Real-world comparison between mechanical and manual cardiopulmonary resuscitation during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has posed significant challenges to healthcare systems worldwide, including an increase in out-of-hospital cardiac arrests (OHCA). Healthcare providers are now required to use personal protective equipment (PPE) during cardiopulmonary resuscitation (CPR). Additionally, mechanical CPR devices have been introduced to reduce the number of personnel required for resuscitation. This study aimed to compare the outcomes of CPR performed with a mechanical device and the outcomes of manual CPR performed by personnel wearing PPE. METHODS: This multicenter observational study utilized data from the Korean Cardiac Arrest Research Consortium registry. The study population consisted of OHCA patients who underwent CPR in emergency departments (EDs) between March 2020 and June 2021. Patients were divided into two equal propensity score matched groups: mechanical CPR group (n = 421) and PPE-equipped manual CPR group (n = 421). Primary outcomes included survival rates and favorable neurological outcomes at discharge. Total CPR duration in the ED was also assessed. RESULTS: There were no significant between-group differences with respect to survival rate at discharge (mechanical CPR: 7.4% vs PPE-equipped manual CPR: 8.3%) or favorable neurological outcomes (3.3% vs. 3.8%, respectively). However, the mechanical CPR group had a longer duration of CPR in the ED compared to the manual CPR group. CONCLUSION: This study found no significant differences in survival rates and neurological outcomes between mechanical CPR and PPE-equipped manual CPR in the ED setting. However, a longer total CPR duration was observed in the mechanical CPR group. Further research is required to explore the impact of PPE on healthcare providers' performance and fatigue during CPR in the context of the pandemic and beyond.

CO2 Curing Efficiency for Cement Paste and Mortars Produced by a Low Water-to-Cement Ratio.

Curing by CO2 is a way to utilize CO2 to reduce greenhouse gas emissions. Placing early-age cement paste in a CO2 chamber or pressure vessel accelerates its strength development. Cement carbonation is attributed to the quickened strength development, and CO2 uptake can be quantitatively evaluated by measuring CO2 gas pressure loss in the pressure vessel. A decrease in CO2 gas pressure is observed with all cement pastes and mortar samples regardless of the mix proportion and the casting method; one method involves compacting a low water-to-cement ratio mix, and the other method comprises a normal mix consolidated in a mold. The efficiency of the CO2 curing is superior when a 20% concentration of CO2 gas is supplied at a relative humidity of 75%. CO2 uptake in specimens with the same CO2 curing condition is different for each specimen size. As the specimen scale is larger, the depth of carbonation is smaller. Incorporating colloidal silica enhances the carbonation as well as the hydration of cement, which results in contributing to the increase in the 28-day strength.

Alkali-Activated Slag Paste with Different Mixing Water: A Comparison Study of Early-Age Paste Using Electrical Resistivity.

This paper reports the electrical resistivity measurements on KOH-activated ground-granulated blast-furnace slag, which was mixed with deionized water or natural seawater at three different activator-to-binder ratios (0.4, 0.45, and 0.5). Compressive strength and X-ray diffraction analyses were performed on the samples after the measurement. The type of mixing water did not affect the setting time of samples, whereas the setting time was delayed with an increase in activator-to-binder (a/b) ratio. Regardless of the mixing water type, the increasing ratio of electrical resistivity between a/b 0.45 and 0.5 was larger than that between a/b 0.4 and 0.45. For the same a/b ratio, the pastes mixed with seawater produced higher electrical resistivity and early strength than those with deionized water. The increase in the electrical resistivity in seawater-mixed pastes could be attributed to the formation of Cl-bearing phases such as Cl-hydrocalumite, AlOCl, and aluminum chloride hydrate. It is believed that the reaction products in seawater-mixed samples were helpful in preventing water percolation, and thus, the electrical resistivity increased compared with the deionized water-mixed sample.

Polyozellin alleviates atopic dermatitis-like inflammatory and pruritic responses in activated keratinocytes and mast cells.

Polyozellus multiplex is an edible mushroom that offers beneficial pharmacological effects against intestinal inflammation and cancer. Previous studies have demonstrated that polyozellin, a major component of P. multiplex, has therapeutic activities against inflammation, cancer, and oxidative stress-related disorders. This study aimed to determine the pharmacological effects of polyozellin on inflammatory and pruritic responses, the major symptoms of atopic dermatitis (AD), and to define its underlying mechanism of action. Our results showed that polyozellin inhibited the expression of inflammatory cytokines and chemokines through blockade of signal transducer and activator of transcription 1 and nuclear factor-κB in activated keratinocytes, the major cells involved in AD progression. Based on the histological and immunological analyses, oral treatment with polyozellin attenuated the Dermatophagoides farinae extract (DFE)/2,4-dinitrochlorobenzene (DNCB)-induced atopic inflammatory symptoms in the skin. Pruritus is an unpleasant sensation for AD patients that causes scratching behavior and ultimately exacerbates the severity of AD. To find a possible explanation for the anti-pruritic effects of polyozellin, we investigated its effects on mast cells and mast cell-derived histamines. Oral treatment with polyozellin reduced the DFE/DNCB-induced tissue infiltration of mast cells, the serum histamine levels, and the histaminergic scratching behaviors. Additionally, polyozellin decreased the immunoglobulin E-stimulated degranulation of mast cells. Taken together, the findings of this study provide us with novel insights into the potential pharmacological targets of polyozellin for treating AD by inhibiting the inflammatory and pruritic responses.

Prunus serrulata var. spontanea inhibits mast cell activation and mast cell-mediated anaphylaxis.

ETHNOPHARMACOLOGICAL RELEVANCE: A promising approach to treat a variety of diseases are considered as complementary and alternative herbal medicines. Prunus serrulata var. spontanea L. (Rosaceae) is used as herbal medicine to treat allergic diseases according to the Donguibogam, a tradition medical book of the Joseon Dynasty in Korea. AIM OF THE STUDY: We prepared the aqueous extract of the bark of P. serrulata (AEBPS) and aimed to investigate the effects in mouse anaphylaxis models and various types of mast cells, including RBL-2H3, primary cultured peritoneal and bone marrow-derived mast cells. MATERIALS AND METHODS: We used ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models, in vivo. The control drug dexamethasone (10 mg/kg) was used to compare the effectiveness of AEBPS (1-100 mg/kg). In vitro, IgE-stimulated mast cells were used to confirm the role of AEBPS (1-100 µg/mL). For statistical analyses, p values less than 0.05 were considered to be significant. RESULTS: In ASA model, oral administration of AEBPS suppressed the hypothermia and increased level of serum histamine in a dose-dependent manner. AEBPS attenuated the serum IgE, OVA-specific IgE, and interleukin (IL)-4. Oral administration of AEBPS also blocked mast cell-dependent PCA. AEBPS suppressed degranulation of mast cells by reducing intracellular calcium level in mast cells. AEBPS inhibited tumor necrosis factor-α and IL-4 expression and secretion in a concentration-dependent manner through the reduction of nuclear factor-κB. CONCLUSIONS: On the basis of these findings, AEBPS could serve as a potential therapeutic target for the management of mast cell-mediated allergic inflammation and as a regulator of mast cell activation.

Effects of CO2 Curing on Alkali-Activated Slag Paste Cured in Different Curing Conditions.

The effect of CO2 curing on alkali-activated slag paste activated by a mixture of sodium hydroxide and sodium silicate solutions is reported in this paper. The paste samples after demolding were cured in three different curing environments as follows: (1) environmental chamber maintained at 85% relative humidity (RH) and 25 °C; (2) 3-bar CO2 pressure vessel; and (3) CO2 chamber maintained at 20% CO2 concentration, 70% RH and 25 °C. The hardened samples were then subjected to compressive strength measurement, X-ray diffraction analysis, and thermogravimetry. All curing conditions used in this study were beneficial for the strength development of the alkali-activated slag paste samples. Among the curing environments, the 20% CO2 chamber was the most effective on compressive strength development; this is attributed to the simultaneous supply of moisture and CO2 within the chamber. The results of X-ray diffraction and thermogravimetry show that the alkali-activated slag cured in the 20% CO2 chamber received a higher amount of calcium silicate hydrate (C-S-H), while calcite formed at an early age was consumed with time. C-S-H was formed by associating the calcite generated by CO2 curing with the silica gel dissolved from alkali-activated slag.

Gomisin M2 Inhibits Mast Cell-Mediated Allergic Inflammation via Attenuation of FcεRI-Mediated Lyn and Fyn Activation and Intracellular Calcium Levels.

Mast cells are effector cells that induce allergic inflammation by secreting inflammatory mediators. Gomisin M2 (G.M2) is a lignan isolated from Schisandra chinensis (Turcz). Baill. exhibiting anti-cancer activities. We aimed to investigate the anti-allergic effects and the underlying mechanism of G.M2 in mast cell-mediated allergic inflammation. For the in vitro study, we used mouse bone marrow-derived mast cells, RBL-2H3, and rat peritoneal mast cells. G.M2 inhibited mast cell degranulation upon immunoglobulin E (IgE) stimulation by suppressing the intracellular calcium. In addition, G.M2 inhibited the secretion of pro-inflammatory cytokines. These inhibitory effects were dependent on the suppression of FcεRI-mediated activation of signaling molecules. To confirm the anti-allergic effects of G.M2 in vivo, IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA) models were utilized. Oral administration of G.M2 suppressed the PCA reactions in a dose-dependent manner. In addition, G.M2 reduced the ASA reactions, including hypothermia, histamine, interleukin-4, and IgE production. In conclusion, G.M2 exhibits anti-allergic effects through suppression of the Lyn and Fyn pathways in mast cells. According to these findings, we suggest that G.M2 has potential as a therapeutic agent for the treatment of allergic inflammatory diseases via suppression of mast cell activation.

Inhibitory effect of ethanol extract of Ampelopsis brevipedunculata rhizomes on atopic dermatitis-like skin inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Extracts from various parts of Ampelopsis brevipedunculata has been used as anti-inflammatory agents in Asian folk medicine. AIM OF THE STUDY: To demonstrate the medicinal effect of the A. brevipedunculata in skin inflammation, specifically atopic dermatitis (AD). MATERIALS AND METHODS: The effect of ethanol extract of A. brevipedunculata rhizomes (ABE) on AD was examined using an AD-like skin inflammation model induced by repeated exposure to house dust mite (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB). The mechanism study was performed using tumor necrosis factor (TNF)-α and interferon (IFN)-γ-activated human keratinocytes (HaCaT). Serum histamine and immunoglobulin levels were quantified using enzymatic kits, while the gene expression of cytokines and chemokines was analyzed using quantitative real time polymerase chain reaction. The expression of signaling molecules was detected using Western blot. RESULTS: Oral administration of ABE alleviated DFE/DNCB-induced ear thickening and clinical symptoms, as well as immune cell infiltration (mast cells and eosinophils) into the dermal layer. Serum Immunoglobulin (Ig) E, DFE-specific IgE, IgG2a, and histamine levels were decreased after the administration of ABE. ABE also inhibited CD4+IFN-γ+ and CD4+IL-4+ lymphocyte polarization in lymph nodes and expression of TNF-α, IFN-γ, IL-4, IL-13, and IL-31 in the ear tissue. In TNF-α/INF-γ-stimulated keratinocytes, ABE inhibited the gene expression of TNF-α, IL-6, IL-1ß, and CCL17. In addition, ABE decreased the nuclear localization of signal transducer and activator of transcription 1 and nuclear factor-κB, and the phosphorylation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. CONCLUSION: Collectively, our data demonstrate the pharmacological role and signaling mechanism of ABE in the regulation of skin allergic inflammation, which supports our suggestion that ABE could be developed as a potential therapeutic agent for the treatment of AD.

Nothofagin suppresses mast cell-mediated allergic inflammation.

Mast cells play a major role in immunoglobulin E-mediated allergic inflammation, which is involved in asthma, atopic dermatitis, and allergic rhinitis. Nothofagin has been shown to ameliorate various inflammatory responses such as the septic response and vascular inflammation. In this study, we assessed the inhibitory effect of nothofagin on allergic inflammation using cultured/isolated mast cells and an anaphylaxis mouse model. Nothofagin treatment prevented histamine and ß-hexosaminidase release by reducing the influx of calcium into the cytosol in a concentration-dependent manner. Nothofagin also inhibited the gene expression and secretion of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-4 by downregulating the phosphorylation of Lyn, Syk, Akt and nuclear translocation of nuclear factor-κB. To confirm these effects of nothofagin in vivo, we used a passive cutaneous anaphylaxis mouse model. Topical administration of nothofagin suppressed local pigmentation and ear thickness. Taken together, these results suggest nothofagin as a potential candidate for the treatment of mast cell-involved allergic inflammatory diseases.

Elaeocarpusin Inhibits Mast Cell-Mediated Allergic Inflammation.

Mast cells are major effector cells for allergic responses that act by releasing inflammatory mediators, such as histamine and pro-inflammatory cytokines. Accordingly, different strategies have been pursued to develop anti-allergic and anti-inflammatory candidates by regulating the function of mast cells. The purpose of this study was to determine the effectiveness of elaeocarpusin (EL) on mast cell-mediated allergic inflammation. We isolated EL from Elaeocarpus sylvestris L. (Elaeocarpaceae), which is known to possess anti-inflammatory properties. For this study, various sources of mast cells and mouse anaphylaxis models were used. EL suppressed the induction of markers for mast cell degranulation, such as histamine and ß-hexosaminidase, by reducing intracellular calcium levels. Expression of pro-inflammatory cytokines, such as tumor necrosis factor-α and IL-4, was significantly decreased in activated mast cells by EL. This inhibitory effect was related to inhibition of the phosphorylation of Fyn, Lyn, Syk, and Akt, and the nuclear translocation of nuclear factor-κB. To confirm the effect of EL in vivo, immunoglobulin E-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA) models were induced. EL reduced the PCA reaction in a dose dependent manner. In addition, EL attenuated ASA reactions such as hypothemia, histamine release, and IgE production. Our results suggest that EL is a potential therapeutic candidate for allergic inflammatory diseases that acts via the inhibition of mast cell degranulation and expression of proinflammatory cytokines.

Esculetin from Fraxinus rhynchophylla attenuates atopic skin inflammation by inhibiting the expression of inflammatory cytokines.

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder afflicting from infancy to adults with itching, scratching, and lichenification. We aimed to investigate the effects of esculetin from Fraxinus rhynchophylla on atopic skin inflammation. For induction of atopic skin inflammation, we exposed the ears of female BALB/c mice to house dust mite (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB) for 4 weeks. Oral administration of esculetin reduced the symptoms of DFE/DNCB-induced atopic skin inflammation, which were evaluated based on ear swelling and number of scratch bouts. The immunoglobulin (Ig) E, IgG2a, and histamine levels in serum were decreased and inflammatory cell infiltration in skin tissue was reduced by the esculetin. It suppressed production of Th1, Th2 and Th17-related cytokines such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-4, IL-13, IL-31 and IL-17 in the ear tissue. Furthermore, we investigated the effects of esculetin on activated keratinocytes, which are representative cells used for studying the pathogenesis of acute and chronic atopic skin inflammation. As results, esculetin suppressed gene expression of Th1, Th2 and Th17 cytokines and the activation of nuclear factor-κB and signal transducer and activator of transcription 1 in TNF-α/IFN-γ-stimulated keratinocytes. Taken together, these results imply that esculetin attenuated atopic skin inflammation, suggesting that esculetin could be a potential therapeutic candidate for the treatment of AD.

Anti­inflammatory effect of Amomum xanthioides in a mouse atopic dermatitis model.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder. The present study investigated the effects of Amomum xanthioides extract (AXE) on AD­like skin inflammation using a Dermatophagoides farinae extract (DFE) and 2,4­dinitrochlorobenzene (DNCB)­induced mouse AD model. Hematoxylin and eosin staining results demonstrated that repeated DFE/DNCB exposure markedly increased the thickening of the dermis and epidermis, in addition to the infiltration of eosinophils and mast cells. However, oral administration of AXE reduced these histopathological alterations in a dose­dependent manner. Elevated serum histamine, total and DFE­specific immunoglobulin E (IgE), and IgG2a were also decreased by treatment with AXE. In addition, reverse transcription­quantitative polymerase chain reaction (RT­qPCR) results demonstrated that the mRNA expression of tumor necrosis factor (TNF)­α, interferon (IFN)­Î³, interleukin (IL)­4, IL­13, IL­31 and IL­17A was reduced in ear skin following AXE administration in AD mice. Fluorescence­activated cell sorting demonstrated that the population of CD4+/IL­4+, CD4+/IFN­Î³+ and CD4+/IL­17A+ cells in draining lymph nodes was also significantly decreased in AXE­treated mice compared with AD mice without AXE treatment. Furthermore, keratinocytes that were stimulated with TNF­α and IFN­Î³ exhibited increased gene expression of pro­inflammatory cytokines and chemokines, including TNF­α, IL­1ß, IL­6, IL­8, C­C motif chemokine ligand (CCL)17 and CCL22, as determined by RT­qPCR. However, upregulation of these genes was reduced by AXE pretreatment. Based on these results, we hypothesize that AXE may be useful in the treatment of allergic skin inflammation, particularly AD.

Tyrosol attenuates lipopolysaccharide-induced acute lung injury by inhibiting the inflammatory response and maintaining the alveolar capillary barrier.

Acute lung injury (ALI) is a life-threatening disease characterized by increased pulmonary vascular permeability because of alveolar capillary barrier dysfunction and increased immune responses. This study determined the anti-inflammatory effect of tyrosol on lipopolysaccharide (LPS)-induced ALI and its underlying mechanisms of action. BALB/c mice were orally administered with tyrosol (0.1, 1, and 10 mg/kg) 1 h before an intratracheal injection of LPS (25 µg/50 µL). Oral treatment with tyrosol inhibited lung vascular permeability, histopathological changes, wet/dry lung weight ratio, and pulmonary vascular cell infiltration. The LPS-induced imbalance in the activity of enzymes, such as superoxide dismutase and myeloperoxidase, was regulated by tyrosol. Pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6, were reduced by tyrosol in bronchoalveolar lavage fluid and lung tissue. The activation of inflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and phosphorylated-IκBα, was suppressed by the presence of tyrosol in the lung tissue. In addition, tyrosol attenuated the production of NO, the expression of pro-inflammatory cytokines, the expression of iNOS and COX-2, and the nuclear translocation of nuclear factor-κB in LPS-stimulated RAW 264.7 macrophages. These results suggested that tyrosol is a potential therapeutic agent for treating inflammatory lung diseases.

Can clinical scoring systems improve the diagnostic accuracy in patients with suspected adult appendicitis and equivocal preoperative computed tomography findings?

OBJECTIVE: Adult appendicitis (AA) with equivocal computed tomography (CT) findings remains a diagnostic challenge for physicians. Herein we evaluated the diagnostic performance of several clinical scoring systems in adult patients with suspected appendicitis and equivocal CT findings. METHODS: We retrospectively evaluated 189 adult patients with equivocal CT findings. Alvarado, Eskelinen, appendicitis inflammatory response, Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA), and adult appendicitis score (AAS) scores were evaluated, receiver operating characteristic analysis was conducted, and the optimal, low, and high cut-off values were determined for patient classification into three groups: low, intermediate, or high. RESULTS: In total, 61 patients were included in the appendicitis group and 128 in the non-appendicitis group. There were no significant differences between the area under the curve of the clinical scoring systems in the final diagnosis of AA for equivocal appendicitis on CT (Alvarado, 0.698; Eskelinen, 0.710; appendicitis inflammatory response, 0.668; RIPASA, 0.653; AAS, 0.726). A RIPASA score greater than 7.5 had a high positive predictive value (90.9) and an AAS score less than or equal to 5 had a high negative predictive value (91.7) in the diagnosis of AA. CONCLUSION: The accuracy of clinical scoring systems in the diagnosis of AA with equivocal CT findings was moderate. Therefore, a high RIPASA score may assist in the diagnosis of AA in patients with equivocal CT findings, and a low AAS score may be used as a criterion for patient discharge. Most patients presented with intermediate scores. The patients with equivocal CT findings may be considered as a third diagnostic category of AA.

Diospyros kaki calyx inhibits immediate-type hypersensitivity via the reduction of mast cell activation.

CONTEXT: Diospyros kaki L. (Ebenaceae) fruit is widely distributed in Asia and is known to exert anti-inflammatory and antithrombotic effects. OBJECTIVE: We evaluated the inhibitory effect of aqueous extract of D. kaki calyx (AEDKC) on mast cell-mediated immediate-type hypersensitivity and underlying mechanism of action. MATERIALS AND METHODS: For in vivo, ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models were used. In the ASA, AEDKC (1-100 mg/kg) was orally administered 3 times during 14 days. In the PCA, AEDKC was orally treated 1 h before the antigen challenge. The control drug dexamethasone was used to compare the effectiveness of AEDKC. For in vitro, IgE-stimulated RBL-2H3 cells and primary cultured peritoneal mast cells were used to determine the role of AEDKC (0.01-1 mg/mL). RESULTS: Oral administration of AEDKC dose dependently suppressed rectal temperature decrease and increases in serum histamine, total IgE, OVA-specific IgE, and interleukin (IL)-4 in the ASA. In the PCA, AEDKC reduced Evans blue pigmentation. Compared to dexamethasone (10 mg/kg), AEDKC (100 mg/kg) showed similar inhibitory effects in vivo. AEDKC concentration dependently suppressed the release of histamine and ß-hexosaminidase through the reduction of intracellular calcium in mast cells. In addition, AEDKC decreased the expression and secretion of tumour necrosis factor-α and IL-4 by the reduction of nuclear factor-κB. The inhibitory potential of AEDKC (1 mg/mL) was similar with dexamethasone (10 µM) in vitro. CONCLUSIONS: We suggest that AEDKC may be a potential candidate for the treatment of mast cell-mediated allergic diseases.

Anti-inflammatory effects of ursolic acid-3-acetate on human synovial fibroblasts and a murine model of rheumatoid arthritis.

Ursolic acid (UA), a pentacyclic triterpenoid, is a common natural substance known to be effective in the treatment of inflammation, oxidative stress, and ulcers in arthritis. This study examined the effects of ursolic acid-3-acetate (UAA), a derivative of UA, on rheumatoid arthritis (RA) and verified the underlying mechanism of action by using a type-II collagen-induced arthritis (CIA) mice model and tumor necrosis factor (TNF)-α-stimulated RA synovial fibroblasts. The oral administration of UAA showed a decrease in clinical arthritis symptoms, paw thickness, histologic and radiologic changes, and serum IgG1 and IgG2a levels. UAA administration reduced Th1/Th17 phenotype CD4+ T lymphocyte expansion and inflammatory cytokine production in draining lymph nodes. In addition, UAA effectively reduced the expression and production of inflammatory mediators, including cytokines and matrix metalloproteinase-1/3 in the knee joint tissue and RA synovial fibroblasts, through the downregulation of IKKα/ß, ΙκBα, and nuclear factor-κB. Our findings showed that UAA modulated helper T cell immune responses and matrix-degrading enzymes. The effects of UAA were comparable with those of the positive control drug, dexamethasone. In summary, all the evidence presented in this paper suggest that UAA could be a therapeutic candidate for the treatment of RA.

Suppressive effect of an aqueous extract of Diospyros kaki calyx on dust mite extract/2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease, affecting 10-20% of individuals worldwide. Therefore, the discovery of drugs for treating AD is an attractive subject and important to human health. Diospyros kaki and Diospyros kaki (D. kaki) folium exert beneficial effects on allergic inflammation. However, the effect of D. kaki calyx on AD remains elusive. The present study evaluated the effects of an aqueous extract of D. kaki calyx (AEDKC) on AD-like skin lesions using mouse and keratinocyte models. We used a mouse AD model by the repeated skin exposure of house dust mite extract [Dermatophagoides farinae extract (DFE)] and 2,4-dinitrochlorobenzene (DNCB) to the ears. In addition, to determine the underlying mechanism of its operation, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-activated keratinocytes (HaCaT) were used. Oral administration of AEDKC decreased AD-like skin lesions, as demonstrated by the reduced ear thickness, serum immunoglobulin E (IgE), DFE-specific IgE, IgG2a, histamine level and inflammatory cell infiltration. AEDKC inhibited the expression of pro-inflammatory cytokines and a chemokine via downregulation of nuclear factor-κB and signal transducer and activator of transcription 1 in HaCaT cells. On examination of the AD-related factors in vivo and in vitro, it was confirmed that AEDKC decreased AD-like skin lesions. Taken together, the results suggest that AEDKC is a potential drug candidate for the treatment of AD.

Synthesis of Gallic Acid Analogs as Histamine and Pro-Inflammatory Cytokine Inhibitors for Treatment of Mast Cell-Mediated Allergic Inflammation.

Gallic acid (3,4,5-trihydroxybenzoic acid), is a natural product found in various foods and herbs that are well known as powerful antioxidants. Our previous report demonstrated that it inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. In this report, various amide analogs of gallic acid have been synthesized by introducing different amines through carbodiimide-mediated amide coupling and Pd/C-catalyzed hydrogenation. These compounds showed a modest to high inhibitory effect on histamine release and pro-inflammatory cytokine expression. Among them, the amide bearing (S)-phenylglycine methyl ester 3d was found to be more active than natural gallic acid. Further optimization yielded several (S)- and (R)-phenylglycine analogs that inhibited histamine release in vitro. Our findings suggest that some gallamides could be used as a treatment for allergic inflammatory diseases.

2-Hydroxy-3-methoxybenzoic acid attenuates mast cell-mediated allergic reaction in mice via modulation of the FcεRI signaling pathway.

Mast cells are important effector cells in immunoglobulin (Ig) E-mediated allergic reactions such as asthma, atopic dermatitis and rhinitis. Vanillic acid, a natural product, has shown anti-oxidant and anti-inflammatory activities. In the present study, we investigated the anti-allergic inflammatory effects of ortho-vanillic acid (2-hydroxy-3-methoxybenzoic acid, o-VA) that was a derivative of vanillic acid isolated from Amomum xanthioides. In mouse anaphylaxis models, oral administration of o-VA (2, 10, 50 mg/kg) dose-dependently attenuated ovalbumin-induced active systemic anaphylaxis and IgE-mediated cutaneous allergic reactions such as hypothermia, histamine release, IgE production and vasodilation; administration of o-VA also suppressed the mast cell degranulator compound 48/80-induced anaphylaxis. In cultured mast cell line RBL-2H3 and isolated rat peritoneal mast cells in vitro, pretreatment with o-VA (1-100 µmol/L) dose-dependently inhibited DNP-HSA-induced degranulation of mast cells by decreasing the intracellular free calcium level, and suppressed the expression of pro-inflammatory cytokines TNF-α and IL-4. Pretreatment of RBL-2H3 cells with o-VA suppressed DNP-HSA-induced phosphorylation of Lyn, Syk, Akt, and the nuclear translocation of nuclear factor-κB. In conclusion, o-VA suppresses the mast cell-mediated allergic inflammatory response by blocking the signaling pathways downstream of high affinity IgE receptor (FcεRI) on the surface of mast cells.