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Cancer Treatment Reviews Feb 2018Chemokines are proteins which induce chemotaxis, promote differentiation of immune cells, and cause tissue extravasation. Given these properties, their role in... (Review)
Review
Chemokines are proteins which induce chemotaxis, promote differentiation of immune cells, and cause tissue extravasation. Given these properties, their role in anti-tumor immune response in the cancer environment is of great interest. Although immunotherapy has shown clinical benefit for some cancer patients, other patients do not respond. One of the mechanisms of resistance to checkpoint inhibitors may be chemokine signaling. The CXCL9, -10, -11/CXCR3 axis regulates immune cell migration, differentiation, and activation, leading to tumor suppression (paracrine axis). However, there are some reports that show involvements of this axis in tumor growth and metastasis (autocrine axis). Thus, a better understanding of CXCL9, -10, -11/CXCR3 axis is necessary to develop effective cancer control. In this article, we summarize recent evidence regarding CXCL9, CXCL10, CXCL11/CXCR3 axis in the immune system and discuss their potential role in cancer treatment.
Topics: Animals; Chemokine CXCL10; Chemokine CXCL11; Chemokine CXCL9; Humans; Lymphocyte Activation; Neoplasms; Receptors, CXCR3
PubMed: 29207310
DOI: 10.1016/j.ctrv.2017.11.007 -
Frontiers in Immunology 2021The gut-brain axis refers to the bidirectional communication between the gut and brain, and regulates intestinal homeostasis and the central nervous system neural... (Review)
Review
The gut-brain axis refers to the bidirectional communication between the gut and brain, and regulates intestinal homeostasis and the central nervous system neural networks and neuroendocrine, immune, and inflammatory pathways. The development of sequencing technology has evidenced the key regulatory role of the gut microbiota in several neurological disorders, including Parkinson's disease, Alzheimer's disease, and multiple sclerosis. Epilepsy is a complex disease with multiple risk factors that affect more than 50 million people worldwide; nearly 30% of patients with epilepsy cannot be controlled with drugs. Interestingly, patients with inflammatory bowel disease are more susceptible to epilepsy, and a ketogenic diet is an effective treatment for patients with intractable epilepsy. Based on these clinical facts, the role of the microbiome and the gut-brain axis in epilepsy cannot be ignored. In this review, we discuss the relationship between the gut microbiota and epilepsy, summarize the possible pathogenic mechanisms of epilepsy from the perspective of the microbiota gut-brain axis, and discuss novel therapies targeting the gut microbiota. A better understanding of the role of the microbiota in the gut-brain axis, especially the intestinal one, would help investigate the mechanism, diagnosis, prognosis evaluation, and treatment of intractable epilepsy.
Topics: Animals; Brain; Brain-Gut Axis; Epilepsy; Gastrointestinal Microbiome; Humans; Neuroimmunomodulation
PubMed: 34707612
DOI: 10.3389/fimmu.2021.742449 -
Biomedicine & Pharmacotherapy =... Jul 2022Approximately, one in three ischemic stroke survivors suffered from depression, namely, post-stroke depression (PSD). PSD affects functional rehabilitation and may lead... (Review)
Review
Approximately, one in three ischemic stroke survivors suffered from depression, namely, post-stroke depression (PSD). PSD affects functional rehabilitation and may lead to poor quality of life of patients. There are numerous explanations about the etiologies of PSD. Here, we speculated that PSD are likely to be the result of specific changes in brain pathology. We hypothesized that the stroke-induced hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis plays an important role in PSD. Stroke initiates a complex sequence of events in neuroendocrine system including HPA axis. The HPA axis is involved in the pathophysiology of depression, especially, the overactivity of the HPA axis occurs in major depressive disorder. This review summarizes the possible etiologies of PSD, focusing on the stroke-induced activation of HPA axis, mainly including the stress followed by severe brain damage and the proinflammatory cytokines release. The role of hyperactive of HPA axis in PSD was discussed in detail, which includes the role of high level corticotropin-releasing hormone in PSD, the effects of glucocorticoids on the alterations in specific brain structures, the expression of enzymes, excitotoxicity, the change in intestinal permeability, and the activation of microglia. The relationship between neuroendocrine regulation and inflammation was also described. Finally, the therapy of PSD by regulating HPA axis, neuroendocrine, and immunity was discussed briefly. Nevertheless, the change of HPA axis and the occurring of PSD maybe interact and promote on each other, and future investigations should explore this hypothesis in more depth.
Topics: Depression; Depressive Disorder, Major; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Quality of Life; Stroke
PubMed: 35643064
DOI: 10.1016/j.biopha.2022.113146 -
Progress in Neuro-psychopharmacology &... Aug 2020Accumulating evidence indicates that patients with severe mental disorders, including major depression, bipolar disorder and schizophrenia present with various... (Review)
Review
Accumulating evidence indicates that patients with severe mental disorders, including major depression, bipolar disorder and schizophrenia present with various alterations of the gut microbiota and increased intestinal permeability. In addition, the hypothalamic-pituitary-adrenal (HPA) axis dysregulation and subclinical inflammation have been reported in this group of patients. Although it has been found that the HPA axis dysregulation appears as a consequence of psychosocial stress, especially traumatic life events, the exact mechanisms of this observation remain unclear. Animal model studies have unraveled several mechanisms linking the gut microbiota with the HPA axis dysfunction. Indeed, the gut microbiota can activate the HPA axis through several mediators that cross the blood-brain barrier and include microbial antigens, cytokines and prostaglandins. There is also evidence that various microbial species can affect ileal corticosterone production that may impact the activity of the HPA axis. However, some metabolites released by various microbes, e.g., short-chain fatty acids, can attenuate the HPA axis response. Moreover, several bacteria release neurotransmitters that can directly interact with vagal afferents. It has been postulated that the HPA axis activation can impact the gut microbiota and intestinal permeability. In this article, we discuss various mechanisms linking the gut microbiota with the HPA axis activity and summarize current evidence for a cross-talk between the gut-brain axis and the HPA axis from studies of patients with mood and psychotic disorders. Finally, we show potential clinical implications that can arise from future studies investigating the HPA axis activity with respect to the gut microbiota in severe mental disorders.
Topics: Gastrointestinal Microbiome; Humans; Hypothalamo-Hypophyseal System; Mental Disorders; Pituitary-Adrenal System
PubMed: 32335265
DOI: 10.1016/j.pnpbp.2020.109951 -
World Journal of Gastroenterology Oct 2020The gut-brain axis is a bidirectional information interaction system between the central nervous system (CNS) and the gastrointestinal tract, in which gut microbiota... (Review)
Review
The gut-brain axis is a bidirectional information interaction system between the central nervous system (CNS) and the gastrointestinal tract, in which gut microbiota plays a key role. The gut microbiota forms a complex network with the enteric nervous system, the autonomic nervous system, and the neuroendocrine and neuroimmunity of the CNS, which is called the microbiota-gut-brain axis. Due to the close anatomical and functional interaction of the gut-liver axis, the microbiota-gut-liver-brain axis has attracted increased attention in recent years. The microbiota-gut-liver-brain axis mediates the occurrence and development of many diseases, and it offers a direction for the research of disease treatment. In this review, we mainly discuss the role of the gut microbiota in the irritable bowel syndrome, inflammatory bowel disease, functional dyspepsia, non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis and hepatic encephalopathy via the gut-liver-brain axis, and the focus is to clarify the potential mechanisms and treatment of digestive diseases based on the further understanding of the microbiota-gut- liver-brain axis.
Topics: Brain; Enteric Nervous System; Gastrointestinal Microbiome; Humans; Irritable Bowel Syndrome; Liver
PubMed: 33177790
DOI: 10.3748/wjg.v26.i40.6141 -
Brain Sciences Sep 2021The hypothalamic-pituitary-adrenal (HPA) axis is involved in the pathophysiology of many neuropsychiatric disorders. Increased HPA axis activity can be observed during... (Review)
Review
The hypothalamic-pituitary-adrenal (HPA) axis is involved in the pathophysiology of many neuropsychiatric disorders. Increased HPA axis activity can be observed during chronic stress, which plays a key role in the pathophysiology of depression. Overactivity of the HPA axis occurs in major depressive disorder (MDD), leading to cognitive dysfunction and reduced mood. There is also a correlation between the HPA axis activation and gut microbiota, which has a significant impact on the development of MDD. It is believed that the gut microbiota can influence the HPA axis function through the activity of cytokines, prostaglandins, or bacterial antigens of various microbial species. The activity of the HPA axis in schizophrenia varies and depends mainly on the severity of the disease. This review summarizes the involvement of the HPA axis in the pathogenesis of neuropsychiatric disorders, focusing on major depression and schizophrenia, and highlights a possible correlation between these conditions. Although many effective antidepressants are available, a large proportion of patients do not respond to initial treatment. This review also discusses new therapeutic strategies that affect the HPA axis, such as glucocorticoid receptor (GR) antagonists, vasopressin V1B receptor antagonists and non-psychoactive CB1 receptor agonists in depression and/or schizophrenia.
PubMed: 34679364
DOI: 10.3390/brainsci11101298 -
Neural Regeneration Research Mar 2024Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated. In the human body, the gut... (Review)
Review
Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated. In the human body, the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks. Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability. In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other. Here, we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis. We found that abnormal intestinal flora, the intestinal microenvironment, lung infection, chronic diseases, and mechanical ventilation can worsen the outcome of ischemic stroke. This review also introduces the influence of the brain on the gut and lungs after stroke, highlighting the bidirectional feedback effect among the gut, lungs, and brain.
PubMed: 37721279
DOI: 10.4103/1673-5374.380869 -
Annals of the Rheumatic Diseases May 2021MAXIMISE (Managing AXIal Manifestations in psorIatic arthritis with SEcukinumab) trial was designed to evaluate the efficacy of secukinumab in the management of axial... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
MAXIMISE (Managing AXIal Manifestations in psorIatic arthritis with SEcukinumab) trial was designed to evaluate the efficacy of secukinumab in the management of axial manifestations of psoriatic arthritis (PsA).
METHODS
This phase 3b, double-blind, placebo-controlled, multi-centre 52-week trial included patients (≥18 years) diagnosed with PsA and classified by ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria, with spinal pain Visual Analogue Score ≥40/100 and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4 despite use of at least two non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomised (1:1:1) to secukinumab 300 mg, secukinumab 150 mg or placebo weekly for 4 weeks and every 4 weeks thereafter. At week 12, placebo patients were re-randomised to secukinumab 300/150 mg. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society) response with secukinumab 300 mg at week 12.
RESULTS
Patients were randomly assigned; 167 to secukinumab 300 mg, 165 to secukinumab 150 mg and 166 to placebo. Secukinumab 300 mg and 150 mg significantly improved ASAS20 response versus placebo at week 12 (63% and 66% vs 31% placebo). The OR (95% CI) comparing secukinumab 300 mg and 150 mg versus placebo, using a logistic regression model after multiple imputation, was 3.8 (2.4 and 6.1) and 4.4 (2.7 and 7.0; p<0.0001).
CONCLUSIONS
Secukinumab 300 mg and 150 mg provided significant improvement in signs and symptoms of axial disease compared with placebo in patients with PsA and axial manifestations with inadequate response to NSAIDs.
TRIAL REGISTRATION NUMBER
NCT02721966.
Topics: Adult; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Psoriatic; Axis, Cervical Vertebra; Double-Blind Method; Female; Humans; Male; Middle Aged; Severity of Illness Index; Treatment Outcome
PubMed: 33334727
DOI: 10.1136/annrheumdis-2020-218808 -
Frontiers in Immunology 2023The female reproductive tract (FRT) and remote/versatile organs in the body share bidirectional communication. In this review, we discuss the framework of the "FRT-organ... (Review)
Review
The female reproductive tract (FRT) and remote/versatile organs in the body share bidirectional communication. In this review, we discuss the framework of the "FRT-organ axes." Each axis, namely, the vagina-gut axis, uterus-gut axis, ovary-gut axis, vagina-bladder axis, vagina-oral axis, uterus-oral axis, vagina-brain axis, uterus-brain axis, and vagina-joint axis, is comprehensively discussed separately. Each axis could be involved in the pathogenesis of not only gynecological diseases but also diseases occurring apart from the FRT. Although the microbiota is clearly a key player in the FRT-organ axes, more quantitative insight into the homeostasis of the microbiota could be provided by host function measurements rather than current microbe-centric approaches. Therefore, investigation of the FRT-organ axes would provide us with a multicentric approach, including immune, neural, endocrine, and metabolic aspects, for understanding the homeostatic mechanism of women's bodies. The framework of the FRT-organ axes could also provide insights into finding new therapeutic approaches to maintain women's health.
Topics: Female; Humans; Genitalia, Female; Uterus; Vagina; Ovary; Microbiota
PubMed: 36798125
DOI: 10.3389/fimmu.2023.1110001