Immunological Implications Research Articles

Beyond the plaque: immunological implications of risk factors in atherosclerosis

The formation of atherosclerotic plaque results from the complex interaction between modifiable and non-modifiable risk factors, through immune mechanisms that orchestrate both inflammatory and anti-inflammatory processes. Atherosclerosis often culminates in ischemic heart disease or cerebrovascular events, which are the leading causes of mortality worldwide. Currently, primary prevention focuses on controlling modifiable risk factors. Therefore, understanding the molecular mechanisms underlying the damage induced by these risk factors is essential to develop more effective treatments. This article provides a detailed review of the immunological processes underlying the initiation and progression of atheroma plaque, exploring their relationship with traditional risk factor such as smoking, diabetes mellitus, dyslipidemia, and hypertension, as well as a new potential risk factor: microbiota dysbiosis. Furthermore, the attributable risk of each factor is independently assessed, and the effectiveness of risk factor control measures is demonstrated as the best strategy to date for the regression of atherosclerosis and the prevention of its complications.

Resolving Ambiguities in Deceased Donor HLA Typing: Next Generation Sequencing’s Role in DPB1 Allele Discrimination and Immunological Implications

Abstract HLA typing is crucial for assessing immunological compatibility between donors and recipients before transplantation. Deceased donor (DD) typing, typically via real-time PCR (rtPCR), provides rapid results vital for organ allocation. rtPCR primarily targets exons encoding the highly polymorphic peptide binding region (PBR) of HLA molecules. rtPCR cannot target all polymorphic sequences. Consequently, several possibilities of allele combinations are provided, leading to ambiguous typing results. As recent evidence suggests antibody responses can target regions in exons outside the PBR, notably in Exon 3 of the DPB1 locus, typing ambiguities can lead to the inability to assess histocompatibility between a donor and recipient. Herein, the aim was to investigate the utility of Next Generation Sequencing (NGS) in resolving DPB1 ambiguities in DD typing. A retrospective analysis of DD typing from February 2022 to January 2024 examined instances where NGS was used to resolve ambiguities reported via rtPCR. Each case was reviewed to understand the reason for resorting to NGS typing. The study focused on DPB1 ambiguities and assessed whether NGS effectively reduced ambiguity and differentiated alleles with polymorphisms outside the PBR. In total, 29 DD cases were found to have NGS testing results. In 14 cases, NGS was specifically performed to resolve DPB1 ambiguities. The ambiguities were significantly reduced from hundreds detected in rtPCR to 4 or fewer possible allele combinations with NGS. Eleven cases demonstrated polymorphism in exons outside the PBRs. Of these, only 2 cases showed no typing ambiguity with NGS. In the remaining 9 cases, though polymorphisms could be resolved in the PBR, ambiguities remained in exon 3, specifically at codon 96. In these cases, NGS could not distinguish lysine (K) from arginine (R). For example, DPB1*835:01 with the 96R motif could not be distinguished from DPB1*34:01with the 96K motif. The current investigation found that NGS cannot resolve all ambiguities at position 96, likely due, at least in part, to persistent cis-trans ambiguities. Our results suggest that although NGS drastically limited the number of ambiguities in 9 of 11 cases, it still could not adequately distinguish all immunologically relevant alleles. Inability to resolve the 96R/K epitope, which has been shown to be immunogenic, could impact solid organ transplantation, potentially leading to rejection in mismatched recipient-donor pairs at this position. Sequencing methods that generate longer reads, such as nanopore, may help resolve some of these cases if they are indeed due to cis-trans ambiguities.

A Comprehensive Revision of Radiation Immunotherapy and the Abscopal Effect in Central Nervous System Metastases: Reassessing the Frontier.

Seventy years ago, Robin Mole introduced the concept of the abscopal effect to describe a rare phenomenon. This occurs when local radiation triggers an immune-mediated reduction in tumors outside the treated area but within the same organism. Observing this effect has been linked to improved overall and progression-free survival in patients who experience it. While the abscopal effect was once considered rare, it is now being observed more frequently due to the combination of radiation with immunotherapy. As a result, more researchers are exploring this study area, which shows promise for excellent results. This review focuses explicitly on the immunological implications of activating the abscopal effect through ionizing radiation in the central nervous system and explores the potentially involved immunological pathways.

COULD THE ACUTE Strongyloides venezuelensis INFECTION CAUSE NON-REVERSIBLE HOST MORPHOLOGICAL CHANGES?

Although research has investigated the host-parasite relationship in Strongyloides venezuelensis infection in the scope of its immunological implications, the morphological consequences of this response for the host organism are yet to be explored. Our objective was to perform an organ morphometric analysis in Wistar rats infected with the intestinal parasite Strongyloides venezuelensis compared with infected rats treated with ivermectin. Twenty-six animals composed three groups: control (non-infected), infected (infected with 2,000 Strongyloides venezuelensis larvae), and infected treated (infected with 2,000 Strongyloides venezuelensis larvae and treated with ivermectin). All rodents were killed 21 days after infection and morphometric analysis of different organs was performed. The results showed significantly higher body and fecal weight in the infected-treated group. The weight of the small intestine increased considerably in the infected group and decreased in the infected-treated group. Pancreas, right kidney, and heart volume increased in the infected group compared with the control group. Despite treatment, the volumes of the stomach, brain, and left kidney increased in both the infected groups compared with the control group indicating the possibility of non-reversible host morphological adaptations. S. venezuelensis infection can augment both, volume and weight of organs – not necessarily related to the Strongyloides expulsion process – even if the acute infection had been in remission. A potential explanation for these host adaptations, including the occurrence of organ plasticity, are briefly discussed. The following steps encompass a histological analysis to verify the occurrence of hypertrophy/hyperplasia and observe if such morphological alterations remain after infection.

Genetic and immunological implications in fibromyalgia: A Literature Review

Fibromyalgia (FM), a musculoskeletal condition characterized by widespread pain and numerous associated symptoms, is a complex disorder with uncertain etiology and pathogenesis. Most of the patients suffering from this syndrome are undiagnosed due to a lack of standard diagnostic criteria. Recent studies have shown the involvement of immune dysfunction and various pro-inflammatory cytokines in FM. Since there is so much uncertainty regarding the pathogenesis of FM, treatment modalities are very limited and ineffective. This review aimed to analyze the immunological mechanisms behind FM, attempting to deepen the understanding of its pathogenesis. Additionally, the review elucidates FM's associations with autoimmune diseases, highlighting shared pathophysiological mechanisms and overlapping symptoms. We synthesized current literature available on Google Scholar, PubMed, Springer, and Web of Science, the review explored the intricate interactions between genetic predisposition, immune dysregulation, and environmental factors in FM pathogenesis. The inclusion criteria prioritized studies focusing on the immunological aspect of FM. In conclusion, immune dysfunction has a role to play in the pathogenesis of FM, and immunomodulatory therapies have proven to be beneficial in the treatment of FM. Genetic variants, epigenetic modifications, and gut microbiome alterations are potential triggers for immune system dysfunction, contributing to the manifestation and exaggeration of FM symptoms. This review provided a comprehensive resource for researchers and clinicians, a guide for future investigations and clinical management towards improved outcomes and enhanced quality of life for individuals with FM.

Physiology and immunology of the adrenergic anti-inflammatory pathway

The adrenergic anti-inflammatory pathway represents a critical intersection between the nervous and immune systems, modulating the body's response to inflammation through the action of catecholamines on adrenergic receptors. This review explored the physiology underlying this pathway, focusing on the mechanisms by which the sympathetic nervous system influences immune function. We delved into the roles of specific adrenergic receptors, primarily the beta-adrenergic receptors, in mediating anti-inflammatory effects, highlighting the involved molecular signaling pathways. Additionally, we examined the immunological implications of adrenergic modulation, discussing how these pathways contributed to the resolution of inflammation and the potential for dysregulation in various disease states. Emerging evidence on the therapeutic potential of targeting the adrenergic anti-inflammatory pathway in conditions such as sepsis, autoimmune diseases, and chronic inflammatory disorders was also reviewed. By integrating current knowledge on the physiology and immunology of this pathway, this review aimed to provide a comprehensive understanding of its role in health and disease, offering insights into future research directions and clinical applications.

Targeted and complete genomic sequencing of the major histocompatibility complex in haplotypic form of individual heterozygous samples.

The human major histocompatibility complex (MHC) is a ∼4 Mb genomic segment on Chromosome 6 that plays a pivotal role in the immune response. Despite its importance in various traits and diseases, its complex nature makes it challenging to accurately characterize on a routine basis. We present a novel approach allowing targeted sequencing and de novo haplotypic assembly of the MHC region in heterozygous samples, using long-read sequencing technologies. Our approach is validated using two reference samples, two family trios, and an African-American sample. We achieved excellent coverage (96.6%-99.9% with at least 30× depth) and high accuracy (99.89%-99.99%) for the different haplotypes. This methodology offers a reliable and cost-effective method for sequencing and fully characterizing the MHC without the need for whole-genome sequencing, facilitating broader studies on this important genomic segment and having significant implications in immunology, genetics, and medicine.

Daily Intake of Household-Produced Milk Kefir on Salmonella Typhimurium Infection in C57BL/6 Mice: Mortality, Microbiota Modulation and Immunological Implications.

Salmonellosis, a major global cause of diarrheal diseases, significantly impacts the intestinal microbiome. Probiotic-rich beverages, such as kefir, are increasingly utilized as alternative health-promoting beverages associated with various microbiota benefits. This study investigated the repercussions of daily consumption of household-produced milk kefir on Salmonella enterica serovar Typhimurium infection in C57BL-6 mice. Kefir consumption pre infection reduced the presence of inflammatory cells in the colon and altered the cytokine profile by reducing IL-10 and increasing IFN-γ. Despite reducing intestinal inflammation, kefir intake did not yield a prompt response to an acute infection caused by the aggressive pathogen Salmonella. This contributed to increased mortality in the mice, evidenced by higher fecal Salmonella counts post-infection. Metabarcoding analysis demonstrated that the use of kefir before infection increases butyric acid by the higher abundance of Lachnospiraceae and Prevotellaceae families and genus in feces, coupled with an increase in Muribaculaceae family and Bacteroides genus among infected kefir-treated mice. While kefir hinted at microbiota alterations reducing enterobacteria (Helicobacter), decrease IL-10, and increased IFN-γ, butyric acid on pre-infection, the beverage potentially facilitated the systemic translocation of pathogens, intensifying the infection's severity by altering the immune response. The use of kefir in the dosage of 10% w/v (109 CFU), for acute infections with Salmonella Typhimurium, may not be enough to combat the infection and worsen the prognosis, leaving the intestine less inflamed, favoring the replication and translocation of the pathogen. These findings underscore the importance of prudently evaluating the widespread use of probiotics and probiotic-rich beverages, especially during acute infections, given their potential association with adverse effects during these diseases.

A comprehensive prognostic and immunological implications of PFKP in pan-cancer

BackgroundPhosphofructokinase P (PFKP) is a key rate-limiting enzyme in glycolysis, playing a crucial role in various pathophysiological processes. However, its specific function in tumors remains unclear. This study aims to evaluate the expression and specific role of PFKP across multiple tumor types (Pan-cancer) and to explore its potential clinical significance as a therapeutic target in cancer treatment.MethodsWe analyzed the expression of PFKP, immune cell infiltration, and patient prognosis across various cancers using data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we conducted a series of experiments in lung cancer cells, including Western blot, CCK-8 assay, colony formation assay, transwell migration assay, scratch wound healing assay, LDH release assay, and flow cytometry, to evaluate the impact of PFKP on tumor cells.ResultsPFKP was found to be highly expressed in most cancers and identified as a prognostic risk factor. Elevated PFKP expression is associated with poorer clinical outcomes, particularly in lung adenocarcinoma (LUAD). Receiver operating characteristic (ROC) curve analysis indicated that PFKP can effectively differentiate between cancerous and normal tissues. The expression of PFKP in most tumors showed significant correlations with tumor mutational burden (TMB), microsatellite instability (MSI), immune score, and immune cell infiltration. In vitro experiments demonstrated that PFKP overexpression promotes lung cancer cell proliferation and migration while inhibiting apoptosis, whereas PFKP deficiency results in the opposite effects.ConclusionPFKP acts as an oncogene involved in tumorigenesis and may influence the immune microenvironment within the tumor. Our findings suggest that PFKP could serve as a potential biomarker for predicting prognosis and the efficacy of immunotherapy in tumors.

Denovo glomerulonephritis associated with IgA anti-GBM alloantibodies after kidney transplantation in Alport syndrome: A case report with diagnostic implications

Alport syndrome (AS) is a hereditary disorder caused by pathogenic variants in COL4A3, COL4A4, or COL4A5 genes expressing α3, α4, and α5 chains of basement membrane type IV collagen (COL4). The triple-helical α3α4α5(IV) protomer is a major component of the mature glomerular basement membrane (GBM) whose defective formation in AS leads to structural GBM disruption and kidney dysfunction, often resulting in kidney replacement therapy. A genetically intact renal graft exposes the immune system to a non-tolerized α3α4α5(IV) component and an alloimmune response eventually ensues. So far, only IgG alloantibodies reacting against COL4 have been reported in AS alloimmune responses. Here, we report alloimmune glomerulonephritis mediated by IgA antibodies against the non-collagenous C-terminal domain 1 of the α5(IV) chain in a patient with autosomal recessive AS following a second kidney transplantation. The patient presented a not previously described biallelic variant in the COL4A4 gene. Immunological, diagnostic, and clinical implications are discussed.

Prognostic and immunological implications of heterogeneous cell death patterns in prostate cancer

BackgroundProstate cancer is one of the most common cancers in men with a significant proportion of patients developing biochemical recurrence (BCR) after treatment. Programmed cell death (PCD) mechanisms are known to play critical roles in tumor progression and can potentially serve as prognostic and therapeutic biomarkers in PCa. This study aimed to develop a prognostic signature for BCR in PCa using PCD-related genes.Materials and methodsWe conducted an analysis of 19 different modes of PCD to develop a comprehensive model. Bulk transcriptomic, single-cell transcriptomic, genomic, and clinical data were collected from multiple cohorts, including TCGA-PRAD, GSE58812, METABRIC, GSE21653, and GSE193337. We analyzed the expression and mutations of the 19 PCD modes and constructed, evaluated, and validated the model.ResultsTen PCD modes were found to be associated with BCR in PCa, with specific PCD patterns exhibited by various cell components within the tumor microenvironment. Through Lasso Cox regression analysis, we established a Programmed Cell Death Index (PCDI) utilizing an 11-gene signature. High PCDI values were validated in five independent datasets and were found to be associated with an increased risk of BCR in PCa patients. Notably, older age and advanced T and N staging were associated with higher PCDI values. By combining PCDI with T staging, we constructed a nomogram with enhanced predictive performance. Additionally, high PCDI values were significantly correlated with decreased drug sensitivity, including drugs such as Docetaxel and Methotrexate. Patients with lower PCDI values demonstrated higher immunophenoscores (IPS), suggesting a potentially higher response rate to immune therapy. Furthermore, PCDI was associated with immune checkpoint genes and key components of the tumor microenvironment, including macrophages, T cells, and NK cells. Finally, clinical specimens validated the differential expression of PCDI-related PCDRGs at both the gene and protein levels.ConclusionIn conclusion, we developed a novel PCD-based prognostic feature that successfully predicted BCR in PCa patients and provided insights into drug sensitivity and potential response to immune therapy. These findings have significant clinical implications for the treatment of PCa.

Pan-Cancer Analysis Confirms the Prognostic and Immunological Implications of the 1,25-Dihydroxy Vitamin D3 Receptor in Cervical Squamous Cell Carcinoma.

Vitamin D receptor (VDR), specifically the 1,25-dihydroxy form, holds significant importance in various types of cancer, including cervical squamous cell carcinoma (CESC), whichposes a significant public health challenge. A pan-cancer analysis was conducted on VDR in CESC, with a focus on its expression and relationship with immune infiltration and genetic alterations. Bioinformatics databases, including TIMER, GEPIA, UALCAN, cBioportal, and Kaplan-Meier Plotter, have been utilized. VDR expression in CESC has been validated using publicly available data. Results were significantly upregulated (P=0.05) in THCA, BRCA, KICH, LUAD, LIHC, STAD, UCEC, CESC, CHOL, ESCA, and HNSC samples. We analyzed the correlation between VDR expression and various clinicopathological factors such as age, race, and cancer stage. VDR expression was significantly upregulated across all age groups, with the highest levels observed in older adults followed by young and middle-aged adults. VDR gene expression was significantly elevated across all races, including Caucasians, African-Americans, and Asians, compared to that in the normal group. Furthermore, VDR expression was significantly upregulated in cancer stages 1, 2, 3, and 4, with the highest increase observed in stage 3 compared to that in normal individuals. We analyzed the expression of the VDRin relation to immune cell type and tumor cell purity in CESC. Our results indicated that VDR expression was positively correlated with neutrophils and dendritic cells and negatively correlated with tumor cell purity in CESC patients. There was no significant correlation between VDR expression and the abundance of B cells, CD8+ T cells, CD4+ T cells, and macrophages. Our study found no significant effect of VDR expression on patient prognosis, although it was positively correlated with CD4+ T cells. The Cox proportional hazards model indicated that age and immune cells did not significantly affect prognosis. Most VDR mutations are concentrated in diffuse large B-cell lymphoma, with an amplification frequency of 4% and a deep deletion frequency of 2.2%. GEO confirmed VDR expression in CESC, identifying 1515 upregulated and 1877 downregulated genes, with volcano plots showing CESC downregulation in patients.

Systemic and skin-limited delayed-type drug hypersensitivity reactions associate with distinct resident and recruited T cell subsets.

Delayed-type drug hypersensitivity reactions are major causes of morbidity and mortality. The origin, phenotype, and function of pathogenic T cells across the spectrum of severity require investigation. We leveraged recent technical advancements to study skin-resident memory T cells (TRMs) versus recruited T cell subsets in the pathogenesis of severe systemic forms of disease, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), and skin-limited disease, morbilliform drug eruption (MDE). Microscopy, bulk transcriptional profiling, and single-cell RNA-sequencing (scRNA-Seq) plus cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) plus T cell receptor sequencing (TCR-Seq) supported clonal expansion and recruitment of cytotoxic CD8+ T cells from circulation into skin along with expanded and nonexpanded cytotoxic CD8+ skin TRM in SJS/TEN. Comparatively, MDE displayed a cytotoxic T cell profile in skin without appreciable expansion and recruitment of cytotoxic CD8+ T cells from circulation, implicating TRMs as potential protagonists in skin-limited disease. Mechanistic interrogation in patients unable to recruit T cells from circulation into skin and in a parallel mouse model supported that skin TRMs were sufficient to mediate MDE. Concomitantly, SJS/TEN displayed a reduced Treg signature compared with MDE. DRESS demonstrated recruitment of cytotoxic CD8+ T cells into skin as in SJS/TEN, yet a pro-Treg signature as in MDE. These findings have important implications for fundamental skin immunology and clinical care.

NME4 suppresses NFκB2-CCL5 axis, restricting CD8+ T cell tumour infiltration in oesophageal squamous cell carcinoma.

Thought of as a metastasis-associated gene, however, NME/NM23 nucleoside diphosphate kinase 4 (NME4) has rarely been described in the context of the tumour microenvironment. To understand the immunological implications of NME4 in oesophageal squamous cell carcinoma (ESCC), we used multiplex immunohistochemistry to analyse the clinicopathological and prognostic importance of NME4 expression. Then, after establishing a syngeneic tumour model with a C57BL/6 mouse strain that can recapitulate the tumour microenvironment of humans, we examined the immunological involvement of NME4 expression. To explore the underlying molecular mechanism, via quantitative proteomics and protein microarray screening, we investigated the potential signalling pathways involved. The clinicopathological and prognostic importance of NME4 expression is limited in ESCC patients. In vivo, single-cell RNA sequencing showed that NME4 strikingly prevented CD8+ T cells from infiltrating the tumour microenvironment in murine ESCC. Mechanistically, we mapped out the NFκB2-CCL5 axis that was negatively controlled by NME4 in the murine ESCC cell line AKR. Collectively, these data demonstrated that regulation of NFκB2-CCL5 axis by NME4 prevents CD8+ T cells infiltration in ESCC.

Basement membrane-associated gene expression as a predictor of survival in oral cancer

BackgroundThis study sought to investigate the prognostic value of basement membrane (BM)-associated gene expressions in oral cancer.MethodsWe harvested and integrated data on BM-associated genes (BMGs), the oral cancer transcriptome, and clinical information from public repositories. After identifying differentially expressed BMGs, we used Cox and Lasso regression analyses to create a BMG-based risk score for overall survival at various intervals. We then validated this score using the GSE42743 cohort as a validation set. The prognostic potential of the risk scores and their relations to clinical features were assessed. Further, we conducted functional pathway enrichment, immune cell infiltration, and immune checkpoint analyses to elucidate the immunological implications and therapeutic potential of the BMG-based risk score and constituent genes. To confirm the expression levels of the BMG LAMA3 in clinical samples of oral cancer tissue, we performed quantitative real-time PCR (qRT-PCR) and immunohistochemical staining.ResultsThe BMGs LAMA3, MMP14, and GPC2 demonstrated notable prognostic significance, facilitating the construction of a BMG-based risk score. A higher risk score derived from BMGs correlated with a poorer survival prognosis for oral cancer patients. Moreover, the risk-associated BMGs exhibited a significant relationship with immune function variability (P < 0.05), discrepancies in infiltrating immune cell fractions, and immune checkpoint expressions (P < 0.05). The upregulated expression levels of LAMA3 in oral cancer tissues were substantiated through qRT-PCR and immunohistochemical staining.ConclusionThe BMG-based risk score emerged as a reliable prognostic tool for oral cancer, meriting further research for validation and potential clinical application.

Vitiligo after borderline lepromatous leprosy: common immunological implications

Vitiligo after borderline lepromatous leprosy: common immunological implications

Comprehensive bioinformatics analytics and in vivo validation reveal SLC31A1 as an emerging diagnostic biomarker for acute myocardial infarction.

Globally, Acute Myocardial Infarction (AMI) is a common cause of heart failure (HF), which has been a leading cause of mortality resulting from non-communicable diseases. On the other hand, increasing evidence suggests that the role of energy production within the mitochondria strongly links to the development and progression of heart diseases, while Cuproptosis, a newly identified cell death mechanism, has not yet been comprehensively analyzed from the aspect of cardiovascular medicine. 8 transcriptome profiles curated from the GEO database were integrated, from which a diagnostic model based on the Stacking algorithm was established. The efficacy of the model was evaluated in a multifaced manner (i.e., by Precision-Recall curve, Receiver Operative Characteristic curve, etc.). We also sequenced our animal models at the bulk RNA level and conducted qPCR and immunohistochemical staining, with which we further validated the expression of the key contributor gene to the model. Finally, we explored the immune implications of the key contributor gene. A merged machine learning model containing 4 Cuproptosis-related genes (i.e., PDHB, CDKN2A, GLS, and SLC31A1) for robust AMI diagnosis was developed, in which SLC31A1 served as the key contributor. Through in vivo modeling, we validated the aberrant overexpression of SLC31A1 in AMI. Besides, further transcriptome analysis revealed that its high expression was correlated with significant potential immunological implications in the infiltration of many immune cell types, especially monocyte. We constructed an AMI diagnostic model based on Cuproptosis-related genes and validated the key contributor gene in animal modeling. We also analyzed the effects on the immune system for its overexpression in AMI.

MHC-Fine: Fine-tuned AlphaFold for precise MHC-peptide complex prediction

The precise prediction of major histocompatibility complex (MHC)-peptide complex structures is pivotal for understanding cellular immune responses and advancing vaccine design. In this study, we enhanced AlphaFold’s capabilities by fine-tuning it with a specialized dataset consisting of exclusively high-resolution class I MHC-peptide crystal structures. This tailored approach aimed to address the generalist nature of AlphaFold’s original training, which, while broad-ranging, lacked the granularity necessary for the high-precision demands of class I MHC-peptide interaction prediction. A comparative analysis was conducted against the homology-modeling-based method Pandora as well as the AlphaFold multimer model. Our results demonstrate that our fine-tuned model outperforms others in terms of root-mean-square deviation (median value for Cα atoms for peptides is 0.66 Å) and also provides enhanced predicted local distance difference test scores, offering a more reliable assessment of the predicted structures. These advances have substantial implications for computational immunology, potentially accelerating the development of novel therapeutics and vaccines by providing a more precise computational lens through which to view MHC-peptide interactions.

Immunological Implications in Diabetes: A Review on Various Diseases and Conditions

Abstract:: Diabetes Mellitus (DM) is a long-term metabolic condition that has significant social, health, and economic consequences. There are various forms of diabetes mellitus, but the two most common varieties are type I and type II. Insulin-dependent diabetes (IDDM) is one of the most wellknown autoimmune illnesses that cause insulin insufficiency and hyperglycemia by either damaging or destroying Langerhans' beta cells. Available scientific data evidenced the greatest genetic contribution of Human Leukocyte Antigen class II in the IDDM. Hyperglycemia and individual components of the insulin resistance (metabolic) syndrome put people with type II diabetes at increased risk for microvascular consequences (retinopathy, nephropathy, and neuropathy) as well as macrovascular issues (cardiovascular comorbidities). A number of pathophysiological abnormalities, including obesity, poor diet, and physical inactivity, as well as genetic variables, are involved in the disturbed glucose homeostasis associated with type II diabetes. Diseases like lipid abnormalities contribute to the progression of diabetes, whereas obesity and its related medical disorders (such as hypertension, diabetes, insulin resistance, and sleep apnea syndrome) are eventually linked to an elevated cardiovascular risk. Diabetes raises the incidence, intensity, and duration of peri-densities in people with diabetes compared to healthy persons, making it a risk factor for periodontal disease. Diabetes conditions in patients concurrently also increase the progression or risk of other diseases, i.e., cardiovascular- related diseases (hypertension, oxidative stress, hyperlipidemia), nervous system-related diseases, and COVID-19, by increasing the overall infection rate. There is widespread evidence that correlates the direct connection between diabetes and other diseases, including immunity disorders, CVS disorders, etc. This review provides a correlation between diabetes and another disease with an overall impact on the progression of cardiovascular diseases, neurological diseases, COVID-19, and periodontal diseases. This current review focuses on the collation of some plants that show antidiabetic activity, including plant part, family, chemical constituent, mechanism of action, and chemical used for extraction. Studies on the role, causes, clinical management, prevention, and treatment of diabetes heavily rely on epidemiological evidence. This review also explains different factors responsible for diabetes, like genetic factors, environmental factors, and viral infections.

Abstract 6633: Tracking cell-cell interactions using intercellular barcode transfer

Abstract Cell-cell interaction is one of the fundamental biological mechanisms by which cells communicate and is a key modality by which cancer cells interact with other cells in their microenvironment. Current methods, such as enzymatic labeling and proximity-based tagging, allow the experimental tracking of these interactions but are not compatible with sequencing-based readouts, which are essential for high-throughput analyses. We have developed a highly scalable intercellular barcode transfer technology that bridges this gap. Our novel “Relay” technology offers a scalable solution to monitor cell-cell interactions with unprecedented single-cell resolution, seamlessly integrating with existing high-throughput and sequencing platforms. Relay employs RNA barcodes to mark and track cell interaction events, providing definitive quantitative data on cell interaction partners. We used Relay to track interactions between cancer cells and T cells, capturing both potent antigen-specific engagements and subtler contacts involved in antigen sampling. Additionally, by integrating CRISPR libraries with Relay, we pioneered a novel approach for pooled CRISPR screens, focusing on intercellular interactions across different cell types. In this context, the cell harboring genetic perturbation may differ from the cell under analysis. To demonstrate this, we are conducting genome-wide perturbations in cancer cells and interrogating cancer cell factors that affect antigen sampling and trogocytosis by T cells and macrophages. Beyond its application in CRISPR screening, Relay can also be used with single-cell RNA sequencing to directly track and measure immune-cancer and immune-immune cell interactions at the single cell level. We applied single-cell Relay to a dendritic cell-T cell system to link dendritic cell signatures to T cell signatures based on direct cell contact and regulatory signaling. The design of Relay as a highly modular system extends its utility beyond cancer research, making it broadly applicable across various biological models and systems where cell-cell communication is a fundamental property in complex multicellular settings. This tool promises to accelerate the transition from theoretical understanding to practical exploration of cell-cell interactions, with profound implications for immunology, oncology, and beyond. Citation Format: Neil Q. Tay, Tiffany Juan, Joseph J. Muldoon, Justin Eyquem, Michael T. McManus. Tracking cell-cell interactions using intercellular barcode transfer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6633.