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1.
J Biomed Sci ; 29(1): 52, 2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35820906

RESUMO

BACKGROUND: Coronavirus-induced disease 19 (COVID-19) infects more than three hundred and sixty million patients worldwide, and people with severe symptoms frequently die of acute respiratory distress syndrome (ARDS). Recent studies indicated that excessive neutrophil extracellular traps (NETs) contributed to immunothrombosis, thereby leading to extensive intravascular coagulopathy and multiple organ dysfunction. Thus, understanding the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced NET formation would be helpful to reduce thrombosis and prevent ARDS in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We incubated SARS-CoV-2 with neutrophils in the presence or absence of platelets to observe NET formation. We further isolated extracellular vesicles from COVID-19 patients' sera (COVID-19-EVs) to examine their ability to induce NET formation. RESULTS: We demonstrated that antagonistic mAbs against anti-CLEC5A mAb and anti-TLR2 mAb can inhibit COVID-19-EVs-induced NET formation, and generated clec5a-/-/tlr2-/- mice to confirm the critical roles of CLEC5A and TLR2 in SARS-CoV-2-induced lung inflammation in vivo. We found that virus-free extracellular COVID-19 EVs induced robust NET formation via Syk-coupled C-type lectin member 5A (CLEC5A) and TLR2. Blockade of CLEC5A inhibited COVID-19 EVs-induced NETosis, and simultaneous blockade of CLEC5A and TLR2 further suppressed SARS-CoV-2-induced NETosis in vitro. Moreover, thromboinflammation was attenuated dramatically in clec5a-/-/tlr2-/- mice. CONCLUSIONS: This study demonstrates that SARS-CoV-2-activated platelets produce EVs to enhance thromboinflammation via CLEC5A and TLR2, and highlight the importance of CLEC5A and TLR2 as therapeutic targets to reduce the risk of ARDS in COVID-19 patients.


Assuntos
COVID-19 , Lectinas Tipo C , Neutrófilos , Pneumonia , Síndrome do Desconforto Respiratório , SARS-CoV-2 , Trombose , Animais , Plaquetas/imunologia , Plaquetas/patologia , Plaquetas/virologia , COVID-19/sangue , COVID-19/imunologia , Humanos , Lectinas Tipo C/imunologia , Camundongos , Neutrófilos/imunologia , Neutrófilos/patologia , Neutrófilos/virologia , Pneumonia/imunologia , Pneumonia/patologia , Pneumonia/virologia , Receptores de Superfície Celular , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/virologia , SARS-CoV-2/imunologia , Trombose/sangue , Trombose/imunologia , Trombose/virologia , Receptor 2 Toll-Like/imunologia
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(3): 975-978, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35680837

RESUMO

Exosomes are subtypes of extracellur vesicles containing a variety of cell-specific proteins, lipids and nucleic acids released during cell activation or apoptosis, and play the role of intercellur communication mediators in different physiological and pathological processes. With the development of research in recent years, the role of platelet-derived exosomes in cardiovascular diseases has attracted extensive attention. This paper reviews the role of platelet-derived exosomes in atherosclerotic thrombosis and the potential role of platelet-derived exosomes as biomarkers for the diagnosis and treatment of atherosclerotic thrombotic disease and the problems to be solved.


Assuntos
Aterosclerose , Exossomos , Trombose , Apoptose , Aterosclerose/metabolismo , Aterosclerose/patologia , Plaquetas/metabolismo , Plaquetas/patologia , Exossomos/metabolismo , Exossomos/patologia , Humanos
3.
BMC Cancer ; 22(1): 653, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35698081

RESUMO

BACKGROUND: Tyrosine kinase inhibitors (TKIs), such as sunitinib, are used for cancer treatment, but may also affect platelet count and function with possible hemostatic consequences. Here, we investigated whether patient treatment with the TKI sunitinib affected quantitative and qualitative platelet traits as a function of the sunitinib level and the occurrence of bleeding. METHODS: Blood was collected from 20 metastatic renal cell carcinoma (mRCC) patients before treatment, and at 2 weeks, 4 weeks and 3 months after sunitinib administration. We measured blood cell counts, platelet aggregation, and concentrations of sunitinib as well as its N-desethyl metabolite in plasma, serum and isolated platelets. Progression of disease (PD) and bleeding were monitored after 3 months. RESULTS: In sunitinib-treated mRCC patients, concentrations of (N-desethyl-)sunitinib in plasma and serum were highly correlated. In the patients' platelets the active metabolite levels were relatively increased as compared to sunitinib. On average, a sustained reduction in platelet count was observed on-treatment, which was significantly related to the inhibitor levels in plasma/serum. Principal component and correlational analysis showed that the (N-desethyl-)sunitinib levels in plasma/serum were linked to a reduction in both platelet count and collagen-induced platelet aggregation. The reduced aggregation associated in part with reported bleeding, but did not correlate to PD. CONCLUSION: The sunitinib-induced reduction in quantitative and qualitative platelet traits may reflect the effective sunitinib levels in the patient. These novel results may serve as a proof-of-principle for other TKI-related drugs, where both platelet count and functions are affected, which could be used for therapeutic drug monitoring.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Antineoplásicos/efeitos adversos , Plaquetas/patologia , Carcinoma de Células Renais/patologia , Humanos , Indóis/efeitos adversos , Neoplasias Renais/patologia , Pirróis/efeitos adversos , Sunitinibe/uso terapêutico
4.
Int J Mol Sci ; 23(9)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35563228

RESUMO

As integral parts of pathological arterial thrombi, platelets are the targets of pharmacological regimens designed to treat and prevent thrombosis. A detailed understanding of platelet biology and function is thus key to design treatments that prevent thrombotic cardiovascular disease without significant disruption of the haemostatic balance. Phosphoinositide 3-kinases (PI3Ks) are a group of lipid kinases critical to various aspects of platelet biology. There are eight PI3K isoforms, grouped into three classes. Our understanding of PI3K biology has recently progressed with the targeting of specific isoforms emerging as an attractive therapeutic strategy in various human diseases, including for thrombosis. This review will focus on the role of PI3K subtypes in platelet function and subsequent thrombus formation. Understanding the mechanisms by which platelet function is regulated by the various PI3Ks edges us closer toward targeting specific PI3K isoforms for anti-thrombotic therapy.


Assuntos
Fosfatidilinositol 3-Quinases , Trombose , Plaquetas/patologia , Humanos , Fosfatidilinositóis , Isoformas de Proteínas , Trombose/tratamento farmacológico , Trombose/patologia , Trombose/prevenção & controle
5.
Acta Otorhinolaryngol Ital ; 42(2): 150-154, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35612506

RESUMO

Objective: The aim of this study was to investigate the relationship between differentiated thyroid carcinomas (DTCs), histopathological findings and systemic immune-inflammation index (SII) [neutrophil (N) x platelet (P) / lymphocyte (L)] values. Methods: 93 patients with DTC were included. N, P and L levels were measured, and the relationship between the SII and histopathological findings was determined. The results were compared with the values of 33 healthy controls. Results: SII values were significantly higher in the patient group than in the control group (p = 0.000). Tumour pathology diagnosis had no significant effect on SII (p = 0.90). Perineural lymphovascular and capsule invasion and extrathyroidal extension also had no significant effect on SII values. SII was significantly higher in patients with more than one tumour focus (p = 0.01). No significant relationship was determined between tumour diameter and SII. Conclusions: SII is higher in patients with DTC compared to the healthy population. High SII values may be associated with multifocality. According to the results of this study, SII does not affect the histological type, perineural, lymphovascular and capsule invasion, or extrathyroidal extension of DTC.


Assuntos
Linfócitos , Neoplasias da Glândula Tireoide , Plaquetas/patologia , Humanos , Inflamação/diagnóstico , Linfócitos/patologia , Neutrófilos/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia
6.
PLoS One ; 17(4): e0265897, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35436305

RESUMO

BACKGROUND: Systemic inflammatory response (SIR) plays important roles in initiation, promotion and progression of tumor. However, the prognostic role of baseline circulating platelet-to-lymphocyte ratio (PLR) (known as a marker of SIR) in human initial stage Ⅳ gastric cancer (GC) remains controversial. Hence, we performed this meta-analysis to assess the value of it in prognosis prediction for these patients. MATERIALS AND METHODS: We searched PubMed, Embase and EBSCO to identify the studies and computed extracted data with STATA 12.0. RESULTS: A total of 3025 patients with initial stage Ⅳ GC from 13 published studies were incorporated into this meta-analysis. We found that elevated baseline circulating PLR was significantly associated with decreased overall survival (OS), but not with progression-free survival (PFS) in stage Ⅳ GC patients. However, in stratified analyses, high PLR was only associated with worse 1-year and 2-year OS, but not with 3-year or 4-year OS; In addition, it was considerably related with reduced 6-month PFS, but not with 1-year or 2-year PFS. Moreover, high PLR markedly correlated with peritoneal metastasis of GC. CONCLUSION: Elevated baseline circulating PLR decreased 1-year OS and 6-month PFS in initial stage Ⅳ GC patients, implicating that it is a valuable prognostic index for these patients and modifying the inflammatory responses may have a potential for effective treatment.


Assuntos
Neoplasias Gástricas , Biomarcadores , Plaquetas/patologia , Humanos , Linfócitos/patologia , Neutrófilos/patologia , Prognóstico , Neoplasias Gástricas/patologia
7.
Blood Adv ; 6(12): 3697-3702, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35452514

RESUMO

Immune complexes form in systemic disorders such as rheumatological, autoimmune, and allergic diseases or in response to infections or medications. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adenoviral vector vaccines have been associated with rare yet serious thrombotic complications in the brain due to the formation of immune complexes that activate platelets. There are currently no data visualizing the interplay of platelets with leukocytes and the brain vasculature endothelium in response to immune complexes. This is in part due to the absence of FcγRIIA in mice, a receptor for immune complexes implicated in these thrombotic incidents. Here, we describe and illustrate events at the cellular level that take place in the brain vasculature in response to systemic administration of surrogate immune complexes. We used Ly6gCre+/-::Rosa26-TdT+/-::CD41-YFP+/- mice expressing the FcγRIIA transgene and fluorescence in neutrophils and platelets. Using real-time videomicroscopy to capture high-velocity events in conjunction with unbiased computer-assisted analyses, we provide images and quantifications of the cellular responses downstream of FcγRIIA stimulation. We observed transient and stable platelet-neutrophil interactions, platelets forming thrombi, and neutrophil adhesion to blood vessel walls. This imaging approach in a quadruple transgenic animal model can be used for the study of the pathogenic roles of immune complexes in disease.


Assuntos
COVID-19 , Trombose , Animais , Complexo Antígeno-Anticorpo , Plaquetas/patologia , Camundongos , Camundongos Transgênicos , Neutrófilos , SARS-CoV-2
8.
Ulus Travma Acil Cerrahi Derg ; 28(4): 471-476, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35485509

RESUMO

BACKGROUND: Acute cholecystitis is a severe disease that requires urgent operation in some cases. To select suitable patients for a conservative approach, there is a need for an affordable and reliable marker for determining complication risk. Evaluation of systemic inflammatory markers in combination with other parameters such as white blood cell and the C-reactive protein might help to decide the appropriate treatment option. This study aims to evaluate the diagnostic value of the neutrophil-lymphocyte ratio (NLR) and thrombocyte-lymphocyte ratio (PLR) in determining the risk of complicated acute cholecystitis and to compare with intraoperative and pathological findings. METHODS: A total of 229 patients operated on for acute cholecystitis were included in this study. Intraoperative and pathologically complicated acute cholecystitis in 78 cases and controls group was 151 cases. The two groups were compared in terms of inflammation markers. Then, we used the receiver operating characteristic curve analysis to determine the optimal value for NLR and PLR concerning the severity of cholecystitis. Then, the differences in clinical symptoms were investigated according to the cutoff value for NLR and PLR. RESULTS: The NLR and PLR levels were found to be significantly higher in the complicated group (4.18±4.53 vs. 15.23±20.99, 145.34±87.58, and 251.92±245.93, respectively, p<0.01). The best cutoff value for NLR and PLR was 5.5 and 146.90, respectively. Sensitivity for NLR was 80% and specificity was 80.1%. Sensitivity for PLR was 66.7% and specificity was 66.2%. CONCLUSION: Systemic inflammation markers can be used to predict the risk of complicated acute cholecystitis. They are inex-pensive tools that can be used to make surgical decisions, especially in resource scarce environments.


Assuntos
Colecistite Aguda , Linfócitos , Biomarcadores , Plaquetas/patologia , Humanos , Inflamação/patologia , Linfócitos/patologia , Neutrófilos/patologia
9.
Eur Rev Med Pharmacol Sci ; 26(6): 1945-1951, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35363344

RESUMO

OBJECTIVE: This study aimed at investigating the laboratory parameters related to the pathogenesis of bone loss, including bone mineral density (BMD), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) in children with thyroid disease and healthy controls. PATIENTS AND METHODS: Children and adolescents with hypothyroidism (n=63) and hyperthyroidism (n=30) as well as 32 age- and sex-matched healthy controls were included in the study. Auxological data, BMD, hemogram parameters, the levels of thyroid hormone, thyroid stimulating hormone (TSH), thyroid autoantibodies, parathyroid hormone, 25-hydroxy vitamin D, alkaline phosphatase, calcium, and phosphorus were analyzed. RESULTS: The mean age of the patients was 12.12±2.7 years (range: 8-17). BMD Z-scores were within the normal range in all the patients and healthy controls. The BMD Z-scores were significantly higher in patients with hyperthyroidism than those in the control group and in patients with hypothyroidism. No significant difference was observed between the control and hypothyroid groups in terms of the BMD Z-scores. A correlation was observed between the BMD Z-scores and NLR, MLR, PLR, and free T4 levels. In patients with hypothyroidism, the BMD Z-scores were significantly positively correlated with the NLR, MLR, PLR, and the TSH level. In the control group, there was a moderate positive correlation between the BMD Z-scores and NLR. In the hyperthyroid group, there were no significant correlations between the BMD Z-scores and other variables. CONCLUSIONS: The study data suggest that in children and adolescents with thyroid disease, the relationship between the BMD Z-scores and NLR, MLR, and PLR at the initial diagnosis in the hypothyroidism group was different from that in their healthy peers.


Assuntos
Hipertireoidismo , Neutrófilos , Adolescente , Plaquetas/patologia , Densidade Óssea , Criança , Humanos , Hipertireoidismo/patologia , Linfócitos/patologia , Monócitos , Neutrófilos/patologia , Estudos Retrospectivos
10.
J Transl Med ; 20(1): 159, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35382857

RESUMO

BACKGROUND: To evaluate the capability of basal and one-month differed white blood cells (WBC), neutrophil, lymphocyte and platelet values and their ratios (neutrophils-to-lymphocytes ratio, NLR, and platelets-to-lymphocytes ratio, PLR) in predicting the response to immune checkpoint inhibitors (ICI) in metastatic melanoma (MM). METHODS: We performed a retrospective study of 272 BRAF wild-type MM patients treated with first line ICI. Bivariable analysis was used to correlate patient/tumor characteristics with clinical outcomes. Variations between time 1 and time 0 (Δ) of blood parameters were also calculated and dichotomized using cut-off values assessed by ROC curve. RESULTS: At baseline, higher neutrophils and NLR negatively correlated with PFS, OS and disease control rate (DCR). Higher PLR was also associated with worse OS. In multivariable analysis, neutrophils (p = 0.003), WBC (p = 0.069) and LDH (p = 0.07) maintained their impact on PFS, while OS was affected by LDH (p < 0.001), neutrophils (p < 0.001) and PLR (p = 0.022), while DCR by LDH (p = 0.03) and neutrophils (p = 0.004). In the longitudinal analysis, PFS negatively correlated with higher Δplatelets (p = 0.039), ΔWBC (p < 0.001), and Δneutrophils (p = 0.020), and with lower Δlymphocytes (p < 0.001). Moreover, higher ΔNLR and ΔPLR identified patients with worse PFS, OS and DCR. In the multivariable model, only ΔNLR influenced PFS (p = 0.004), while OS resulted affected by higher ΔWBC (p < 0.001) and lower Δlymphocytes (p = 0.038). Higher ΔWBC also affected the DCR (p = 0.003). When clustering patients in 4 categories using basal LDH and ΔNLR, normal LDH/lower ΔNLR showed a higher PFS than high LDH/higher ΔNLR (20 vs 5 months). Moreover, normal LDH/higher Δlymphocytes had a higher OS than high LDH/lower Δlymphocytes (50 vs. 10 months). CONCLUSIONS: Baseline and early variations of blood cells, together with basal LDH, strongly predict the efficacy of ICI in MM. Our findings propose simple, inexpensive biomarkers for a better selection of patient treatments. Prospective multicenter studies are warranted to confirm these data.


Assuntos
Melanoma , Neutrófilos , Plaquetas/patologia , Humanos , Imunoterapia , Linfócitos/patologia , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Neutrófilos/patologia , Prognóstico , Estudos Prospectivos , Proteínas Proto-Oncogênicas B-raf , Estudos Retrospectivos
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(2): 565-570, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35395998

RESUMO

AbstractObjective: To investigate the clinical phenotype and genotype of an ACTN1-associated thrombocytopenic family and explore its molecular pathogenesis. METHODS: All the family members' peripheral blood was collected for routine blood tests, blood smear, coagulation function, and platelet aggregation test. Flow cytometry was used to detect the expression of platelet CD41 and CD61. The proband and her father were tested bone marrow cytomorphology. Whole-exome sequencing techniques were performed to detect and uncover mutant loci of suspected pathogenic genes. Bioinformatics was used to assess the conserved nature of the mutated loci and to analyze the effect of the mutated genes leading to the function of the corresponding amino acid sequences. RESULTS: The platelet count of the proband was 88×109/L, and the blood smear showed dumbbell-shaped platelets, snake-shaped platelets and platelets of various sizes. Her bone marrow cytomorphology revealed normal megakaryocyte morphology with a count of 270. The platelet count of the proband's father was 74×109/L, with large platelets and platelets of various sizes observed in the blood smear, and the morphology of megakaryocytes was normal in bone marrow with a megakaryocyte count of 239. Her grandfather had a platelet count of 83×109/L, with snake-shaped platelets and platelets of various sizes on blood smears. Other family members were normal in all tests. The missense mutation c.2396G > A in exon 20 of the ACTN1 gene in the proband resulted in the mutation of 799 amino acids of the encoded protein, i.e., Arg, to His. The sequencing results of her father and grandfather at this locus were found to be consistent with her. Furthermore, bioinformatics analysis indicated that the locus was highly conserved across species and that variation in this locus might lead to functional impairment of the protein. The protein model analysis demonstrated that α-actin-1 at position 799 Arg and Glu at position 811 could form a critical salt bridge which stabilizes the conformation of the Ca2+ binding loop within the calmodulin-like motif. the mutation of R799H lost this critical salt bridge and destabilized this structural domain. CONCLUSION: In the present study, the newly uncovered missense mutation c.2396G>A in exon 20 of the ACTN1 gene is potentially the molecular mechanism for the thrombocytopenia.


Assuntos
Actinina , Anemia , Trombocitopenia , Actinina/genética , Plaquetas/metabolismo , Plaquetas/patologia , Feminino , Humanos , Masculino , Megacariócitos , Mutação de Sentido Incorreto , Linhagem , Trombocitopenia/genética
12.
Hematology ; 27(1): 426-430, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35413229

RESUMO

BACKGROUND: Recently, platelet to white blood cell ratio (PWR) was reported as an independent prognostic predictor in acute promyelocytic leukemia. Acute myeloid leukemia (AML) often presents with abnormal platelet counts and white blood cell counts (WBC) at disease diagnosis. However, the clinical impact of PWR on cytogenetically normal AML (CN-AML) is still unclear. Therefore, we evaluate its prognostic impact on CN-AML patients. METHODS: We recorded the clinical information at the time of disease diagnosis, and calculated the ratio of platelet counts to WBC in 338 patients with CN-AML. To assess the prognostic value of PWR, we divided patients into low, intermediate and high group based on the values of PWR. The independent prognostic value of PWR was investigated in the context of the well-established predictors including white blood cell counts, age, and genes of NPM1, FLT3-ITD, CEBPA, and DNMT3A mutations. Receiver operating characteristic (ROC) curve was used to assess the performance of its prognostic prediction. RESULTS: Higher PWR have the higher levels of platelet counts, but lower levels of white blood cell counts, percentage of bone marrow blasts, FLT3-ITD and NPM1 mutations. The performance of survival prediction was comparable between PWR alone and combined molecular biomarkers. Moreover, PWR had the additional prognostic information to the molecular biomarkers. Finally, PWR was associated with favorable overall survival and event free survival in CN-AML patients independent of genetic subtypes and clinical parameters. CONCLUSION: We found PWR was an independent prognostic predictor in CN-AML.


Assuntos
Plaquetas , Leucemia Mieloide Aguda , Leucócitos , Plaquetas/patologia , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucócitos/patologia , Mutação , Proteínas Nucleares/genética , Prognóstico
13.
Cancer Biomark ; 34(4): 583-590, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431231

RESUMO

BACKGROUND: The inflammatory markers are associated with adverse clinical outcomes in endometrial cancers (EC), but hematopoietic aging may affect the results. OBJECTIVE: To compare inflammatory markers in geriatric and nongeriatric EC. METHODS: This study included 342 women with endometrial cancers (n: 171) and age-matched controls (n: 171). Geriatric (⩾ 65 years old) and nongeriatric women in each group was compared for inflammatory markers, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), mean platelet volume (MPV), and platelet distribution width (PDW). RESULTS: Geriatric EC had more common nonendometrioid tumors, myometrial invasion, lymph node metastasis, advanced stage, and low overall survival (OS). Nongeriatric EC had low MPV, high NLR, and PDW compared to nongeriatric control. Geriatric EC had low MPV, lymphocyte, and high NLR, PLR compared to geriatric control (p< 0.05). Geriatric EC had significantly low PDW and high NLR, PLR compared to nongeriatric EC in early stages, not in advanced stages. Lymphocyte count was significantly low in geriatric EC with all stages (p< 0.05). In nongeriatric EC, stage was related to platelet count (r: 0.341, p: 0.0019), and PLR (r: 0.252, p: 0.01). OS was negatively related to PLR (r: -0.267, p: 0.007) and NLR (r: -0.353, p: 0.000). In geriatric EC, myometrium invasion was negatively related to lymphocyte count (r: -0.268, p: 0.035). OS was related to neutrophil count (p: 0.352, p: 0.01). MPV was negatively related to stage (r: -0.335, p: 0.01) and OS (r: -0.337, p: 0.02). CONCLUSIONS: The inflammatory responses of geriatric and nongeriatric EC were different in the early and advanced stages. Geriatric EC had low PDW and high NLR, PLR compared to nongeriatric EC in early stages. Decreased lymphocyte count was the most prominent feature of geriatric EC in the early and advanced stages. These results suggested that decreased lymphocyte count may reflect an aggressive course of disease in the elderlies. Future inflammation studies may direct anticancer treatment strategies in geriatric EC. Further research on inflammaging and geriatric EC is needed to increase our understanding of aging and carcinogenesis.


Assuntos
Neoplasias do Endométrio , Linfócitos , Idoso , Biomarcadores , Plaquetas/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Contagem de Linfócitos , Linfócitos/patologia , Volume Plaquetário Médio , Neutrófilos/patologia , Contagem de Plaquetas , Estudos Retrospectivos
14.
J Clin Lab Anal ; 36(6): e24443, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35441746

RESUMO

OBJECTIVES: The incidence of papillary thyroid carcinoma (PTC) has increased more rapidly than that of any other cancer type in China. Early indicators with high sensitivity and specificity during diagnosis are required. To date, there has been a paucity of studies investigating the relationship between preoperative platelet distribution width-to-platelet count ratio (PPR) and PTC. This study thus aimed to assess the diagnostic value of PPR combined with serum thyroglobulin (Tg) in patients with PTC. METHODS: A total of 1001 participants were included in our study. 876 patients who underwent surgery for nodular goiter were divided into the PTC group or benign thyroid nodule (BTN) group according to pathology reports, and 125 healthy controls (HCs) were included. Preoperative hemogram parameters and serum Tg levels were compared among three groups. Receiver operating characteristic (ROC) curve was used to evaluate the value of PPR combined with serum Tg for diagnosing PTC. RESULTS: Platelet distribution width (PDW) and PPR levels were higher in the PTC group than in the BTN and HC groups (both p < 0.05) but did not significantly differ between the BTN and HC groups. PDW and PPR levels significantly differed in the presence/absence of lymph node metastasis, the presence/absence of capsule invasion (p = 0.005), and TNM stages (p < 0.001). Multivariable analyses indicated that high serum Tg levels [adjusted odds ratio (OR), 1.007; 95% confidence interval (CI), 1.004-1.009; p < 0.001], high neutrophil-to-lymphocyte ratio (NLR,adjusted OR, 1.928; 95% CI, 1.619-2.295; p < 0.001), and high PPR (adjusted OR, 1.378; 95% CI, 1.268-1.497; p < 0.001) were independent risk factors for PTC. In ROC analysis, the areas under the curves (AUCs) of serum Tg, PDW, PPR, and NLR for predicting PTC were 0.603, 0.610, 0.706, and 0.685, respectively. PPR combined with serum Tg (PPR + Tg) had a higher diagnostic value (AUC, 0.738; sensitivity, 60%; specificity, 74.7%) compared with PDW + Tg (AUC, 0.656; sensitivity, 64.4%; specificity, 59.9%) and NLR + Tg (AUC, 0.714; sensitivity, 61.6%; specificity, 71.1%). CONCLUSIONS: Preoperative PPR combined with serum Tg may be objective and popularizable indicators for effective predicting PTC.


Assuntos
Plaquetas , Bócio Nodular , Contagem de Plaquetas , Tireoglobulina , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Plaquetas/patologia , Bócio Nodular/sangue , Bócio Nodular/patologia , Bócio Nodular/cirurgia , Humanos , Metástase Linfática , Contagem de Plaquetas/métodos , Período Pré-Operatório , Estudos Retrospectivos , Tireoglobulina/sangue , Câncer Papilífero da Tireoide/sangue , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia
15.
Sci Rep ; 12(1): 6480, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35444195

RESUMO

The ratio of mean platelet volume (MPV) to count (PC) (MPV/PC) has been applied in the diagnosis and prognosis of various malignancies. However, the prognostic value of MPV/PC in gastric cancer has not been studied yet. This study aims to explore the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), combined neutrophil-platelet score (CNPS), systemic immune-inflammation index (SII) and MPV/PC in patients with resectable gastric cancer. In this study, the medical records of patients with gastric cancer in two centers were retrospectively analyzed. Kaplan-Meier and log-rank were tests applied to analyze the survival differences of patients with various inflammation indexes. A nomogram prognostic model was established to predict the 3- and 5-year survival rate of patients with resectable gastric cancer. In the two cohorts, Kaplan-Meier analysis that the postoperative survival time of gastric cancer patients with low MPV/PC, high NLR, high PLR and high SII was significantly shorter than that of patients with high MPV/PC, low NLR, low PLR or low SII. Compared with NLR, PLR, SII and CNPS, MPV/PC was more accurate in determining the prognosis of patients with gastric cancer than other indexes, and multivariate analysis confirmed that MPV/PC was an independent prognostic factor for patients with resectable gastric cancer. The nomogram model established based on tumor size, TNM stage and MPV/PC was more accurate than TNM stage in predicting the 3- and 5-year survival rate of patients with resectable gastric cancer. Preoperative MPV/PC is a new independent prognostic index and a potential marker for treatment response monitoring in patients with resectable gastric cancer. The nomogram model for postoperative prognosis of gastric cancer established based on MPV/PC, tumor size and TNM stage is helpful for developing more accurate and timely individualized therapeutic regimens.


Assuntos
Neoplasias Gástricas , Plaquetas/patologia , Humanos , Inflamação/patologia , Linfócitos/patologia , Neutrófilos/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia
16.
Int J Mol Sci ; 23(7)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35409226

RESUMO

There is accumulating evidence that platelets play roles beyond their traditional functions in thrombosis and hemostasis, e.g., in inflammatory processes, infection and cancer, and that they interact, stimulate and regulate cells of the innate immune system such as neutrophils, monocytes and macrophages. In this review, we will focus on platelet activation in hemostatic and inflammatory processes, as well as platelet interactions with neutrophils and monocytes/macrophages. We take a closer look at the contributions of major platelet receptors GPIb, αIIbß3, TLT-1, CLEC-2 and Toll-like receptors (TLRs) as well as secretions from platelet granules on platelet-neutrophil aggregate and neutrophil extracellular trap (NET) formation in atherosclerosis, transfusion-related acute lung injury (TRALI) and COVID-19. Further, we will address platelet-monocyte and macrophage interactions during cancer metastasis, infection, sepsis and platelet clearance.


Assuntos
COVID-19 , Trombose , Plaquetas/patologia , Hemostasia , Humanos , Imunidade Inata , Inflamação/patologia , Neutrófilos/patologia , Ativação Plaquetária , Trombose/patologia
17.
Cells ; 11(6)2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35326465

RESUMO

Platelets play important roles in thrombosis-dependent obstructive cardiovascular diseases. In addition, it has now become evident that platelets also participate in the earliest stages of atherosclerosis, including the genesis of the atherosclerotic lesion. Moreover, while the link between platelet activity and hemostasis has been well established, the role of platelets as modulators of inflammation has only recently been recognized. Thus, through their secretory activities, platelets can chemically attract a diverse repertoire of cells to inflammatory foci. Although monocytes and lymphocytes act as key cells in the progression of an inflammatory event and play a central role in plaque formation and progression, there is also evidence that platelets can traverse the endothelium, and therefore be a direct mediator in the progression of atherosclerotic plaque. This review provides an overview of platelet interactions and regulation in atherosclerosis.


Assuntos
Aterosclerose , Trombose , Aterosclerose/patologia , Plaquetas/patologia , Hemostasia , Humanos , Inflamação/patologia
18.
Immunobiology ; 227(3): 152193, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35240404

RESUMO

Uncontrolled inflammation is the underlining mechanism of many human diseases and the increasing prevalence of such diseases mandate to develop new anti-inflammatory treatments. Utilizing the anti-inflammatory properties as well as other protective/beneficial features of natural IgMs (nIgMs) for treatment of human disorders seems as an easily accessible goal by the use of blood-purified IgMs as an alternative for polyclonal nIgMs. Despite the other blood cells, the functions of platelets have not been inspected under the influence of blood IgMs adequately. However, platelets, the second most numerous blood cells, are involved in the pathology of many inflammatory disorders through the production/expression of many inflammatory molecules. Thus, in the present study, we purified IgMs from serum of healthy donors and plasma of patients with systemic lupus erythematosus (SLE). Subsequently, we carried out comparative analysis of the inflammatory functions of normal platelets (P-selectin expression, GPIIb/IIIa activation, and secretion of soluble CD40L and TNF-α) that were stimulated by SLE microparticles (as key endogenous inflammation-drivers) in the presence or absence of the two IgM preparations; one with normal level of nIgMs (healthy blood IgMs) and the other with likely altered nIgM content (SLE blood IgMs). Both blood IgM preparations could suppress the elevated activation parameters of platelets in response to SLE microparticles. Additionally, the impact of SLE blood IgMs on the platelets was not superior to that of normal blood IgMs. The anti-inflammatory effects of blood IgMs on the activated platelets have been shown for the first time in the present study. Thus, this study provides evidence in favor of use of healthy blood IgMs as an anti-inflammatory therapy in clinical settings.


Assuntos
Micropartículas Derivadas de Células , Lúpus Eritematoso Sistêmico , Plaquetas/metabolismo , Plaquetas/patologia , Micropartículas Derivadas de Células/metabolismo , Humanos , Imunoglobulina M/metabolismo , Inflamação/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo
19.
Int J Biol Markers ; 37(2): 123-133, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35238678

RESUMO

The platelet-lymphocyte ratio (PLR) has been assessed in some studies on renal cell carcinoma (RCC), but the results have been inconsistent. This meta-analysis aims to review and report the latest data regarding the prognostic role of the PLR in RCC patients. Articles were searched in the PubMed, EMBASE, and Cochrane Library electronic databases. Studies were filtered according to a selection strategy, and data corresponding to the index of interest were extracted. A fixed-effects model or random-effects model was selected based on heterogeneity. The sensitivity analysis was carried out by eliminating the studies one by one. Finally, funnel plots and Egger's test were used to assess publication bias, and the trim and fill method was used to assess the impact of bias on the results. In total, 15,193 patients with RCC from 44 studies were included in this meta-analysis. The pooled analysis indicated that the higher the PLR was, the poorer the prognosis for RCC patients in terms of overall survival (hazard ratio (HR) = 1.01 (95% confidence interval (CI) 1.00, 1.02), P = 0.010), cancer-special survival (CSS) (HR = 1.21 (95% CI 1.00, 1.46), P = 0.05), progression-free survival (HR = 1.44 (95% CI 1.28, 1.62), P < 0.00001), recurrence-free survival (HR = 1.73 (95% CI 1.11, 2.71), P = 0.02), disease-free survival (HR = 1.63 (95% CI 0.91, 2.94), P = 0.01) and metastasis-free survival (HR = 1.223 (95% CI 0.712, 2.099), P = 0.466). In the subgroup analysis of high PLR, targeted treatment, TKI use, nivolumab use, surgical treatment, clear cell RCC, metastasis, Asian race, and high PLR were related to poor prognosis. This study showed that a high PLR was associated with the poor prognosis of RCC patients, but more studies are needed to confirm the value of the PLR.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Plaquetas/patologia , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Linfócitos/patologia , Prognóstico
20.
Vet Clin Pathol ; 51(2): 216-224, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35274337

RESUMO

INTRODUCTION: Thrombocytopenia has been associated with some neoplastic processes, including hematologic neoplasia. There is no information regarding specific changes in platelet measurands in dogs with hematologic neoplasia compared with healthy dogs. The objectives of our study were to establish RIs, evaluate platelet measurands in dogs with hematologic neoplasia, and compare these measurands in patients with hematologic malignancies with or without thrombocytopenia. METHODS: This was a retrospective study. Platelet measurands were determined using the ADVIA 120 Hematology analyzer when a CBC was performed and included the platelet count, MPV, platelet distribution width (PDW), plateletcrit (PCT), mean platelet component (MPC), platelet component distribution width (PCDW), mean platelet mass (MPM), platelet mass distribution width (PMDW), and number of large platelets. Reference intervals were determined retrospectively using data from 129 healthy dogs. Patients with hematologic neoplasia (n = 50) were identified through retrospective evaluation of medical records from the Auburn University Veterinary Teaching Hospital and separated into thrombocytopenic (n = 20) and nonthrombocytopenic groups (n = 30). RESULTS: Platelet count and PCT were significantly higher in older healthy dogs compared with younger dogs. Significant differences were identified when comparing healthy dogs with those with hematologic neoplasia without thrombocytopenia for PDW, PCDW, PMDW, and the number of large platelets, indicating the presence of more heterogeneous platelets. Thrombocytopenic dogs with hematologic neoplasia had significantly decreased MPCs and increased MPVs, MPMs, and PCDWs compared with nonthrombocytopenic dogs with neoplasia. CONCLUSIONS: Dogs with hematologic neoplasia had more heterogeneous platelets, whereas thrombocytopenic patients with neoplasia had more activated platelets.


Assuntos
Doenças do Cão , Neoplasias Hematológicas , Trombocitopenia , Animais , Plaquetas/patologia , Doenças do Cão/patologia , Cães , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/veterinária , Hospitais Veterinários , Hospitais de Ensino , Humanos , Volume Plaquetário Médio/veterinária , Contagem de Plaquetas/veterinária , Estudos Retrospectivos , Trombocitopenia/patologia , Trombocitopenia/veterinária
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