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1.
Anat Histol Embryol ; 53(3): e13054, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38735037

RESUMO

Identifying and analysing distinct blood cells is crucial for the diagnosis and treatment of diseases in the field of biomedicine. The present study was undertaken to study the cytomorphological and cytochemical characteristics of the blood cells of Zoar, a non-descript indigenous breed of chicken extensively reared under backyard poultry farming in Mizoram, India. For this study, 2 mL of blood samples were aseptically collected from the wings veins of 12 chickens and were processed for light microscopic study under standard protocols. The matured erythrocytes were elliptical, while the immature erythrocytes appeared oval. The heterophils were positive for SBB (SBB), Periodic Acid Schiff (PAS), acid phosphatase, alkaline phosphatase and Arylsulphatase while the eosinophils were positive for SBB, PAS, alkaline phosphatase, cytochrome oxidase and peroxidase. The basophils of were positive for toluidine blue while the thrombocytes were positive for PAS. These cytochemical and cytoenzymatic staining properties plays a very important role in diagnosis, differentiation, and classification of leukaemias.


Assuntos
Galinhas , Eosinófilos , Eritrócitos , Animais , Galinhas/anatomia & histologia , Índia , Eritrócitos/citologia , Eosinófilos/citologia , Células Sanguíneas/citologia , Plaquetas/citologia , Fosfatase Alcalina/sangue , Basófilos/citologia , Fosfatase Ácida/sangue , Complexo IV da Cadeia de Transporte de Elétrons/análise
2.
J Vis Exp ; (205)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38558008

RESUMO

Induced pluripotent stem cell (iPSC)-based models are excellent platforms to understand blood development, and iPSC-derived blood cells have translational utility as clinical testing reagents and transfusable cell therapeutics. The advent and expansion of multiomics analysis, including but not limited to single nucleus RNA sequencing (snRNAseq) and Assay for Transposase-Accessible Chromatin sequencing (snATACseq), offers the potential to revolutionize our understanding of cell development. This includes developmental biology using in vitro hematopoietic models. However, it can be technically challenging to isolate intact nuclei from cultured or primary cells. Different cell types often require tailored nuclear preparations depending on cellular rigidity and content. These technical difficulties can limit data quality and act as a barrier to investigators interested in pursuing multiomics studies. Specimen cryopreservation is often necessary due to limitations with cell collection and/or processing, and frozen samples can present additional technical challenges for intact nuclear isolation. In this manuscript, we provide a detailed method to isolate high-quality nuclei from iPSC-derived cells at different stages of in vitro hematopoietic development for use in single-nucleus multiomics workflows. We have focused the method development on the isolation of nuclei from iPSC-derived adherent stromal/endothelial cells and non-adherent hematopoietic progenitor cells, as these represent very different cell types with regard to structural and cellular identity. The described troubleshooting steps limited nuclear clumping and debris, allowing the recovery of nuclei in sufficient quantity and quality for downstream analyses. Similar methods may be adapted to isolate nuclei from other cryopreserved cell types.


Assuntos
Núcleo Celular , Células Endoteliais , Núcleo Celular/metabolismo , Criopreservação/métodos , Células-Tronco Hematopoéticas , Células Sanguíneas
3.
BMC Med Imaging ; 24(1): 83, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589793

RESUMO

The research focuses on the segmentation and classification of leukocytes, a crucial task in medical image analysis for diagnosing various diseases. The leukocyte dataset comprises four classes of images such as monocytes, lymphocytes, eosinophils, and neutrophils. Leukocyte segmentation is achieved through image processing techniques, including background subtraction, noise removal, and contouring. To get isolated leukocytes, background mask creation, Erythrocytes mask creation, and Leukocytes mask creation are performed on the blood cell images. Isolated leukocytes are then subjected to data augmentation including brightness and contrast adjustment, flipping, and random shearing, to improve the generalizability of the CNN model. A deep Convolutional Neural Network (CNN) model is employed on augmented dataset for effective feature extraction and classification. The deep CNN model consists of four convolutional blocks having eleven convolutional layers, eight batch normalization layers, eight Rectified Linear Unit (ReLU) layers, and four dropout layers to capture increasingly complex patterns. For this research, a publicly available dataset from Kaggle consisting of a total of 12,444 images of four types of leukocytes was used to conduct the experiments. Results showcase the robustness of the proposed framework, achieving impressive performance metrics with an accuracy of 97.98% and precision of 97.97%. These outcomes affirm the efficacy of the devised segmentation and classification approach in accurately identifying and categorizing leukocytes. The combination of advanced CNN architecture and meticulous pre-processing steps establishes a foundation for future developments in the field of medical image analysis.


Assuntos
Aprendizado Profundo , Humanos , Curadoria de Dados , Leucócitos , Redes Neurais de Computação , Células Sanguíneas , Processamento de Imagem Assistida por Computador/métodos
4.
Reprod Toxicol ; 125: 108581, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38552991

RESUMO

Maternal smoking during pregnancy increases oxidative stress and decreases antioxidant capacity in newborns. Uncontrolled oxidative stress plays a role in fetal development disorders and in adverse perinatal outcomes. In order to identify molecular pathways involved in low fetal growth, epigenetic modifications in newborns of smoking and non-smoking mothers were examined. Low birth weight newborns of mothers who smoked more than 10 cigarettes per day during the first trimester of pregnancy and normal birth weight newborns of mothers who did not smoke during pregnancy were included in the study. DNA was extracted from umbilical cord blood of term newborns. 125 differentially methylated regions were identified by MeDIP-Seq. Functional analysis revealed several pathways, such as ferroptosis, that were enriched in differentially methylated genes after prenatal smoke exposure. GPX4 and PCBP1 were found to be hypermethylated and associated with low fetal growth. These epigenetic modifications in ferroptosis pathway genes in newborns of smoking mothers can potentially contribute to intrauterine growth restriction through the induction of cell death via lipid peroxidation of cell membranes. The identification of epigenetic modifications in the ferroptosis pathway sheds light on the potential mechanisms underlying the pathophysiology of low birth weight in infants born to smoking mothers.


Assuntos
Ferroptose , Sangue Fetal , Gravidez , Feminino , Lactente , Recém-Nascido , Humanos , Peso ao Nascer , Ferroptose/genética , Desenvolvimento Fetal , Células Sanguíneas , Epigênese Genética
6.
Cancer Med ; 13(3): e6860, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38366800

RESUMO

The immune response-gut microbiota interaction is implicated in various human diseases, including cancer. Identifying the link between the gut microbiota and systemic inflammatory markers and their association with cancer will be important for our understanding of cancer etiology. The current study was performed on 8090 participants from the population-based Rotterdam study. We found a significant association (false discovery rate [FDR] ≤0.05) between lymphocytes and three gut microbial taxa, namely the family Streptococcaceae, genus Streptococcus, and order Lactobacillales. In addition, we identified 95 gut microbial taxa that were associated with inflammatory markers (p < 0.05). Analyzing the cancer data, we observed a significant association between higher systemic immune-inflammation index (SII) levels at baseline (hazard ratio (HR): 1.65 [95% confidence interval (CI); 1.10-2.46, p ≤ 0.05]) and a higher count of lymphocytes (HR: 1.38 [95% CI: 1.15-1.65, p ≤ 0.05]) and granulocytes (HR: 1.69 [95% CI: 1.40-2.03, p ≤ 0.05]) with increased risk of lung cancer after adjusting for age, sex, body mass index (BMI), and study cohort. This association was lost for SII and lymphocytes after additional adjustment for smoking (SII = HR:1.46 [95% CI: 0.96-2.22, p = 0.07] and lymphocytes = HR: 1.19 [95% CI: 0.97-1.46, p = 0.08]). In the stratified analysis, higher count of lymphocyte and granulocytes at baseline were associated with an increased risk of lung cancer in smokers after adjusting for age, sex, BMI, and study cohort (HR: 1.33 [95% CI: 1.09-1.62, p ≤0.05] and HR: 1.57 [95% CI: 1.28-1.92, p ≤0.05], respectively). Our study revealed a positive association between gut microbiota, higher SII levels, and higher lymphocyte and granulocyte counts, with an increased risk of developing lung cancer.


Assuntos
Microbioma Gastrointestinal , Neoplasias Pulmonares , Humanos , Incidência , Índice de Massa Corporal , Inflamação/epidemiologia , Células Sanguíneas
7.
Cell Rep ; 43(2): 113736, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38308842

RESUMO

Previous studies have suggested that the endocardium contributes to hematopoiesis in murine embryos, although definitive evidence to demonstrate the hematopoietic potential of the endocardium is still missing. Here, we use a zebrafish embryonic model to test the emergence of hematopoietic progenitors from the endocardium. By using a combination of expression analysis, time-lapse imaging, and lineage-tracing approaches, we demonstrate that myeloid cells emerge from the endocardium in zebrafish embryos. Inhibition of Etv2/Etsrp or Scl/Tal1, two known master regulators of hematopoiesis and vasculogenesis, does not affect the emergence of endocardial-derived myeloid cells, while inhibition of Hedgehog signaling results in their reduction. Single-cell RNA sequencing analysis followed by experimental validation suggests that the endocardium is the major source of neutrophilic granulocytes. These findings will promote our understanding of alternative mechanisms involved in hematopoiesis, which are likely to be conserved between zebrafish and mammalian embryos.


Assuntos
Proteínas Hedgehog , Peixe-Zebra , Animais , Camundongos , Endocárdio , Células Sanguíneas , Embrião de Mamíferos , Mamíferos
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 269-273, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38387933

RESUMO

OBJECTIVE: To study the correlation between the number of hemophagocytes and peripheral blood cells in bone marrow of patients with fever of unknown origin. METHODS: A total of 465 patients with fever of unknown origin in our hospital from January 2019 to December 2021 were selected as the research objects, which was to reviewed retrospectively the correlation between the number of hemophagocytes and peripheral blood cells in bone marrow. RESULTS: The positive rates of hemophagocytes detected in the three lines decreased group, the two lines decreased group, the one line decreased group, normal group of the three lines and at least one of the three lines increased group were 86.4%, 62.1%, 38.3%, 34.6% and 33.3%, respectively. The number of hemophagocytes per unit area in the three lines decreased group was significantly higher than that in the other four groups ( P < 0.001). The number of hemophagocytes per unit area in the two lines decreased group was higher than that in the one line decreased group, normal group of three lines and at least one of the three lines increased group ( P < 0.01). There was no significant difference in the number of hemophagocytes per unit area between the group with a decreased number of one line and the other two groups with a normal number of three lines and the group with at least one increased number of three lines (P >0.05). The missed rates of hemophagocytes in the five groups were 15.78%, 22.03%, 62.22%, 77.78% and 53.84%, respectively. CONCLUSION: For patients with fever of unknown origin, especially those with obvious decrease in the number of three lines and two lines in peripheral blood cells, which should pay attention to the detection of hemophagocytes in bone marrow. Meanwhile, if the number of three lines was normal even at least one of the three lines increased, the presence of hemophagocytes in the bone marrow slice should be also carefully observed.


Assuntos
Medula Óssea , Febre de Causa Desconhecida , Humanos , Estudos Retrospectivos , Células Sanguíneas , Células da Medula Óssea
9.
Lab Chip ; 24(4): 697-706, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38273802

RESUMO

Separation of malignant tumor cells (MTCs) from large background cells in untreated malignant pleural and peritoneal effusions (MPPEs) is critical for improving the sensitivity and efficiency of cytological diagnosis. Herein, we proposed a cascaded elasto-inertial cell separation (CEICS) device integrating an interfacial elasto-inertial microfluidic channel with a symmetric contraction expansion array (CEA) channel for pretreatment-free, high-recovery-ratio, and high-purity separation of MTCs from clinical MPPEs. First, the effects of flow-rate ratio, cell concentration, and cell size on separation performances in two single-stage channels were investigated. Then, the performances of the integrated CEICS device were characterized using blood cells spiked with three different tumor cells (MCF-7, MDA-MB-231, and A549 cells) at a high total throughput of 240 µL min-1. An average recovery ratio of ∼95% and an average purity of ∼61% for the three tumor cells were achieved. Finally, we successfully applied the CEICS device for the pretreatment-free separation of MTCs from clinical MPPEs of different cancers. Our CEICS device may provide a preparation tool for improving the sensitivity and efficiency of cytological examination.


Assuntos
Técnicas Analíticas Microfluídicas , Líquido Ascítico , Microfluídica , Células Sanguíneas , Separação Celular
10.
Sci Adv ; 10(4): eadk2132, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38277455

RESUMO

Individual hematopoietic stem cells (HSCs) produce different amounts of blood cells upon transplantation. Taking advantage of the intercellular variation, we developed an experimental and bioinformatic approach to evaluating the quantitative association between gene expression and blood cell production across individual HSCs. We found that most genes associated with blood production exhibit the association only at some levels of blood production. By mapping gene expression with blood production, we identified four distinct patterns of their quantitative association. Some genes consistently correlate with blood production over a range of levels or across all levels, and these genes are found to regulate lymphoid but not myeloid production. Other genes exhibit one or more clear peaks of association. Genes with overlapping peaks are found to be coexpressed in other tissues and share similar molecular functions and regulatory motifs. By dissecting intercellular variations, our findings revealed four quantitative association patterns that reflect distinct dose-response molecular mechanisms modulating the blood cell production of HSCs.


Assuntos
Células Sanguíneas , Células-Tronco Hematopoéticas , Camundongos , Animais , Células-Tronco Hematopoéticas/metabolismo , Expressão Gênica , Diferenciação Celular
11.
Int J Radiat Biol ; 100(2): 197-208, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37812067

RESUMO

BACKGROUND: Radiation burden from CT examinations increases rapidly with the increased clinical use frequency. Previous studies have disclosed the association between radiation exposure and increased double-strand breaks (DSBs) and changes in DNA methylation. However, whether the induced DSBs by CT examination recover within 24h and whether a CT examination induces detectable gene-specific methylation changes are still unclear. The aim of the present study was to analyze γ-H2AX in the peripheral blood lymphocyte (PBL) of healthy adults before and after CT examination and to discover the differentially methylated positions (DMPs) along with an analysis of DNA methylation changes caused by CT examination. MATERIALS AND METHODS: Peripheral blood samples of 4 ml were drawn from 20 healthy volunteers at three time points: before CT examination, after CT examination 1h, and after CT examination 24h. γ-H2AX immunofluorescence and Illumina Infinium Human Methylation EPIC BeadChip (850k BeadChip) were used respectively for the test of DSBs and the epigenome-wide DNA methylation analysis. Linear mixed-effect (LME) models were used to evaluate the impacts of doses represented by different parameters and foci on genome-wide DNA methylation. RESULTS: The number of γ-H2AX foci per cell at 1h showed linear dose-responses for the radiation doses represented by CT index volume (CTDIvol), dose length product (DLP), and blood absorbed dose, respectively. Residual γ-H2AX foci was observed after CT examination at 24h (p < .001). DMPs and γ-H2AX foci changes could be found within 1h. One CpG site related to PAX5 was significantly changed by using most of the parameters in LME models and did not recover till 24h. CONCLUSIONS: Residual γ-H2AX foci exist after CT examination at 24h. The DNA methylation changes induced by CT examination may not recover within 24h. The DNA methylation had been changed as early as at 1h. The PAX5-related CpG site may be a potential biomarker of low-dose radiation. CLINICAL RELEVANCE: The biological effects and the cancer risks of CT examination are still unclear. The present study is an effort to document the CT scan-induced events in 24h in vivo. The CT scanning area should be strictly limited, and non-essential repeated operations shouldn't be performed within 24h.


Assuntos
Quebras de DNA de Cadeia Dupla , Metilação de DNA , Adulto , Humanos , Linfócitos/efeitos da radiação , Tomografia Computadorizada por Raios X , Dano ao DNA , Células Sanguíneas , DNA , Relação Dose-Resposta à Radiação
12.
Nucleic Acids Res ; 52(D1): D1138-D1142, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37933860

RESUMO

BloodSpot is a specialised database integrating gene expression data from acute myeloid leukaemia (AML) patients related to blood cell development and maturation. The database and interface has helped numerous researchers and clinicians to quickly get an overview of gene expression patterns in healthy and malignant haematopoiesis. Here, we present an update to our framework that includes protein expression data of sorted single cells. With this update we also introduce datasets broadly spanning age groups, which many users have requested, with particular interest for researchers studying paediatric leukaemias. The backend of the database has been rewritten and migrated to a cloud-based environment to accommodate the growth, and provide a better user-experience for our many international users. Users can now enjoy faster transfer speeds and a more responsive interface. In conclusion, the continuing popularity of the database and emergence of new data modalities has prompted us to rewrite and futureproof the back-end, including paediatric centric views, as well as single cell protein data, allowing us to keep the database updated and relevant for the years to come. The database is freely available at www.bloodspot.eu.


Assuntos
Hematopoese , Leucemia Mieloide Aguda , Criança , Humanos , Células Sanguíneas , Diferenciação Celular , Bases de Dados Genéticas , Hematopoese/genética , Leucemia Mieloide Aguda/genética , Proteínas/genética
13.
Anal Chem ; 95(49): 18180-18187, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-38018866

RESUMO

The counts and phenotypes of circulating tumor cells (CTCs) in whole blood are useful for disease monitoring and prognostic assessment of cancer. However, phenotyping CTCs in the blood is difficult due to the presence of a large number of background blood cells, especially some blood cells with features similar to those of tumor cells. Herein, we presented a viscoelastic-sorting integrated deformability cytometer (VSDC) for high-throughput label-free sorting and high-precision mechanical phenotyping of tumor cells. A sorting chip for removing large background blood cells and a detection chip for detecting multiple cellular mechanical properties were integrated into our VSDC. Our VSDC has a sorting efficiency and a purity of over 95% and over 81% for tumor cells, respectively. Furthermore, multiple mechanical parameters were used to distinguish tumor cells from white blood cells using machine learning. An accuracy of over 97% for identifying tumor cells was successfully achieved with the highest identification accuracy of 99.4% for MCF-7 cells. It is envisioned that our VSDC will open up new avenues for high-throughput and label-free single-cell analysis in various biomedical applications.


Assuntos
Técnicas Analíticas Microfluídicas , Células Neoplásicas Circulantes , Humanos , Separação Celular , Células MCF-7 , Células Sanguíneas/patologia , Leucócitos , Células Neoplásicas Circulantes/patologia , Linhagem Celular Tumoral
14.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 41(10): 827-831, 2023 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-37935548

RESUMO

Objective: To explore the influencing factors of whole blood cells and genetics of medical radiation workers, and provide technical support for improving occupational health management and strengthening radiation protection. Methods: In January 2022, a total of 4180 medical radiation workers who underwent occupational health examination in Gansu Provincial Center for Disease Control and Prevention from January 2020 to December 2021 were collected as the research objects, and the results of demographic characteristics, whole blood cells, chromosome aberrations, lymphocyte micronucleus and other results were collected. The whole blood cells and genetic abnormalities of different demographic characteristics of medical radiation workers were compared. And the influencing factors of whole blood cells and genetic abnormalities were analyzed by multivariate logistic regression. Results: The rates of hemoglobin (HGB), chromosome aberration and lymphocyte micronucleus abnormality were the highest in the nuclear medicine group, and the rate of white blood cell (WBC) abnormality in the radiotherapy group was higher than those in other occupational groups, the differences were statistically significant (P<0.05). The abnormal rates of WBC, HGB and lymphocyte micronucleus in female radiation workers were significantly higher than those in male radiation workers (P<0.001). The abnormal rates of HGB and lymphocyte micronucleus were statistically different among different working years and different age radiation workers (P<0.001). And the abnormal rate of platelet (PLT) was statistically different among different working years radiation workers (P<0.05). The abnormal rate of HGB in radiation workers of different hospital levels was statistically different (P<0.001). Logistic regression analysis showed that the risk of abnormal WBC and HGB in females radiation workers were 3.048 times and 13.122 times of those in males, respectively (P<0.001). The abnormal risks of WBC in the 6-20 working years group and >20 working years group were 1.517 times and 1.874 times of that in the ≤5 working years group, respectively (P<0.05). The abnormal risk of PLT in the >20 working years group was 2.643 times of that in ≤5 working years group (P<0.05). The abnormal risk of WBC in radiotherapy group and intervention group were 2.407 times and 1.341 times of that in general radiotherapy group, respectively (P<0.05) . Conclusion: Ionizing radiation has different effects on the whole blood cells and genetic indexes of workers in the nuclear medicine, interventional group and radiotherapy group. The occupational health protection of female radiation workers should be paid attention to.


Assuntos
Células Sanguíneas , Exposição Ocupacional , Masculino , Humanos , Feminino , Linfócitos/efeitos da radiação , Radiação Ionizante , Núcleo Celular/efeitos da radiação , Aberrações Cromossômicas , Exposição Ocupacional/efeitos adversos
15.
Artigo em Inglês | MEDLINE | ID: mdl-37770146

RESUMO

Can human peripheral blood cells be used as a surrogate for bone marrow cells, in evaluating the genotoxic effects of stressors? We searched the Pubmed/Medline and PubChem databases to identify publications relevant to this question. Micronucleus formation was the genotoxicity endpoint. Three publications comparing exposed vs. non-exposed individuals are included in this analysis; the exposures were to ethylene oxide or ionising radiation (atomic bomb, thorotrast, or radioiodine therapy). Information was extracted on the types of exposure, the numbers of participants, and the micronucleus frequencies. Relative differences (odds ratios) and absolute differences (risk differences) in the numbers of micronuclei between exposed and non-exposed persons were calculated separately for individual cell types (peripheral blood and bone marrow). Random effects meta-analyses for the relative differences in cell abnormalities were performed. The results showed very small differences in the frequencies of micronuclei between exposed and non-exposed individuals, as measured in either peripheral blood or bone marrow cell populations, on both absolute and relative scales. No definite conclusion concerning the relative sensitivities of bone marrow and peripheral blood cells can be made, based on these publications.


Assuntos
Medula Óssea , Radioisótopos do Iodo , Humanos , Radioisótopos do Iodo/farmacologia , Testes para Micronúcleos/métodos , Células Sanguíneas , Células da Medula Óssea , Dano ao DNA , Micronúcleos com Defeito Cromossômico
16.
Front Immunol ; 14: 1206953, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37705980

RESUMO

Background: The search for biomarkers to identify ideal candidates for immune checkpoint inhibitor (ICI) therapy is fundamental. In this study, we analyze peripheral blood CD3+HLADR+ cells (activated T-cells) as a novel biomarker for ICI therapy and how its association to certain gut microbiome species can indicate individual treatment outcomes. Methods: Flow cytometry analysis of peripheral mononuclear blood cells (PBMCs) was performed on n=70 patients undergoing ICI therapy for solid malignancies to quantify HLA-DR on circulating CD3+ cells. 16s-rRNA sequencing of stool samples was performed on n=37 patients to assess relative abundance of gut microbiota. Results: Patients with a higher frequency of CD3+HLADR+ cells before treatment initiation showed a significantly reduced tumor response and overall survival (OS), a worst response and experienced less toxicities to ICI therapy. As such, patients with a frequency of CD3+HLADR+ cells above an ideal cut-off value of 18.55% had a median OS of only 132 days compared to 569 days for patients below. Patients with increasing CD3+HLADR+ cell counts during therapy had a significantly improved OS. An immune signature score comprising CD3+HLADR+ cells and the neutrophil-lymphocyte ratio (NLR) was highly significant for predicting OS before and during therapy. When allied to the relative abundance of microbiota from the Burkholderiales order and the species Bacteroides vulgatus, two immune-microbial scores revealed a promising predictive and prognostic power. Conclusion: We identify the frequencies and dynamics of CD3+HLADR+ cells as an easily accessible prognostic marker to predict outcome to ICIs, and how these could be associated with immune modulating microbiome species. Two unprecedented immune-microbial scores comprising CD3+HLADR+, NLR and relative abundance of gut bacteria from the Burkhorderiales order or Bacteroides vulgatus species could accurately predict OS to immune checkpoint blockade.


Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , Inibidores de Checkpoint Imunológico , Células Sanguíneas
17.
BMC Cancer ; 23(1): 861, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700230

RESUMO

BACKGROUND: Recent achievements in cancer therapy are the use of alternating electrical fields at intermediate frequencies (100-300 kHz) and low intensities (1-3 V/cm), which specifically target cell proliferation while affecting different cellular activities depending on the frequency used. METHODS: In this article, we examine the effect of electric fields on spherical suspended cells and propose the combination of Daunorubicin, a chemotherapy agent widely used in the treatment of acute myeloid leukemia, with electric field exposure. U937 cells were subjected to an electric field with a frequency of 200 kHz and an intensity of 0.75 V/cm, or to a combination of Daunorubicin and electric field exposure, resulting in a significant reduction in cell proliferation. Furthermore, the application of an electric field to U937 cells increased Daunorubicin uptake. RESULTS: Apoptosis and DNA damage were induced by the electric field or in conjunction with Daunorubicin. Notably, normal cells exposed to an electric field did not show significant damage, indicating a selective effect on dividing cancer cells (U937). Moreover, the electric field affects the U937 cell line either alone or in combination with Daunorubicin. This effect may be due to increased membrane permeability. CONCLUSIONS: Our findings suggest that the use of electric fields at intermediate frequencies and low intensities, either alone or in combination with Daunorubicin, has potential as a selective anti-cancer therapy for dividing cancer cells, particularly in the treatment of acute myeloid leukemia. Further research is needed to fully understand the underlying mechanisms and to optimize the use of this therapy.


Assuntos
Células Sanguíneas , Neoplasias Hematológicas , Humanos , Células U937 , Resultado do Tratamento , Daunorrubicina/farmacologia , Daunorrubicina/uso terapêutico
18.
Cancer Res ; 83(17): 2807-2808, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37655431

RESUMO

Genome instability due to the loss of DNA repair factors can drive developmental defects, autoinflammatory disease, and cancer. Two major signaling pathways are activated by genome instability-DNA damage checkpoint signaling, leading to p53 activation, and innate immunity, largely driven by the DNA sensor cGAS. Like p53, cGAS is thought to drive cell death and senescence during genotoxic stress in addition to its canonical inflammatory functions, but its role during cellular differentiation and carcinogenesis is poorly understood. Furthermore, it is heavily debated whether the cGAS pathway primarily has tumor-suppressive or oncogenic functions. A study in this issue of Cancer Research used a hematopoietic lineage-specific knockout of the ribonucleotide repair gene Rnaseh2b to introduce genotoxic stress, resulting in severe hematopoiesis defects and increased incidence of hematologic cancers. These two effects were driven by and antagonized by p53, respectively. Surprisingly, despite increased innate immune signaling, the cGAS pathway did not seem to play a role in either process. These findings suggest that innate immune responses to genotoxic stress may be more subtle and context-specific than appreciated, indicating that a more detailed understanding of pathway activation and signaling consequences is needed. See related article by Dressel et al., p. 2858.


Assuntos
Leucemia , Neoplasias , Humanos , Proteína Supressora de Tumor p53/genética , Neoplasias/genética , Carcinogênese , Cromogranina A , Instabilidade Genômica , Células Sanguíneas
19.
Methods Cell Biol ; 179: 103-112, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37625868

RESUMO

Macrophages have both a protective and pathological role in many autoimmune and inflammatory diseases. Macrophages phenotype is regulated by the environment that affects their polarization toward a pro- or anti-inflammatory phenotype. We describe a protocol for in vitro differentiation of macrophages from blood peripheral monocytes, that may be adopted to study different pathologies. Here, we are interested to study the phenotype of macrophages differentiated from patients affected by acute celiac disease (CD) or subjects following a gluten free diet (GFD), after in vitro gliadin challenge. We assess the pro-inflammatory phenotype of these macrophages by cytokines quantization on the cell supernatant. Moreover, our proposed protocol allows the preparation of total RNA to analyze the expression profile of many genes.


Assuntos
Células Sanguíneas , Macrófagos , Diferenciação Celular , Fenótipo
20.
Health Phys ; 125(5): 332-337, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37552111

RESUMO

ABSTRACT: Workers are frequently exposed to the occupational hazards of ionizing radiation and noise. Co-exposure to these hazards is not well understood in terms of their physiological effects. The aim of this study was to investigate the physiological effects of co-exposure to ionizing radiation and noise within the occupational limit. This study extracted the physical examination parameters of workers who met the screening criteria from the occupational health surveillance database. The workers were divided into three groups: the co-exposure (COE) group, the ionizing radiation exposure (ION) group, and the non-exposure (NON) group. The age and sex of the three groups were matched with a sample size ratio of 1:3:3. The physical examination parameters of the three groups of workers were compared. The results showed that there was no significant difference in blood pressure and blood biochemical parameters among the three groups. The COE group had higher levels of free triiodothyronine than the ION group, but there was no difference with the NON group. Moreover, the COE group had lower levels of free tetraiodothyronine than the ION group and the NON group. There was no significant difference in thyroid stimulating hormone, total triiodothyronine, and total tetraiodothyronine among the three groups. Additionally, the number of white blood cells of the COE group was lower than that of ION group and NON group. This study suggests that co-exposure to low-dose ionizing radiation and noise can cause alterations in thyroid hormone and peripheral white blood cells. These alterations are different from those observed after single exposure to low-dose ionizing radiation and require further research.


Assuntos
Exposição Ocupacional , Exposição à Radiação , Humanos , Tri-Iodotironina , Células Sanguíneas , Exposição Ocupacional/efeitos adversos , Radiação Ionizante
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