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• HMGB1 is a non-histone DNA-binding nuclear protein. • HMGB1 can actively secreted in the form of intracellular vesicles. • HMGB1 can also be released from necrotic cells or injured cells passively. • After binding with its receptors, HMGB1 trigger a series of biological effects. • HMGB1 was involved in the occurrence and development of asthma. High-mobility group box protein 1 (HMGB1) is a non-histone deoxyribonucleic acid-binding nuclear protein. In physiological state it is involved in gene transctioripn regulation and cell replication, differentiation and maturation. HMGB1 is actively secreted into the extracellular space in the form of intracellular vesicles, upon stimulation of inflammation and infection, by monocytes, macrophages, dendritic cells (DCs), and other immune cells, and can also be passively released by necrotic or injured cells. After binding with the corresponding receptors, HMGB1 can activate the downstream substrate and trigger a series of biological effects. HMGB1 was mainly dependent on toll-like re ceptors (TLR) 2 and 4, and receptors for advanced glycation end products (RAGE) to trigger intracellular signal transduction, and mediate innate and adoptive immune responses. Besides these, studies have reported the participation of TLR3, TLR9, T-cell immunoglobulin mucin (TIM) 3, CD24, anti-N-methyl-D-aspartate receptor (NMDAR) in Th2 inflammatory response, eosinophilic airway inflammation, and airway hyperresponsiveness, mediated by HMGB1 in asthma. Both clinical and experimental studies suggested that HMGB1 was involved in the pathogenesis of asthma probably by regulating the downstream signaling pathways via corresponding receptors. This article reviews the role of HMGB1 in pathogenesis of asthma, and provides a new theoretical basis for the diagnosis and treatment of asthma. [ABSTRACT FROM AUTHOR]

The ATP/P2X7 axis of dendritic cells (DCs) mediates the activation of NLRP3 inflammasome and promotes secretion of interleukin (IL)−1β and IL-18 to induce T helper (Th) 2, Th17 differentiation in the pathogenesis of asthma. NLRP3 inflammasome also regulates high mobility protein 1 (HMGB1) release in DCs. Recent studies demonstrated the correlation between HMGB1 expression and airway inflammation and hyper-responsiveness (AHR) in asthma. However, the relationship between the ATP/P2X7-NLRP3 axis and HMGB1 in DCs in asthma is still unclear. ATP, apyrase, Brilliant Blue G, BzATP, glibenclamide, and Z-YVAD-FMK were administered to ovalbumin (OVA)-induced murine asthmatic model. For in vitro studies, bone marrow-derived mononuclear cells (BMDCs) were primed with LPS and stimulated with the same reagents. Activation of the ATP/P2X7 axis aggravated airway inflammation and AHR in the lung and induced Th2, Th17 polarization in asthmatic mice. Inhibition of NLRP3 inflammasome weakened cardinal features of asthma and blocked Th2, Th17 polarization. In vitro and vivo, ATP/P2X7 axis activated NLRP3 inflammasome and induced HMGB1 expression and release from DCs. Inhibition of NLRP3 inflammasome reduced HMGB1 expression and release. The ATP/P2X7-NLRP3 axis of DCs participates in mediating airway inflammation, AHR, and promoting Th2, Th17 inflammatory responses in asthmatic mice by inducing HMGB1 expression and secretion. [ABSTRACT FROM AUTHOR]

• HMGB1 aggravates acute lung injury by suppressing immunosuppressive function of Tregs. • HMGB1 reduces the number and activity of Tregs. • HMGB1 reduces the secretion of anti-inflammatory cytokines (IL-10, TGF-β) from Tregs. • Tregs stimulated by HMGB1 regulate the macrophage polarization, as well as the proinflammatory response of macrophages. CD4+CD25+FoxP3+ T helper cells (Tregs), a subgroup of CD4+ T helper cells, are critical effectors that protect against acute lung injury (ALI) by contact-dependent suppression or releasing anti-inflammatory cytokines including interleukin-10 (IL-10), and transforming growth factor (TGF-β). HMGB1 (High mobility group box 1 protein) was identified as a nuclear non-histone DNA-binding chromosomal protein, which participates in the regulation of lung inflammatory response and pathological processes in ALI. Previous studies have suggested that Tregs overexpresses the HMGB1-recognizing receptor. However, the interaction of HMGB1 with Tregs in ALI is still unclear. To investigate whether HMGB1 aggravates ALI by suppressing immunosuppressive function of Tregs. Anti-HMGB1 antibody and recombinant mouse HMGB1 (rHMGB1) were administered in lipopolysaccharide (LPS)-induced ALI mice and polarized LPS-primed Tregs in vitro. The Tregs pre-stimulated with or without rHMGB1 were adoptively transferred to ALI mice and depleted by Diphtheria toxin (DT). For coculture experiment, isolated Tregs were first pre-stimulated with or without rHMGB1 or anti-HMGB1 antibody, then they were cocultured with bone marrow-derived macrophages (BMMs) under LPS stimulation. Tregs protected against acute lung pathological injury. HMGB1 modulated the suppressive function of Tregs as follows: reduction in the number of the cells and the activity of Tregs, the secretion of anti-inflammatory cytokines (IL-10, TGF-β) from Tregs, the production of IL-2 from CD4+ T cells and CD11c+ DCs, and the M2 polarization of macrophages, as well as inducing proinflammatory response of macrophages. HMGB1 could aggravate LPS induced-ALI through suppressing the activity and function of Tregs. [ABSTRACT FROM AUTHOR]

Recent studies revealed that macrophages are polarized towards the M2 phenotype in an ovalbumin (OVA)-induced asthmatic model. Alveolar macrophages (AMs) are immune barriers in alveoli to various pathogens in the respiratory tract; AMs suppress Th2 cell proliferation, inhibit interleukin (IL)-4, IL-5, and IL-13 secretion, and protect against airway hyperresponsiveness in allergic asthma. However, the polarization status and effects of different types of AMs in the pathogenesis of asthma are not known. ATP/P2X7r, expressed mainly on macrophages and dendritic cells, is associated with acute and chronic asthmatic airway inflammation and Th2 immune responses in mice and humans and functions by activating the NLRP3 inflammasome complex and inducing proinflammatory cytokine release (IL-1β and IL-18). Therefore, we evaluated the association between the ATP/P2X7r axis and different types of AMs in the pathology of allergic asthma. A murine AM-depleted asthma model was established by administration of clodronate-encapsulated liposomes, and M1-or M2-AMs were adoptively transferred to confirm the effects of different AMs in allergic asthma. Brilliant Blue G and BzATP were administered to OVA/HDM-induced mice in vivo. Lipopolysaccharide + OVA, ATP, Brilliant Blue G, and BzATP were used to stimulate AMs isolated from control and asthmatic mice. We found that selective depletion of AMs aggravated lung inflammation in asthmatic mice. Further, M2-type AMs may play a key role in mediating asthmatic inflammatory responses via the adoptive transfer of M2-type AMs to AM-depleted asthmatic mice, and the phenotype of AMs differentiated to M2 type in asthma. P2X7r expression in M2-type AMs was higher than that in M1-type AMs. Activating P2X7r induced polarization of M2-type AMs and inhibited polarization of M1-type AMs, while blockage of P2X7r had the opposite effect. The ATP/P2X7r axis may participate in the pathogenesis of asthma by mediating the M2-type AM polarization. • M2-type AMs activate Th2 cell inflammatory response in allergic asthma. • The AM phenotype switches to M2 type in an OVA-induced asthmatic mice model. • M2-type alveolar macrophages preferentially express P2X7r. • The ATP/P2X7r axis induces M2-type and inhibits M1-type polarization of AMs. [ABSTRACT FROM AUTHOR]

• Medical staff experience mental health disturb during the COVID-19 pandemic. • Direct and indirect exposure to COVID-19 affects the mental health profoundly. • Psychological materials and resources provide some protection. • Interventions with appropriate level are urgent. The severe 2019 outbreak of novel coronavirus disease (COVID-19), which was first reported in Wuhan, would be expected to impact the mental health of local medical and nursing staff and thus lead them to seek help. However, those outcomes have yet to be established using epidemiological data. To explore the mental health status of medical and nursing staff and the efficacy, or lack thereof, of critically connecting psychological needs to receiving psychological care, we conducted a quantitative study. This is the first paper on the mental health of medical and nursing staff in Wuhan. Notably, among 994 medical and nursing staff working in Wuhan, 36.9% had subthreshold mental health disturbances (mean PHQ-9: 2.4), 34.4% had mild disturbances (mean PHQ-9: 5.4), 22.4% had moderate disturbances (mean PHQ-9: 9.0), and 6.2% had severe disturbance (mean PHQ-9: 15.1) in the immediate wake of the viral epidemic. The noted burden fell particularly heavily on young women. Of all participants, 36.3% had accessed psychological materials (such as books on mental health), 50.4% had accessed psychological resources available through media (such as online push messages on mental health self-help coping methods), and 17.5% had participated in counseling or psychotherapy. Trends in levels of psychological distress and factors such as exposure to infected people and psychological assistance were identified. Although staff accessed limited mental healthcare services, distressed staff nonetheless saw these services as important resources to alleviate acute mental health disturbances and improve their physical health perceptions. These findings emphasize the importance of being prepared to support frontline workers through mental health interventions at times of widespread crisis. [ABSTRACT FROM AUTHOR]

Dynamic changes in triacylglycerol composition during complete crystallization were investigated by separating crystals from molten cocoa butter (CB) over different lengths of crystallization time. The dynamic crystallization behavior of CB was described by solid fat content (SFC), crystal morphology, and microstructure. The crystallization process was divided into stages, based on the growth mode of crystals: the induction, primary crystallization, and secondary crystallization stages. As crystallization progressed, the relative content of 1,3-dipalmitoyl-2-oleoylglycerol (POP) increased from 12.1% to 29.8%; that of 1,3-distearoyl-2-oleoylglycerol (StOSt) decreased from 37.1% to 20.2%; and that of tristearin (StStSt) decreased from 4.9% to 0.2%. Circular crystals were formed at the induction and primary crystallization stages, and β′-III form and β′-IV form polymorphisms were exhibited. When crystallization entered the secondary crystallization stage, the crystal morphology changed from circular to acicular, and polymorphic transformation from the β′-III form and β′-IV form to the β-form was observed. Image 1 • Dynamic crystallization behavior of triacylglycerol in cocoa butter was explored. • The crystallization process was divided into three stages based on growth mode. • The melting point of seed crystals in cocoa butter was above 57 °C. [ABSTRACT FROM AUTHOR]