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Endocrine Reviews Jun 2020The past decade has seen several critical advances in our understanding of hypothalamic-pituitary-adrenal (HPA) axis regulation. Homeostatic physiological circuits need... (Review)
Review
The past decade has seen several critical advances in our understanding of hypothalamic-pituitary-adrenal (HPA) axis regulation. Homeostatic physiological circuits need to integrate multiple internal and external stimuli and provide a dynamic output appropriate for the response parameters of their target tissues. The HPA axis is an example of such a homeostatic system. Recent studies have shown that circadian rhythmicity of the major output of this system-the adrenal glucocorticoid hormones corticosterone in rodent and predominately cortisol in man-comprises varying amplitude pulses that exist due to a subhypothalamic pulse generator. Oscillating endogenous glucocorticoid signals interact with regulatory systems within individual parts of the axis including the adrenal gland itself, where a regulatory network can further modify the pulsatile release of hormone. The HPA axis output is in the form of a dynamic oscillating glucocorticoid signal that needs to be decoded at the cellular level. If the pulsatile signal is abolished by the administration of a long-acting synthetic glucocorticoid, the resulting disruption in physiological regulation has the potential to negatively impact many glucocorticoid-dependent bodily systems. Even subtle alterations to the dynamics of the system, during chronic stress or certain disease states, can potentially result in changes in functional output of multiple cells and tissues throughout the body, altering metabolic processes, behavior, affective state, and cognitive function in susceptible individuals. The recent development of a novel chronotherapy, which can deliver both circadian and ultradian patterns, provides great promise for patients on glucocorticoid treatment.
Topics: Adrenocorticotropic Hormone; Animals; Bodily Secretions; Circadian Rhythm; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Secretory Pathway
PubMed: 32060528
DOI: 10.1210/endrev/bnaa002 -
Indian Journal of Ophthalmology Apr 2023Dry eye disease (DED) is a commonly occurring, multifactorial disease characterized by reduced tear film stability and hyperosmolarity at the ocular surface, leading to... (Review)
Review
Dry eye disease (DED) is a commonly occurring, multifactorial disease characterized by reduced tear film stability and hyperosmolarity at the ocular surface, leading to discomfort and visual compromise. DED is driven by chronic inflammation and its pathogenesis involves multiple ocular surface structures such as the cornea, conjunctiva, lacrimal glands, and meibomian glands. The tear film secretion and its composition are regulated by the ocular surface in orchestration with the environment and bodily cues. Thus, any dysregulation in ocular surface homeostasis causes an increase in tear break-up time (TBUT), osmolarity changes, and reduction in tear film volume, all of which are indicators of DED. Tear film abnormalities are perpetuated by underlying inflammatory signaling and secretion of inflammatory factors, leading to the recruitment of immune cells and clinical pathology. Tear-soluble factors such as cytokines and chemokines are the best surrogate markers of disease severity and can also drive the altered profile of ocular surface cells contributing to the disease. Soluble factors can thus help in disease classification and planning treatment strategies. Our analysis suggests increased levels of cytokines namely interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-9, IL-12, IL-17A, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α); chemokines (CCL2, CCL3, CCL4, CXCL8); MMP-9, FGF, VEGF-A; soluble receptors (sICAM-1, sTNFR1), neurotrophic factors (NGF, substance P, serotonin) and IL1RA and reduced levels of IL-7, IL-17F, CXCL1, CXCL10, EGF and lactoferrin in DED. Due to the non-invasive sample collection and ease of quantitively measuring soluble factors, tears are one of the best-studied biological samples to molecularly stratify DED patients and monitor their response to therapy. In this review, we evaluate and summarize the soluble factors profiles in DED patients from the studies conducted over the past decade and across various patient groups and etiologies. The use of biomarker testing in clinical settings will aid in the advancement of personalized medicine and represents the next step in managing DED.
Topics: Humans; Dry Eye Syndromes; Tears; Cytokines; Chemokines; Biomarkers; Lacrimal Apparatus
PubMed: 37026250
DOI: 10.4103/IJO.IJO_2981_22 -
Revista Da Associacao Medica Brasileira... Sep 2016In the critical phase of immunological immaturity of the newborn, particularly for the immune system of mucous membranes, infants receive large amounts of bioactive... (Review)
Review
In the critical phase of immunological immaturity of the newborn, particularly for the immune system of mucous membranes, infants receive large amounts of bioactive components through colostrum and breast milk. Colostrum is the most potent natural immune booster known to science. Breastfeeding protects infants against infections mainly via secretory IgA (SIgA) antibodies, but also via other various bioactive factors. It is striking that the defense factors of human milk function without causing inflammation; some components are even anti-inflammatory. Protection against infections has been well evidenced during lactation against, e.g., acute and prolonged diarrhea, respiratory tract infections, including otitis media, urinary tract infection, neonatal septicemia, and necrotizing enterocolitis. The milk's immunity content changes over time. In the early stages of lactation, IgA, anti-inflammatory factors and, more likely, immunologically active cells provide additional support for the immature immune system of the neonate. After this period, breast milk continues to adapt extraordinarily to the infant's ontogeny and needs regarding immune protection and nutrition. The need to encourage breastfeeding is therefore justifiable, at least during the first 6 months of life, when the infant's secretory IgA production is insignificant.
Topics: Colostrum; Humans; Immune System; Milk, Human
PubMed: 27849237
DOI: 10.1590/1806-9282.62.06.584 -
International Journal of Molecular... Dec 2023Bacteria have existed on Earth for billions of years, exhibiting ubiquity and involvement in various biological activities. To ensure survival, bacteria usually release... (Review)
Review
Bacteria have existed on Earth for billions of years, exhibiting ubiquity and involvement in various biological activities. To ensure survival, bacteria usually release and secrete effector proteins to acquire nutrients and compete with other microorganisms for living space during long-term evolution. Consequently, bacteria have developed a range of secretion systems, which are complex macromolecular transport machines responsible for transporting proteins across the bacterial cell membranes. Among them, one particular secretion system that stands out from the rest is the type V secretion system (T5SS), known as the "autotransporter". Bacterial activities mediated by T5SS include adherence to host cells or the extracellular matrix, invasion of host cells, immune evasion and serum resistance, contact-dependent growth inhibition, cytotoxicity, intracellular flow, protease activity, autoaggregation, and biofilm formation. In a bacterial body, it is not enough to rely on T5SS alone; in most cases, T5SS cooperates with other secretion systems to carry out bacterial life activities, but regardless of how good the relationship is, there is friction between the secretion systems. T5SS and T1SS/T2SS/T3SS/T6SS all play a synergistic role in the pathogenic processes of bacteria, such as nutrient acquisition, pathogenicity enhancement, and immune modulation, but T5SS indirectly inhibits the function of T4SS. This could be considered a love-hate relationship between secretion systems. This paper uses the systematic literature review methodology to review 117 journal articles published within the period from 1995 to 2024, which are all available from the PubMed, Web of Science, and Scopus databases and aim to elucidate the link between T5SS and other secretion systems, providing clues for future prevention and control of bacterial diseases.
Topics: Type V Secretion Systems; Bacteria; Bodily Secretions; Cell Aggregation; Cell Membrane
PubMed: 38203452
DOI: 10.3390/ijms25010281 -
Frontiers in Immunology 2020Helminth-modulated macrophages contribute to attenuating inflammation in inflammatory bowel diseases. The programmed death 1 (PD-1) plays an important role in macrophage...
Helminth-modulated macrophages contribute to attenuating inflammation in inflammatory bowel diseases. The programmed death 1 (PD-1) plays an important role in macrophage polarization and is essential in the maintenance of immune system homeostasis. Here, we investigate the role of PD-1-mediated polarization of M2 macrophages and the protective effects of excretory/secretory products from adult worms (AES) on DSS-induced colitis in mice. Colitis in mice was induced by oral administration of dextran sodium sulfate (DSS) daily. Mice with DSS-induced colitis were treated with AES intraperitoneally, and pathological manifestations were evaluated. Macrophages in mice were depleted with liposomal clodronate. Markers for M1-type (iNOS, TNF-α) and M2-type (CD206, Arg-1) macrophages were detected by qRT-PCR and flow cytometry. Macrophage expression of PD-1 was quantified by flow cytometry; RAW 264.7 cells and peritoneal macrophages were used for tests, and PD-1 gene knockout mice were used for investigation of the role of PD-1 in AES-induced M2 macrophage polarization. Macrophage depletion was found to reduce DSS-induced colitis in mice. Treatment with AES significantly increased macrophage expression of CD206 and Arg-1 and simultaneously attenuated colitis severity. We found AES to enhance M2 macrophage polarization; these findings were confirmed studying cultures of RAW264.7 cells and peritoneal macrophages from mice. Further experimentation revealed that AES upregulated PD-1 expression, primarily on M2 macrophages expressing CD206. The AES-induced M2 polarization was found to be decreased in PD-1 deficient macrophages, and the therapeutic effects of AES on colitis was reduced in PD-1 knockout mice. In conclusion, the protective effects of AES on DSS-induced colitis were found to associate with PD-1 upregulation and M2 macrophage polarization. Thus, PD-1-mediated M2 macrophage polarization is a key mechanism of helminth-induced modulation of the host immune system.
Topics: Animals; Bodily Secretions; Cell Polarity; Colitis; Dextran Sulfate; Disease Models, Animal; Female; Gene Knockout Techniques; Macrophage Activation; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Programmed Cell Death 1 Receptor; RAW 264.7 Cells; Rats; Trichinella spiralis
PubMed: 33117347
DOI: 10.3389/fimmu.2020.563784 -
Mediators of Inflammation 2023Most patients diagnosed with chronic obstructive pulmonary disease (COPD) present with hallmark features of airway mucus hypersecretion, including cough and... (Review)
Review
Most patients diagnosed with chronic obstructive pulmonary disease (COPD) present with hallmark features of airway mucus hypersecretion, including cough and expectoration. Airway mucus function as a native immune system of the lung that severs to trap particulate matter and pathogens and allows them to clear from the lung via cough and ciliary transport. Chronic mucus hypersecretion (CMH) is the main factor contributing to the increased risk of morbidity and mortality in specific subsets of COPD patients. It is, therefore, primarily important to develop medications that suppress mucus hypersecretions in these patients. Although there have been some advances in COPD treatment, more work remains to be done to better understand the mechanism underlying airway mucus hypersecretion and seek more effective treatments. This review article discusses the structure and significance of mucus in the lungs focusing on gel-forming mucins and the impacts of CMH in the lungs. Furthermore, we summarize the article with pharmacological and nonpharmacological treatments as well as novel and interventional procedures to control CMH in COPD patients.
Topics: Humans; Cough; Pulmonary Disease, Chronic Obstructive; Mucus; Lung; Sputum
PubMed: 37457746
DOI: 10.1155/2023/8840594 -
Parasites & Vectors Jan 2022Apicomplexans are important pathogens that cause severe infections in humans and animals. The biology and pathogeneses of these parasites have shown that proteins are... (Review)
Review
Apicomplexans are important pathogens that cause severe infections in humans and animals. The biology and pathogeneses of these parasites have shown that proteins are intrinsically modulated during developmental transitions, physiological processes and disease progression. Also, proteins are integral components of parasite structural elements and organelles. Among apicomplexan parasites, Eimeria species are an important disease aetiology for economically important animals wherein identification and characterisation of proteins have been long-winded. Nonetheless, this review seeks to give a comprehensive overview of constitutively expressed Eimeria proteins. These molecules are discussed across developmental stages, organelles and sub-cellular components vis-à-vis their biological functions. In addition, hindsight and suggestions are offered with intention to summarise the existing trend of eimerian protein characterisation and to provide a baseline for future studies.
Topics: Animals; Antigens, Protozoan; Apicomplexa; Bodily Secretions; Chickens; Coccidiosis; Eimeria; Eimeria tenella; Genes, Protozoan; Host-Parasite Interactions; Humans; Membrane Proteins; Merozoites; Oocysts; Organelles; Peptide Hydrolases; Poultry Diseases; Protein Transport; Sporozoites
PubMed: 35073987
DOI: 10.1186/s13071-022-05159-0 -
Bone Research Aug 2023Proper regulation of Wnt signaling is critical for normal bone development and homeostasis. Mutations in several Wnt signaling components, which increase the activity of...
Proper regulation of Wnt signaling is critical for normal bone development and homeostasis. Mutations in several Wnt signaling components, which increase the activity of the pathway in the skeleton, cause high bone mass in human subjects and mouse models. Increased bone mass is often accompanied by severe headaches from increased intracranial pressure, which can lead to fatality and loss of vision or hearing due to the entrapment of cranial nerves. In addition, progressive forehead bossing and mandibular overgrowth occur in almost all subjects. Treatments that would provide symptomatic relief in these subjects are limited. Porcupine-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled receptor. Chemical inhibition of porcupine is a highly selective method of Wnt signaling inhibition. We treated three different mouse models of high bone mass caused by aberrant Wnt signaling, including homozygosity for loss-of-function in Sost, which models sclerosteosis, and two strains of mice carrying different point mutations in Lrp5 (equivalent to human G171V and A214V), at 3 months of age with porcupine inhibitors for 5-6 weeks. Treatment significantly reduced both trabecular and cortical bone mass in all three models. This demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.
Topics: Animals; Humans; Mice; Adaptor Proteins, Signal Transducing; Bodily Secretions; Disease Models, Animal; Gain of Function Mutation; Hyperostosis; Low Density Lipoprotein Receptor-Related Protein-5; Mutation
PubMed: 37612291
DOI: 10.1038/s41413-023-00278-5 -
International Journal of Molecular... Apr 2020Exosomes are extracellular vesicles (EV) of endosomal origin (multivesicular bodies, MVB) constitutively released by many different eukaryotic cells by fusion of MVB to... (Review)
Review
Exosomes are extracellular vesicles (EV) of endosomal origin (multivesicular bodies, MVB) constitutively released by many different eukaryotic cells by fusion of MVB to the plasma membrane. However, inducible exosome secretion controlled by cell surface receptors is restricted to very few cell types and a limited number of cell surface receptors. Among these, exosome secretion is induced in T lymphocytes and B lymphocytes when stimulated at the immune synapse (IS) via T-cell receptors (TCR) and B-cell receptors (BCR), respectively. IS formation by T and B lymphocytes constitutes a crucial event involved in antigen-specific, cellular, and humoral immune responses. Upon IS formation by T and B lymphocytes with antigen-presenting cells (APC), the convergence of MVB towards the microtubule organization center (MTOC), and MTOC polarization to the IS, are involved in polarized exosome secretion at the synaptic cleft. This specialized mechanism provides the immune system with a finely-tuned strategy to increase the specificity and efficiency of crucial secretory effector functions of B and T lymphocytes. As inducible exosome secretion by antigen-receptors is a critical and unique feature of the immune system this review considers the study of the traffic events leading to polarized exosome secretion at the IS and some of their biological consequences.
Topics: Animals; Antigen Presentation; Antigen-Presenting Cells; Antigens; B-Lymphocytes; Biological Transport; Bodily Secretions; Cell Communication; Exosomes; Humans; Immunological Synapses; Immunomodulation; Lymphocyte Activation; T-Lymphocytes
PubMed: 32290050
DOI: 10.3390/ijms21072631 -
Experimental Eye Research Oct 2017Meibum is a lipid-rich secretion that is produced by fully differentiated meibocytes in the holocrine Meibomian glands (MG) of humans and most mammals. The secretion is... (Review)
Review
Meibum is a lipid-rich secretion that is produced by fully differentiated meibocytes in the holocrine Meibomian glands (MG) of humans and most mammals. The secretion is a part of a defense mechanism that protects the ocular surface from hazardous environmental factors, and from desiccation. Meibomian lipids that have been identified in meibum are very diverse and unique in nature. The lipid composition of meibum is different from virtually any other lipid pool found in the human body. In fact, meibum is quite different from sebum, which is the closest secretion that is produced by anatomically, physiologically, and biochemically related sebaceous glands. However, meibum of mice have been shown to closely resemble that of humans, implying similar biosynthetic mechanisms in MG of both species. By analyzing available genomic, immunohistochemical, and lipidomic data, we have envisioned a unifying network of enzymatic reactions that are responsible for biosynthesis of meibum, which we call meibogenesis. Our current theory is based on an assumption that most of the biosynthetic reactions of meibogenesis are catalyzed by known enzymes. However, the main features that make meibum unique - the ratio of identified classes of lipids, the extreme length of its components, extensive ω-hydroxylation of fatty acids and alcohols, iso- and anteiso-branching of meibomian lipids (e.g. waxes), and the presence of rather unique complex lipids with several ester bonds - make it possible that either the activity of known enzymes is altered in MG, or some unknown enzymes contribute to the processes of meibogenesis, or both. Studies are in progress to elucidate meibogenesis on molecular level.
Topics: Bodily Secretions; Humans; Lipid Metabolism; Lipids; Meibomian Glands; Tears
PubMed: 28669846
DOI: 10.1016/j.exer.2017.06.020