N-(3′,4′,5′-Trimethoxycinnamoyl)ortho-aminobenzoic acid(TOA),at the concentration of 80μg/ml,significantly inhibited the antigen-induced contraction of ileum isolated from the actively sensitized guinea-pig.At the...N-(3′,4′,5′-Trimethoxycinnamoyl)ortho-aminobenzoic acid(TOA),at the concentration of 80μg/ml,significantly inhibited the antigen-induced contraction of ileum isolated from the actively sensitized guinea-pig.At the concentrations of 25 and 50μg/ml, TOA inhibited homocytotropic antibody-mediated degranulation of mast cells in the rat mesentery,and also inhibited anaphylactic histamine release from rat peritoneal mast cells.展开更多
Objective:Avidly phagocytosed hemozoin(malarial pigment) alters several functions of human monocytes and stimulates generation of several cytokines.Recently,we showed that phagocytosis of hemozoin by human monocytes i...Objective:Avidly phagocytosed hemozoin(malarial pigment) alters several functions of human monocytes and stimulates generation of several cytokines.Recently,we showed that phagocytosis of hemozoin by human monocytes increases expression and activity of matrix metalloproteinase-9,a proteolytic enzyme available in specific gelatinase granules,which contain several enzymes including lysozyme.Present work investigated active lysozyme release after phagocytosis of hemozoin and its dependence on production of tumor necrosis factor alpha. Methods:After phagocytosis of hemozoin,hemozoin-containing trophozoites or control meals(opsonized nonparasitized red blood cells and latex particles),monocyte supematants were monitored for 2 hours,in presence of blocking anti-human tumor necrosis factor alpha antibodies or recombinant human tumor necrosis factor alpha cytokine in selected experiments.Lysozyme release was evaluated by a specific spectrometric assay measuring lysozyme activity after coincubation of cell supematants with suspensions of Mycrococcus Lysodeikticus,while levels of soluble tumor necrosis factor alpha were analyzed by specific enzyme-linked immunodsorbent assay. Results:Levels of lysozyme activity and soluble tumor necrosis factor alpha protein were increased in hemozoin in-or trophozoites-laden monocytes supematants.Phagocytosis per se(control meals) also increased lysozyme release,but levels were significantly lower than those obtained after phagocytosis of hemozoin or trophozoites. Interestingly,all effects on lysozyme release observed after phagocytosis were abrogated by blocking anti-human tumor necrosis factor alpha antibodies,while they were mimicked by recombinant human tumor necrosis factor alpha cytokine.Conclusions:Present work shows that phagocytosis of hemozoin promotes monocyte degranulation and enhances active lysozyme release.The effect requires tumor necrosis factor alpha mediation.展开更多
Aims: To study RBL-2H3 cell degranulation phenomena induced by some TCMIs through cell morphological and ultra-structural observation, released enzyme activity and establish RBL-2H3 cell degranulation test indicated ...Aims: To study RBL-2H3 cell degranulation phenomena induced by some TCMIs through cell morphological and ultra-structural observation, released enzyme activity and establish RBL-2H3 cell degranulation test indicated by β- hexosaminidase activity as a method to evaluate TCMIs at nonclinical stage. Methods: RBL-2H3 cells were used to study the degranulation by co-culture with positive control C48/80 and some TCMIs through morphological and ultra-structure observation, β-hexosaminidase activity detection. RBL-2H3 cell degranulation test was established to detect β-hexosaminidase activity caused by 17 kinds of TCMIs and their ingredients. The cytotoxicity effect of some TCMIs on both RBL 2H3 and BRL cells was measured by CCK-8 assay. Results: Toluidine blue staining and ultra-structure of electronic microscope observation of treated RBL-2H3 cells showed degranulation morphologically. Detection of β-hexosaminidase activity in the supernatant of treated cells showed some TCMIs had elevated enzyme release rates. Further analysis of the ingredients and compound in Tanreqing Injection and Shengmai Injection showed Scutellaria baicalensis Georgi in Tanreqing Injection, Red ginseng and Fructus Schisandrae Chinensis in Shengmai Injection were responsible to the degranulation of RBL-2H3 cells. Osmotic pressures and pH influenced RBL-2H3 degranulation. High Osmotic pressure of Tanreqing Injection and low pH of chlorogenic acid at 2.5 and 5.0 mmol/L congcentration might be responsible to high β-hexosaminidase activity. Most of the TCMIs inducing degranulation had cytotoxicity effect for both RBL-2H3 and BRL cells, but some TCMIs inducing degranulation had no cytotoxicity effect. Conclusion: Some TCMIs can induce degranulation of RBL-2H3 cells;RBL-2H3 cell degranulation test can be used in non-clinical stage to detect the risk causing anaphylactoid reactions. Osmotic pressures and pH influenced RBL-2H3 degranulation, and they should be measured before testing. The mechanism of degranulation caused by some TCMIs is cytotoxic, and some are non-cytotoxic and may be through exicytosis.展开更多
ObjectiveTo investigate the effects of friedelin (terpenoid) and 8-hydroxyisocapnolactone-2-3-diol (coumarin) with concentration 10 μM, 30 μM, and 100 μM on inhibiting mast cells (MCs) degranulation....ObjectiveTo investigate the effects of friedelin (terpenoid) and 8-hydroxyisocapnolactone-2-3-diol (coumarin) with concentration 10 μM, 30 μM, and 100 μM on inhibiting mast cells (MCs) degranulation.MethodsThe investigation was performed in vitro by administering each compound into rat peritoneal MCs and rat basophilic leukemia-2H3 cells followed by activation with 50 μg/mL of compound 48/80 or 1 μM of ionomycin. The concentration of histamine released from each group was measured by a high-performance liquid chromatography-fluorometry system with post-column derivatization using o-phthalaldehyde.Results8-Hydroxyisocapnolactone-2-3-diol inhibited degranulation of compound 48/80 activated-rat peritoneal MCs with the histamine release percentages of 74.57%, 72.21% and 51.79% when the 10 μM, 30 μM and 100 μM concentrations were used, respectively. Where as about 81% histamine was released by the control group. Degranulation inhibition ability was also observed in ionomycin-activated rat basophilic leukemia-2H3 cells. In contrast, friedelin failed to inhibit degranulation in either cell type. The inhibition of 8-hydroxyisocapnolactone-2-3-diol was not related to the depletion of histamine synthesis as implied by the total histamine measurement.ConclusionsThese results exhibit the promising of 8-hydroxyisocapnolactone-2-3-diol is a potential parent structure for developing a MCs stabilizer.展开更多
Background:In this study,we investigated whether prophylactic treatment with Guizhi-Shaoyao-Zhimu decoction(GSZ)could delay the onset of rheumatoid arthritis by targeting mast cells.Methods:Collagen-induced arthritis ...Background:In this study,we investigated whether prophylactic treatment with Guizhi-Shaoyao-Zhimu decoction(GSZ)could delay the onset of rheumatoid arthritis by targeting mast cells.Methods:Collagen-induced arthritis was used to evaluate the effect of GSZ in preventing arthritis and joint destruction.Immunohistochemical staining revealed the accumulation of histamine H4 receptor and tryptase alpha/beta-1 in the ankle joint of the model.Then,we explored the effect of GSZ serum on fibroblast-like synoviocytes using standard transwell invasion and migration assays.Real-time quantitative polymerase chain reaction and western blot were used to detect the expression of toll-like receptor 4(TLR4)/myeloid differentiationfactor 88(MyD88)/nuclear factor-κB p65(NF-κB p65).Results:The results showed that pre-rheumatoid arthritis treatment with GSZ could reduce inflammation and maintain cartilage structure in the collagen-induced arthritis model.Moreover,GSZ significantly blocked mast cell degranulation and inhibited the TLR4/MyD88/NF-κB p65 pathway.Since the combined activation of mast cells via TLR4 and immune complexes enhances inflammation in synovial tissue,we concluded that GSZ may block mast cell degranulation by inhibiting the TLR4/MyD88/NF-κB p65 pathway and thus influence rheumatoid arthritis onset.Conclusion:Taken together,our data suggested that GSZ may be a promising therapeutic decoction for the prophylactic treatment of rheumatoid arthritis.展开更多
The correlation between the activities of the outer menbrane proteins （OMPs） of Bordetella pertussis and the lgE-mediated asthma was investigated in the present study, in which the OMPs of B. pertussis and their com...The correlation between the activities of the outer menbrane proteins （OMPs） of Bordetella pertussis and the lgE-mediated asthma was investigated in the present study, in which the OMPs of B. pertussis and their components were prepared by detergent treatment and chromatography, and the molecular weights of the OMPs components were determined by SDS-PAGE. The amounts of total as well as the ovalbumin （OVA）-specific IgE induced by dead B. pertussis whole bacterial vaccine on guinea pigs were detected by ELISA. Meanwhile, the effect of the OMPs and their components to promote the degranulation of guinea pig mast cells was observed by using the mast cell degranulation test, and ELISA assay was used to measure the histatmine levels in the supematants from the mast cell cultures. Histamine sensitive test was used to demonstrate the effects of the OMPs and their components to increase the histamine lethal sensitivity in mice. It was found that four components with molecular weights of 30, 32, 38 and 69 kDa could be obtained from the OMPs of B. pertussts, and the dead whole bacteria vaccine of B. pertussis had the ability to increase the levels of the total as well as the OVA-specific IgE in sera of guinea pigs. The OMPs and their 30 and 32 kDa components demonstrated significantly enhancing effect on the degranulation of guinea pig mast cells, and the histamine levels in the supematants from the mast cell culture treated with OMPs and their 30 and 32 kDa components were also significantly increased. It is evident that the strong adjuvant activity and the enhancing effect to degranulation of mast cells and the release of histamine of certain outer membrane components of B. pertussis could be demonstrated as revealed by the results of the present study, suggesting the possibility of a close relationship between the infection of vaccination with B. pertussis and the IgE-mediated asthma.展开更多
Background:Both intestinal and pulmonary systems are parts of the mucosal immune system,comprising~80%of all immune cells.These immune cells migrate or are transported between various mucosal tissues to maintain tissu...Background:Both intestinal and pulmonary systems are parts of the mucosal immune system,comprising~80%of all immune cells.These immune cells migrate or are transported between various mucosal tissues to maintain tissue homeostasis.Methods:In this study,we isolated neutrophils from the peripheral blood of patients and utilized immunofluorescence,flow cytometry,and Western blotting to confirm the incidence of“nucleus-directed degranulation”in vitro.Subsequently,we conducted a precise analysis using arivis software.Furthermore,using the Dss mouse model of colitis and tissue clearing technologies,we validated the“targeted nuclear degranulation”of neutrophils and their migration to the lungs in an inflammatory intestinal environment.Result:In this study,we found that among patients with ulcerative colitis,the migration of neutrophils with“targeted nuclear degran-ulation”from the intestinal mucosa to the lungs significantly exacerbates lung inflammation during pulmonary infections.Notably,patients with ulcerative colitis exhibited a higher abundance of neutrophils with targeted nuclear degranulation.Using DsS mice,we observed that neutrophils with targeted nuclear degranulation from the intestinal mucosa migrated to the lung and underwent activation during pulmonary infections.These neutrophils rapidly released a high amount of neutrophil extracellular traps to medi-ate the progression of lung inflammation.Alterations in the neutrophil cytoskeleton and its interaction with the nuclear membrane represent the primary mechanisms underlying targeted nuclear degranulation.Conclusion:This study revealed that neutrophils accelerate lung inflammation progression in colitis,offering new insights and po-tential treatment targets for lung infections for patients with colitis.展开更多
Food allergy is a major health issue worldwide. Mast cells play a very important role in the immediate hypersensitivity for which mast cell degranulation needs to be studied extensively. In this study, an approach was...Food allergy is a major health issue worldwide. Mast cells play a very important role in the immediate hypersensitivity for which mast cell degranulation needs to be studied extensively. In this study, an approach was taken to study the characteristics of sensitized mast cell degranulation in vitro, which associated with the study of mast cells and animal models. BALB/c mice were immunized respectively by several food allergens, then blood and peritoneal mast cells were collected at different time points. A dynamic determination was carried out between mast cells and serumal IgE. Comparative analysis on sequential time points showed that there was a close coincidence between mast cell degranulation and IgE antibody titers in sensitized BALB/c mice. Furthermore, it is interesting that sensitized mast cells could implement specific degranulation against the challenges in vitro, but the closely tropomyosins induced mast cell degranulation displayed cross reactions. This is very similar to IgE resisting the allergens in vivo. The study disclosed some characteristics on mast cells, coming from sensitized BALB/c mice, degranulation in vitro.展开更多
Early after priming, effector CD8 T cells are distinguished into memory precursor and short-lived effector cell subsets （MPECs and SLECs）. Here, we delineated a distinct in vivo heterogeneity in killer cell lectin-l...Early after priming, effector CD8 T cells are distinguished into memory precursor and short-lived effector cell subsets （MPECs and SLECs）. Here, we delineated a distinct in vivo heterogeneity in killer cell lectin-like receptor G1 （KLRG-1） expression, which was strongly associated with diverse MPEC and SLEC fates. These in vivo MPECs and SLECs expressed equivalent levels of cytotoxic molecules and effector cytokines. Using a unique in vivodegranulation assay, we found that the MPECs and SLECs similarly encountered infected target cells and elaborated equivalent levels of cytotoxicity in vivo. These data provide direct in vivoevidence that memory-fated ceils pass through a robust effector phase. Additionally, the preferential localization of the MPECs in the lymph nodes, where a lesser degree of cytotoxicity was elaborated, suggests that the MPECs may be protected from excessive stimulation and terminal differentiation by virtue of their differential tissue localization. These data provide novel mechanistic insights into the linear decreasing potential model of memory differentiation.展开更多
Polymorphonuclear neutmphils （PMNs） have a major role in the innate immune system. However, little is known about PMN contribution in relation to oral health. The objective of this study was to investigate the numbe...Polymorphonuclear neutmphils （PMNs） have a major role in the innate immune system. However, little is known about PMN contribution in relation to oral health. The objective of this study was to investigate the numbers and functional characteristics of oral PMNs （oPMNs） compared with circulatory PMNs （cPMNs）. Oral rinse and venous blood samples were obtained from 268 systemically and orally healthy volunteers in a cross-sectional observational study. PMN counts, cell cycle analysis and cellular activation state were investigated. Also, reactive oxygen species （ROS） production was analyzed, with and without bacterial stimulation （Fusobacterium nucleatum）. In males, 1.2 × 10^6- 1.0 ×10^6 oPMNs were collected, and showed a tendency to correlate with the levels of gingival bleeding （r= 0.215, P= 0.008）. Comparable oPMNs counts were found among females （1.0 ×10^6＋ 0.7 × 10^6）. More late-stage apoptotic/necrotic cells were found among the oPMNs （53.1%） compared with the cPMNs （8.5%; P〈 0.001）. Without additional stimulation, oPMNs were more activated than cPMNs, as indicated by higher expression of CD11b, CD63 and CD66b, and higher constitutive ROS levels （P〈 0.001）. Notably, in response to bacterial stimulation, oPMNs released comparable ROS levels as cPMNs （P= 0.042）. In conclusion, this study provides data on viable oPMNs showing high levels of activation in orally and systemically healthy individuals, free of apparent caries lesions and periodontal disease. These data suggests that although the oPMNs are in a more mature stage of their life cycle compared with the cPMNs, oPMNs are still responsive to stimulation, which indicates their functional potential and possible contribution to a healthy oral ecosystem.展开更多
Kounis syndrome seems to be not a rare disease but a rarely diagnosed disorder. Multiple causes can join forc-es and trigger the development of this syndrome. We report the first case of Kounis syndrome manifesting as...Kounis syndrome seems to be not a rare disease but a rarely diagnosed disorder. Multiple causes can join forc-es and trigger the development of this syndrome. We report the first case of Kounis syndrome manifesting as myocardial infarction with cardiovascular collapse that occurred in the dialysis room following an allergic reac-tion. The dialysis apparatus material of polyurethane, polyamide, polycarbonate, silicon rubber and polypro-pylene were incriminated causes. Physicians should be aware of the causality and existence of this disorder in order to achieve early and correct diagnosis and apply the appropriate therapeutic measures.展开更多
Quail egg ovomucoid can inhibit activation of basophils and eosinophils,while hen egg ovomucoid has been shown to be a major allergen,named Gal d 1.At present,the differences in structure and function between two ovom...Quail egg ovomucoid can inhibit activation of basophils and eosinophils,while hen egg ovomucoid has been shown to be a major allergen,named Gal d 1.At present,the differences in structure and function between two ovomucoid are unclear.We found the homology of ovomucoid in quail eggs and hen eggs reached77%.Compared with hen egg ovomucoid,the distribution of secondary structure was different in AA52-53,AA57-58,AA66-68,AA71-72,AA131-133,AA139-140,AA157-159 and AA184-185.Among 9 epitopes of egg ovomucoid,there were different amino acids from quail egg ovomucoid in 8 epitopes.Recombination quail egg ovomucoid had trypsin inhibition activity and quail egg ovomucoid didn't specifically bind to serum of eggs allergic patients.Quail egg ovomucoid can significantly inhibit RBL-2 H3 cells degranulation and protect cells morphology to a certain extent,indicating quail egg ovomucoid can inhibit cells activation and have potential anti-allergic effects,which is related to trypsin inhibitory activity.The difference in sensitization compare to hen egg ovomucoid may be due to amino acids differences affecting protein structure by changing antigenic epitopes.展开更多
We studied morphofunctional properties of human platelets, treated with low doses of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). It was shown that platelet incubation with 20 - 75 <em>...We studied morphofunctional properties of human platelets, treated with low doses of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). It was shown that platelet incubation with 20 - 75 <em>μ</em>M H<sub>2</sub>O<sub>2</sub> during 24 hours at 20<span style="white-space:nowrap;">°</span>C - 22<span style="white-space:nowrap;">°</span>C did not cause visible structural deficiencies in cells. Platelets maintained their adhesion activity and velocity of degranulation at 20 <em>μ</em>M H<sub>2</sub>O<sub>2</sub>. 30 - 60 μM H<sub>2</sub>O<sub>2</sub> dose-dependently reduced lamella’s growth and allowed retaining granule bulk inside cytoplasm of spreading platelets. After 1 - 2 hours, the most effect of platelet granules’ stabilization was registered at samples, previously incubated with 60 μM H<sub>2</sub>O<sub>2</sub>. Adrenalin activation led to rapid degranulation of stabilized platelets, whereas lamella’s growth in activated platelets was low or medium.展开更多
AIM： To study the bacteriocidal or bacteriostatic role of mast cells during infection with Mycobacterium.METHODS： Mycobacterium marinum （M. marinum） （BAA-535/M strain） was investigated for its ability to grow a...AIM： To study the bacteriocidal or bacteriostatic role of mast cells during infection with Mycobacterium.METHODS： Mycobacterium marinum （M. marinum） （BAA-535/M strain） was investigated for its ability to grow at a temperature relevant to the mammalian host. Primary mast cells were differentiated from bone marrows of mice, a human mast cell line （HMC-1） and a human monocytic cell line （MonoMac6） were maintained in culture. Mice were stimulated by intra-peritoneal injection of heat-killed M. marinum to study cytochemically the degranulation of peritoneal mast cells. HMC-1 cells were stimulated with M. marinum to analyse mRNA expression for inflammatory reactant genes, while HMC-1 and primary mouse mast cells were infected with M. marinum to establish in parallel cell viability （lactate dehydrogenase release and cell counts） and viable mycobacterial counts. Flow cytometry was used to assess intracellular presence of fluorescein isothiocyanate labelled M. marinum after trypan blue quenching and to measure the extent of infection-induced apoptosis or necrosis in HMC-1. A GFP expressing recombinant M. marinum strain was used to assess intracellular location by fuorescence microscopy. Light microscopy of osmium tetroxide and Gram Twortstained sections of 0.5 μm and transmission electron microscopy were undertaken as sensitive methods. RESULTS： Since its isolation, M. marinum has adapted to grow at 37 ℃. This study found that M. marinum infects HMC-1 cells and primary murine mast cells, where they survive, replicate, and cause dose dependent cell damage over the analysis period of up to 120 h. Amikacin was an effective aminoglycoside antibiotic to eliminate extracellular or membrane attached M. marinum in order to adequately quantify the intracellular bacterial loads. In vivo, intraperitoneal injection of heat-killed M. marinum led to the release of mast cell granules in mice. HMC-1 cells stimulated with M. marinum showed a biphasic pattern of increased mRNA expression for LL-37 and COX-2/TNF-a during 24 h of stimulation. In HMC-1, M. marinum localised to the cytoplasm whereas in primary mast cells, M. marinum were found in vacuoles.CONCLUSION： The effector role of mast cells in infection with M. marinum can be studied in vitro and in vivo.展开更多
<span style="font-family:Verdana;">Backgrou</span><span style="font-family:Verdana;">nd/Aim: Kuji amber is an interesting natural source for drug discovery</span><span>...<span style="font-family:Verdana;">Backgrou</span><span style="font-family:Verdana;">nd/Aim: Kuji amber is an interesting natural source for drug discovery</span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">because a new anti-allergic compound, named kujigamberol and several new compounds have been isolatated from it. It was important to evaluate the yield, biological activities and constituents of each methanol extract</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">of Kuji, Iwaki, Choshi, Mizunami and Ube ambers in Japan in order to establish if additional new compounds could be identified in these ambers. Materia</span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">ls and </span><span style="font-family:Verdana;">Method: Biological activities of each extract were evaluated using growth-restoring </span><span style="font-family:Verdana;">activity of the mutant yeast strain involving Ca</span><sup><span style="font-family:Verdana;">2+</span></sup><span style="font-family:Verdana;">-signal transduction and inhibi</span><span style="font-family:Verdana;">tion activity of degranulation in rat basophilic leukemia (RBL)-2H3 cells. Constituents</span><span style="font-family:Verdana;"> of each extract were analyzed by high performance liquid chromatography (HPLC). Results: All ambers except Ube amber have growth-restoring activity against the mutant yeast. Both Kuji and Iwaki ambers inhibited the degranulation of RBL-2H3 cells induced by the calcium ionophore A23187 in a dose dependent manner. The main biologically active compound in Kuji amber, kujigamberol, was also isolated from Iwaki amber and analyzed by mass spectrometry (MS) and nuclear magnetic resonance (NMR). Conclusion: Kuji and Iwaki ambers appeared to have the same origin. Choshi, Mizunami, and Ube ambers are valuable sources for biologically active compounds which are different from those of Kuji amber.</span></span></span></span>展开更多
During the past decades,populous expansion in mast cell scientific literature came forth with more,than forty-four thousand PubMed publications available to date.Such surge is due to the appreciation of the momentous ...During the past decades,populous expansion in mast cell scientific literature came forth with more,than forty-four thousand PubMed publications available to date.Such surge is due to the appreciation of the momentous role of mast cells in the evolution of species,in the development and maintenance of vital physiological functions,such as reproduction,homeostasis,and fluids,diverse immunological roles,and the potential of far-reaching effects despite minute numbers.While the emerging knowledge of the importance of mast cells in equilibrium comes of age when looking at the matter from an evolutionary perspective,the recognition of mast cells beyond detrimental performance in allergies and asthma,during protection against parasites,falters.Beyond wellknown classical functions,mast cells can process and present antigens,can serve as a viral reservoir,can respond to hormones and xenobiotics,initiate antiviral and antibacterial responses,phagocytosis,apoptosis,and participate in important developmental cornerstones.During evolution,upon the development of a sophisticated niche of innate and adaptive cell populations,certain mast cell functions became partially transmutable,yet the potency of mast cells remained considerable.Reviewing mast cells enables us to reflect on the certitude,that our sophisticated,complex physiology is rooted deeply in evolution,which we carry ancient remnants of,ones that may have decisive roles in our functioning.This communication sets out the goal of characterizing mast cells,particularly the aspects less in limelight yet of immense significance,without the aspiration exhaust it all.展开更多
Chronic eosinophilic leukemia (CEL) is a rare disorder that is characterized by hypereosinophilia with increased number of blood or marrow blasts (>5% and <20%). CEL is distinguished from hypereosinophilic syndr...Chronic eosinophilic leukemia (CEL) is a rare disorder that is characterized by hypereosinophilia with increased number of blood or marrow blasts (>5% and <20%). CEL is distinguished from hypereosinophilic syndrome (HES) by the presence of eosinophilic clonality. Chronic eosinophilic leukemia not otherwise specified (CEL-NOS) diagnosis is made when no fusion genes are detected by most modern molecular testing, particularly the most common fusion gene FIP1L-1/PDGFRA (Factor Interacting with PAP like-1/Platelet-Derived Growth Factor Receptor Alpha). This disease is very rare, and its description in the literature is not well characterized. We report a fetal case of severe CEL-NOS in a 19-year-old male who presented with a plethora of clinical features consists of constitutional symptoms, pancytopenia, intravascular thrombosis, acute stroke and endomyocardial infiltrates. The course of his disease was aggressive and resistant to conventional treatment. After a short period of improvement, an acute transformation into blast crisis (BC) had occurred. The diagnosis was confirmed by morphology and immunophenotyping of bone marrow biopsy. The patient eventually died of heart failure and sepsis. To our knowledge this is the first case report of fatal CEL-NOS transforming into severe blast crisis.展开更多
Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesi...Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture.This paper investigated the role of acupuncture needle surface textures on acupuncture’s analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation.Methods Four types of acupuncture needles with different surface textures(the lined needle,circle needle,sandpaper needle,and threaded needle)were designed.Additionally,the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation.To perform acupuncture analgesia experiments,four experimental acupuncture needles and a normal needle were inserted into the Zusanli(ST36)acupoint of rats with inflammatory pain.By comparing the force and torque and the analgesic efficacy of the different acupuncture needles,these experiments tested the role of acupuncture needle body texture on acupuncture analgesia.Results The analgesic effects of different acupuncture needle body textures varied.Specifically,the force required to penetrate the skin with the lined needle was not greater than that for the normal needle;however,the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion.Additionally,the torque of the lined needle reached 2×10^(-4)N·m under twisting manipulation,which was four times greater the torque of a normal needle(5×10^(-5)N·m).Furthermore,the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle.Conclusion Optimizing the texture of acupuncture needles can enhance acupuncture analgesia.The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle;it was also linked to variable analgesic effects.This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy.展开更多
The prevalence of food allergies is increasing dramatically and causing serious public health concerns.Notably,melatonin metabolism imbalance in patients with food allergies;however,the role of melatonin in food aller...The prevalence of food allergies is increasing dramatically and causing serious public health concerns.Notably,melatonin metabolism imbalance in patients with food allergies;however,the role of melatonin in food allergies remains unclear.Here,we demonstrated that melatonin suppresses food allergy responses and reprograms the gut microbiota of food-allergic mice,while melatonin aggravates food allergy during gut microbiota depletion.Mechanistically,melatonin boosts the degranulation of mast cells by up-regulating the expression of membrane high-affinity immunoglobulin E(IgE)receptor(FcεRI).Melatonin increases the mRNA expression of Rabenosyn-5(a component of factors for endosome recycling and Rab interactions)through melatonin receptor 2(MT2)-extracellular signal-regulated kinase(ERK)signaling,thereby driving the recycling of FcεRI and elevating the abundance of membrane FcεRI.Likewise,the inhibition of MT2 attenuates melatonin-induced food allergy in mice with gut microbiota depletion.Collectively,our finding provides insights into the pathogenesis of food allergies and provides a potential therapeutic target for the prevention and treatment of food allergies.展开更多
文摘N-(3′,4′,5′-Trimethoxycinnamoyl)ortho-aminobenzoic acid(TOA),at the concentration of 80μg/ml,significantly inhibited the antigen-induced contraction of ileum isolated from the actively sensitized guinea-pig.At the concentrations of 25 and 50μg/ml, TOA inhibited homocytotropic antibody-mediated degranulation of mast cells in the rat mesentery,and also inhibited anaphylactic histamine release from rat peritoneal mast cells.
基金supported in the context of the Italian Malaria Network by grants from Compagnia di San Paolo-IMIthe University of Torino Intramural FundsRegione Piemonte,Ricerca Sanitaria Finalizzata 2007 to PA
文摘Objective:Avidly phagocytosed hemozoin(malarial pigment) alters several functions of human monocytes and stimulates generation of several cytokines.Recently,we showed that phagocytosis of hemozoin by human monocytes increases expression and activity of matrix metalloproteinase-9,a proteolytic enzyme available in specific gelatinase granules,which contain several enzymes including lysozyme.Present work investigated active lysozyme release after phagocytosis of hemozoin and its dependence on production of tumor necrosis factor alpha. Methods:After phagocytosis of hemozoin,hemozoin-containing trophozoites or control meals(opsonized nonparasitized red blood cells and latex particles),monocyte supematants were monitored for 2 hours,in presence of blocking anti-human tumor necrosis factor alpha antibodies or recombinant human tumor necrosis factor alpha cytokine in selected experiments.Lysozyme release was evaluated by a specific spectrometric assay measuring lysozyme activity after coincubation of cell supematants with suspensions of Mycrococcus Lysodeikticus,while levels of soluble tumor necrosis factor alpha were analyzed by specific enzyme-linked immunodsorbent assay. Results:Levels of lysozyme activity and soluble tumor necrosis factor alpha protein were increased in hemozoin in-or trophozoites-laden monocytes supematants.Phagocytosis per se(control meals) also increased lysozyme release,but levels were significantly lower than those obtained after phagocytosis of hemozoin or trophozoites. Interestingly,all effects on lysozyme release observed after phagocytosis were abrogated by blocking anti-human tumor necrosis factor alpha antibodies,while they were mimicked by recombinant human tumor necrosis factor alpha cytokine.Conclusions:Present work shows that phagocytosis of hemozoin promotes monocyte degranulation and enhances active lysozyme release.The effect requires tumor necrosis factor alpha mediation.
文摘Aims: To study RBL-2H3 cell degranulation phenomena induced by some TCMIs through cell morphological and ultra-structural observation, released enzyme activity and establish RBL-2H3 cell degranulation test indicated by β- hexosaminidase activity as a method to evaluate TCMIs at nonclinical stage. Methods: RBL-2H3 cells were used to study the degranulation by co-culture with positive control C48/80 and some TCMIs through morphological and ultra-structure observation, β-hexosaminidase activity detection. RBL-2H3 cell degranulation test was established to detect β-hexosaminidase activity caused by 17 kinds of TCMIs and their ingredients. The cytotoxicity effect of some TCMIs on both RBL 2H3 and BRL cells was measured by CCK-8 assay. Results: Toluidine blue staining and ultra-structure of electronic microscope observation of treated RBL-2H3 cells showed degranulation morphologically. Detection of β-hexosaminidase activity in the supernatant of treated cells showed some TCMIs had elevated enzyme release rates. Further analysis of the ingredients and compound in Tanreqing Injection and Shengmai Injection showed Scutellaria baicalensis Georgi in Tanreqing Injection, Red ginseng and Fructus Schisandrae Chinensis in Shengmai Injection were responsible to the degranulation of RBL-2H3 cells. Osmotic pressures and pH influenced RBL-2H3 degranulation. High Osmotic pressure of Tanreqing Injection and low pH of chlorogenic acid at 2.5 and 5.0 mmol/L congcentration might be responsible to high β-hexosaminidase activity. Most of the TCMIs inducing degranulation had cytotoxicity effect for both RBL-2H3 and BRL cells, but some TCMIs inducing degranulation had no cytotoxicity effect. Conclusion: Some TCMIs can induce degranulation of RBL-2H3 cells;RBL-2H3 cell degranulation test can be used in non-clinical stage to detect the risk causing anaphylactoid reactions. Osmotic pressures and pH influenced RBL-2H3 degranulation, and they should be measured before testing. The mechanism of degranulation caused by some TCMIs is cytotoxic, and some are non-cytotoxic and may be through exicytosis.
文摘ObjectiveTo investigate the effects of friedelin (terpenoid) and 8-hydroxyisocapnolactone-2-3-diol (coumarin) with concentration 10 μM, 30 μM, and 100 μM on inhibiting mast cells (MCs) degranulation.MethodsThe investigation was performed in vitro by administering each compound into rat peritoneal MCs and rat basophilic leukemia-2H3 cells followed by activation with 50 μg/mL of compound 48/80 or 1 μM of ionomycin. The concentration of histamine released from each group was measured by a high-performance liquid chromatography-fluorometry system with post-column derivatization using o-phthalaldehyde.Results8-Hydroxyisocapnolactone-2-3-diol inhibited degranulation of compound 48/80 activated-rat peritoneal MCs with the histamine release percentages of 74.57%, 72.21% and 51.79% when the 10 μM, 30 μM and 100 μM concentrations were used, respectively. Where as about 81% histamine was released by the control group. Degranulation inhibition ability was also observed in ionomycin-activated rat basophilic leukemia-2H3 cells. In contrast, friedelin failed to inhibit degranulation in either cell type. The inhibition of 8-hydroxyisocapnolactone-2-3-diol was not related to the depletion of histamine synthesis as implied by the total histamine measurement.ConclusionsThese results exhibit the promising of 8-hydroxyisocapnolactone-2-3-diol is a potential parent structure for developing a MCs stabilizer.
基金funded by Zhejiang Nature Science Foundation(LQ20H270006)National Key R&D Program of China(No.2018YFC1705500).
文摘Background:In this study,we investigated whether prophylactic treatment with Guizhi-Shaoyao-Zhimu decoction(GSZ)could delay the onset of rheumatoid arthritis by targeting mast cells.Methods:Collagen-induced arthritis was used to evaluate the effect of GSZ in preventing arthritis and joint destruction.Immunohistochemical staining revealed the accumulation of histamine H4 receptor and tryptase alpha/beta-1 in the ankle joint of the model.Then,we explored the effect of GSZ serum on fibroblast-like synoviocytes using standard transwell invasion and migration assays.Real-time quantitative polymerase chain reaction and western blot were used to detect the expression of toll-like receptor 4(TLR4)/myeloid differentiationfactor 88(MyD88)/nuclear factor-κB p65(NF-κB p65).Results:The results showed that pre-rheumatoid arthritis treatment with GSZ could reduce inflammation and maintain cartilage structure in the collagen-induced arthritis model.Moreover,GSZ significantly blocked mast cell degranulation and inhibited the TLR4/MyD88/NF-κB p65 pathway.Since the combined activation of mast cells via TLR4 and immune complexes enhances inflammation in synovial tissue,we concluded that GSZ may block mast cell degranulation by inhibiting the TLR4/MyD88/NF-κB p65 pathway and thus influence rheumatoid arthritis onset.Conclusion:Taken together,our data suggested that GSZ may be a promising therapeutic decoction for the prophylactic treatment of rheumatoid arthritis.
文摘The correlation between the activities of the outer menbrane proteins （OMPs） of Bordetella pertussis and the lgE-mediated asthma was investigated in the present study, in which the OMPs of B. pertussis and their components were prepared by detergent treatment and chromatography, and the molecular weights of the OMPs components were determined by SDS-PAGE. The amounts of total as well as the ovalbumin （OVA）-specific IgE induced by dead B. pertussis whole bacterial vaccine on guinea pigs were detected by ELISA. Meanwhile, the effect of the OMPs and their components to promote the degranulation of guinea pig mast cells was observed by using the mast cell degranulation test, and ELISA assay was used to measure the histatmine levels in the supematants from the mast cell cultures. Histamine sensitive test was used to demonstrate the effects of the OMPs and their components to increase the histamine lethal sensitivity in mice. It was found that four components with molecular weights of 30, 32, 38 and 69 kDa could be obtained from the OMPs of B. pertussts, and the dead whole bacteria vaccine of B. pertussis had the ability to increase the levels of the total as well as the OVA-specific IgE in sera of guinea pigs. The OMPs and their 30 and 32 kDa components demonstrated significantly enhancing effect on the degranulation of guinea pig mast cells, and the histamine levels in the supematants from the mast cell culture treated with OMPs and their 30 and 32 kDa components were also significantly increased. It is evident that the strong adjuvant activity and the enhancing effect to degranulation of mast cells and the release of histamine of certain outer membrane components of B. pertussis could be demonstrated as revealed by the results of the present study, suggesting the possibility of a close relationship between the infection of vaccination with B. pertussis and the IgE-mediated asthma.
基金supported by grants from the National Natural Science Foundation of China(Grants No.82270562,82302800)China Postdoctoral Science Foundation(Grant No.2024M751108)+3 种基金Tai Shan Young Scholar Foundation of Shandong Province(Grant No.tsqn202103190)Postdoctoral Fund of The Affiliated Hospital of Jining Medical University(Grant No.JYFY364862)Postdoctoral Innovation Program in Shandong Province(Grant No.SDCX-ZG-202400032)Doctor Fund of The Affiliated Hospital of Jining Medical University(Grant No.2022-BS-07)。
文摘Background:Both intestinal and pulmonary systems are parts of the mucosal immune system,comprising~80%of all immune cells.These immune cells migrate or are transported between various mucosal tissues to maintain tissue homeostasis.Methods:In this study,we isolated neutrophils from the peripheral blood of patients and utilized immunofluorescence,flow cytometry,and Western blotting to confirm the incidence of“nucleus-directed degranulation”in vitro.Subsequently,we conducted a precise analysis using arivis software.Furthermore,using the Dss mouse model of colitis and tissue clearing technologies,we validated the“targeted nuclear degranulation”of neutrophils and their migration to the lungs in an inflammatory intestinal environment.Result:In this study,we found that among patients with ulcerative colitis,the migration of neutrophils with“targeted nuclear degran-ulation”from the intestinal mucosa to the lungs significantly exacerbates lung inflammation during pulmonary infections.Notably,patients with ulcerative colitis exhibited a higher abundance of neutrophils with targeted nuclear degranulation.Using DsS mice,we observed that neutrophils with targeted nuclear degranulation from the intestinal mucosa migrated to the lung and underwent activation during pulmonary infections.These neutrophils rapidly released a high amount of neutrophil extracellular traps to medi-ate the progression of lung inflammation.Alterations in the neutrophil cytoskeleton and its interaction with the nuclear membrane represent the primary mechanisms underlying targeted nuclear degranulation.Conclusion:This study revealed that neutrophils accelerate lung inflammation progression in colitis,offering new insights and po-tential treatment targets for lung infections for patients with colitis.
基金supported by National High Technology Research and Development Program of China (863 Program) (NO.2006AA09Z427)Nature Science Foundation of China (No. 30800859 and No. 30871948)
文摘Food allergy is a major health issue worldwide. Mast cells play a very important role in the immediate hypersensitivity for which mast cell degranulation needs to be studied extensively. In this study, an approach was taken to study the characteristics of sensitized mast cell degranulation in vitro, which associated with the study of mast cells and animal models. BALB/c mice were immunized respectively by several food allergens, then blood and peritoneal mast cells were collected at different time points. A dynamic determination was carried out between mast cells and serumal IgE. Comparative analysis on sequential time points showed that there was a close coincidence between mast cell degranulation and IgE antibody titers in sensitized BALB/c mice. Furthermore, it is interesting that sensitized mast cells could implement specific degranulation against the challenges in vitro, but the closely tropomyosins induced mast cell degranulation displayed cross reactions. This is very similar to IgE resisting the allergens in vivo. The study disclosed some characteristics on mast cells, coming from sensitized BALB/c mice, degranulation in vitro.
文摘Early after priming, effector CD8 T cells are distinguished into memory precursor and short-lived effector cell subsets （MPECs and SLECs）. Here, we delineated a distinct in vivo heterogeneity in killer cell lectin-like receptor G1 （KLRG-1） expression, which was strongly associated with diverse MPEC and SLEC fates. These in vivo MPECs and SLECs expressed equivalent levels of cytotoxic molecules and effector cytokines. Using a unique in vivodegranulation assay, we found that the MPECs and SLECs similarly encountered infected target cells and elaborated equivalent levels of cytotoxicity in vivo. These data provide direct in vivoevidence that memory-fated ceils pass through a robust effector phase. Additionally, the preferential localization of the MPECs in the lymph nodes, where a lesser degree of cytotoxicity was elaborated, suggests that the MPECs may be protected from excessive stimulation and terminal differentiation by virtue of their differential tissue localization. These data provide novel mechanistic insights into the linear decreasing potential model of memory differentiation.
基金supported by a grant from the University of Amsterdam for research into the focal point “Oral Infections and Inflammation”The study was financed in part by ACTA Dental Research BV (ADR)ADR has received funding from TI Food and Nutrition,a public-private partnership on precompetitive research in food and nutrition
文摘Polymorphonuclear neutmphils （PMNs） have a major role in the innate immune system. However, little is known about PMN contribution in relation to oral health. The objective of this study was to investigate the numbers and functional characteristics of oral PMNs （oPMNs） compared with circulatory PMNs （cPMNs）. Oral rinse and venous blood samples were obtained from 268 systemically and orally healthy volunteers in a cross-sectional observational study. PMN counts, cell cycle analysis and cellular activation state were investigated. Also, reactive oxygen species （ROS） production was analyzed, with and without bacterial stimulation （Fusobacterium nucleatum）. In males, 1.2 × 10^6- 1.0 ×10^6 oPMNs were collected, and showed a tendency to correlate with the levels of gingival bleeding （r= 0.215, P= 0.008）. Comparable oPMNs counts were found among females （1.0 ×10^6＋ 0.7 × 10^6）. More late-stage apoptotic/necrotic cells were found among the oPMNs （53.1%） compared with the cPMNs （8.5%; P〈 0.001）. Without additional stimulation, oPMNs were more activated than cPMNs, as indicated by higher expression of CD11b, CD63 and CD66b, and higher constitutive ROS levels （P〈 0.001）. Notably, in response to bacterial stimulation, oPMNs released comparable ROS levels as cPMNs （P= 0.042）. In conclusion, this study provides data on viable oPMNs showing high levels of activation in orally and systemically healthy individuals, free of apparent caries lesions and periodontal disease. These data suggests that although the oPMNs are in a more mature stage of their life cycle compared with the cPMNs, oPMNs are still responsive to stimulation, which indicates their functional potential and possible contribution to a healthy oral ecosystem.
文摘Kounis syndrome seems to be not a rare disease but a rarely diagnosed disorder. Multiple causes can join forc-es and trigger the development of this syndrome. We report the first case of Kounis syndrome manifesting as myocardial infarction with cardiovascular collapse that occurred in the dialysis room following an allergic reac-tion. The dialysis apparatus material of polyurethane, polyamide, polycarbonate, silicon rubber and polypro-pylene were incriminated causes. Physicians should be aware of the causality and existence of this disorder in order to achieve early and correct diagnosis and apply the appropriate therapeutic measures.
基金supported by the Beijing Municipal Natural Science Foundation of China(7202100)。
文摘Quail egg ovomucoid can inhibit activation of basophils and eosinophils,while hen egg ovomucoid has been shown to be a major allergen,named Gal d 1.At present,the differences in structure and function between two ovomucoid are unclear.We found the homology of ovomucoid in quail eggs and hen eggs reached77%.Compared with hen egg ovomucoid,the distribution of secondary structure was different in AA52-53,AA57-58,AA66-68,AA71-72,AA131-133,AA139-140,AA157-159 and AA184-185.Among 9 epitopes of egg ovomucoid,there were different amino acids from quail egg ovomucoid in 8 epitopes.Recombination quail egg ovomucoid had trypsin inhibition activity and quail egg ovomucoid didn't specifically bind to serum of eggs allergic patients.Quail egg ovomucoid can significantly inhibit RBL-2 H3 cells degranulation and protect cells morphology to a certain extent,indicating quail egg ovomucoid can inhibit cells activation and have potential anti-allergic effects,which is related to trypsin inhibitory activity.The difference in sensitization compare to hen egg ovomucoid may be due to amino acids differences affecting protein structure by changing antigenic epitopes.
文摘We studied morphofunctional properties of human platelets, treated with low doses of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). It was shown that platelet incubation with 20 - 75 <em>μ</em>M H<sub>2</sub>O<sub>2</sub> during 24 hours at 20<span style="white-space:nowrap;">°</span>C - 22<span style="white-space:nowrap;">°</span>C did not cause visible structural deficiencies in cells. Platelets maintained their adhesion activity and velocity of degranulation at 20 <em>μ</em>M H<sub>2</sub>O<sub>2</sub>. 30 - 60 μM H<sub>2</sub>O<sub>2</sub> dose-dependently reduced lamella’s growth and allowed retaining granule bulk inside cytoplasm of spreading platelets. After 1 - 2 hours, the most effect of platelet granules’ stabilization was registered at samples, previously incubated with 60 μM H<sub>2</sub>O<sub>2</sub>. Adrenalin activation led to rapid degranulation of stabilized platelets, whereas lamella’s growth in activated platelets was low or medium.
基金Supported by Faculty for the Future Fellowship grant by the Schlumberger Foundation(recipient Siad S)
文摘AIM： To study the bacteriocidal or bacteriostatic role of mast cells during infection with Mycobacterium.METHODS： Mycobacterium marinum （M. marinum） （BAA-535/M strain） was investigated for its ability to grow at a temperature relevant to the mammalian host. Primary mast cells were differentiated from bone marrows of mice, a human mast cell line （HMC-1） and a human monocytic cell line （MonoMac6） were maintained in culture. Mice were stimulated by intra-peritoneal injection of heat-killed M. marinum to study cytochemically the degranulation of peritoneal mast cells. HMC-1 cells were stimulated with M. marinum to analyse mRNA expression for inflammatory reactant genes, while HMC-1 and primary mouse mast cells were infected with M. marinum to establish in parallel cell viability （lactate dehydrogenase release and cell counts） and viable mycobacterial counts. Flow cytometry was used to assess intracellular presence of fluorescein isothiocyanate labelled M. marinum after trypan blue quenching and to measure the extent of infection-induced apoptosis or necrosis in HMC-1. A GFP expressing recombinant M. marinum strain was used to assess intracellular location by fuorescence microscopy. Light microscopy of osmium tetroxide and Gram Twortstained sections of 0.5 μm and transmission electron microscopy were undertaken as sensitive methods. RESULTS： Since its isolation, M. marinum has adapted to grow at 37 ℃. This study found that M. marinum infects HMC-1 cells and primary murine mast cells, where they survive, replicate, and cause dose dependent cell damage over the analysis period of up to 120 h. Amikacin was an effective aminoglycoside antibiotic to eliminate extracellular or membrane attached M. marinum in order to adequately quantify the intracellular bacterial loads. In vivo, intraperitoneal injection of heat-killed M. marinum led to the release of mast cell granules in mice. HMC-1 cells stimulated with M. marinum showed a biphasic pattern of increased mRNA expression for LL-37 and COX-2/TNF-a during 24 h of stimulation. In HMC-1, M. marinum localised to the cytoplasm whereas in primary mast cells, M. marinum were found in vacuoles.CONCLUSION： The effector role of mast cells in infection with M. marinum can be studied in vitro and in vivo.
文摘<span style="font-family:Verdana;">Backgrou</span><span style="font-family:Verdana;">nd/Aim: Kuji amber is an interesting natural source for drug discovery</span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">because a new anti-allergic compound, named kujigamberol and several new compounds have been isolatated from it. It was important to evaluate the yield, biological activities and constituents of each methanol extract</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">of Kuji, Iwaki, Choshi, Mizunami and Ube ambers in Japan in order to establish if additional new compounds could be identified in these ambers. Materia</span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">ls and </span><span style="font-family:Verdana;">Method: Biological activities of each extract were evaluated using growth-restoring </span><span style="font-family:Verdana;">activity of the mutant yeast strain involving Ca</span><sup><span style="font-family:Verdana;">2+</span></sup><span style="font-family:Verdana;">-signal transduction and inhibi</span><span style="font-family:Verdana;">tion activity of degranulation in rat basophilic leukemia (RBL)-2H3 cells. Constituents</span><span style="font-family:Verdana;"> of each extract were analyzed by high performance liquid chromatography (HPLC). Results: All ambers except Ube amber have growth-restoring activity against the mutant yeast. Both Kuji and Iwaki ambers inhibited the degranulation of RBL-2H3 cells induced by the calcium ionophore A23187 in a dose dependent manner. The main biologically active compound in Kuji amber, kujigamberol, was also isolated from Iwaki amber and analyzed by mass spectrometry (MS) and nuclear magnetic resonance (NMR). Conclusion: Kuji and Iwaki ambers appeared to have the same origin. Choshi, Mizunami, and Ube ambers are valuable sources for biologically active compounds which are different from those of Kuji amber.</span></span></span></span>
文摘During the past decades,populous expansion in mast cell scientific literature came forth with more,than forty-four thousand PubMed publications available to date.Such surge is due to the appreciation of the momentous role of mast cells in the evolution of species,in the development and maintenance of vital physiological functions,such as reproduction,homeostasis,and fluids,diverse immunological roles,and the potential of far-reaching effects despite minute numbers.While the emerging knowledge of the importance of mast cells in equilibrium comes of age when looking at the matter from an evolutionary perspective,the recognition of mast cells beyond detrimental performance in allergies and asthma,during protection against parasites,falters.Beyond wellknown classical functions,mast cells can process and present antigens,can serve as a viral reservoir,can respond to hormones and xenobiotics,initiate antiviral and antibacterial responses,phagocytosis,apoptosis,and participate in important developmental cornerstones.During evolution,upon the development of a sophisticated niche of innate and adaptive cell populations,certain mast cell functions became partially transmutable,yet the potency of mast cells remained considerable.Reviewing mast cells enables us to reflect on the certitude,that our sophisticated,complex physiology is rooted deeply in evolution,which we carry ancient remnants of,ones that may have decisive roles in our functioning.This communication sets out the goal of characterizing mast cells,particularly the aspects less in limelight yet of immense significance,without the aspiration exhaust it all.
文摘Chronic eosinophilic leukemia (CEL) is a rare disorder that is characterized by hypereosinophilia with increased number of blood or marrow blasts (>5% and <20%). CEL is distinguished from hypereosinophilic syndrome (HES) by the presence of eosinophilic clonality. Chronic eosinophilic leukemia not otherwise specified (CEL-NOS) diagnosis is made when no fusion genes are detected by most modern molecular testing, particularly the most common fusion gene FIP1L-1/PDGFRA (Factor Interacting with PAP like-1/Platelet-Derived Growth Factor Receptor Alpha). This disease is very rare, and its description in the literature is not well characterized. We report a fetal case of severe CEL-NOS in a 19-year-old male who presented with a plethora of clinical features consists of constitutional symptoms, pancytopenia, intravascular thrombosis, acute stroke and endomyocardial infiltrates. The course of his disease was aggressive and resistant to conventional treatment. After a short period of improvement, an acute transformation into blast crisis (BC) had occurred. The diagnosis was confirmed by morphology and immunophenotyping of bone marrow biopsy. The patient eventually died of heart failure and sepsis. To our knowledge this is the first case report of fatal CEL-NOS transforming into severe blast crisis.
基金funded by National Natural Science Foundation of China(No.12172092,82174488,and 82305416)Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function(No.21DZ2271800)+1 种基金Shanghai Municipal Science and Technology Commission(No.23YF1418300)Scientific Research Project on Traditional Chinese Medicine of Shanghai Municipal Health Commission—Youth Guidance Category(No.2022QN018).
文摘Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture.This paper investigated the role of acupuncture needle surface textures on acupuncture’s analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation.Methods Four types of acupuncture needles with different surface textures(the lined needle,circle needle,sandpaper needle,and threaded needle)were designed.Additionally,the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation.To perform acupuncture analgesia experiments,four experimental acupuncture needles and a normal needle were inserted into the Zusanli(ST36)acupoint of rats with inflammatory pain.By comparing the force and torque and the analgesic efficacy of the different acupuncture needles,these experiments tested the role of acupuncture needle body texture on acupuncture analgesia.Results The analgesic effects of different acupuncture needle body textures varied.Specifically,the force required to penetrate the skin with the lined needle was not greater than that for the normal needle;however,the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion.Additionally,the torque of the lined needle reached 2×10^(-4)N·m under twisting manipulation,which was four times greater the torque of a normal needle(5×10^(-5)N·m).Furthermore,the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle.Conclusion Optimizing the texture of acupuncture needles can enhance acupuncture analgesia.The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle;it was also linked to variable analgesic effects.This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy.
基金supported by the National Natural Science Foundation of China(U22A20510 and 32225047)Laboratory of Lingnan Modern Agriculture Project(NT2021005)+1 种基金Double first-class discipline promotion project(2023B10564001)National Center of Technology Innovation for Pigs(NCTIP-XD/B13).
文摘The prevalence of food allergies is increasing dramatically and causing serious public health concerns.Notably,melatonin metabolism imbalance in patients with food allergies;however,the role of melatonin in food allergies remains unclear.Here,we demonstrated that melatonin suppresses food allergy responses and reprograms the gut microbiota of food-allergic mice,while melatonin aggravates food allergy during gut microbiota depletion.Mechanistically,melatonin boosts the degranulation of mast cells by up-regulating the expression of membrane high-affinity immunoglobulin E(IgE)receptor(FcεRI).Melatonin increases the mRNA expression of Rabenosyn-5(a component of factors for endosome recycling and Rab interactions)through melatonin receptor 2(MT2)-extracellular signal-regulated kinase(ERK)signaling,thereby driving the recycling of FcεRI and elevating the abundance of membrane FcεRI.Likewise,the inhibition of MT2 attenuates melatonin-induced food allergy in mice with gut microbiota depletion.Collectively,our finding provides insights into the pathogenesis of food allergies and provides a potential therapeutic target for the prevention and treatment of food allergies.
