The Evaluation of Selected Trace Elements in Blood, Serum and Blood Cells of Type 2 Diabetes Patients with and without Renal Disorder.

BACKGROUND: An appropriate diet is the basis for the treatment of type 2 diabetes (T2DM). However, there are no strict recommendations regarding the content of micronutrients and their modifications in the presence of chronic kidney disease (CKD). Therefore, we decided to investigate whether T2DM patients, including those with CKD, have different levels of chromium, nickel, cobalt, magnesium, and zinc in various blood elements compared to healthy individuals. METHODS: We divided our subjects into three groups: the control group (individuals without T2DM and proper renal function), those with T2DM and proper renal function, and those with T2DM and GFR < 60 mL/min/1.73 m2. RESULTS: We observed higher levels of chromium in all materials examined in patients with T2DM and impaired renal function. Both study groups found higher levels of nickel in samples of whole blood and red blood cells. Patients with T2DM and proper renal function had higher levels of serum manganese. Both study groups had lower levels of serum zinc. We observed higher levels of chromium in all materials examined in patients with T2DM and impaired renal function. Both study groups found higher levels of nickel in samples of whole blood and red blood cells. Patients with T2DM and proper renal function had higher levels of serum manganese. Both study groups had lower levels of serum zinc. CONCLUSIONS: In order to ensure effective care for patients with T2DM, it is necessary to improve the standard diet, including the content of micronutrients and their modification in patients with concomitant CKD.

Immunophenotyping of Peripheral Blood Cells in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib.

Chronic lymphocytic leukemia (CLL) is a B-cell-derived hematologic malignancy whose progression depends on active B-cell receptor (BCR) signaling. Despite the spectacular efficacy of Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), resistance can develop in CLL patients, and alternative therapeutic strategies are therefore required. Cancer immunotherapy has revolutionized cancer care and may be an attractive approach in this context. We speculated that characterizing the immune responses of CLL patients may highlight putative immunotherapeutic targets. Here, we used high-dimensional spectral flow cytometry to compare the distribution and phenotype of non-B-cell immune populations in the circulating blood of CLL patients treated with Ibrutinib displaying a complete response or secondary progression. Although no drastic changes were observed in the composition of their immune subsets, the Ibrutinib-resistant group showed increased cycling of CD8+ T cells, leading to their overabundance at the expense of dendritic cells. In addition, the expression of 11 different surface checkpoints was similar regardless of response status. Together, this suggests that CLL relapse upon Ibrutinib treatment may not lead to major alterations in the peripheral immune response.

Application of image recognition technology in pathological diagnosis of blood smears.

Traditional manual blood smear diagnosis methods are time-consuming and prone to errors, often relying heavily on the experience of clinical laboratory analysts for accuracy. As breakthroughs in key technologies such as neural networks and deep learning continue to drive digital transformation in the medical field, image recognition technology is increasingly being leveraged to enhance existing medical processes. In recent years, advancements in computer technology have led to improved efficiency in the identification of blood cells in blood smears through the use of image recognition technology. This paper provides a comprehensive summary of the methods and steps involved in utilizing image recognition algorithms for diagnosing diseases in blood smears, with a focus on malaria and leukemia. Furthermore, it offers a forward-looking research direction for the development of a comprehensive blood cell pathological detection system.

The predictive value of peripheral blood cell mitochondrial gene expression in identifying the prognosis in pediatric sepsis at preschool age.

Background: Sepsis represents a severe manifestation of infection often accompanied by metabolic disorders and mitochondrial dysfunction. Notably, mitochondrial DNA copy number (mtDNA-CN) and the expression of specific mitochondrial genes have emerged as sensitive indicators of mitochondrial function. To investigate the utility of mitochondrial gene expression in peripheral blood cells for distinguishing severe infections and predicting associated outcomes, we conducted a prospective cohort study. Methods: We established a prospective cohort comprising 74 patients with non-sepsis pneumonia and 67 cases of sepsis induced by respiratory infections, aging from 2 to 6 years old. We documented corresponding clinical data and laboratory information and collected blood samples upon initial hospital admission. Peripheral blood cells were promptly isolated, and both total DNA and RNA were extracted. We utilized absolute quantification PCR to assess mtDNA-CN, as well as the expression levels of mt-CO1, mt-ND1, and mt-ATP6. Subsequently, we extended these comparisons to include survivors and non-survivors among patients with sepsis using univariate and multivariate analyses. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic potential. Results: The mtDNA-CN in peripheral blood cells was significantly lower in the sepsis group. Univariate analysis revealed a significant reduction in the expression of mt-CO1, mt-ND1, and mt-ATP6 in patients with sepsis. However, multivariate analysis did not support the use of mitochondrial function in peripheral blood cells for sepsis diagnosis. In the comparison between pediatric sepsis survivors and non-survivors, univariate analysis indicated a substantial reduction in the expression of mt-CO1, mt-ND1, and mt-ATP6 among non-survivors. Notably, total bilirubin (TB), mt-CO1, mt-ND1, and mt-ATP6 levels were identified as independent risk factors for sepsis-induced mortality. ROC curves were then established for these independent risk factors, revealing areas under the curve (AUCs) of 0.753 for TB (95% CI 0.596-0.910), 0.870 for mt-CO1 (95% CI 0.775-0.965), 0.987 for mt-ND1 (95% CI 0.964-1.000), and 0.877 for mt-ATP6 (95% CI 0.793-0.962). Conclusion: MtDNA-CN and mitochondrial gene expression are closely linked to the severity and clinical outcomes of infectious diseases. Severe infections lead to impaired mitochondrial function in peripheral blood cells. Notably, when compared to other laboratory parameters, the expression levels of mt-CO1, mt-ND1, and mt-ATP6 demonstrate promising potential for assessing the prognosis of pediatric sepsis.

[Opportunities and expectations brought by artificial intelligence assisted peripheral blood cell morphology examination].

The morphological examination of blood cells under manual microscopes is a classic method, but the obvious shortcomings limit the extensive development of peripheral blood cell morphological examination. By using the manual microscope method, it is difficult to ensure the effective implementation of reviewing rules on blood cell analysis, fails to meet the needs of clinical diagnosis and treatment activities, and exposes the risk of missing diagnosis and early detection of some blood system diseases. Artificial Intelligence-assisted peripheral blood cell morphological examination is an important development direction in blood cell morphological examination and diagnosis. This article primarily introduces the characteristics and current application status of artificial intelligence-assisted blood cell morphological examination, as well as the functional requirements and expectations for future technological advancements. Furthermore, it provides an outlook on potential clinical and laboratory application scenarios.With the rapid development of artificial intelligence in blood cell morphology testing, the performance of automated blood cell morphology analysis systems will be greatly improved, which can fully meet the needs of clinical diagnosis, treatment, and health management.

Revealing differential expression patterns of piRNA in FACS blood cells of SARS-CoV-2 infected patients.

Non-coding RNA expression has shown to have cell type-specificity. The regulatory characteristics of these molecules are impacted by changes in their expression levels. We performed next-generation sequencing and examined small RNA-seq data obtained from 6 different types of blood cells separated by fluorescence-activated cell sorting of severe COVID-19 patients and healthy control donors. In addition to examining the behavior of piRNA in the blood cells of severe SARS-CoV-2 infected patients, our aim was to present a distinct piRNA differential expression portrait for each separate cell type. We observed that depending on the type of cell, different sorted control cells (erythrocytes, monocytes, lymphocytes, eosinophils, basophils, and neutrophils) have altering piRNA expression patterns. After analyzing the expression of piRNAs in each set of sorted cells from patients with severe COVID-19, we observed 3 significantly elevated piRNAs - piR-33,123, piR-34,765, piR-43,768 and 9 downregulated piRNAs in erythrocytes. In lymphocytes, all 19 piRNAs were upregulated. Monocytes were presented with a larger amount of statistically significant piRNA, 5 upregulated (piR-49039 piR-31623, piR-37213, piR-44721, piR-44720) and 35 downregulated. It has been previously shown that piR-31,623 has been associated with respiratory syncytial virus infection, and taking in account the major role of piRNA in transposon silencing, we presume that the differential expression patterns which we observed could be a signal of indirect antiviral activity or a specific antiviral cell state. Additionally, in lymphocytes, all 19 piRNAs were upregulated.

Interspecies regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epigenomes.

Knowledge of locations and activities of cis-regulatory elements (CREs) is needed to decipher basic mechanisms of gene regulation and to understand the impact of genetic variants on complex traits. Previous studies identified candidate CREs (cCREs) using epigenetic features in one species, making comparisons difficult between species. In contrast, we conducted an interspecies study defining epigenetic states and identifying cCREs in blood cell types to generate regulatory maps that are comparable between species, using integrative modeling of eight epigenetic features jointly in human and mouse in our Validated Systematic Integration (VISION) Project. The resulting catalogs of cCREs are useful resources for further studies of gene regulation in blood cells, indicated by high overlap with known functional elements and strong enrichment for human genetic variants associated with blood cell phenotypes. The contribution of each epigenetic state in cCREs to gene regulation, inferred from a multivariate regression, was used to estimate epigenetic state regulatory potential (esRP) scores for each cCRE in each cell type, which were used to categorize dynamic changes in cCREs. Groups of cCREs displaying similar patterns of regulatory activity in human and mouse cell types, obtained by joint clustering on esRP scores, harbor distinctive transcription factor binding motifs that are similar between species. An interspecies comparison of cCREs revealed both conserved and species-specific patterns of epigenetic evolution. Finally, we show that comparisons of the epigenetic landscape between species can reveal elements with similar roles in regulation, even in the absence of genomic sequence alignment.

Inter-subject cerebrovascular variability: a source of uncertainty for dose calculation to circulating blood cells for glioblastoma patients treated with modern radiotherapy techniques.

Purpose.To assess how inter-subject variations in brain vasculature among glioblastoma (GBM) patients affects the calculated dose received by circulating blood cells (CBC) during radiotherapy and its subsequent impact on CBC depletion.Methods.Ten GBM patients treated with either intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) were selected. For each patient, 23 cerebrovascular models were developed based on 23 healthy subject MR-angiography data to simulate intra- and inter-subject blood vessel diversity. Based on the corresponding treatment plan of the patient, the dose to CBC was calculated for all the 230 scenarios. The impact of inter-subject variation on fraction of irradiated blood volume (VD>0 cGy) and lymphocyte kill rates as a function of the clinical target volume (CTV) size and treatment technique were analyzed.Results.The dose fluctuation to CBC was higher in IMRT plans compared to VMAT plans. The uncertainty in theVD>0 cGywas 18.3% for IMRT and 2.0% (CI95%) for VMAT and the dispersion of theD2%index was 6 cGy for IMRT and 1 cGy for VMAT (CI95%) for one single treatment fraction of 200 cGy. The uncertainty in killed CBC due to inter-subject diversity in brain blood vessel increased with increasing CTV size and wasσ= 11.2%.Conclusions. VMAT showed greater robustness against inter-subject variation in blood vessels compared to IMRT. We recommend considering the uncertainty in depleting CBC resulting from the use of less patient-specific and generic blood vessel phantoms to improve the radiation-induced lymphopenia assessments.

[Chinese expert consensus on the technical and clinical practice specifications of artificial intelligence assisted morphology examination of blood cells (2024)].

Blood cell morphological examination is a crucial method for the diagnosis of blood diseases, but traditional manual microscopy is characterized by low efficiency and susceptibility to subjective biases. The application of artificial intelligence (AI) technology has improved the efficiency and quality of blood cell examinations and facilitated the standardization of test results. Currently, a variety of AI devices are either in clinical use or under research, with diverse technical requirements and configurations. The Experimental Diagnostic Study Group of the Hematology Branch of the Chinese Medical Association has organized a panel of experts to formulate this consensus. The consensus covers term definitions, scope of application, technical requirements, clinical application, data management, and information security. It emphasizes the importance of specimen preparation, image acquisition, image segmentation algorithms, and cell feature extraction and classification, and sets forth basic requirements for the cell recognition spectrum. Moreover, it provides detailed explanations regarding the fine classification of pathological cells, requirements for cell training and testing, quality control standards, and assistance in issuing diagnostic reports by humans. Additionally, the consensus underscores the significance of data management and information security to ensure the safety of patient information and the accuracy of data.

Evaluation of the Role of Potassium Channels in the Proliferation, Migration, and Invasion of Blood Cells.

The potassium channels are one of the key regulators of cell membrane potential and permeability properties of blood cells. The changes in functioning of potassium channels control crucial cell processes such as proliferation, viability, migration, and invasion. The correct estimation of these processes is important for the characterization of physiological and pathophysiological cell states. Here, we present the experimental protocol for evaluation of the role of potassium ion channels in the proliferation, migration, and invasion of blood cells.

Biological functions and biomedical applications of extracellular vesicles derived from blood cells.

There is a growing interest in using extracellular vesicles (EVs) for therapeutic applications. EVs are composed of cytoplasmic proteins and nucleic acids and an external lipid bilayer containing transmembrane proteins on their surfaces. EVs can alter the state of the target cells by interacting with the receptor ligand of the target cell or by being internalised by the target cell. Blood cells are the primary source of EVs, and 1 µL of plasma contains approximately 1.5 × 107 EVs. Owing to their easy acquisition and the avoidance of cell amplification in vitro, using blood cells as a source of therapeutic EVs has promising clinical application prospects. This review summarises the characteristics and biological functions of EVs derived from different blood cell types (platelets, erythrocytes, and leukocytes) and analyses the prospects and challenges of using them for clinical therapeutic applications. In summary, blood cell-derived EVs can regulate different cell types such as immune cells (macrophages, T cells, and dendritic cells), stem cells, and somatic cells, and play a role in intercellular communication, immune regulation, and cell proliferation. Overall, blood cell-derived EVs have the potential for use in vascular diseases, inflammatory diseases, degenerative diseases, and injuries. To promote the clinical translation of blood cell-derived EVs, researchers need to perform further studies on EVs in terms of scalable and reproducible isolation technology, quality control, safety, stability and storage, regulatory issues, cost-effectiveness, and long-term efficacy.

Nanoscale insights into hematology: super-resolved imaging on blood cell structure, function, and pathology.

Fluorescence nanoscopy, also known as super-resolution microscopy, has transcended the conventional resolution barriers and enabled visualization of biological samples at nanometric resolutions. A series of super-resolution techniques have been developed and applied to investigate the molecular distribution, organization, and interactions in blood cells, as well as the underlying mechanisms of blood-cell-associated diseases. In this review, we provide an overview of various fluorescence nanoscopy technologies, outlining their current development stage and the challenges they are facing in terms of functionality and practicality. We specifically explore how these innovations have propelled forward the analysis of thrombocytes (platelets), erythrocytes (red blood cells) and leukocytes (white blood cells), shedding light on the nanoscale arrangement of subcellular components and molecular interactions. We spotlight novel biomarkers uncovered by fluorescence nanoscopy for disease diagnosis, such as thrombocytopathies, malignancies, and infectious diseases. Furthermore, we discuss the technological hurdles and chart out prospective avenues for future research directions. This review aims to underscore the significant contributions of fluorescence nanoscopy to the field of blood cell analysis and disease diagnosis, poised to revolutionize our approach to exploring, understanding, and managing disease at the molecular level.

Transplantation of Donor-Recipient Chimeric Cells Restores Peripheral Blood Cell Populations and Increases Survival after Total Body Irradiation-Induced Injury in a Rat Experimental Model.

Current therapies for acute radiation syndrome (ARS) involve bone marrow transplantation (BMT), leading to graft-versus-host disease (GvHD). To address this challenge, we have developed a novel donor-recipient chimeric cell (DRCC) therapy to increase survival and prevent GvHD following total body irradiation (TBI)-induced hematopoietic injury without the need for immunosuppression. In this study, 20 Lewis rats were exposed to 7 Gy TBI to induce ARS, and we assessed the efficacy of various cellular therapies following systemic intraosseous administration. Twenty Lewis rats were randomly divided into four experimental groups (n = 5/group): saline control, allogeneic bone marrow transplantation (alloBMT), DRCC, and alloBMT + DRCC. DRCC were created by polyethylene glycol-mediated fusion of bone marrow cells from 24 ACI (RT1a) and 24 Lewis (RT11) rat donors. Fusion feasibility was confirmed by flow cytometry and confocal microscopy. The impact of different therapies on post-irradiation peripheral blood cell recovery was evaluated through complete blood count, while GvHD signs were monitored clinically and histopathologically. The chimeric state of DRCC was confirmed. Post-alloBMT mortality was 60%, whereas DRCC and alloBMT + DRCC therapies achieved 100% survival. DRCC therapy also led to the highest white blood cell counts and minimal GvHD changes in kidney and skin samples, in contrast to alloBMT treatment. In this study, transplantation of DRCC promoted the recovery of peripheral blood cell populations after TBI without the development of GVHD. This study introduces a novel and promising DRCC-based bridging therapy for treating ARS and extending survival without GvHD.

Light microscopic morphology of blood cells of non-descript indigenous Zoar chicken of Mizoram, India.

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.

Gender-specific association between blood cell parameters and hyperuricemia in high-altitude areas.

Background: Hyperuricemia is a common metabolic disorder linked to various health conditions. Its prevalence varies among populations and genders, and high-altitude environments may contribute to its development. Understanding the connection between blood cell parameters and hyperuricemia in high-altitude areas can shed light on the underlying mechanisms. This study aimed to investigate the relationship between blood cell parameters and hyperuricemia in high-altitude areas, with a particular focus on gender differences. Methods: We consecutively enrolled all eligible Tibetan participants aged 18-60 who were undergoing routine medical examinations at the People's Hospital of Chaya County between January and December 2022. During this period, demographic and laboratory data were collected to investigate the risk factors associated with hyperuricemia. Results: Among the participants, 46.09% were diagnosed with hyperuricemia. In the male cohort, significant correlations were found between serum uric acid (SUA) levels and red blood cell (RBC) count, creatinine (Cr). Urea, alanine transaminase (ALT), and albumin (ALB). Notably, RBC exhibited the strongest association. Conversely, in the female cohort, elevated SUA levels were associated with factors such as white blood cell (WBC) count. Urea, ALT, and ALB, with WBC demonstrating the most significant association. Further analysis within the female group revealed a compelling relationship between SUA levels and specific white blood cell subtypes, particularly neutrophils (Neu). Conclusion: This study revealed gender-specific associations between SUA levels and blood cell parameters in high-altitude areas. In males, RBC count may play a role in hyperuricemia, while in females, WBC count appears to be a significant factor. These findings contribute to our understanding of metabolic dynamics in high-altitude regions but require further research for comprehensive mechanistic insights.

Nuclear Isolation from Cryopreserved In Vitro Derived Blood Cells.

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.

Blood cell parameters and risk of nonalcoholic fatty liver disease: a comprehensive Mendelian randomization study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is on the rise globally, and past research suggests a significant association with various blood cell components. Our goal is to explore the potential correlation between whole blood cell indices and NAFLD risk using Mendelian randomization (MR). METHODS: We analyzed data from 4,198 participants in the 2017-2018 National Health and Nutrition Examination Survey to investigate the link between blood cell indicators and NAFLD. Using various methods like weighted quantile sum and multivariate logistic regression, we assessed the association. Additionally, two-sample Mendelian randomization were employed to infer causality for 36 blood cell indicators and NAFLD. RESULTS: Multivariate logistic regression identified 10 NAFLD risk factors. Weighted quantile sum revealed a positive correlation (p = 6.03e-07) between total blood cell indices and NAFLD, with hemoglobin and lymphocyte counts as key contributors. Restricted cubic spline analysis found five indicators with significant nonlinear correlations to NAFLD. Mendelian randomization showed a notable association between reticulocyte counts and NAFLD using the inverse-variance weighted method. CONCLUSIONS: Hematological markers pose an independent NAFLD risk, with a positive causal link found for reticulocyte count. These results emphasize the importance of monitoring NAFLD and investigating specific underlying mechanisms further.

Numerous Serine/Threonine Kinases Affect Blood Cell Homeostasis in Drosophila melanogaster.

Blood cells in Drosophila serve primarily innate immune responses. Various stressors influence blood cell homeostasis regarding both numbers and the proportion of blood cell types. The principle molecular mechanisms governing hematopoiesis are conserved amongst species and involve major signaling pathways like Notch, Toll, JNK, JAK/Stat or RTK. Albeit signaling pathways generally rely on the activity of protein kinases, their specific contribution to hematopoiesis remains understudied. Here, we assess the role of Serine/Threonine kinases with the potential to phosphorylate the transcription factor Su(H) in crystal cell homeostasis. Su(H) is central to Notch signal transduction, and its inhibition by phosphorylation impedes crystal cell formation. Overall, nearly twenty percent of all Drosophila Serine/Threonine kinases were studied in two assays, global and hemocyte-specific overexpression and downregulation, respectively. Unexpectedly, the majority of kinases influenced crystal cell numbers, albeit only a few were related to hematopoiesis so far. Four kinases appeared essential for crystal cell formation, whereas most kinases restrained crystal cell development. This group comprises all kinase classes, indicative of the complex regulatory network underlying blood cell homeostasis. The rather indiscriminative response we observed opens the possibility that blood cells measure their overall phospho-status as a proxy for stress-signals, and activate an adaptive immune response accordingly.

Molecular insights into PCB neurotoxicity: Comparing transcriptomic responses across dopaminergic neurons, population blood cells, and Parkinson's disease pathology.

Parkinson's disease (PD) is a complex neurodegenerative disorder influenced by genetic factors and environmental exposures. Polychlorinated biphenyls (PCBs), a group of synthetic organic compounds, have been identified as potential environmental risk factors for neurodegenerative diseases, including PD. We explored PCB-induced neurotoxicity mechanisms using iPSC-derived dopaminergic neurons and assessed their transcriptomic responses to varying PCB concentrations (0.01 µM, 0.5 µM, and 10 µM). Specifically, we focused on PCB-180, a congener known for its accumulation in human brains. The exposure durations were 24 h and 74 h, allowing us to capture both short-term and more prolonged effects on gene expression patterns. We observed that PCB exposure led to the suppression of oxidative phosphorylation, synaptic function, and neurotransmitter release, implicating these pathways in PCB-induced neurotoxicity. In our comparative analysis, we noted similarities in PCB-induced changes with other PD-related compounds like MPP+ and rotenone. Our findings also aligned with gene expression changes in human blood derived from a population exposed to PCBs, highlighting broader inflammatory responses. Additionally, molecular patterns seen in iPSC-derived neurons were confirmed in postmortem PD brain tissues, validating our in vitro results. In conclusion, our study offers novel insights into the multifaceted impacts of PCB-induced perturbations on various cellular contexts relevant to PD. The use of iPSC-derived dopaminergic neurons allowed us to decipher intricate transcriptomic alterations, bridging the gap between in vitro and in vivo findings. This work underscores the potential role of PCB exposure in neurodegenerative diseases like PD, emphasizing the need to consider both systemic and cell specific effects.