Correlation between the Expression of AHA1 mRNA and LOXL2 mRNA in Osteosarcoma Patients Tissues with mRNA Expression of Invasion and Metastasis Genes and Their Clinical Significance / 现代检验医学杂志

Objective To investigate the correlation between the expression of the activator of HSP90 ATPase-1(AHA1),lysyl oxidase like-2 protein(LOXL2)in osteosarcoma tissues with mRNA expression of invasion and metastasis genes and their clinical significance.Methods A total of 90 osteosarcoma patients diagnosed and treated in North China Medical and Health Group Fengfeng General Hospital from February 2016 to March 2017 were selected as the research object.The expression of AHA1 mRNA,LOXL2 mRNA and invasion and metastasis genes Wnt family member 9A(Wnt9a)mRNA,zinc finger E-box binding homologous box 1(ZEB1)mRNA,zinc finger E-box binding homologous box 1(ZEB2)mRNA,N-cadherin(N-cad)mRNA,and vimentin(Vim)mRNA in tissues were detected by real-time fluorescence quantitative PCR.Pearson correlation analysis was used for correlation analysis.The differences in expression of AHA1 mRNA and LOXL2 mRNA in osteosarcoma patients among different clinical characteristics were compared.Kaplan-Meier survival analysis was used to analyze the effect of AHA1 mRNA and LOXL2 mRNA on the prognosis of osteosarcoma patients.The prognostic factors of osteosarcoma patients were analyzed by univariate and multivariate COX regression.Results The expressions of AHA1 mRNA(3.16±0.59),LOXL2 mRNA(2.84±0.44)and invasion and metastasis genes[Wnt9a mRNA(3.23±0.42),ZEB1 mRNA(2.73±0.39),ZEB2 mRNA(2.52±0.56),N-cad mRNA(2.71±0.65)and Vim mRNA(2.81±0.73)]in osteosarcoma tissues were higher than those in paracancerous tissues(1.10±0.21,0.95±0.18,0.79±0.15,0.64±0.11,0.98±0.19,0.68±0.14,0.72±0.15),and the differences were statissically significant(t=31.206,37.716,51.903,48.931,24.706,28.964,26.605,all P<0.05).There was a significant positive correlation between AHA1 mRNA and LOXL2 mRNA expression in osteosarcoma(r=0.712,P<0.05).The expressions of AHA1 mRNA and LOXL2 mRNA were significantly positively correlated with the expressions of invasion and metastasis genes(Wnt9a,ZEB1,ZEB2,N-cad,and Vim mRNA)in tumor tissue of osteosarcoma group(r=0.504～0.720,all P<0.05).The expressions of AHA1 mRNA and LOXL2 mRNA in osteosarcoma tissues with Eneeking stage Ⅲ,soft tissue infiltration,and lung metastasis were higher than those in patients with Eneeking stage Ⅰ～Ⅱ,no soft tissue infiltration,and no lung metastasis,with significant differences(t=14.122～171.054,all P<0.05).The 5-year survival rates of patients in the AHA1 mRNA high expression group and low expression group were 36.36%(16/44)and 78.26%(36/46),respectively.The 5-year cumulative survival rate of patients in the AHA1 mRNA high expression group was significantly lower than that in the low expression group(Log-rank χ2=16.081,P<0.05).The 5-year survival rates of patients with high and low expression of LOXL2 mRNA were 34.88%(15/43)and 78.72%(37/47),respectively.The 5-year cumulative survival rate of patients in the LOXL2 mRNA high expression group was significantly lower than that in the low expression group(Log-rank χ2=15.880,P<0.05).Lung metastasis(OR=1.921,P<0.05),Eneeking stage Ⅲ(OR=1.906,P<0.05),AHA1 mRNA high expression(OR=1.405,P<0.05),and LOXL2 mRNA high expression(OR=1.733,P<0.05)were independent risk factors affecting the poor survival prognosis of osteosarcoma patients.Conclusion The expressions of AHA1 mRNA and LOXL2 mRNA in osteosarcoma were increased,and they were correlated with the expression of invasion and metastasis genes,indicating they may be independent risk factors affecting the poor survival and prognosis of osteosarcoma patients.

Study on the Mechanism of Astragalosides Against Biliary Fibrosis by Inhibiting Ductular Reaction / 世界科学技术-中医药现代化

Objective To study the partial mechanism of astragalosides(ASTs)against biliary fibrosis through inhibiting ductular reaction.Methods Rats were randomly divided into sham operation group,bile duct ligation(BDL)group and ASTs group(n=8 in each group).On the first day of the second week after BDL,the rats in ASTs group were given intragastric administration of ASTs for 3 weeks(160 mg·kg-1·d-1,once a day).Rats in sham operation group and BDL group were given the same volume of water.At the end of the fourth week,all rats were euthanasia.HE staining and sirius red staining were used to observe the pathological changes and collagen deposition.The degree of liver fibrosis was evaluated by semi-quantitative analysis of positive area of sirius red staining and the content of hydroxyproline.The expression changes of α smooth muscle actin(α-SMA),Desmin,cytokeratin(CK)19,CK7,epithelial cell adhesion molecule(Epcam),OV6 and lysyl oxidase(LOX)family proteins in liver tissue were detected by immunohistochemistry,Western blot,and real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).In vitro,hepatic progenitor cell line WB-F344 cells were induced by sodium butyrate to differentiate into biliary epithelial cells,intervented of ASTs,and collected after 4 days.The expression changes of CK19,LOXL1 and LOXL2 of cells were detected by qRT-PCR.Results Compared with BDL group,serum ALT and AST activities in ASTs group were significantly decreased(P<0.01).Histopathological injury of liver tissue was significantly reduced,Hyp content and percentage of positive area of sirius red were significantly decreased(P<0.01).Immunohistochemical staining showed that the positive expressions of α-SMA,Desmin,CK19,CK7,Epcam and OV6 were significantly decreased in the ASTs group.The mRNA expressions of α-SMA,CK7,LOX and LOXL1 were significantly decreased.The protein expressions of Epcam and LOXL1 were significantly reduced.In vitro results showed that the gene expressions of CK19,LOXL1 and LOXL2 were significantly increased after sodium butyrate induction(P<0.01).Compared with sodium butyrate group,the gene expressions of CK19,LOXL1 and LOXL2 were significantly decreased in ASTs group(P<0.01).Conclusion ASTs improved biliary fibrosis by inhibiting ductular reaction,and the mechanism may be related to the down-regulation of LOXL1.

Proteins: Neglected active ingredients in edible bird's nest / 中草药·英文版

Edible bird's nest (EBN) is a kind of natural invigorant with a long history of consumption in Asia, especially in China. EBN is formed by mixing the saliva of swiftlets (Aerodramus) with feathers and other components during the breeding season. Proteins are the most important nutrient in EBN. By studying proteins in EBN, we can not only elucidate their components at the molecular level, but also study their bioactivities. Therefore, it is of great significance to study the proteins in EBN. Previous research on the proteins in EBN was preliminary and cursory, and no one has summarized and analyzed the proteins in EBN and correlated the bioactivities of these proteins with the biological functions of EBN. This article focused on the proteins in EBN, listed the proteins identified in different proteomic studies, and introduced the sources, structures and bioactivities of the most frequently identified proteins, including acidic mammalian chitinase, lysyl oxidase homolog 3, mucin-5AC, ovoinhibitor, nucleobindin-2, calcium-binding protein (MW: 4.5 × 104) and glucose-regulated protein (MW: 7.8 × 104). The properties of these proteins are closely related to the bioactivities of EBN. Therefore, this article can provide inspiration for further research on the efficacy of EBN.

Prevalence of risk alleles in the lysyl oxidase-like 1 gene in pseudoexfoliation glaucoma patients in India

Purpose: The purpose of this study was to genotype two previously identified SNPs (rs1048661:R141L, and rs3825942:G153D) in the lysyl oxidase?like 1 (LOXL1) gene and determine their association with pseudoexfoliation glaucoma (XFG) in patients from Pune, India. Methods: All subjects underwent detailed phenotyping, and DNA extraction was performed on blood samples by using standardized techniques. Exon 1 of the LOXL1 gene containing the SNPs (rs3825942:G153D; rs1048661:R141L) were Sanger sequenced, and the results were analyzed using sequence analysis software SeqScape 2.1.1. Results: Data were analyzed from 71 patients with XFG and 81 disease?negative, age?matched controls. There was a strong association between the G allele of rs3825942 and XFG with an odds ratio of 10.2 (CI: 3.92–26.6; P < 0.001). The G allele of rs1048661 also showed an increase in risk relative to the T allele (OR = 1.49; CI: 0.88–2.51; P = 0.13), but this was not significant. Haplotype combination frequencies were estimated for rs1048661 and rs3825942; the GG haplotype was associated with a significant increase in risk (OR = 3.91; CI: 2.27–6.73; P < 0.001). Both the GA and TG haplotypes were associated with decreased XFG risk, although the latter was not significant (GA: OR = 0.08; CI: 0.03–0.21; P < 0.001; TG: OR = 0.67; CI: 0.40–1.13; P = 0.13). Conclusion: The risk G allele in rs3852942 (G153D) is strongly associated with the development of XFG in the Western Indian population. Genetic screening strategies to identify LOXL1 risk alleles in the population can assist in case definition and early diagnosis, targeting precious resources to high?risk patients.

The Dual Role of LOXL4 in Pathogenesis and Development of Human Malignant Tumors / 中国生物化学与分子生物学报

Lysyl oxidase like 4 (LOXL4) is one member of the LOX protein family and is a secreted copper-dependent amine oxidase involved in the assembly and maintenance of extracellular matrix (ECM). LOXL4 is up-regulated in human liver cancer, gastric cancer, breast cancer, cervical cancer, head and neck squamous cell carcinoma, esophageal carcinoma and colorectal cancer, but down-regulated in human bladder and lung cancer. It also inhibits tumor growth in bladder and lung cancer, suggesting that L0XL4 has a dual role of promoting or inhibiting tumors in different types of human malignant tumors. L0XL4 in tumor cell exosomes promotes cell matrix adhesion and cell migration by activating the FAK/Src pathway, which is dependent on its amine oxidase activity through a hydrogen peroxide-mediated mechanism. Exosome-mediated L0XL4 can also promote tumor cell proliferation and immune escape by activating the PI3K/Akt signaling pathway. L0XL4 can be transported to macrophages via exosomes in tumor cells, where it further activates the immunosuppression function of cells and the expression of programmed death ligand 1 (PD-L1) via STAT1- and STAT3-mediated signaling pathways. It then will trigger the immunosuppressive function of macrophages and promote the immune escape of tumor cells. In addition, LOXL4 can also exert the tumor suppressive function by activating p53 and inhibiting the Ras/ERK pathway. This paper mainly reviews the structure and the function of LOXL4, and the relationship between LOXL4 and the pathogenesis and development of human malignant tumors. We then further explore the application of LOXL4 in the study of malignant tumors, laying a theoretical foundation for its future utilization in the clinical diagnosis and treatment, and screening of prognostic markers of human malignant tumors.

Anti-lysyl oxidase combined with a vacuum device induces penile lengthening by remodeling the tunica albuginea / 亚洲男科学杂志(英文版)

This study aimed to explore whether and how anti-lysyl oxidase (anti-LOX) combined with a vacuum device (VD) could promote penile lengthening and to evaluate the effect on erectile function. This study was performed on four groups of adult rats: control, anti-LOX, VD (negative pressure value of -300 mmHg), and anti-LOX + VD. Penile length was measured by a modified VD method and verified on exposed length data. Intracavernous pressure (ICP) and maximum ICP/mean arterial pressure (MAP) ratio were recorded to assess erectile function. For corpus cavernosum, LOX activity and concentrations of pyridinoline, desmosine, hydroxyproline, and elastin were analyzed; transmission electron microscope and Hart's elastin staining were performed to monitor microstructural changes. Anti-LOX and VD significantly lengthened the penis by 10.8% (3.75 mm) and 8.2% (2.48 mm) compared with the control group, respectively, while anti-LOX + VD achieved the longest penile size (40.58 ± 0.40 mm) which was 17.4% longer than the control group (34.58 ± 0.54 mm). After 1-week washout, no penile retraction was observed. Meanwhile, exposed penile length data confirmed that the penis in the anti-LOX + VD group was also significantly longer. Anti-LOX inhibited LOX activity to reduce pyridinoline level, which led the penile tunica albuginea remodeling. However, it had no effect on hydroxyproline, desmosine, and elastin levels. Moreover, anti-LOX had no impact on erectile function, which was determined by ICP and ICP/MAP ratio. These results suggest that anti-LOX elongates the penis by reducing pyridinoline, which induces tunica albuginea remodeling. This lengthening effect was more obvious when combined with a VD. All procedures had no impact on erectile function.

Research progress of lysyl oxidase and ophthalmic diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Lysyl oxidase(LOX), an amino oxidase with copper binding site outside the cell, has been confirmed that may be involved in the pathogenesis of many diseases by a large number of studies. At present, although the potential mechanism of common variants of LOX in the development of disease is still unknown, but the potential role may be to affect the biological activity of LOX through tissue-specific alternative splicing or expression regulation.However, no matter under normal or pathological conditions, there is still little information about LOX in eye tissue yet.In recent years, it has been found that LOX may be involved in the occurrence and development of many eye diseases in related studies. Based on this, the review will summarize the research progress of eye diseases in which LOX is involved of recent years.

Lox Family and Their Role in Tumour Formation: An Overview

@#The lysyl oxidase family has five family members which are; Lysyl Oxidase (LOX), Lysyl Oxidase Like-1 (LOXL1), Lysyl Oxidase Like-2 (LOXL2), Lysyl Oxidase Like-3 (LOXL3), and Lysyl Oxidase Like-4 (LOXL4). These are amine oxidases which are copper (Cu) dependent. The main function of these secreted enzymes is covalently crosslinking extracellular collagens and elastins, making the extracellular matrix (ECM) stable. Association with LOX family enzymes has been found in various diseases including tumours, suggesting that it may be involved in the pathogenesis of the lesions. To add to the complexity, some of the LOX family members have been linked with tumour suppression while the other members were associated with tumour promotion, progression and metastasis. Thus, this review will explore further insight into the role of LOX family in tumour formation.

Exfoliation syndrome associated with LOXL1 gene polymorphisms in a Black patient from Latin America: a case report / Síndrome de esfoliação associada a polimorfismos do gene LOXL1 em paciente negro da América Latina: relato de caso

ABSTRACT A 89-year-old Black female with a 6-year history of advanced open-angle glaucoma was referred to the Glaucoma Service of the Ophthalmology Department - Federal University of São Paulo (UNIFESP). Best-corrected visual acuity was 20/400 in the right eye and 20/60 in the left eye. Pseudoexfoliation material was observed at the iris border, angle, and the anterior lens surface. Anterior biomicroscopy revealed exfoliation material forming an evident peripheral zone and a central disc separated by a clear intermediate zone on the anterior lens surface OU. Gonioscopy showed an open-angle Sampaolesis's line and whitish material deposits OU. Fundus examination revealed a cup-to-disc ratio of 1.0 OU with peripapillary atrophy. Genetic analysis for single nucleo­tide polymorphisms of the lysyl oxidase-like 1 gene linked to exfoliation syndrome identified two such single nucleotide polymorphisms, rs1048661 and rs216524.

RESUMO Uma mulher negra de 89 anos com um histórico de seis anos de glaucoma avançado de ângulo aberto avançado foi encaminhada ao Serviço de Glaucoma do Departamento de Oftalmologia da Universidade Federal de São Paulo (UNIFESP). A acuidade visual melhor corrigida era 20/400 no olho direito e 20/60 no olho esquerdo. Material pseudo-exfoliativo foi observado na borda iriana, ângulo e superfície anterior do cristalino. A biomicroscopia de segmento anterior demonstrou material exfoliativo formando uma zona periférica evidente e um disco central separado por uma zona intermediária livre na cápsula anterior do cristalino. A gonioscopia mostrou uma linha de Sampaolesi de ângulo aberto e depósitos esbranquiçados. O exame de fundo de olho revelou disco óptico com escavação total em ambos os olhos com atrofia peripapilar. A análise genética para polimorfismos de nucleotídeo único do gene semelhante à lysyl oxidase-like 1 ligado à síndrome de esfoliação identificou dois desses polimorfismos de nucleotídeo único, rs1048661 e rs216524.

A Novel Association between Lysyl Oxidase Gene Polymorphism and Intracranial Aneurysm in Koreans

PURPOSE: Lysyl oxidase (LOX) controls the cross-linking and maturation of elastin and collagen fibers. In this study, we investigated the association between LOX gene polymorphisms and intracranial aneurysm (IA) formation in a homogeneous Korean population. MATERIALS AND METHODS: This cross-sectional study involved 80 age-sex matched patients with IA and controls. Fisher's exact test was performed to analyze allelic associations between ten single nucleotide polymorphisms (SNPs) and IA, including 41 ruptured and 39 unruptured cases. Haplotype-specific associations were analyzed using the omnibus test estimating asymptotic chi-square statistics. RESULTS: Of ten SNPs, three SNPs (rs2303656, rs3900446, and rs763497) were significantly associated with IA (p<0.01). The C allele of rs3900446 was significantly related to increased IA risk with a significant threshold [odds ratio (OR)=20.15, p=4.8×10⁻⁵]. Meanwhile, the A allele of rs2303656 showed a preventive effect against IA formation (p=8.2×10⁻⁴). Seventeen of 247 haplotype structures showed a suggestive association with IA (asymptotic p<0.001). Of ten SNP haplotype combinations, the CG combination of rs3900446 and rs763497 reached Bonferroni-adjusted significant threshold in IA patients (minor haplotype frequency=0.113, asymptotic p=1.3×10⁻⁵). However, there was no association between aneurysm rupture and the LOX gene. CONCLUSION: This preliminary study indicated that LOX gene polymorphisms, such as rs2303656, rs3900446, and rs763497, may play crucial roles in IA formation in the Korean population. Our novel findings need to be validated in a large-scale independent population.

The Role of the Lysyl Oxidases in Tissue Repair and Remodeling: A Concise Review

Tissue injury provokes a series of events containing inflammation, new tissue formation and tissue remodeling which are regulated by the spatially and temporally coordinated organization. It is an evolutionarily conserved, multi-cellular, multi-molecular process via complex signalling network. Tissue injury disorders present grievous clinical prob-lems and are likely to increase since they are generally associated with the prevailing diseases such as diabetes, hyper-tension and obesity. Although these dynamic responses vary not only for the different types of trauma but also for the different organs, a balancing act between the tissue degradation and tissue synthesis is the same. In this process, the degradation of old extracellular matrix (ECM) elements and new ones' synthesis and deposition play an essential role, especially collagens. Lysyl oxidase (LOX) and four lysyl oxidase-like proteins are a group of enzymes capable of catalyzing cross-linking reaction of collagen and elastin, thus initiating the formation of covalent cross-links that insolubilize ECM proteins. In this way, LOX facilitates ECM stabilization through ECM formation, development, maturation and remodeling. This ability determines its potential role in tissue repair and regeneration. In this review, based on the current in vitro, animal and human in vivo studies which have shown the significant role of the LOXs in tissue repair, e.g., tendon regeneration, ligament healing, cutaneous wound healing, and cartilage remodeling, we focused on the role of the LOXs in inflammation phase, proliferation phase, and tissue remodeling phase of the repair process. By summarizing its healing role, we hope to shed light on the understanding of its potential in tissue repair and provide up to date therapeutic strategies towards related injuries.

Effect of hypercapnia on lysyl oxidase-dependent collagen cross-linking and hypoxia-induced pulmonary hypertension in rat / 中国病理生理杂志

AIM: To investigate the effect of hypercapnia on hypoxia-induced pulmonary hypertension and the changes of lysyl oxidase (LOX) and extracellular matrix collagen cross-links in the rat.METHODS: Sprague-Dawley rats were randomly divided into 4 groups: normoxia group, hypoxia group, hypercapnia group and hypoxia+hypercapnia group.LOX activity was detected by fluorescence spectrophotometry.LOX protein expression was detected by immunohistochemistry and Western blot.The mRNA expression of LOX in the pulmonary artery was detected by real-time PCR.RESULTS: The levels of mean pulmonary artery pressure (mPAP), RV/(LV+S) and WA/TA in hypoxia group were significantly higher than those in normoxia group (P<0.01).Moreover, the levels of mPAP and RV/(LV+S) in hypoxia+hypercapnia group were significantly lower than those in hypoxia group (P<0.01).However, no significant difference of mPAP and RV/(LV+S) between hypercapnia group and normoxia group was observed.In hypoxia group, the collagen cross-links in the lung tissue was significantly higher than that in normoxia group and hypercapnia group (P<0.01).Importantly, collagen cross-links in the lung tissue of hypoxia+hypercapnia group was significantly lower than that in hypoxia group (P<0.01).There was no significant difference in collagen cross-links between hypercapnia group and normoxia group.The expression of LOX at mRNA and protein levels and its activity in the pulmonary arteries of hypoxia group were significantly increased as compared with normoxia group (P<0.01).Furthermore, the expression of LOX at mRNA and protein levels and its activity in the pulmonary arteries in hypoxia+hypercapnia group were lower than those in hypoxia group (P<0.01).CONCLUSION: Hypoxia not only up-regulates LOX but also promotes collagen cross-linking in the rat lung, which contributes to the development of pulmonary hypertension.Hypercapnia inhibits hypoxia-induced LOX expression and collagen cross-linking, therefore impairing the progress in hypoxia-induced pulmonary hypertension.

Función e importancia clínica de la enzima lisil-oxidasa / Role and clinical significance of the lysyl oxidase enzyme / Funções e importância clínicas da enzima lisil-oxidase

La lisil-oxidasa (LOX) es una quinoenzima que contiene cobre y lisil-tirosilquinona como cofactor. Esta amino-oxidasa actúa en la catálisis de la desaminación oxidativa de residuos de lisina en los precursores del colágeno y de elastina. Anteriormente se ha informado sobre su biosíntesis, sus propiedades catalíticas y mecanismo de reacción, cofactores e inhibidores, así como la expresión y respuesta a diversos efectores celulares. En este trabajo se analizan las funciones e implicancias clínicas de LOX ya que sus niveles aumentan en muchas enfermedades fibróticas y en algunos tumores, con lo que promueven metástasis, mientras que la expresión de la enzima está disminuida en enfermedades que involucran un deterioro en el metabolismo del cobre. LOX tiene funciones paradójicas en cáncer puesto que actúa tanto en la supresión como en la promoción tumoral. Se plantea su rol en la aterogénesis y la disfunción endotelial, en trastornos oculares, fibrosis, enfermedades iatrogénicas, regeneración ósea y aumento del riesgo de enfermedades cardiovasculares, entre otras. Se encaran los últimos avances referidos a la acción proangiogénica del cobre y las funciones de la proteína precursora de LOX, cuyos niveles de expresión están asociados con diversos tipos de cáncer.

Lysyl oxidase (LOX) is a copper-containing quinoenzyme, having lysyl-tyrosyl-quinone as cofactor. This amino oxidase catalyzes the oxidative deamination of lysine residues in collagen and elastin precursors. Its biosynthesis, catalytic properties and reaction mechanism, cofactors and inhibitors as well as expression and response to various cellular effectors have previously been reported. In the present paper, functions and clinical implications of LOX are analyzed, since LOX levels are increased in many fibrotic diseases, and in some tumors promoting metastasis, whereas the expression of the enzyme is decreased in diseases involving deterioration in copper metabolism. LOX shows paradoxical roles in cancer both suppressing and promoting tumors. The role of LOX in atherogenesis and endothelial dysfunction, eye disorders, fibrosis, iatrogenic diseases, bone regeneration, and increased risk of cardiovascular disease, among others, are addressed. Recent developments related to the proangiogenic action of copper and functions of LOX precursor protein, whose expression levels are associated with various cancers, are discussed.

A lisil oxidase (LOX) é uma quinoenzima contendo cobre e lisil-tirosil-quinona como cofator. Esta amino oxidase atua na catálise da desaminação oxidativa de resíduos de lisina de precursores de colágeno e elastina. Anteriormente foi informado sobre sua biossíntese, suas propriedades catalíticas e mecanismo de reação, cofatores e inibidores, bem como a expressão e resposta a vários efetores celulares. Neste trabalho as funções e implicações clínicas de LOX são analisadas visto que seus níveis aumentam em muitas doenças fibróticas e em alguns tumores promovendo metástases, enquanto que a expressão da enzima está reduzida em doenças que envolvem deterioração no metabolismo do cobre. LOX tem funções paradoxais em câncer, uma vez que atua tanto na supressão quanto na promoção tumoral. Discute-se ser papel na aterogênese e disfunção endotelial, distúrbios oculares, fibrose, doenças iatrogênicas, regeneração óssea e aumento do risco de doença cardiovascular, dentre outras. São encarados os últimos avanços associados com a ação pró-angiogênica do cobre e as funções da proteína precursora de LOX, cujos níveis de expressão estão associadas com vários tipos de câncer.

Comparison of LOXL-2 Expression between Active Systematic Scleroderma and Active Mixed Connective Tissue Disease / 中国医科大学学报

Objective To investigate the expression of lysyl oxidase like protein?2(LOXL?2)in the sera of patients with active systemic scleroder?ma(SSc)and mixed connective tissue disease(MCTD). Methods An enzyme?linked immunosorbent assay was adopted to measure LOXL?2 in the serum of 20 patients with active SSc,20 patients with active MCTD,and 20 healthy controls. The measurements among different groups was com?pared,and correlations between LOXL?2 levels and clinical manifestations of SSc and MCTD were examined. Results The levels of LOXL?2 ex?pression in MCTD and SSc groups were significantly higher than those in control group(P<0.05 for all groups). LOXL?2 expression is also related to the presence of skin lesions in SSc(r=0.982 P=0.001). Conclusion High serum level of LOXL?2 in these patients with active SSc and active MCTD suggests that LOXL?2 may be involved in the process of fibrosis and the resulting vasculitis in multiple organs.

The expression and significance of lysyl oxidase like-2 in pulmonary fibrosis mice / 中华风湿病学杂志

Objective To assess whether lysyl oxidase like-2 (LOXL2) has a predictive or prognostic value in pulmonary fibrosis mice,and identify the relationship between LOXL2 and transforming growth factor (TGF)-β 1.Methods Male C57BL/6 mice (n=50) were randomly divided into the experimental group (n=40) and controls (n=10).Each mouse in the experimental group was induced by injecting bleomycin into trachea and mice were sacrificed on day 3,7,14 and 28,respectively.The concentrations of LOXL2,TGF-β 1 of the serum and lung homogenates were measured by enzyme-linked immunosorbent assay.One-factor analysis of variance (ANOVA) and nonparametric rank sum test was used for the comparisons between the two groups.Associations between these factors were analyzed by Spearman's test.Results ① The levels of serum and lung homogenates LOXL2 in the experimental group were obviously increased as compared to those in the controls [serum:(56±48) vs (25±23),P＜0.05;lung homogenates:(61±32) vs (22±16),P＜0.05].And in the experimental group,a positive correlation was found between the level of LOXL2 and the radiological index,the pathological score of inflammation and fibrosis.(Serum:r=0.435,0.533,0.335,P＜0.05;lung homogenates:0.675,0.736,0.526,P＜0.05).② The levels of lung homogenates TGF-β 1 in the experimental group were obviously increased as compared to those in the controls [(302±197) vs (64±16),P＜0.05].A positive correlation was found between the level of lung homogenates LOXL2 and the level of lung homogenates TGF-β1 (r=0.520,P＜0.05).Conclusion LOXL2 participates in the pathological process of bleomycin induced pulmonary fibrosis in mice.It predicts pulmonary fibrosis in the preclinical stage and is associated with increased risk for disease progression.The elevated levels of LOXL2 and TGF-β 1 may have some relationship.They both are involved in the disease progression of pulmonary fibrosis.

Association between single nucleotide polymorphisms at LOXL1 promoter and Uygur patients with exfoliation syndrome / 中华实验眼科杂志

Background Exfoliation syndrome (XFS) is a systemic disease with abnormal accumulation of extracellular matrix.Researches showed that the single nucleotide polymorphisms (SNPs) of lysyl oxidase-like 1 (LOXL1) gene is associated with the pathogenesis of XFS in global population.However,the results are varied among different ethnicity and regions.Objective This study aimed to assess the association between LOXL1 gene polymorphisms and XFS in Uygur population.Methods One-hundred and fifty-two Uygur XFS patients without relativeness were enrolled from January to August in 2014,and 228 ethnicity-and gender-matched normal controls were recruited at the same period from the same region.Each individual underwent comprehensive eye examinations and 5 ml peripheral blood was collected.Genomic DNA was extracted from peripheral blood.PCR-ligase detection response (LDR) was used to determine the allele and genotype frequencies of the six SNPs rs12914489,rs4886467,rs4558370,rs4461027,rs4886761 and rs16958477 in the promoter region of LOXL1 gene.The distribution frequency between the patients and normal controls was compared by x2 test.Logistic regression analysis was used for age adjustment.This study was approved by Ethic Committe of Xinjiang Medical University,and informed consent was obtained from the subjects.Results rs12914489 site in the normal control group diverged from Hardy-Weinberg equilibrium (HWE) (P =0.033),and the rs4886467,rs4558370,rs4461027,rs4886761 and rs16958477 sites followed HWE.The frequencies of G allele and GG genotype of rs4886467 in the XFS group were lower than those in the control group (both at P =0.00) and were protective factors of XFS (OR =0.54,95 ％ CI:0.40-0.74,P =0.000;OR=0.51,95％ CI:0.33-0.78,P=0.001);the frequencies of T allele and TT genotype of rs4558370 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR=1.96,95％ CI:1.23-3.11,P =0.004;OR =2.18,95％ CI:1.31-3.64,P =0.002);the frequencies of C allele and CC genotype of rs4461027 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR=2.25,95％ CI:1.67-3.04,P=0.000;OR=3.06,95％ CI:1.89-4.96,P=0.000);the frequencies of T allele and TT genotype of rs4886761 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR=2.44,95％ CI:1.79-3.33,P =0.000;OR =3.02,95％ CI:1.63-5.60,P =0.000);the frequencies of C allele and CC genotype of rs16958477 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR =2.00,95 ％ CI:1.47-2.71,P =0.000;OR =2.37,95 ％ CI:1.31-4.27,P =0.004).Conclusions The SNPs of promoter region of LOXL1 gene are associated with hereditary susceptibility of XFS individually in Uygur population.The SNPs of rs4886467 locus are protective factor,while the SNPs of rs4558370,rs4461027,rs4886761 and rs16958477 locus are risk factors for pathogenesis of XFS.

Effects of LOX Gene Expression on Proliferation, Invasion and Radiosensitivity of Laryngeal Cancer Hep-2 Cells / 天津医药

Objective To investigate the effect of lysyl oxidase (LOX) gene expression on proliferation, invasion and radiotherapy sensitivity in laryngeal cancer Hep-2 cells. Methods Hep-2 cells were divided into control group (normal cultured), negative control group (transfection reagent) and transfection group (LOX siRNA transfected). The expressions of LOX, Ki-67, PCNA, MMP-2 and MMP-9 mRNA were detected by real time-PCR and Western blot methods. The cell sur-vival rate and apoptosis irradiated by different doses of X-rays (0, 3, 6, 9, 12, 15 and 18 Gy) were detected by MTT and flow cytometry (FCM). Results The expression levels of LOX, Ki-67, PCNA, MMP-2 and MMP-9 protein and mRNA were sig-nificantly lower in Hep-2 cells after transfection than those of control group and negative control group (P<0.05). The cell survival rate was significantly inhibited 24 hours after irradiation (12, 15 and 18 Gy) in a dose-dependent manner (P<0.05). The apoptotic rate of transfection cells combined with radiotherapy was significantly higher than that of control and the nega-tive control groups (%:79.11 ± 1.26 vs 5.01 ± 1.02, 4.95 ± 1.12, 43.21 ± 2.1,P<0.05). Conclusion The expression of LOX can be down-regulated after LOX siRNA transfection, inhibiting proliferation and enhancing radiosensitivity, which may be related to the down-regulation of Ki-67, PCNA, MMP-2 and MMP-9 protein expression.

Anti-lung cancer effect of total flavonoids from Camptosorus sibiricus and their inhibition on lysyl oxidase / 中草药

Objective: To observe the intervention of total flavonoids from Camptosorus sibiricus (TFCS) on lung cancer in mice and to study its possible antitumor mechanism. Methods: The lung cancer model induced by urethane was used to investigate the preventive action of TFCS on lung cancer, the passive pulmonary metastatic model of Lewis lung cancer was used to evaluate the effect of TFCS on tumor metastasis, the scavenger effect of TFCS on system microenvironment was observed in the recurrent tumor model of Lewis lung cancer, the effect of TFCS on lysyl oxidase (LOX) was investigated by Western blotting and immunohistochemical staining, and the vascular normalization function of TFCS was examined by capillary permeability in carcinogenetic lung tissues. Results: TFCS (30 and 100 mg/kg) could decrease the lung carcinogenesis induced by urethane and reduce the passive pulmonary metastasis and recurrence after tumor removal in Lewis lung cancer-bearing mice. TFCS (30 and 100 mg/kg) could also downregulate the expression of LOX in lung cancer tissue, prevent serum lipid peroxide formation in mice with tumor removal, and promote vascular normalization of lung cancer tissue. Conclusion: TFCS as an LOX inhibitor has a definite preventive action on lung cancer.

Lisil-oxidasa (LOX) y proteinas tipo LOX: rol de amino-oxidasas, propiedades moleculares y cataliticas / Lysyl oxidase (LOX) and LOX-like proteins: role of amino-oxidases, molecular and catalytic properties / Lisil-oxidase (LOX) e proteinas tipo LOX: papel da amino-oxidases, propriedades moleculares e catalíticas

Las amino-oxidasas pertenecen a dos grupos de proteinas: flavoenzimas y quinoenzimas. La lisil-oxidasa (LOX) es una quinoenzima que contiene cobre y lisil-tirosil-quinona como cofactor. Los niveles de LOX aumentan en muchas enfermedades fibroticas y en algunos tumores promoviendo metastasis, mientras que la expresion de la enzima esta disminuida en enfermedades que involucran un deterioro en el metabolismo del cobre. Se discute el rol de LOX como amino-oxidasa en la catalisis de la desaminacion oxidativa de residuos de lisina en los precursores del colageno y de elastina, y la participacion de los restantes miembros de esta familia genica: LOXL1, LOXL2, LOXL3 y LOXL4, asi como sus propiedades moleculares. Se analizan su biosintesis, sus propiedades cataliticas y mecanismo de reaccion, cofactores e inhibidores y la expresion y respuesta a diversos efectores celulares.

Amino-oxidases belong to two groups of proteins: flavoenzymes and quinoenzymes. Lysyl oxidase (LOX) is a copper-containing quinoenzime, having lysyl-tyrosyl-quinone as cofactor. LOX levels are increased in many fibrotic diseases, and in some tumors promoting metastasis, while the enzyme expression is decreased in diseases that involve deterioration in copper metabolism. The role of LOX as amino oxidase in catalyzing the oxidative deamination of lysine residues in precursors of collagen and elastin is discussed, as well as the participation of other members of this gene family: LOXL1, LOXL2, LOXL3, and LOXL4, and their molecular properties. The biosynthesis, catalytic properties and reaction mechanism, cofactors and inhibitors, and the expression and response to various cellular effectors are analyzed.

As amina oxidases pertencem a dois grupos de proteínas: flavoenzimas e quinoenzimas. A lisil-oxidase (LOX) é uma quinoenzima contendo cobre e lisil-tirosil-quinona como cofator. Os níveis da enzima LOX aumentam em muitas doenças fibróticas e em alguns tumores promovendo metástase, enquanto que a expressão da enzima está reduzida em doenças que envolvem a deterioração no metabolismo do cobre. Discute-se o papel de LOX como amina oxidase na catálise a desaminação oxidativa de resíduos de lisina de precursores de colágeno e de elastina, e a participação dos outros membros desta família gênica: LOXL1, LOXL2, LOXL3 e LOXL4, bem como as suas propriedades moleculares. A sua biossíntese, as suas propriedades catalíticas e mecanismo de reação, cofatores e inibidores e a expressão e resposta a diversos efetores celulares são analisados.

Comparison of lysyl oxidase expression between active rheumatoid arthritis and active osteoarthritis / 中华风湿病学杂志

Objective To investigate the role of lysyl oxidase (LOX) in synovitis and cartilage destruction by comparing the expression of LOX in synovial fluid and synovium of active rheumatoid arthritis (RA) and active osteoarthritis (OA).Methods LOX in the synovium was detected by immunohistochemistry from 14 patients with active RA,24 patients with active OA and 20 patients with knee injury (the control group).LOX in the synovial fluid was measured by enzyme linked immunosorbent assay (ELISA) from 14 patients with active RA and 24 patients with active OA.T-test was used for statistical analysis.Results The level of LOX expression in active RA synovium (0.012±0.007) was similar to that in active OA synovium (0.013±0.011,P＞0.05).But the expression of LOX in synovium of active RA and active OA was significantly higher than that in synovium of the control group (0.003±0.004,P＜0.01).The amount of LOX in the synovial fluid of active RA [(1.9±1.4) μg/ml] was significantly higher than that of active OA [(1.0±0.4) μg/ml,P＜0.05].Conclusion High expression of LOX in the synovial fluid and synovium of active RA and active OA suggest that LOX may be involved in chronic synovitis and cartilage destruction,and may be related with the extent of synovitis and cartilage destruction.