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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 -
Nutrients Jan 2021Colostrum is the milk produced during the first few days after birth and contains high levels of immunoglobulins, antimicrobial peptides, and growth factors. Colostrum... (Review)
Review
Colostrum is the milk produced during the first few days after birth and contains high levels of immunoglobulins, antimicrobial peptides, and growth factors. Colostrum is important for supporting the growth, development, and immunologic defence of neonates. Colostrum is naturally packaged in a combination that helps prevent its destruction and maintain bioactivity until it reaches more distal gut regions and enables synergistic responses between protective and reparative agents present within it. Bovine colostrum been used for hundreds of years as a traditional or complementary therapy for a wide variety of ailments and in veterinary practice. Partly due to concerns about the side effects of standard Western medicines, there is interest in the use of natural-based products of which colostrum is a prime example. Numerous preclinical and clinical studies have demonstrated therapeutic benefits of bovine colostrum for a wide range of indications, including maintenance of wellbeing, treatment of medical conditions and for animal husbandry. Articles within this Special Issue of cover the effects and use bovine colostrum and in this introductory article, we describe the main constituents, quality control and an overview of the use of bovine colostrum in health and disease.
Topics: Animal Diseases; Animals; Animals, Newborn; Anti-Infective Agents; Cattle; Colostrum; Cytokines; Dietary Supplements; Female; Gastrointestinal Diseases; Hormones; Humans; Immunoglobulins; Intercellular Signaling Peptides and Proteins; Micronutrients; Milk; Nutrients
PubMed: 33477653
DOI: 10.3390/nu13010265 -
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 -
Nutrients Mar 2021Human milk represents a cornerstone for growth and development of infants, with extensive array of benefits. In addition to exceptionally nutritive and bioactive... (Review)
Review
Human milk represents a cornerstone for growth and development of infants, with extensive array of benefits. In addition to exceptionally nutritive and bioactive components, human milk encompasses a complex community of signature bacteria that helps establish infant gut microbiota, contributes to maturation of infant immune system, and competitively interferes with pathogens. Among bioactive constituents of milk, human milk oligosaccharides (HMOs) are particularly significant. These are non-digestible carbohydrates forming the third largest solid component in human milk. Valuable effects of HMOs include shaping intestinal microbiota, imparting antimicrobial effects, developing intestinal barrier, and modulating immune response. Moreover, recent investigations suggest correlations between HMOs and milk microbiota, with complex links possibly existing with environmental factors, genetics, geographical location, and other factors. In this review, and from a physiological and health implications perspective, milk benefits for newborns and mothers are highlighted. From a microbiological perspective, a focused insight into milk microbiota, including origins, diversity, benefits, and effect of maternal diet is presented. From a metabolic perspective, biochemical, physiological, and genetic significance of HMOs, and their probable relations to milk microbiota, are addressed. Ongoing research into mechanistic processes through which the rich biological assets of milk promote development, shaping of microbiota, and immunity is tackled.
Topics: Bacteria; Female; Humans; Microbiota; Milk, Human; Oligosaccharides
PubMed: 33805503
DOI: 10.3390/nu13041123 -
Gaceta Medica de Mexico 2021The coronavirus disease 2019 (COVID-19) pandemic has affected all dimensions of health care, including exclusive breastfeeding assurance and its promotion. The risk of...
The coronavirus disease 2019 (COVID-19) pandemic has affected all dimensions of health care, including exclusive breastfeeding assurance and its promotion. The risk of contagion and the consequences of the pandemic have raised concerns among future mothers or in those who are already breastfeeding due to the risk of possible transmission of the virus through breast milk, although active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not yet been detected in breast milk. The fear of contagion has favored mother-child isolation policies. So far, there is no evidence of vertical transmission, and the risk of horizontal transmission in the infant is similar to that of the general population. In infants with COVID-19, breastfeeding can even favorably change the clinical course of the disease.
Topics: Breast Feeding; COVID-19; Colostrum; Disease Transmission, Infectious; Female; Gastrointestinal Microbiome; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Milk, Human; Pandemics; SARS-CoV-2; Time Factors
PubMed: 34270527
DOI: 10.24875/GMM.20000665 -
Nutrients Aug 2021Human milk oligosaccharides (HMOs) are non-digestible and structurally diverse complex carbohydrates that are highly abundant in human milk. To date, more than 200... (Review)
Review
Human milk oligosaccharides (HMOs) are non-digestible and structurally diverse complex carbohydrates that are highly abundant in human milk. To date, more than 200 different HMO structures have been identified. Their concentrations in human milk vary according to various factors such as lactation period, mother's genetic secretor status, and length of gestation (term or preterm). The objective of this review is to assess and rank HMO concentrations from healthy mothers throughout lactation at a global level. To this aim, published data from pooled (secretor and non-secretor) human milk samples were used. When samples were reported as secretor or non-secretor, means were converted to a pooled level, using the reported mean of approximately 80/20% secretor/non-secretor frequency in the global population. This approach provides an estimate of HMO concentrations in the milk of an average, healthy mother independent of secretor status. Mean concentrations of HMOs were extracted and categorized by pre-defined lactation periods of colostrum (0-5 days), transitional milk (6-14 days), mature milk (15-90 days), and late milk (>90 days). Further categorizations were made by gestational length at birth, mother's ethnicity, and analytical methodology. Data were excluded if they were from preterm milk, unknown sample size and mothers with any known disease status. A total of 57 peer-reviewed articles reporting individual HMO concentrations published between 1996 and 2020 were included in the review. Pooled HMO means reported from 31 countries were analyzed. In addition to individual HMO concentrations, 12 articles reporting total HMO concentrations were also analyzed as a basis for relative HMO abundance. Total HMOs were found as 17.7 g/L in colostrum, 13.3 g/L in transitional milk, and 11.3 g/L in mature milk. The results show that HMO concentrations differ largely for each individual HMO and vary with lactation stages. For instance, while 2'-FL significantly decreased from colostrum (3.18 g/L ± 0.9) to late milk (1.64 g/L ± 0.67), 3-FL showed a significant increase from colostrum (0.37 g/L ± 0.1) to late milk (0.92 g/L ± 0.5). Although pooled human milk contains a diverse HMO profile with more than 200 structures identified, the top 10 individual HMOs make up over 70% of total HMO concentration. In mature pooled human milk, the top 15 HMOs in decreasing order of magnitude are 2'-FL, LNDFH-I (DFLNT), LNFP-I, LNFP-II, LNT, 3-FL, 6'-SL, DSLNT, LNnT, DFL (LDFT), FDS-LNH, LNFP-III, 3'-SL, LST c, and TF-LNH.
Topics: Colostrum; Female; Humans; Lactation; Maternal Nutritional Physiological Phenomena; Milk, Human; Oligosaccharides; Pregnancy
PubMed: 34444897
DOI: 10.3390/nu13082737 -
Internal Medicine (Tokyo, Japan) Jul 2021
Topics: Humans; Lung Neoplasms; Sputum
PubMed: 33551412
DOI: 10.2169/internalmedicine.6602-20