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Designing and implementing successful dietary intervention is integral to the role of sport nutrition professionals as they attempt to positively change the dietary behavior of athletes. High-performance sport is a time-pressured environment where immediate results can often supersede pursuit of the most effective evidence-based practice. However, efficacious dietary intervention necessitates comprehensive, systematic, and theoretical behavioral design and implementation, if the habitual dietary behaviors of athletes are to be positively changed. Therefore, this case study demonstrates how the Behaviour Change Wheel was used to design and implement an effective nutritional intervention within a professional rugby league. The eight-step intervention targeted athlete consumption of a high-quality dietary intake of 25.1 MJ each day to achieve an overall body mass increase of 5 kg across a 12-week intervention period. The capability, opportunity, motivation, and behavior model and affordability, practicability, effectiveness/cost-effectiveness, acceptability, safety, and equity criteria were used to identify population-specific intervention functions, policy categories, behavior change techniques, and modes of intervention delivery. The resulting intervention was successful, increasing the average daily energy intake of the athlete to 24.5 MJ, which corresponded in a 6.2 kg body mass gain. Despite consuming 0.6 MJ less per day than targeted, secondary outcome measures of diet quality, strength, body composition, and immune function all substantially improved, supporting sufficient energy intake and the overall efficacy of a behavioral approach. Ultimately, the Behaviour Change Wheel provides sport nutrition professionals with an effective and practical stepwise method to design and implement effective nutritional interventions for use within high-performance sport. [ABSTRACT FROM AUTHOR]

Most studies in comparative immunology involve investigations into the detailed mechanisms of the immune system of a nonmodel organism. Although this approach has been insightful, it has promoted a deep understanding of only a handful of species, thus inhibiting the recognition of broad taxonomic patterns. Here, we call for investigating the immune defenses of numerous species within a pointillist framework, that is, the meticulous, targeted collection of data from dozens of species and investigation of broad patterns of organismal, ecological, and evolutionary forces shaping those patterns. Without understanding basic immunological patterns across species, we are limited in our ability to extrapolate and/or translate our findings to other organisms, including humans. We illustrate this point by focusing predominantly on the biological scaling literature with some integrations of the pace of life literature, as these perspectives have been the most developed within this framework. We also highlight how the more traditional approach in comparative immunology works synergistically with a pointillist approach, with each approach feeding back into the other. We conclude that the pointillist approach promises to illuminate comprehensive theories about the immune system and enhance predictions in a wide variety of domains, including host-parasite dynamics and disease ecology.

Behavior is tightly synchronized with bodily physiology. Internal needs from the body drive behavior selection, while optimal behavior performance requires a coordinated physiological response. Internal state is dynamically represented by the nervous system to influence mood and emotion, and body-brain signals also direct responses to external sensory cues, enabling the organism to adapt and pursue its goals within an ever-changing environment. In this review, we examine the anatomy and function of the brain-body connection, manifested across local, reflex, and central regulation levels. We explore these hierarchical loops in the context of the immune system, specifically through the lens of immunoception, and discuss the impact of its dysregulation on human health., Competing Interests: Declaration of interests S.D.L. is a co-founder and consultant for Nilo Therapeutics., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This review highlights the significance of interactions between the microbiota, immune system, nervous and hormonal systems, and the brain on periodontal health and disease. Microorganisms in the microbiota, immune cells, and neurons communicate via homeostatic nervous and hormonal systems, regulating vital body functions. By modulating pro-inflammatory and anti-inflammatory adaptive immune responses, these systems control the composition and number of microorganisms in the microbiota. The strength of these brain-controlled responses is genetically determined but is sensitive to early childhood stressors, which can permanently alter their responsiveness via epigenetic mechanisms, and to adult stressors, causing temporary changes. Clinical evidence and research with humans and animal models indicate that factors linked to severe periodontitis enhance the responsiveness of these homeostatic systems, leading to persistent hyperactivation. This weakens the immune defense against invasive symbiotic microorganisms (pathobionts) while strengthening the defense against non-invasive symbionts at the gingival margin. The result is an increased gingival tissue load of pathobionts, including Gram-negative bacteria, followed by an excessive innate immune response, which prevents infection but simultaneously destroys gingival and periodontal tissues. Thus, the balance between pro-inflammatory and anti-inflammatory adaptive immunity is crucial in controlling the microbiota, and the responsiveness of brain-controlled homeostatic systems determines periodontal health., (© 2024 The Author(s). Periodontology 2000 published by John Wiley & Sons Ltd.)

Although coming down with an illness or receiving a vaccine are both common experiences, the influence of such acute immune system activations on cognitive processes, such as inhibitory control, has received relatively little attention. We addressed that issue by assessing the effects of acute immune system activation on inhibitory control in a randomized controlled experiment, and by conducting a meta-analysis of similar studies in humans. In our experiment, we found-somewhat surprisingly-that influenza vaccination improved performance on both of our inhibitory control outcomes (i.e., stop-signal reaction times and flanker interference effects). At the meta-analytic level, we found that at a short delay (1.5-4 hours post-injection) between immune activation and inhibitory control assessment, such activation impaired multiple forms of inhibitory control, whereas after a longer delay (e.g., > 18 hours post-injection), such activation improved inhibitory control-consistent with our experiment. Moreover, proinflammatory cytokine activity predicted poorer interference control but better response inhibition, even with a long delay between injection and testing. Together, these results highlight nuanced, time-dependent, and-perhaps-multiple-mechanism-driven effects of acute immune system activity on inhibitory control., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Ageing as a natural irreversible process inherently results in the functional deterioration of numerous organ systems and tissues, including the skeletal and immune systems. Recent studies have elucidated the intricate bidirectional interactions between these two systems. In this review, we provide a comprehensive synthesis of molecular mechanisms of cell ageing. We further discuss how age-related skeletal changes influence the immune system and the consequent impact of immune system alterations on the skeletal system. Finally, we highlight the clinical implications of these findings and propose potential strategies to promote healthy ageing and reduce pathologic deterioration of both the skeletal and immune systems., (© 2024. The Author(s).)

The primary sensory neurons involved in pain perception express various types of receptor-type ion channels at their nerve endings. These molecules are responsible for triggering neuronal excitation, translating environmental stimuli into pain signals. Recent studies have shown that acute nociception, induced by neuronal excitation, not only serves as a sensor for signaling life-threatening situations but also modulates our pathophysiological conditions. This modulation occurs through the release of neuropeptides by primary sensory neurons excited by nociceptive stimuli, which directly or indirectly affect peripheral systems, including immune function. Senso-immunology, an emerging research field, integrates interdisciplinary studies of pain and immunology and has garnered increasing attention in recent years. This review provides an overview of the systemic pathophysiological functions regulated by receptor-type ion channels, such as transient receptor potential (TRP) channels in primary sensory neurons, from the perspective of senso-immunology., (© 2024. The Japanese Society Bone and Mineral Research.)

Purpose: To examine the response or pre- and postmatch salivary immunoglobulin A concentration ([s-IgA]) to Australian Football League (AFL) match play and investigate the acute and cumulative influence of player workload and postmatch [s-IgA] after repeated participation in AFL match play. Methods: Eleven elite AFL athletes (21.8 ± 2.4 y, 186.9 ± 7.9 cm, 87.4 ± 7.5 kg) were monitored throughout 3 matches during the preseason that were separated by 7 d. Saliva samples were collected across each AFL match at 24 h and 1 h prematch and 1, 12, 36, and 60 h postmatch to determine [s-IgA]. Global positioning systems (GPS) with integrated triaxial accelerometers were used to determine total player workload during match play. Hypothesis testing was conducted for time-dependent changes in [s-IgA] and player load using a repeated-measures ANOVA. Results: Player load during match 3 (1266 ± 124.6 AU) was significantly (P < .01) greater than in match 1 (1096 ± 115.1 AU) and match 2 (1082 ± 90.4 AU). Across match 3, [s-IgA] was significantly (P < .01) suppressed at 2 postmatch measures (12 and 36 h) compared with prematch measures (24 and 1 h), which coincided with significantly (P < .01) elevated player load. Conclusion: The findings indicate that an increase in player load during AFL preseason match play resulted in compromised postmatch mucosal immunological function. Longitudinal assessment of AFL-match player load and mucosal immunological function across the first 60 h of recovery may augment monitoring and preparedness strategies for athletes. [ABSTRACT FROM AUTHOR]

Context: Resistance training is a common form of exercise for competitive and recreational athletes. Enhancing recovery from resistance training may improve the muscle-remodeling processes, stimulating a faster return to peak performance. Objective: To examine the effects of 2 different recovery modalities, neuromuscular electrical stimulation (NMES) and cold-water immersion (CWI), on performance and biochemical and ultrasonographic measures. Participants: Thirty resistance-trained men (23.1 ± 2.9 y, 175.2 ± 7.1 cm, 82.1 ± 8.4 kg) were randomly assigned to NMES, CWI, or control (CON). Design and Setting: All participants completed a high-volume lower-body resistance-training workout on d 1 and returned to the human performance laboratory 24 (24H) and 48 h (48H) postexercise for follow-up testing. Measures: Blood samples were obtained preexercise (PRE) and immediately (IP), 30 min (30P), 24 h (24H), and 48 h (48H) post. Subjects were examined for performance changes in the squat exercise (total repetitions and average power per repetition), biomarkers of inflammation, and changes in cross-sectional area and echo intensity (EI) of the rectus femoris (RF) and vastus lateralis muscles. Results: No differences between groups were observed in the number of repetitions (P = .250; power: P = .663). Inferential-based analysis indicated that increases in C-reactive protein concentrations were likely increased by a greater magnitude after CWI compared with CON, while NMES possibly decreased more than CON from IP to 24H. Increases in interleukin-10 concentrations between IP and 30P were likely greater in CWI than NMES but not different from CON. Inferential-based analysis of RF EI indicated a likely decrease for CWI between IP and 48H. No other differences between groups were noted in any other muscle-architecture measures. Conclusions: Results indicated that CWI induced greater increases in pro- and anti-inflammatory markers, while decreasing RF EI, suggesting that CWI may be effective in enhancing short-term muscle recovery after high-volume bouts of resistance exercise. [ABSTRACT FROM AUTHOR]

Regular physical exercise has been recognized as a potent modulator of immune function, with its effects including enhanced immune surveillance, reduced inflammation, and improved overall health. While strong evidence exists that physical exercise affects the specific expression and activity of non-coding RNAs (ncRNAs) also involved in immune system regulation, heterogeneity in individual study designs and analyzed exercise protocols exists, and a condensed list of functional, exercise-dependent ncRNAs with known targets in the immune system is missing from the literature. A systematic review and qualitative analysis was used to identify and categorize ncRNAs participating in immune modulation by physical exercise. Two combined approaches were used: (a) a systematic literature search for "ncRNA and exercise immunology", (b) and a database search for microRNAs (miRNAs) (miRTarBase and DIANA-Tarbase v8) aligned with known target genes in the immune system based on the Reactome database, combined with a systematic literature search for "ncRNA and exercise". Literature searches were based on PubMed, Web of Science, and SPORTDiscus; and miRNA databases were filtered for targets validated by in vitro experimental data. Studies were eligible if they reported on exercise-based interventions in healthy humans. After duplicate removal, 95 studies were included reporting on 164 miRNAs, which were used for the qualitative synthesis. Six studies reporting on long-noncoding RNAs (lncRNAs) or circular RNAs were also identified. Results were analyzed using ordering tables that included exercise modality (endurance/resistance exercise), acute or chronic interventions, as well as the consistency in reported change between studies. Evaluation criteria were defined as "validated" with 100% of ≥3 independent studies showing identical direction of regulation, "plausible" (≥80%), or "suggestive" (≥70%). For resistance exercise, upregulation of miR-206 was validated while downregulation of miR-133a appeared plausible. For endurance exercise, 15 miRNAs were categorized as validated, with 12 miRNAs being consistently elevated and 3 miRNAs being downregulated, most of them after acute exercise training. In conclusion, our approach provides evidence that miRNAs play a major role in exercise-induced effects on the innate and adaptive immune system by targeting different pathways affecting immune cell distribution, function, and trafficking as well as production of (anti-)inflammatory cytokines. miRNAs miR-15, miR-29c, miR-30a, miR-142/3, miR-181a, and miR-338 emerged as key players in mediating the immunomodulatory effects of exercise predominantly after acute bouts of endurance exercise., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type, dose (frequency/duration, intensity), and individual characteristics. Similarly, reduced availability of ambient oxygen (hypoxia) modulates immune functions depending on the hypoxic dose and the individual capacity to respond to hypoxia. How combined exercise and hypoxia (e.g., high-altitude training) sculpts immune responses is not well understood, although such combinations are becoming increasingly popular. Therefore, in this paper, we summarize the impact on immune responses of exercise and of hypoxia, both independently and together, with a focus on specialized cells in the innate and adaptive immune system. We review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia, then we discuss how they may be modulated by nutritional strategies. Mitochondrial, antioxidant, and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism, resilience, and overall immune functions by regulating the survival, differentiation, activation, and migration of immune cells. This review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system functions. Appropriate acclimatization, training, and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Androgens can modulate immune cell function and may contribute to differences in the prevalence and severity of common inflammatory conditions. Although most immune cells are androgen targets, our understanding of how changes in androgen bioavailability can affect immune responses is incomplete. Androgens alter immune cell composition, phenotype, and activation by modulating the expression and secretion of inflammatory mediators or by altering the development and maturation of immune cell precursors. Androgens are generally associated with having suppressive effects on the immune system, but their impacts are cell and tissue context-dependent and can be highly nuanced even within immune cell subsets. In response to androgens, innate immune cells such as neutrophils, monocytes, and macrophages increase the production of the anti-inflammatory cytokine IL-10 and decrease nitric oxide production. Androgens promote the differentiation of T cell subsets and reduce the production of inflammatory mediators, such as IFNG, IL-4 and IL-5. Additionally, androgens/androgen receptor can promote the maturation of B cells. Thus, androgens can be considered as immunomodulatory agents, but further work is required to understand the precise molecular pathways that are regulated at the intersection between endocrine and inflammatory signals. This narrative review focusses on summarising our current understanding of how androgens can alter immune cell function and how this might affect inflammatory responses in health and disease.

Skin is now emerging as a complex realm of three chief systems viz. immune system, nervous system, and endocrine system. The cells involved in their intricate crosstalk, namely native skin cells, intra-cutaneous immune cells and cutaneous sensory neurons have diverse origin and distinct functions. However, recent studies have explored their role beyond their pre-defined functional boundaries, such that the cells shun their traditional functions and adopt unconventional roles. For example, the native skin cells, apart from providing for basic structural framework of skin, also perform special immune functions and participate in extensive neuro-endocrine circuitry, which were traditionally designated as functions of cutaneous resident immune cells and sensory neurons respectively. At the cellular level, this unique collaboration is brought out by special molecules called neuromediators including neurotransmitters, neuropeptides, neurotrophins, neurohormones and cytokines/chemokines. While this intricate crosstalk is essential for maintaining cutaneous homeostasis, its disruption is seen in various cutaneous diseases. Recent study models have led to a paradigm shift in our understanding of pathophysiology of many such disorders. In this review, we have described in detail the interaction of immune cells with neurons and native skin cells, role of neuromediators, the endocrine aspect in skin and current understanding of cutaneous neuro-immuno-endocrine loop in one of the commonest skin diseases, psoriasis. An accurate knowledge of this unique crosstalk can prove crucial in understanding the pathophysiology of different skin diseases and allow for generation of targeted therapeutic modalities., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To monitor resting salivary secretory immunoglobulin A (SIgA) levels in international soccer players during the short-term training period that precedes international match play. Methods: In a repeated-measure design, saliva samples were obtained from 13 outfield soccer players who participated in the training camps preceding 7 games (5 home and 2 away) of the 2014 FIFA World Cup qualifying campaign. Samples were obtained daily for 4 d preceding each game (and analyzed for SIgA using the IPRO oral-fluid-collection system) at match day minus 1 (MD-1), minus 2 (MD-2), minus 3 (MD-3), and minus 4 (MD-4). Results: SIgA displayed a progressive decline (P = .01) during the 4-d training period (MD-4, 365 ± 127 μg/mL; MD-3, 348 ± 154 μg/mL; MD-2, 290 ± 138 μg/mL; MD-1, 256 ± 90 μg/mL) such that MD-1 values were significantly lower (P = .01) than both MD-4 and MD-3. The 95% confidence intervals for the differences between MD-1 and MD-4 were –191 to –26 and between MD-1 and MD-3 were –155 to –28. Conclusions: Data demonstrate that a short-term soccer-training camp in preparation for international competition induces detectable perturbations to mucosal immunity. Future studies should monitor SIgA (as a practical and noninvasive measure of immunity) alongside internal and external measures of training load in an attempt to strategically individualize training and nutritional strategies that may support optimal preparation for high-level competition. [ABSTRACT FROM AUTHOR]

Background: More than a century ago, experimental work and clinical observations revealed the functional communication between the brain and the peripheral immune system. This is documented on the one hand by studies first demonstrating the effects of catecholamines on the circulation of leukocytes in experimental animals and humans, and on the other hand via the work of Russian physiologist Ivan Petrovic Pavlov and his coworkers, reporting observations that associative learning can modify peripheral immune functions. This work later fell into oblivion since little was known about the endocrine and immune system's function and even less about the underlying mechanisms of how learning, a central nervous system activity, could affect peripheral immune responses., Summary: In this article, we embark on a fascinating exploration of the historical trajectory of behaviorally conditioned immune responses., Key Message: We will pay homage to the visionary scientists who laid the groundwork for this field of research, tracing its evolution from early theories of how associative learning can affect immunity to the modern-day insights that behavioral conditioning of pharmacological responses can be exploited to improve the efficacy of medical interventions for patients., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

By definition, individuals granted refugee and asylum status have fled frightening, often traumatic circumstances. Not surprisingly, the prevalence of psychological concerns is elevated among refugee children and adults relative to rates in their host communities. Substantial proportions of refugees and asylum seekers evidence stress‐sensitive psychological disorders such as post‐traumatic stress disorder (PTSD), depression, anxiety, and substance use disorders; in some refugee populations, prevalence of stress‐sensitive disorders has been reported to be as high as 90%. [ABSTRACT FROM AUTHOR]

Bone erosion is one of the central hallmarks of RA and is caused by excessive differentiation and activation of osteoclasts. Presence of autoantibodies in seropositive arthritis is associated with radiographic disease progression. ICs, formed by autoantibodies and their antigens, activate Fcγ-receptor signalling in immune cells, and as such stimulate inflammation-mediated bone erosion. Interestingly, ICs can also directly activate osteoclasts by binding to FcγRs on their surface. Next to autoantibodies, high levels of alarmins, among which is S100A8/A9, are typical for RA and they can further activate the immune system but also directly promote osteoclast function. Therefore, IC-activated FcγRs and S100A8/A9 might act as partners in crime to stimulate inflammation and osteoclasts differentiation and function, thereby stimulating bone erosion. This review discusses the separate roles of ICs, FcγRs and alarmins in bone erosion and sheds new light on the possible interplay between them, which could fuel bone erosion. [ABSTRACT FROM AUTHOR]

Background: Sympathetic neural activation plays a key role in the incidence and maintenance of acute myocardial infarction (AMI) induced ventricular arrhythmia (VA). Furthermore, previous studies showed that AMI might induce microglia and sympathetic activation and that microglial activation might contribute to sympathetic activation. Recently, studies showed that light emitting diode (LED) therapy might attenuate microglial activation. Therefore, we hypothesized that LED therapy might reduce AMI‐induced VA by attenuating microglia and sympathetic activation. Methods: Thirty anesthetized rats were randomly divided into three groups: the Control group (n = 6), AMI group (n = 12), and AMI + LED group (n = 12). Electrocardiogram (ECG) and left stellate ganglion (LSG) neural activity were continuously recorded. The incidence of VAs was recorded during the first hour after AMI. Furthermore, we sampled the brain and myocardium tissue of the different groups to examine the microglial activation and expression of nerve growth factor (NGF), interleukin‐18 (IL‐18), and IL‐1β, respectively. Results: Compared to the AMI group, LED therapy significantly reduced the incidence of AMI‐induced VAs (ventricular premature beats [VPB] number: 85.08 ± 13.91 vs 27.5 ± 9.168, P < .01; nonsustained ventricular tachycardia (nSVT) duration: 34.39 ± 8.562 vs 9.005 ± 3.442, P < .05; nSVT number: 18.92 ± 4.52 vs 7.583 ± 3.019, P < .05; incidence rate of SVT/VF: 58.33% vs. 8.33%, P < .05) and reduced the LSG neural activity (P < .01) in the AMI + LED group. Furthermore, LED significantly attenuated microglial activation and reduced IL‐18, IL‐1β, and NGF expression in the peri‐infarct myocardium. Conclusion: LED therapy may protect against AMI‐induced VAs by suppressing sympathetic neural activity and the inflammatory response. [ABSTRACT FROM AUTHOR]

Purpose: Sepsis stimulates pro- and anti-inflammatory immune responses. The innate immune response is critical to organ injury repair. We tested for an association between innate immune function and organ function recovery in a prospective cohort of immune-competent adults with sepsis. Methods: We conducted a prospective observational cohort study enrolling immune-competent adults with sepsis. We tested innate immune function by quantification of lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) α production capacity in whole blood samples on hospital days 1, 4, and 6. The primary outcome was organ function recovery on day 4 defined as a 4-point decrease in the composite cardiovascular and respiratory Sequential Organ Failure Assessment (SOFA) score components or a SOFA score ≤2. Results: Patients with sepsis who recovered organ function by day 4 (n = 11) had similar baseline characteristics when compared to those with ongoing organ failure (n = 13). Tumor necrosis factor α production capacity was similar between the 2 groups on hospital days 1 and 4 but significantly different on day 6. Patients who regained organ function recovery had significantly higher TNF-α production capacity on day 6 (P =.01), which persisted after adjustment for age, Acute Physiology and Chronic Health Evaluation III score, and steroid administration (P =.03). There was no difference in TNF-α production capacity over time in those who survived to hospital discharge versus nonsurvivors. Conclusion: Increasing TNF-α production capacity is associated with improved organ failure recovery. Further studies are needed to evaluate a causal association between innate immune suppression and organ failure recovery as well as predictive accuracy for hospital survival. Impaired TNF-α production as a marker of sepsis-associated innate immune dysfunction may be a feasible target for immune stimulation to decrease time to organ failure recovery. [ABSTRACT FROM AUTHOR]

Trichinellosis caused by parasitic nematodes of the genus Trichinella may result in human morbidity and mortality worldwide. Deciphering processes that drive species diversity and adaptation are key to understanding parasitism and developing effective control strategies. Our goal was to identify genes that are under positive selection and possible mechanisms of adaptive evolution of Trichinella spiralis genes using a comparative genomic analysis with the genomes of Brugia malayi, Trichuris suis, Ancylostoma ceylanicum, and Caenorhabditis elegans. The CODEML program derived from the PAML package was used to deduce the most probable dN/dS ratio, a measurement to detect genes/proteins undergoing adaptation. For each pair of sequences, those with a dN/dS ratio > 1 were considered positively selected genes (PSGs). Altogether, 986 genes were positively selected (p-value < 0.01). Genes involved in metabolic pathways, signaling pathways, and cytosolic DNA-sensing pathways were significantly enriched among the PSGs. Several PSGs are associated with exploitation of the host: modification of the host's metabolism, creation of new parasite-specific morphological structures between T. spiralis and the host interface, xenobiotic metabolism to combat low oxygen concentrations and host toxicity, muscle cell transformation, cell cycle arrest, DNA repair processes during nurse cell formation, antiapoptotic factors, immunomodulation, and regulation of epigenetic processes. Some of the T. spiralis PSGs have C. elegans orthologs that confer severe or lethal RNAi phenotypes. Fifty-seven PSGs in T. spiralis were analyzed to encode differentially expressed proteins. The present study utilized an overall comparative genomic analysis to discover PSGs within T. spiralis and their relationships with biological function and organism fitness. This analysis adds to our understanding of the possible mechanism that contributes to T. spiralis parasitism and biological adaptation within the host, and thus these identified genes may be potential targets for drug and vaccine development. [ABSTRACT FROM AUTHOR]

The use of regular infusions of immunoglobulin is well established as a treatment for patients with antibody deficiency and for patients requiring immunomodulation. Although efficacy is believed to be equivalent for the different immunoglobulin products, it is generally regarded as best practice not to switch from one product to another unless there is a clinical reason to change. Changes in commissioning guidance and issues with the supply of some immunoglobulin products to the UK resulted in a requirement for a significant number of patients to switch between immunoglobulin products in 2017-2018. Data from the 2018 UK Primary Immunodeficiency census has been used to evaluate the clinical results of switching. Results from 30 immunology centres reported a total of 802 immunoglobulin product switches. Twelve reactions were recorded, none of which required admission to hospital, one patient was treated with oral corticosteroids, the others required either no treatment or treatment with oral antihistamines. This review of immunoglobulin product switch reactions gives a clearer indication regarding the safety of product switching than has previously been published. [ABSTRACT FROM AUTHOR]

Background: Involvement of the immune system is one of the issues raised in the pathophysiology of depression. BCL2 and BAX genes are related to immune system regulation. We investigated the BCL2 and BAX expression as a probable mechanism of immune system involvement in depression. Materials and Methods: This case-control study was conducted on 28 patients with major depression (case) and 28 nondepressed individuals (control) within the age range of 18-55 years in the Isfahan University of Medical Sciences. Clinical interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, were conducted to detect depression, and Beck's Depression Inventory was used to measure the severity of depression in the individuals. In addition, a real-time polymerase chain reaction was employed to compare the level of Bax and Bcl-2 gene expression in peripheral blood lymphocytes. The multivariate covariance analysis was used to explore the correlation between BCL2 and BAX gene expression and to control the effect of duration and severity of depression. Results: The results showed that none of the variables including group membership, the duration of depression, and the severity of depression were not significantly correlated with the expression of BCL2 and BAX genes. Furthermore, there was no statistically significant relationship between the Bax and Bcl-2 genes expression in case and control groups (P > 0.05). Conclusion: Depression may have no impact on Bax and Bcl-2 gene expression in patients with major depression. Studies with larger sample size are recommended. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is termed as an obstetric issue that is characterized by hypertension (≧140/90 mm Hg), together with proteinuria following 20 weeks of pregnancy. Until today, PE still constitutes a severe threat to the lives of both the mothers and fetuses. In the past, long noncoding RNAs (lncRNAs) were considered as the transcriptional noise. However, some investigations have indicated that lncRNAs could be used as innovative indicators in PE. The current review aims to discuss the relationship between lncRNAs and PE in recent years. According to the retrieved data, we concluded that lncRNAs can exert an impact on both the occurrence and development of PE through the changes in the biological functions of trophoblasts, immune regulation, epigenetic regulation, decidualization, and energy metabolism. The mechanisms of lncRNAs in PE will help us to better understand the pathogenesis of PE and help us to find targets for predicting and diagnosing PE in the future. [ABSTRACT FROM AUTHOR]

There are about 1-2 million follicles presented in the ovary at birth, while only around 1000 primordial follicles are left at menopause. The ovarian function also decreases in parallel with aging. Folliculogenesis is vital for ovarian function, no matter the synthesis of female hormones or ovulation, yet the mechanisms for its changing with increasing age are not fully understood. Early follicle growth up to the large preantral stage is independent of gonadotropins in rodents and relies on intraovarian factors. To further understand the age-related molecular changes in the process of folliculogenesis, we performed microarray gene expression profile analysis using total RNA extracted from young (9 weeks old) and old (32 weeks old) mouse ovarian secondary follicles. The results of our current microarray study revealed that there were 371 (≥2-fold, q-value ≤0.05) genes differentially expressed in which 174 genes were upregulated and 197 genes were downregulated in old mouse ovarian secondary follicles compared to young mouse ovarian secondary follicles. The gene ontology and KEGG pathway analysis of differentially expressed genes uncovered critical biological functions such as immune system process, aging, transcription, DNA replication, DNA repair, protein stabilization, and apoptotic process were affected in the process of aging. The considerable changes in gene expression profile may have an adverse influence on follicle quality and folliculogenesis. Our study provided information on the processes that may contribute to age-related decline in ovarian function. [ABSTRACT FROM AUTHOR]

Contrasting studies are reported on the induction of IL-10 and IFN-γ via chitin microparticles (CMPs) during immune stimulation. Our previous studies have shown marked protection among CMP treated Leishmania-infected mice via regulated IL-10/IFN-γ response, at the present study, once more, examined the inconsistent responses regarding the immunologic response of CMPS. To verify whether CMPs could indeed up-regulate IL-10/IFN-γ axis, isolated spleen cells from the myelin oligodendrocyte glycoprotein (MOG) induced experimental autoimmune encephalomyelitis (EAE) mice were cultured in the presence of MOG peptide and/or CMPs. The effects of CMPs on IL-10, IFN-γ and IL-17 production were evaluated by Enzyme-linked Immunosorbent Assay (ELISA). Moreover, GATA binding protein 3 (Gata3), T-box transcription factor TBX21 (Tbx21), and RAR-related orphan receptor gamma (RORγT) expressions (real-time PCR) were investigated. MOG alone stimulated the production of IFN-γ (p≤0.004) but not, IL-10 (p≤0.140). MOG/chitin stimulation resulted in a significant increase in IFN-γ and IL-10 levels, respectively; (p≤0.004 and p≤0.003) rather than MOG. Additionally, the expression of Tbx21 (p≤0.001), but not Gata3 (p≤0.08), was increased in the MOG/chitin-treated spleen cells. All in all, CMP supports Gata3 independent IL-10 production and promotes Tbx21 dependent IFN-γ induction. These results, alongside our previous data, indicate that CMPs has particular adjuvant effects. [ABSTRACT FROM AUTHOR]

Adult multipotent stem/progenitor cells, with remarkable regenerative potential, have been isolated from various components of the human periodontium. These multipotent stem/progenitor cells include the periodontal ligament stem/progenitor cells (PDLSCs), stem cells from the apical papilla (SCAP), the gingival mesenchymal stem/progenitor cells (G‐MSCs), and the alveolar bone proper stem/progenitor cells (AB‐MSCs). Whereas inflammation is regarded as the reason for tissue damage, it also remains a fundamental step of any early healing process. In performing their periodontal tissue regenerative/reparative activity, periodontal stem/progenitor cells interact with their surrounding inflammatory micro‐environmental, through their expressed receptors, which could influence their fate and the outcome of any periodontal stem/progenitor cell‐mediated reparative/regenerative activity. The present review discusses the current understanding about the interaction of periodontal stem/progenitor cells with their surrounding inflammatory micro‐environment, elaborates on the inflammatory factors influencing their stemness, proliferation, migration/homing, differentiation, and immunomodulatory attributes, the possible underlying intracellular mechanisms, as well as their proposed relationship to the canonical and noncanonical Wnt pathways. [ABSTRACT FROM AUTHOR]

The aging of the Baby Boomer generation and the general rise in life expectancy continue to expand the proportion of older adults (≥65 years of age) across global and US populations. As the adult years progress, so do the chances for a diagnosis of cancer. The need to determine whether evolving trends in cancer treatment benefit an aging population is vital. Immune checkpoint inhibitors (ICIs) represent a radically new approach in modern cancer treatment. They target the immune system instead of the disease and unleash the body's natural defenses against tumor growth. ICIs are valued for their reduction in toxicity and superior treatment effect compared with many conventional therapies. Although clinical trial results show generally comparable efficacy and safety in younger and older populations, the proportion of older cancer trial participants does not accurately reflect the general population. This article describes the body's cycle of immunity in combatting mutations and how ICIs can aid the most vulnerable aspect of that cycle. The article discusses the challenges and possible opportunities in an aging immune system, the immune-related side effects of ICIs, and the role of genomic biomarkers in predicting response to treatment. Regulators and activists are advocating for better representation of older patients in clinical trials; however, comprehensive investigation into the risks and benefits of immune-modulating therapies for this growing population is still needed. [ABSTRACT FROM AUTHOR]

This repeated-measures case series describes the changes in cardiorespiratory fitness, body composition and systemic inflammation in 4 well-trained athletes pre- and post-completion of an unsupported transatlantic rowing race. The acute effects of endurance exercise have been well described previously, but the enduring consequences of ultra-endurance on the cardiorespiratory, metabolic and immune systems are largely unknown. This study explores these physiological adaptations following 2 weeks of recovery. Cardiorespiratory fitness testing, body composition analysis, and blood sampling for inflammatory cytokines were recorded immediately before race departure and repeated 14 days following race completion. Mean VO2max (ml/kg/min) was similar pre- (48.2±2.8) and post-race (46.7±1.5). Heart rate responses were equivalent at incremental workloads. Mean blood lactate (mmol/L) was higher at low to moderate power outputs and lower at maximal effort (14.6±1.85 vs. 13.1±2.5). Percentage body fat (17.7 ± 7.9 vs. 16.2±7.4) was analogous to pre-race analysis. Low-grade inflammation persisted, indicated by an increase in IL-1β (69%), IL-8 (10%), TNF-α (8%), IL-6 (5.4%), and C-reactive protein (22.4%). VO2max and heart rate responses were similar pre- and post-race, but sub-maximal efficiency measures of cardiorespiratory fitness were consistent with persistent fatigue. Body composition had returned to baseline but low-grade systemic inflammation persisted. Persistent pro-inflammatory cytokinaemia is known to exert deleterious consequences on immune, metabolic, and psychological function. Adequate recovery is necessary to re-establish inflammatory homeostasis, and the results of this study may inform these decisions. [ABSTRACT FROM AUTHOR]

A series of polyurethanes with low modulus of elasticity for soft tissue implantation was synthesized. Polyurethane samples were implanted into mice for seven days, after which histological studies of capsule formation were carried out. The mechanical properties of polyurethane were found to affect the organism's immune response at sites close to implants at which specific conditions concentrating biomechanical stress in tissues, particularly around the ends of polyurethane films, occur. Softer polyurethane with a modulus of elasticity close to the modulus of elasticity of tissues produced essentially no reaction to biomechanical stress, though reactions to the foreign surface of the implant remained. [ABSTRACT FROM AUTHOR]

Background: Dental caries is one of the most common diseases during childhood. Saliva can modulate the process of decay, as a rich source of host factors. It has been shown that tumor necrosis factor-alpha (INF-α) is secreted more in the saliva of individuals with active caries. No study has addressed the relationship between INF-α levels and age or compared children's immune response at different age groups and during adolescence. Objectives: The present study aimed at evaluating the pro-inflammatory cytokine level of INF-α in saliva and its association with caries in different age groups of children and adolescents. Methods: In this case-control study, 128 children and adolescents were divided to four age groups of 32. In each group, half of the individuals had no decay (control group) and the other half had > 4 decayed teeth (case group). Overall, 5 mL of non-stimulated saliva was spitted in sterile tubes for 15 minutes. Furthermore, 1 mL of each sample was centrifuged for five minutes at 120 00 rpm. Salivary level of INF-α was measured using the Enzyme Linked Immunosorbent Assay (ELISA) standard kit. Results: A total of 79 children were studied. The mean INF-α levels in the case group was 35.20 ± 1623 Pg/mL and in the control group, this was 2620 ± 6.25 Pg/mL (P value = 0.001). The mean INF-α level was significantly higher in the age group of six to 12 years than the age group of 13 to 18 years (P value = 0.01). Conclusions: The results of this study indicated that decay plays an important role in increasing cytokine INF-α in non-stimulatory saliva, there is no confirming evidence of the direct effect of age on immune function yet. [ABSTRACT FROM AUTHOR]

Abstract Less schooling is associated with increased biological risks for chronic disease, but whether increasing years of schooling through policy interventions reduces these risks remains unclear. We examine the effect of a major education reform introduced in 1959 that raised the minimum school leaving age from 14 to 16 years in France, offering a unique natural experiment. We assess the causal impact of increased schooling duration on 16 biomarkers of cardiovascular, metabolic, organ and immune function in a large cohort of men and women born around 1953. Using a Regression Discontinuity Design, we find that the reform led to a significant increase in schooling duration among children from disadvantaged families; but longer schooling did not translate into better biomarker profiles in adulthood. Eligibility to the reform had no impact on the biomarker profile of respondents from intermediate or high social class families, while it led to increased blood pressure and white cells counts in adulthood among those from low parental social class. These findings were robust across several sensitivity analyses. They emphasize the importance of considering the institutional context and the respondents' social origins when evaluating the health effects of compulsory schooling reforms. Our results do not necessarily question the premise that education leads to better health, but they suggest that law-mandated increases in schooling alone may not improve the health of disadvantaged groups. Highlights • We provide new evidence on the effect of compulsory schooling reforms on biomarkers. • Increased schooling duration was not associated with improved biological profiles. • It led to increased blood pressure and inflammation in respondents from poor families. • Trade-offs of schooling policies as tools to improve health need to be considered. [ABSTRACT FROM AUTHOR]

With the emerging popularity of immune-modulatory therapies to treat human diseases there is a need to step back from hypotheses aimed at assessing a condition in a single-system context and instead take into account the disease pathology as a whole. In complex diseases, such as amyotrophic lateral sclerosis (ALS), the use of these therapies to treat patients has been largely unsuccessful and likely premature given our lack of understanding of how the immune system influences disease progression and initiation. In addition, we still have an incomplete understanding of the role of these responses in our model systems and how this may translate clinically to human patients. In this review we discuss preclinical evidence and clinical trial results for a selection of recently conducted studies in ALS. We provide evidence-based reasoning for the failure of these trials and offer suggestions to improve the design of future investigations. Muscle Nerve 59:23-33, 2019. [ABSTRACT FROM AUTHOR]

Background: Juvenile recurrent parotitis (JRP) is defined as recurrent parotid inflammation, generally associated with nonobstructive sialectasis of the parotid gland. In addition, the etiology remains unclear, probably immunologically mediated. Aim: The purposes of the present study were to report the relationship between JRP and immune function from the measurement of the JRP patients' immunoglobulins and T-lymphocyte subset. Methods: Immunologic assay from 2014 to 2017 of 100 children diagnosed with JRP at Shanghai Ninth Hospital compared with the 100 normal children by age. Results: The CD4 level of JRP children aged >6 years was significant lower than the one of JRP preschool children (p < .05), while the IgG level was significant higher than the one of the JRP preschool children (p < .05). In comparison with the normal children, the value of CD8 T cells, immunoglobulin G (IgG), immunoglobulin E (IgE), immunoglobulin A (IgA) and C3 (p < .01) of JRP children was significant higher, while the value of CD4 T cells was lower (p < .01) in spite of age. What is more, the value of CD8 T cells of JRP preschool children was much significant higher than the one of the normal preschool children (p < .01). Conclusion: The immune function of JRP patients may become disorder: the suppression cellular immune function and inadequate humoral immune expression. [ABSTRACT FROM AUTHOR]

Objective: Secukinumab (anti–interleukin‐17A [anti–IL‐17A]) is an effective therapy for ankylosing spondylitis and psoriatic arthritis, the prototypical forms of spondyloarthritis (SpA). We undertook this study to determine whether secukinumab modulates the immunopathology of target lesions without blunting systemic immune responses, using peripheral SpA as a model. Methods: Twenty patients with active peripheral SpA were included in a 12‐week open‐label trial with secukinumab (300 mg once weekly from baseline to week 4 and then every 4 weeks thereafter). Outcomes included clinical response, cytokine production by peripheral blood cells using TruCulture technology, and histologic and real‐time quantitative polymerase chain reaction analysis of synovial biopsy samples before and after treatment. Results: All patients completed the 12‐week study without severe adverse events (AEs) or severe treatment‐related AEs. The efficacy end point, the number of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 weeks, was achieved by 13 of the 20 patients, of whom 8 achieved an ACR50 response and 5 achieved an ACR70 response, with rapid and significant improvements in all clinical disease activity measures. Clinical improvement in joint counts was associated with a histologic decrease in synovial sublining macrophages (P = 0.028) and neutrophils (P = 0.004), both of which are sensitive synovial biomarkers of inflammatory response in peripheral SpA, as well as with decreased synovial expression of IL‐17A messenger RNA (mRNA) (P = 0.010) but not of tumor necrosis factor mRNA. Systemically, secukinumab treatment decreased the C‐reactive protein level and the erythrocyte sedimentation rate (both P < 0.01), and also decreased matrix metalloproteinase 3 production in the TruCulture system (P < 0.05). However, with the exception of IL‐17A itself, the capacity of peripheral blood cells to produce a broad panel of cytokines and chemokines upon stimulation with microbial antigens was not affected. Conclusion: This mechanism‐of‐action study in peripheral SpA indicates that clinical improvement with secukinumab treatment is paralleled by immunomodulation of inflamed target tissues without compromising systemic immune responses. [ABSTRACT FROM AUTHOR]

The behavioral immune system (BIS) is characterized by affective, cognitive and behavioral processes that work in an articulated manner to prevent the occurrence of infections. Attention and memory evolved to enhance the organism's chances of survival and have been proposed to play an important role in the BIS. The present study investigated the effects of attention and memory for neutral faces after a contextual activation of the BIS. Participants were primed, by the use of film clips, either with infectious disease concerns or non‐infectious disease concerns. They performed an exogenous attentional task involving the discrimination of target letters, with face stimuli presented as distractors, which was then followed by a surprise recognition task for the faces. The results showed that participants in the infectious disease condition were more accurate in the attentional task than participants in the control condition. No significant difference between groups was found in the response times during the attention task nor in memory performance. Overall, these results suggest that the BIS might be associated with a hypervigilant state towards cues in general and that BIS activation through this type of priming may not be sufficient to clearly activate mnemonic mechanisms. [ABSTRACT FROM AUTHOR]

Tuberculosis is one of the 10 leading causes of death in the world. The current treatment is based on a combination of antimicrobials administered for six months. It is essential to find therapeutic agents with which the treatment time can be shortened and strengthen the host immune response against Mycobacterium tuberculosis. M. tuberculosis needs cholesterol to infect and survive inside the host, but the progression of the infection depends to a large extent on the capacity of the immune response to contain the infection. Statins inhibit the synthesis of cholesterol and have pleiotropic effects on the immune system, which have been associated with better results in the treatment of several infectious diseases. Recently, it has been reported that cells treated with statins are more resistant to M. tuberculosis infection, and they have even been proposed as adjuvants in the treatment of M. tuberculosis infection. The aim of this review is to summarize the immunopathogenesis of tuberculosis and its mechanisms of evasion and to compile the available scientific information on the effect of statins in the treatment of tuberculosis. [ABSTRACT FROM AUTHOR]

Abstract Dabry's sturgeon (Acipenser dabryanus) is a useful model for the study of fish evolution, as it is one of the most primitive actinopterygian species. However, studies of the immune system of this fish are limited. Here, we identified three toll-like receptors (adaTLR21, adaTLR22, and adaTLR25) from Dabry's sturgeon. The three sturgeon TLRs had characteristic TLR features, including a signal peptide, several leucine rich repeat (LRR) domains, a transmembrane domain, and a Toll/interleukin-1 receptor (TIR) domain. Although the predicted amino acid sequences encoded by the sturgeon adaTLR21, adaTLR22, and adaTLR25 had somewhat low levels of sequence identity and similarity with TLRs from other fish species, the three sturgeon TLRs fell in well-supported clades with other teleost TLRs in our neighbor-joining phylogenetic tree. Real-time quantitative PCR showed that the three sturgeon TLRs were ubiquitously expressed in all examined tissues from healthy adult sturgeon, but that their expression patterns varied greatly among the different tissues. The three sturgeon TLRs were also expressed across all embryonic developmental stages that were examined, but their expression levels differed between developmental stages. All three TLRs were upregulated in head–kidney primary leucocytes following lipopolysaccharide (LPS) and polyinosinic: polycytidylic acid (polyI:C) stimulation. To the best of our knowledge, this is the first characterization of these three TLRs in Darby's sturgeon. Our results provide a framework for further studies of TLR ligand specificity and signaling pathways in sturgeon, and increase our understanding of the functional evolution of TLRs in vertebrates. Highlights • TLR21, TLR22 and TLR25 were identified from the endangered fish cipenser dabryanus. • Sequence features of TLR21, TLR22 and TLR25 were analyzed. • Expression patterns of TLR21, TLR22 and TLR25 in normal tissues were analyzed. • Expression patterns of TLR21, TLR22 and TLR25 in embryonic stages were analyzed. • Expression patterns of TLR21, TLR22 and TLR25 in the HK leucocytes were analyzed. [ABSTRACT FROM AUTHOR]

Fetomaternal immune tolerance is required to prevent fetal rejection during pregnancy; simultaneously, the maternal immune system must also protect the fetus from harmful endogenous and exogenous antigens, including those associated with viral and bacterial infections. Therefore, a delicate immune balance is critical for the maintenance of a successful pregnancy, while disruption of this balance can induce complications such as implantation failure, miscarriage, preterm birth/labor, preeclampsia and fetal growth restriction. While the adaptive immune system is critical for the development of tolerance, this review summarizes evidence that modulation of the innate immunity is also essential for achieving this delicate balance between tolerance and protection. Canonical cells of the innate immune system, including dendritic cells, macrophages, natural killer cells and invariant natural killer T cells, contribute to the modulation of the immune balance at the fetomaternal interface. The newly identified myeloid‐derived suppressor cells and innate lymphoid cells also appear important for successful reproduction. Moreover, it is possible that sterile inflammation facilitates complications of pregnancy via the innate immune system. In this review, the characteristic features and functions of innate immune cells in fetomaternal immunity and their contributions to pregnancy complications related to sterile inflammation are discussed. These insights on innate immune system function in reproduction may provide new perspectives for understanding the mechanisms of fetomaternal tolerance and the etiology of pregnancy complications. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a group of intestinal non-specific inflammatory diseases with unclear pathogenesis, characterized with the impaired intestinal mucosal barriers and the activated immune system. Mucus layer is the vital protector over the intestinal epithelia cells (IECs). Mucus layer with impaired function could not provide isolated protection for IECs and thus proteases and pathogens from the gut lumen attacked and damaged the epithelial layer. Clinical manifestation and histopathology suggest that IBD might be a self-digestive inflammatory disease caused by digestive enzymes. In this review, we specifically focus on the role of intestinal mucosal barriers and aim to summarize the relationship among mucus layer, self-digestion and inflammation in IBD. We also propose a "Two Hits" Self-Digestion theory to explain the role of self-digestion in IBD and assess the application of mucus protectors to treat IBD. [ABSTRACT FROM AUTHOR]

The animal gut effectively prevents the entry of hazardous substances and microbes while permitting the transfer of nutrients, such as water, electrolytes, vitamins, proteins, lipids, carbohydrates, minerals and microbial metabolites, which are intimately associated with intestinal homoeostasis. The gut maintains biological functions through its nutrient-sensing receptors, including the Ca-sensing receptor (CaSR), which activates a variety of signalling pathways, depending on cellular context. CaSR coordinates food digestion and nutrient absorption, promotes cell proliferation and differentiation, regulates energy metabolism and immune response, stimulates hormone secretion, mitigates secretory diarrhoea and enhances intestinal barrier function. Thus, CaSR is crucial to the maintenance of gut homoeostasis and protection of intestinal health. In this review, we focused on the emerging roles of CaSR in the modulation of intestinal homoeostasis including related underlying mechanisms. By elucidating the relationship between CaSR and animal gut homoeostasis, effective and inexpensive methods for treating intestinal health imbalance through nutritional manipulation can be developed. This article is expected to provide experimental data of the effects of CaSR on animal or human health. [ABSTRACT FROM AUTHOR]

Cross-talk between the nervous and immune systems has been well described in the context of adult physiology and disease. Recent advances in our understanding of immune cell ontogeny have revealed a notable interplay between neurons and microglia during the prenatal and postnatal emergence of functional circuits. This Review focuses on the brain, where the early symbiotic relationship between microglia and neuronal cells critically regulates wiring, contributes to sex-specific differences in neural circuits, and relays crucial information from the periphery, including signals derived from the microbiota. These observations underscore the importance of studying neurodevelopment as part of a broader framework that considers nervous system interactions with microglia in a whole-body context. [ABSTRACT FROM AUTHOR]

The complement system plays an important role in innate immunity inducing liver diseases as well as signaling immune cell activation in local inflammation regulating immunomodulatory effects such as liver damage and/or liver regeneration. Our aim is to evaluate the role of complement components in acute liver failure (ALF) caused by viral hepatitis, involving virus-induced ALF in human subjects using peripheral blood, samples of liver tissues, and ex vivo assays. Our findings displayed low levels of C3a in plasma samples with high frequency of C3a, C5a, and C5b/9 deposition in liver parenchyma. Meanwhile, laboratory assays using HepG2 (hepatocyte cell line) showed susceptibility to plasma samples from ALF patients impairing in vitro cell proliferation and an increase in apoptotic events submitting plasma samples to heat inactivation. In summary, our data suggest that the complement system may be involved in liver dysfunction in viral-induced acute liver failure cases using ex vivo assays. In extension to our findings, we provide insights into future studies using animal models for viral-induced ALF, as well as other associated soluble components, which need further investigation. [ABSTRACT FROM AUTHOR]

Highlights • Complement proteins in neuromuscular junctions as first sign of pathology implicate systemic innate immune system in the pathophysiology of ALS. • Increasing complement activation in spinal cord during progression suggests that the complement system contributes to the pathogenesis of ALS. • Cross-talk between microglia and motor neurons via imbalanced local complement seems to exacerbate the destruction of ALS motor neurons. • Cytotoxicity in plasma/serum from ALS patients indicates systemic involvement of the innate immune system. Abstract Amyotrophic lateral sclerosis (ALS) is a devastating, neurodegenerative motor neuron disease. The aetiology of ALS remains an enigma which hinders the design of an effective treatment to prevent, postpone, or reverse the pathophysiological changes occurring during the aggressive progression of this disease. During the last decade, basic research within the innate immune system, and in particular the complement system, has revealed new, important roles of the innate immune system during development, homeostasis, and ageing within as well as outside the central nervous system. Several lines of evidence indicate that aberrant activation of the complement system locally in the central nervous system as well as systemically may be involved in the pathophysiology of ALS. This exciting new knowledge could point towards the innate immune system as a potential target of medical intervention in ALS. Recently, the historic perception of ALS as a central neurodegenerative disease has been challenged due to the significant amount of evidence of a dying-back mechanism causing the selective destruction of the motor neurons, indicating that disease onset occurs outside the borders of the blood-brain-barrier. This review addresses the function of the innate immune system during ALS. We emphasize the role of the complement system and specifically suggest the involvement of ficolin-3 from the lectin pathway in the pathophysiology of ALS. [ABSTRACT FROM AUTHOR]

Abstract Relationship between mood disorders and inflammation is now well-documented, although molecular mechanisms are not understood. Previously mostly pro-inflammatory cytokines of immune system (IL-6, TNF, etc.) were taken into account. However, recent understanding of resolution of inflammation as an active process drew attention to mediators of resolution, which include both proteins and ω-3 and ω-6 polyunsaturated fatty acids derivatives (resolvins, cyclopentenone prostaglandins, etc.). This review takes into account new data on resolution of inflammation and action of mediators of resolution in models of depression. New facts and ideas about mechanisms of chronic inflammation onset are considered in relation to mood disorders. Basic control mechanisms of inflammation at the cellular level and the role of resolution substances in regulation of depression and other mood disorders are discussed. Signaling systems of innate immunity located in non-immune cells and their ability to generate substances that affect an onset of depression are reviewed. A novel hypothesis of depression as a type of abnormal resolution is proposed. Highlights • Inflammation accompanies depression and other mood disorders in 30-50% of cases. • Chronic inflammatory diseases have comorbidity with mood disorders in 10-80% of cases. • Antidepressants as anti-inflammatory agents and anti-inflammatory substances as antidepressants. • Concept of resolution of inflammation is applicable for mood disorders. • Specialized pro-resolving mediators (SPM) can prove to be a new type of antidepressants. [ABSTRACT FROM AUTHOR]

Few studies to date have reported on the myelodysplastic features of children with juvenile idiopathic arthritis (JIA). Bone marrow specimens were collected from 107 patients aged from 7-12 years who were initially diagnosed with JIA between May 2013 and October 2015. In 107 patients with JIA, bone marrow proliferation was higher than normal and hemophagocytes were more easily observed than usual. The characteristics of bone marrow cells in 107 patients with JIA were investigated and the associations of these characteristics with the disease was discussed in the present study. It was noticed that there were similar changes in the myeloid, erythropoietic and megakaryopoietic series in the majority of bone marrow specimens; the presence of hemophagocytes was also reported. The present findings suggest that JIA is associated with specific myelodysplastic changes, and that cellular immune system dysfunction and overreactive inflammatory cytokines may contribute to the development of these myelodysplastic changes in the bone marrow. [ABSTRACT FROM AUTHOR]

Highlights • Findings on microglia activation upon maternal immune activation are divergent. • Several methodological factors could underlie these divergent study outcomes. • More consistent methodological approaches and new technologies are needed. Abstract Activation of the maternal immune system during pregnancy is a well-established risk factor for neuropsychiatric disease in the offspring, yet, the underlying mechanisms leading to altered brain function remain largely undefined. Microglia, the resident immune cells of the brain, are key to adequate development of the central nervous system (CNS), and are prime candidates to mediate maternal immune activation (MIA)-induced brain abnormalities. As such, the effects of MIA on the immunological phenotype of microglia has been widely investigated. However, contradicting results due to differences in read-out and methodological approaches impede final conclusions on MIA-induced microglial alterations. The aim of this review is to critically discuss the evidence for an activated microglial phenotype upon MIA. [ABSTRACT FROM AUTHOR]

Complex Regional Pain Syndrome (CRPS) has defied a clear unified pathological explanation to date. Not surprisingly, treatments for the condition are limited in number, efficacy and their ability to enact a cure. Whilst many observations have been made of physiological abnormalities, how these explain the condition and who does and doesn't develop CRPS remains unclear. We propose a new overarching hypothesis to explain the condition that invokes four dynamically changing and interacting components of tissue trauma, pathological pain processing, autonomic dysfunction (both peripheral and central) and immune dysfunction, primarily involving excessive and pathological activation of dendritic cells following trauma or atrophy. We outline pathophysiological changes that may initiate a cascade of events involving dendritic cells and the cholinergic anti-inflammatory pathway resulting in the condition, and the changes that maintain the condition into its chronic phase. This hypothesis should provide fertile ground for further investigations and development of new treatments that holistically address the nature of the disorder along its developmental continuum. [ABSTRACT FROM AUTHOR]