β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to...β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to be highly related to ischemic stroke,the specific role and underlying mechanistic action ofβ2M are poorly understood.In this study,we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery.We found thatβ2M levels in the cerebral spinal fluid,serum,and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period.RNA interference was used to inhibitβ2M expression in the acute period of cerebral stroke.Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreasedβ2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits,respectively.Notably,glial cell,caspase-1(p20),and Nod-like receptor pyrin domain containing 3(NLRP3)inflammasome activation as well as production of the inflammatory cytokines interleukin-1β,interleukin-6,and tumor necrosis factor-αwere also effectively inhibited byβ2M silencing.These findings suggest thatβ2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.展开更多
AIM: To investigate the diagnostic utility of beta 2 microglobulin (B2-M) levels and analyze this correlation with the activity of inflammatory bowel disease (IBD).
BACKGROUND Retinopathy is the most common microvascular disease of type 2 diabetes,and seriously threatens the life,health and quality of life of patients.It is worth noting that the development of diabetic retinopath...BACKGROUND Retinopathy is the most common microvascular disease of type 2 diabetes,and seriously threatens the life,health and quality of life of patients.It is worth noting that the development of diabetic retinopathy(DR)can be hidden,with few symptoms.Therefore,the preliminary screening of diabetic patients should identify DR as soon as possible,delay disease progression,and play a vital role in its diagnosis and treatment.AIM To investigate the correlation between glycated hemoglobin A1c(HbA1c),urinary microalbumin(U-mALB),urinary creatinine(U-CR),mALB/U-CR ratio,β2 microglobulin(β2MG),retinol binding protein(RBP)and DR.METHODS A total of 180 patients with type 2 diabetes mellitus attending the Second People’s Hospital of Hefei from January 2022 to August 2022 were retrospectively enrolled by ophthalmologists.Based on whether they had combined retinopathy and its degree,68 patients with diabetes mellitus without retinopathy(NDR)were assigned to the NDR group,54 patients with non-proliferative DR(NPDR)to the NPDR group,and 58 patients with proliferative DR to the PDR group.General data,and HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR results were collected from the patients and compared among the groups.Pearson's correlation method was used to analyze the correlation between HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR indices,and multiple linear regression was applied to identify the risk factors for DR.Receiver operator characteristic(ROC)curves were also drawn.RESULTS The differences in age,gender,systolic and diastolic blood pressure between the groups were not statistically significantly(P>0.05),but the difference in disease duration was statistically significant(P<0.05).The differences in fasting blood glucose,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,total cholesterol,and triglyceride between the groups were not statistically significant(P>0.05).HbA1c in the PDR group was higher than that in the NPDR and NDR groups(P<0.05).The levels of mALB,β2MG,RBP,mALB/U-CR and UCR in the PDR group were higher than those in the NPDR and NDR groups(P<0.05).Multiple linear regression analysis showed that disease duration,HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR were risk factors for the development of DR.The ROC curve showed that the area under the curve(AUC)for the combination of indices(HbA1c+mALB+mALB/U-CR+U-CR+β2MG+RBP)was 0.958,with a sensitivity of 94.83%and specificity of 96.72%,which was higher than the AUC for single index prediction(P<0.05).CONCLUSION HbA1c,mALB,mALB/U-CR,U-CR,β2MG and RBP can reflect the development of DR and are risk factors affecting PDR,and the combination of these six indices has predictive value for PDR.展开更多
Objective To evaluate the effect of revascularization of the renal artery on urinary microglobulin in patients with coronaryartery disease and significant renal artery stenosis(RAS).Methods Forty-four patients with co...Objective To evaluate the effect of revascularization of the renal artery on urinary microglobulin in patients with coronaryartery disease and significant renal artery stenosis(RAS).Methods Forty-four patients with coronary artery disease and severe RAS(luminal narrowing>70%)underwent percutaneous transluminal renal artery angioplasty(PTRA)and stenting,as well as percutaneous coronary intervention.The urine-microglobulin(α_(1)-MG)andβ_(2)-Cmicroglobulin(β_(2)-MG)at baseline and at 3 months after the procedures were measured.Procedural success rate,procedural complications,serum creatinine concentration at baseline and at 3-months were also recorded.Results At 3-months after the renal revascularization therapy,there was no significant change of urineα_(1)-MG ompared with that of the baseline,however,the urineβ_(2)-MG decreased significantly 3-months after the treatment(237±187μg/L vs 377±173μg/L,P<0.01).Multivariate analysis revealed that persistent elevation of urine was an independent predictor of severe events(including re-admission and renal failure)after renal revascularization therapy in patients with severe RAS(OR=3.01,95%CI 1.01-8.95,P=0.036).Conclusions In patients with coronary artery disease and severe RAS,revascularization with PTRA and stenting may improve renal tubular function,but a continuous high level of urinary microglobulins after intervention is associated with more frequent re-hospitalization and renal failure.展开更多
Urineβ_2-microglobulin (β_2-m) was measured in 433 persons with low-level, long-term environmental exposure to Cd, and in 124 control persons from unpolluted area. In 152 of the exposed persons, and some of the cont...Urineβ_2-microglobulin (β_2-m) was measured in 433 persons with low-level, long-term environmental exposure to Cd, and in 124 control persons from unpolluted area. In 152 of the exposed persons, and some of the controls, the urine β-m exceeded the limit. Of the 433 exposed persons, 74 cases with both urine Cd and β_2-m exceeding the limit were matched by the control. This study suggests that after the stratification of the degrees of renal tubular injury according to the fractional β_2-m excretion (FE β_2-m) and coordination of clinical examination, FE β_2-m could contribute to identifying renal tubular dysfunction due to Cd exposure and kidney lesion when both Cd exposure and original nephropathy exist.展开更多
Objectives: Evaluation of diagnostic performance of rapid testing of cervico-vaginal fluid (CVF) for fetal fibronectin (FFN) and placental α-microglobulin 1 (PAMG-1) as screening of women presented by threatened pret...Objectives: Evaluation of diagnostic performance of rapid testing of cervico-vaginal fluid (CVF) for fetal fibronectin (FFN) and placental α-microglobulin 1 (PAMG-1) as screening of women presented by threatened preterm labor (TPTL) with intact membranes for duration till getting spontaneous labor (SL). Patients & Methods: 37 women presenting with TPTL underwent CVF samplings before digital examination and then underwent transvaginal ultrasonography for estimation of cervical length (CL). All women received fluid and anxiolytic therapy and if uterine contractions persisted, all had received tocolytic therapy with oral nifedipine or intravenous magnesium sulphate according to requirements. Incidence of SL within Results: Incidence of SL was 13.5%, 35.2% and 51.3% within 48-hr, 2 - 7 and 7 - 14 days, respectively. Duration till labor after sampling was positively correlated with CL, while was negatively correlated with positive FFN and PAMG-1 tests. Positive FFN test had high specificity, while positive PAMG-1 test had high sensitivity for labor within 7 days. Regression analysis defined short CL and positive PAMG-1 test as significant predictors for short duration till SL. ROC curve analysis defined short cervix and positive PAMG-1 test as significant predictors for labor within 48-hr and within 2 - 7 days respectively and combined negative PAMG-1 test and CL of 20 - 25 mm were significant predictors for labor within 7 - 14 days. Conclusion: PAMG-1 test had high specificity, if positive, for predicting SL and high NPP, if negative, for excluding labor within 7 days, so it can be used as rapid adjuvant to clinical evaluation to help management decision-making. Moreover, PAMG-1 test is recommended screening test for being easy-to-use bedside test, provides rapid results, can be used after vaginal exam and coitus and does not require a speculum examination or specialized equipment to analyze results.展开更多
Chronic inflammation in adipose tissue is widely recognized as a pivotal link connecting obesity to a spectrum of related chronic diseases,including type 2 diabetes,non-alcoholic fatty liver disease,and cardiovascular...Chronic inflammation in adipose tissue is widely recognized as a pivotal link connecting obesity to a spectrum of related chronic diseases,including type 2 diabetes,non-alcoholic fatty liver disease,and cardiovascular disorders.In this pathogenic process,the dysregulated interaction between adipocytes and adipose-resident immune cells plays a critical regulatory role;however,the underlying mechanisms governing this abnormal interaction remain largely unknown.In this study,we showed that upregulatedβ2-microglobulin expression in hypertrophic adipocytes during obesity not only mediated the activation of adipose-resident CD8+T cells in a cell contact-dependent manner but also facilitated iron overload and the ferroptosis of adipocytes,thereby promoting the M1 polarization of adipose tissue macrophages.Conversely,specific ablation ofβ2-microglobulin in adipocytes effectively suppressed the activation and accumulation of adipose-resident CD8+T cells,as well as adipocyte ferroptosis and M1 polarization,ultimately preventing high-fat diet-induced obesity and its related inflammation and metabolic disorders.Additionally,adenoassociated virus-mediated adipose-targeted knockdown ofβ2-microglobulin has been demonstrated to therapeutically alleviate high-fat diet-induced obesity,as well as its related chronic inflammation and metabolic disorders.Furthermore,our bioinformatic analysis of human adipose transcriptome data revealed a strong correlation between adiposeβ2-microglobulin and obesity.More importantly,β2-microglobulin is significantly upregulated in adipocytes isolated from patients with obesity.Thus,our findings highlight the pivotal role of adipocytes in obesity-associated chronic inflammation and metabolic disorders viaβ2-microglobulindependent mechanisms.展开更多
Objective： This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin （β2M）, a conservative immune molecule in vertebrate.Data Sources： The data used in this review w...Objective： This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin （β2M）, a conservative immune molecule in vertebrate.Data Sources： The data used in this review were obtained from PubMed up to October 2015.Terms of β2M, immune response, and infection were used in the search.Study Selections： Articles related to β2M were retrieved and reviewed.Articles focusing on the characteristic and function of β2M were selected.The exclusion criteria of articles were that the studies on β2M-related molecules.Results： β2M is critical for the immune surveillance and modulation in vertebrate animals.The dysregulation of β2M is associated with multiple diseases, including endogenous and infectious diseases.β2M could directly participate in the development of cancer cells, and the level of β2M is deemed as a prognostic marker for several malignancies.It also involves in forming major histocompatibility complex （MHC class Ⅰ or MHC Ⅰ） or like heterodimers, covering from antigen presentation to immune homeostasis.Conclusions： Based on the characteristic of β2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools.Moreover, β2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of β2M on applications.展开更多
Background Acute renal failure （ARF） after liver transplantation is associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of early effective prognostic fa...Background Acute renal failure （ARF） after liver transplantation is associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of early effective prognostic factors. Recent studies indicated that serum levels of cystatin C and β2-microglobulin （β2 MG） as well as urinary β2 MG and N-acetyI-β-D- glucosaminidase （NAG） would increase in patients with early and mild renal impairment. In this study, these factors were detected during the different stages in patients who accepted orthotopic liver transplantation （OLT）, and their feasibilities to predict early ARF after OLT were also analyzed. Methods Sixty patients with normal blood urea nitrogen （BUN） and serum creatinine （SCr） who received modified piggyback liver transplantation without veno-venous bypass were prospectively studied. Blood samples were drawn from patients for the determination of serum β2 MG（n=60）, SCr （n=60） and serum Cystatin C （n=39） at following 5 intervals： before operation （TO）, 20 minutes before anhepatic phase （T1）, 25 minutes in anhepatic （T2）, 60 minutes after reperfusion （T3） and at the end of operation（T4）. Urinary B2 MG （n=60） and NAG （n=60） were also examined at following 3 intervals： before operation （TO）, 60 minutes after reperfusion （T3） and at the end of operation （T4）. According to the Rimola A criteria of ARF in 24 hours after operation, all the patients were divided into two groups： ARF group and non-ARF group. The data were statistically analyzed to evaluate the feasibiliy of regarding these factors as prognostic factors for early ARF after liver transplantation in patients with normal SCr and BUN before operation. Results Ten of sixty cases showed ARF（16.7%）. The Logistic regression analysis showed that the levels of serum and urinary β2 MG as well as serum cystatin C before operation were correlated with early ARF after liver transplantation （P 〈0.05）, while only serum levels of cystatin C and Cr at the end of operation correlated with early ARF （P〈0.05, P〈0.01） after liver transplantation. The serum β2 MG, Cystatin C, SCr and urinary β2 MG levels in ARF group were much more higher than that in non-ARF group（P 〈0.05, P 〈0.01）. There were significant differences between the correct and false predictive positive ratios of serum cystatin C, serum and urinary β2 MG levels before operation （P 〈0.05, P 〈0.01）, while only SCr showed significant difference between these groups at the end of operation （P 〈0.01）. Conclusions The results revealed that there was potential renal damage among those patients who demonstrated normal SCr and BUN before operation, and that liver transplantation could aggravate this damage and causing ARF. Here we provided the prognostic values of serum Cystatin C, β2 MG, urinary β2 MG and NAG in patients with early acute renal failure after liver transplantation.展开更多
Background：As a major complication after orthotopic liver transplantation （OLT）,the occurrence of acute kidney injury （AKI） is frequently defined by serum creatinine （Cr）;however,the accuracy of commonly used b...Background：As a major complication after orthotopic liver transplantation （OLT）,the occurrence of acute kidney injury （AKI） is frequently defined by serum creatinine （Cr）;however,the accuracy of commonly used blood urea nitrogen （BUN）,uric acid （UA）,and β2-microglobulin （β2-MG） remains to be explored.This retrospective study compared the accuracy of these parameters for post-OLT AKI evaluation.Methods：Patients who underwent OLT in three centers between July 2003 and December 2013 were enrolled.The postoperative AKI group was diagnosed by the Kidney Disease Improving Global Outcomes （KDIGO） criteria and classified by stage.Measurement data were analyzed using the t-test or Wilcoxon rank-sum test;enumerated data were analyzed using the Chi-square test or Fisher＇s exact test.Diagnostic reliability and predictive accuracy were evaluated using receiver operating characteristic （ROC） curve analysis.Results：This study excluded 976 cases and analyzed 697 patients （578 men and 1 1 9 women）;the post-OLT AKI incidence was 0.409.Compared with the no-AKI group,the AKI group showed very significant differences in Model for End-stage Liver Disease score （14.74 ± 9.91 vs.11.07 ± 9.54,Z =5.404;P ＜ 0.001）,hepatic encephalopathy （45 [15.8％] vs.30 [7.3％],x2 =12.699;P ＜ 0.001）,hemofiltration （28 [9.8％] vs.0 [0.0％],x2 =42.171;P ＜ 0.001）,and 28-day mortality （23 [8.1％] vs.9 [2.2％],x2 13.323;P ＜0.001）.Moreover,mean values of Cr,BUN,UA,and β2-MG in the AKI group differed significantly at postoperative days 1,3,and 7 （all P ＜0.001）.ROC curve area was 0.847 of Cr for the detection of AKI Stage 1 （sensitivity 80.1％,specificity 75.7％,cutoffvalue 88.23 μmol/L）,0.916 for Stage 2 （sensitivity 87.6％,specificity 82.6％,cutoff value 99.9 μmol/L）,and 0.972 for Stage 3 （sensitivity 94.1％,specificity 88.2％,cutoff value 122.90 μmol/L）.Conclusion：The sensitivity and specificity of serum Cr might be a high-value indicator for the diagnosis and grading of post-OLT AKI.展开更多
Recent research by Gao et al.published in Cell proposes that circulatingβ2-microglobulin impairs synaptic function through antagonizing NMDA receptors in two mouse models of Down syndrome(DS),providing a potentially ...Recent research by Gao et al.published in Cell proposes that circulatingβ2-microglobulin impairs synaptic function through antagonizing NMDA receptors in two mouse models of Down syndrome(DS),providing a potentially novel therapeutic target to combat cognitive deficits in the early stage of DS.^(1)展开更多
基金supported by the National Natural Science Foundation of China,No.81771337(to RQY).
文摘β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to be highly related to ischemic stroke,the specific role and underlying mechanistic action ofβ2M are poorly understood.In this study,we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery.We found thatβ2M levels in the cerebral spinal fluid,serum,and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period.RNA interference was used to inhibitβ2M expression in the acute period of cerebral stroke.Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreasedβ2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits,respectively.Notably,glial cell,caspase-1(p20),and Nod-like receptor pyrin domain containing 3(NLRP3)inflammasome activation as well as production of the inflammatory cytokines interleukin-1β,interleukin-6,and tumor necrosis factor-αwere also effectively inhibited byβ2M silencing.These findings suggest thatβ2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.
文摘AIM: To investigate the diagnostic utility of beta 2 microglobulin (B2-M) levels and analyze this correlation with the activity of inflammatory bowel disease (IBD).
文摘BACKGROUND Retinopathy is the most common microvascular disease of type 2 diabetes,and seriously threatens the life,health and quality of life of patients.It is worth noting that the development of diabetic retinopathy(DR)can be hidden,with few symptoms.Therefore,the preliminary screening of diabetic patients should identify DR as soon as possible,delay disease progression,and play a vital role in its diagnosis and treatment.AIM To investigate the correlation between glycated hemoglobin A1c(HbA1c),urinary microalbumin(U-mALB),urinary creatinine(U-CR),mALB/U-CR ratio,β2 microglobulin(β2MG),retinol binding protein(RBP)and DR.METHODS A total of 180 patients with type 2 diabetes mellitus attending the Second People’s Hospital of Hefei from January 2022 to August 2022 were retrospectively enrolled by ophthalmologists.Based on whether they had combined retinopathy and its degree,68 patients with diabetes mellitus without retinopathy(NDR)were assigned to the NDR group,54 patients with non-proliferative DR(NPDR)to the NPDR group,and 58 patients with proliferative DR to the PDR group.General data,and HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR results were collected from the patients and compared among the groups.Pearson's correlation method was used to analyze the correlation between HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR indices,and multiple linear regression was applied to identify the risk factors for DR.Receiver operator characteristic(ROC)curves were also drawn.RESULTS The differences in age,gender,systolic and diastolic blood pressure between the groups were not statistically significantly(P>0.05),but the difference in disease duration was statistically significant(P<0.05).The differences in fasting blood glucose,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,total cholesterol,and triglyceride between the groups were not statistically significant(P>0.05).HbA1c in the PDR group was higher than that in the NPDR and NDR groups(P<0.05).The levels of mALB,β2MG,RBP,mALB/U-CR and UCR in the PDR group were higher than those in the NPDR and NDR groups(P<0.05).Multiple linear regression analysis showed that disease duration,HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR were risk factors for the development of DR.The ROC curve showed that the area under the curve(AUC)for the combination of indices(HbA1c+mALB+mALB/U-CR+U-CR+β2MG+RBP)was 0.958,with a sensitivity of 94.83%and specificity of 96.72%,which was higher than the AUC for single index prediction(P<0.05).CONCLUSION HbA1c,mALB,mALB/U-CR,U-CR,β2MG and RBP can reflect the development of DR and are risk factors affecting PDR,and the combination of these six indices has predictive value for PDR.
文摘Objective To evaluate the effect of revascularization of the renal artery on urinary microglobulin in patients with coronaryartery disease and significant renal artery stenosis(RAS).Methods Forty-four patients with coronary artery disease and severe RAS(luminal narrowing>70%)underwent percutaneous transluminal renal artery angioplasty(PTRA)and stenting,as well as percutaneous coronary intervention.The urine-microglobulin(α_(1)-MG)andβ_(2)-Cmicroglobulin(β_(2)-MG)at baseline and at 3 months after the procedures were measured.Procedural success rate,procedural complications,serum creatinine concentration at baseline and at 3-months were also recorded.Results At 3-months after the renal revascularization therapy,there was no significant change of urineα_(1)-MG ompared with that of the baseline,however,the urineβ_(2)-MG decreased significantly 3-months after the treatment(237±187μg/L vs 377±173μg/L,P<0.01).Multivariate analysis revealed that persistent elevation of urine was an independent predictor of severe events(including re-admission and renal failure)after renal revascularization therapy in patients with severe RAS(OR=3.01,95%CI 1.01-8.95,P=0.036).Conclusions In patients with coronary artery disease and severe RAS,revascularization with PTRA and stenting may improve renal tubular function,but a continuous high level of urinary microglobulins after intervention is associated with more frequent re-hospitalization and renal failure.
文摘Urineβ_2-microglobulin (β_2-m) was measured in 433 persons with low-level, long-term environmental exposure to Cd, and in 124 control persons from unpolluted area. In 152 of the exposed persons, and some of the controls, the urine β-m exceeded the limit. Of the 433 exposed persons, 74 cases with both urine Cd and β_2-m exceeding the limit were matched by the control. This study suggests that after the stratification of the degrees of renal tubular injury according to the fractional β_2-m excretion (FE β_2-m) and coordination of clinical examination, FE β_2-m could contribute to identifying renal tubular dysfunction due to Cd exposure and kidney lesion when both Cd exposure and original nephropathy exist.
文摘Objectives: Evaluation of diagnostic performance of rapid testing of cervico-vaginal fluid (CVF) for fetal fibronectin (FFN) and placental α-microglobulin 1 (PAMG-1) as screening of women presented by threatened preterm labor (TPTL) with intact membranes for duration till getting spontaneous labor (SL). Patients & Methods: 37 women presenting with TPTL underwent CVF samplings before digital examination and then underwent transvaginal ultrasonography for estimation of cervical length (CL). All women received fluid and anxiolytic therapy and if uterine contractions persisted, all had received tocolytic therapy with oral nifedipine or intravenous magnesium sulphate according to requirements. Incidence of SL within Results: Incidence of SL was 13.5%, 35.2% and 51.3% within 48-hr, 2 - 7 and 7 - 14 days, respectively. Duration till labor after sampling was positively correlated with CL, while was negatively correlated with positive FFN and PAMG-1 tests. Positive FFN test had high specificity, while positive PAMG-1 test had high sensitivity for labor within 7 days. Regression analysis defined short CL and positive PAMG-1 test as significant predictors for short duration till SL. ROC curve analysis defined short cervix and positive PAMG-1 test as significant predictors for labor within 48-hr and within 2 - 7 days respectively and combined negative PAMG-1 test and CL of 20 - 25 mm were significant predictors for labor within 7 - 14 days. Conclusion: PAMG-1 test had high specificity, if positive, for predicting SL and high NPP, if negative, for excluding labor within 7 days, so it can be used as rapid adjuvant to clinical evaluation to help management decision-making. Moreover, PAMG-1 test is recommended screening test for being easy-to-use bedside test, provides rapid results, can be used after vaginal exam and coitus and does not require a speculum examination or specialized equipment to analyze results.
基金financial support from the National Natural Science Foundation of China(No.32470987)the Special Program of the National Natural Science Foundation of China(No.32141005)+1 种基金the Major Program of the National Natural Science Foundation of China(No.82394410)We are also grateful for the technical support of the Central Laboratory of the Army Military Medical University。
文摘Chronic inflammation in adipose tissue is widely recognized as a pivotal link connecting obesity to a spectrum of related chronic diseases,including type 2 diabetes,non-alcoholic fatty liver disease,and cardiovascular disorders.In this pathogenic process,the dysregulated interaction between adipocytes and adipose-resident immune cells plays a critical regulatory role;however,the underlying mechanisms governing this abnormal interaction remain largely unknown.In this study,we showed that upregulatedβ2-microglobulin expression in hypertrophic adipocytes during obesity not only mediated the activation of adipose-resident CD8+T cells in a cell contact-dependent manner but also facilitated iron overload and the ferroptosis of adipocytes,thereby promoting the M1 polarization of adipose tissue macrophages.Conversely,specific ablation ofβ2-microglobulin in adipocytes effectively suppressed the activation and accumulation of adipose-resident CD8+T cells,as well as adipocyte ferroptosis and M1 polarization,ultimately preventing high-fat diet-induced obesity and its related inflammation and metabolic disorders.Additionally,adenoassociated virus-mediated adipose-targeted knockdown ofβ2-microglobulin has been demonstrated to therapeutically alleviate high-fat diet-induced obesity,as well as its related chronic inflammation and metabolic disorders.Furthermore,our bioinformatic analysis of human adipose transcriptome data revealed a strong correlation between adiposeβ2-microglobulin and obesity.More importantly,β2-microglobulin is significantly upregulated in adipocytes isolated from patients with obesity.Thus,our findings highlight the pivotal role of adipocytes in obesity-associated chronic inflammation and metabolic disorders viaβ2-microglobulindependent mechanisms.
基金This study was funded by the grant from the National Nature Science Foundation of China
文摘Objective： This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin （β2M）, a conservative immune molecule in vertebrate.Data Sources： The data used in this review were obtained from PubMed up to October 2015.Terms of β2M, immune response, and infection were used in the search.Study Selections： Articles related to β2M were retrieved and reviewed.Articles focusing on the characteristic and function of β2M were selected.The exclusion criteria of articles were that the studies on β2M-related molecules.Results： β2M is critical for the immune surveillance and modulation in vertebrate animals.The dysregulation of β2M is associated with multiple diseases, including endogenous and infectious diseases.β2M could directly participate in the development of cancer cells, and the level of β2M is deemed as a prognostic marker for several malignancies.It also involves in forming major histocompatibility complex （MHC class Ⅰ or MHC Ⅰ） or like heterodimers, covering from antigen presentation to immune homeostasis.Conclusions： Based on the characteristic of β2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools.Moreover, β2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of β2M on applications.
基金This study was supported by a grant from National Natural Science Foundation of China （No. 30271254）.
文摘Background Acute renal failure （ARF） after liver transplantation is associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of early effective prognostic factors. Recent studies indicated that serum levels of cystatin C and β2-microglobulin （β2 MG） as well as urinary β2 MG and N-acetyI-β-D- glucosaminidase （NAG） would increase in patients with early and mild renal impairment. In this study, these factors were detected during the different stages in patients who accepted orthotopic liver transplantation （OLT）, and their feasibilities to predict early ARF after OLT were also analyzed. Methods Sixty patients with normal blood urea nitrogen （BUN） and serum creatinine （SCr） who received modified piggyback liver transplantation without veno-venous bypass were prospectively studied. Blood samples were drawn from patients for the determination of serum β2 MG（n=60）, SCr （n=60） and serum Cystatin C （n=39） at following 5 intervals： before operation （TO）, 20 minutes before anhepatic phase （T1）, 25 minutes in anhepatic （T2）, 60 minutes after reperfusion （T3） and at the end of operation（T4）. Urinary B2 MG （n=60） and NAG （n=60） were also examined at following 3 intervals： before operation （TO）, 60 minutes after reperfusion （T3） and at the end of operation （T4）. According to the Rimola A criteria of ARF in 24 hours after operation, all the patients were divided into two groups： ARF group and non-ARF group. The data were statistically analyzed to evaluate the feasibiliy of regarding these factors as prognostic factors for early ARF after liver transplantation in patients with normal SCr and BUN before operation. Results Ten of sixty cases showed ARF（16.7%）. The Logistic regression analysis showed that the levels of serum and urinary β2 MG as well as serum cystatin C before operation were correlated with early ARF after liver transplantation （P 〈0.05）, while only serum levels of cystatin C and Cr at the end of operation correlated with early ARF （P〈0.05, P〈0.01） after liver transplantation. The serum β2 MG, Cystatin C, SCr and urinary β2 MG levels in ARF group were much more higher than that in non-ARF group（P 〈0.05, P 〈0.01）. There were significant differences between the correct and false predictive positive ratios of serum cystatin C, serum and urinary β2 MG levels before operation （P 〈0.05, P 〈0.01）, while only SCr showed significant difference between these groups at the end of operation （P 〈0.01）. Conclusions The results revealed that there was potential renal damage among those patients who demonstrated normal SCr and BUN before operation, and that liver transplantation could aggravate this damage and causing ARF. Here we provided the prognostic values of serum Cystatin C, β2 MG, urinary β2 MG and NAG in patients with early acute renal failure after liver transplantation.
文摘Background：As a major complication after orthotopic liver transplantation （OLT）,the occurrence of acute kidney injury （AKI） is frequently defined by serum creatinine （Cr）;however,the accuracy of commonly used blood urea nitrogen （BUN）,uric acid （UA）,and β2-microglobulin （β2-MG） remains to be explored.This retrospective study compared the accuracy of these parameters for post-OLT AKI evaluation.Methods：Patients who underwent OLT in three centers between July 2003 and December 2013 were enrolled.The postoperative AKI group was diagnosed by the Kidney Disease Improving Global Outcomes （KDIGO） criteria and classified by stage.Measurement data were analyzed using the t-test or Wilcoxon rank-sum test;enumerated data were analyzed using the Chi-square test or Fisher＇s exact test.Diagnostic reliability and predictive accuracy were evaluated using receiver operating characteristic （ROC） curve analysis.Results：This study excluded 976 cases and analyzed 697 patients （578 men and 1 1 9 women）;the post-OLT AKI incidence was 0.409.Compared with the no-AKI group,the AKI group showed very significant differences in Model for End-stage Liver Disease score （14.74 ± 9.91 vs.11.07 ± 9.54,Z =5.404;P ＜ 0.001）,hepatic encephalopathy （45 [15.8％] vs.30 [7.3％],x2 =12.699;P ＜ 0.001）,hemofiltration （28 [9.8％] vs.0 [0.0％],x2 =42.171;P ＜ 0.001）,and 28-day mortality （23 [8.1％] vs.9 [2.2％],x2 13.323;P ＜0.001）.Moreover,mean values of Cr,BUN,UA,and β2-MG in the AKI group differed significantly at postoperative days 1,3,and 7 （all P ＜0.001）.ROC curve area was 0.847 of Cr for the detection of AKI Stage 1 （sensitivity 80.1％,specificity 75.7％,cutoffvalue 88.23 μmol/L）,0.916 for Stage 2 （sensitivity 87.6％,specificity 82.6％,cutoff value 99.9 μmol/L）,and 0.972 for Stage 3 （sensitivity 94.1％,specificity 88.2％,cutoff value 122.90 μmol/L）.Conclusion：The sensitivity and specificity of serum Cr might be a high-value indicator for the diagnosis and grading of post-OLT AKI.
文摘Recent research by Gao et al.published in Cell proposes that circulatingβ2-microglobulin impairs synaptic function through antagonizing NMDA receptors in two mouse models of Down syndrome(DS),providing a potentially novel therapeutic target to combat cognitive deficits in the early stage of DS.^(1)
