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Topic Review
Comparison of HMGB1 in Asthma and in COPD
The airway epithelium, through pattern recognition receptors expressed transmembrane or intracellularly, acts as a first line of defense for the lungs against many environmental triggers. It is involved in the release of alarmin cytokines, which are important mediators of inflammation, with receptors widely expressed in structural cells as well as innate and adaptive immune cells. Knowledge of the role of epithelial cells in orchestrating the immune response and mediating the clearance of invading pathogens and dead/damaged cells to facilitate resolution of inflammation is necessary to understand how, in many chronic lung diseases, there is a persistent inflammatory response that becomes the basis of underlying pathogenesis, in particular thymic stromal lymphopoietin (TSLP) and high mobility group box 1 (HMGB1), as key mediators in driving the inflammation of chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), evaluating the similarities and differences.
  • 385
  • 09 Feb 2023
Topic Review
Targeting Immunosuppressive Adenosine Signaling
The tumor microenvironment regulates many aspects of cancer progression and anti-tumor immunity. Cancer cells employ a variety of immunosuppressive mechanisms to dampen immune cell function in the tumor microenvironment. While immunotherapies that target these mechanisms, such as immune checkpoint blockade, have had notable clinical success, resistance is common, and there is an urgent need to identify additional targets. Extracellular adenosine, a metabolite of ATP, is found at high levels in the tumor microenvironment and has potent immunosuppressive properties. Targeting members of the adenosine signaling pathway represents a promising immunotherapeutic modality that can potentially synergize with conventional anti-cancer treatment strategies. 
  • 385
  • 25 May 2023
Topic Review
COVID-19 in Solid Organ Transplant Recipient
It is still uncertain whether recipients of solid organ transplant (SOT) are at increased risk of SARS-CoV-2 infection and/or poor outcomes due to COVID-19 in comparison to the general population. In this study, we report the cumulative incidence and outcomes of SARS-CoV-2 infection in a cohort of 291 SOT recipients. The COVID-19 cumulative incidence in SOT recipients resulted slightly higher compared to that of age-matched population during the study period. Moreover, the SARS-CoV-2 antibody frequency was around 2.6-fold higher than the incidence of cases who tested positive for SARS-CoV-2 RT-PCR, suggesting that the number of SOT recipients infected with SARS-CoV-2 is likely higher than described. In symptomatic recipients, kidney transplant was associated with a higher risk of developing moderate/critical disease, while common risk factors, including age and comorbidities, resulted less relevant for COVID-19 severity. Due to the high estimated crude mortality, symptomatic SOT recipients should be considered at high risk in case of SARS-CoV-2 infection.
  • 384
  • 19 Jan 2022
Topic Review
Potential of NK Cell-Based Immunotherapies against Multiple Myeloma
Natural killer (NK) cell-based therapies have emerged as promising anticancer treatments due to their potency as cytolytic effectors and synergy with concurrent treatments. Multiple myeloma (MM) is an aggressive B-cell malignancy that, despite development of novel therapeutic agents, remains incurable with a high rate of relapse. In MM, the inhospitable tumor microenvironment prevents host NK cells from exerting their cytolytic function. The development of NK cell immunotherapy works to overcome this altered immune landscape and can be classified in two major groups based on the origin of the cell: autologous or allogeneic. 
  • 384
  • 29 Mar 2022
Topic Review
Emerging Immunotherapies in Breast Cancer
Immunotherapy is a highly emerging form of breast cancer therapy that enables clinicians to target cancers with specific receptor expression profiles. Two popular immunotherapeutic approaches involve chimeric antigen receptor-T cells (CAR-T) and bispecific antibodies (BsAb). Briefly mentioned in this review as well is the mRNA vaccine technology recently popularized by the COVID-19 vaccine. These forms of immunotherapy can highly select for the tumor target of interest to generate specific tumor lysis. Combining emerging immunotherapeutics with tumor marker discovery sets the stage for highly targeted immunotherapy to be the future of cancer treatments. This review highlights the principles of CAR-T and BsAb therapy, improvements in CAR and BsAb engineering, and recently identified human breast cancer markers in the context of in vitro or in vivo CAR-T or BsAb treatment. 
  • 383
  • 06 Dec 2021
Topic Review
Mechanisms of Immunosuppression in Sepsis
Severe infection can lead to sepsis. In sepsis, the host mounts an inappropriately large inflammatory response in an attempt to clear the invading pathogen. This sustained high level of inflammation may cause tissue injury and organ failure. Later in sepsis, a paradoxical immunosuppression occurs, where the host is unable to clear the preexisting infection and is susceptible to secondary infections. A major issue with sepsis treatment is that it is difficult for physicians to ascertain which stage of sepsis the patient is in. Sepsis treatment will depend on the patient’s immune status across the spectrum of the disease, and these immune statuses are nearly polar opposites in the early and late stages of sepsis.
  • 382
  • 01 Feb 2024
Topic Review
Natural Polyphenols in Inflammatory Intestinal Diseases
The intestine is critically crucial for nutrient absorption and host defense against exogenous stimuli. Inflammation-related intestinal diseases, including enteritis, inflammatory bowel disease (IBD), and colorectal cancer (CRC), are heavy burdens for human beings due to their high incidence and devastating clinical symptoms. Studies have confirmed that inflammatory responses, along with oxidative stress and dysbiosis as critical pathogenesis, are involved in most intestinal diseases. Polyphenols are secondary metabolites derived from plants, which possess convincible anti-oxidative and anti-inflammatory properties, as well as regulation of intestinal microbiome, indicating the potential applications in enterocolitis and CRC.
  • 382
  • 24 Jul 2023
Topic Review
Natural Killer Cells in Liver Fibrosis
Natural killer (NK) cells are a key component of innate immunity and have miscellaneous roles in liver health and disease. Accumulating evidence shows that NK cells play dual roles in the development and progression of liver fibrosis, including profibrotic and anti-fibrotic functions.
  • 381
  • 18 May 2023
Topic Review
Lectins as Toxins from Marine Animals
Due to their remarkable structural diversity, glycans play important roles as recognition molecules on cell surfaces of living organisms. Carbohydrates exist in numerous isomeric forms and can adopt diverse structures through various branching patterns. Despite their relatively small molecular weights, they exhibit extensive structural diversity. On the other hand, lectins, also known as carbohydrate-binding proteins, not only recognize and bind to the diverse structures of glycans but also induce various biological reactions based on structural differences. Initially discovered as hemagglutinins in plant seeds, lectins have been found to play significant roles in cell recognition processes in higher vertebrates. 
  • 381
  • 13 Jul 2023
Topic Review
Innate Immunity in Disease and Adaptation to Stress
Since first being documented in ancient times, the relation of inflammation with injury and disease has evolved in complexity and causality. Early observations supported a cause (injury) and effect (inflammation) relationship, but the number of pathologies linked to chronic inflammation suggests that inflammation itself acts as a potent promoter of injury and disease. Additionally, results from studies over the last decades point to chronic inflammation and innate immune signaling as a critical link between stress (exogenous and endogenous) and adaptation.
  • 380
  • 06 Jun 2022
Topic Review
The Role of Hydrogen Sulfide in Macrophage Biology
Macrophages are cells in the innate immune system that provide the first line of defense against invading pathogens. Macrophages are classified broadly within two types of polarization states: classically activated (M1) and alternatively activated (M2). Hydrogen sulfide (H2S) has been increasingly recognized as a crucial inflammatory mediator in immune cells, particularly macrophages, due to its direct and indirect effects on cellular signaling, redox homeostasis, and energy metabolism. The intricate regulation of endogenous H2S production and metabolism involves the coordination of transsulfuration pathway (TSP) enzymes and sulfide oxidizing enzymes, with TSP’s role at the intersection of the methionine pathway and glutathione synthesis reactions.
  • 379
  • 08 May 2023
Topic Review
Targeted Accumulation of Macrophages Induced by Microbeam Irradiation
Macrophages are some of the first cells recruited to sites of radiation-induced injury where they can aid in tissue repair, propagate radiation-induced fibrogenesis and influence tumour dynamics. Radiation therapy (RT) is a vital component of multimodal cancer treatment, and its immunomodulatory effects are a major focus of current therapeutic strategies. Microbeam radiation therapy (MRT) is a unique, spatially fractionated radiation modality that has demonstrated exceptional tumour control and reduction in normal tissue toxicity, including fibrosis. 
  • 378
  • 02 Apr 2022
Topic Review
IgG N-glycan Signatures as Diagnostic and Prognostic Biomarkers
IgG N-glycans are an emerging source of disease-specific biomarkers. The continued development of glycomic databases and the evolution of glyco-analytic methods have resulted in increased throughput, resolution, and sensitivity. IgG N-glycans promote adaptive immune responses through antibody-dependent cellular cytotoxicity (ADCC) and complement activation to combat infection or cancer and promote autoimmunity. In addition to the functional assays, researchers are examining the ability of protein-specific glycosylation to serve as biomarkers of disease. 
  • 377
  • 28 Mar 2023
Topic Review
Animal Models of Neutropenia
Animal models of neutropenia are indispensable tools in biomedical research, offering unique insights into the causes, mechanisms, and potential treatments for this hematologic disorder. Neutropenia, characterized by a decreased number of neutrophils in the blood, can result from diverse factors, including chemotherapy, genetic mutations, autoimmune processes, and infections. Understanding these varied etiologies necessitates the use of different animal models, each tailored to specific research goals. Chemotherapy-induced neutropenia is a critical concern in cancer treatment, and mouse and rat models provide valuable platforms for studying drug-induced hematopoietic toxicity. These models enable precise control over drug exposure and dose, facilitating the development of supportive therapies. Genetic neutropenias, often associated with specific mutations, are investigated using murine and zebrafish models. These models allow researchers to replicate genetic conditions and explore potential therapeutic targets. Immune-mediated neutropenias, characterized by autoimmune responses against neutrophils, are studied in mice and non-human primates, providing insights into the immunopathological mechanisms involved and the testing of immunosuppressive interventions. Infection-induced neutropenia models, employing mice, zebrafish, and fruit flies, help elucidate host-pathogen interactions and the impact of infections on neutrophil production. By harnessing the strengths of these diverse animal models, scientists can deepen their understanding of neutropenia, advancing diagnostics and treatments for this clinically significant condition.
  • 377
  • 11 Oct 2023
Topic Review
MiR-223 as Diagnostic and Prognostic Markers in Cancer
MicroRNAs (miRNAs) are endogenous small non-coding RNAs that function in the regulation of gene expression and regulate a wide array of biological processes, including carcinogenesis. Several mechanisms are involved in miRNA-associated cancer development, such as amplification or deletion of miRNA genes, abnormal transcriptional control of miRNAs, dysregulated epigenetic changes, and defects in miRNA biogenesis machinery. MiRNA-223 has been found to be a critical miRNA that is involved in a wide range of molecular processes. It is involved in the regulation of inflammatory cytokines, epithelial homeostasis, immune checkpoint signaling pathways, apoptosis, cell cycle, cell proliferation, invasion, and chemosensitivity. Published literature has demonstrated that miRNA-223 expression is associated with cancer development and prevention. Mir-223 functions as either a tumor suppressor or oncogene under certain circumstances, containing multiple targets or specific targets. Hence, miR-223 could be a potential candidate diagnostic biomarker, prognostic biomarker, or therapeutic target of cancer. 
  • 376
  • 28 Feb 2022
Topic Review
The Intricate Role of Non-Coding RNAs in DIC
Disseminated Intravascular Coagulation (DIC) is a type of tissue and organ dysregulation in sepsis, due mainly to the effect of the inflammation on the coagulation system. MicroRNAs, long non-coding RNAs, and circular RNAs are studied in relation to DIC. Specifically, the axis between these non-coding RNAs and the corresponding affected pathway has been identified, including inflammation, alteration of the coagulation cascade, and endothelial damage. 
  • 376
  • 23 Feb 2023
Topic Review
Extracellular Vesicles in Triple-Negative Breast Cancer
Triple-negative breast cancer (TNBC) is the most aggressive and refractory subtype of breast cancer, often occurring in younger patients with poor clinical prognosis. Given the current lack of specific targets for effective intervention, the development of better treatment strategies remains an unmet medical need. Over the last decade, the field of extracellular vesicles (EVs) has grown tremendously, offering immense potential for clinical diagnosis/prognosis and therapeutic applications. While TNBC-EVs have been shown to play an important role in tumorigenesis, chemoresistance and metastasis, they could be repurposed as potential biomarkers for TNBC diagnosis and prognosis. 
  • 375
  • 29 Mar 2022
Topic Review
Natural Killer Cells in Myelodysplastic Syndrome
Myelodysplastic syndrome (MDS) treatment remains a big challenge due to the heterogeneous nature of the disease and its ability to progress to acute myeloid leukemia (AML). The only curative option is allogeneic hematopoietic stem cell transplantation (HSCT), but most patients are unfit for this procedure and are left with only palliative treatment options, causing a big unmet need in the context of this disease. Natural killer (NK) cells are attractive candidates for MDS immunotherapy due to their ability to target myeloid leukemic cells without prior sensitization.
  • 375
  • 28 Feb 2023
Topic Review
The Purinergic Landscape of Non-Small Cell Lung Cancer
Lung cancer (LC) is the most prevalent cancer worldwide, with an estimated 2.1 million new cases and 1.8 million related deaths annually. More than 70% of LC patients are diagnosed at an advanced stage, with a 5-year survival rate of less than 10%, whereas the survival rate for patients with early-stage disease ranges from 50 to 70%. Adenosine triphosphate (ATP) and adenosine are components of the tumor microenvironment (TME). Extracellular ATP (eATP) promotes tumor growth but also immune-mediated tumor eradication, mainly via the well-documented purinergic P2RX7 receptor. Adenosine, on the other hand, is generated from eATP via the ectonucleotidases CD39 and CD73 and is an immunosuppressant that acts at the A2A receptor (A2AR) level.
  • 372
  • 22 Apr 2022
Topic Review
The Neonatal Immune System
The immune system is a complex network of cells and signals which regulate the host’s response to self and foreign antigens. This delicate system requires substantial regulation to prevent severe damage to the host but is also balanced against the potential damage that could be inflicted if a response is not generated. Thus, responses are primarily dependent on the needs of the hosts and the nature of the signal. In the case of immune stimulation by pathogens, the primary goal of the immune system is to mediate clearance of the pathogen while minimizing damage inflicted to the host by the immune response itself. The adult immune system, which is better studied and understood than is the neonatal one, efficiently generates pro-inflammatory responses which mediate the efficient control of most pathogens. The neonatal immune system, however, is evolved to respond to the unique challenges of the rapid transition from the near-sterile womb to the microbe-rich world beyond. This suddenly introduces millions of new antigens for potential immune recognition and response, a seemingly impossible feat. Therefore, during this transition from near-sterile-fetal to microbe-rich neonatal environment, the immune system is evolved to respond to novel antigens primarily with anti-inflammatory TH2 responses to prevent unnecessary inflammation which can severely harm the infant.
  • 372
  • 29 Jun 2023
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