ABSTRACT
SeviL, a galactoside-binding lectin previously isolated from the mussel Mytilisepta virgata, was demonstrated to trigger apoptosis in HeLa ovarian cancer cells. Here, we show that this lectin can promote the polarization of macrophage cell lines toward an M1 functional phenotype at low concentrations. The administration of SeviL to monocyte and basophil cell lines reduced their growth in a dose-dependent manner. However, low lectin concentrations induced proliferation in the RAW264.7 macrophage cell line, which was supported by the significant up-regulation of TOM22, a component of the mitochondrial outer membrane. Furthermore, the morphology of lectin-treated macrophage cells markedly changed, shifting from a spherical to an elongated shape. The ability of SeviL to induce the polarization of RAW264.7 cells to M1 macrophages at low concentrations is supported by the secretion of proinflammatory cytokines and chemokines, as well as by the enhancement in the expression of IL-6- and TNF-α-encoding mRNAs, both of which encode inflammatory molecular markers. Moreover, we also observed a number of accessory molecular alterations, such as the activation of MAP kinases and the JAK/STAT pathway and the phosphorylation of platelet-derived growth factor receptor-α, which altogether support the functional reprogramming of RAW264.7 following SeviL treatment. These results indicate that this mussel ß-trefoil lectin has a concentration-dependent multifunctional role in regulating cell proliferation, phenotype, and death in macrophages, suggesting its possible involvement in regulating hemocyte activity in vivo.
Subject(s)
Bivalvia , Lectins , Macrophages , Animals , Mice , Macrophages/drug effects , Macrophages/metabolism , RAW 264.7 Cells , Lectins/pharmacology , Cell Proliferation/drug effects , Humans , Cytokines/metabolism , Phenotype , Signal Transduction/drug effectsABSTRACT
BACKGROUND: We investigated the effect of sublingual immunotherapy (SLIT) on Japanese cedar and cypress pollinosis in a mass scattering year of cedar pollen (total counts: 12353 grains/cm2, approximately four times the average). METHODS: SLIT patients of 84 in the first year, 107 in the second year and 67 in the third year treated with Cedarcure® were included. During the 2023 cedar and cypress pollen dispersal season, nasal and eye symptoms and general symptoms were examined using a visual analog scale (VAS). RESULTS: The VAS during the cedar season significantly decreased to improve with the number of years of SLIT, but the VAS during the cypress period slightly increased. A questionnaire survey before SLIT revealed that only 0.9% to 3.6% of patients had strong cypress symptoms. However, sneezing (pï¼0.01), rhinorrhea, itchy eyes and total symptoms (pï¼0.05) in the third year of SLIT were significantly stronger during the cypress period than during the cedar period. The VAS of total symptoms during the Japanese cedar pollen season were not affected by the pollen count, and the cure rate was affected by SLIT in the third year. CONCLUSION: The clinical efficacy of cedar SLIT on cedar pollinosis was high even in a mass scattering year, and the effect increased with the number of years of treatment. On the other hand, it was shown that the clinical efficacy on cypress pollinosis was insufficient.
Subject(s)
Cryptomeria , Cupressus , Rhinitis, Allergic, Seasonal , Sublingual Immunotherapy , Humans , Rhinitis, Allergic, Seasonal/therapy , Pollen , Treatment Outcome , AllergensABSTRACT
R-type lectins are a widespread group of sugar-binding proteins found in nearly all domains of life, characterized by the presence of a carbohydrate-binding domain that adopts a ß-trefoil fold. Mytilectins represent a recently described subgroup of ß-trefoil lectins, which have been functionally characterized in a few mussel species (Mollusca, Bivalvia) and display attractive properties, which may fuel the development of artificial lectins with different biotechnological applications. The detection of different paralogous genes in mussels, together with the description of orthologous sequences in brachiopods, supports the formal description of mytilectins as a gene family. However, to date, an investigation of the taxonomic distribution of these lectins and their molecular diversification and evolution was still lacking. Here, we provide a comprehensive overview of the evolutionary history of mytilectins, revealing an ancient monophyletic evolutionary origin and a very broad but highly discontinuous taxonomic distribution, ranging from heteroscleromorphan sponges to ophiuroid and crinoid echinoderms. Moreover, the overwhelming majority of mytilectins display a chimera-like architecture, which combines the ß-trefoil carbohydrate recognition domain with a C-terminal pore-forming domain, suggesting that the simpler structure of most functionally characterized mytilectins derives from a secondary domain loss.
Subject(s)
Bivalvia , Lectins , Animals , Lectins/chemistry , Evolution, Molecular , Bivalvia/metabolism , Carbohydrates/geneticsABSTRACT
We reported the results of three years of house dust mite sublingual immunotherapy with Miticure® tablets. METHODS: Subjects of 115 cases (63 males, median 12.9 years old, 74 children under 15 years old) were evaluated with Japanese Rhino-conjunctivitis Quality of Life Questionnaire No1 (JRQLQ No1) and visual analog scale (VAS) of 100mm length for rhino-ocular and general symptoms. Annual survey was conducted for three years. RESULTS: Symptoms in all items of 1 to 3 years later by JRQLQ No1 and VAS were significantly improved (p<0.01). There was no difference from 1 year to 3 years later. The VAS value for total symptoms decreased from 41 (18-70) mm before treatment to 10 (4-40) mm after 1 year and 10 (3-30) mm after 3 years (median (IQR)). Concomitant medications used in all patients at the start of treatment were not needed in 60.8% after 1 year and 65.2% after 3 years. After 3 years, 16.5% of the patients were completely cured with no concomitant medication and had a symptom score of 0, and 53.0% were in remission with a score of 1 or less. There was no difference in all items between children and adults, and symptoms improved equally. CONCLUSION: The efficacy of house dust mite sublingual immunotherapy from 1 to 3 years was demonstrated.
Subject(s)
Pyroglyphidae , Sublingual Immunotherapy , Adult , Child , Male , Animals , Humans , Adolescent , Quality of Life , TabletsABSTRACT
BACKGROUND: We examined the clinical effects of Cedarcure® tablets for sublingual immunotherapy (SLIT), and examined the enhancement of the effects over the years of treatment. METHODS: The subjects were 358 patients who treated with SLIT (126 of third year of treatment, 102 of second year, 130 of first year) in a single clinic. The clinical efficacy was evaluated with visual analog scale (VAS) of nose, eye and total symptoms during the peak season of moderate amount of pollen dispersal (2485 grains/cm2/season) in 2022. Concomitant medication scores were calculated by Japanese guidelines. Because many cases of combined use of mite SLIT (dual SLIT) were included in the subjects, we compared cedar SLIT alone and dual SLIT as a secondary analysis. RESULTS: Clinical efficacy improved with the years of treatment, and all assessments of VAS in the 3rd year were significantly better than in the 1st year of treatment (p<0.01). The third year was better with sneezing and nasal discharge than the 2nd year, and the 2nd year was better with itchy eyes than the 1st year (p<0.05). Drug scores were also lower in the 3rd and 2nd years than in the 1st year (p<0.05). Additional mite SLIT did not affect the results. CONCLUSION: Cedarcure® showed enhancement of the effects over the years of treatment by the analysis up to the third year. Both Cedar SLIT alone and Dual SLIT showed similar efficacy on cedar pollinosis.
Subject(s)
Cryptomeria , Rhinitis, Allergic, Seasonal , Sublingual Immunotherapy , Humans , Rhinitis, Allergic, Seasonal/therapy , Administration, Sublingual , Treatment Outcome , Tablets , AllergensABSTRACT
Novel pyridine-based fluorescing compounds, viz. pyrido[1,2-a]pyrrolo[3,4-d]pyrimidines 3a,b and N-methyl-4-((pyridin-2-yl)amino)maleimides 4a-e, were selectively prepared by a one-pot reaction between a functionalized maleimide and 2-aminopyridines with electron-donating or electron-withdrawing groups at position 5 and were investigated photophysically and computationally. The photophysical studies revealed that all the synthesized compounds exhibited fluorescence in organic solvents, while N-methyl-4-((pyridin-2-yl)amino)-substituted maleimide derivatives 4a-e, which are based on an acceptor-donor-acceptor (A-D-A) system, exhibited aggregation-induced emission enhancement (AIEE) properties in aqueous media. Compounds 4a and 4e, bearing electron-withdrawing groups (Br and CF3, respectively) showed 7.0 and 15 times fluorescence enhancement. Time-dependent density functional theory (TD-DFT) calculations were performed to gain better insight into the electronic nature of the compounds with and without AIEE properties.
ABSTRACT
Carbohydrate esters are significant in medicinal chemistry because of their efficacy for the synthesis of biologically active drugs. In the present study, methyl ß-D-galactopyranoside (MGP) was treated with various acyl halides to produce 6-O-acyl MGP esters by direct acylation method with an excellent yield. To obtain newer products for antimicrobial assessment studies, the 6-O-MGP esters were further modified into 2,3,4-tri-O-acyl MGP esters containing a wide variety of functionalities in a single molecular framework. The chemical structures of the newly synthesized compounds were elucidated by analyzing their physicochemical, elemental, and spectroscopic data. In vitro antimicrobial testing against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) revealed that these MGP estes have promising antifungal functionality compared to their antibacterial activities. The antimicrobial tests demonstrated that the compounds 3 and 10 were the most potent against Bacillus subtilis and Escherichia coli strains, with the minimum inhibitory concentration (MIC) values ranging from 0.352 ± 0.02 to 0.703 ± 0.01 mg/ml and minimum bactericidal concentration (MBC) values ranging from 0.704 ± 0.02 to 1.408 ± 0.04 mg/ml. Density functional theory (DFT) at the B3LYP/3-21G level of theory was employed to enumerate, frontier orbital energy, enthalpy, free energy, electronic energy, MEP, dipole moment which evaluated the effect of certain groups (aliphatic and aromatic) on drug properties. They discovered that all esters were more thermodynamically stable than the parent molecule. Molecular docking is performed using AutoDock Vina to determine the binding affinities and interactions between the MGP esters and the SARS-CoV-2 main protease. The modified esters strongly interact with the prime Cys145, His41, MET165, GLY143, THR26, and ASN142 residues. The MGP esters' shape and ability to form multiple electrostatic and hydrogen bonds with the active site match other minor-groove binders' binding modes. The molecular dynamics simulation validates the molecular docking results. The pharmacokinetic characterization of the optimized inhibitor demonstrates that these MGP esters appear to be safer inhibitors and a combination of in silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) prediction and drug-likeness had promising results due to their improved kinetic properties. Structure activity relationships (SAR) study including in vitro and silico results revealed that the acyl chain, palmitoyl (C16) and 4-chlorobenzoyl (4.ClC6H4CO-) in combination with sugar were found the most potential activates against human and fungal pathogens. After all, our comprehensive computational and statistical analysis shows that these selected MGP esters can be used as potential inhibitors against the SARS-CoV-2.
Subject(s)
Anti-Infective Agents , COVID-19 , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Esters/pharmacology , Galactose , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Peptide Hydrolases , SARS-CoV-2ABSTRACT
In recent years, there has been considerable interest in lectins from marine invertebrates. In this study, the biological activities of a lectin protein isolated from the eggs of Sea hare (Aplysia kurodai) were evaluated. The 40 kDa Aplysia kurodai egg lectin (or AKL-40) binds to D-galacturonic acid and D-galactose sugars similar to previously purified isotypes with various molecular weights (32/30 and 16 kDa). The N-terminal sequence of AKL-40 was similar to other sea hare egg lectins. The lectin was shown to be moderately toxic to brine shrimp nauplii, with an LC50 value of 63.63 µg/mL. It agglutinated Ehrlich ascites carcinoma cells and reduced their growth, up to 58.3% in vivo when injected into Swiss albino mice at a rate of 2 mg/kg/day. The morphology of these cells apparently changed due to AKL-40, while the expression of apoptosis-related genes (p53, Bax, and Bcl-XL) suggested a possible apoptotic pathway of cell death. AKL-40 also inhibited the growth of human erythroleukemia cells, probably via activating the MAPK/ERK pathway, but did not affect human B-lymphoma cells (Raji) or rat basophilic leukemia cells (RBL-1). In vitro, lectin suppressed the growth of Ehrlich ascites carcinoma and U937 cells by 37.9% and 31.8%, respectively. Along with strong antifungal activity against Talaromyces verruculosus, AKL showed antibacterial activity against Staphylococcus aureus, Shigella sonnei, and Bacillus cereus whereas the growth of Escherichia coli was not affected by the lectin. This study explores the antiproliferative and antimicrobial potentials of AKL as well as its involvement in embryo defense of sea hare.
Subject(s)
Anti-Bacterial Agents/pharmacology , Aplysia , Lectins/pharmacology , Animals , Aquatic Organisms , Eggs , Escherichia coli/drug effects , Staphylococcus aureus/drug effectsABSTRACT
BACKGROUND: We studied clinical efficacy and safety after 1 year of mite sublingual immunotherapy (SLIT) for perennial allergic rhinitis in children, compared with adults. METHODS: We compared 121 children under 15 yeas old (81 male, aged 5-14 years, a median of 12 years) and 77 adults (36 male, aged 15-65 years, a median of 26 years) treated with mite SLIT tablet (10000 Japanese Allergy Unit). The clinical efficacy before and 1 year after SLIT was evaluated by assessing symptom scores by Japanese rhino-conjunctivitis quality of life questionnaire (JRQLQ No1) and visual analog scale (VAS). Combined medication was also compared. Adverse events of SLIT were checked at every visit. RESULTS: All items of JRQLQ No1 scores and VAS after 1 year of mite SLIT, except eye symptoms in adults by JRQLQ No1, were significantly improved in both children and adults. Comparing children and adults, there were no differences in symptoms before and after 1 year. Combined medication score showed a similar result. Adverse events were observed in 57.9% of children and 58.4% of adults, but there were no serious adverse reactions. CONCLUSION: There was no difference between children and adults in efficacy and safety of mite SLIT, and both group showed significant improvement of symptoms.
Subject(s)
Rhinitis, Allergic, Perennial , Rhinitis, Allergic , Sublingual Immunotherapy , Adolescent , Adult , Aged , Animals , Antigens, Dermatophagoides , Child , Child, Preschool , Humans , Male , Middle Aged , Pyroglyphidae , Quality of Life , Rhinitis, Allergic/therapy , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: We studied clinical efficacy and safety of pediatric sublingual immunotherapy of cedar pollinosis in the first follow-up year, compared with adult cases or untreated cases. METHODS: We compared 103 pediatrics under 15 yeas old (age, 10.8±2.6 years; male-to-female ratio, 68;35) and 89 adults (age, 38.9±12.5 years; male-to-female ratio, 34;55) treated with Cidarcure®, and untreated 299 patients (age, 31.3±16.0; male-to-female ratio, 144;155). The clinical efficacy was evaluated by assessing symptom scores by Japanese rhino-conjunctivitis quality of life questionnaire and visual analog scale (VAS) during the peak season of moderate amount of pollen dispersal (3582 grains/cm2/season) in 2020. Adverse events of sublingual immunotherapy were also checked at every visits. RESULTS: All patients in both pediatric and adult group successfully maintained the highest dose of 5000JAU as planned. Pediatrics compared with adults showed slightly better effects in all the assessments, but they were not significant. Both pediatrics and adults of sublingual immunotherapy showed significant better effects in all the assessments compared with untreated group. Percentage of total cases of adverse events in pediatric group was low, but it was not significant. Percentage of pruritus of ear and throat was significantly low in pediatric group. CONCLUSION: Pediatric sublingual immunotherapy for cedar pollinosis was treated in safe, and reduced symptoms as well as the effects of adults.
Subject(s)
Cryptomeria , Rhinitis, Allergic, Seasonal , Sublingual Immunotherapy , Adolescent , Adult , Child , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pediatrics , Quality of Life , Rhinitis, Allergic, Seasonal/therapy , Young AdultABSTRACT
Haprin (TRIM36) is a ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. It is expressed in the testes in both mice and humans and is thought to be involved in spermiogenesis, the acrosome reaction, and fertilization. However, the functional role of Haprin is poorly understood. The aim of this study was to investigate the physiological role of Haprin in fertility. Homozygous haprin-deficient mice were generated and these mice, and their spermatozoa, were analyzed to detect morphological and fertility-related abnormalities. In these models, normal spermatogenesis was observed but sperm quality was reduced with haprin-deficient mice having poorer sperm morphology and motility than wild-type mice. Interestingly, haprin-deficient mice showed normal in vivo fertility but could not fertilize oocytes under standard in vitro fertilization conditions. In conclusion, this study demonstrated that Haprin deficiency causes morphological abnormalities in spermatozoa, indicating that Haprin is involved in spermiogenesis.
Subject(s)
Carrier Proteins/genetics , Infertility, Male/genetics , Seminal Plasma Proteins/genetics , Spermatozoa/physiology , Acrosome Reaction/genetics , Animals , Carrier Proteins/metabolism , Female , Fertilization/genetics , Fertilization in Vitro , Infertility, Male/metabolism , Male , Mice , Mice, Knockout , Seminal Plasma Proteins/metabolism , Spermatogenesis/genetics , Spermatozoa/metabolismABSTRACT
A 15-kDa lectin, termed SeviL, was isolated from Mytilisepta virgata (purplish bifurcate mussel). SeviL forms a noncovalent dimer that binds strongly to ganglio-series GM1b oligosaccharide (Neu5AcÉ2-3Galß1-3GalNAcß1-4Galß1-4Glc) and its precursor, asialo-GM1 (Galß1-3GalNAcß1-4Galß1-4Glc). SeviL also interacts weakly with the glycan moiety of SSEA-4 hexaose (Neu5Acα2-3Galß1-3GalNAcß1-3Galα1-4Galß1-4Glc). A partial protein sequence of the lectin was determined by mass spectrometry, and the complete sequence was identified from transcriptomic analysis. SeviL, consisting of 129 amino acids, was classified as an R(icin B)-type lectin, based on the presence of the QxW motif characteristic of this fold. SeviL mRNA is highly expressed in gills and, in particular, mantle rim tissues. Orthologue sequences were identified in other species of the family Mytilidae, including Mytilus galloprovincialis, from which lectin MytiLec-1 was isolated and characterized in our previous studies. Thus, mytilid species contain lectins belonging to at least two distinct families (R-type lectins and mytilectins) that have a common ß-trefoil fold structure but differing glycan-binding specificities. SeviL displayed notable cytotoxic (apoptotic) effects against various cultured cell lines (human breast, ovarian, and colonic cancer; dog kidney) that possess asialo-GM1 oligosaccharide at the cell surface. This cytotoxic effect was inhibited by the presence of anti-asialo-GM1 oligosaccharide antibodies. With HeLa ovarian cancer cells, SeviL showed dose- and time-dependent activation of kinase MKK3/6, p38 MAPK, and caspase-3/9. The transduction pathways activated by SeviL via the glycosphingolipid oligosaccharide were triggered apoptosis. DATABASE: Nucleotide sequence data have been deposited in the GenBank database under accession numbers MK434191, MK434192, MK434193, MK434194, MK434195, MK434196, MK434197, MK434198, MK434199, MK434200, and MK434201.
Subject(s)
G(M1) Ganglioside/analogs & derivatives , Lectins/chemistry , Lectins/metabolism , Mitogen-Activated Protein Kinases/metabolism , Mytilidae/chemistry , Oligosaccharides/metabolism , Animals , Binding Sites , G(M1) Ganglioside/chemistry , G(M1) Ganglioside/metabolism , HeLa Cells , Humans , Lectins/isolation & purification , Mitogen-Activated Protein Kinases/chemistry , Mytilidae/metabolism , Oligosaccharides/chemistry , Species SpecificityABSTRACT
Sublingual immunotherapy (SLIT) with Japanese cedar (JCe) pollinosis was expected to be effective for Japanese cypress (JCy) pollinosis. However, only a half of JCy pollinosis patients clinically improved. Therefore, we examined the immunological effect of SLIT for JCy pollinosis. Peripheral blood mononuclear cells (PBMCs) from patients with JCe and JCy pollinosis who did and did not receive SLIT were incubated with Cry j 1, Cha o 1 and Cha o 3 antigens. Basophil activation test (BAT) were performed. Production of IL-5 and IL-17 induced by antigens was inhibited in the SLIT group. Cry j 1-specific production of IL-10 was increased, and serum Cry j 1-specific IgE and -IgG4 were elevated. However, Cha o 1- or Cha o 3-specific production of IL-10 and specific IgG4 was not increased. Antigens-specific BAT did not decrease after SLIT. New SLIT with JCe and JCy is needed for patients with combined JCe and JCy pollinosis.
Subject(s)
Leukocytes, Mononuclear/immunology , Rhinitis, Allergic, Seasonal/therapy , Sublingual Immunotherapy/methods , Adult , Antigens, Plant/immunology , Basophil Degranulation Test , Cells, Cultured , Chamaecyparis/immunology , Cryptomeria/immunology , Cytokines/metabolism , Female , Humans , Immunoglobulin E/metabolism , Immunoglobulin G/metabolism , Male , Middle Aged , Plant Extracts/immunology , Plant Proteins/immunology , Pollen/immunology , Prospective Studies , Rhinitis, Allergic, Seasonal/immunologyABSTRACT
BACKGROUND: There have been no studies of dual administration of sublingual immunotherapy (SLIT) tablets for perennial and seasonal allergic rhinitis. This trial (JapicCTI-184014) was conducted to investigate the safety profile and immunological response during dual therapy with SQ house dust mite (HDM) and Japanese cedar pollen (JCP) SLIT tablets. METHODS: This was a multicenter, open-label, randomized trial of 109 Japanese patients with coexisting HDM and JCP allergic rhinitis who had positive tests for HDM- and JCP specific IgE (≥0.7 kU/L). Patients were allocated to receive HDM (N = 54) or JCP (N = 55) SLIT tablets alone for 4 weeks followed by 8 weeks of dual therapy with both SLIT tablets administered within 5 min of each other. Adverse events (AEs), adverse drug reactions (ADRs), and serum IgE and IgG4 specific for HDM (Dermatophagoides farinae, Dermatophagoides pteronyssinus) and JCP were recorded. RESULTS: The percentage of subjects with AEs and ADRs was similar between the two groups and between the two periods of monotherapy and dual therapy. Most AEs and ADRs were mild in severity, and no serious events were observed. The most common ADRs were local events in the oral cavity. Levels of IgE and IgG4 specific for HDM (D. farinae, D. pteronyssinus) and JCP were increased after treatment with HDM and JCP SLIT tablets, respectively. CONCLUSIONS: Dual therapy with both SLIT tablets administered within 5 min after 4 weeks of monotherapy with HDM or JCP tablet was well tolerated and induced the expected immunological responses.
Subject(s)
Rhinitis, Allergic/drug therapy , Sublingual Immunotherapy/adverse effects , Sublingual Immunotherapy/methods , Adolescent , Adult , Animals , Antigens, Dermatophagoides/administration & dosage , Child , Cryptomeria/immunology , Female , Humans , Male , Middle Aged , Pollen/immunology , Pyroglyphidae/immunology , Rhinitis, Allergic/etiology , Tablets , Young AdultABSTRACT
Previously, we isolated and examined a bacterial strain designated as TM-I-3, belonging to the genus Bacillus, from soil in Nagasaki, Japan. This bacterium was able to inhibit the growth of molds, without coming into direct contact with them. Non-contact antifungals are capable of providing multidirectional inhibition and may contribute to disease prevention. In this study, we revealed the bacteriological properties of TM-I-3 and evaluated the antifungal activity of the compounds emitted from this bacterium. In addition, we analyzed the antimicrobial substances released from TM-I-3 using GC/MS to elucidate the mechanism of its action. Antimicrobial compounds from strain TM-I-3 were identified as acetic acid, propanoic acid, isovaleric acid, 2-methylbutanoic acid, and benzaldehyde, which are all reported to have antimicrobial activity. TM-I-3 demonstrated possible efficacy in inhibiting the growth of Aspergillus fumigatus, Cladosporium cladosporioides and Penicillium expansum, which may lead to inhibition of common fungal contaminants of household products and prevention of some pulmonary diseases.
Subject(s)
Antifungal Agents/pharmacology , Aspergillus fumigatus/drug effects , Bacillus/metabolism , Cladosporium/drug effects , Penicillium/drug effects , Volatile Organic Compounds/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/metabolism , Aspergillus fumigatus/growth & development , Bacillus/classification , Bacillus/genetics , Cladosporium/growth & development , Cluster Analysis , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Gas Chromatography-Mass Spectrometry , Japan , Penicillium/growth & development , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/metabolismABSTRACT
BACKGROUND: Cedarcure® for sublingual immunotherapy of cedar pollinosis was purchased in 2018. We studied clinical efficacy of Cedarcure® in the first year. METHODS: We compared 69 patients treated with Cedarcure® (age, 18.0±13.5 years; male-to-female ratio, 40;29) and a control group of 97 patients treated with Cedartolen® (age, 29.8±16.2 years; male-to-female ratio, 44;53) during the peak season of large amount of pollen dispersal (10933 grains/cm2/season) in 2019. The clinical efficacy was evaluated by assessing symptom scores by Japanese rhino-conjunctivitis quality of life questionnaire and visual analog scale (VAS). RESULTS: All the assessments except nasal congestion were slightly better in Cedarcure® group, but they were not significant. There was no difference of concomitant medication in both groups. Because insurance coverage of Cedartolen® is for patients over 12 years old in Japan, the efficacy in Cedarcure® group enhanced better in all assessments if comparing the patients of over 12 years old. Percentage of adverse events was even in both over and under 12 years old. CONCLUSION: Cedarcure® was treated in safe, and reduced symptoms as well as Cedartolen®.