Research progress of adipokines and diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)is one of the common microangiopathy in diabetes and the main cause of blindness in adults. It can be seen that it is very important to find the specific target of DR prevention and treatment. Adipose tissue is not only an energy storage tissue, but also an active endocrine organ, which can release a variety of cytokines, called adipokines. Studies have shown that adipokines play an important role in the occurrence and development of DR. Adipokines can not only directly act on vascular endothelium through blood circulation, but also indirectly affect vascular endothelial function by affecting the activity of sympathetic nervous system and insulin sensitivity, which leads to dysfunction of vascular endothelial cells, increased retinal vascular permeability, neurodegeneration and neovascularization, and finally leads to the destruction of blood-retinal barrier. In recent years, the role of some new adipokines in DR has been paid more and more attention. This paper reviews the related research of several new adipokines in DR.

Cerebrospinal fluid levels of sortilin-1, lipocalin-2, autotaxin, decorin and interleukin-33 in patients with idiopathic intracranial hypertension / Níveis de sortilina-1, lipocalina-2, autotaxina, decorina e interleucina-33 no líquido cefalorraquidiano em pacientes com hipertensão intracraniana idiopática

Abstract Background Idiopathic intracranial hypertension (IIH) is characterized by increased cerebrospinal fluid (CSF) pressure of unknown cause. It has been suggested that the inflammatory process plays a role in the pathophysiology of the disease. Sortilin-1, lipocalin-2, autotaxin, decorin, and interleukin-33 (IL-33) are among the factors involved in inflammatory processes. Objective To investigate the CSF levels of sortilin-1, lipocalin-2, autotaxin, decorin, and IL-33 in patients with IIH. Methods A total of 24 IIH patients and 21 healthy controls were included in the study. Demographic characteristics of the patients and of the control group as well as CSF pressures were evaluated. Sortilin-1, lipocalin-2, autotaxin, decorin and IL-33 levels in the CSF were measured. Results The CSF levels lipocalin-2, sortilin-1, autotaxin, IL-33 and CSF pressure were significantly higher in the patients group compared with the control group (p < 0.001). Decorin levels were reduced in patients (p < 0.05). There was no correlation between the autotaxin and IL-33 levels and age, gender, CSF pressure, and body mass index. The results of our study showed that inflammatory activation plays an important role in the development of the pathophysiology of IIH. In addition, the fact that the markers used in our study have never been studied in the etiopathogenesis of IIH is important in explaining the molecular mechanism of this disease. Conclusion Studies are needed to evaluate the role of these cytokines in the pathophysiology of the disease. It is necessary to evaluate the effects of these molecules on this process.

Resumo Antecedentes A hipertensão intracraniana idiopática (HII) é caracterizada pelo aumento da pressão do líquido cefalorraquidiano (LCR) de causa desconhecida. Tem sido sugerido que o processo inflamatório desempenha um papel na fisiopatologia da doença. Sortilina-1, lipocalina-2, autotaxina, decorina e interleucina-33 (IL-33) estão entre os fatores envolvidos nos processos inflamatórios. Objetivo Investigar os níveis de sortilina-1, lipocalina-2, autotaxina, decorina e IL-33 no LCR de pacientes com HII. Métodos Um total de 24 pacientes com HII e 21 controles saudáveis foram incluídos no estudo. Foram avaliadas as características demográficas dos pacientes e do grupo controle, bem como as pressões liquóricas. Os níveis de sortilina-1, lipocalina-2, autotaxina, decorina e IL-33 no LCR foram medidos. Resultados Os níveis no líquido cefalorraquidiano lipocalina-2, sortilina-1, autotaxina, IL-33 e pressão liquórica foram significativamente maiores no grupo de pacientes em comparação com o grupo controle (p < 0,001). Os níveis de decorina foram reduzidos nos pacientes (p < 0,05). Não houve correlação entre os níveis de autotaxina e IL-33 e idade, sexo, pressão liquórica e índice de massa corporal. Os resultados do nosso estudo mostraram que a ativação inflamatória desempenha um papel importante no desenvolvimento da fisiopatologia da HII. Além disso, o fato de os marcadores utilizados em nosso estudo nunca terem sido estudados na etiopatogenia da HII é importante para explicar o mecanismo molecular dessa doença. Conclusão Estudos são necessários para avaliar o papel dessas citocinas na fisiopatologia da doença. É necessário avaliar os efeitos dessas moléculas nesse processo

Correlation between serum lipocalin-2 and white matter hyperintensities in patients with ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between the lipocalin-2 (LCN-2) level and white matter hyperintensities (WMHs) in patients with ischemic stroke.Methods:Consecutive patients with ischemic stroke admitted to the Department of Neurology, Jinling Hospital, Medical School of Nanjing University from September 2021 to November 2021 and whose duration from onset to hospitalization <14 d were prospectively enrolled. Enzyme-linked immunosorbent assay was used to detect the serum LCN-2. Fazekas scale was used to assess the severity of periventricular and subcortical WMHs. A total WMHs score ≥3 was defined as severe WMHs. Multivariate logistic regression analysis was used to determine the correlation between serum LCN-2 level and WMHs. Results:A total of 179 patients were enrolled, including 122 males (68.2%), aged 64.7±11.6 years. The median serum LCN-2 level was 387.1 g/L, and 86 patients (48.0%) had severe WMHs. Serum LCN-2 in the severe WMH group was significantly higher than that in the non-severe WMH group (505.3±342.4 g/L vs. 367.8±224.5 g/L; t=3.110, P=0.002). Multivariable logistic regression analysis showed that after adjusting for the relevant confounding factors, there was a significant correlation between higher serum LCN-2 and severe WMHs (odds ratio 2.32, 95% confidence interval 1.17-4.63; P=0.017) and higher total WMHs score (odds ratio 1.62, 95% confidence interval 1.12-2.35; P=0.011). Conclusion:Higher serum LCN-2 level is associated with severe WMHs in patients with ischemic stroke.

Role of lipocalin-2 in the development and progression of liver diseases / 临床肝胆病杂志

Lipocalin-2 (LCN2) is a secreted glycoprotein originally purified from mouse kidney cells infected with simian virus 40 and plays a key role in the control of cellular homeostasis during inflammation and the response to cellular stress or injury, and it is considered a potential biomarker for rheumatic diseases, cancer, liver diseases, and inflammatory diseases. Studies have shown that LCN2 is expressed in hepatic parenchymal and nonparenchymal cells and is secreted into the bloodstream, and it is closely associated with the development and progression of acute liver injury, liver cirrhosis, viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. This article summarizes the animal experiments and clinical studies on the association of LCN2 with the pathogenesis of liver diseases, in order to provide new ideas and therapeutic targets for the prevention and treatment of liver diseases.

Inhibiting ferroptosis attenuates myocardial injury in septic mice: the role of lipocalin-2 / 南方医科大学学报

OBJECTIVE@#To explore the contribution of ferroptosis to myocardial injury in mouse models of sepsis and the role lipocalin-2 (Lcn2) in ferroptosis.@*METHODS@#Adult male C57BL/6 mice were randomized equally into sham-operated group, cecal ligation and puncture (CLP)-induced sepsis group, and CLP + Fer-1 group where the mice received intraperitoneal injection of 5 mg/mL Fer-1 (5 mg/kg) 1 h before CLP. The left ventricular functions (including LVEF%, LVFS%, LVIDd and LVIDs) of the mice were assessed by echocardiography at 24 h after CLP. Myocardial injury in the mice was observed with HE staining, and the changes of myocardial ultrastructure and mitochondria were observed using transmission electron microscopy (TEM). Serum TNF-α level was measured with ELISA, and the changes of myocardial iron content were detected using tissue iron kit. The protein expressions of myocardial Lcn2, glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) were determined with Western blotting.@*RESULTS@#The septic mice showed significantly decreased LVEF%, LVFS% and LVIDd and increased LVIDs at 24 h after CLP (P < 0.05), and these changes were significantly improved by Fer-1 treatment. Sepsis caused obvious myocardial pathologies and changes in myocardial ultrastructure and mitochondria, which were significantly improved by Fer-1 treatment. Fer-1 treatment also significantly ameliorated sepsis-induced elevations of serum TNF-α level, myocardial tissue iron content, and Lcn2 protein expression and the reduction of GPX4 and FSP1 protein expression levels (P < 0.05).@*CONCLUSION@#GPX4- and FSP1-mediated ferroptosis are involved in myocardial injury in mice with CLP-induced sepsis, and inhibition of ferroptosis can attenuate septic myocardial injury, in which Lcn2 may play a role.

Could CA 19-9 be a useful biomarker in the diagnosis, prognosis, and prediction of adequate relief in lower urinary tract obstructions? / O antígeno carboidrato CA 19-9 poderia ser um biomarcador útil no diagnóstico, prognóstico e acompanhamento da obstrução baixa do trato urinário?

ABSTRACT Introduction: posterior urethral valves represent an important cause of childhood chronic kidney disease. The identification of biomarkers that indicate early kidney damage and even adequate clearance could reduce how many patients head towards kidney failure. Objective: this study evaluated how this easy-analysis biomarker (CA 19-9) could help identifying potential renal damage and adequate clearance in obstructive uropathies. Methods: 46 female Wistar rats were divided into 5 groups, with different patterns of partial urinary tract obstruction: group control; group OIV: infravesical obstruction; group OIVd: infravesical obstruction with reversion, obstruction relief 7 postoperative days later; group OUu: unilateral ureteral obstruction; group OUb: bilateral ureteral obstruction. The CA 19-9s performance was compared to another biomarker: Ngal. Determination of basal CA 19-9 and Ngal in urine and blood and serum creatinine levels was performed in the rats prior to surgery (T0) and after 14 days (T1). Group OIVd underwent intermediate (Ti) collection before clearance. Results: the urinary concentration of CA 19-9 increased in groups OIV, OIVd and OUb; elevation at T1 and Ti, reached statistical significance compared to the T0 value (p<0,05). Changes in urinary CA 19-9 were more expressive in infravesical obstruction groups (AUC 0.81). Obstruction relief in group OIVd promoted significant urinary CA 19-9 reduction (p<0,05) in the final evaluation. Conclusions: CA 19-9 urinary concentration increased in partial urinary tract obstruction. Its best performance was in the bladder neck obstruction group, in which the elevation was detected early (6 days after infravesical obstruction) and the CA19-9 urinary concentration declined after clearance.

RESUMO Introdução: a válvula de uretra posterior representa uma importante causa de doença renal crônica na infância. A identificação de biomarcadores que monitorem danos renais precoces e o sucesso da desobstrução do trato urinário podem reduzir o número de pacientes que evoluem para insuficiência renal. Objetivo: avaliar o desempenho do biomarcador antígeno carboidrato CA 19-9 nas obstruções parciais do trato urinário. Método: 46 ratas Wistar foram divididas em 5 grupos: grupo controle; grupo OIV: obstrução infravesical; grupo OIVd: obstrução infravesical com alívio da obstrução após 7 dias; grupo OUu: obstrução ureteral unilateral; grupo OUb: obstrução ureteral bilateral. O desempenho do CA 19-9 foi comparado a outro biomarcador, a Ngal. A dosagem de CA 19-9 e Ngal na urina e no sangue, e os níveis de creatinina sérica foram avaliados nas ratas antes da cirurgia (T0) e após 14 dias (T1). O grupo OIVd foi submetido a uma coleta intermediária (Ti). Resultados: a concentração urinária de CA19-9 aumentou nos grupos OIV, OIVd e OUb; a elevação em T1 e Ti alcançou significância estatística em relação ao valor de T0 (p<0,05). As alterações no CA 19-9 urinário foram mais expressivas nos grupos de obstrução infravesical (AUC 0,81). O alívio da obstrução no grupo OIVd promoveu redução do CA 19-9 urinário (p<0,05). Conclusões: a concentração urinária de CA19-9 aumentou na obstrução parcial do trato urinário. Seu melhor desempenho foi no grupo de obstrução infravesical, no qual a elevação foi detectada precocemente (6 dias de pós-operatório) com queda após a retirada do fator obstrutivo.

Biomarkers of acute kidney injury in patients with nephrotic syndrome / Biomarcadores de lesão renal aguda em pacientes com síndrome nefrótica

ABSTRACT Introduction: Emergence of acute kidney injury (AKI) in patients with nephrotic syndrome (NS) requires prompt diagnosis and differentiation between acute tubular necrosis (ATN) and proliferative glomerulonephritis. We studied the potential use of commercial urinary biomarkers' tests in the diagnosis of AKI in patients with NS. Methods: A cross sectional estimate of urinary concentrations of KIM-1 and NGAL was performed in 40 patients with NS: 9 with proliferative glomerulopathy, being 4 with AKI and 31 without proliferative glomerulopathy, being 15 with AKI. AKI was defined using the KDIGO criteria. Results: The mean age was 35 ± 16 years. The main diagnoses were focal and segmental glomerulosclerosis (10, 25%), membranous glomerulopathy (10, 25%), minimal change disease (7, 18%), lupus nephritis (6, 15%), and proliferative glomerulonephritis (3, 8%). Patients with ATN had higher levels of urinary KIM-1 (P = 0.0157) and NGAL (P = 0.023) than patients without ATN. The urinary concentrations of KIM-1 (P= 0.009) and NGAL (P= 0.002) were higher in patients with AKI than in patients without AKI. Urinary NGAL and KIM-1 levels were significantly higher in patients with ATN without proliferative glomerulonephritis than in patients with proliferative glomerulonephritis (P = 0.003 and P=0.024, respectively). Conclusions: Neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) estimates correlated with histological signs of ATN and were able to discriminate patients with AKI even in conditions of NS. Furthermore, urinary levels of NGAL and KIM-1 may be useful in the differential diagnosis of acute tubular necrosis and exudative glomerulonephritis in patients with nephrotic syndrome.

RESUMO Introdução: O surgimento de lesão renal aguda (LRA) em pacientes com síndrome nefrótica (SN) requer diagnóstico imediato e diferenciação entre necrose tubular aguda (NTA) e glomerulonefrite proliferativa. Avaliamos o uso potencial de testes de biomarcadores urinários comerciais no diagnóstico de LRA em pacientes com SN. Métodos: Uma estimativa transversal das concentrações urinárias de KIM-1 e NGAL foi realizada em 40 pacientes com SN: 9 com glomerulopatia proliferativa, sendo 4 com LRA e 31 sem glomerulopatia proliferativa, sendo 15 com LRA. A LRA foi definida usando os critérios da KDIGO. Resultados: A média de idade foi de 35 ± 16 anos. Os principais diagnósticos foram glomeruloesclerose segmentar e focal (10, 25%), glomerulopatia membranosa (10, 25%), doença por lesão mínima (7, 18%), nefrite lúpica (6, 15%) e glomerulonefrite proliferativa (3, 8 %). Os pacientes com NTA apresentaram níveis mais elevados de KIM-1 urinário (P = 0,0157) e NGAL (P = 0,023) do que pacientes sem NTA. As concentrações urinárias de KIM-1 (P = 0,009) e NGAL (P = 0,002) foram maiores em pacientes com LRA do que em pacientes sem LRA. Os níveis urinários de NGAL e KIM-1 foram significativamente maiores em pacientes com NTA sem glomerulonefrite proliferativa do que em pacientes com glomerulonefrite proliferativa (P = 0,003 e P = 0,024, respectivamente). Conclusões: As estimativas de lipocalina associada a gelatinase de neutrófilos (NGAL) e molécula de lesão renal 1 (KIM-1) se correlacionaram com sinais histológicos de NTA, e foram capazes de discriminar pacientes com LRA mesmo em condições de SN. Além disso, os níveis urinários de NGAL e KIM-1 podem ser úteis no diagnóstico diferencial de necrose tubular aguda e glomerulonefrite exsudativa em pacientes com síndrome nefrótica.

Expression and Clinical Significance of Lipocalin-2 in the Serum of Lung Cancer Patients / 中国肺癌杂志

BACKGROUND@#Lung cancer is the highest incidence of cancer in the world, which seriously threatens human health. Early diagnosis and treatment of lung cancer is particularly important for the survival of lung cancer patients. Serum tumor markers have been widely used as an important method for early diagnosis of tumor. However, there are few early diagnostic markers for lung cancer. Therefore, the aim of this study was to investigate the expression level of Lipocalin-2 and its clinical significance in serum of patients with lung cancer.@*METHODS@#The serum levels of Lipocalin-2 in 60 lung cancer patients and 63 healthy people were detected by enzyme-linked immunosorbent assay (ELISA), and the relationship between the expression level of Lipocalin-2 and the clinical characteristics of lung cancer was analyzed.@*RESULTS@#The expression level of Lipocalin-2 in peripheral blood serum of patients with lung cancer was significantly higher than that of healthy people, and the difference was statistically significant (P<0.001). The expression of Lipocalin-2 in patients with lung cancer was related to the differentiation, stage and lymph node metastasis of pathological tissues, and the difference was statistically significant (P<0.05). The expression level of Lipocalin-2 in serum of patients with poorly differentiated lung cancer was higher than that of patients with well differentiated lung cancer; the expression level of Lipocalin-2 in serum of patients with lymph node metastasis was higher than that of patients without lymph node metastasis; the expression level of Lipocalin-2 in patients with clinical stage III + IV lung cancer was significantly higher than that of patients with clinical stage I + II lung cancer, and the differences were statistically significant (P<0.05).@*CONCLUSIONS@#Lipocalin-2 is highly expressed in serum of patients with lung cancer, which is related to pathological differentiation, stage and lymph node metastasis. It is expected to become a potential new tumor marker for clinical diagnosis of lung cancer.

Cardiac output values and correlation of renal injury with neutrophil gelatinase-associated lipocalin levels in off-pump coronary artery bypass patients

Abstract Objective: To investigate the correlation between cardiac output values and renal neutrophil gelatinase-associated lipocalin (NGAL) levels as a biomarker of renal ischemia. Methods: Forty patients, who underwent off-pump coronary artery bypass (OPCAB) surgery and in whom the positioning of the heart was fixed with simple suspension sutures without a mechanical stabilizer, were included in the study. Continuous cardiac output (CO) measurements were recorded using the arterial pressure waveform analysis method (FloTrac sensor system) in the perioperative period. CO was recorded every minute during non-anatomical cardiac positioning for left anterior descending artery (LAD), diagonal artery (D), circumflex artery (Cx), and right coronary artery (RCA) bypasses. Serum NGAL samples were analyzed in the preoperative, perioperative, and postoperative periods. Results: The CO values measured at various non-anatomical cardiac positions during distal anastomosis for LAD, D, Cx, and RCA were significantly lower than pre- and postoperative values measured with the heart in normal anatomical position (3.45±0.78, 2.9±0.71, 3.11±0.56, 3.19±0.81, 5.03±1.4, and 4.85±0.78, respectively, P=0.008). There was no significant difference between CO values measured at various non-anatomical cardiac positions during distal anastomosis. Although there was no significant correlation between NGAL levels and age, duration of surgery, preoperative CO, D-CO, RCA-CO, and postoperative CO measurements, there was a significant correlation between NGAL levels and LAD-CO (P=0.044) and Cx-CO (P=0.018) at the postoperative 12th hour. Conclusion: Full revascularization may be achieved by employing the OPCAB technique while using simple suspension sutures without a mechanical stabilizer and by providing safe CO levels and low risk of renal ischemia.

Investigation of aki with early biomarkers after cardiac surgery

Abstract Objective: To provide a new interpretation of the effect of intraoperative hemodynamic data on postoperative acute kidney injury (AKI) development and to determine the accuracy of some biomarkers which are thought to be the early markers of renal injury. Methods: One hundred adult patients who were connected to the heart-lung pump during open-heart surgery were included in this study. Hemodynamic data, oxygen delivery, and transfusions were recorded intraoperatively, and the preoperative and 3. postoperative hour cystatin C, interleukin-18 (IL-18), and neutrophil gelatinase-associated lipocalin (NGAL) parameters were measured for early detection of kidney damage. In the analysis, 95% significance level was used to determine the difference. Results: According to the Kidney Disease Improving Global Outcomes criterion, AKI developed in 24 patients, 18 of whom were stage 1, two were stage 2, and four were stage 3. AKI (+) patients had more transfusions in the intraoperative period and AKI development was a risk factor for postoperative complications. NGAL and IL-18 levels were found to be approximately two-fold in the postoperative period in AKI (+) patients, whereas cystatin C was not sensitive in AKI detection. Conclusion: AKI development increases the risk of postoperative complications. NGAL and IL-18 were successful in detecting AKI in the early postoperative period.

Associations of Plasma Neutrophil Gelatinase-associated Lipocalin, Anemia, and Renal Scarring in Children with Febrile Urinary Tract Infections

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), a bacteriostatic agent, is known to inhibit erythropoiesis leading to anemia. We aimed to investigate the associations of NGAL, anemia, and renal scarring in children with febrile urinary tract infections (UTIs).METHODS: We retrospectively reviewed the medical records of 261 children with febrile UTIs. The relationship between the presence of anemia and plasma NGAL levels was investigated. NGAL performance in comparison with serum C-reactive protein (CRP) at admission and after 72 hours of treatment was also evaluated for the prediction of renal scarring as well as acute pyelonephritis (APN) and vesicoureteral reflux (VUR).RESULTS: Plasma NGAL levels were elevated in patients with anemia compared with those without anemia. Multiple linear regression analysis showed an inverse relationship between NGAL levels and erythrocyte counts (standard β = −0.397, P < 0.001). Increased NGAL, but not CRP, was independently associated with the presence of anemia (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.07–5.27; P < 0.05). Receiver operating curve analyses showed good diagnostic profiles of pre- and post-treatment NGAL for identifying APN, VUR, and renal scarring (all P < 0.05). For detecting renal scars, the area under the curve of post-treatment NGAL (0.730; 95% CI, 0.591–0.843) was higher than that of post-treatment CRP (0.520; 95% CI, 0.395–0.643; P < 0.05). The presence of anemia and elevated NGAL at admission (> 150 ng/mL) were independent risk factors for renal scarring in children with febrile UTIs. With anemia, NGAL levels increased consecutively in children with febrile UTI without renal involvement, with APN without scar, and with APN with renal scarring.CONCLUSION: Increased plasma NGAL levels may be associated with the presence of anemia and renal scarring in children with febrile UTIs.

Polymorphism of bovine lipocalin-2 gene and its impact on milk production traits and mastitis in Holstein Friesian cattle

Background: Mastitis is one of the most serious diseases of dairy cattle, causing substantial financial losses. While predisposition to reduced somatic cell count in milk has been considered for in cattle breeding programs as the key indicator of udder health status, scientists are seeking genetic markers of innate immune response, which could be helpful in selecting cows with improved immunity to mastitis. Lipocalin-2 (LCN2) is a protein involved in the response of the immune system by eliminating iron ions which are necessary for the growth of pathogenic bacteria, so LCN2 may be considered as a natural bacteriostatic agent and could become a marker of infection. Results: A total of five SNPs were identified in LCN2 gene (one in the promoter, three in exon 1, and one in intron 1). A single haplotype block was identified. The locus g.98793763GNC was found to have a significant impact on protein levels in milk, and alleles of this locus were identified to have a significant positive dominance effect on this trait. None of the four analysed loci had a statistically significant impact on the milk yield, fat levels in milk or the somatic cell score. LCN-2 gene had no significant impact on the incidence of mastitis in the cows. Conclusions: Although the identified SNPs were not found to have any impact on the somatic cell count or the incidence of mastitis in cows, it seems that further research is necessary, covering a larger population of cattle, to confirm the association between lipocalin-2 and milk production traits and mastitis.

Detection and significance of LCN2 and PDGF-BB in serum and metastasis of lung cancer patients with bone metastasis / 临床与实验病理学杂志

Purpose To investigate the expression of lipocalin-2 (LCN2) and plateled derived growth factor-BB (PDGF-BB) in serum,carcinoma and bone metastases of lung cancer patients. Methods Protein chip were used to screen the differential expression of cytokines in serum of 19 lung cancer patients (9 patients with bone metastasis and 10 patients freedistant metastasis) . Immunohistochemistry was performed to assess the differential expression of LCN2 and PDGF-BB cytokines in 12 cases of primary lung cancer without distant metastasis and 12 cases of primary lung cancer with only bone metastasis. Results Serum level of lipid transport factor (LCN2) and PDGFBB in non-small cell lung cancer patients with bone metastasis were significantly higher than that without distant metastasis(P< 0. 05) . There was no difference cytokines between small cell lung cancer patients with bone metastasis and without metastasis group (P > 0. 05) . The results of immunohistochemistry showed that high expression of LCN2 and PDGF-BB in bone metastasis tissues was significantly higher than that in primary lung cancer tissues. Conclusions High expression of LCN2 and PDGF-BB in serum and bone metastasis tissue of patients with non-small cell lung cancer might be involved in the occurrence,development of bone metastasis of lung cancer in the bone marrow,may be an important biomarker and potential therapeutic target for bone metastasis of lung cancer.

Effects of caloric restriction on the expression of lipocalin-2 and its receptor in the brown adipose tissue of high-fat diet-fed mice

Obesity causes inflammation and impairs thermogenic functions in brown adipose tissue (BAT). The adipokine lipocalin 2 (LCN2) has been implicated in inflammation and obesity. Herein, we investigated the protective effects of caloric restriction (CR) on LCN2-mediated inflammation and oxidative stress in the BAT of high-fat diet (HFD)-fed mice. Mice were fed a HFD for 20 weeks and then either continued on the HFD or subjected to CR for the next 12 weeks. CR led to the browning of the white fat-like phenotype in HFD-fed mice. Increased expressions of LCN2 and its receptor in the BAT of HFD-fed mice were significantly attenuated by CR. Additionally, HFD+CR-fed mice had fewer neutrophils and macrophages expressing LCN2 and iron-positive cells than HFD-fed mice. Further, oxidative stress and mitochondrial fission induced by a HFD were also significantly attenuated by CR. Our findings indicate that the protective effects of CR on inflammation and oxidative stress in the BAT of obese mice may be associated with regulation of LCN2.

Diagnostic value of serum lipocalin 2 combined with prostate-specific antigen in prostate cancer / 国际肿瘤学杂志

Objective To investigate the diagnostic value of lipocalin 2 (LCN2) combined with prostate-specific antigen (PSA) in prostate cancer (PCa).Methods Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of serum LCN2 in patients with PCa (PCa group,n =82),patients with benign prostatic hyperplasia (BPH group,n =40) and healthy subjects (NC group,n =30).The levels of serum PSA were measured by chemiluminescence.The diagnostic value of LCN2 combined with PSA in PCa was analyzed by the receiver operating characteristic (ROC) curve.The relationship between the level of LCN2 and clinical parameters in PCa patients was analyzed.Results The levels of serum LCN2 in PCa group,BPH group and NC group were (88.97 ±40.83) pg/ml,(53.12 ±25.66) pg/ml,(13.34 ±4.86) pg/ml (F=61.306,P ＜0.001).The level of LCN2 in PCa group was significantly higher than that in BPH group and NC group (both P＜0.001).The levels of serum PSA in PCa group,BPH group and NC group were (17.65 ± 8.43) ng/ml,(11.27 ±3.56) ng/ml,(2.61 ±0.87) ng/ml (F=60.959,P＜0.001).The level of serum PSA in PCa group was significantly higher than that in BPH group and NC group (both P ＜0.001).There was positive correlation between serum LCN2 and PSA levels (r =0.360,P ＜ 0.001).The levels of serum LCN2 in PCa patients with different Gleason score,TNM stage and distant metastasis were significantly different (F =8.546,P ＜ 0.001;t =3.421,P =0.001;t =3.622,P =0.010).The area under the curve (AUC) of serum LCN2 was 0.763 (95％ CI:0.677-0.850,P ＜0.001).The sensitivity and specificity of serum LCN2 were 62.2％ and 85.0％.The AUC of PSA was 0.750 (95％ CI:0.665-0.836,P ＜ 0.001).The sensitivity and specificity of serum PSA were 51.2％ and 87.5％.The AUC of LCN2 combined with PSA was 0.822 (95％ CI:0.749-0.895,P ＜0.001).Conclusion Serum LCN2 level in the patients with PCa is significantly higher,which participates in tumor invasion.LCN2 may be a potential serum marker for the diagnosis of PCa.Combined detection of LCN2 and PSA contributes to the early diagnosis of PCa.

Effect of lipocalin-2 on angiogenesis of murine retinal vascular endothelial cells / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the role of lipocalin-2(LCN-2)in retinal angiogenesis <i>in vitro</i> by observing its effects on proliferation, migration and capillary-like tube formation of murine retinal vascular endothelial cells(RVECs). <p>METHODS: Well cultured RVECs were divided to different groups which were treated with 0, 5, 10 μmol/L LCN-2 for 48h, respectively. Cell proliferation, migration and tube formation were detected by using the EDU assay, transwell assay and matrigel assay, respectively. <p>RESULTS: The cell proliferation rate was promoted in both low and high dose of LCN-2 groups compared to the control cells(<i>P</i><0.05). The number of migrated cells in both LCN-2 groups was significantly larger than that of the control group(<i>P</i><0.05). The number of capillary-like tube structures of both LCN-2 groups was significantly larger than that of the control cells(<i>P</i><0.05). In addition, cell proliferation, migration and tube formation were all increased with the increase of LCN-2 concentration. <p>CONCLUSION: LCN-2 could obviously promote the angiogenesis capacity of RVECs, suggesting that LCN-2 is an important pro-angiogenic factor in retinal angiogenesis.

Perspectives in Lipocalin-2: Emerging Biomarker for Medical Diagnosis and Prognosis for Alzheimer's Disease

Lipocalin-2 (LCN2), a secreted glycoprotein belonging to the lipocalin superfamily was reported to participate in various biological processes including cell migration, cell survival, inflammatory responses, and insulin sensitivity. LCN2 is expressed in the multiple tissues such as kidney, liver, uterus, and bone marrow. The receptors for LCN2 were additionally found in microglia, astrocytes, epithelial cells, and neurons, but the role of LCN2 in the central nervous system (CNS) has not been fully understood yet. Recently, in vitro, in vivo, and clinical studies reported the association between LCN2 and the risk of Alzheimer's disease (AD). Here, we reviewed the significant evidences showing that LCN2 contributes to the onset and progression of AD. It may suggest that the manipulation of LCN2 in the CNS would be a crucial target for regulation of the pathogenesis and risk of AD.

Atorvastatin pretreatment attenuates kainic acid-induced hippocampal neuronal death via regulation of lipocalin-2-associated neuroinflammation

Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.

Focusing on bone—new means for the management of diabetes / 中华内分泌代谢杂志

In the past decade, mounting evidence points to the possibility of targeting bone for treating, preventing, and predicting type 2 diabetes mellitus. Osteoblast-derived osteocalcin (OCN) can stimulate insulin secretion, enhance insulin sensitivity, and favor glucose and fatty acid uptake and utilization. Lipocalin 2 is another osteokine secreted by osteoblasts and acts in appetite suppression. Neuropeptide Y may function in browning of white adipose tissue and energy expenditure. Osteocytes are proposed to have impact on the browning of white adipose tissue and energy expenditure through the secretion of bone morphogenetic protein 7 and sclerostin. Active bone resorption is also implicated in glucose homeostasis. In addition, there is evidence indicating the involvement of bone-derived receptor activator of nuclear factor κ-B ligand in the regulation of energy metabolism. We collect and summarize recent advances and the rationales for treating, preventing, and predicting diabetes by targeting skeleton. (Chin J Endocrinol Metab, 2018, 34: 543-548)