Anti-tumor Mechanism and Clinical Application of Pseudomonas Aeruginosa-Mannose-Sensitive Hemagglutinin / 医药导报

The application of Pseudomonas aeruginosa-mannose-sensitive hemagglutinin(PA-MSHA)in the field of an-titumors has been increasing.PA-MSHA has been found to promote tumor cell apoptosis,inhibit tumor cell invasion and migration,differentiation,and change drug resistance and epithelial-mesenchymal transformation(EMT)by inhibiting the EGFR pathway.Meanwhile,PA-MSHA also enhances the immune killing and inhibition of macrophages and T cells to tumor cells through toll-like receptors(TLRs).In this paper,we reviewed the reported anti-tumor mechanism and clinical application of PA-MSHA,suggesting that PA-MSHA may alter the glycosylation of EGFR and TLR proteins by acting on the regulatory process of the cellular mannosy-lation process.PA-MSHA can act on cell membrane proteins,including more receptors with high-mannosylation of signaling path-ways.Elucidating the deep relationship between PA-MSHA and mannosylation is of great significance for the mechanism research and clinical application of PA-MSHA.

Complement lectins and respiratory diseases / 中国免疫学杂志

The complement lectin pathway is an important means to exert immune effect.Ficolin and Mannan-binding lectin(MBL)are the initiators of complement pathway.Both structure and function are very similar.They can activate the complement path-way by recognizing certain substances on the surface of pathogens,emphasizing phagocytosis or directly kill and dissolve related patho-gens,thereby playing an important role in the immune system,especially in fighting infection.The respiratory system diseases are mostly infectious diseases.In recent years,there have been reports that ficolin/MBL is related to many other respiratory diseases.This article discusses the related research of ficolin/MBL and respiratory diseases,hopes to provide theoretical support for related research.

Estudos de síntese de dendrons dirigidos de NFOH com potencial antichagásico e modelagem molecular do receptor de manose de macrófagos / Studying the synthesis of NFOH targeted dendrons, potentially active in Chagas disease, and the molecular modeling of manose receptor from macrophages

A doença de Chagas, considerada doença extremamente negligenciada, acomete mais de 6 milhões de pessoas ao redor do mundo e mais de 75 milhões de pessoas vivem sob risco da doença. Considerada endêmica em 21 países da América Latina. No Brasil, grassa, sobretudo, na região Norte, especialmente, na região amazônica. Apesar de se constituir em risco global, a doença de Chagas conta com apenas com dois fármacos, o benznidazol e o nifurtimox, que, além de tóxicos, não apresentam eficácia significativa na fase crônica da parasitose. Assim sendo, torna-se imperativa a busca por quimioterápicos mais eficazes, mormente na fase crônica da doença. A introdução de novos fármacos da terapêutica várias fases, consumindo tempo e recursos. No entanto, há processos que permitem a otimização de fármacos já existentes e de compostos bioativos, com vistas à busca de candidatos a fármacos, que, uma vez bem-sucedidos nos ensaios clínicos, são aprovados para uso terapêutico. Entre esses processos, destaca-se a latenciação, forma de aprimoramento de propriedades farmacêuticas, farmacocinéticas e, indiretamente, farmacodinâmicas, que utiliza, em geral, transportadores para a resolução de problemas dessas naturezas. Os transportadores variam de acordo com o problema a ser resolvido e, entre eles, os dendrons e dendrímeros podem ser ressaltados pela sua natureza química, que permite a ligação de várias moléculas de fármacos/compostos bioativos e, também, de grupos diretores para certos compartimentos ou células. Dessa forma, podem-se obter fármacos dirigidos, que se constituem em formas latentes de alta seletividade. Face ao exposto e, estimulados pela busca de novas alternativas terapêuticas para a doença de Chagas, o objetivo deste trabalho foi a obtenção de dendrons dirigidos, por meio de manose, derivados de hidroximetilnitrofural (NFOH). Esse composto foi mostrou-se altamente ativo contra T. cruzi, também na fase crônica NFOH e menos tóxico que o protótipo e o benznidazol. Efetuaram-se estudos para a síntese desses compostos derivados de dendron triazólico, sintetizado através de click chemistry, tendo a manose como grupo diretor para os macrófagos, onde, também, são encontrados os amastigotas de Trypanosoma cruzi. Obtiveram-se alguns intermediários, que foram caracterizados por RMN 1H e 13C. A rota sintética proposta não pôde ser finalizada. Por outro lado, efetuaram-se estudos de modelagem molecular, utilizando-se dinâmica molecular, com o intuito de conhecer como se dá a interação da manose e de polimanosídeos com seu respectivo receptor e como se realiza a liberação do composto bioativo da ligação com o dendron. Anteriormente, procedeu-se à caracterização da biologia estrutural do receptor de manose e de suas estruturas primárias, secundárias e terciárias, com ênfase para o domínio CRD4 o papel do cálcio principal na interação com o monossacarídeo. A movimentação do domínio foi muito pouco diferente nos meios simulados (neutro, ácido, contendo ligantes e contendo o cálcio auxiliar), evidenciado pelo RMSF e estudo de PCA desses sistemas. Foi possível concluir que este domínio não apresenta nenhuma alteração conformacional responsável pela liberação de ligantes em meio lisossômico, e que o cálcio auxiliar e os ligantes não causam impactos na estabilidade conformacional do CRD4. Há necessidade de mais estudos para o conhecimento dos requisitos estruturais envolvidos na da formação do complexo receptor-composto bioativo

Chagas disease, considered an extremely neglected one, affects more than 6 million people all over de world, with more than 75 million people living under its risk, while endemics in 21 countries in Latin America. In Brazil, it propagates, mainly in North region, especially in Amazon region. Although being a global risk, only two drugs, benznidazole and nifurtimox, are currently available for Chagas disease. These drugs are toxic and not significantly efficient against the chronic phase of the disease. Therefore, the search for more active chemotherapeutic agents, mainly against the chronic phase of the parasitosis, is imperative. The introduction of new drugs in the therapeutics involves many phases, consuming time, and money. Notwithstanding, there are processes that allow either drugs or bioactive compounds to be optimized, towards drug candidates. These derivatives, once well-succeeded in the clinical trials, can be approved for therapeutic uses. Among those processes, prodrug design stands out. It is a way to improve the pharmaceutics, pharmacokinetics and, indirectly, pharmacodynamics, properties of drugs/bioactive compounds, which requires adequate carriers, in general, for these problems´ solution. The carriers vary according to the problem to be solved, and, among them, dendrons and dendrimers can be emphasized due to their chemical nature, which allows the link of many molecules/bioactive compounds and of directing groups to specific compartments or cells. Thus, targeted drugs, which are latent forms of drugs/bioactive compounds with high selectivity. In this connection and stimulated by the search for new therapeutic alternatives for Chagas disease, the objective of this work was obtaining hydroxymethylnitrofurazone (NFOH) targeted dendrons, by means of mannose, as directing groups. NFOH is highly active against T. cruzi, even in chronic phase of the disease, and less toxic than the prototype and benznidazole. Studies have been developed to synthesize these compounds with a triazole dendron, planned to be obtained by click chemistry. Mannose was designed to be the directing groups to macrophages, where the T. cruzi amastigotes can also be found. Some intermediaries have been obtained and structurally characterized by 1H and 13C NMR, but the proposed synthetic route could not be finished. On the other hand, molecular modeling studies have been developed, using molecular dynamics, with the aim to know how the interaction of mannose, and also of polymannoside, occur with the specific receptor, and how NFOH is released from its linkage to the dendron. The structural biology characterization, as well as of primary, secondary and tertiary structures of the mannose receptor was previously performed, with emphasis onCRD4 and main calcium role in the interaction of the mannoside. All systems simulated (neutral medium, acid medium, complexes with ligands and auxiliary calcium) showed little movement differences when analyzed by RMSF and PCA calculations. It was possible to conclude that this domain shows no conformational changes involved in ligand releasing in lysosomal environment and its conformation is not altered when in presence of ligands or the auxiliary calcium. Much more studies are needed to the knowledge of the structural requirements to the complex receptor-drug-compound bioactive to the receptor

Evaluation of Mannose Binding Lectin Levels in Hypertensive Patients of Tertiary Care Teaching Hospital in Central India

Background: The present study was conducted for evaluating Mannose Binding Lectin levels in hypertensive patients. Materials & Methods: The study included 100 hypertension cases and 100 controls who met the inclusion requirements. All subjects had 5 mL of blood drawn into serum tubes after an overnight fast. After letting the blood clot for 15 minutes at 3000 RPM, the serum was centrifuged out. For the mannose binding lectin test, 0.5 mL of serum had to be stored at - 20°C. ELISA technique was used for evaluating the serum mannose binding lectin levels. All the results were recorded on a Microsoft excel sheet followed by statistical analysis using SPSS software. Results: The mean Mannose Binding Lectin (MBL) in Cases was more (912.56 ± 43.51) as compared to Controls (612.18 ± 21.43) shows statistically significant. (By Un-paired T test; p>0.05). The above table shows the association of type (NYHA) of hypertension and MBL among cases. The mean MBL in Stage II was more (968.39 ± 46.41) as compared to Stage I (856.13 ± 40.56) shows statistically significant. (By Un- paired T test; p>0.05) Conclusion: The present study concludes that, high MBL levels are associated with an increased risk of coronary artery disease and are high in the serum prior to the development of hypertensive symptoms.

Characterization of a D-mannitol oxidase from Paenibacillus sp. and its application in the preparation of D-mannose / 生物工程学报

D-mannose has many functional activities and is widely used in food, medicine, agriculture and other industries. D-mannitol oxidase that can efficiently convert D-mannitol into D-mannose has potential application in the enzymatic preparation of D-mannose. A D-mannitol oxidase (PsOX) was found from Paenibacillus sp. HGF5. The similarity between PsOX and the D-mannitol oxidase (AldO) from Streptomyces coelicolor was 50.94%. The molecular weight of PsOX was about 47.4 kDa. A recombinant expression plasmid pET-28a-PsOX was constructed and expressed in Escherichia coli BL21(DE3). The Km and kcat/Km values of PsOX for D-mannitol were 5.6 mmol/L and 0.68 L/(s·mmol). Further characterization of PsOX showed its optimal pH and temperature were 7.0 and 35 ℃, respectively, while its enzyme activity could be stably remained below 60 ℃. The molar conversion rate of 400 mmol/L D-mannitol by PsOX was 95.2%. The whole cells of PsOX and AldO were used to catalyze 73 g/L D-mannitol respectively. The reaction catalyzed by PsOX completed in 9 h and 70 g/L D-mannose was produced. PsOX showed a higher catalytic efficiency compared to that of AldO. PsOX may facilitate the enzymatic preparation of D-mannose as a novel D-mannose oxidase.

An antigen self-assembled and dendritic cell-targeted nanovaccine for enhanced immunity against cancer

The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.

Research progress of mannose phosphate isomerase-congenital disorders of glycosylation / 中华实用儿科临床杂志

Mannose phosphate isomerase-congenital disorders of glycosylation (MPI-CDG) is a treatable congenital genetic metabolic disease caused by the pathogenic variation of the gene encoding MPI.It is mainly manifested as diarrhea, hepatomegaly, hypoglycemia, and coagulation dysfunction.This review described the pathogenesis, clinical manifestations, genotypes, diagnosis, treatment and management of MPI-CDG, aiming to enhance the understanding of MPI-CDG.

Enhanced uptake and anti-maturation effect of celastrol-loaded mannosylated liposomes on dendritic cells for psoriasis treatment

Psoriasis is an autoimmune skin disease in which dendritic cells (DCs) trigger the progression of psoriasis by complex interactions with keratinocytes and other immune cells. In the present study, we aimed to load celastrol, an anti-inflammatory ingredient isolated from Chinese herbs, on mannosylated liposomes to enhance DC uptake as well as to induce DC tolerance in an imiquimod-induced psoriasis-like mouse model. Mannose was grafted onto liposomes to target mannose receptors on DCs. The results demonstrated that compared with unmodified liposomes, DCs preferred to take up more fluorescence-labeled mannosylated liposomes. After loading celastrol into mannose-modified liposomes, they effectively inhibited the expression of maturation markers, including CD80, CD86 and MHC-II, on DCs both in vitro and in vivo. Additionally, after intradermal injection with a microneedle, celastrol-loaded mannose-modified liposomes (CEL-MAN-LPs) achieved a superior therapeutic effect compared with free drug and celastrol-loaded unmodified liposomes in the psoriasis mouse model in terms of the psoriasis area and severity index, histology evaluation, spleen weight, and expression of inflammatory cytokines. In conclusion, our results clearly revealed that CEL-MAN-LPs was an effective formulation for psoriasis treatment and suggested that this treatment has the potential to be applied to other inflammatory diseases triggered by activated DCs.

Influence of the presence of mannose-binding lectin polymorphisms on the occurrence of leishmaniasis: a systematic review and meta-analysis

Abstract Background Leishmaniasis is caused by an intracellular protozoan of the Leishmania genus. Mannose-binding lectin (MBL) is a serum complement protein and recognizes lipoprotein antigens in protozoa and the bacterial plasma membrane. Nucleotide variants in the promoter region and exon 1 of the MBL gene can influence its expression or change its molecular structure. Objective To evaluate, through a systematic review, case-control studies of the genetic association of variants in the MBL2 gene and the risk of developing leishmaniasis. Methods This review carried out a search in PubMed, Science Direct, Cochrane Library, Scopus and Lilacs databases for case-control publications with six polymorphisms in the mannose-binding Lectin gene. The following strategy was used: P = Patients at risk of leishmaniasis; I = Presence of polymorphisms; C = Absence of polymorphisms; O = Occurrence of leishmaniasis. Four case/control studies consisting of 791 patients with leishmaniasis and 967 healthy subjects (Control) are included in this meta-analysis. The association of variants in the mannose-binding Lectin gene and leishmaniasis under the allelic genetic model, -550 (Hvs. L), -221 (X vs. Y), +4 (Q vs. P), CD52 (A vs. D), CD54 (A vs. B), CD57 (A vs. C) and A/O genotype (A vs. O) was evaluated. International Prospective Register of Systematic Reviews (PROSPERO): CRD42020201755. Results The meta-analysis results for any allelic genetic model showed no significant association for the variants within the promoter, the untranslated region, and exon 1, as well as for the wild-type A allele and mutant allele O with leishmaniasis. Study limitations Caution should be exercised when interpreting these results, as they are based on a few studies, which show divergent results when analyzed separately. Conclusions This meta-analysis showed a non-significant association between the rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, and rs1800451 polymorphisms of the Mannose-binding Lectin gene and leishmaniasis in any allelic and heterogeneous evaluation.

Evaluation of the Lectin Pathway in the Serum of Patients with Chronic Chagas Disease by Detection of C4 by Elisa / Avaliação da via das lectinas no soro de pacientes com doença de Chagas crônica pela detecção de C4 por Elisa

ABSTRACT Chagas disease (CD) is a chronic tropical disease caused by Trypanosoma cruzi , affecting about 8 million people in Latin America. The lectin pathway (LP) of the complement system is one of the first lines of host defense in the response against T. cruzi , and can continue to be activated in chronic infection due to the escape of the parasite to its action. Although some components of this pathway have been investigated in CD, there are no reports on its activation in patient serum. In this context, our objective was to evaluate the activation of LP in chronic chagasic patients and controls by the detection of the C4 component, using the direct ELISA assay. For this purpose, serum of 80 patient with chronic CD (clinical forms: asymptomatic n=17; symptomatic n=63; cardiac n=45; cardio digestive n=13; digestive n=5) followed at the Ambulatory of Attention to Chagasic Patients (HC/UFPR) and 80 healthy controls (donors of the Blood Bank of HC) were evaluated regarding the evaluation of the LP. The results showed that LP activation by mannose-binding lectin (MBL) was found reduced while activation by ficolins was increased in patients with CD when compared to controls. The same results were observed when the patients were categorized according to the indeterminate and symptomatic clinical forms. We conclude that the detection of the C4 component by ELISA is an efficient methodology to assess LP activation in serum from patients with chronic CD, enabling to differentiate the activation profile between patients and controls..

RESUMO A doença de Chagas (DC) é uma doença tropical crônica causada pelo Trypanosoma cruzi, atingindo cerca de 8 milhões de pessoas na América Latina. A via das lectinas (VL) do sistema complemento é uma das primeiras linhas de defesa na resposta imunológica contra a infecção pelo T. cruzi, e pode continuar sendo ativada na infecção crônicadevido ao escape do parasito à sua ação. Embora alguns componentes dessa via tenham sido investigados na DC, não existem relatos sobre sua ativação em soro de pacientes. Neste contexto, nosso objetivo foi avaliar a ativação da VL no soro de pacientes com DC crônica e controles pela detecção do componente C4 empregando a técnica de ELISA. Para isso, amostras de soro de 80 pacientes com DC crônica (formas clínicas: indeterminada n=17; sintomática n=63; cardíaca n=45; cardiodigestiva n=13; digestiva n=5) atendidos no Ambulatório de Atenção ao Paciente Chagásico (HC/UFPR) e 80 controles saudáveis (doadores do Banco de Sangue do HC) foram avaliados quanto a ativação da VL. Os resultados demonstraram que a ativação da VL pela lectina ligante de manose (MBL) encontra-se reduzida, enquanto que a ativação pelas ficolinas está aumentada em pacientes com DC quando comparados aos controles. Os mesmos resultados foram observados quando os pacientes foram categorizados quanto às formas clínicas indeterminada e sintomática. Concluímos que a detecção do componente C4 por ELISA é uma metodologia eficiente para avaliar a ativação da VL em soro de pacientes com DC crônica possibilitando diferenciar o perfil de ativação entre pacientes e controles.

POST1/C12ORF49 regulates the SREBP pathway by promoting site-1 protease maturation

Sterol-regulatory element binding proteins (SREBPs) are the key transcriptional regulators of lipid metabolism. The activation of SREBP requires translocation of the SREBP precursor from the endoplasmic reticulum to the Golgi, where it is sequentially cleaved by site-1 protease (S1P) and site-2 protease and releases a nuclear form to modulate gene expression. To search for new genes regulating cholesterol metabolism, we perform a genome-wide CRISPR/Cas9 knockout screen and find that partner of site-1 protease (POST1), encoded by C12ORF49, is critically involved in the SREBP signaling. Ablation of POST1 decreases the generation of nuclear SREBP and reduces the expression of SREBP target genes. POST1 binds S1P, which is synthesized as an inactive protease (form A) and becomes fully mature via a two-step autocatalytic process involving forms B'/B and C'/C. POST1 promotes the generation of the functional S1P-C'/C from S1P-B'/B (canonical cleavage) and, notably, from S1P-A directly (non-canonical cleavage) as well. This POST1-mediated S1P activation is also essential for the cleavages of other S1P substrates including ATF6, CREB3 family members and the α/β-subunit precursor of N-acetylglucosamine-1-phosphotransferase. Together, we demonstrate that POST1 is a cofactor controlling S1P maturation and plays important roles in lipid homeostasis, unfolded protein response, lipoprotein metabolism and lysosome biogenesis.

Association of the polymorphism Exon 1 (A/O) region of the mannose-binding lectin gene and periportal fibrosis regression in schistosomiasis after specific treatment

Abstract INTRODUCTION: We evaluated the association between genetic polymorphisms in exon 1 (A/O alleles) and promoter regions at positions -550 (H/L variant, rs11003125) and -221 (X/Y variant, rs7096206) MBL2 and periportal fibrosis regression. METHODS: This was a retrospective cohort study involving 114 Brazilians infected with Schistosoma mansoni, who were subjected to follow-up for three years after specific treatment for schistosomiasis to estimate the probability of periportal fibrosis regression. RESULTS: A risk association was observed between polymorphism at the exon 1 MBL2 and periportal fibrosis regression. CONCLUSIONS: This study suggests that the polymorphism of exon 1 MBL2 may potentially be used to predict periportal fibrosis regression in this population.

Chronic mucocutaneous candidiasis associated with paracoccidioidomycosis in a patient with mannose receptor deficiency: First case reported in the literature

Abstract We describe the first report of a patient with chronic mucocutaneous candidiasis associated with disseminated and recurrent paracoccidioidomycosis. The investigation demonstrated that the patient had a mannose receptor deficiency, which would explain the patient's susceptibility to chronic infection by Candida spp. and systemic infection by paracoccidioidomycosis. Mannose receptors are responsible for an important link between macrophages and fungal cells during phagocytosis. Deficiency of this receptor could explain the susceptibility to both fungal species, suggesting the impediment of the phagocytosis of these fungi in our patient.

Mannose-binding lectin gene polymorphism and its effect on short term outcomes in preterm infants / Polimorfismo do gene da lectina ligante de manose e seu efeito em desfechos de curto prazo em bebês prematuros

Abstract Objective: Mannose-binding lectin, which belongs to the collectin family, is an acute-phase reactant that activates the complement system. This study aimed to investigate the effect of MBL2 gene polymorphism on short-term outcomes in preterm infants. Method: Infants of <37 gestational weeks who were admitted to the neonatal intensive care unit during a two-year period were enrolled in this prospective study. The neonates were categorized into two groups according to their MBL2 genotypes. Normal MBL2 genotype was defined as MBL2 wild-type (AA genotype), whereas mutant MBL2 genotype was defined as MBL2 variant-type (AO/OO genotype). The relationship between MBL2 genotype and short-term morbidity and mortality was evaluated. Results: During the two-year study period, 116 preterm infants were enrolled in this study. In MBL2 variant-type, mannose-binding lectin levels were significantly lower and incidences of mannose-binding lectin deficiency (MBL level < 700 ng/mL) were higher (p < 0.001). In this group, the prevalence of respiratory distress syndrome and mortality was significantly higher (p < 0.001, p = 0.03 respectively). In the MBL2 wild-type group, the prevalence of necrotizing enterocolitis (NEC) was higher (p = 0.01). Logistic regression analyses revealed that MBL2 variant-type had a significant effect on respiratory distress syndrome development (odds ratio, 5.1; 95% confidence interval, 2.2-11.9; p < 0.001). Conclusions: MBL2 variant-type and mannose-binding lectin deficiency are important risk factors for respiratory distress syndrome development in preterm infants. Additionally, there is an association between MBL2 wild-type and NEC. Further studies on this subject are needed.

Resumo Objetivo: A lectina ligante de manose (MBL, do inglês mannose-binding lectin), que pertence à família das colectinas, é um reagente de fase aguda que ativa o sistema complemento. Este estudo teve como objetivo investigar o efeito do polimorfismo do gene MBL2 em desfechos de curto prazo em prematuros. Método: Este estudo prospectivo incluiu crianças com menos de 37 semanas de gestação admitidas na unidade de terapia intensiva neonatal durante dois anos. Os neonatos foram categorizados em dois grupos de acordo com os genótipos do MBL2. O genótipo normal do gene MBL2 foi definido como MBL2 do tipo selvagem (genótipo AA), enquanto o genótipo mutante do gene MBL2 foi definido como o gene variante (genótipo AO/OO). Foi avaliada a relação entre o genótipo MBL2 e a morbidade e mortalidade em curto prazo. Resultados: Durante o período de dois anos, 116 bebês prematuros foram incluídos neste estudo. Os níveis de lectina ligante de manose foram significativamente menores nos variantes do MBL2 e as incidências de deficiência de lectina ligante de manose (nível de MBL < 700 ng/mL) foram maiores (p < 0,001). Nesse grupo, a prevalência de síndrome do desconforto respiratório (SDR) e a mortalidade foram significativamente maiores (p < 0,001, p = 0,03, respectivamente). No grupo MBL2 do tipo selvagem, a prevalência de enterocolite necrosante foi maior (p = 0,01). Análises de regressão logística revelaram que os genes variantes do MBL2 apresentaram um efeito significativo no desenvolvimento da síndrome do desconforto respiratório (odds ratio, 5,1; intervalo de confiança de 95%, 2,2-11,9; p < 0,001). Conclusões: As variantes do MBL2 e a deficiência de lectina ligante de manose são importantes fatores de risco para o desenvolvimento da síndrome do desconforto respiratório em neonatos prematuros. Além disso, existe uma associação entre MBL2 do tipo selvagem e a enterocolite necrosante. Mais estudos são necessários sobre esse assunto.

Short Communication: Predicting receptor for mannose-binding lectin on neutrophil surface

Neutrophils play as major phagocytes that participate in the various effector phase of immunity. Mannosebinding lectin (MBL) assisted priming of neutrophils could trigger various processes including modulationof endocytosis rate, reactive oxygen production, chemotaxis, etc., through interactions with cell surfacereceptors. The physiological receptor for MBL on neutrophil's surface is still unreported. Macromoleculardocking could be attempted to determine the protein-protein interactions which are important forunderstanding cellular function and organization. The study was performed to identify the interacting partnerof MBL present on neutrophils surface which leads to the activation of various cell processes. Protein networkanalysis, homology modeling, and Rigid docking were performed to explore structural features and bindingmechanism of MBL with its cellular receptors. The results indicates that CR1 interact with the MBL and mayact as MBL receptor.

The value of the Luminex magnetic bead immunoassay in detecting serum MBL in kidney transplantation patients / 中华检验医学杂志

Objective@#To evaluate the performance of serum mannose-binding lectin(MBL) using Luminex magnetic bead immunoassay, and further clarify the value of serum MBL in the patients of renal transplantation.@*Methods@#A retrospective study based on 110 patients who had underwent renal transplantation in Peking University First Hospital from February 2012 to May 2016 was carried out, and 50 healthy persons were selected as controls. The precision, linearity and correlation of serum MBL were evaluated using Luminex magnetic bead immunoassay, and compared with the traditional ELISA method. The frequency of infection and clinical rejection after transplantation was evaluated according to serum pre-transplant MBL level before transplantation, based on the Luminex method. Statistics analysis was implemented with SPSS 19.0 and MedCalc 12.7.0 software.@*Results@#The repeatability precision and inter-day precision were less than 7.15% and 8.44% respectively, and linear range was 0.05-11 233.00 μg/L detected by Luminex immunoassay.The linear range of MBL detected by ELISA was 3.20-4 202.70 μg/L. The Luminex method had a wider range compared with ELISA. Correlation analysis showed that the regression equation was Y=1.248 6X+231.81, and the correlation coefficient was r=0.978 (P<0.01). Bland-Altman analysis showed that the average deviation percentage was 37.4% (95%CI 33.7%-41.1%).The median (quartile) of pre-transplant serum MBL was 4 164.00 (2 124.00, 7 064.50) μg/L. Patients with a serum MBL<4 164.00 μg/L and MBL≥4 164.00 μg/L were defined as low-and high-level group, respectively. The incidence of infection among the low-level group and high-level group was 47.4% (27/57) and 28.3% (15/53)respectively, which showed a statistical difference(χ2=4.230, P<0.05). The incidence of rejection among the low-level group and high-level group was 43.9% (25/57) and 20.8% (11/53)respectively, which also showed a statistical difference(χ2=6.659, P<0.05).@*Conclusions@#The Luminex magnetic bead immunoassay has a wider linearity compared with ELISA in detecting serum MBL. Additionally, serum pre-transplant MBL level has a good predictive value for the infection and rejection reaction after transplantation.

Correlation between gene polymorphism of mannose-binding lectin 2 and posttraumatic susceptibility to sepsis in Hainan Province / 中华创伤杂志

Objective To investigate the clinical relevance of mannose-binding lectin 2 (MBL2) gene polymorphism with traumatic sepsis in Hainan Province. Methods A retrospective case control study was conducted to analyze the clinical data of 112 severe trauma patients admitted to the First Affiliated Hospital of Hainan Medical College and Haikou People's Hospital from June 2017 to June 2018. There were 73 males and 39 females, aged 17-83 years [(41. 8 ± 8. 9)years]. There were 48 patients in the sepsis group and 64 patients in the non-sepsis group. Multiplex single nucleotide extension polymorphism ( SNaPshot ) typing technique was used to detect the MBL2 gene polymorphism. The correlation between different genotypes and the risk of sepsis was analyzed. ELISA method was used to detect the level of MBL2 in plasma of each group. Results Among the three polymorphic loci of MBL2 gene (rs5030737, rs1800450 and rs1800451), the mutation frequency of rs1800450 was 27. 7％, while the mutation frequency of rs5030737 and of rs1800451 was 0. The genotype distribution in two groups was in accordance with Hardy-Weinberg equilibrium. The frequency of GA genotype in sepsis group was significantly higher than that in non-sepsis group (P<0. 05). A allele frequency in sepsis group was also much higher than that in non-sepsis group (P<0. 05). Patients with GA genotype had increased risk of traumatic sepsis when compared to GG genotype(OR=3. 442, 95％CI 1. 447-8. 187). Allele A increased the prevalence of sepsis significantly as well when compared to allele G(OR =2. 799, 95％CI 1. 270-6. 170). The MBL2 level in serum in sepsis patients with genotype GG and GA was significantly lower than that in non-sepsis group (P<0. 05). In sepsis group, the MBL2 serum level of patients with genotype GA was obviously lower than that in patients with genotype GG (P<0. 05). Conclusion MBL2 rs1800450G/A polymorphism is closely related to the occurrence of sepsis in Hainan province, and may be related to the decrease of serum MBL2 level in patients with mutant type.

Diagnostic value of serum soluble mannose receptor for hepatic fibrosis in patients with chronic hepatitis B / 中华临床感染病杂志

Objective To assess the diagnostic value of serum soluble mannose receptor (sMR) for hepatic fibrosis in patients with chronic hepatitis B (CHB).Methods Fifty patients with CHB undergoing liver biopsy in the Department of Infectious Diseases , Taizhou Hospital of Zhejiang Province from November 2016 to October 2018 were enrolled, including 28 males and 22 females.According to the stage of liver fibrosis, there were 15 cases without fibrosis (S0 group), 12 cases of mild fibrosis (S1-2 group), and 15 cases of moderate-severe fibrosis ( S3-4 group).Twenty healthy subjects (12 males and 8 females) were recruited as controls.Enzyme linked immunosorbent assay (ELISA) was used to detect the serum hyaluronic acid (HA), laminin (LN), procollagen type ⅢN-terminal peptide (PⅢP), collagen type IV (CIV) and sMR in all groups.One-way ANOVA, Spearman correlation analysis and receiver operating characteristic (ROC) curve were used to analyze the data.Results The serum levels of sMR, HA, LN, CIV and PⅢP in S3-4 group were significantly higher than those in S 0 group ( t＝10.20, 4.69, 8.94, 2.35 and 4.34, respectively; all P＜0.05) and S1-2 group (t＝5.77, 4.23, 7.88, 2.71 and 3.43, respectively; all P＜0.05); and serum sMR level in S1-2 group was higher than that in S0 group ( t ＝6.23, P ＜0.05). Spearman rank correlation demonstrated that serum sMR level was positively correlated with the degree of liver fibrosis (r＝0.860, P＜0.01).ROC curve analysis showed that when 228.69 ng／mL was taken as cut-off value of sMR, its specificity and sensitivity for diagnosis of hepatic fibrosis were 93.3%and 88.6%, respectively.The diagnostic efficacy of sMR was significantly better than that of HA , LN, CIV and PⅢP (Z＝3.179, 3.467, 5.241 and 3.567, respectively; all P＜0.05).When 345.80 ng／mL was taken as cut-off value of sMR, the specificity and sensitivity for diagnosis of moderate to severe hepatic fibrosis were 85.7%and 86.7%, respectively; and its diagnostic efficacy was better than that of HA , CIV and PⅢP (Z＝2.253, 2.475 and 2.092, all P ＜0.05).Conclusion Serum sMR level is associated with the progression of liver fibrosis, it may be used as a new serological marker for non-invasive assessment of liver fibrosis.

Correlation between gene polymorphism of mannose-binding lectin 2 and posttraumatic susceptibility to sepsis in Hainan Province / 中华创伤杂志

Objective@#To investigate the clinical relevance of mannose-binding lectin 2 (MBL2) gene polymorphism with traumatic sepsis in Hainan Province.@*Methods@#A retrospective case control study was conducted to analyze the clinical data of 112 severe trauma patients admitted to the First Affiliated Hospital of Hainan Medical College and Haikou People's Hospital from June 2017 to June 2018. There were 73 males and 39 females, aged 17-83 years [(41.8±8.9)years]. There were 48 patients in the sepsis group and 64 patients in the non-sepsis group. Multiplex single nucleotide extension polymorphism (SNaPshot) typing technique was used to detect the MBL2 gene polymorphism. The correlation between different genotypes and the risk of sepsis was analyzed. ELISA method was used to detect the level of MBL2 in plasma of each group.@*Results@#Among the three polymorphic loci of MBL2 gene (rs5030737, rs1800450 and rs1800451), the mutation frequency of rs1800450 was 27.7%, while the mutation frequency of rs5030737 and of rs1800451 was 0. The genotype distribution in two groups was in accordance with Hardy-Weinberg equilibrium. The frequency of GA genotype in sepsis group was significantly higher than that in non-sepsis group (P<0.05). A allele frequency in sepsis group was also much higher than that in non-sepsis group (P<0.05). Patients with GA genotype had increased risk of traumatic sepsis when compared to GG genotype(OR=3.442, 95%CI 1.447-8.187). Allele A increased the prevalence of sepsis significantly as well when compared to allele G(OR=2.799, 95%CI 1.270-6.170). The MBL2 level in serum in sepsis patients with genotype GG and GA was significantly lower than that in non-sepsis group (P<0.05). In sepsis group, the MBL2 serum level of patients with genotype GA was obviously lower than that in patients with genotype GG (P<0.05).@*Conclusion@#MBL2 rs1800450G/A polymorphism is closely related to the occurrence of sepsis in Hainan province, and may be related to the decrease of serum MBL2 level in patients with mutant type.

Content Comparison of Mannose,Glucose and Narinhenin in Dendrobium officinale and Dendrobium huoshanense / 中国实验方剂学杂志

Objective: To optimize the pre-column derivation high performance liquid chromatography (HPLC) content determination method of D-mannose and D-glucose as well as the content determination method of narinhenin in Dendrobium officinale and D. huoshanense, and compare the contents of D-mannose,D-glucose and narinhenin between D. officinale and D. huoshanense. Method: A pre-column derivation HPLC method modified by Chinese Pharmacopoeia(Ch.P) 2015 was used to simultaneously determine the contents of D-mannose and D-glucose,with acetonitrile-0.02 mol·L-1 ammonium acetate solution as mobile phase for gradient elution. Kromasil 100-5 C18 was performed with the wavelength set at 250 nm,and the flow rate was 1 mL·min-1;column temperature was 30℃. HPLC content determination of narinhenin was performed on Kromasil 100-5 C18 with the acetonitrile-methanol-0.4% phosphoric acid solution as mobile phase for gradient elution,and the wavelength was set at 290 nm; the flow rate was 0.8 mL·min-1,and column temperature was 40℃. Result: D-mannose and D-glucose showed a good linear relationship within the range of 0.15-3.0 μg and 0.075-2.25 μg (r=0.999 9); and their average recoveries were 99.01% (RSD 2.1%) and 101.69% (RSD 2.0%) respectively. In addition, the other methodological researches such as repeatability and durability all met the requirements. The contents of D-mannose(Cm),D-glucose(Cg) and sum of them (Cm+Cg) were 12.75%-36.40%,2.93%-18.39% and 19.23%-54.58% in 43 batch of D. officinale. Almost all of the results except very few samples reached the D-mannose standard in Ch.P 2015, and the total content of D-mannose and D-glucose was also up to the total polysccharide standard in Ch.P. The correlation between content and origin was not significant. The contents of D-mannose(Cm),D-glucose(Cg) and sum of them (Cm+Cg) were 14.33%-29.47%,6.64%-15.20%,and 25.73%-44.37% in 12 batch of D. huoshanense. These contents and ratio of peak areas of D-mannose to D-glucose (Am/Ag) were within the scope of D. officinale's; in addition, their average contents were basically the same with those in D. officinale (about 33%).Next,naringenin showed a good linear relationship within the range of 0.020 8-0.832 0 μg (r=0.999 9),and its average recovery was 101.96% (RSD 1.8%). The content of naringenin was 0.053 2-0.122 4 mg·g-1 (average value of 0.081 0 mg·g-1) in 11 batch of D. officinale, slightly higher than 0.040 3-0.090 0 mg ·g-1 (average value of 0.068 3 mg ·g-1) in 7 batch of D. huoshanense. All of these results of narinfenin did not reach the content lower limit in Ch.P. Conclusion: The method used to determinate the content of D-mannose and D-glucose is reproducible, and their sum content is possible to substitute the total polysccaride determination (with higher errors) in D. officinale; monosaccharide content determination can be used for quantitative quality control of D. huoshanense. However, it could not distinguish D. officinale and D. huoshanense by determining the contents of polysccharide,D-glucose,D-mannose and narinhenin, and shall be combined with other specificity methods for further identification.