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1.
Chinese Journal of Burns ; (6): 629-639, 2022.
Article in Chinese | WPRIM | ID: wpr-940969

ABSTRACT

Objective: To explore the heterogeneity and growth factor regulatory network of dermal fibroblasts (dFbs) in mouse full-thickness skin defect wounds based on single-cell RNA sequencing. Methods: The experimental research methods were adopted. The normal skin tissue from 5 healthy 8-week-old male C57BL/6 mice (the same mouse age, sex, and strain below) was harvested, and the wound tissue of another 5 mice with full-thickness skin defect on the back was harvested on post injury day (PID) 7. The cell suspension was obtained by digesting the tissue with collagenase D and DNase Ⅰ, sequencing library was constructed using 10x Genomics platform, and single-cell RNA sequencing was performed by Illumina Novaseq6000 sequencer. The gene expression matrices of cells in the two kinds of tissue were obtained by analysis of Seurat 3.0 program of software R4.1.1, and two-dimensional tSNE plots classified by cell group, cell source, and gene labeling of major cells in skin were used for visual display. According to the existing literature and the CellMarker database searching, the expression of marker genes in the gene expression matrices of cells in the two kinds of tissue was analyzed, and each cell group was numbered and defined. The gene expression matrices and cell clustering information were introduced into CellChat 1.1.3 program of software R4.1.1 to analyze the intercellular communication in the two kinds of tissue and the intercellular communication involving vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF) signal pathways in the wound tissue, the relative contribution of each pair of FGF subtypes and FGF receptor (FGFR) subtypes (hereinafter referred to as FGF ligand receptor pairs) to FGF signal network in the two kinds of tissue, and the intercellular communication in the signal pathway of FGF ligand receptor pairs with the top 2 relative contributions in the two kinds of tissue. The normal skin tissue from one healthy mouse was harvested, and the wound tissue of one mouse with full-thickness skin defect on the back was harvested on PID 7. The multiple immunofluorescence staining was performed to detect the expression and distribution of FGF7 protein and its co-localized expression with dipeptidyl peptidase 4 (DPP4), stem cell antigen 1 (SCA1), smooth muscle actin (SMA), and PDGF receptor α (PDGFRα) protein. Results: Both the normal skin tissue of healthy mice and the wound tissue of full-thickness skin defected mice on PID 7 contained 25 cell groups, but the numbers of cells in each cell group between the two kinds of tissue were different. Genes PDGFRα, platelet endothelial cell adhesion molecule 1, lymphatic endothelial hyaluronic acid receptor 1, receptor protein tyrosine phosphatase C, keratin 10, and keratin 79 all had distinct distributions on two-dimensional tSNE plots, indicating specific cell groups respectively. The 25 cell groups were numbered by C0-C24 and divided into 9 dFb subgroups and 16 non-dFb groups. dFb subgroups included C0 as interstitial progenitor cells, C5 as adipose precursor cells, and C13 as contractile muscle cells related fibroblasts, etc. Non-dFb group included C3 as neutrophils, C8 as T cells, and C18 as erythrocytes, etc. Compared with that of the normal skin tissue of healthy mice, the intercellular communication in the wound tissue of full-thickness skin defected mice on PID 7 was more and denser, and the top 3 cell groups in intercellular communication intensity were dFb subgroups C0, C1, and C2, of which all communicated with other cell groups in the wound tissue. In the wound tissue of full-thickness skin defected mice on PID 7, VEGF signals were mainly sent by the dFb subgroup C0 and received by vascular related cell groups C19 and C21, PDGF signals were mainly sent by peripheral cells C14 and received by multiple dFb subgroups, EGF signals were mainly sent by keratinocyte subgroups C9 and C11 and received by the dFb subgroup C0, and the main sender and receiver of FGF signals were the dFb subgroup C6. In the relative contribution rank of FGF ligand receptor pairs to FGF signal network in the normal skin tissue of healthy mice and the wound tissue of full-thickness skin defected mice on PID 7, FGF7-FGFR1 was the top 1, and FGF7-FGFR2 or FGF10-FGFR1 was in the second place, respectively; compared with those in the normal skin tissue, there was more intercellular communication in FGF7-FGFR1 signal pathway, while the intercellular communication in FGF7-FGFR2 and FGF10-FGFR1 signal pathways decreased slightly or did not change significantly in the wound tissue; the intercellular communication in FGF7-FGFR1 signal pathway in the wound tissue was stronger than that in FGF7-FGFR2 or FGF10-FGFR1 signal pathway; in the two kinds of tissue, FGF7 signal was mainly sent by dFb subgroups C0, C1, and C2, and received by dFb subgroups C6 and C7. Compared with that in the normal skin tissue of healthy mouse, the expression of FGF7 protein was higher in the wound tissue of full-thickness skin defected mouse on PID 7; in the normal skin tissue, FGF7 protein was mainly expressed in the skin interstitium and also expressed in the white adipose tissue near the dermis layer; in the two kinds of tissue, FGF7 protein was co-localized with DPP4 and SCA1 proteins and expressed in the skin interstitium, co-localized with PDGFRα protein and expressed in dFbs, but was not co-localized with SMA protein, with more co-localized expression of FGF7 in the wound tissue than that in the normal skin tissue. Conclusions: In the process of wound healing of mouse full-thickness skin defect wound, dFbs are highly heterogeneous, act as potential major secretory or receiving cell populations of a variety of growth factors, and have a close and complex relationship with the growth factor signal pathways. FGF7-FGFR1 signal pathway is the main FGF signal pathway in the process of wound healing, which targets and regulates multiple dFb subgroups.


Subject(s)
Animals , Dipeptidyl Peptidase 4 , Epidermal Growth Factor , Fibroblasts , Imidazoles , Ligands , Male , Mice , Mice, Inbred C57BL , Receptor, Platelet-Derived Growth Factor alpha , Sequence Analysis, RNA , Skin Abnormalities , Soft Tissue Injuries , Spinocerebellar Ataxias , Sulfonamides , Thiophenes , Vascular Endothelial Growth Factor A
2.
Article in Chinese | WPRIM | ID: wpr-935784

ABSTRACT

Pulmonary fibrosis is an irreversible interstitial lung disease characterized by lung parenchyma remodeling and collagen deposition. In recent years, the incidence and mortality of pulmonary fibrosis caused by unknown causes have risen. However, its pathogenesis is still unclear. C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C chemokine receptor 4 (CXCR4)/CXCR7 signal axis plays a critical regulatory role in pulmonary fibrosis disease. In addition, the signal axis has been shown to regulate recruitment and migration of circulating fibrocytes, mesenchymal stem cells to the damage lung tissue, the migration of endothelial cells, the proliferation and differentiation of fibroblasts and endothelial cells, which further affects the occurrence and progression of pulmonary fibrosis. In this review, we summarized the pathogenesis and treatment research progress of CXCL12 and its receptor CXCR4/CXCR7 in the occurrence and progression of pulmonary fibrosis.


Subject(s)
Chemokine CXCL12 , Endothelial Cells/pathology , Humans , Ligands , Lung/pathology , Pulmonary Fibrosis/pathology , Receptors, CXCR4
3.
Article in Chinese | WPRIM | ID: wpr-928727

ABSTRACT

OBJECTIVE@#To detect the expression level of suppressors of cytokine signaling 3 (SOCS3) in acute lymphoblastic leukemia (ALL), and to observe the effect of over-expresson of SOCS3 in Jurkat cells on the cytotoxicity of NK cells.@*METHODS@#The expression levels of SOCS3 mRNA in peripheral blood mononuclear cells of 20 children with ALL and 20 healthy children (normal control group) were detected by RT-PCR. The peripheral blood NK cells from healthy subjects were selected by immunomagnetic technique, and the purity was detected by flow cytometry. SOCS3 was overexpressed in Jurkat cells infected with lentivirus vector, and SOCS3 mRNA expression was detected by RT-PCR after lentivirus infection. The NK cells were co-cultured with the infected Jurkat, and LDH release method was used to detect the cytotoxicity of NK cells on the infected Jurkat cells. The concentrations of TNF-α and IFN-γ were determined by ELISA. The expression of NKG2D ligands MICA and MICB on the surface of Jurkat cells were detected by flow cytometry. Western blot was used to detect the effect of SOCS3 overexpression on STAT3 phosphorylation in Jurkat cells.@*RESULTS@#Compared with the control group, the mRNA expression of SOCS3 in the peripheral blood mononucleated cells of ALL children was significantly decreased. The purity of NK cells isolated by flow cytometry could reach more than 70%. The expression of SOCS3 mRNA in Jurkat cells increased significantly after lentivirus infection. Overexpression of SOCS3 in Jurkat cells significantly promoted the killing ability of NK cells and up-regulated the secretion of TNF-α and IFN-γ from NK cells. The results of flow cytometry showed that the expression of NKG2D ligands MICA and MICB on Jurkat cells increased significantly after SOCS3 overexpression. Western blot results showed that overexpression of SOCS3 significantly reduced the phosphorylation level of STAT3 protein in Jurkat cells.@*CONCLUSION@#SOCS3 mRNA expression was significantly decreased in ALL patients, and overexpression of SOCS3 may up-regulate the expression of MICA and MICB of NKG2D ligands on Jurkat cell surface through negative regulation of JAK/STAT signaling pathway, thereby promoting the cytotoxic function of NK cells.


Subject(s)
Child , Histocompatibility Antigens Class I/metabolism , Humans , Killer Cells, Natural/cytology , Leukocytes, Mononuclear/cytology , Ligands , NK Cell Lectin-Like Receptor Subfamily K/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , RNA, Messenger/genetics , Suppressor of Cytokine Signaling 3 Protein/metabolism , Tumor Necrosis Factor-alpha/metabolism
4.
Asian Journal of Andrology ; (6): 97-101, 2022.
Article in English | WPRIM | ID: wpr-928516

ABSTRACT

To efficiently remove all recurrent lymph nodes (rLNs) and minimize complications, we developed a combination approach that consisted of 68Gallium prostate-specific membrane antigen (PSMA) ligand positron emission tomography (PET)/computed tomography (CT) and integrated indocyanine green (ICG)-guided salvage lymph node dissection (sLND) for rLNs after radical prostatectomy (RP). Nineteen patients were enrolled to receive such treatment. 68Ga-PSMA ligand PET/CT was used to identify rLNs, and 5 mg of ICG was injected into the space between the rectum and bladder before surgery. Fluorescent laparoscopy was used to perform sLND. While extensive LN dissection was performed at level I, another 5 mg of ICG was injected via the intravenous route to intensify the fluorescent signal, and laparoscopy was introduced to intensively target stained LNs along levels I and II, specifically around suspicious LNs, with 68Ga-PSMA ligand PET/CT. Next, both lateral peritonea were exposed longitudinally to facilitate the removal of fluorescently stained LNs at levels III and IV. In total, pathological analysis confirmed that 42 nodes were rLNs. Among 145 positive LNs stained with ICG, 24 suspicious LNs identified with 68Ga-PSMA ligand PET/CT were included. The sensitivity and specificity of 68Ga-PSMA ligand PET/CT for detecting rLNs were 42.9% and 96.6%, respectively. For ICG, the sensitivity was 92.8% and the specificity was 39.1%. At a median follow-up of 15 (interquartile range [IQR]: 6-31) months, 15 patients experienced complete biochemical remission (BR, prostate-specific antigen [PSA] <0.2 ng ml-1), and 4 patients had a decline in the PSA level, but it remained >0.2 ng ml-1. Therefore, 68Ga-PSMA ligand PET/CT integrating ICG-guided sLND provides efficient sLND with few complications for patients with rLNs after RP.


Subject(s)
Gallium Isotopes , Gallium Radioisotopes , Humans , Indocyanine Green , Ligands , Lymph Node Excision , Lymphatic Metastasis/diagnostic imaging , Male , Neoplasm Recurrence, Local/surgery , Positron Emission Tomography Computed Tomography , Prostate , Prostatectomy , Prostatic Neoplasms/surgery , Salvage Therapy
5.
Article in Chinese | WPRIM | ID: wpr-928445

ABSTRACT

OBJECTIVE@#To investigate the association of molecular genetic polymorphism of KIR-HLA systems with acute lymphoblastic leukemia (ALL) and acute myelocytic leukemia (AML) in southern Chinese Han.@*METHODS@#A total number of 323 cases of adult ALL patients, 350 adult AML, and 745 random healthy controls were tested by KIR PCR-SSP and HLA-A, -B, -C sequence-based typing (PCR-SBT) methods. The molecular genetic polymorphisms of KIR genes and KIR gene profiles, classⅠ HLA ligands, and KIR receptor +HLA ligand combinations were compared between patient and healthy control groups.@*RESULTS@#A total number of 32 and 33 different kinds of KIR profiles were identified in the ALL and AML patient groups. Compared with the observed frequencies of KIR profiles in healthy controls, the observed frequencies of KIR profile AA1 were significantly lower in both the ALL and AML groups (ALL group: 45.79% vs. 55.30%, Pc=0.004; AML group: 48.27% vs. 55.30%, Pc=0.030). In the ALL group, the observed frequencies of 2DL2 gene and 2DL2+HLA-C1 combination, 2DS2 gene and 2DS2+HLA-C1 combination were significantly higher than those in healthy controls (P<0.05), whereas the frequencies of 2DL3 gene, HLA-A3/A11 ligand and 3DL2+HLA-A3/A11 combination were significantly lower than those in healthy controls. However, no significant differences remained after Bonferroni correction (Pc>0.05). In AML group, the observed frequencies of both 2DS1 and 2DL5 genes were significantly higher than that in healthy controls, whereas the frequencies of HLA-C2 ligand and 2DL1+HLA-C2 combination were significantly lower than that in healthy controls(P<0.05). However, no significant difference existed after Bonferroni correction (Pc>0.05).@*CONCLUSION@#This study revealed some potential susceptibility or protective factors related to acute leukemia in southern Chinese Han, especially the protective factor KIR profile AA1, which might provide new clues and theoretical basis for the pathogenesis of acute leukemia and individualized immunotherapy.


Subject(s)
Adult , China , Gene Frequency , Genotype , HLA-A3 Antigen/genetics , Humans , Leukemia, Myeloid, Acute/genetics , Ligands , Polymorphism, Genetic , Receptors, KIR/genetics
6.
Article in Chinese | WPRIM | ID: wpr-928342

ABSTRACT

OBJECTIVE@#To investigate the effect of intra-articular berberine injection on the structural remodeling of subchondral bone plate and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand(OPG/RANKL) system expression in rabbits with osteoarthritis(OA).@*METHODS@#Forty 12-month-old male rabbits with an average of(2.73±0.18) kg of body weight, underwent left anterior cruciate ligament transection(ACLT), and were divided into berberine group and placebo groups after operation, 20 rabbits in each group. The berberine group received intra-articular injection of 100 μmol/L berberine 0.3 ml every week for 6 weeks. In placebo group, the same dose of 0.9% sodium chloride injection was injected into the left knee joint cavity every week for 6 weeks. Another 20 12-month-old male rabbits, weighing (2.68±0.18) kg, underwent sham operation on the left knee joint without intra-articular injection intervention (sham operation group). On the last day of the sixth week after operation, three groups of animals were sacrificed to obtain knee joint specimens. The femoral medial condyle samples were obtained for histological evaluation of cartilage and subchondral bone, Mankin scoring system was used to evaluate articular cartilage structure. Image-Pro Plus(IPP) software was used to evaluate subchondral bone plate bone volume(BV), bone volume/total volume(BV/TV), trabecular circumference(TC), mean trabecular thickness (Tb.Th). Real-time quantitative reverse transcription polymerization Enzyme chain reaction(reverse transcription-polymerase chain reaction, RT-PCR) was used to detect the mRNA expression levels of OPG and RANKL in subchondral bone tissue at 6 weeks after operation.@*RESULTS@#The cartilage structure evaluation showed that the surface of cartilage tissue in the sham operation group was smooth and flat, and the safranin coloration was full in the full thickness of the cartilage;the cartilage tissue in the berberine group showed uneven surface layer, and the staining of safranin O was mildly decreased;the surface layer fibrosis was seen in placebo group, Safranin O faded significantly. The Mankin score in the berberine group was lower than that in placebo group(P<0.01), but higher than that in sham operation group(P<0.01). The structural evaluation of subchondral bone plate showed that the trabecular bone in sham-operated group was densely arranged;after berberine intervention, the trabeculae were closely arranged;the subchondral bone trabeculae in placebo group were relatively sparse, and the distance between trabeculae was wider. Subchondral bone plate IPP software evaluation showed that BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), while lower than the sham operation group (P<0.01). PCR test results showed that the expression of OPG mRNA in the berberine group was significantly higher than that in placebo group(P<0.01), and OPG mRNA in the berberine group was lower than that in sham operation group (P<0.01). There was no significant difference in mRNA expression of RANKL among three groups(P>0.05);the ratio of OPG/RANKL in berberine group was higher than that in placebo group(P<0.01), but lower than that in sham operation group(P<0.01).@*CONCLUSION@#Intra-articular injection of berberine can effectively inhibit the resorption of subchondral bone in the early stage of OA and delay the development of the disease. The specific mechanism may be that berberine maintains the balance of OPG/RANKL system by up-regulating the expression of OPG gene in subchondral bone.


Subject(s)
Animals , Berberine/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Plates , Cartilage, Articular , Humans , Ligands , Male , NF-kappa B/metabolism , Osteoarthritis/metabolism , Osteoprotegerin/metabolism , RNA, Messenger/therapeutic use , Rabbits
7.
Article in Chinese | WPRIM | ID: wpr-928089

ABSTRACT

Bombesin receptor subtype-3(BRS-3) is an orphan receptor in the bombesin receptor family. Its signal transduction mechanism and biological function have attracted much attention. Seeking the ligand for BRS-3 is of great significance for exploring its function. Considering the fact that the activation of BRS-3 receptor can induce the change in intracellular Ca~(2+) concentration, the fluo-rometric imaging plate reader(FLIPR) was utilized for ligand screening at the cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine from Corydalis Rhizoma and sophoraisoflavanone A and licoriphenone from Glycyrrhizae Radix et Rhizoma antagonized BRS-3 to varying degrees. It was confirmed in HEK293 cells expressing BRS-3 that yuanhunine, sophoraisoflavanone A, and licoriphenone inhibited the calcium current response after the activation of BRS-3 by [D-Phe~6,β-Ala~(11),Phe~(13),Nle~(14)]bombesin-(6-14) in a dose-dependent manner with the IC_(50) values being 8.58, 4.10, and 2.04 μmol·L~(-1), respectively. Further study indicated that yuanhunine and sophoraisoflavanone A exhibited good selectivity for BRS-3. In this study, it was found for the first time that monomers derived from Chinese herbs had antagonistic activity against orphan receptor BRS-3, which has provided a tool for further study of BRS-3 and also the potential lead compounds for new drug discovery. At the same time, it provides reference for the research and development of innovative drugs based on the active ingredients of Chinese herbs.


Subject(s)
Drugs, Chinese Herbal/chemistry , HEK293 Cells , Humans , Ligands , Receptors, Bombesin
8.
Chinese Journal of Biotechnology ; (12): 1518-1526, 2022.
Article in Chinese | WPRIM | ID: wpr-927797

ABSTRACT

Covalently anchoring of a ligand/metal via polar amino acid side chain(s) is often observed in metalloenzyme, while the substitutability of metal-binding sites remains elusive. In this study, we utilized a zinc-dependent alcohol dehydrogenase from Thermoanaerobacter brockii (TbSADH) as a model enzyme, analyzed the sequence conservation of the three residues Cys37, His59, and Asp150 that bind the zinc ion, and constructed the mutant library. After experimental validation, three out of 224 clones, which showed comparative conversion and ee values as the wild-type enzyme in the asymmetric reduction of the model substrate tetrahydrofuran-3-one, were screened out. The results reveal that the metal-binding sites in TbSADH are substitutable without tradeoff in activity and stereoselectivity, which lay a foundation for designing ADH-catalyzed new reactions via metal ion replacement.


Subject(s)
Alcohol Dehydrogenase/metabolism , Catalytic Domain , Ligands , Protein Domains , Zinc/metabolism
9.
São Paulo; s.n; s.n; 2022. 191 p. tab, graf.
Thesis in English | LILACS | ID: biblio-1378632

ABSTRACT

The interaction of the organic ligands with metal nanoparticle has a very important role for applications in catalysis, as well as other processes involving ligands that can activate or poison the surface of metal nanoparticles. Very little has been studied so far on the role of organic ligands used either in the preparation of nanoparticles for applications in catalysis or addition in the reaction to activate the catalyst. In this thesis, we have studied strategies for the synthesis of metal nanoparticles, their use as components for the preparation of supported catalysts and activation and deactivation processes involving the ligands used as stabilizers or purposely added to the reaction medium or support for stimulate new reactivity and selectivity in reactions of industrial interest, such as hydrogenation. Here, the concept of frustrated Lewis pairs (FLPs) has been expanded to surface-FLP analogous formed by combining gold nanoparticles (NPs) and Lewis bases, such as amines or phosphines, creating a new channel for the heterolytic cleavage of H2, and thereby performing selective hydrogenation reactions with gold. A first approach to improve the catalytic activity of gold nanoparticles was to analyze the effect of nitrogen-containing bases. The starting inactive gold nanoparticles became highly active for the selective hydrogenation of alkyne into cis-alkenes. The hydrogenation proceeded smoothly and fully selective using H2 as the hydrogen source and under relatively mild conditions (80 °C, 6 bar H2). Our studies also have revealed that the presence of capping ligands blocks the adsorption of the amine to the gold surface, avoiding the FLPs interface and thereby leading to low catalytic activity. When the capping ligands were removed from the catalyst surface and an amine ligand was added, the FLPs interface is recovered and an enhanced catalytic activity was observed. Furthermore, we have demonstrated the successful use of simple organophosphorus ligands to boost the catalytic activity of Au NPs for a range of important reduction reactions, namely, epoxides, N-oxides, sulfoxides, and alkynes. Furthermore, the choice of phosphorus-containing ligands resulted in a decrease in the amount necessary to reach high conversion and selectivity in comparison with our previous study with N-containing ligands. The ligand-to-metal ratio decreased from 100 (amine/Au) to 1 (phosphite/Au). The synthesis of gold nanoparticles supported on N-doped carbon supports was used as an alternative method for the synthesis of a heterogeneous active gold catalyst for selective hydrogenations. The main advantage with respect to previous studies was to avoid the addition of external ligands, in large excess, for the activation of gold surfaces via FLP, making the whole process environmentally and economically attractive


A interação dos ligantes orgânicos com nanopartículas de metal certamente tem um papel muito importante para aplicações em catálise, bem como outros processos envolvendo ligantes que podem ativar ou envenenar a superfície de nanopartículas metálicas. Até agora, muito pouco foi estudado sobre o papel dos ligantes orgânicos utilizados na preparação de nanopartículas para aplicações em catálise ou adição na reação para ativar o catalisador. Nesta tese, foram estudadas estratégias para a síntese de nanopartículas metálicas, seu uso como componentes para a preparação de catalisadores suportados e processos de ativação e desativação envolvendo ligantes empregados como estabilizantes ou propositalmente adicionados ao meio de reação ou suporte para estimular novas reatividades e seletividade em reações de interesse industrial, como reações de hidrogenação. Aqui, o conceito de pares de Lewis frustrados (FLPs) foi expandido para o seu análogo de superfície formado pela combinação de nanopartículas (NPs) de ouro e bases de Lewis, como aminas ou fosfinas, criando um novo canal para a clivagem heterolítica de H2 e, assim, realizando reações seletivas de hidrogenação com ouro. Uma primeira abordagem para melhorar a atividade catalítica das nanopartículas de ouro foi analisar o efeito de bases contendo nitrogênio. As nanopartículas de ouro inicialmente inativas tornaram-se altamente ativas para a hidrogenação seletiva de alquino em cis-alquenos. A hidrogenação prosseguiu foi factível e totalmente seletiva usando H2 como fonte de hidrogênio e sob condições relativamente amenas (80 °C, 6 bar de H2). Nossos estudos também revelaram que a presença de estabilizantes pode bloquear a adsorção da base na superfície do ouro, impedindo a formação da interface FLPs e, portanto, levando a baixa atividade catalítica. Quando os estabilizantes foram removidos da superfície do catalisador e um ligante foi adicionado, o FLPs é formado sendo a atividade catalítica aprimorada. Além disso, demonstramos o uso bem-sucedido de ligantes organofosforados atuando como ativadores de Au NPs em uma série de importantes reações de redução, como, epóxidos, N-óxidos, sulfóxidos e alquinos. Além disso, a escolha do ligante fosforado resultou em uma diminuição na quantidade necessária para alcançar alta conversão mantendo a seletividade inalterada. A relação ligante/metal diminuiu de 100/1 (amina/Au) para 1/1 (fosfito/Au). A síntese de nanopartículas de ouro suportadas em carbono dopado com nitrogênio foi utilizada como método alternativo para a síntese de um catalisador heterogêneo de ouro ativo para hidrogenações seletivas. A principal vantagem em relação aos estudos anteriores foi evitar a adição de ligantes externos, em grande excesso, para a ativação de superfícies de ouro via FLP, tornando todo o processo ambiental e economicamente atraente


Subject(s)
Catalysis , Catalyzer , Lewis Bases/antagonists & inhibitors , Gold/agonists , Ligands , Carbon/agonists , Health Strategies , Alkenes/classification , Metal Nanoparticles , Occupational Groups
10.
Braz. j. biol ; 82: e232525, 2022. tab, graf
Article in English | LILACS | ID: biblio-1249239

ABSTRACT

Abstract The coupling of a ligand with a molecular receptor induces a signal that travels through the receptor, reaching the internal domain and triggering a response cascade. In previous work on T-cell receptors and their coupling with foreign antigens, we observed the presence of planar molecular patterns able to generate electromagnetic fields within the proteins. These planes showed a coherent (synchronized) behavior, replicating immediately in the intracellular domain that which occurred in the extracellular domain as the ligand was coupled. In the present study, we examined this molecular transduction - the capacity of the coupling signal to penetrate deep inside the receptor molecule and induce a response. We verified the presence of synchronized behavior in diverse receptor-ligand systems. To appreciate this diversity, we present four biochemically different systems - TCR-peptide, calcium pump-ADP, haemoglobin-oxygen, and gp120-CD4 viral coupling. The confirmation of synchronized molecular transduction in each of these systems suggests that the proposed mechanism would occur in all biochemical receptor-ligand systems.


Resumo A ligação de um ligante com um receptor molecular induz um sinal que viaja através do receptor, chegando ao domínio interno e disparando uma cascata de resposta. Em trabalhos anteriores em receptores de células T e sua ligação com antígenos estranhos, observamos a presença de padrões moleculares planares capazes de gerar campos eletromagnéticos dentro das proteínas. Esses planos mostraram um comportamento coerente (sincronizado), replicando, instantaneamente, no domínio intracelular o que ocorreu no domínio extracelular, enquanto o ligante era acoplado. No presente estudo, examinamos essa transdução - a capacidade de um sinal de acoplamento de penetrar profundamente a molécula receptora e induzir uma resposta. Verificamos a presença de um comportamento coerente em sistemas diversos de receptor-ligante. Para apreciar essa diversidade, apresentamos quatro sistemas bioquímicos diferentes: TCR-peptídeo, ADP-bomba de cálcio, hemoglobina-oxigênio e gp120-CD4 acoplamento viral. A confirmação de transdução molecular sincronizada em cada um desses sistemas sugere que o mecanismo proposto ocorreria em todos os sistemas bioquímicos receptor-ligante.


Subject(s)
Signal Transduction , Electromagnetic Fields , Receptors, Antigen, T-Cell/genetics , Ligands
11.
Chinese Journal of Biotechnology ; (12): 2379-2392, 2021.
Article in Chinese | WPRIM | ID: wpr-887804

ABSTRACT

TetR family transcriptional regulators (TFRs) are widely distributed in bacteria and archaea, and the first discovered TFR was confirmed to control the expression of tetracycline efflux pump in Escherichia coli. TFRs can bind DNAs and ligands. Small molecule ligands can induce conformational changes of TFRs, inhibiting or promoting TFRs to control target gene expression. Currently, TFRs have a wide variety of ligands, including carbohydrates, proteins, fatty acids and their derivatives, metal ions, and so on. Due to the diversity of ligands, TFRs regulate a wide range of physiological processes, from basic carbon metabolism and nitrogen metabolism to quorum sensing and antibiotic biosynthesis. On the basis of the recent studies in our laboratory and the literature, we review here the regulatory mechanism mediated by ligands of TFRs in primary and secondary metabolism, as well as the application of ligands for TFRs in the development of gene route and the activation of antibiotic biosynthesis.


Subject(s)
Anti-Bacterial Agents , Bacteria/metabolism , Bacterial Proteins/metabolism , Gene Expression Regulation, Bacterial , Ligands , Quorum Sensing
12.
Article in English | WPRIM | ID: wpr-887751

ABSTRACT

OBJECTIVES@#This study aimed to determine whether a correlation existed between CXC chemokine ligand 10 (CXCL10)-CXC chemokine receptor 3 (CXCR3) and CC chemokine ligand 17 (CCL17)-CC chemokine receptor 4 (CCR4) in the pathogenesis of oral lichen planus (OLP).@*METHODS@#Peripheral blood of OLP patients (non-erosive and erosive groups) and healthy controls were collected, and T cells were isolated and purified. T cells were co-cultured with three groups: blank, anti-CXCR3, and anti-CCR4. CXCR3 and CCR4 expression were detected by flow cytometry, and CXCL10 and CCL17 were detected by enzyme-linked immunosorbent assay, respectively.@*RESULTS@#The purities of T cells were all >95% in the three groups (@*CONCLUSIONS@#Two axes interact with each other in the pathogenesis of OLP and may play different roles in its occurrence and development.


Subject(s)
Chemokine CCL17 , Chemokine CXCL10 , Humans , Lichen Planus, Oral , Ligands , Receptors, CCR4 , Receptors, CXCR3
13.
Chinese Medical Journal ; (24): 1610-1615, 2021.
Article in English | WPRIM | ID: wpr-887581

ABSTRACT

BACKGROUND@#Perioperative neurocognitive disorders (PND) are a series of severe complications in the perioperative and anesthetic periods with a decline in memory, execution ability, and information processing speed as the primary clinical manifestation. This study aimed to evaluate the impact of edaravone (EDA) on PND and peripheral blood C-X-C motif chemokine ligand 13 (CXCL13) levels in elderly patients with hip replacement.@*METHODS@#A total of 160 elderly patients undergoing hip arthroplasty in Affiliated Dongguan People's Hospital of Southern Medical University (from March 2016 to March 2018) were randomly and double-blindly categorized into an EDA group and a control group (CON). Group EDA was administered intravenously EDA 30 min before surgery, and group CON was administered intravenously saline. The cognitive function of the two groups was evaluated 1-day before the operation and at 1 and 12 months after surgery, and the incidence of post-operative delirium was tested on days 1, 3, and 7 after surgery using the Chinese version of the confusion assessment method. Serum CXCL13 and interleukin (IL)-6 concentrations were measured before anesthesia, during surgery (30 min after skin incision), and on days 1, 3, and 7 after surgery. The continuous variables in accordance with normal distribution were tested using the Student's t test, the continuous variables without normal distribution using the Mann-Whitney U test, and categorical variables by the χ2 test or Fisher exact test.@*RESULTS@#The incidence of post-operative delirium within 7 days after surgery was significantly higher in group CON than that in group EDA (31.3% vs. 15.0%, t = -5.6, P < 0.001). The modified telephone interview for cognitive status and activities of daily life scores were significantly higher in the group EDA than those in the group CON at 1 month (39.63 ± 4.35 vs. 33.63 ± 5.81, t = -2.13, P < 0.05 and 74.3 ± 12.6 vs. 61.2 ± 13.1, t = -1.69, P < 0.05) and 12 months (40.13 ± 5.93 vs. 34.13 ± 5.36, t = -3.37, P < 0.05 and 79.6 ± 11.7 vs. 65.6 ± 16.6, t = -2.08, P < 0.05) after surgery; and the incidence of neurocognitive dysfunction was significantly lower in the group EDA than that in the group CON (P < 0.05). Serum CXCL13 and IL-6 concentrations were significantly lower in the group EDA than those in the group CON during and after surgery (P < 0.05).@*CONCLUSION@#EDA can significantly reduce the serum concentrations of CXCL13 and IL-6 and improve the PND of patients.


Subject(s)
Aged , Arthroplasty, Replacement, Hip/adverse effects , Chemokines, CXC/drug effects , Delirium , Double-Blind Method , Edaravone , Humans , Ligands , Postoperative Complications
14.
São Paulo; s.n; s.n; 2021. 150 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1379876

ABSTRACT

Neste trabalho foram sintetizados e caracterizados três complexos de cobre com ligantes imínicos, com o objetivo de avaliar sua atividade tripanocida. Esses complexos foram caracterizados por diversas técnicas espectroscópicas, como UV-Vis, Infravermelho e EPR, além de análise elementar e espectrometria de massa. Juntamente com outros complexos similares previamente sintetizados pelo nosso grupo, tiveram suas atividades avaliadas frente à forma tripomastigota do parasita T. cruzi, responsável pela fase aguda da doença de Chagas, por ensaios de viabilidade celular, com determinação do valor de seus IC50, concentração em que observamos a morte de 50% da cultura celular, pela metodologia denominada MTT. Todos os complexos mostraram-se eficientes frente a tripomastigotas, apresentando valores de IC50 abaixo de 10 µM, com quatro deles obtendo índice de seletividade maior que 10, fator importante para definir agentes promissores antichagásicos. Complexos selecionados também tiveram sua atividade verificada frente à forma amastigota do parasita, responsável pela fase crônica da doença, utilizando método de imageamento por microscópio de fluorescência e contagem celular. Estudos de inibição da cruzaína, uma cisteíno-protease importante para o metabolismo do parasita foram conduzidos em colaboração com o laboratório do Prof. Wagner Alves de Souza Júdice, da Universidade de Mogi das Cruzes. Quatro dos compostos testados apresentaram atividade inibitória frente a cruzaína, sendo dois de cobre, um de zinco e um ligante livre. Os estudos também permitiram diferenciar os mecanismos de inibição dos compostos, com os complexos de cobre apresentando um mecanismo de inibição clássico e o composto de zinco e o ligante livre apresentando o mecanismo de inibição competitiva parabólica com cooperatividade


In this work, three copper complexes with iminic ligands were synthesized and characterized, with the objective of evaluating their trypanocidal activity. These complexes were characterized by several spectroscopic techniques, such as UV-Vis, Infrared and EPR, in addition to elementary analysis and mass spectrometry. Together with other similar complexes previously synthesized by our group, their activities were evaluated against the trypomastigote form of the parasite T. cruzi, responsible for the acute phase of Chagas disease, by cell viability tests, with determination of the value of their IC50, concentration in that we observed the death of 50% of the cell culture, by the methodology called MTT, all presenting IC50 values below 10 µM, with four of them obtaining a selectivity index greater than 10, important factor for defining promising antichagasic agents. Selected complexes also had their activity verified against the amastigote form of the parasite, responsible for the chronic phase of the disease, using a fluorescence microscope and cell counting imaging method. Inhibition studies of cruzain, a cysteine protease important for the metabolism of the parasite, were conducted in collaboration with the laboratory of Professor Wagner Alves de Souza Júdice at the University of Mogi das Cruzes. Four of the tested compounds showed inhibitory activity against cruzain, two of copper, one of zinc and a free ligand. The studies also allowed to differentiate the mechanisms of inhibition of the compounds, with the copper complexes presenting a classic inhibition mechanism and the zinc compound and the free ligand presenting the competitive parabolic inhibition mechanism with cooperativity


Subject(s)
Chagas Disease/pathology , Copper/chemistry , Imines/agonists , Antiparasitic Agents , Mass Spectrometry/methods , Trypanocidal Agents/administration & dosage , Cell Culture Techniques/instrumentation , Cysteine Proteases/chemistry , Ligands
15.
Clinics ; 76: e1713, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153987

ABSTRACT

OBJECTIVES: The chemokine ligand (CCL) 21 regulates the maturation, migration, and function of dendritic cells, and has been implicated in the pathogenesis of asthma. This study aimed to investigate the association between serum CCL21 levels and asthma control. METHODS: The serum levels of CCL21 and other inflammatory cytokines were analyzed in patients with asthma (n=44) and healthy controls (n=35) by enzyme-linked immunosorbent assay. IgE levels and eosinophil counts were determined by turbidimetric inhibition immunoassay and fully automatic blood analysis, respectively. The Asthma Control Test (ACT) questionnaire was used, and spirometry and fractional exhaled nitric oxide (FENO) measurements were performed. A multiple unpaired Student's t-test was performed to analyze the differences in CCL21 and interleukin levels between patients with asthma and healthy controls. The correlation of CCL21 levels with disease severity was evaluated using the Pearson's rank correlation test. RESULTS: Serum CCL21 levels were lower in patients with asthma (254.78±95.66 pg/mL) than in healthy controls (382.95±87.77 pg/mL) (p<0.001). Patients with asthma had significantly higher levels of IL-1β (19.74±16.77 vs. 2.63±5.22 pg/mL), IL-6 (7.55±8.65 vs. 2.37±2.47 pg/mL), and tumor necrosis factor-α (12.70±12.03 vs. 4.82±3.97 pg/mL) compared with the controls. CCL21 levels were positively correlated with the ACT score (rs=0.1653, p=0.0062), forced expiratory volume in 1s (FEV1)/forced vital capacity (rs=0.3607, p<0.0001), and FEV1 (rs=0.2753, p=0.0003), and negatively correlated with FENO (rs=0.1060, p=0.0310). CCL21 levels were negatively correlated with serum IgE levels (rs=0.1114, p=0.0268) and eosinophil counts (rs=0.3476, p<0.0001). CONCLUSIONS: Serum CCL21 levels may be a new biomarker for assessing asthma control.


Subject(s)
Humans , Adult , Asthma , Chemokine CCL21/blood , Forced Expiratory Volume , Chemokines , Exhalation , Ligands , Nitric Oxide
16.
J. bras. nefrol ; 42(3): 280-289, July-Sept. 2020. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1134858

ABSTRACT

ABSTRACT Introduction: Glomerular hyperfiltration may lead to proteinuria and chronic kidney disease in unilateral multicystic dysplastic kidney (MCDK). We aimed to investigate the urine neutrophil-gelatinase-associated lipocalin (NGAL), netrin-1, hepcidin, and C-C motif chemokine ligand-2 (MCP-1/CCL-2) levels in patients with MCDK. Methods: Thirty-two patients and 25 controls were included. The urine hepcidin, netrin-1, NGAL, and MCP-1/CCL-2 levels were determined by ELISA. Results: The patients had higher serum creatinine (Cr) levels, urine albumin, and netrin-1/Cr ratio with lower GFR. There were positive correlations between urine protein/Cr, MCP-1/CCL-2/Cr, and netrin-1 with NGAL (r = 0.397, p = 0.031; r = 0.437, p = 0.041, r = 0.323, p = 0.042, respectively). Urine netrin-1/Cr was positively correlated with MCP-1/CCL-2/Cr (r = 0.356, p = 0.045). There were positive associations between the presence of proteinuria and netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr [Odds ratio (OR): 1.423, p = 0.037, OR: 1.553, p = 0.033, OR: 2.112, p = 0.027, respectively)]. ROC curve analysis showed that netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr had high predictive values for determining proteinuria p = 0.027, p = 0.041, p = 0.035, respectively). Urine hepcidin/Cr was negatively correlated with tubular phosphorus reabsorption and was positively correlated with urine NGAL/Cr (r = -0.418, p = 0.019; r = 0.682, p = 0.000; respectively). Conclusions: MCP-1/CCL-2 may play a role in the development of proteinuria in MCDK. Netrin-1 may be a protective factor against proteinuria-induced renal injury. Urine hepcidin/Cr may reflect proximal tubule damage in MCDK. Urine NGAL/Cr may be a predictor of tubule damage by proteinuria.


Resumo Introdução: A hiperfiltração glomerular pode causar proteinúria e doença renal crônica no rim displásico multicístico unilateral (RDM). Nosso objetivo foi investigar os níveis de lipocalina associada à gelatinase neutrofílica na urina (NGAL), netrina-1, hepcidina e quimiocina C-C com ligante-2 (MCP-1/CCL-2) em pacientes com RDM. Métodos: Trinta e dois pacientes e 25 controles foram incluídos. Os níveis urinários de hepcidina, netrin-1, NGAL e MCP-1/CCL-2 foram determinados por ELISA. Resultados: Os pacientes apresentaram níveis séricos mais elevados de creatinina (Cr), albumina na urina e relação netrina-1/Cr com menor TFG. Houve correlação positiva entre proteína na urina/Cr, MCP-1/CCL-2/Cr e netrina-1 com NGAL (r = 0,397, p = 0,031; r = 0,437, p = 0,041, r = 0,323, p = 0,042, respectivamente). A netrina-1/Cr na urina foi correlacionada positivamente com MCP-1/CCL-2/Cr (r = 0,356, p = 0,045). Houve associações positivas entre a presença de proteinúria e netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr [Odds ratio (OR): 1,423, p = 0,037, OR: 1,553, p = 0,033, OR: 2,112, p = 0,027, respectivamente) ]. A análise da curva ROC mostrou que netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr apresentaram altos valores preditivos para determinar a proteinúria p = 0,027, p = 0,041, p = 0,035, respectivamente). A hepcidina/Cr na urina foi correlacionada negativamente com a reabsorção tubular de fósforo e positivamente com a NGAL/Cr na urina (r = -0,418, p = 0,019; r = 0,682, p = 0,000; respectivamente). Conclusões: MCP-1/CCL-2 pode ter participação no desenvolvimento de proteinúria no RDM. A Netrina-1 pode ser um fator protetor contra lesão renal induzida por proteinúria. Hepcidina/Cr na urina pode refletir danos em túbulos proximais no RDM. O valor de NGAL/Cr urinário pode ser um preditor de danos nos túbulos por proteinúria.


Subject(s)
Humans , Female , Multicystic Dysplastic Kidney/metabolism , Biomarkers , Proto-Oncogene Proteins , Chemokines , Creatinine , Hepcidins , Lipocalin-2 , Netrin-1 , Ligands
17.
Article in Chinese | WPRIM | ID: wpr-828487

ABSTRACT

OBJECTIVE@#To provide data support for the study of pathogenic mechanism of SARS-CoV-2 at the molecular level, and provide suitable candidate targets for vaccine, antibody and drug research and development through comparative analysis for structural characteristics and epitopes of S protein of SARS-CoV-2 and SARS-CoV.@*METHODS@#Based on the reference sequences of S protein, physical and chemical properties, hydrophobicity, signal peptide, transmembrane region, domain, secondary structure, tertiary structure analysis and antigenic epitopes prediction were carried out. Meanwhile, the tissue expression, related pathways and reactome pathways of angiotensis Ⅰ converting enzyme 2 (ACE2) and C-type lectin domain family 4 member M (CLEC4M) receptors were analyzed.@*RESULTS@#The amino acid sequence of S protein of SARS-CoV-2 and SARS-CoV has a 75.80% consistency. The structural characteristics of the two coronaviruses are highly consistent, but the secondary structure and tertiary structure of SARS-CoV-2 is not as obvious as SARS-CoV. ACE2 and CLEC4M are expressed in alimentary system, heart, kidney, lung and placenta. The main related the pathways of renin-angiotensin system, protein digestion and absorption pathway, and the reactome pathways of metabolism of angiotensinogen to angiotensins, GPCR ligand binding, are related to typical symptoms of coronavirus disease 2019 induced by SARS-CoV-2. Three pairs of highly or completely homologous epitopes of S protein were obtained. The 600-605, 695-703 and 888-896 amino acid residues in SARS-CoV-2 were highly homologous with 586-591, 677-685 and 870-878 amino acid residues in SARS-CoV, respectively.@*CONCLUSIONS@#The similarity of S protein of SARS-CoV-2 and SARS-CoV determines that they have similar infection patterns and clinical manifestations. The candidate epitopes with high reliability can provide reference for virus diagnosis and vaccine development.


Subject(s)
Betacoronavirus , Cell Adhesion Molecules , Coronavirus Infections , Epitopes , Humans , Lectins, C-Type , Ligands , Pandemics , Peptidyl-Dipeptidase A , Pneumonia, Viral , Receptors, Cell Surface , Receptors, Virus , Reproducibility of Results , Spike Glycoprotein, Coronavirus
18.
Article in Chinese | WPRIM | ID: wpr-828368

ABSTRACT

G-quadruplex DNA has become an important target for tumor therapy and anti-tumor development. Modern pharmacology has proved that Macleaya cordata has anti-inflammatory, antibacterial, anti-tumor and other pharmacological effects. Affinity ultrafiltration method can screen active ingredients from compounds rapidly, but G-quadruplex DNA ligands are difficult to dissociate, which is a key step in conventional ultrafiltration method. In this paper, the filtrates after ultrafiltration were determined by HPLC-MS in substitution. The peaks with 20% reduction of MS response from the incubation vs control were considered to be ligand components to G-quadruplex. Two of the peaks with the relative abundance above 30% were identified as sanguinarine(SAN) and chelerine(CHE). Their circular dichroism conformations further proved that SAN and CHE are active ligands of HT4. In addition, another two gradients with high relative abundance were identified as protopine(PRO) and allpcryprotopine(ALL). The binding rate of SAN, CHE, PRO and ALL was calculated according to the HPLC-MS results, and the results showed a consistency with that of the molecular docking method. The proposed method can be used to screen active components from mixture.


Subject(s)
Chromatography, High Pressure Liquid , Chromatography, Liquid , G-Quadruplexes , Ligands , Mass Spectrometry , Molecular Docking Simulation , Ultrafiltration
19.
Journal of Experimental Hematology ; (6): 1826-1830, 2020.
Article in Chinese | WPRIM | ID: wpr-879978

ABSTRACT

OBJECTIVE@#To investigate the regulatory effects of Olaparib on natural killer cell activating receptor (NKG2D) ligands expression on human acute myeloid leukemia (AML) cell line HL-60, and to explore the molecular mechanism of Olaparib on HL-60 cells.@*METHODS@#After HL-60 cells in logarithmic growth phase were treated with Olaparib at different concentrations for different times (24, 48 h), the expression of NKG2D ligand on the surface of HL-60 cells was detected by flow cytometry. Western blot was used to dectect the expression of ERK expression in HL-60 cells. The killing effect of NK cells to HL-60 cells was detected by CFSE/PI method.@*RESULTS@#10 μmol/L Olaparib could upregulate the expression of NKG2D ligand on the surface of HL-60 cell at 24 and 48 hours, while 5 μmol/L Olaparib could induce up-regulation of the expression of ULBP-2 and ULBP-3 at 48 hours. Western blot analysis showed that ERK phosphorylation of HL-60 cells was enhanced after treating with Olaparib. The killing effect of NK cells to HL-60 cells could be enhanced by Olaparib, however, ERK inhibitor could suppress the killing effect of NK cells to HL-60 cells.@*CONCLUSION@#Olaparib can upregulate NKG2D ligands expression on the surface of HL-60 cells and enhance the cytotoxicity of NK cell to HL-60 cells. The mechanism may be related to Olaparib promoting ERK phosphorylation expression.


Subject(s)
Cell Line, Tumor , Cytotoxicity, Immunologic , HL-60 Cells , Histocompatibility Antigens Class I , Humans , Ligands , NK Cell Lectin-Like Receptor Subfamily K , Phthalazines , Piperazines , Poly(ADP-ribose) Polymerase Inhibitors
20.
Immune Network ; : 5-2020.
Article in English | WPRIM | ID: wpr-811177

ABSTRACT

The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.


Subject(s)
Allergy and Immunology , Communicable Diseases , Cytokines , Homeostasis , Humans , Interleukin-17 , Ligands , Lymphocytes , Mevalonic Acid , Plastics , Population Characteristics , Protein C , Receptors, Antigen, T-Cell, gamma-delta , Receptors, Growth Factor , T-Lymphocyte Subsets , T-Lymphocytes , Terpenes , Tumor Microenvironment
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