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Frontiers in Immunology 2023Brain metastases (BMs) are the most common form of intracranial malignant neoplasms in adults, with a profound impact on quality of life and traditionally associated... (Review)
Review
Brain metastases (BMs) are the most common form of intracranial malignant neoplasms in adults, with a profound impact on quality of life and traditionally associated with a dismal prognosis. Lung cancer accounts for approximately 40%-50% of BM across different tumors. The process leading to BMs is complex and includes local invasion, intravasation, tumor cells circulation into the bloodstream, disruption of the blood-brain barrier, extravasation of tumor cells into the brain parenchyma, and interaction with cells of the brain microenvironment, among others. Once the tumor cells have seeded in the brain parenchyma, they encounter different glial cells of the brain, as well as immune cells. The interaction between these cells and tumor cells is complex and is associated with both antitumoral and protumoral effects. To overcome the lethal prognosis associated with BMs, different treatment strategies have been developed, such as immunotherapy with immune checkpoint inhibitors, particularly inhibitors of the PD-1/PD-L1 axis, which have demonstrated to be an effective treatment in both non-small cell lung cancer and small cell lung cancer. These antibodies have shown to be effective in the treatment of BM, alone or in combination with chemotherapy or radiotherapy. However, many unsolved questions remain to be answered, such as the sequencing of immunotherapy and radiotherapy, the optimal management in symptomatic BMs, the role of the addition of anti-CTLA-4 antibodies, and so forth. The complexity in the management of BMs in the era of immunotherapy requires a multidisciplinary approach to adequately treat this devastating event. The aim of this review is to summarize evidence regarding epidemiology of BM, its pathophysiology, current approach to treatment strategies, as well as future perspectives.
Topics: Adult; Humans; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Quality of Life; Immunotherapy; Brain Neoplasms; Tumor Microenvironment
PubMed: 37876939
DOI: 10.3389/fimmu.2023.1221097 -
Frontiers in Psychiatry 2023Numerous studies have now implicated a role for inflammation in schizophrenia. However, many aspects surrounding this aspect of the disease are still controversial. This... (Review)
Review
Numerous studies have now implicated a role for inflammation in schizophrenia. However, many aspects surrounding this aspect of the disease are still controversial. This controversy has been driven by conflicting evidence on the role of both pro-and anti-inflammatory factors and by often contentious findings concerning cytokine and immune cell profiles in the central nervous system and periphery. Current evidence supports the point that interleukin-6 is elevated in CSF, but does not support activation of microglia, resident macrophage-like cells in the brain. Furthermore, the mechanisms involving transit of the peripheral immune system factors across the blood brain barrier to central parenchyma have still not been completely elucidated. This process appears to involve perivascular macrophages and accompanying dendritic cells retained in the parenchyma by the chemokine and cytokine composition of the surrounding milieu. In addition, a number of studies have shown that this can be modulated by infection with viruses such as herpes simplex virus type I which may disrupt antigen presentation in the perivascular space, with long-lasting consequences. In this review article, we discuss the role of inflammation and viral infection as potential disease modifiers in schizophrenia. The primary viral hit may occur in the fetus , transforming the immune response regulatory T-cells or the virus may secondarily remain latent in immune cells or neurons and modify further immune responses in the developing individual. It is hoped that unraveling this pathway further and solidifying our understanding of the pathophysiological mechanisms involved will pave the way for future studies aimed at identification and implementation of new biomarkers and drug targets. This may facilitate the development of more effective personalized therapies for individuals suffering with schizophrenia.
PubMed: 37850104
DOI: 10.3389/fpsyt.2023.1231750 -
Journal of Tissue Engineering 2024The selective permeability of the blood-brain barrier (BBB) enables the necessary exchange of substances between the brain parenchyma and circulating blood and is... (Review)
Review
The selective permeability of the blood-brain barrier (BBB) enables the necessary exchange of substances between the brain parenchyma and circulating blood and is important for the normal functioning of the central nervous system. Ischemic stroke inflicts damage upon the BBB, triggering adverse stroke outcomes such as cerebral edema, hemorrhagic transformation, and aggravated neuroinflammation. Therefore, effective repair of the damaged BBB after stroke and neovascularization that allows for the unique selective transfer of substances from the BBB after stroke is necessary and important for the recovery of brain function. This review focuses on four important therapies that have effects of BBB tissue repair after stroke in the last seven years. Most of these new therapies show increased expression of BBB tight-junction proteins, and some show beneficial results in terms of enhanced pericyte coverage at the injured vessels. This review also briefly outlines three effective classes of approaches and their mechanisms for promoting neoangiogenesis following a stroke.
PubMed: 38304736
DOI: 10.1177/20417314241226551 -
International Journal of Molecular... Apr 2024Although the CNS has been considered for a long time an immune-privileged organ, it is now well known that both the parenchyma and non-parenchymal tissue (meninges,... (Review)
Review
Although the CNS has been considered for a long time an immune-privileged organ, it is now well known that both the parenchyma and non-parenchymal tissue (meninges, perivascular space, and choroid plexus) are richly populated in resident immune cells. The advent of more powerful tools for multiplex immunophenotyping, such as single-cell RNA sequencing technique and upscale multiparametric flow and mass spectrometry, helped in discriminating between resident and infiltrating cells and, above all, the different spectrum of phenotypes distinguishing border-associated macrophages. Here, we focus our attention on resident innate immune players and their primary role in both CNS homeostasis and pathological neuroinflammation and neurodegeneration, two key interconnected aspects of the immunopathology of multiple sclerosis.
Topics: Immunity, Innate; Humans; Homeostasis; Animals; Central Nervous System; Multiple Sclerosis; Macrophages; Microglia
PubMed: 38732082
DOI: 10.3390/ijms25094865 -
Biomedicines Oct 2023Pancreatic adenocarcinoma (PDAC) is well known for its poor survival time. Clinical symptoms are painless jaundice or abdominal or back pain. Less specific symptoms... (Review)
Review
Pancreatic adenocarcinoma (PDAC) is well known for its poor survival time. Clinical symptoms are painless jaundice or abdominal or back pain. Less specific symptoms often appear that make diagnosis difficult, e.g., weight loss, loss of appetite, nausea and vomiting, and general weakness. Only 10-20% of patients are diagnosed at an early stage. A cure is practically only possible with a radical surgical operation. In the case of locally advanced findings, neoadjuvant therapy is administered. Among the therapeutic options offered are chemotherapy, radiotherapy (including stereotactic radiotherapy-SBRT), targeted treatment, or immunotherapy. In the case of metastatic disease, of which more than half are present at diagnosis, the goal is to relieve the patient of problems. Metastatic PDAC can cause problems arising from the localization of distant metastases, but it also locally affects the organs it infiltrates. In our review article, we focus on the largest group of patients, those with locally advanced disease and metastatic disease-symptoms related to the infiltration or destruction of the pancreatic parenchyma and the growth of the tumor into the surrounding. Therefore, we deal with biliary or duodenal obstruction, gastric outlet syndrome, bleeding and thromboembolic diseases, pain, depression, and fatigue, as well as pancreatic exocrine insufficiency and malnutrition. Metastatic spread is most often to the liver, peritoneum, or lungs. The presented overview aims to offer current therapeutic options across disciplines. In accordance with modern oncology, a multidisciplinary approach with a procedure tailored to the specific patient remains the gold standard.
PubMed: 37893064
DOI: 10.3390/biomedicines11102690 -
Metabolites Jan 2024Ecological theories suggest that environmental factors significantly influence obesity risk and related syndemic morbidities, including metabolically abnormal obesity... (Review)
Review
Ecological theories suggest that environmental factors significantly influence obesity risk and related syndemic morbidities, including metabolically abnormal obesity associated with nonalcoholic fatty liver disease (MASLD). These factors encompass anthropogenic influences and endocrine-disrupting chemicals (EDCs), synergistically interacting to induce metabolic discrepancies, notably in early life, and disrupt metabolic processes in adulthood. This review focuses on endocrine disruptors affecting a child's MASLD risk, independent of their role as obesogens and thus regardless of their impact on adipogenesis. The liver plays a pivotal role in metabolic and detoxification processes, where various lipophilic endocrine-disrupting molecules accumulate in fatty liver parenchyma, exacerbating inflammation and functioning as new anthropogenics that perpetuate chronic low-grade inflammation, especially insulin resistance, crucial in the pathogenesis of MASLD.
PubMed: 38276306
DOI: 10.3390/metabo14010071 -
Frontiers in Immunology 2024The central nervous system (CNS) harbors its own special immune system composed of microglia in the parenchyma, CNS-associated macrophages (CAMs), dendritic cells,... (Review)
Review
The central nervous system (CNS) harbors its own special immune system composed of microglia in the parenchyma, CNS-associated macrophages (CAMs), dendritic cells, monocytes, and the barrier systems within the brain. Recently, advances in the immune cells in the CNS provided new insights to understand the development of tuberculous meningitis (TBM), which is the predominant form of () infection in the CNS and accompanied with high mortality and disability. The development of the CNS requires the protection of immune cells, including macrophages and microglia, during embryogenesis to ensure the accurate development of the CNS and immune response following pathogenic invasion. In this review, we summarize the current understanding on the CNS immune cells during the initiation and development of the TBM. We also explore the interactions of immune cells with the CNS in TBM. In the future, the combination of modern techniques should be applied to explore the role of immune cells of CNS in TBM.
Topics: Humans; Tuberculosis, Meningeal; Central Nervous System; Mycobacterium tuberculosis; Brain; Microglia
PubMed: 38361935
DOI: 10.3389/fimmu.2024.1326859