Research progress on treatment strategies for related diseases based on Parthanatos / 中国生物制品学杂志

@#Parthanatos is a form of programmed cell death,which is also known as poly(ADP-ribose)polymerase 1(PARP1)-mediated apoptosis-inducing factor(AIF)and macrophage migration inhibitory factor(MIF)-dependent cell death according to its molecular mechanism. Parthanatos is the main cause of a variety of neurodegenerative diseases,such as Parkinson's disease(PD),Alzheimer's disease(AD),motor neuron disease,and is also involved in the pathogenesis of some tumors,such as lung cancer and breast cancer. Therefore,a thorough understanding of the molecular mechanism of Parthanatos is crucial for the therapeutic strategies of related diseases. In recent years,studies have found that effective regulation of the occurrence of Parthanatos by regulating the key proteins PARP1,AIF and MIF is expected to become a therapeutic target for many diseases. Based on the specific molecular mechanism of Parthanatos,this paper reviewed the research progress of therapeutic strategies for related diseases from the aspects of inhibiting and promoting Parthanatos.

Influencing Factors Regulating the Expression of the Macrophage Migration Inhibitor Factor (MIF) Gene / 中国生物化学与分子生物学报

Macrophage migration inhibitory factor (MIF) is a widely expressed multipotent cytokine that participates and plays an important role in various inflammatory and immune diseases‚ and is a biomarker or therapeutic target of many diseases. MIF is highly conserved in phylogeny and there are specific binding sites of various transcription factors in its promoter region‚ which can regulate the expression of MIF. MIF functions both inside and outside cells‚ and MIF is constitutively expressed. Therefore‚ it is of great significance to study the related factors that regulate MIF gene expression and stimulate MIF secretion. This article summarizes and classifies the related factors affecting MIF gene expression by briefly describing the binding sites on the MIF gene and MIF promoter. According to the way of binding with the MIF gene‚ it can be divided into:(1) binding to specific sites of MIF gene promoters to change transcription activity; (2) binding to MIF CATT5-8 microsatellite repeats to change highly expressed MIF alleles (3) non-coding RNAs regulating MIF expression; (4) related factors affecting MIF secretion. By reviewing the four types of related factors that regulate MIF gene expression‚ we will understand the regulatory mechanism and influencing factors of MIF gene expression‚ in order to provide a theoretical basis for its treatment of related diseases.

Advances in researches on mechanism of macrophage migration inhibitory factor regulating parasite-host immune interaction / 中国血吸虫病防治杂志

Macrophage migration inhibitory factor (MIF), a type of pleiotropic immunoregulatory cytokine with a specific structure, participates in the regulation of host cell growth and migration and immune responses. Following parasitic infections, hosts may produce MIF and then participate in the parasite-host interactions. In addition, parasites may secrete parasite-derived MIF, and they jointly participate in parasite-host interactions. This paper reviews the regulation of MIF gene expression following parasitic infections, the role of MIF in parasite-host immune system interactions, and important signaling pathways of MIF-mediated immune responses.

Advances in researches on mechanism of macrophage migration inhibitory factor regulating parasite-host immune interaction / 中国血吸虫病防治杂志

Macrophage migration inhibitory factor (MIF), a type of pleiotropic immunoregulatory cytokine with a specific structure, participates in the regulation of host cell growth and migration and immune responses. Following parasitic infections, hosts may produce MIF and then participate in the parasite-host interactions. In addition, parasites may secrete parasite-derived MIF, and they jointly participate in parasite-host interactions. This paper reviews the regulation of MIF gene expression following parasitic infections, the role of MIF in parasite-host immune system interactions, and important signaling pathways of MIF-mediated immune responses.

Efficacy of Yanhuning injection in the treatment of acute viral myocarditis with Xiedu Qinxin syndrome / 中国基层医药

Objective To investigate the effect of Yanhuning injection antiviral therapy in the treatment of acute viral myocarditis patients with Xiedu Qinxin syndrome.Methods From May 2016 to August 2017,84 acute viral myocarditis patients with Xiedu Qinxin syndrome in the Integrated Traditional Chinese and Western Medicine Hospital of Wenzhou were enrolled in this study.According to the digital table,they were randomly divided into observation group and the control group,with 42 cases in each group.The control group received conventional antiviral therapy,and the observation group was given Yanhuning injection.The heart type free fatty acid binding protein (H－FABP),serum troponin Ⅰ (cTnI),macrophage migration inhibitory factor(MIF)and interleukin 4(IL－4)were measured before and after treatment for 4 weeks.The clinical symptoms score and the effective rate were compared between the two groups at the same time.Results The serum levels of cTnI,H－FABP,MIF and IL－4 of the two groups after treatment were lower than those before treatment(all P＜0.05 ),which of the observation group after treatment were significantly lower than those of the control group (t＝3.012,P＝0.039;t＝2.835,P＝0.040;t＝3.534,P＝0.032;t＝3.323,P＝0.033).The effective rate of the observation group was significantly higher than that of the control group (90.48% vs.80.95%,χ2＝3.432,P＝0.038).The scores of palpitations,sore throat,upsetting the chest tightness of the observation group after treatment were significantly lower than those of the control group (t＝3.045,P＝0.038;t＝2.946,P＝0.039;t＝3.467,P＝0.031;t ＝3.358,P＝0.032).Conclusion Yanhuning injection antiviral therapy in the treatment of acute viral myocarditis patients with Xiedu Qinxin syndrome can signifi-cantly improve the efficacy of patients.

Expression and Clinical Significance of Macrophage Migration Inhibitory Factor in the Serum and Lung Tissues in Patients with Non-Small Cell Lung Cancer / 中山大学学报(医学科学版)

[Objective]To investigate the expression and the clinical significance of macrophage migration inhibitory factor (MIF)in the serum and lung tissues of the patients with non-small cell lung cancer(NSCLC).[Methods]Eighty-eight eligible inpatients were confirmed by pathology of lung tissues ,including 66 patients with NSCLC and 22 patients with benign lung lesions. ELISA was performed to measure serum concentration of MIF of these patients ,which was compared with 30 healthy individuals. Meanwhile,immunohistochemistry(IHC)was performed to examine the expression of MIF in the lung tissues of the two groups. MIF expression level was compared between two groups and among different subgroups of NSCLC. The correlationship between serum MIF level and high expression rate in lung tissues was also analyzed. All the data were analyzed by SPSS17.0.[Results]The serum concentration of MIF in NSCLC group was significantly higher than that in healthy control(14.79 ng/mL vs 10.69 ng/mL,P=0.001), and was slightly higher but not significantly different from benign lung lesions group(14.79 ng/mL vs 13.68 ng/mL,P=0.580). The comparison among subgroups of NSCLC showed that the serum MIF level was not only correlated with the histological grade and clini?cal stage of the cancer,but also correlated with the gender and smoking history of the host. Immunohistochemistry showed that the MIF high expression rate in the lung tissues of NSCLC was markedly higher than that of benign lung lesions group(30.3%vs 4.5%, P=0.014). Among the subgroups of NSCLC,IHC showed MIF high expression rate was correlated with the histopathologic types and clinical stage of the cancer. Simultaneously ,the serum MIF level showed a positive correlation with MIF expression rate in the lung tissues in all patients and NSCLC group(P<0.05).[Conclusion]MIF was strongly related to the clinicopathological characteristics of NSCLC. It could be helpful for the diagnosis and clinical evaluation of NSCLC.

Effects of berberine on serum inflammatory factors and carotid atherosclerotic plaques in patients with acute cerebral ischemic stroke / 中国中药杂志

This study aims to analyze the effect of berberine on serum inflammatory factors and carotid atherosclerotic plaques in ppatients with acute cerebral ischemic stroke(AIS). In the study, 120 patients with AIS were randomly divided into berberine group(n=60) and general group (n=60). The 60 cases in the general group were provided with general therapy according to the latest guidelines of diagnosis and treatment of AIS. The berberine group received berberine 300 mg(tid) in addition to the therapy of the general group. The levels of serum inflammatory factors, the nerve function defect grades and the indexes of carotid atherosclerosis plaques [including the total plaque area(TPA), intima-media thickness(IMT) and the number of unstable carotid atherosclerotic plaques] were measured and compared. The results indicated that the levels of serum inflammatory factors, the NIHSS(national institute of health stroke scales) cores and the indexes of carotid atherosclerosis plaques were not significantly different between the berberine groups of general group, with positive correlation between serum inflammatory factors and NIHSS scores(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine groups on 14 d were significantly lower than those on 1 d(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine group on 14 d were significantly lower than those of the general group(P<0.05). The TPA and the number of unstable carotid atherosclerotic plaques of the berberine groups on 90 d were significantly lower than those of general group, with significant differences(P<0.05). The IMT showed a downward trend, but with significant difference.The mRS(modified rankin scale) scores of the berberine group on 90 d were significantly lower, with a higher rate of short-term favorable prognosis (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups. This study showed that berberine in addition to the general therapy can significantly lower the levels of serum MIF and IL-6, reduce the degree of carotid atherosclerosis to some extent and improve neurological impairment and the prognosis of patients with AIS.

Increased circulating macrophage migration inhibitory factor levels are associated with coronary artery disease

BACKGROUND: To evaluate the macrophage migration inhibitory factor and E-selectin levels in patients with acute coronary syndrome. MATERIALS/METHODS: We examined the plasma migration inhibitory factor and E-selectin levels in 87 patients who presented with chest pain at our hospital. The patients were classified into two groups according to their cardiac status. Sixty-five patients had acute myocardial infarction, and 22 patients had non-cardiac chest pain (non-coronary disease). We designated the latter group of patients as the control group. The patients who presented with acute myocardial infarction were further divided into two subgroups: ST-elevated myocardial infarction (n = 30) and non-ST elevated myocardial infarction (n = 35). RESULTS: We found higher plasma migration inhibitory factor levels in both acute myocardial infarction subgroups than in the control group. However, the E-selectin levels were similar between the acute myocardial infarction and control patients. In addition, we did not find a significant difference in the plasma migration inhibitory factor levels between the ST elevated myocardial infarction and NST-elevated myocardial infarction subgroups. DISCUSSION: The circulating concentrations of migration inhibitory factor were significantly increased in acute myocardial infarction patients, whereas the soluble E-selectin levels were similar between acute myocardial infarction patients and control subjects. Our results suggest that migration inhibitory factor may play a role in the atherosclerotic process. .

Expression of MIF in molecular subtypes of breast cancer and its clinical significance / 西安交通大学学报(医学版)

Objective To determine the expression of macrophage migration inhibitory factor (MIF)in different molecular subtypes of breast cancer and its clinical significance so as to detect the biological markers of different molecular subtypes of breast cancer.Methods We divided 100 breast cancer patients into four molecular subtypes by immunostaining:luminal subtype,HER-2(+)subtype,basal-like (BLs)subtype and normal breast-like (NBLs)subtype,and then compared the expression of MIF in the groups.We analyzed the associations of MIF-positive expression rate with age,menstruation,tumor size,auxiliary lymph node metastasis,histological type and grade,and clinical stage of the breast cancer patients.We also compared MVD level and 5-year overall survival rate between MIF-positive patients and MIF-negative ones.Results The positive expression of MIF was correlated with HER2(+)subtype breast cancer and auxiliary lymph node metastasis (P < 0.05 ).The patients with MIF-positive expression had a significantly higher level of MVD than those with MIF-negative expression (P < 0.05 ). Kaplan-Meier method showed that MIF-positive patients had a poor prognosis than MIF-negative ones (Log-rank=1 9.5 1 6,P = 0.000).Conclusion Breast cancer patients with MIF-positive expression may be mostly of HER2 (+)subtype,and tend to develop auxiliary lymph node metastasis.These patients have a significantly higher level of MVD and poor prognosis than those with MIF-negative expression.

Research progress on liver injury in acute pancreatitis / 中华肝胆外科杂志

Considerable clinical and experimental evidence supports that liver injury in acute pancreatitis (AP) is a sign for the potential progression to systemic inflammatory reaction.The Kupffer cells,various cytokines and macrophage migration inhibitory factor (MIF) play important roles in the pathogenesis of AP associated liver injury.However,the specific molecular mechanism of the liver damage remains uncertain.Therefore,efforts should be made to clarify the regulatory mechanism and related cell signaling disorders of liver injury in AP,which could not only identify novel therapeutic targets,but also provide new insight into improving the clinical treatment.Here our review discusses the recent research progress on the etiology,pathology and diagnosis and treatments of liver injury in AP.

Radioimmunoassay for Determination of Serum Macrophage Migration Inhibitory Factor / 대한핵의학회잡지

PURPOSE: There has been a renewal of interest in Macrophage migration inhibitory factor (MIF), especially correlation in pathogenesis of sepsis by many infectious diseases and in regulation of host inflammatory and immune response. We developed immunoradiometric assay (IRMA) to determine serum human MIF concentration. MATERIALS AND METHODS: The IRMA system utilizes solid phase bound monoclonal anti-recombinant human MIF (rhMIF) antibody as a capture antibody, biotinylated polyclonal anti-rhMIF antibody as a detector antibody. We applied with rhMIF that concentration of standard solutions increased from 0 ng/ml to 100 ng/ml. We used 125I-streptavidin (SA) as radiotracer to determination of rhMIF concentration. Streptavidin was labeled with 125I by Chloramine-T method and 125I-SA was purified by ultracentrifugation. 125I-SA stability was evaluated by ITLC analysis at 4 degrees C and room temperatures until 60days. To validate IRMA system for MIF, we experimented intra-assay and inter-assay coefficients of variation, recovery test and dilution test. RESULTS: Radiolabeling yield of 125I-SA was 87% and purified 125I-SA retained above 99% radiochemical purity. 125I-SA showed above 93% stability in 4 degrees C until 60days that it is good for immunoradiometric assay as radiotracer. Plotted standard dose response curve showed that increased concentration of rhMIF linearly correlated (R2=0.99) with bound radioactivity of 125I-SA. The highest intra- and inter-assay coefficients of variation were 5.5% and 7.6%, respectively. The average of recovery of MIF in samples was 102%. In dilution test, linear response curves were obtained (R2=0.97). CONCLUSION: Radioimmunoassay using 125I-SA as radiotracer thought to be useful for the determination of serum MIF concentration, and further, its data will be used to evaluate the correlation between clinical significance and serum MIF concentration in patients with various inflammatory diseases.

Elevated Serum Levels of Macrophage Migration Inhibitory Factor (MIF) in Patients with Behcet's Disease / 대한류마티스학회지

OBJECTIVE: Macrophage migration inhibitory factor (MIF) has emerged recently as an important regulator of inflammatory and immune responses. This work was undertaken to evaluate serum levels of MIF and in vitro MIF production by whole blood cells in patients with Behcet's disease and investigate the relationship between serum levels of MIF and clinical manifestations. METHODS: Sixty-five patients with Behcet's disease and forty-eight healthy controls were studied to evaluate serum levels of MIF. Six patients with Behcet's disease and Five healthy controls were studied for evaluating the production of MIF by whole blood cells. Serum and culture supernatant levels of MIF were measured by enzyme-linked immunosorbent assay (ELISA). The production of MIF by whole blood cells was investigated by culturing peripheral blood cells in the absence or presence of Concanavalin A (Con A). RESULTS: Serum levels of MIF were higher in patients with Behcet's disease than in healthy controls. Serum levels of MIF were changed in each patient with Behcet's disease according to clinical disease activity (higher at active state). The MIF production by Con A-stimulated peripheral blood cell culture was higher in patients with Behcet's disease than in healthy controls. CONCLUSION: Circulating levels of MIF are higher in patients with Behcet's disease than in healthy controls and the levels of MIF may be associated with clinical disease activity. MIF may play an important role as a mediator of inflammation in Behcet's disease and provide opportunity for the development of anti-MIF strategy for the treatment of patients with Behcet's disease.

Normal Serum Macrophage Migration Inhibitory Factor Concentrations of Korean people According to Age

BACKGROUND: Macrophage migration inhibitory factor(MIF) was discovered in 1960s as a T-cell cytokine which inhibited random migration of macrophages. MIF is a multifunctional protein acting as cytokine, hormone, or enzyme. It plays a pivotal role in innate and adaptive immune responses and early phase of inflammatory response, as well as cell proliferation, differentiation, and tumor progression. Many inflammatory diseases and cancers show increased activity and serum concentration. The purpose of this study was to measure the normal serum MIF concentration of Korean people to be utilized as base data for future MIF research. METHODS: Sera of 20 healthy adults from each groups of 20's to 60's(total 100 persons) who visited the Health Promotion center of Inha university Hospital were collected. The MIF concentration in each serum was measured by enzyme-linked immunosorbent assay(ELISA). RESULTS: The average serum MIF concentration was 1.49 ng/ml(ranging from 0 to 3.33), and there was no significant difference between age groups. CONCLUSION: The normal serum MIF concentration of Korean people is 1.49 ng/ml, and seems to be unchanged with aging.