Immune Disturbances Research Articles

Longitudinal 1H NMR-Based Metabolomics in Saliva Unveils Signatures of Transition from Acute to Post-Acute Phase of SARS-CoV-2 Infection

COVID-19 can range from a mild to severe acute respiratory syndrome and also could result in multisystemic damage. Additionally, many people develop post-acute symptoms associated with immune and metabolic disturbances in response to viral infection, requiring longitudinal and multisystem studies to understand the complexity of COVID-19 pathophysiology. Here, we conducted a 1H Nuclear Magnetic Resonance metabolomics in saliva of symptomatic subjects presenting mild and moderate respiratory symptoms to investigate prospective changes in the metabolism induced after acute-phase SARS-CoV-2 infection. Saliva from 119 donors presenting non-COVID and COVID-19 respiratory symptoms were evaluated in the acute phase (T1) and the post-acute phase (T2). We found two clusters of metabolite fluctuation in the COVID-19 group. Cluster 1, metabolites such as glucose, (CH3)3 choline-related metabolites, 2-hydroxybutyrate, BCAA, and taurine increased in T2 relative to T1, and in cluster 2, acetate, creatine/creatinine, phenylalanine, histidine, and lysine decreased in T2 relative to T1. Metabolic fluctuations in the COVID-19 group were associated with overweight/obesity, vaccination status, higher viral load, and viral clearance of the respiratory tract. Our data unveil metabolic signatures associated with the transition to the post-acute phase of SARS-CoV-2 infection that may reflect tissue damage, inflammatory process, and activation of tissue repair cascade. Thus, they contribute to describing alterations in host metabolism that may be associated with prolonged symptoms of COVID-19.

Immunological role of zinc in preterm neonates

Zinc (Zn), an essential trace element, plays a significant role in fetal development and biological defense during the embryonic and neonatal periods. Therefore, exploring the kinetics of Zn related to immune disturbances in preterm neonates is important. We here performed the measurement of Zn concentration along with immunological analysis of neonates and investigated the role of Zn in the neonatal period. Serum Zn concentrations were measured immediately after birth in neonates (329 cases). Moreover, for 25 cases, the kinetics of various immune cells and cytokines were measured by flow cytometry and electrochemiluminescence. We observed that Zn levels were inversely correlated with gestational weeks. Immune cell and cytokine analysis revealed an inverse correlation between HLA-DR on monocytes and Zn levels and between inflammatory cytokine interleukin-12 and Zn levels. Furthermore, oxidative stress status was inversely correlated with Zn levels. Our results suggested that the Zn dynamics immediately after birth, which show a negative correlation with the gestational week, can provide an anti-inflammatory and anti-oxidative environment for preterm neonates. The increased Zn concentration in the blood of preterm neonates may consequently protect neonates from perinatal stress.

Disturbances of Interoception in Schizophrenia – Focus on Neuroimaging

Abstract: The current paper presents the most recent theoretical understanding of interoception (INTC) in light of the predictive processing framework and the Embodied Predictive Interoceptive Coding model and reviews recent experimental data on different interoceptive disturbances in schizophrenia (SCZ) such as lower interoceptive accuracy, nociceptive dysfunction reflected by reduced pain sensitivity, disturbed thermoregulation, impaired gastrointestinal regulation, cardiovascular and respiratory dysfunction, and immune disturbances. The immense clinical implications of these disturbances are discussed in the context of the high rates of morbidity and mortality in SCZ related to suicide and cardiac death. Next, the potential of INTC-related treatments is reviewed, and conclusions are made on the evidence for the use of vagus nerve stimulation, mindfulness-based interventions, and exercise therapy. The neuroimaging perspective is given in a brief account of the INTC-related findings in healthy individuals suggesting the right anterior insula and anterior cingulate cortex as key brain areas for interoceptive awareness, accuracy, and sensibility, by supporting higher-order representation and integration of visceral, and somatosensory interoception with exteroceptive information. In SCZ, on the other hand, neuroimaging research on specific interoceptive abilities is lacking but indirect evidence points to disrupted activation of major INTC network hubs. There is converging evidence of changes in these hubs in terms of both structure and function (volume reductions, aberrant activation, and connectivity). This narrative review identifies several gaps in contemporary INTC-related research in SCZ that need to be addressed in future experimental and clinical studies to elucidate the exact nature of the disturbances of interoceptive abilities in modalities other than cardioception; the interactions between different interoceptive modalities; the association between interoceptive abilities and other mental functions (such as emotion recognition and regulation, decision making, learning, memory, etc.); the efficacy of nonpharmacological and pharmacological INTC-based interventions; and the relation of disturbed interoceptive abilities with brain structure and function.

Multiple organ failure: What you need to know.

Multiple organ failure (MOF) remains a significant challenge for the acute care surgeon, often leading to poor patient outcomes. This comprehensive review explores the etiology, pathophysiology, clinical presentation, diagnosis, management strategies, prognosis, and prevention strategies associated with MOF and chronic critical illness. Understanding the intricate etiology and pathophysiology of MOF and chronic critical illness is essential for effectively managing these syndromes and developing targeted treatment strategies aimed at mitigating the underlying inflammatory, immune, and microvascular disturbances, in order to redirect patients onto a trajectory of recovery.

P-762 Discovery and quantification of microplastics in human cumulus granulosa cells

Abstract Study question The impact of microplastics (MPs) on human health has received increasing attention; their accumulation in female reproductive system and possible harms have not been quantified. Summary answer This study firstly reveals the contamination of human cumulus granulosa cells and follicular fluid by MPs and the effects of these contaminants on ART outcomes. What is known already MPs are ubiquitous in soil, sea, air, fresh water, and other environments. MPs are ingested by humans through the food chain, air and direct contact, resulting in various health problems, such as endocrine disruption, immune disturbance and reproductive toxicity. MPs exposure has been found to have a great impact on females, as MPs may accumulate in the ovaries and reduce the number of follicles, ovarian size, pregnancy rate, embryo production and fertility. To date, one study has found evidence of MPs in human placentas for the first time, but MPs contamination in other human reproductive systems has not been identified. Study design, size, duration The inclusion criteria comprised female patients of infertile couples excluding male factors who visited the outpatient department of the Reproductive and Genetic Hospital of CITIC-Xiangya between January 2019 and January 2021.We randomly selected 16 women who met the criteria and assessed their CCs and follicular fluid samples for the presence of MPs. Participants/materials, setting, methods In the present study, 16 cumulus granulosa cell samples and 2 follicular fluid samples were collected, and MPs were detected via pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). Main results and the role of chance MPs were detected in both cumulus granulosa cells and follicular fluid, with an average abundance of 313.14±246.69 mg/kg in cumulus granulosa cellsand 12.88±15.54 mg/kg in follicular fluid. Polyethylene terephthalate was the predominant polymer in cumulus granulosa cells. There were no significant differences in the IVF fertilization rates, ICSI fertilization rates, IVF good-quality embryo rates, or ICSI good-quality embryo rates between the high-MP group and low-MP group. However, embryos in the high-MP group exhibited a lower normal cleavage rate than did those in the low-MP group, while the embryos in the high-MP group exhibited a greater proportion of noncleavage than did those in the low-MP group. Limitations, reasons for caution It is not clear how long these particles may persist in the human body. The method we used can detect only the concentration of MPs but not the size of MP particles. Moreover, our method cannot be used to quantify smaller-diameter nanoplastics, which are considered to pose greater risks. Wider implications of the findings This is the first study in which MPs were identified and characterized in human ovarian granulosa cells, providing reference data for evaluating their toxicity to the human female reproductive system. Trial registration number Not applicable

O-032 Intravenous immunoglobulin and prednisolone to women with unexplained recurrent pregnancy loss undergoing assisted reproductive technology treatment: a randomized, double-blinded, placebo-controlled trial

Abstract Study question Does intravenous immunoglobulin (IVIG) and prednisolone in combination affect ongoing pregnancy rate among patients with recurrent pregnancy loss (RPL) after assisted reproductive technology (ART) treatment? Summary answer The results of this trial will provide important information about whether immunomodulatory treatment to RPL patients undergoing ART treatment can increase clinical pregnancy rate. What is known already Two retrospective cohort studies suggest that IVIG and prednisolone in combination result in a 34-37% live birth rate in RPL patients undergoing ART which is higher than the expected 12% for patients with RPL after ART. A randomized controlled trial (RCT) testing IVIG in RPL patients conceiving naturally indicated that very early administration of IVIG caused more positive effects than late administration, and prospective cohort studies suggest that treatment efficacy depends on presence of immune disturbances. No RCT has tested the IVIG/prednisolone combination starting before implantation and continued in very early pregnancy for RPL patients undergoing ART. Study design, size, duration In a randomized, double-blinded, placebo-controlled trial, patients undergoing IVF/ICSI/FET were treated with 400mg/kg IVIG and 5-10mg/day oral prednisolone or IV human albumin and oral placebo between January 2021 and March 2024. Oral treatment was administered from day one of menstrual cycle to GW 8 + 4, while IV treatment was given once in a short time interval before or after embryo transfer and repeated three times before GW 8 + 0. Primary outcome was ongoing pregnancy in GW 12 Participants/materials, setting, methods Seventy-four women <41 years old with ≥2 consecutive biochemical or clinical early pregnancy losses after ART were randomized 1:1 and underwent trial treatment along with their next IVF/ICSI/FET treatment. Patients were followed with weekly ultrasound scans in first trimester, however, if no implantation occurred, trial participation ended, and no re-entry was allowed. Exclusion criteria included antiphospholipid syndrome, BMI >35, uterine malformations, parental chromosomal translocations, AMH <4 pmol/l, drug contraindications, thyroid disease, and prior IVIG treatment. Main results and the role of chance Seventy-four patients have been randomized, and currently we are awaiting the last two patients to complete the treatment protocol before the code can be disclosed. Blinded interim analysis after inclusion of 38 patients showed no serious adverse events and an ongoing pregnancy rate of 30.0% and 9.5% (RR 1.8, 95% CI 1.0-3.1, Fisher’s exact test: p = 0.13), in the two allocation groups, respectively. Final, unblinded data on ongoing pregnancy rate, miscarriage rate and adverse events will be presented at the Congress if selected for presentation. Limitations, reasons for caution No published study has tested the same treatments in comparable patient groups which could have been the basis for the sample-size calculation, and the study is therefore at risk for being underpowered to evaluate the treatment effect in patients suffering from a combination of infertility, recurrent implantation failure, and RPL. Wider implications of the findings Blood samples were collected before first IV treatment and approximately 4 weeks later, which allow analysis for immunological disturbances and searching for biomarkers identifying those who will benefit from the treatment. This treatment could potentially increase success rate in patients undergoing ART after multiple unsuccessful treatment attempts. Trial registration number NCT04701034

Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE).

New-onset refractory status epilepticus (NORSE) occurs in previously healthy children or adults, often followed by refractory epilepsy and poor outcomes. The mechanisms that transform a normal brain into an epileptic one capable of seizing for prolonged periods despite treatment remain unclear. Nonetheless, several pieces of evidence suggest that immune dysregulation could contribute to hyperexcitability and modulate NORSE sequelae. We used single-nucleus RNA sequencing to delineate the composition and phenotypic states of the CNS of 4 patients with NORSE, to better understand the relationship between hyperexcitability and immune disturbances. We compared them with 4 patients with chronic temporal lobe epilepsy (TLE) and 2 controls with no known neurologic disorder. Patients with NORSE and TLE exhibited a significantly higher proportion of excitatory neurons compared with controls, with no discernible difference in inhibitory GABAergic neurons. When examining the ratio between excitatory neurons and GABAergic neurons for each patient individually, we observed a higher ratio in patients with acute NORSE or TLE compared with controls. Furthermore, a negative correlation was found between the ratio of excitatory to GABAergic neurons and the proportion of GABAergic neurons. The ratio between excitatory neurons and GABAergic neurons correlated with the proportion of resident or infiltrating macrophages, suggesting the influence of microglial reactivity on neuronal excitability. Both patients with NORSE and TLE exhibited increased expression of genes associated with microglia activation, phagocytic activity, and NLRP3 inflammasome activation. However, patients with NORSE had decreased expression of genes related to the downregulation of the inflammatory response, potentially explaining the severity of their presentation. Microglial activation in patients with NORSE also correlated with astrocyte reactivity, possibly leading to higher degrees of demyelination. Our study sheds light on the complex cellular dynamics in NORSE, revealing the potential roles of microglia, infiltrating macrophages, and astrocytes in hyperexcitability and demyelination, offering potential avenues for future research targeting the identified pathways.

Ovarian microenvironment: challenges and opportunities in protecting against chemotherapy-associated ovarian damage.

Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance of ovarian hormone levels, reduced or lost fertility, and an increased risk of early menopause. Previous studies have often focused on the direct effects of chemotherapeutic drugs on ovarian follicles, such as direct DNA damage-mediated apoptotic death and primordial follicle burnout. Emerging evidence has revealed an imbalance in the ovarian microenvironment during chemotherapy. The ovarian microenvironment provides nutritional support and transportation of signals that stimulate the growth and development of follicles, ovulation, and corpus luteum formation. The close interaction between the ovarian microenvironment and follicles can determine ovarian function. Therefore, designing novel and precise strategies to manipulate the ovarian microenvironment may be a new strategy to protect ovarian function during chemotherapy. This review details the changes that occur in the ovarian microenvironment during chemotherapy and emphasizes the importance of developing new therapeutics that protect ovarian function by targeting the ovarian microenvironment during chemotherapy. A comprehensive review of the literature was performed by searching PubMed up to April 2024. Search terms included 'ovarian microenvironment' (ovarian extracellular matrix, ovarian stromal cells, ovarian interstitial, ovarian blood vessels, ovarian lymphatic vessels, ovarian macrophages, ovarian lymphocytes, ovarian immune cytokines, ovarian oxidative stress, ovarian reactive oxygen species, ovarian senescence cells, ovarian senescence-associated secretory phenotypes, ovarian oogonial stem cells, ovarian stem cells), terms related to ovarian function (reproductive health, fertility, infertility, fecundity, ovarian reserve, ovarian function, menopause, decreased ovarian reserve, premature ovarian insufficiency/failure), and terms related to chemotherapy (cyclophosphamide, lfosfamide, chlormethine, chlorambucil, busulfan, melphalan, procarbazine, cisplatin, doxorubicin, carboplatin, taxane, paclitaxel, docetaxel, 5-fluorouraci, vincristine, methotrexate, dactinomycin, bleomycin, mercaptopurine). The ovarian microenvironment shows great changes during chemotherapy, inducing extracellular matrix deposition and stromal fibrosis, angiogenesis disorders, immune microenvironment disturbance, oxidative stress imbalances, ovarian stem cell exhaustion, and cell senescence, thereby lowering the quantity and quality of ovarian follicles. Several methods targeting the ovarian microenvironment have been adopted to prevent and treat CAOD, such as stem cell therapy and the use of free radical scavengers, senolytherapies, immunomodulators, and proangiogenic factors. Ovarian function is determined by its 'seeds' (follicles) and 'soil' (ovarian microenvironment). The ovarian microenvironment has been reported to play a vital role in CAOD and targeting the ovarian microenvironment may present potential therapeutic approaches for CAOD. However, the relation between the ovarian microenvironment, its regulatory networks, and CAOD needs to be further studied. A better understanding of these issues could be helpful in explaining the pathogenesis of CAOD and creating innovative strategies for counteracting the effects exerted on ovarian function. Our aim is that this narrative review of CAOD will stimulate more research in this important field. Not applicable.

Peripheral Th17/Treg imbalance in Chinese patients with untreated antisynthetase syndrome associated interstitial lung disease

Interstitial lung disease (ILD) is a common and fatal manifestation of antisynthetase syndrome (ASS). The aim of this study was to provide new insight into investigate peripheral blood lymphocytes, CD4+ T cells, cytokine levels and their relation to the clinical profile of untreated patients with ASS-ILD. The retrospective study population included thirty patients diagnosed with ASS-ILD and 30 healthy controls (HCs). Baseline clinical and laboratory data were collected for all subjects, including peripheral blood lymphocyte, CD4+ T cell subsets measured by flow cytometry, and serum cytokine levels measured by multiple microsphere flow immunofluorescence. Their correlations with clinical and laboratory findings were analyzed by Pearson’s or Spearman’s correlation analysis. In addition, the Benjamini-Hochberg method was used for multiple correction to adjust the p-values. Patients with ASS-ILD had lower CD8+ T cells, higher proportion of Th17 cells and Th17/Treg ratio than HCs. Serum cytokine levels (IL-1β, IL-6, IL-12, IL-17, IL-8, IL-2, IL-4, IL-10, TNF-α and IFN-γ) were higher in patients with ASS-ILD than HCs. Moreover, Th17/Treg ratio was negatively correlated with diffusing capacity of carbon monoxide (DLCO)%. Our study demonstrated abnormalities of immune disturbances in patients with ASS-ILD, characterized by decreased CD8+ T cells and an increased Th17/Treg ratio, due to an increase in the Th17 cells. These abnormalities may be the immunological mechanism underlying the development of ILD in ASS.

Overexpression of solute carrier family 6 member 12 promotes cell injury in Parkinson's disease via MAPK signaling pathway

BackgroundNeurotransmitter transport disorders may play a crucial role in Parkinson's Disease (PD), and Solute carrier family 6 member 12 (SLC6A12) encodes a neurotransmitter transporter. However, the relationship between SLC6A12 and PD remains largely unexplored. MethodsWe utilized the GEO database (107 samples) and clinical data (80 samples) to investigate the role of SLC6A12 in PD through differential expression analysis, ROC analysis, and RT-qPCR experiments. Subsequently, in vitro model, axon length measurement, CCK8 assay, flow cytometry, and JC-1 assays were conducted. Additionally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, protein-protein interaction (PPI) network, gene set enrichment analysis (GSEA), and western blot experiments were assessed to explore the functional and mechanistic pathways of SLC6A12 in PD. Finally, CIBERSORT analysis was performed to investigate the correlation between SLC6A12 and immune cells in PD. ResultsThe expression of SLC6A12 was significantly higher in individuals with PD compared to healthy controls. Inhibiting SLC6A12 expression in PD models enhanced neuronal growth and proliferation activity while reducing cell apoptosis. Furthermore, SLC6A12 was found to be involved in neuronal development, synaptic function, and neural protein transport processes in PD, potentially regulating the MAPK signaling pathway through the Ras/Raf/MEK/ERK axis, contributing to the pathological process of PD. Additionally, SLC6A12 was implicated in immune environment disturbances in PD, notably affecting CD4 T cell expression. ConclusionThis study documented the pathogenicity of SLC6A12 in PD for the first time, expanding the understanding of its molecular function and providing a potential target for precise treatment of PD.

Immune Checkpoints in Endometriosis-A New Insight in the Pathogenesis.

Endometriosis (EMS) is an oestrogen-dependent, chronic disease affecting women of a reproductive age. One of the important factors involved in the development of this disease is the complex disorders associated with the functioning of the immune system. Recent evidence has shown that EMS development is associated with changes in systemic and local immunity, including functional disturbances of effector and antigen-presenting cells. One of the reasons for immune imbalance can be the improper expression of immune checkpoints (ICPs). ICPs and their ligands are responsible for maintaining self-tolerance and the modulation of the initiation, duration, and magnitude of the immune response of effector cells in normal tissues to avoid tissue damage. Considering the complex nature of co-stimulatory or co-inhibitory ICPs and the signalling between effector cells and APCs, we hypothesise that changes in cells' activity caused by ICPs may lead to serious immune system disturbances in patients with endometriosis. Moreover, both upregulation and downregulation in the expression of ICPs may be implicated in this process, including the reduced activity of effector cells against endometrial implants and disturbances in the antigen-presenting process. In this narrative review, we discuss, for the first time, key findings from the emerging literature, describing the associations between ICPs and their possible implication in the pathogenesis of endometriosis.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating disease characterised by a wide range of symptoms that severely impact all aspects of life. Despite its significant prevalence, ME/CFS remains one of the most understudied and misunderstood conditions in modern medicine. ME/CFS lacks standardised diagnostic criteria owing to variations in both inclusion and exclusion criteria across different diagnostic guidelines, and furthermore, there are currently no effective treatments available. Moving beyond the traditional fragmented perspectives that have limited our understanding and management of the disease, our analysis of current information on ME/CFS represents a significant paradigm shift by synthesising the disease's multifactorial origins into a cohesive model. We discuss how ME/CFS emerges from an intricate web of genetic vulnerabilities and environmental triggers, notably viral infections, leading to a complex series of pathological responses including immune dysregulation, chronic inflammation, gut dysbiosis, and metabolic disturbances. This comprehensive model not only advances our understanding of ME/CFS's pathophysiology but also opens new avenues for research and potential therapeutic strategies. By integrating these disparate elements, our work emphasises the necessity of a holistic approach to diagnosing, researching, and treating ME/CFS, urging the scientific community to reconsider the disease's complexity and the multifaceted approach required for its study and management.

Clinical Characteristics of 427 Unvaccinated Chinese Adult Patients with Maintenance Hemodialysis Infected with the SARS-CoV-2 Omicron Variant: A Retrospective Study

Background: Maintenance hemodialysis (MHD) patients constitute a distinctive population characterized by unique traits, such as hemodialysis-related immune disturbances, and increased vulnerability to infections, heart failure, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite considerable research on MHD patients with coronavirus disease 2019 (COVID-19), there is limited information available on the clinical characteristics and outcomes of unvaccinated adult MHD patients infected with the SARS-CoV-2 Omicron variant. Methods: A retrospective investigation was conducted in a cohort of 427 unvaccinated MHD patients diagnosed with SARS-CoV-2 Omicron infection. The clinical symptoms, laboratory results, and treatment regimens were comprehensively examined. Multivariate regression identified independent risk factors for disease severity, and two-month follow-up assessments were conducted. Results: The cohort exhibited a spectrum of disease severity, with 37.5% classified as mild, 35.3% as common, 22.5% as severe, and 4.7% as critical. Serum C-reactive protein level, procalcitonin level, and bicarbonate concentration are related to the severity of the disease. Tailored treatment strategies—including nutritional support, hemodialysis management, anti-bacterial interventions, and more—were implemented. There was a 5.6% mortality rate, with a higher prevalence of deaths in the critical subtype. Independent risk factors for disease severity included fever, age, cycle threshold values (Ct values) of ORF1ab gene, and arterial oxygen partial pressure. Follow-up assessments revealed a median duration of 11 days for the negative nucleic acid of SARS-CoV-2. Twelve patients presented a second positive ORF1ab gene during follow-up but remained asymptomatic. Conclusion: These findings suggest the intricate clinical characteristics and outcomes of MHD patients with the SARS-CoV-2 Omicron infection. Tailored treatment strategies, continuous surveillance, and understanding prognostic factors are imperative for managing this high-risk population. Further research is warranted to validate these findings.

Decoding Behcet's Uveitis: an In-depth review of pathogenesis and therapeutic advances.

Behcet's disease (BD) is a rare but globally distributed vasculitis that primarily affects populations in the Mediterranean and Asian regions. Behcet's uveitis (BU) is a common manifestation of BD, occurring in over two-thirds of the patients. BU is characterized by bilateral, chronic, recurrent, non-granulomatous uveitis in association with complications such as retinal ischemia and atrophy, optic atrophy, macular ischemia, macular edema, and further neovascular complications (vitreous hemorrhage, neovascular glaucoma). Although the etiology and pathogenesis of BU remain unclear, numerous studies reveal that genetic factors (such as HLA-B51), dysregulated immune responses of both the innate and adaptive immune systems, infections (such as streptococcus), and environmental factors (such as GDP) are all involved in its development. Innate immunity, including hyperactivity of neutrophils and γδT cells and elevated NK1/NK2 ratios, has been shown to play an essential role in this disease. Adaptive immune system disturbance, including homeostatic perturbations, Th1, Th17 overaction, and Treg cell dysfunction, is thought to be involved in BU pathogenesis. Treatment of BU requires a tailored approach based on the location, severity of inflammation, and systemic manifestations. The therapy aims to achieve rapid inflammation suppression, preservation of vision, and prevention of recurrence. Systemic corticosteroids combined with other immunosuppressive agents have been widely used to treat BU, and beneficial effects are observed in most patients. Recently, biologics have been shown to be effective in treating refractory BU cases. Novel therapeutic targets for treating BU include the LCK gene, Th17/Treg balance, JAK pathway inhibition, and cytokines such as IL-17 and RORγt. This article summarizes the recent studies on BU, especially in terms of pathogenesis, diagnostic criteria and classification, auxiliary examination, and treatment options. A better understanding of the significance of microbiome composition, genetic basis, and persistent immune mechanisms, as well as advancements in identifying new biomarkers and implementing objective quantitative detection of BU, may greatly contribute to improving the adequate management of BU patients.

Pediatric Dermatitis Seborrhoica - A Clinical and Therapeutic Review

Abstract Pediatric dermatitis seborrhoica (DS) is a common inflammatory disorder of infancy and adolescence distinct from atopic dermatitis. We performed a narrative review on clinical and therapeutic aspects of the disease. The prevalence varies geographically and can reach up to 10%. There is a slight male predominance. Although etiopathology is not well known, both endogenous and exogenous factors contribute. Skin microbiome and its interaction with sebaceous gland function is crucial. The inflammatory pathways include innate immune function and skin barrier disturbances. Malassezia spp. and certain bacteria are increased in lesional skin. DS develops in different clinical subtypes, from localized cephalic to disseminated disease with a risk of erythroderma and eczema herpeticatum. Treatment consists of skin care and topical and rarely systemic medical therapy. Cornerstones of treatment are antifungals and mild corticosteroids. Targeted treatment is on the horizon. Pediatric DS is a common disorder important in the differential diagnosis of skin problems in infants and and children. Due to better understanding of its pathogenesis, new treatment options are developed.

Inflammation and immunological disarrays are associated with acute exercise in type 2 diabetes.

Type 2 diabetes (T2D) is the most common metabolic disorder that is associated with insulin resistance. The aim of the present study is to discover details of the molecular mechanism of exercise on control or progress of diabetic condition in patients via network analysis. Gene expression profiles of patients with T2D before and after doing exercise are retrieved from Gene Expression Omnibus (GEO) and are pre-evaluated by the GEO2R program. Data are studied based on expression values, regulatory relationships between the differentially expressed genes (DEGs), gene ontology analyses, and protein-protein interaction PPI network analysis. A number of 118 significant DEGs were identified and classified based on fold change (FC) values as most dysregulated genes and dysregulated individuals. Action map analysis revealed that 18 DEGs appeared as the critical genes. Gene ontology analysis showed that 24 DEGs are connected to at least four pathways. JUN, IL6, IL1B, PTGS2, FOS, MYC, ATF3, CXCL8, EGR1, EGR2, NR4A1, PLK3, TTN, and UCP3 were identified as central DEGs. Finally; JUN, IL6, IL1B, PTGS2, FOS, ATF3, CXCL8, EGR1, and EGR2 were introduced as the critical targeted genes by exercise. Since the critical genes after exercise are upregulated and mostly are known as the risk factors of T2D, it can be concluded that unsuitable exercise can develop diabetic conditions in patients. Acute exercise-induced inflammation and immune disturbances seem to be associated with the development of T2D in patients.

The role and therapeutic potential of SIRTs in sepsis.

Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection. Abnormal activation of the immune system and disturbance of energy metabolism play a key role in the development of sepsis. In recent years, the Sirtuins (SIRTs) family has been found to play an important role in the pathogenesis of sepsis. SIRTs, as a class of histone deacetylases (HDACs), are widely involved in cellular inflammation regulation, energy metabolism and oxidative stress. The effects of SIRTs on immune cells are mainly reflected in the regulation of inflammatory pathways. This regulation helps balance the inflammatory response and may lessen cell damage and organ dysfunction in sepsis. In terms of energy metabolism, SIRTs can play a role in immunophenotypic transformation by regulating cell metabolism, improve mitochondrial function, increase energy production, and maintain cell energy balance. SIRTs also regulate the production of reactive oxygen species (ROS), protecting cells from oxidative stress damage by activating antioxidant defense pathways and maintaining a balance between oxidants and reducing agents. Current studies have shown that several potential drugs, such as Resveratrol and melatonin, can enhance the activity of SIRT. It can help to reduce inflammatory response, improve energy metabolism and reduce oxidative stress, showing potential clinical application prospects for the treatment of sepsis. This review focuses on the regulation of SIRT on inflammatory response, energy metabolism and oxidative stress of immune cells, as well as its important influence on multiple organ dysfunction in sepsis, and discusses and summarizes the effects of related drugs and compounds on reducing multiple organ damage in sepsis through the pathway involving SIRTs. SIRTs may become a new target for the treatment of sepsis and its resulting organ dysfunction, providing new ideas and possibilities for the treatment of this life-threatening disease.

Crosstalk between hypoxia-inducible factor-1α and short-chain fatty acids in inflammatory bowel disease: key clues toward unraveling the mystery.

The human intestinal tract constitutes a complex ecosystem, made up of countless gut microbiota, metabolites, and immune cells, with hypoxia being a fundamental environmental characteristic of this ecology. Under normal physiological conditions, a delicate balance exists among these complex "residents", with disruptions potentially leading to inflammatory bowel disease (IBD). The core pathology of IBD features a disrupted intestinal epithelial barrier, alongside evident immune and microecological disturbances. Central to these interconnected networks is hypoxia-inducible factor-1α (HIF-1α), which is a key regulator in gut cells for adapting to hypoxic conditions and maintaining gut homeostasis. Short-chain fatty acids (SCFAs), as pivotal gut metabolites, serve as vital mediators between the host and microbiota, and significantly influence intestinal ecosystem. Recent years have seen a surge in research on the roles and therapeutic potential of HIF-1α and SCFAs in IBD independently, yet reviews on HIF-1α-mediated SCFAs regulation of IBD under hypoxic conditions are scarce. This article summarizes evidence of the interplay and regulatory relationship between SCFAs and HIF-1α in IBD, pivotal for elucidating the disease's pathogenesis and offering promising therapeutic strategies.

Anexelekto (AXL) no more: microRNA-155 (miR-155) controls the "Uncontrolled" in SARS-CoV-2.

AXL is the gene that encodes the Anexelekto (AXL) receptor tyrosine kinase that demonstrates significant roles in various cellular processes, including cell growth, survival, and migration. Anexelekto is a Greek word meaning excessive and uncontrolled, semantically implying the crucial involvement of AXL in cancer and immune biology, and in promoting cancer metastasis. AXL overexpression appears to drive epithelial to mesenchymal transition, tumor angiogenesis, decreased antitumor immune response, and resistance to therapeutic agents. Recently, AXL has been reported to play important roles in several viral infections, including SARS-CoV-2. We have previously outlined the importance of microRNAs (miRNAs, miRs) and especially miR-155 in SARS-CoV-2 pathophysiology through regulation of the Renin-AngiotensinAldosterone System (RAAS) and influence on several aspects of host innate immunity. MiRNAs are negative regulators of gene expression, decreasing the stability of target RNAs or limiting their translation and, enthrallingly, miR-155 is also involved in AXL homeostasis-both endogenously and pharmaceutically using repurposed drugs (e.g., metformin)-highlighting thrifty evolutionary host innate immunity mechanisms that successfully can thwart viral entry and replication. Cancer, infections, and immune system disturbances will increasingly involve miRNA diagnostics and therapeutics in the future.

Preliminary Study on Total Glucoside of Peony (TGP) Administration in Organ-Specific Autoimmune Diseases at Prof. dr. R. D. Kandou Hospital, Indonesia

Autoimmune diseases are a diverse group of conditions characterized by immune disturbances that cause aberrant B cell and T cell reactivity to normal constituents of the host. These diseases can involve essentially any organ system and affect individuals of any age, with a much greater prevalence among women. Although certain mechanisms unite these conditions into a single category, the clinical manifestations of autoimmune disease are highly varied. This research is an original and interventional study. It is a preliminary with analytic observational. The design is “the one group pre-test – post-test design”. This study was conducted at RSUP Prof. dr. R. D. Kandou over a six-month period from July 2016 to December 2016. The study included patients diagnosed with Graves’ disease, Hashimoto’s disease, and aplastic anemia, who were diagnosed based on their medical history, physical examination, and diagnostic workups. This study also aimed to evaluate the improvement in clinical symptoms within the Aplastic Anemia group, tracking the number of complaints reported each week. Four patients were included in the study, each receiving individualized basic therapy.