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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 -
BioMed Research International 2018
Topics: Amylases; Animals; Humans; Proteomics; Saliva; Salivation
PubMed: 30046604
DOI: 10.1155/2018/7406312 -
Nature Biotechnology Apr 2019Wearable biosensors are garnering substantial interest due to their potential to provide continuous, real-time physiological information via dynamic, noninvasive... (Review)
Review
Wearable biosensors are garnering substantial interest due to their potential to provide continuous, real-time physiological information via dynamic, noninvasive measurements of biochemical markers in biofluids, such as sweat, tears, saliva and interstitial fluid. Recent developments have focused on electrochemical and optical biosensors, together with advances in the noninvasive monitoring of biomarkers including metabolites, bacteria and hormones. A combination of multiplexed biosensing, microfluidic sampling and transport systems have been integrated, miniaturized and combined with flexible materials for improved wearability and ease of operation. Although wearable biosensors hold promise, a better understanding of the correlations between analyte concentrations in the blood and noninvasive biofluids is needed to improve reliability. An expanded set of on-body bioaffinity assays and more sensing strategies are needed to make more biomarkers accessible to monitoring. Large-cohort validation studies of wearable biosensor performance will be needed to underpin clinical acceptance. Accurate and reliable real-time sensing of physiological information using wearable biosensor technologies would have a broad impact on our daily lives.
Topics: Biosensing Techniques; Biotechnology; Body Fluids; Computer Systems; Humans; Iontophoresis; Lab-On-A-Chip Devices; Monitoring, Physiologic; Saliva; Sweat; Tears; Wearable Electronic Devices
PubMed: 30804534
DOI: 10.1038/s41587-019-0045-y -
Periodontology 2000 Feb 2016Saliva plays a major role in determining the composition and activity of the oral microbiota, via a variety of mechanisms. Molecules, mainly from saliva, form a... (Review)
Review
Saliva plays a major role in determining the composition and activity of the oral microbiota, via a variety of mechanisms. Molecules, mainly from saliva, form a conditioning film on oral surfaces, thus providing receptors for bacterial attachment. The attached cells use saliva components, such as glycoproteins, as their main source of nutrients for growth. Oral bacteria work sequentially and in a concerted manner to catabolize these structurally complex molecules. Saliva also buffers the pH in the biofilm to around neutrality, creating an environment which is conducive to the growth of many oral bacteria that provide important benefits to the host. Components of the adaptive and innate host defences are delivered by saliva, and these often function synergistically, and at sublethal concentrations, so a complex relationship develops between the host and the resident microbiota. Dysbiosis can occur rapidly if the flow of saliva is perturbed.
Topics: Humans; Microbiota; Mouth; Saliva; Salivary Proteins and Peptides
PubMed: 26662484
DOI: 10.1111/prd.12098 -
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 -
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 -
Annals of Medicine Dec 2023Dry eye disease (DED) is a multifactorial disorder characterized by loss of tear film homeostasis with an estimated worldwide prevalence of 5% to 50%. In DED,... (Review)
Review
Dry eye disease (DED) is a multifactorial disorder characterized by loss of tear film homeostasis with an estimated worldwide prevalence of 5% to 50%. In DED, dysfunction of the ocular structures that create and regulate the tear film components-including the lacrimal glands, meibomian glands, cornea, and conjunctiva-causes a qualitative and/or quantitative tear deficiency with resultant tear film instability and hyperosmolarity. This initiates a vicious cycle of ocular surface inflammation and damage that may ultimately impair the quality of life and vision of affected patients. Many factors can contribute to the development of DED, including ocular and systemic diseases, topical and systemic medications, and environmental conditions. Because DED is a chronic disorder, treatment is most often long term and may utilize both pharmacologic and nonpharmacologic interventions to address all etiologic components. The long-term management of DED can be challenging and most often should involve eye care specialist referral. However, primary care clinicians (PCCs) are often the first points of contact for patients with DED and importantly provide initial diagnosis and preliminary patient education about the disease process. Consideration of DED is also vital for the practice of various specialties due to the large number of comorbidities and medications that can contribute to DED pathogenesis and progression. Therefore, it is important that PCCs and clinical specialists be aware of the etiology of DED and its available therapeutic options. This manuscript provides an overview of DED pathophysiology and treatment and discusses specific considerations regarding DED management for PCCs and clinical specialists.Key messagesSuccessful management of dry eye disease often requires the use of various pharmacologic and/or nonpharmacologic therapies, as well as environmental and lifestyle modifications, to mitigate the underlying etiologies and restore tear film homeostasis.Primary care clinicians play an essential role in dry eye disease management by establishing a diagnosis, educating patients about the disorder, and providing referrals to eye care specialists for initiation of specialized treatment and long-term follow-up.Primary care clinicians and clinical specialists should consider prescribing medications with fewer ocular surface effects whenever possible in patients at risk for or with existing dry eye disease.
Topics: Humans; Quality of Life; Dry Eye Syndromes; Conjunctiva; Tears; Primary Health Care
PubMed: 36576348
DOI: 10.1080/07853890.2022.2157477 -
Frontiers in Cellular and Infection... 2023The female reproductive tract harbours hundreds of bacterial species and produces numerous metabolites. The uterine cervix is located between the upper and lower parts... (Review)
Review
The female reproductive tract harbours hundreds of bacterial species and produces numerous metabolites. The uterine cervix is located between the upper and lower parts of the female genital tract. It allows sperm and birth passage and hinders the upward movement of microorganisms into a relatively sterile uterus. It is also the predicted site for sexually transmitted infection (STI), such as Chlamydia, human papilloma virus (HPV), and human immunodeficiency virus (HIV). The healthy cervicovaginal microbiota maintains cervical epithelial barrier integrity and modulates the mucosal immune system. Perturbations of the microbiota composition accompany changes in microbial metabolites that induce local inflammation, damage the cervical epithelial and immune barrier, and increase susceptibility to STI infection and relative disease progression. This review examined the intimate interactions between the cervicovaginal microbiota, relative metabolites, and the cervical epithelial-, immune-, and mucus barrier, and the potent effect of the host-microbiota interaction on specific STI infection. An improved understanding of cervicovaginal microbiota regulation on cervical microenvironment homeostasis might promote advances in diagnostic and therapeutic approaches for various STI diseases.
Topics: Male; Female; Humans; Semen; Cervix Uteri; Sexually Transmitted Diseases; Microbiota; Mucus; Vagina
PubMed: 36909729
DOI: 10.3389/fcimb.2023.1124591 -
Annual Review of Pathology Jan 2023Despite the advent of sophisticated and efficient new biologics to treat inflammation in asthma, the disease persists. Even following treatment, many patients still... (Review)
Review
Despite the advent of sophisticated and efficient new biologics to treat inflammation in asthma, the disease persists. Even following treatment, many patients still experience the well-known symptoms of wheezing, shortness of breath, and coughing. What are we missing? Here we examine the evidence that mucus plugs contribute to a substantial portion of disease, not only by physically obstructing the airways but also by perpetuating inflammation. In this way, mucus plugs may act as an immunogenic stimulus even in the absence of allergen or with the use of current therapeutics. The alterations of several parameters of mucus biology, driven by type 2 inflammation, result in sticky and tenacious sputum, which represents a potent threat, first due to the difficulties in expectoration and second by acting as a platform for viral, bacterial, or fungal colonization that allows exacerbations. Therefore, in this way, mucus plugs are an overlooked but critical feature of asthmatic airway disease.
Topics: Humans; Asthma; Mucus; Sputum; Inflammation
PubMed: 36270294
DOI: 10.1146/annurev-pathol-042220-015902