Sepsis is a syndrome characterized by systemic inflammatory responses to a severe infection. Acute hyper-inflammatory reactions in the acute phase of sepsis have been considered as a primary reason for organ dysfunction and mortality, and advances in emergency intervention and improved intensive care management have reduced mortalities in the early phase. However it has been recognized that increased deaths in the late phase still maintain sepsis mortality high worldwide. Patients recovered from early severe illness are unable to control immune system with sepsis-induced immunosuppression such as immunological tolerance, exhaustion and apoptosis, which make them vulnerable to nosocomial and opportunistic infections ultimately leading to threat to life. Based on strategies to reverse immunosuppression, recent developments in sepsis therapy are focused on molecules having immune enhancing activities. These efforts are focused on defining and revising the immunocompromised status associated with long-term mortality.
Apoptosis ; Critical Care ; Emergencies ; Humans ; Immune System ; Immunosuppression* ; Immunotherapy ; Mortality ; Opportunistic Infections ; Precision Medicine ; Sepsis* ; Theranostic Nanomedicine

Atopic dermatitis (AD) is the most common pruritic inflammatory skin disease characterized by thickening of epidermis and dermis as well as by the infiltration of multiple pathogenic polarized T lymphocytes, including Th2, Th17, and Th22 cells. Significant progress has been made to develop targeted therapeutics for treating AD, e.g., Food and Drug Administration-approved dupilumab, an antibody for dual targeting of IL-4 and IL-13 signaling pathways. Additionally, a growing body of published evidence and a promising result from the early stage of the clinical trial with ILV-094, an anti-IL-22 antibody, strongly support the notion that IL-22 is a potential therapeutic target for treating AD. Moreover, we also experimentally proved that IL-22 contributes to the pathophysiology of AD by employing a murine model of AD induced by epicutaneous sensitization. Here, we review recent preclinical and clinical findings that have advanced our understanding of the roles of IL-22 and Th22 cells in skin inflammation. We conclude that blockade of IL-22 signaling may be a promising therapeutic approach for the treatment of AD.
Dermatitis, Atopic* ; Dermis ; Epidermis ; Inflammation ; Interleukin-13 ; Interleukin-4 ; Skin ; Skin Diseases ; T-Lymphocytes

OBJECTIVES: Effects of multiple trauma are complex and extend beyond core PTSD symptoms. However, few psychological instruments for trauma assessment address this issue of symptom complexity. The Trauma Symptom Checklist-40 (TSC-40) is a self-report scale that assesses wide range of symptoms associated with childhood or adult traumatic experience. The purpose of the present study was to evaluate the validity of the Korean Version of the TSC-40 in a sample of psychiatric outpatients. METHODS: Data of 367 treatment-seeking patients with DSM-IV diagnoses were obtained from an outpatient department of psychiatric unit at a university hospital. The diagnoses were anxiety disorder, posttraumatic stress disorder, depressive disorder, adjustment disorder and others. Included in the psychometric data were the TSC-40, the Life events checklist, the Impact of Event Scale-Revised, the Zung's Self-report Depression Scale, and the Zung's Self-report Anxiety Scale. Cronbach's α for internal consistency were calculated. Convergent and concurrent validity was approached with correlation between the TSC-40 and other scales (PTSD, anxiety and depression). RESULTS: Exploratory factor analysis of the Korean Version of TSC-40 extracted seven-factor structure accounted for 59.55% of total variance that was contextually similar to a six-factor structure and five-factor structure of the original English version. The Korean Version of TSC-40 demonstrated a high level of internal consistency. (Cronbach's α=0.94) and good concurrent and convergent validity with another PTSD scale and anxiety and depression scales. CONCLUSIONS: Excellent construct validity of The Korean Version of TSC-40 was proved in this study. And subtle difference in the factor structure may reflect the cultural issues and the sample characteristics such as heterogeneous clinical population (including non-trauma related disorders) and outpatient status. Overall, this study TSCdemonstrated that the Korean version of TSC-40 is psychometrically sound and can be used for Korean clinical population.
Adjustment Disorders ; Adult ; Anxiety ; Anxiety Disorders ; Checklist ; Depression ; Depressive Disorder ; Diagnosis ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Multiple Trauma ; Outpatients ; Psychometrics ; Stress Disorders, Post-Traumatic ; Weights and Measures

Mast cells integrate innate and adaptive immunity and are implicated in pathophysiological conditions, including allergy, asthma, and anaphylaxis. Cross-linking of the high-affinity IgE receptor (FcεRI) initiates diverse signal transduction pathways and induces release of proinflammatory mediators by mast cells. In this study, we demonstrated that hyperactivation of mechanistic target of rapamycin (mTOR) signaling using the mTOR activator MHY1485 suppresses FcεRI-mediated mast cell degranulation and cytokine secretion. MHY1485 treatment increased ribosomal protein S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation, which are downstream targets of mTOR complex 1 (mTORC1), but decreased phosphorylation of Akt on mTOR complex 2 (mTORC2) target site serine 473. In addition, this activator decreased β-hexosaminidase, IL-6, and tumor necrosis factor α (TNF-α) release in murine bone marrow-derived mast cells (BMMCs) after FcεRI stimulation. Furthermore, MHY1485-treated BMMCs showed significantly decreased proliferation when cultured with IL-3. These findings suggested hyperactivation of mTORC1 as a therapeutic strategy for mast cell-related diseases.
Adaptive Immunity ; Anaphylaxis ; Asthma ; Cell Degranulation ; Cell Proliferation ; Hypersensitivity ; Immunoglobulin E ; Interleukin-3 ; Interleukin-6 ; Mast Cells* ; Peptide Initiation Factors ; Phosphorylation ; Ribosomal Protein S6 Kinases ; Serine ; Signal Transduction ; Sirolimus ; Tumor Necrosis Factor-alpha

Depression is a neuropsychiatric disorder associated with persistent stress and disruption of neuronal function. Persistent stress causes neuronal atrophy, including loss of synapses and reduced size of the hippocampus and prefrontal cortex. These alterations are associated with neural dysfunction, including mood disturbances, cognitive impairment, and behavioral changes. Synaptic plasticity is the fundamental function of neural networks in response to various stimuli and acts by reorganizing neuronal structure, function, and connections from the molecular to the behavioral level. In this review, we describe the alterations in synaptic plasticity as underlying pathological mechanisms for depression in animal models and humans. We further elaborate on the significance of phytochemicals as bioactive agents that can positively modulate stress-induced, aberrant synaptic activity. Bioactive agents, including flavonoids, terpenes, saponins, and lignans, have been reported to upregulate brain-derived neurotrophic factor expression and release, suppress neuronal loss, and activate the relevant signaling pathways, including TrkB, ERK, Akt, and mTOR pathways, resulting in increased spine maturation and synaptic numbers in the neuronal cells and in the brains of stressed animals. In clinical trials, phytochemical usage is regarded as safe and well-tolerated for suppressing stress-related parameters in patients with depression. Thus, intake of phytochemicals with safe and active effects on synaptic plasticity may be a strategy for preventing neuronal damage and alleviating depression in a stressful life.

The L-gulono-gamma-lactone oxidase gene (Gulo) encodes an essential enzyme in the synthesis of ascorbic acid from glucose. On the basis of previous findings of bone abnormalities in Gulo-/- mice under conditions of ascorbic acid insufficiency, we investigated the effect of ascorbic acid insufficiency on factors related to bone metabolism in Gulo-/- mice. Four groups of mice were raised for 4 weeks under differing conditions of ascorbic acid insufficiency, namely, wild type; ascorbic acid-sufficient Gulo-/- mice, 3-week ascorbic acid-insufficient Gulo-/- mice, and 4-week ascorbic acid-insufficient Gulo-/- mice. Four weeks of ascorbic acid insufficiency resulted in significant weight loss in Gulo-/- mice. Interestingly, average plasma osteocalcin levels were significantly decreased in Gulo-/- mice after 3 weeks of ascorbic acid insufficiency. In addition, the tibia weight in ascorbic acid-sufficient Gulo-/- mice was significantly higher than that in the other three groups. Moreover, significant decreases in trabecular bone volume near to the growth plate, as well as in trabecular bone attachment to the growth plate, were evident in 3- or 4-week ascorbic acid-insufficient Gulo-/-. In summary, ascorbic acid insufficiency in Gulo-/- mice results in severe defects in normal bone formation, which are closely related to a decrease in plasma osteocalcin levels.
Animals ; Ascorbic Acid* ; Down-Regulation* ; Glucose ; Growth Plate ; L-Gulonolactone Oxidase ; Metabolism ; Mice ; Osteocalcin* ; Osteogenesis* ; Plasma ; Tibia ; Weight Loss