Gender differences in Damp-Heat Syndrome: A review.

Gender differences have important biological significance for medical research. In this study, a bias towards males was identified in animal experiments of Damp-Heat Syndrome in traditional Chinese medicine, as was first proposed by a data mining method. Combined with the correlation between Damp-Heat Syndrome in traditional Chinese medicine and Gender differences, it was considered that Gender-related factors have a significant influence on the development of Damp-Heat Syndrome in traditional Chinese medicine. However, most traditional Chinese medicine studies ignore the key significance of Gender-related factors. This study emphasises that the development of modern traditional Chinese medicine research needs to pay full attention to the biological significance of Gender-related factors and to apply this concept to the research on the Gender equivalence strategy in basic research and the practice of personalised medical diagnosis and clinical treatment.

Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences.

Racial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P < 0.001) and ETS (P = 0.02) expression, decreased SPINK1 expression (P < 0.001), and basal-like (P < 0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p < 0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM.

Effects of anxiety sensitivity, disgust, and intolerance of uncertainty on the COVID stress syndrome: a longitudinal assessment of transdiagnostic constructs and the behavioural immune system.

Excessive fear and worry in response to the COVID-19 pandemic (e.g., COVID stress syndrome) is prevalent and associated with various adverse outcomes. Research from the current and past pandemics supports the association between transdiagnostic constructs-anxiety sensitivity (AS), disgust, and intolerance of uncertainty (IU)-and pandemic-related distress. Recent research suggests a moderating effect of disgust on the relationship of AS-physical concerns and COVID-19-related distress, suggesting that transdiagnostic constructs underlie individual differences in activation of the behavioral immune system (BIS). No previous study has examined the independent and conjoint effects of pre-COVID-19 AS-physical concerns, disgust propensity (DP), disgust sensitivity (DS), and IU in this context; thus, we did so using longitudinal survey data (N = 3,062 Canadian and American adults) with simple and moderated moderations controlling for gender, mental health diagnosis, and COVID-19 diagnosis. Greater AS-physical concerns, DP, and DS predicted more severe COVID stress syndrome assessed one month later. Either DP or DS further amplified the effect of AS-physical concerns on COVID stress syndrome, except danger and contamination fears. IU did not interact with AS-physical concerns and DS or DP. Theoretical and clinical implications pertaining to delivery of cognitive behavioural therapy for pandemic-related distress are discussed.

The Interplay Between Neuroinfections, the Immune System and Neurological Disorders: A Focus on Africa.

Neurological disorders related to neuroinfections are highly prevalent in Sub-Saharan Africa (SSA), constituting a major cause of disability and economic burden for patients and society. These include epilepsy, dementia, motor neuron diseases, headache disorders, sleep disorders, and peripheral neuropathy. The highest prevalence of human immunodeficiency virus (HIV) is in SSA. Consequently, there is a high prevalence of neurological disorders associated with HIV infection such as HIV-associated neurocognitive disorders, motor disorders, chronic headaches, and peripheral neuropathy in the region. The pathogenesis of these neurological disorders involves the direct role of the virus, some antiretroviral treatments, and the dysregulated immune system. Furthermore, the high prevalence of epilepsy in SSA (mainly due to perinatal causes) is exacerbated by infections such as toxoplasmosis, neurocysticercosis, onchocerciasis, malaria, bacterial meningitis, tuberculosis, and the immune reactions they elicit. Sleep disorders are another common problem in the region and have been associated with infectious diseases such as human African trypanosomiasis and HIV and involve the activation of the immune system. While most headache disorders are due to benign primary headaches, some secondary headaches are caused by infections (meningitis, encephalitis, brain abscess). HIV and neurosyphilis, both common in SSA, can trigger long-standing immune activation in the central nervous system (CNS) potentially resulting in dementia. Despite the progress achieved in preventing diseases from the poliovirus and retroviruses, these microbes may cause motor neuron diseases in SSA. The immune mechanisms involved in these neurological disorders include increased cytokine levels, immune cells infiltration into the CNS, and autoantibodies. This review focuses on the major neurological disorders relevant to Africa and neuroinfections highly prevalent in SSA, describes the interplay between neuroinfections, immune system, neuroinflammation, and neurological disorders, and how understanding this can be exploited for the development of novel diagnostics and therapeutics for improved patient care.

Life Course Socioeconomic Disadvantage and the Aging Immune System: Findings From the Health and Retirement Study.

OBJECTIVES: Previous research has documented a consistent association between current socioeconomic status (SES) and cytomegalovirus (CMV). Early life is likely a critical period for CMV exposure and immune development, but less is known about early-life socioeconomic factors and CMV, particularly in older age populations. Using data from the Health and Retirement Study, we investigated the association between life course socioeconomic disadvantage and immune response to CMV among older adults. METHODS: Using ordered logit models, we estimated associations between several measures of socioeconomic disadvantage and the odds of being in a higher CMV Immunoglobulin G (IgG) response category in a sample of 8,168 respondents aged older than 50 years. RESULTS: We found a significant association between educational attainment and CMV IgG response. Those with less than a high school education had 2.00 (95% confidence interval [CI]: 1.67-2.40) times the odds of being in a higher CMV category compared to those with a college degree or greater. In addition, we also observed a significant association with parental education and CMV response. Individuals with parents having 8 years or less of schooling had 2.32 (95% CI: 2.00-2.70) times the odds of higher CMV response compared to those whose parents had greater than high school education. DISCUSSION: CMV IgG levels in older adults are associated with both early-life and adult SES. Life course socioeconomic disadvantage may contribute to disparities in immunological aging.

The prospects of single-cell analysis in autoimmunity.

In the last decade, there has been a tremendous development of technologies focused on analysing various molecular attributes in single cells, with an ever-increasing number of parameters becoming available at the DNA, RNA and protein levels. Much of this progress has involved cells in suspension, but also in situ analysis of tissues has taken great leaps. Paralleling the development in the laboratory, and because of increasing complexity, the analysis of single-cell data is also constantly being updated with new algorithms and analysis platforms. Our immune system shares this complexity, and immunologists have therefore been in the forefront of this technological development. These technologies clearly open new avenues for immunology research, maybe particularly within autoimmunity where the interaction between the faulty immune system and the thymus or the target organ is important. However, the technologies currently available can seem overwhelming and daunting. The aim of this review is to remedy this by giving a balanced overview of the prospects of using single-cell analysis in basal and clinical autoimmunity research, with an emphasis on endocrine autoimmunity.

An Assessment of the Glyconutrient Ambrotose™ on Immunity, Gut Health, and Safety in Men and Women: A Placebo-Controlled, Double-Blind, Randomized Clinical Trial.

BACKGROUND: Certain dietary fibers have been reported to improve gut health and cellular immunity. Ambrotose is a glyconutrient supplement that contains mannose-rich polysaccharides (acemannan), reported to improve immune function. A more nutrient-dense version of this dietary supplement has been developed recently, with added aloe leaf gel powder (acemannan). The purpose of this study was to evaluate the impact of the traditional and newly developed Ambrotose products on immunity, gut health, and psychological well-being in healthy men and women. METHODS: Seventy-five men and women were randomly assigned in double-blind manner to one of five treatments, as follows: Ambrotose Advanced (AA) at 2 or 4 g daily, Ambrotose LIFE (AL) at 2 or 4 g daily, or placebo. Subjects ingested their assigned treatment daily for eight weeks. Resting heart rate, blood pressure, and measures of psychological well-being were analyzed before and after four and eight weeks of supplementation. Blood samples were collected at the same times and analyzed for zonulin, hematology measures, and cytokines-IL-6, IL-10, IL-1ß, and TNF-α (analyzed both with and without stimulation via lipopolysaccharide [LPS]). RESULTS: All Ambrotose treatments were well-tolerated. There were no differences among treatments in heart rate or blood pressure across time. Self-reported well-being scores were generally higher for the Ambrotose treatments but there were no changes of statistical significance across time (p > 0.05). Differences of statistical significance were noted for select biochemical variables, the most notable being a dramatic decrease in monocytes in the Ambrotose groups. No change was noted in the cytokine response to LPS stimulation in all groups, indicating a maintenance of a healthy immune response. Conclusion: Regular supplementation with Ambrotose is safe and can improve subclinical cellular adversity (as evidenced by a decrease in monocytes), without unnecessary activation of an immune response.

The Heart as a Psychoneuroendocrine and Immunoregulatory Organ.

The heart can be viewed not just as muscle pump but also as an important checkpoint for a complex network of nervous, endocrine, and immune signals. The heart is able to process neurological signals independently from the brain and to crosstalk with the endocrine and immune systems. The heart communicates with the psyche through the neuro-endocrine-immune system in a highly integrated way, in order to maintain the homeostasis of the whole body with peculiarities specific to males and females.

Immunological and toxicological risk assessment of e-cigarettes.

Knowledge of the long-term toxicological and immunological effects of e-cigarette (e-cig) aerosols remains elusive due to the relatively short existence of vaping. Therefore, we performed a systematic search of articles published in public databases and analysed the research evidence in order to provide critical information regarding e-cig safety. Electronic nicotine delivery systems (or e-cigs) are an alternative to traditional cigarettes for the delivery of nicotine and are typically filled with glycerol or propylene glycol-based solutions known as e-liquids. Though present in lower quantities, e-cig aerosols are known to contain many of the harmful chemicals found in tobacco smoke. However, due to the paucity of experimental data and contradictory evidence, it is difficult to draw conclusive outcomes regarding toxicological, immunological and clinical impacts of e-cig aerosols. Excessive vaping has been reported to induce inflammatory responses including mitogen-activated protein kinase, Janus tyrosine kinase/signal transducer and activator of transcription and nuclear factor-κB signalling, similar to that induced by tobacco smoke. Based on recent evidence, prolonged exposure to some constituents of e-cig aerosols might result in respiratory complications such as asthma, chronic obstructive pulmonary disease and inflammation. Future studies are warranted that focus on establishing correlations between e-cig types, generations and e-liquid flavours and immunological and toxicological profiles to broaden our understanding about the effects of vaping.

Application of Monte Carlo cross-validation to identify pathway cross-talk in neonatal sepsis.

To explore genetic pathway cross-talk in neonates with sepsis, an integrated approach was used in this paper. To explore the potential relationships between differently expressed genes between normal uninfected neonates and neonates with sepsis and pathways, genetic profiling and biologic signaling pathway were first integrated. For different pathways, the score was obtained based upon the genetic expression by quantitatively analyzing the pathway cross-talk. The paired pathways with high cross-talk were identified by random forest classification. The purpose of the work was to find the best pairs of pathways able to discriminate sepsis samples versus normal samples. The results found 10 pairs of pathways, which were probably able to discriminate neonates with sepsis versus normal uninfected neonates. Among them, the best two paired pathways were identified according to analysis of extensive literature. Impact statement To find the best pairs of pathways able to discriminate sepsis samples versus normal samples, an RF classifier, the DS obtained by DEGs of paired pathways significantly associated, and Monte Carlo cross-validation were applied in this paper. Ten pairs of pathways were probably able to discriminate neonates with sepsis versus normal uninfected neonates. Among them, the best two paired pathways ((7) IL-6 Signaling and Phospholipase C Signaling (PLC); (8) Glucocorticoid Receptor (GR) Signaling and Dendritic Cell Maturation) were identified according to analysis of extensive literature.

Unmet Needs in Systemic Sclerosis Understanding and Treatment: the Knowledge Gaps from a Scientist's, Clinician's, and Patient's Perspective.

Systemic sclerosis (SSc) is a highly heterogeneous disease caused by a complex molecular circuitry. For decades, clinical and molecular research focused on understanding the primary process of fibrosis. More recently, the inflammatory, immunological and vascular components that precede the actual onset of fibrosis, have become a matter of increasing scientific scrutiny. As a consequence, the field has started to realize that the early identification of this syndrome is crucial for optimal clinical care as well as for understanding its pathology. The cause of SSc cannot be appointed to a single molecular pathway but to a multitude of molecular aberrances in a spatial and temporal matter and on the backbone of the patient's genetic predisposition. These alterations underlie the plethora of signs and symptoms which patients experience and clinicians look for, ultimately culminating in fibrotic features. To solve this complexity, a close interaction among the patient throughout its "journey," the clinician through its clinical assessments and the researcher with its experimental design, seems to be required. In this review, we aimed to highlight the features of SSc through the eyes of these three professionals, all with their own expertise and opinions. With this unique setup, we underscore the importance of investigating the role of environmental factors in the onset and perpetuation of SSc, of focusing on the earliest signs and symptoms preceding fibrosis and on the application of holistic research approaches that include a multitude of potential molecular alterations in time in an unbiased fashion, in the search for a patient-tailored cure.

Social status alters immune regulation and response to infection in macaques.

Social status is one of the strongest predictors of human disease risk and mortality, and it also influences Darwinian fitness in social mammals more generally. To understand the biological basis of these effects, we combined genomics with a social status manipulation in female rhesus macaques to investigate how status alters immune function. We demonstrate causal but largely plastic social status effects on immune cell proportions, cell type-specific gene expression levels, and the gene expression response to immune challenge. Further, we identify specific transcription factor signaling pathways that explain these differences, including low-status-associated polarization of the Toll-like receptor 4 signaling pathway toward a proinflammatory response. Our findings provide insight into the direct biological effects of social inequality on immune function, thus improving our understanding of social gradients in health.

Assessment of bone marrow lymphocytic status during tyrosine kinase inhibitor therapy and its relation to therapy response in chronic myeloid leukaemia.

PURPOSE: Tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukaemia have been reported to induce immunomodulatory effects. We aimed to assess peripheral blood (PB) and bone marrow (BM) lymphocyte status at the diagnosis and during different TKI therapies and correlate it with treatment responses. METHODS: BM and PB samples were acquired from 105 first-line TKI-treated patients. Relative number of BM lymphocytes was evaluated from MGG-stained BM aspirates, and immunophenotypic analyses were performed with multicolour flow cytometry. RESULTS: Early 3-month expansion of BM lymphocytes was found during all different TKIs (imatinib n = 71, 20 %; dasatinib n = 25, 21 %; nilotinib n = 9, 22 %; healthy controls n = 14, 12 %, p < 0.0001). Increased PB lymphocyte count was only observed during dasatinib therapy. The BM lymphocyte expansion was associated with early molecular response; patients with 3-month BCR-ABL1 <10 % showed higher lymphocyte counts than patients with BCR-ABL1 >10 % (23 vs. 17 %, p < 0.05). Detailed phenotypic analysis showed that BM lymphocyte expansion consisted of various lymphocyte subclasses, but especially the proportion of CD19+ B cells and CD3negCD16/56+ NK cells increased from diagnostic values. During dasatinib treatment, the lymphocyte balance in both BM and PB was shifted more to cytotoxic direction (increased CD8+CD57+ and CD8+HLA-DR+ cells, and low T regulatory cells), whereas no major immunophenotypic differences were observed between imatinib and nilotinib patients. CONCLUSIONS: Early BM lymphocytosis occurs with all current first-line TKIs and is associated with better treatment responses. PB and BM immunoprofile during dasatinib treatment markedly differs from both imatinib- and nilotinib-treated patients.

Sex and Gender Impact Immune Responses to Vaccines Among the Elderly.

In response to the recommended vaccines in older-aged individuals, sex differences occur in response to those that protect against influenza, tetanus, pertussis, shingles, and pneumococcal infections. The efficacy of vaccines recommended for older-aged adults is consistently greater for females than for males. Gender differences as well as biological sex differences can influence vaccine uptake, responses, and outcome in older-aged individuals, which should influence guidelines, formulations, and dosage recommendations for vaccines in the elderly.

Assessment of ixekizumab, an interleukin-17A monoclonal antibody, for potential effects on reproduction and development, including immune system function, in cynomolgus monkeys.

The reproductive and developmental toxicity of ixekizumab, a selective inhibitor of interleukin-17A (IL-17A), was assessed in the following studies in cynomolgus monkeys: fertility (3-month dosing), embryo-fetal development (EFD; dosing from gestation day (GD) 20 through 139), and pre-postnatal development (PPND; dosing from GD 20 through parturition). Because IL-17A has functional roles in innate and humoral immunity, immune system modulation was evaluated in the EFD and PPND studies; immunological evaluations in infants comprised peripheral blood immunophenotyping, Natural Killer cell cytolytic activity, and T-cell-dependent antibody (IgG and IgM) primary and secondary responses to antigen challenge. Ixekizumab exposure was sustained during the dosing periods in most adult monkeys. Fetal exposure at Cesarean section (GD 140-142; EFD study) was 18-25% of maternal exposure and ixekizumab was present in infants for up to 29 weeks postpartum. There were no adverse effects attributed to ixekizumab in any study. Importantly, immune system development and maturation were unaffected.

Activation of the immune system incurs energetic costs but has no effect on the thermogenic performance of house sparrows during acute cold challenge.

Trade-offs between the immune system and other condition-dependent life-history traits (reproduction, predator avoidance and somatic growth) have been well documented in both birds and mammals. However, no studies have examined the impact of immune activation on thermoregulatory performance during acute cold exposure. Because of their high surface-area-to-volume ratios, small birds incur high energetic costs associated with thermoregulation during cold exposure. Consequently, we predicted that the immune system and the thermoregulatory system would compete for energetic resources. To test this, we immunologically challenged adult house sparrows (Passer domesticus) with 5 mg kg(-1) of lipopolysaccharide (LPS) to induce an acute phase response and measured both resting (RMR; minimum metabolic rate) and summit ( ; maximal metabolic rate during cold exposure) metabolic rates. We found that birds injected with LPS had significantly higher RMR and than birds injected with phosphate-buffered saline, indicating that LPS-treated birds were able to support the cost of both immune activation and thermoregulation under conditions eliciting maximal thermogenic performance. These results suggest that, in the absence of a pathogen, birds that experience short-term activation of the immune system have higher energetic costs during cold exposure, but immune activation does not compromise maximum thermoregulatory performance.

Survey: immune function and immunotoxicity assessment in dogs.

While immunotoxicology evaluations are often conducted in either rodents or non-human primates, findings in standard toxicology studies may trigger additional investigations in dogs. A survey sponsored by the HESI Immunotoxicology Technical Committee, and described herein, was conducted to gather information regarding the extent and nature of immunology and immunotoxicity assessments available in the dog, and the need thereof. The survey was issued via e-mail to scientists affiliated with 39 organizations in industry and academia, including contract research organizations, academic research organizations, pharmaceutical companies, and veterinary practices. Fifteen institutions responded, including 10 biotechnology or pharmaceutical industry organizations, 4 contract research organizations, and 1 academic institution. Responses indicated that indeed, immunological assessments in dogs are necessary for research and/or toxicology purposes. The survey demonstrated that multiple types of assays are used in the dog model, including assessment of T-cell-dependent antibody responses, immunoglobulins, complement CH(50), cytokines and cytokine mRNAs, lymphocyte proliferation in response to T-cell mitogens, neutrophil activation, phagocytosis, and immunophenotyping of several cell types. The survey also revealed that certain assays/endpoints are not available in the dog (complement components, NK immunophenotyping, T-cell activation and memory immunophenotyping) or require further optimization (ex vivo cytolysis assays such as CTL and NK function, B-cell proliferation in response to LPS). In addition, the survey indicated that a greater understanding of the specificity of the available immunophenotyping reagents is needed.

Quantitative assessment of immune cells in the injured spinal cord tissue by flow cytometry: a novel use for a cell purification method.

Detection of immune cells in the injured central nervous system (CNS) using morphological or histological techniques has not always provided true quantitative analysis of cellular inflammation. Flow cytometry is a quick alternative method to quantify immune cells in the injured brain or spinal cord tissue. Historically, flow cytometry has been used to quantify immune cells collected from blood or dissociated spleen or thymus, and only a few studies have attempted to quantify immune cells in the injured spinal cord by flow cytometry using fresh dissociated cord tissue. However, the dissociated spinal cord tissue is concentrated with myelin debris that can be mistaken for cells and reduce cell count reliability obtained by the flow cytometer. We have advanced a cell preparation method using the OptiPrep gradient system to effectively separate lipid/myelin debris from cells, providing sensitive and reliable quantifications of cellular inflammation in the injured spinal cord by flow cytometry. As described in our recent study (Beck & Nguyen et al., Brain. 2010 Feb; 133 (Pt 2): 433-47), the OptiPrep cell preparation had increased sensitivity to detect cellular inflammation in the injured spinal cord, with counts of specific cell types correlating with injury severity. Critically, novel usage of this method provided the first characterization of acute and chronic cellular inflammation after SCI to include a complete time course for polymorphonuclear leukocytes (PMNs, neutrophils), macrophages/microglia, and T-cells over a period ranging from 2 hours to 180 days post-injury (dpi), identifying a surprising novel second phase of cellular inflammation. Thorough characterization of cellular inflammation using this method may provide a better understanding of neuroinflammation in the injured CNS, and reveal an important multiphasic component of neuroinflammation that may be critical for the design and implementation of rational therapeutic treatment strategies, including both cell-based and pharmacological interventions for SCI.

Life is a huge compromise: is the complexity of the vertebrate immune-neuroendocrine system an advantage or the price to pay?

Recent advances in comparative immunology have established that invertebrates produce hypervariable molecules probably related to immunity, suggesting the possibility of raising a specific immune response. "Priming" and "tailoring" are terms now often associated with the invertebrate innate immunity. Comparative immunologists contributed to eliminate the idea of a static immune system in invertebrates, making necessary to re-consider the evolutive meaning of immunological memory of vertebrates. If the anticipatory immune system represents a maximally efficient immune system, why can it be observed only in vertebrates, especially in consideration that molecular hypervariability exists also in invertebrates? Using well-established theories concerning the evolution of the vertebrate immunity as theoretical basis we analyze from an Eco-immunology-based perspective why a memory-based immune system may have represented an evolutive advantage for jawed vertebrates. We hypothesize that for cold-blooded vertebrates memory represents a complimentary component that flanks the robust and fundamental innate immunity. Conversely, immunological memory has become indispensable and fully exploited in warm-blooded vertebrates, due to their stable inner environment and high metabolic rate, respectively.