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Topic Review
Immune Responses Potentially Involved in Brucella-Induced Pregnancy Complications
Infection by Brucella species in pregnant animals and humans is associated with an increased risk of abortion, preterm birth, and transmission of the infection to the offspring. The pathogen has a marked tropism for the placenta and the pregnant uterus and has the ability to invade and replicate within cells of the maternal–fetal unit, including trophoblasts and decidual cells. Placentitis is a common finding in infected pregnant animals. Several proinflammatory factors have been found to be increased in both the placenta of Brucella-infected animals and in trophoblasts or decidual cells infected in vitro. As normal pregnancies require an anti-inflammatory placental environment during most of the gestational period, Brucella-induced placentitis is thought to be associated with the obstetric complications of brucellosis.
  • 540
  • 22 Jan 2024
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.
  • 539
  • 02 Aug 2023
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. 
  • 539
  • 07 Oct 2023
Topic Review
Crosstalk between ILC3s and Microbiota
In recent years, growing evidence has suggested that the gut microbiome can significantly influence antitumor immunity, both within and outside the gastrointestinal tract, thereby affecting the efficacy of immune checkpoint inhibitors (ICIs). A link between microbiota composition and response to ICIs has been reported in both mouse and human studies. Gut microbial features depend on a delicate balance of tolerance for commensal microbiota and defense against various potentially pathogenic microbiota orchestrated by host immune system. Type 3 innate lymphoid cells (ILC3s) are a group of tissue-resident innate lymphocytes related to host immune cell–microbiome interactions. They orchestrate immunity, inflammation and tolerance in the intestines and any alterations in their functions can cause gut inflammation, colon cancer and immunotherapy resistance.
  • 536
  • 05 Sep 2023
Topic Review
Alcohol-Induced Liver Injury in Brief
Alcoholic liver disease (ALD) is a global health concern, representing a spectrum of liver disorders resulting from chronic alcohol consumption. To decipher the intricate mechanisms underlying ALD and develop effective therapies, researchers have turned to experimental models. Among these, the alcohol-induced liver injury model, accomplished through chronic alcohol administration to animals, has been pivotal in elucidating key pathophysiological aspects of ALD. This research navigates through the methodologies employed to induce liver injury, highlights the diverse pathological features observed, explores the underlying mechanisms, and discusses the model's relevance in advancing our understanding of ALD. Additionally, it delves into the multifaceted applications of this model in the quest for novel therapeutic strategies to combat ALD.
  • 533
  • 08 Oct 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. 
  • 528
  • 19 Dec 2023
Topic Review
miRNAs Released by Osteoclasts
Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation, pain, and ultimately, bone erosion of the joints. The causes of this disease are multifactorial, including genetic factors, such as the presence of the human leukocyte antigen (HLA)-DRB1*04 variant, alterations in the microbiota, or immune factors including increased cytotoxic T lymphocytes (CTLs), neutrophils, or elevated M1 macrophages which, taken together, produce high levels of pro-inflammatory cytokines. The function exerted by osteoclasts on osteoblasts and other osteoclasts by means of the release of exosomal microRNAs (miRNAs) was focused on. Based on a thorough revision, researchers classified these molecules into three categories according to their function: osteoclast inhibitors (miR-23a, miR-29b, and miR-214), osteoblast inhibitors (miR-22-3p, miR-26a, miR-27a, miR-29a, miR-125b, and miR-146a), and osteoblast enhancers (miR-20a, miR-34a, miR-96, miR-106a, miR-142, miR-199a, miR-324, and miR-486b). 
  • 528
  • 20 Feb 2024
Topic Review
Exploitation of Neutrophil Functions to Combat Disease
Neutrophils are crucial innate immune cells and comprise 50–70% of the white blood cell population under homeostatic conditions. Upon infection and in cancer, blood neutrophil numbers significantly increase because of the secretion of various chemo- and cytokines by, e.g., leukocytes, pericytes, fibroblasts and endothelial cells present in the inflamed tissue or in the tumor microenvironment (TME). The function of neutrophils in cancer has recently gained considerable attention, as they can exert both pro- and anti-tumorigenic functions, dependent on the cytokine milieu present in the TME. Here, several promising therapeutic options are addressed, such as cytokine therapy, immunocytokines and immunotherapy, which aim to exploit the anti-tumorigenic potential of neutrophils in cancer treatment or block excessive neutrophil-mediated inflammation in autoimmune diseases.
  • 526
  • 16 Aug 2023
Topic Review
T Cell Response to SARS-CoV-2 Coinfection and Comorbidities
COVID-19 has become an increasing global health issue. Adaptive immune cells, especially T cells, have been extensively investigated in regard to SARS-CoV-2 infection. However, human health and T cell responses are also impacted by many other pathogens and chronic diseases.
  • 524
  • 22 Feb 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.
  • 522
  • 22 Jan 2024
Topic Review
Long COVID in Older Adults
As time has passed following the COVID-19 pandemic, individuals infected with SARS-CoV-2 have gradually exhibited a variety of symptoms associated with long COVID in the postacute phase of infection. Simultaneously, in many countries worldwide, the process of population aging has been accelerating.
  • 520
  • 14 Nov 2023
Topic Review
Anakinra Therapy for Deficiency of Interleukin-1 Receptor Antagonist
Deficiency of interleukin-1 receptor antagonist (DIRA) is a rare life-threatening autosomal recessive autoinflammatory disease with symptoms including but not limited to osteomyelitis, periostitis, and systemic inflammation. DIRA is developed from the loss-of-function biallelic mutations of the IL1RN gene that encodes IL-1 receptor antagonist (IL-1RA), leading to the unchecked pro-inflammatory signaling and subsequent systemic inflammation. 
  • 516
  • 01 Mar 2024
Topic Review
CD123 in Blastic Plasmacytoid Dendritic Cell Neoplasm
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic cancer originating from the malignant transformation of plasmacytoid dendritic cell precursors. The exploration of combinations such as CD123-targeted immunotherapies with azacitidine and venetoclax is suggested to enhance antineoplastic responses and improve survival rates in BPDCN patients.
  • 513
  • 30 Jan 2024
Topic Review
Functional T-Cell Changes with Aging, CMV Influence
Cytomegalovirus (CMV) latent infection and aging contribute to alterations in the function and phenotype of the T-cell pool. Researchers have demonstrated that CMV-seropositivity is associated with the expansion of polyfunctional CD57+ T-cells in young and middle-aged individuals in response to different stimuli. Researchers expand their results on the effects of age and CMV infection on T-cell functionality in a cohort of healthy middle-aged and older individuals stratified by CMV serostatus. Specifically, researchers studied the polyfunctional responses (degranulation, IFN-γ and TNF-α production) of CD4+, CD8+, CD8+CD56+ (NKT-like), and CD4-CD8- (DN) T-cells according to CD57 expression in response to Staphylococcal Enterotoxin B (SEB). 
  • 512
  • 20 Dec 2023
Topic Review
Role of Neutrophils in Immune-Related Diseases
Neutrophils are the most abundant of the circulating immune cells and are the first to be recruited to sites of inflammation. Neutrophils are a heterogeneous group of immune cells from which are derived extracellular traps (NETs), reactive oxygen species, cytokines, chemokines, immunomodulatory factors, and alarmins that regulate the recruitment and phenotypes of neutrophils, macrophages, dendritic cells, T cells, and B cells. In addition, cytokine-stimulated neutrophils can express class II major histocompatibility complex and the internal machinery necessary for successful antigen presentation to memory CD4+ T cells. This may be relevant in the context of vaccine memory. Neutrophils thus emerge as orchestrators of immune responses that play a key role in determining the outcome of infections, vaccine efficacy, and chronic diseases like autoimmunity and cancer.
  • 512
  • 09 Jan 2024
Topic Review
Antimicrobial Peptides in the Nervous System
Antimicrobial peptides (AMPs) are short, mainly positively charged, amphipathic molecules. AMPs are important effectors of the immune response in insects with a broad spectrum of antibacterial, antifungal, and antiparasitic activity. In addition to these well-known roles, AMPs exhibit many other, often unobvious, functions in the host.
  • 511
  • 31 Mar 2023
Topic Review
Host Immune Responses to Clostridioides difficile Infection
Clostridioides difficile infection (CDI) is a leading nosocomial infection, posing a substantial public health challenge within the United States and globally. C. difficile releases toxins, which damage large intestinal epithelium, leading to toxic megacolon, sepsis, and even death.
  • 509
  • 07 Feb 2024
Topic Review
Roles of Myeloid-Derived Suppressor Cells in Liver Disease
Liver disease-related mortality is a major cause of death worldwide. Hepatic innate and adaptive immune cells play diverse roles in liver homeostasis and disease. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells. MDSCs can be broadly divided into monocytic MDSCs and polymorphonuclear or granulocytic MDSCs, and they functionally interact with both liver parenchymal and nonparenchymal cells, such as hepatocytes and regulatory T cells, to impact liver disease progression. The infiltration and activation of MDSCs in liver disease can be regulated by inflammatory chemokines and cytokines, tumor-associated fibroblasts, epigenetic regulation factors, and gut microbiota during liver injury and cancer.
  • 508
  • 31 Jan 2024
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. 
  • 502
  • 19 Jan 2024
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.
  • 501
  • 08 Aug 2023
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