.Methods:The drug-resistant K562/ADM cells were cultured with 1000 ng/mL doxorubicin for two weeks followed by Artesunate treatment with different concentrations (12.5 μg/mL,25μg/mL and 50 μg/mL) or different time (12 h,24 h,36 h,and 48 h).The content of transferrin receptor in K562/ADM cells was determined by flow cytometry.The effect of Artesunate on the expression of transferrin receptor protein in K562/ADM cells was measured by Westem blot.Cell counting kit-8 (CCK-8) assay was used to evaluate inhibitory effect of Art combined with doxorubicin (ADM) in K562/ADM cells.The reversal index was defined as the IC50 of the experimental group divided by the IC50 of the control group in K562/ADM cells.Results:Art effectively decreased the content of transferrin receptor and the expression of transferrin receptor protein in K562/ADM cells in a dose-dependent manner.Moreover,Art also inhibited transferrin receptor protein expression in K562/ADM cells in a time-dependent manner.The different concentrations of Art(12.5 μg/mL,25μg/mL and 50 μg/mL) could induce reversal of drug-resistance with the reversal index being 1.38,2.12 and 2.95 times (P＜0.05).Art inhibited cell proliferation of K562/ADM cells,and the IC50 werel9.7 μmol/L.Conclusions:Art effectively down-regulated the transferrin receptor content as well as transferrin receptor protein expression in K562/ADM cells,which resulted in reversal of drug resistance of K562/ADM cells.Art also inhibited K562/ADM cells proliferation,which has great value in clinical treatment of leukemia.

Effect of Yi Xuesheng Jiaonang combined with Iron Sucrose Injection on serum transferrin receptor and pregnancy outcome with anemia patients in pregnancy / 中国生化药物杂志

Objective To explore the effect of Yi Xuesheng Jiaonang combined with Iron Sucrose Injection on anemia in pregnancy on serum transferrin receptor and pregnancy outcome.Methods 78 patients with anemia in pregnancy form December 2014 to December 2015 of the third people’s Hospital of Cixi were collected and randomly divided into control group and treatment group,each had 39 cases.Control group was given 200 mg Iron Sucrose Injection with 100 mL 0.9%sodium chloride injection intravenous infusion,2 times a week; experiment group were treated on the base of control group with 4 pills of Yi Xuesheng Jiaonang,3 times daily.The course was 28d,and two groups all with a course treatment.After the end of treatment,clinical curative effect,serum transferrin receptor level,liver and renal function and the incidence of adverse pregnancy outcome were observed and compared. Results Serum transferrin receptor levels were increased in two groups after treatment (P<0.05),compared with control group,serum transferrin receptor level of treatment group was even higher (P<0.05), alanine aminotransferase (ALT),aspartate aminotransferase (AST),serum creatinine (Cr) and urea nitrogen ( BUN) and other indicators of liver and kidney function of experiment group had no statistical significance.Adverse pregnancy outcome rate betwen two groups was not statistically significant.Conclusion Yi Xuesheng Jiaonang combined with Sucrose Iron Injection therapy for patients with anemia of pregnancy can significantly increased serum transferrin receptor levels,has higher safety and low adverse pregnancy outcomes rate.

Glicanos de la vellosidad trofoblástica en la anemia ferropénica y la preeclampsia grave / Glycans in villus trophoblast in iron deficiency anemia and early-onset severe preeclampsia

Glycoproteins attached to cell membrane of syncytiotrophoblast are in close contact with maternal blood, thus these molecules could participate in cell-to-cell communication and biological functions involving ligand-receptors in the maternal-fetal interphase. The attached glycans are involved in the stability, folding and exportation of the protein towards the cell membrane. The objective of this study was to characterize the glycan profile of third trimester placental villi obtained from pregnant women with early-onset severe preeclampsia and gestational anemia compared with normal pregnant women. Protein extracts from placental villi were used in lectin blot assays. -2,3 N- and O-linked sialic acid was over-expressed in villous of severe preeclamptic placentas measured by MAA lectin staining. High mannose glycans and Gal-GlcNAc patterns were also increased in severe preeclampsia compared with the other groups. These findings can explain changes in the cell membrane expression of glycoproteins.

Introducción: Las glicoproteínas de la membrana del sincitiotrofoblasto (STB) se encuentran en contacto con la sangre materna, por lo que pueden participar en la comunicación en la interface materno-fetal. Objetivo: caracterizar patrones de glicanos de la vellosidad trofoblástica de mujeres sanas, anémicas por deficiencia de hierro y preeclámpticas graves de inicio temprano. Materiales y métodos: se obtuvieron extractos proteínicos de vellosidad placentaria de tercer trimestre y se determinó la expresión de patrones de glicanos, usando lectinas. Para la comparación de los grupos se utilizó la prueba de Kruskal-Wallis. Resultados: Se encontró una sobreexpresión en los patrones de glicosilación Gal-GlcNAc, manosa y ácido siálico α2-3 en el grupo con preeclampsia. Conclusiones: El aumento en los patrones Gal-GlcNAc, alta manosilación y ácido siálico α2-3, en proteínas de vellosidad placentaria en los pesos moleculares encontrados, pudiera explicar cambios en la expresión de proteínas de membrana del STB.

Expression of transferrin in hematoma brain tissue at different stages after intra cerebral hemorrhage in rats

Objective: To explore the expression of transferrin (Tf) and transferrin receptor (TfR) in hematoma brain tissue at different stage after intracerebral hemorrhage (ICH) in rats. Methods: ICH rats model were established by collagenase method, and rats were sacrificed at 24 h, 72 h, 7 d and 14 d after operation. The levels of Tf and TfR in different periods of rats were detected by immunohistochemical method, and correlation between two groups was analyzed. Results: Tf, TfR-positive cells at each time after operation in observation group were significantly higher than that in control group (P < 0.05). Tf, TfR-positive cells began to increase from 24 h after the operation and reached the peak 72 h-7 d after surgery, but then gradually decreased. Tf was mainly expressed in nucleus and cytoplasm of neurons and glial cells around the hematoma, but TfR was mainly expressed in nucleus and cytoplasm of neurons and choroid plexus endothelial cells. Correlation analysis showed that the Tf-positive cell was significantly positively correlated with TfR-positive cell expression (r = 0.447, P = 0.022). Conclusions: Tf and TfR were important transporters in brain tissue excessive load iron transport after ICH, and detecting the expression levels of the two indicators can provide a reference for prognosis treatment in ICH.