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Topic Review
Earlier Studies of Zanubrutinib in Chronic Lymphocytic Leukemia
Due to improved selectivity and favorable toxicity profiles, the next-generation Bruton’s tyrosine kinase inhibitors (BTKis) are replacing ibrutinib in the treatment of B-cell malignancies including chronic lymphocytic leukemia (CLL). While efficacy between different BTKi agents is probably similar, there are important differences in toxicity profiles (including lower incidences of cardiovascular complications) that favor the choice of second-generation BTKis such as zanubrutinib.
  • 300
  • 08 Aug 2023
Topic Review
Oxazolone-Induced Colitis in Brief
Inflammatory bowel disease (IBD) represents a complex and debilitating group of disorders that include Crohn's disease and ulcerative colitis. Understanding the pathogenesis and developing effective treatments for IBD necessitate reliable experimental models. Oxazolone-induced colitis is one such model that has contributed significantly to our understanding of mucosal immune responses and potential therapeutic interventions. This research explores the utility of the oxazolone-induced colitis model, covering its induction methods, histopathological features, immune responses, and applications in drug development. While this model offers valuable insights into IBD, it also presents certain limitations that must be considered. By providing an in-depth analysis of oxazolone-induced colitis, this research highlights its significance in advancing IBD research and the quest for improved therapies.
  • 299
  • 08 Oct 2023
Topic Review
Mitochondrial Impairment in the Cardiorenal Syndrome Type 4
Cardiorenal syndrome type 4 (CRS type 4) occurs when chronic kidney disease (CKD) leads to cardiovascular damage, resulting in high morbidity and mortality rates. Mitochondria, vital organelles responsible for essential cellular functions, can become dysfunctional in CKD. This dysfunction can trigger inflammatory responses in distant organs by releasing Damage-associated molecular patterns (DAMPs). These DAMPs are recognized by immune receptors within cells, including Toll-like receptors (TLR) like TLR2, TLR4, and TLR9, the nucleotide-binding domain, leucine-rich-containing family pyrin domain-containing-3 (NLRP3) inflammasome, and the cyclic guanosine monophosphate (cGMP)–adenosine monophosphate (AMP) synthase (cGAS)–stimulator of interferon genes (cGAS-STING) pathway. Activation of these immune receptors leads to the increased expression of cytokines and chemokines. Excessive chemokine stimulation results in the recruitment of inflammatory cells into tissues, causing chronic damage. Experimental studies have demonstrated that chemokines are upregulated in the heart during CKD, contributing to CRS type 4. 
  • 299
  • 19 Jan 2024
Topic Review
Targets on Astrocytes for the Treatment of ALS
Astrocytes, the most numerous and giant glial cells in the central nervous system (CNS), possess the unique ability to divide and proliferate throughout life. The cytosol of astrocytes exhibits a distinctive star-shaped morphology, housing a critical structural component known as the glial filament. Comprised of glial fibrillary acidic protein (GFAP), this intermediate filament is essential to the cytoskeleton and serves as a standard marker for astrocytes. Importantly, it is not entirely exclusive to astrocytes but also labels neural stem cells. Apart from organizing the blood–brain barrier (BBB) and supporting, sequestering, and isolating neurons, these cells perform a multitude of vital biological functions. These include the metabolism, synthesis, and secretion of neurotrophic factors, regulation of neurotransmitters and calcium homeostasis, maintenance of mitochondrial function, participation in nervous system and circuit development, and regulation of the immune status of the CNS. However, these functions are partially or wholly lost in reactive astrocytes. Amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by the degeneration of upper and lower motor neurons (MNs), with an average survival of 3–5 years.
  • 298
  • 18 Feb 2024
Topic Review
Precision Vaccinology Approaches for Adjuvanted Vaccines
Infection persists as one of the leading global causes of morbidity and mortality, with particular burden at the extremes of age and in populations who are immunocompromised or suffer chronic co-morbid diseases. By focusing discovery and innovation efforts to better understand the phenotypic and mechanistic differences in the immune systems of diverse vulnerable populations, emerging research in precision vaccine discovery and development has explored how to optimize immunizations across the lifespan. 
  • 296
  • 07 Oct 2023
Topic Review
Complement Dysregulation in Glaucoma Patients
Glaucoma is a progressive neurodegenerative disease characterized by damage to the optic nerve that results in irreversible vision loss. While the exact pathology of glaucoma is not well understood, emerging evidence suggests that dysregulation of the complement system, a key component of innate immunity, plays a crucial role. In glaucoma, dysregulation of the complement cascade and impaired regulation of complement factors contribute to chronic inflammation and neurodegeneration.
  • 294
  • 04 Mar 2024
Topic Review
Natural Killer Cells in Brief
Natural Killer (NK) cells are innate immune cells that play a multifaceted role in immune surveillance, host defense, and immune regulation. This research explores the fascinating world of NK cells, encompassing their discovery, classification, mechanisms of recognition, activation, and effector functions. 
  • 293
  • 08 Oct 2023
Topic Review
P2RX7
P2RX7 belongs to the family of P2X receptors that are assembled and active when in their trimeric form. Each monomer is composed of two transmembrane domains that are connected by a large extracellular loop, and an N- and C- termini domain located intracellularly. However, unlike other members, P2RX7 has a long intracellular C-terminal domain that structurally distinguishes it from the others and confers its unique biological activities. Even though all seven members of the P2X receptors recognize eATP, they are activated with various affinities that range from 0.5 µM for P2RX3 to over 100 µM for P2RX7. Thus, activation of P2RX7 requires high levels of eATP, levels that are found in the tumor microenvironment (TME) which controls the three main activities of the receptor: cationic exchange, macropore opening and NLRP3 inflammasome activation.
  • 292
  • 09 Jun 2023
Topic Review
The Roles of MicroRNAs in Asthma
Asthma is one of the most common chronic non-communicable diseases worldwide, characterized by variable airflow limitation secondary to airway narrowing, airway wall thickening, and increased mucus resulting from chronic inflammation and airway remodeling. Current epidemiological studies reported that hypovitaminosis D is frequent in patients with asthma and is associated with worsening the disease and that supplementation with vitamin D3 improves asthma symptoms. However, despite several advances in the field, the molecular mechanisms of asthma have yet to be comprehensively understood. MicroRNAs play an important role in controlling several biological processes and their deregulation is implicated in diverse diseases, including asthma.
  • 292
  • 31 Jan 2024
Topic Review
Regulation of PD-L1 Expression by Nuclear Receptors
The suppression of excessive immune responses is necessary to prevent injury to the body, but it also allows cancer cells to escape immune responses and proliferate. Programmed cell death 1 (PD-1) is a co-inhibitory molecule that is present on T cells and is the receptor for programmed cell death ligand 1 (PD-L1). The binding of PD-1 to PD-L1 leads to the inhibition of the T cell receptor signaling cascade. PD-L1 has been found to be expressed in many types of cancers, such as lung, ovarian, and breast cancer, as well as glioblastoma. Furthermore, PD-L1 mRNA is widely expressed in normal peripheral tissues including the heart, skeletal muscle, placenta, lungs, thymus, spleen, kidney, and liver. The expression of PD-L1 is upregulated by proinflammatory cytokines and growth factors via a number of transcription factors. In addition, various nuclear receptors, such as androgen receptor, estrogen receptor, peroxisome-proliferator-activated receptor γ, and retinoic-acid-related orphan receptor γ, also regulate the expression of PD-L1. 
  • 289
  • 20 Jun 2023
Topic Review
Interleukin-1Beta Signalin in Non-Small Cell Lung Cancer
Targeted therapies for solid tumors, including non-small cell lung cancer (NSCLC), have advanced significantly, offering tailored treatment options for patients. However, individuals without targetable mutations pose a clinical challenge, as they may not respond to standard treatments like immune-checkpoint inhibitors (ICIs) and novel targeted therapies; further, there is an unmet need to identify prognostic biomarkers of response to treatment. Inflammatory cytokines such as interleukin-1 beta (IL-1β) have emerged as a key area of focus and hold significant potential implications for future clinical practice. Combinatorial approaches of IL-1β inhibitors and ICIs may provide a potential therapeutic modality for NSCLC patients without targetable mutations and offer insight into the continued search for prognostic biomarkers.
  • 288
  • 02 Aug 2023
Topic Review
Allergenic and Anti-Allergenic Antibodies in Food Allergy
Food allergies are a growing public health concern worldwide, especially in children and young adults. Allergen-specific IgE plays a central role in the pathogenesis of food allergies, but their titers poorly correlate with allergy development. Host immune systems yield allergen-specific immunoglobulin (Ig)A, IgE and IgG subclasses with low or high affinities and differential Fc N-glycosylation patterns that can affect the allergic reaction to food in multiple ways. High-affinity IgE is required to induce strong mast cell activation eventually leading to allergic anaphylaxis, while low-affinity IgE can even inhibit the development of clinically relevant allergic symptoms. IgA and IgG antibodies can inhibit IgE-mediated mast cell activation through various mechanisms, thereby protecting IgE-positive individuals from allergy development. The production of IgE and IgG with differential allergenic potential seems to be affected by the signaling strength of individual B cell receptors, and by cytokines from T cells. 
  • 287
  • 19 Dec 2023
Topic Review
Immunity and Metabolism in Aortic Dissection
Aortic dissection (AD) is a cardiovascular disease that seriously endangers the lives of patients. The mortality rate of this disease is high, and the incidence is increasing annually, but the pathogenesis of AD is complicated. In recent years, an increasing number of studies have shown that immune cell infiltration in the media and adventitia of the aorta is a novel hallmark of AD. These cells contribute to changes in the immune microenvironment, which can affect their own metabolism and that of parenchymal cells in the aortic wall, which are essential factors that induce degeneration and remodeling of the vascular wall and play important roles in the formation and development of AD.
  • 287
  • 09 May 2024
Topic Review
Immune Stimulation Mechanism of Aluminum Phosphate
Aluminum phosphate is a compound of hydroxy-aluminum phosphate, similar to aluminum hydroxide, and the hydroxyl group on its surface can also lose or gain protons under different pH conditions, thus changing the surface charge. Aluminum phosphate can reduce the effective dose for inducing protective immune response against Lactobacillus mexicana of plasmid DNA.
  • 286
  • 29 Jun 2023
Topic Review
Models of Protective Immunity against Schistosomes
A schistosome vaccine still looks to be a distant prospect. These helminths can live in the human bloodstream for years, even decades, surrounded by and feeding on the components of the immune response they provoke. The original idea of a vaccine based on the killing of invading cercariae in the skin has proven to be illusory. There has also been a realisation that even if humans develop some protection against infection over a protracted period, it very likely involves IgE-mediated responses that cannot provide the basis for a vaccine. However, it has also become clear that both invasive migrating larvae and adult worms must expose proteins and release secretions into the host environment as part of their normal biological activities. These antigens are now the focus of current vaccine developments.
  • 286
  • 13 Nov 2023
Topic Review
Inflammasomes in Inflammatory Diseases
Inflammasomes, a group of multiprotein complexes, are essential in regulating inflammation and immune responses. Several inflammasomes, including nucleotide-binding domain leucine-rich repeat-containing protein 1 (NLRP1), NLRP3, NLRP6, NLRP7, NLRP12, interferon-inducible protein 16 (IFI16), NOD-like receptor family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and pyrin, have been studied in various inflammatory diseases. Activating inflammasomes leads to the processing and production of proinflammatory cytokines, such as interleukin (IL)-1β and IL-18. The NLRP3 inflammasome is the most extensively studied and well characterized. Consequently, targeting inflammasomes (particularly NLRP3) with several compounds, including small molecule inhibitors and natural compounds, has been studied as a potential therapeutic strategy. 
  • 284
  • 17 Nov 2023
Topic Review
Trabectedin and Lurbinectedin in the Tumour Microenvironment
Trabectedin (TRB) and Lurbinectedin (LUR) are alkaloid compounds originally isolated from Ecteinascidia turbinata with proven antitumoral activity. Both molecules are structural analogues that differ on the tetrahydroisoquinoline moiety of the C subunit in TRB, which is replaced by a tetrahydro-β-carboline in LUR.
  • 281
  • 22 Jan 2024
Topic Review
Role of Complement System in Alzheimer’s Disease Pathogenesis
As an essential component of the innate immune system, the complement system is responsible for the defense against pathogens. The complement cascade has complex roles in the central nervous system (CNS), numerous reports have implicated the classical complement cascade in both brain development and decline. More specifically, complement dysfunction has been implicated in neurodegenerative disorders, such as Alzheimer’s disease (AD), which is the most common form of dementia. Synapse loss is one of the main pathological hallmarks of AD and correlates with memory impairment. 
  • 280
  • 18 Jan 2024
Topic Review
Regulatory TR3-56 Cells in Immune Activation and Regulation
The interplay between immune activation and immune regulation is a fundamental aspect of the functional harmony of the immune system. This delicate balance is essential to triggering correct and effective immune responses against pathogens while preventing excessive inflammation and the immunopathogenic mechanisms of autoimmunity. The knowledge of all the mechanisms involved in immune regulation is not yet definitive, and, probably, the overall picture is much broader than what has been described in the scientific literature so far. Given the plasticity of the immune system and the diversity of organisms, it is highly probable that numerous other cells and molecules are still to be ascribed to the immune regulation process. 
  • 278
  • 25 Dec 2023
Topic Review
Diseases with Potential Lectin Pathway Involvement
The complement system is the other major proteolytic cascade in the blood of vertebrates besides the coagulation-fibrinolytic system. Among the three main activation routes of complement, the lectin pathway (LP) has been discovered the latest, and it is still the subject of intense research. Uncontrolled complement activation can contribute to the progression of many diseases (e.g. stroke, kidney diseases, thrombotic complications, and COVID-19). In most cases the lectin pathway has also been implicated. 
  • 277
  • 31 Jan 2024
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