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1.
Blood Cells Mol Dis ; 97: 102678, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35716403

RESUMEN

The T cell-mediated immune responses associated with asymptomatic infection (AS) of SARS-CoV-2 remain largely unknown. The diversity of T-cell receptor (TCR) repertoire is essential for generating effective immunity against viral infections in T cell response. Here, we performed the single-cell TCR sequencing of the PBMC samples from five AS subjects, 33 symptomatic COVID-19 patients and eleven healthy controls to investigate the size and the diversity of TCR repertoire. We subsequently analyzed the TCR repertoire diversity, the V and J gene segment deference, and the dominant combination of αß VJ gene pairing among these three study groups. Notably, we revealed significant TCR preference in the AS group, including the skewed usage of TRAV1-2-J33-TRBV6-4-J2-2 and TRAV1-2-J33-TRBV6-1-J2-3. Our findings may shed new light on understanding the immunopathogenesis of COVID-19 and help identify optimal TCRs for development of novel therapeutic strategies against SARS-CoV-2 infection.


Asunto(s)
COVID-19 , Humanos , Leucocitos Mononucleares , Receptores de Antígenos de Linfocitos T/genética , SARS-CoV-2 , Linfocitos T
2.
J Bone Miner Metab ; 36(4): 488-497, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28884379

RESUMEN

Osteoporosis (OP) is an increasing public health problem worldwide. Genetic factors are considered to be major contributors to the pathogenesis of OP. The aim of this study was to investigate the association of the purinergic P2X7 receptor (P2X7R) and estrogen receptor-α (ER-α) genes with OP risk, and the effect of the possible interaction between the two genes on predisposition to OP in Chinese postmenopausal women. A total of 596 subjects, including 350 OP patients and 246 controls, were recruited in this case-control study. Five functional single-nucleotide polymorphisms (SNPs) in the P2X7R gene (rs2393799, rs7958311, rs1718119, rs2230911, rs3751143) and two ER-α PvuII and XbaI polymorphisms were genotyped and analyzed. Single-gene variant analysis showed that the carriers of the CC genotype of P2X7R rs3751143 revealed an increased OP risk. Haplotype rs1718119G-rs2230911G-rs3751143C also appeared to be a significant 'risk' haplotype with OP. For the ER-α gene, no evidence of significant association of PvuII or XbaI polymorphism with OP risk was found. Moreover, there was a significant gene-gene interaction between P2X7R rs3751143 and ER-α PvuII; the cross-validation consistency was 10/10 and the testing accuracy was 0.5818 (P = 0.0107). A 1.67-fold-increased risk for OP was detected in individuals carrying the genotypes of AC or CC of rs3751143 and Pp or PP of PvuII compared to subjects with AA of rs3751143 and pp of PvuII. Our findings suggest an important association of the P2X7R rs3751143CC genotype and the rs1718119G-rs2230911G-rs3751143C haplotype with an increased OP risk. Also, the P2X7R rs3751143 and ER-α PvuII two-locus interaction confers a significantly high susceptibility to OP in Chinese postmenopausal women.


Asunto(s)
Pueblo Asiatico/genética , Epistasis Genética , Receptor alfa de Estrógeno/genética , Predisposición Genética a la Enfermedad , Osteoporosis Posmenopáusica/genética , Polimorfismo Genético , Receptores Purinérgicos P2X7/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Haplotipos/genética , Humanos , Modelos Logísticos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo
3.
Purinergic Signal ; 13(3): 339-346, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28497417

RESUMEN

Osteoporosis (OP) is a major public health problem worldwide. Genetic factors are considered to be major contributors to the pathogenesis of OP. The purinergic P2X7 receptor (P2X7R) has been shown to play a role in the regulation of osteoblast and osteoclast activity and has been considered as an important candidate gene for OP. A case-control study was performed to investigate the associations of functional single nucleotide polymorphisms (SNPs) in the P2X7R gene (rs2393799, rs7958311, rs1718119, rs2230911, and rs3751143) with susceptibility to OP in 400 Chinese OP patients and 400 controls. Results showed that rs3751143 was associated with OP; in particular, carriers of the C allele and CC/(AC + CC) genotypes were at a higher risk of OP, but no significant association of rs2230911, rs7958311, rs1718119, and rs2393799 with OP risk was observed. Analysis of the haplotypes revealed one haplotype (rs1718119G-rs2230911G-rs3751143C) that appeared to be a significant "risk" haplotype with OP. The rs3751143 polymorphism was associated with osteoclast apoptosis; ATP-induced caspase-1 activity of osteoclasts with AC and CC genotypes is lower than that of osteoclasts with AA genotype in vitro. The findings suggest that the P2X7R rs3751143 functional polymorphism might contribute to OP susceptibility in Chinese postmenopausal women.


Asunto(s)
Predisposición Genética a la Enfermedad , Osteoporosis/genética , Posmenopausia/genética , Receptores Purinérgicos P2X7/genética , Pueblo Asiatico , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Genotipo , Humanos , Polimorfismo de Nucleótido Simple/genética , Factores Sexuales
4.
Platelets ; 28(8): 829-831, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28580830

RESUMEN

A 38-year-old female patient was diagnosed with anemia for 3 years. Medical examination showed slight splenomegaly (250 × 62 mm), thrombocytopenia (platelets 51 × 109/L), anemia (Hb levels 107 g/L), and ß-glucocerebrosidase activity (GBA) in leukocytes was lower than normal. Microscopic findings of bone marrow smear demonstrated that Gaucher cells in bone marrow and periodic acid-Schiff staining of them were positive. Sequencing of GBA genomic and cDNA identified one novel homozygous mutation, c.484A> G (p.Met162Val). This case suggests that we should pay attention to adult Gaucher disease as a differential diagnosis for cryptogenic thrombocytopenia and one novel homozygous mutation in GBA gene was reported for the first time. The novel mutation in homozygosity is apparently associated with mild, non-neuronopathic type 1 disease which is relatively uncommon in Asian populations.


Asunto(s)
Enfermedad de Gaucher/complicaciones , Trombocitopenia/etiología , Adulto , Femenino , Enfermedad de Gaucher/patología , Humanos , Mutación , Trombocitopenia/patología
5.
Reprod Fertil Dev ; 27(8): 1262-71, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25782073

RESUMEN

Extracellular ATP regulates cellular function in an autocrine or paracrine manner through activating purinergic signalling. Studies have shown that purinergic receptors were expressed in mammalian ovaries and they have been proposed as an intra-ovarian regulatory mechanism. P2X7 was expressed in porcine ovarian theca cells and murine and human ovarian surface epithelium and is involved in ATP-induced apoptotic cell death. However, the role of P2X7 in corpus luteum is still unclear. The aim of this study was to investigate the role of ATP signalling in murine luteal cells and the possible mechanism(s) involved. We found that P2X7 was highly expressed in murine small luteal cells. The agonists of P2X7, ATP and BzATP, inhibited the proliferation of luteal cells. P2X7 antagonist BBG reversed the inhibition induced by ATP and BzATP. Further studies showed that ATP and BzATP inhibited the expression of cell cycle regulators cyclinD2 and cyclinE2. ATP and BzATP also inhibited the p38-mitogen-activated protein kinase (MAPK) signalling pathway. These results reveal that P2X7 receptor activation is involved in corpus luteum formation and function.


Asunto(s)
Adenosina Trifosfato/análogos & derivados , Adenosina Trifosfato/farmacología , Proliferación Celular/efectos de los fármacos , Células Lúteas/efectos de los fármacos , Agonistas del Receptor Purinérgico P2X/farmacología , Animales , Células Cultivadas , Femenino , Células Lúteas/citología , Células Lúteas/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Antagonistas del Receptor Purinérgico P2X/farmacología , Receptores Purinérgicos P2X7/metabolismo
6.
Iran J Immunol ; 20(4): 456-465, 2023 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-37865874

RESUMEN

Background: Natural killer (NK) cells play a role in the pathogenesis of various metabolic diseases related to obesity. While our initial findings have indicated a potential involvement of NK cells in the pathogenesis of type 2 diabetes mellitus, the precise mechanism underlying NK cell-mediated development of this form of diabetes remains inadequately comprehended. Objective: To investigate the impact and the underlying mechanism of high glucose and elevated levels of free fatty acids (FFAs) on immune and inflammatory responses and oxidative stress in NK92 cells. Methods: In this experiment, the CCK8 cytotoxicity assay was used to select the 44.4 mM and 1.5 mM concentrations of high glucose and high FFAs, respectively, to treat NK92 cells for 4 days. The concentrations of superoxide dismutase (SOD) and glutathione (GSH) were determined using a biochemical analyzer. Intracellular reactive oxygen species (ROS) levels, cytokines concentrations (TNF-α, IFN-γ, IL-6, and IL-10), and the expression levels of intracellular molecules (perforin and granzyme B) were assessed by flow cytometry. Results: The number of NK92 cell clumps was significantly reduced in the high-FFA (HF) group. In addition, the production of ROS and levels of cytokines (TNF-α, IFN-γ, IL-6, and IL-10) significantly decreased in the HF group but showed no significant change in the high-glucose (HG) group. This observation was consistent with the expression levels of perforin and granzyme B that decreased in the HF group. Conclusion: High FFAs induced morphological changes and serious damage to oxidative stress and inflammatory response in NK92 cells.


Asunto(s)
Diabetes Mellitus Tipo 2 , Factor de Necrosis Tumoral alfa , Humanos , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-10/metabolismo , Granzimas/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Interleucina-6/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Perforina/metabolismo , Células Asesinas Naturales , Citocinas/metabolismo , Antiinflamatorios/farmacología , Línea Celular , Glucosa/metabolismo
7.
Immunol Lett ; 249: 23-32, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36055412

RESUMEN

B cell-mediated immune responses play important roles in controlling SARS-CoV infection. Here, we performed the single-cell B cell receptor sequencing (scBCR-seq) of the PBMC samples from eleven healthy controls, five asymptomatic subjects and 33 symptomatic COVID-19 patients with various clinical presentations, and subsequently analyzed the abundance and diversity of the BCR repertoires in different groups, respectively. We revealed the skewed usage of the IGHV, IGLV and IGKV genes and identified a number of heavy or light chain VDJ gene pairs and combinational preference in each group, such as IGKV3-7 and IGKV2-24 enriched in the asymptomatic subjects, whereas IGHV3-13, IGHV3-23-IGHJ4, IGHV1-18-IGLV3-19, IGHV1-18-IGLV3-21, and IGHV1-18-IGLV3-25 enriched in the recovery patients with severe diseases. We also observed the differential expression of IGHV3-23 in various B cell clusters by analysis of the scRNA-seq data. Additional dock analysis indicated that IGHV3-13 could bind to the spike protein of SARS-CoV-2. These findings may advance our understanding of the humoral immune responses in COVID-19 patients and help develop novel vaccine candidates as well as therapeutical antibodies against SASR-CoV-2 infections.


Asunto(s)
COVID-19 , COVID-19/genética , Humanos , Leucocitos Mononucleares , Receptores de Antígenos de Linfocitos B/genética , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus
8.
Exp Ther Med ; 20(6): 230, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33224283

RESUMEN

Diabetes and non-coding RNAs are receiving increasing attention in contemporary medical research. The present study aimed to explore the role of the long non-coding RNA uc.48+ in the pathological changes of type 2 diabetes mellitus (T2DM) by observing the effects of uc.48+ small interfering RNA (siRNA) on the abdominal cells of a mouse model of T2DM. Mice with T2DM (DM group) were established by feeding with a high-sugar and -fat diet combined with intraperitoneal injections of low-dose streptozotocin. An intraperitoneal injection of uc.48+ siRNA was administered to the diabetic mice, and the serum levels of cytokines together with other clinical parameters, namely blood pressure, heart rate, mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were examined. Following the collection and identification of abdominal cells from the mice, the mRNA levels of uc.48+, mRNA and protein levels of the P2X7 receptor, and phosphorylation levels of ERK1/2 were evaluated by reverse transcription-PCR and western blotting, respectively. The MWT and TWL were significantly decreased in the DM group compared with the non-diabetic control group. However, the reductions in MWT and TWL were significantly attenuated following uc.48+ siRNA injection. The systolic and diastolic blood pressure, as well as the serum levels of tumor necrosis factor α and interleukin 1ß of mice in the DM group were significantly increased compared with those in the control group, whereas these changes were significantly attenuated following the injection of uc.48+ siRNA. In addition, the expression levels of P2X7 receptor mRNA and protein, and the degree of phosphorylation of ERK1/2 in the abdominal cells were significantly increased in the DM group compared with the control group. These changes were also significantly attenuated following transfection with uc.48+ siRNA in vivo. In conclusion, these data suggest that uc.48+ may play an important role in the pathological changes of blood pressure, neurology and abdominal cell function in T2DM via interaction with the P2X7 receptor.

9.
Int J Mol Med ; 42(2): 1152-1160, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29750294

RESUMEN

High glucose combined with high FFAs can contribute to the unfavorable development of type 2 diabetes mellitus (T2DM) and monocytes/macrophages are important in the occurrence and development of T2DM, which is regarded as a type of low­grade inflammation. Although our previous study demonstrated that increased expression of P2X7 receptor (P2X7R) in peripheral blood monocytes may alter the innate immune system and that long non­coding (lnc)RNA uc.48+ was involved in diabetic neuropathic pain, the involvement of uc.48+ mediated by the P2X7R in monocyte/macrophages during T2DM has not been reported. In the present study, the effectsof uc.48+ small interference RNA (siRNA) on factors, including the mRNA and protein expression of P2X7R, apoptosis and proliferation, levels of reactive oxygen species (ROS), cytokine levels, and expression of phosphorylated (p­) extracellular signal­regulated kinase (ERK)1/2, were examined in RAW264.7 macrophages following exposure to high glucose and high plasma free fatty acids (FFAs). After RAW264.7 cells were transfected with uc.48+ siRNA under high glucose conditions and FFAs treatment, the mRNA expression levels of uc.48+ and P2X7 receptor were detected by reverse transcription­polymerase chain reaction. The protein mass of P2X7 receptor and ERK signaling pathway were assessed by western blotting. ROS and calcium concentrations, and culture supernatant cytokine content [tumor necrosis factor­α, interleukin (IL)­10, IL­1ß] were detected by fluorescent probes and ELISA respectively. Cell viability and apoptosis were determined by MTS test and flow cytometry, respectively. It was found that treatment of RAW264.7 cells with high glucose and FFAs, which exhibited increased expression of uc.48+, evoked P2X7R­mediated immune and inflammatory responses through several means, including cytokine secretion, ROS formation, and activation of the ERK signaling pathway. The uc.48+ siRNA regulated these factors and thus influenced the course and outcome of the immune and inflammatory responses mediated by P2X7R.


Asunto(s)
Glucosa/inmunología , Hiperglucemia/inmunología , Inflamación/inmunología , Macrófagos/inmunología , ARN Largo no Codificante/inmunología , Receptores Purinérgicos P2X7/inmunología , Adulto , Animales , Citocinas/inmunología , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/inmunología , Ácidos Grasos no Esterificados/inmunología , Regulación de la Expresión Génica , Humanos , Hiperglucemia/genética , Inflamación/genética , Macrófagos/metabolismo , Ratones , Persona de Mediana Edad , Células RAW 264.7 , Interferencia de ARN , ARN Largo no Codificante/genética , ARN Interferente Pequeño/genética , Receptores Purinérgicos P2X7/genética
10.
Exp Ther Med ; 13(5): 2480-2482, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28565867

RESUMEN

Hemophagocytic lymphohistiocytosis (HLH), also termed hemophagocytic syndrome, is a severe, life-threatening inflammatory condition that results from an excessive, prolonged and ineffective immune response. The syndrome occurs due to overactive macrophages from the bone marrow or lymph tissue that phagocytose erythrocytes leukocytes and platelets. HLH in a patient with human immunodeficiency virus infection has rarely been studied. The present case study described an uncommon case of this syndrome in combination with human immunodeficiency virus infection in a patient, who eventually succumbed to severe infection and multiple organ failure following the refusal of medical treatment.

11.
Oncol Lett ; 14(3): 2864-2868, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28928825

RESUMEN

The effect of nerve growth factor (NGF) and its receptors on the onset and diagnosis of ovarian cancer was investigated. A total of 35 patients with ovarian tumor admitted in the First Affiliated Hospital of Nanchang University from July 2014 to July 2015 were selected as study subjects and were divided into an observation group (including 21 patients with benign ovarian tumor, and 14 patients with malignant ovarian tumor), and a control group (21 healthy women). The quantity of expression of mRNA in NGF and its receptors (TrkA and p75NTR) was detected using fluorescent quantitative PCR. The protein expression of NGF, TrkA and p75NTR in different study samples was detected using ELISA and western blot analysis. The location of expression was determined using immunohistochemistry. The positive cell rate in different samples was analyzed. Compared with healthy women, the quantity of expression of mRNA in NGF, TrkA and p75NTR in patients with ovarian cancer was increased significantly. The results of ELISA showed that the quantity of protein expression of NGF, TrkA and p75NTR was 0.98±0.12, 1.23±0.14 and 0.76±0.07 µg/l in healthy women, and was 3.21±0.16, 5.28±0.25 and 2.97±0.13 µg/l, respectively, in women with ovarian tumor, and there were statistically significant differences (P<0.05), and the level of expression in patients with malignant ovarian tumor was significantly higher than that in patients with benign ovarian cancer. Western blot analysis also showed that the quantity of expression of NGF, TrkA and p75NTR gene in women with ovarian cancer was significantly higher than that in healthy women. Immunohistochemical results showed that the number of positive cells of NGF, TrkA and p75NTR gene in the tissue of patients with ovarian cancer (89.5, 93.4 and 82.5%, respectively) was significantly higher than those in healthy ovarian tissue (9.4, 10.3 and 7.9%, respectively). In conclusion, NGF and its receptor can contribute to the occurrence of ovarian cancer, and the onset condition of ovarian cancer can be diagnosed through the detection of high or low expression of NGF and its receptors.

12.
Ann Clin Lab Sci ; 46(3): 254-9, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27312548

RESUMEN

Symptoms of hyperthyroidism manifest mainly as changes in the nervous and metabolic systems. Whether P2X receptors (ionotropic ATP purinergic receptors, including P2X3 receptor and P2X7 receptor) are involved in the alterations of these disorders still remains unclear. Thus, this study aimed to assess the association of hyperthyroidism with the expression of P2X3 and P2X7 receptors and the concentrations of ATP in blood leukocytes and catecholamine. Twelve healthy subjects and twelve patients diagnosed with hyperthyroidism were recruited. Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels had been detected by chemiluminescence method. Meanwhile, the catecholamine levels (including adrenaline, noradrenaline, and dopamine) in plasma, ATP level and P2X receptors (including P2X3 receptor and P2X7 receptor) in peripheral blood had been detected by high performance liquid chromatography, bioluminescence method, and reverse transcription polymerase chain reaction, respectively. Levels of epinephrine and norepinephrine were significantly higher in the hyperthyroidism group compared with the control group. The concentration of ATP in the hyperthyroidism group was significantly higher than its in the control group. The expression of P2X3 mRNA and P2X7 mRNA in hyperthyroidism group were significantly increased compared with those in control group. In a conclusion, there is a relationship between the elevated expression of P2X3 receptor and P2X7 receptor in peripheral blood leukocytes and high serum epinephrine and norepinephrine levels in hyperthyroidism patients.


Asunto(s)
Hipertiroidismo/metabolismo , Hipertiroidismo/patología , Receptores Purinérgicos P2X3/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Adenosina Trifosfato/sangre , Adulto , Catecolaminas/sangre , Demografía , Femenino , Regulación de la Expresión Génica , Humanos , Leucocitos/metabolismo , Masculino , Proyectos Piloto , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Purinérgicos P2X3/genética , Receptores Purinérgicos P2X7/genética
13.
Inflammation ; 38(6): 2076-81, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26021292

RESUMEN

Chronic inflammation plays a major role in development of type 2 diabetes mellitus (T2DM). C-reactive protein (CRP) and inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß) are directly involved in the occurrence of insulin resistance. Increased extracellular ATP levels can amplify the inflammatory response in vivo via the P2X7 receptor. The present study aimed to assess the relationship between P2X7 receptor expression in human peripheral blood monocytes and plasma levels of TNF-α, IL-1ß, and CRP in T2DM patients. The results showed the association of increased P2X7 receptor expression of monocytes with high serum CRP, TNF-α, and IL-1ß levels. TNF-α and IL-1ß levels were lowest in healthy subjects; in T2DM patients, these inflammatory markers were less abundant in individuals with normal CRP levels compared to those with high CRP contents. In contrast, IL-10 levels in T2DM patients with high CRP levels were dramatically decreased. P2X7 receptor expression in monocytes from T2DM patients with high CRP levels was significantly increased in comparison with healthy individuals and T2DM patients with normal CRP levels. These findings indicated that P2X7 receptor in peripheral blood monocytes may be involved in the pathological changes of T2DM, particularly affecting patients with high CRP levels.


Asunto(s)
Proteína C-Reactiva/análisis , Citocinas/sangre , Diabetes Mellitus Tipo 2/sangre , Mediadores de Inflamación/sangre , Monocitos/metabolismo , Receptores Purinérgicos P2X7/sangre , Adulto , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Humanos , Interleucina-1beta/sangre , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/sangre
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