Diagnostic and Prognostic Significance of Histidine-Rich Glycoprotein in Acute Lymphoblastic Leukemia

Background: Histidine-rich glycoprotein (HRG), a multifunctional plasma protein, has a regulatory role in homeostasis, angiogenesis, and immunity;which in turn could greatly affect tumor control and metastasis. Objectives: To assess the possible role of HRG in acute lymphoblastic leukemia (ALL) tumorgenesis and follow-up. Design and Methods: HRG was quantitatively measured in serum by ELISA and its expression was assessed by real-time PCR (qPCR) in 35 patients with ALL and compared to same 25 ALL patients after induction therapy and 30 age and sex matched healthy control subjects. Results: HRG-serum protein (at cutoff value 63.55 pg/ml) and HRG-RNA (at cut-off value 0.955) were positive in all ALL patients before therapy, but in only 76% after therapy for HRG-protein and 60% for HRG-RNA and they could not be detected in the control group;P < 0.001. Additionally, the serum HRG level showed a significant positive correlation with its expression level, bone marrow blast percentage, peripheral blood blast count, P < 0.01. Also its serum and expression levels were positively related to the poor risk Philadelphia chromosome;P < 0.01. Conclusions: HRG (protein and RNA) might be considered as a novel diagnostic and prognostic marker in ALL. HRG-serum protein level, detected by simple methodology of ELISA, has more significant advantages than its expression level, motivating its application in large clinical studies as a potential marker.

Histidine-rich glycoprotein (HRGP):Pleiotropic and paradoxical effects on macrophage,tumor microenvironment,angiogenesis,and other physiological and pathological processes

Histidine-rich glycoprotein(HRGP)is a relatively less known glycoprotein,but it is abundant in plasma with a multidomain structure,which allows it to interact with many ligands and regulate various biological processes.HRGP ligands includes heme,Zn^(2+),thrombospondin,plasmin/plasminogen,heparin/heparan sulfate,fibrinogen,tropomyosin,IgG,FcγR,C1q.In many conditions,the histidine-rich region of HRGP strengthens ligand binding following interaction with Zn^(2+)or exposure to low pH,such as sites of tissue injury or tumor growth.The multidomain structure and diverse ligand binding attributes of HRGP indicates that it can act as an extracellular adaptor protein,connecting with different ligands,especially on cell surfaces.Also,HRGP can selectively target IgG,which blocks the production of soluble immune complexes.The most common cell surface ligand of HRGP is heparan sulfate proteoglycan,and the interaction is also potentiated by elevated Zn^(2+)concentration and low pH.Recent reports have shown that HRGP can modulate macrophage polarization and possibly regulate other physiological processes such as angiogenesis,anti-tumor immune response,fibrinolysis and coagulation,soluble immune complex clearance and phagocytosis of apoptotic/necrosis cells.In addition,it has also been reported that HRGP has antibacterial and anti-HIV infection effects and may be used as a novel clinical biomarker accordingly.This review outlines the molecular,structural and biological properties of HRGP as well as presenting an update on the function of HRGP in various physiological processes.

The role of glycoproteins in nasopharyngeal carcinoma pathogenesis

Nasopharyngeal carcinoma(NPC)is a malignant tumor arising from the nasopharyngeal epithelium.It consists of undifferentiated squamous cells in the nasopharynx.This type of epithelial cell neoplasm is globally distributed,with the highest prevalence observed in certain regions of the world.It has been known since ancient times.The incidence of NPC is steadily decreasing as data on the molecular factors involved in the pathogenesis of NPC accumulate.Glycoproteins are characterized by polymers of saccharides attached to the amino acid sequences of proteins during the process of glycosylation.They are present in all animal cells and are especially abundant on the surface of tumor cells.Alterations in expression of cellular glycoproteins have recently attracted attention as a key component of neoplastic progression.Tumor-associated glycoproteins may serve as a hallmark of cancer cells and thus represent novel diagnostic and even therapeutic targets.Interest in the role of glycoproteins in cancer in general and specifically in NPC pathology has steadily increased over the past fifty years,reaching over thousands and two hundred publications in the last five years,respectively.Here,data on a specific class of proteins,glycoproteins,involved in tumorigenesis of NPCs are summarized,with a focus on a few of the best-studied ones.Relevant studies performed mainly in the last five years were retrieved and collected through the PubMed system.

Myelin oligodendrocyte glycoprotein-associated transverse myelitis after SARS-CoV-2 infection:A case report

BACKGROUND Cases of myelin oligodendrocyte glycoprotein(MOG)antibody-related disease have a history of coronavirus disease 2019 infection or its vaccination before disease onset.Severe acute respiratory syndrome virus 2(SARS-CoV-2)infection has been considered to be a trigger of central nervous system autoimmune diseases.CASE SUMMARY Here we report a 20-year male with MOG-associated transverse myelitis after a SARS-CoV-2 infection.The patient received a near-complete recovery after standard immunological treatments.CONCLUSION Attention should be paid to the evaluation of typical or atypical neurological symptoms that may be triggered by SARS-CoV-2 infection.

局灶性脑缺血大鼠脑内mdr1／P-glycoprotein表达的变化

目的观察大鼠局灶性脑缺血损害后脑内mdr1／P—glycoprotein的表达变化。方法大鼠大脑中动脉栓塞法(MCAO法)制作局灶性脑缺血模型,脑切片免疫组织化学染色检测mdr-1／P—glycoprotein在脑内的表达部位及表达时程的变化。结果 mdr-1／P—glycoprootein在缺血侧皮层和纹状体的血管内皮细胞表达增多,并出现在同侧损伤部位的神经元,其在损伤后2h开始出现,6h达到高峰,之后开始下降,到24h不能被检测到。结论大脑中动脉阻塞后可以诱导缺血损伤侧的血管内皮细胞P—glycoprotein过量表达,而同侧的神经元短暂表达P-glyco- protein．

海胆胚胎不同发育期P-糖蛋白(P-glycoprotein)药物外排功能的研究

通过研究添加维拉帕米(Verapamil,VER)后,灭蝇胺(Cyromazine)和杀虫丹(Ethiofencarb)对海胆胚胎致死中浓度(LC50)的变化,探讨了不同发育期海胆胚胎P-糖蛋白(P-glycoprotein,P-gp)的功能.结果表明:灭蝇胺和杀虫丹对海胆胚胎的平均LC50分别为2.50mg·L-1和3.50mg·L-1,在加入0.75μmol·L-1P-gp抑制剂VER后,其LC50平均降低40%～42%,说明海胆胚胎P-gp具有药物外排作用.药物浓度可影响P-gp功能,随药物浓度的升高,P-gp外排功能逐渐减弱,甚至达到饱和.实验同时通过分子模拟方法研究了灭蝇胺和杀虫丹的分子结构特征,实验和理论结果均证实了这两种药物分子为海胆胚胎P-gp的底物.

Apolipoprotein E elicits targetdirected miRNA degradation to maintain neuronal integrity

Apolipoprotein E has diverse functions in neurons:Apolipoprotein E(ApoE)is a glycoprotein that primarily regulates lipid metabolism and transport in the central nervous system.There are three predominant human ApoE protein isoforms with cysteine and arginine substitutions at amino acid positions 112 and 158 that impact their lipidation and related functions(Flowers and Rebeck,2020).ApoE2 is characterized by Cys112 and Cys158,ApoE3 by Cys112 and Arg158,whereas ApoE4 contains Arg112 and Arg158.

核偏最小二乘法及其在P-glycoprotein抑制剂设计中应用

介绍了一个新的基于优化推导出的核偏最小二乘(kernel partial least squares,K-PLS)的算法原理和实现步骤,并且给出了利用K-PLS法构建P-糖蛋白(P-glycoprotein,P-gp)黄酮类抑制剂的定量构效关系(QSAR)模型.利用该方法结合几个简单的分子拓扑参数,构建了具有高准确率的预测模型.该模型将有助于P-gp黄酮类抑制剂的虚拟筛选和理性设计.结果证明K-PLS是一个十分稳定可靠的方法,将会在化学计量学领域得到较好的应用和推广.

P-glycoprotein的新功能在肿瘤研究中的进展

肿瘤多药耐药性(multiple drug resistance,MDR)的发生往往伴随着多药耐药基因如MDR1、MRP1和BCRP等高表达,其中MDR1基因编码的P-糖蛋白(P-glycoprotein,P-gp)是目前公认可以诱发癌细胞发生MDR的重要分子。传统研究认为P-gp主要是作为一个药物泵将化疗药物从细胞内排出从而导致MDR。然而系列研究发现,除了介导MDR以外,P-gp还能够调节癌细胞的生长、增殖、凋亡、迁移和侵袭等其他生物学行为;而且研究表明P-gp的这些作用可以依赖,也可以不依赖于其药物泵的功能。这些结果表明P-gp能够通过一些新的机制促进肿瘤的进展。本文主要针对P-gp在促进肿瘤进展中的作用进行综述。

Characterization of an Estrus-Associated Glycoprotein in Oviductal Fluid of Sheep

Estrus-associated glycoprotein (EGP) is a special protein in oviductal fluid which appears before ovulation and fertilization and disappears after the embryo passes into the uterus. One-and two dimensional SDS-PAGE and Western blotting with monoclonal antibody or peanut agglutinin were used to characterize the glycoprotein,The specificity of the marking agents enabled the study to proceed without purification. EGP was found to include two proteins: one is acidic with a pH of 4.5 while the other is basic with a pH of 8.0 The molecular weights of their subunits are the same, that is 110 kD. This study may shed light on the mechanism of reproductive Process and be helpful to the development of a more cffective culture medium for in vitro culture of early embryo.

ILTV Glycoprotein B(gB)与鸡Interleukin-18(IL-18)真核双表达载体的构建及表达

将ILTVgB基因和鸡IL-18基因插入到真核双表达载体pIRES中,构建共表达gB和IL-18基因的重组质粒pIRES-gB/IL18和表达gB基因的pIRES-gB质粒。通过脂质体将其转染鸡胚成纤维细胞,利用RT-PCR及间接免疫荧光检测重组质粒在体外的表达。将重组质粒通过腿部肌肉多点注射免疫21日龄雏鸡,应用ELISA和流式细胞仪分别检测免疫鸡的体液免疫及细胞免疫水平。结果显示,pIRES-gB/IL18和pIRES-gB转染细胞中分别含gB/IL-18基因的mRNA和gB基因的mRNA。间接免疫荧光检测表明,pIRES-gB/IL18和pIRES-gB在CEF细胞中有效地转录并表达gB蛋白。pIRES-gB/IL18和pIRES-gB免疫雏鸡后均能促进外周血T淋巴细胞亚群数量和血清中特异性抗体水平的增加,但前者的免疫效果明显优于后者,表明gB基因和鸡IL-18基因均获得了表达,且鸡IL-18能明显增强ILTV DNA疫苗诱发的免疫应答。

Macular microvascular and structural changes on optical coherence tomography angiography in atypical optic neuritis

BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NMOSD)or myelin oligodendrocyte glycoprotein antibody disease(MOGAD),has a very similar presentation but different prognostic implications and longterm management strategies.Vascular and metabolic factors are being thought to play a role in such autoimmune neuro-inflammatory disorders,apart from the obvious immune mediated damage.With the advent of optical coherence tomography angiography(OCTA),it is easy to pick up on these subclinical macular microvascular and structural changes.AIM To study the macular microvascular and structural changes on OCTA in atypical optic neuritis.METHODS This observational cross-sectional study involved 8 NMOSD and 17 MOGAD patients,diagnosed serologically,as well as 10 healthy controls.Macular vascular density(MVD)and ganglion cell+inner plexiform layer thickness(GCIPL)were studied using OCTA.RESULTS There was a significant reduction in MVD in NMOSD and MOGAD affected as well as unaffected eyes when compared with healthy controls.NMOSD and MOGAD affected eyes had significant GCIPL thinning compared with healthy controls.NMOSD unaffected eyes did not show significant GCIPL thinning compared to healthy controls in contrast to MOGAD unaffected eyes.On comparing NMOSD with MOGAD,there was no significant difference in terms of MVD or GCIPL in the affected or unaffected eyes.CONCLUSION Although significant microvascular and structural changes are present on OCTA between atypical optic neuritis and normal patients,they could not help in differentiating between NMOSD and MOGAD cases.

Acrosome reaction： relevance of zona pellucida glycoproteins

During mammalian fertilisation, the zona pellucida （ZP） matrix surrounding the oocyte is responsible for the binding of the spermatozoa to the oocyte and induction of the acrosome reaction （AR） in the ZP-bound spermatozoon. The AR is crucial for the penetration of the ZP matrix by spermatozoa. The ZP matrix in mice is composed of three glycoproteins designated ZP1, ZP2 and ZP3, whereas in humans, it is composed of four （ZP1, ZP2, ZP3 and ZP4）. ZP3 acts as the putative primary sperm receptor and is responsible for AR induction in mice, whereas in humans （in addition to ZP3）, ZP1 and ZP4 also induce the AR. The ability of ZP3 to induce the AR resides in its C-terminal fragment. O-linked glycans are critical for the murine ZP3-mediated AR. However, N-linked glycans of human ZP1, ZP3 and ZP4 have important roles in the induction of the AR. Studies with pharmacological inhibitors showed that the ZP3-induced AR involves the activation of the Gi-coupled receptor pathway, whereas ZP1- and ZP4-mediated ARs are independent of this pathway. The ZP3-induced AR involves the activation of T-type voltage-operated calcium channels （VOCCs）, whereas ZP1- and ZP4-induced ARs involve both T- and L-type VOCCs. To conclude, in mice, ZP3 is primarily responsible for the binding of capacitated spermatozoa to the ZP matrix and induction of the AR, whereas in humans （in addition to ZP3）, ZP1 and ZP4 also participate in these stages of fertilisation.

Identification and Purification of an Allergic Glycoprotein from Ginkgo biloba Kernel

Glycoprotein from Ginkgo biloba kernel may be allergic. In this paper, the allergic proteins were identified with Western blotting, and the 32 kDa glycoprotein was purified with ion exchange chromatography and gel chromatography. With Western blotting, there were 3 allergic proteins with molecular weight 21, 32, and 36 kDa. With SDS-PAGE analysis and measurements of the protein and sugar contents, the isolation and purification technology of 32 kDa was confirmed. Ginkgo crude protein extract was precipitated with ammonium sulphate （saturation gradient： 40-80%）. The precipitate was purified by chromatography with DEAE-cellulose 52, then chromatography with Sephadex G-200 and the target glycoprotein was finally obtained. The analysis results showed the molecule of the glycoprotein was 32.12 kDa and the ratio of protein to sugar was 20.56：1. In conclusion, the purification method could be used in preparation of the glycoprotein, and the study could provide a basis for the further research of the glycoprotein.

Cloning and Sequence of Glycoprotein H Gene of Duck Plague Virus

The glycoprotein H （gH） gene homologue of duck plague virus （DPV） was cloned by degenerate polymerase chain reaction （PCR） and sequenced. It was located immediately downstream from the thymidine kinase gene （TK）. In addition, the 3＇-end of the gene homologue to herpesvirus UL21 was located downstream from the gH gene. DPV gH gene open reading frame （ORF） was 2 505 bp in length and its primary translation product was a polypeptide of 834 amino acids long. It possessed several characteristics of membrane glycoproteins, including an N-terminal hydrophobic signal sequence, an external domain containing eight putative N-linked glycosylation sites, a C-terminal transmembrane domain, and a charged cytoplasmic tail. Comparison with other herpesvirus revealed identities of 20.2, 25.1, 23.0, 23.0, 26.5 and 26.0% with the gH counterparts of the human herpesvirus virus 1 （HSV1）, equine herpesvirus 4 （EHV4）, bovine herpesvirus 1 （BHV1）, pseudorabies virus （PRV）, gallid herpesvirus 2 （GHV2） and gallid herpesvirus 3 （GHV3）, respectively.

Glycoprotein biomarkers for the detection of pancreatic ductal adenocarcinoma

Pancreatic cancer(Pa C) shows a clear tendency to increase in the next years and therefore represents an important health and social challenge. Currently, there is an important need to find biomarkers for PaC early detection because the existing ones are not useful for that purpose. Recent studies have indicated that there is a large window of time for PaC early detection, which opens the possibility to find early biomarkers that could greatly improve the dismal prognosis of this tumor. The present manuscript reviews the state of the art of the existing PaC biomarkers. It focuses on the anomalous glycosylation process and its role in PaC. Glycan structures of glycoconjugates such as glycoproteins are modified in tumors and these modifications can be detected in biological fluids of the cancer patients. Several studies have found serum glycoproteins with altered glycan chains in PaC patients, but they have not shown enough specificity for PaC. To find more specific cancer glycoproteins we propose to analyze the glycan moieties of a battery of glycoproteins that have been reported to increase in PaC tissues and that can also be found in serum. The combination of these new candidate glycoproteins with their aberrant glycosylation together with the existing biomarkers could result in a panel, which would expect to give better results as a new tool for early diagnosis of PaC and to monitor the disease.

Skin whitening and anti-corrugation activities of glycoprotein fractions from liquid extracts of boiled sea cucumber

Objective: To determine skin whitening and wrinkle improvement efficacy, glycoprotein fractions were extracted from liquid extracts of boiled sea cucumber and their effects on tyrosine and elastase inhibitory activities were assayed. Methods: Fractions above and below 50 k Da(>50 kD a and <50 kD a) were extracted via a series of steps invovling: boiling, filtering, desalting and freeze drying. Cytotoxicity, skin whitening and wrinkle-removing effects of boiled liquid were determined. Results: Our MTT data showed that neither glycoprotein fraction of boiled liquid induces cellular cytotoxicity up to a concentration of 10 mg/m L treatment of the mouse melanoma cell line, B16F10, with 10 mg/m L >50 kDa enhanced tyrosinase and elastase inhibitory activities by 50.84% and 28.78%, respectively. Correlations of the >50 kD a concentration with tyrosinase inhibitory(R^2=0.968) and elastase inhibitory(R2=0.983) efficacy were significant. Conclusions: >50 kD a glycoprotein fraction isolated from liquid extracts of boiled sea cucumber, which can serve as a functional cosmetic ingredient for whitening and wrinkle improvement of skin.

Effect of Rare Earths on Composition and Activities of Rare Earth Elements Binding Glycoprotein in Tea

The effects of spraying rare earths(RE) on composition and activities of tea polysaccharide were measured by inductively coupled plasma mass spectrometry (ICP-MS), gas chromatography(GC), amino acid analyzer and animal models. The results show that there are rare earth elements binding glycoprotein in tea (REE-TGP). The effects of RE on composition and content of saccharides in REE-TGP are not obvious. The contents of Hypro and Ser in REE-TGP are evidently enhanced in comparison with that in control (not treated with rare earth), but the content of Glu is smaller than that from control. The content of La in REE-TGP from the tea garden sprayed rare earth is 193% higher than that in control. REE-TGP declines content of blood sugar in mice and enhances immunization of rat, which are very evident when the animals are treated by REE-TGP from the tea garden sprayed RE.

Differential screening and characterization analysis of the egg envelope glycoprotein ZP3 cDNAs between gynogenetic and gonochoristic cruciancarp

Gynogenetic silver crucian carp, Carassius auratus gibelio, is an intriguing model system. In the present work, a systemic study has been initiated by introducing suppression subtractive hybridization technique into this model system to identify the differentially expressed genes in oocytes between gynogenetic silver crucian carp and its closely related gonochoristic color crucian carp. Five differential cDNA fragments were identified from the preliminary screening, and two of them are ZP3 homologues. Moreover, the full length ZP3 cDNAs were cloned from their oocyte cDNA libraries. The length of ZP3 cDNAs were 1378 bp for gyno-carp and 1367 bp for gono-carp, and they can be translated into proteins with 435 amino acids. Obvious differences are not only in the composition of amino acids, but also in the number of potential O-linked oligosaccharide sites. In addition, gyno-carp ZP3 amino acid sequence has an unexpected higher identity value with common carp (83.5%) than that with the closely related gono-carp (74.7%). The unique homology may be originated from the ancient hybridization. Northern blot analysis confirmed that expression of the ZP3 gene occurred exclusively in the oocytes. Because O-linked oligosaccharides on ZP3 have been demonstrated to play very important roles in fertilization, it is suggested that the extra O-linked glycosylation sites may be related to the unique sperm-egg recognition mechanism in gynogenesis.

Glycoproteins and glycoproteomics in pancreatic cancer

Aberrations in protein glycosylation and polysaccharides play a pivotal role in pancreatic tumorigenesis, influencing cancer progression, metastasis, immunoresponse and chemoresistance. Abnormal expression in sugar moieties can impact the function of various glycoproteins, including mucins, surface receptors, adhesive proteins, proteoglycans, as well as their effectors and binding ligands, resulting in an increase in pancreatic cancer invasiveness and a cancerfavored microenvironment. Recent advance in glycoproteomics, glycomics and other chemical biology techniques have been employed to better understand the complex mechanism of glycosylation events and how they orchestrate molecular activities in genomics, proteomics and metabolomics implicated in pancreatic adenocarcinoma. A variety of strategies have been demonstrated targeting protein glycosylation and polysaccharides for diagnostic and therapeutic development.