Contributions of the N-terminal flanking residues of an antigenic peptide from the Japanese cedar pollen allergen Cry j 1 to the T-cell activation by HLA-DP5.

Cry j 1 is a major allergen present in Japanese cedar (Cryptomeria japonica) pollens. Peptides with the core sequence of KVTVAFNQF from Cry j 1 ('pCj1') bind to HLA-DP5 and activate Th2 cells. In this study, we noticed that Ser and Lys at positions -2 and -3, respectively, in the N-terminal flanking (NF) region to pCj1 are conserved well in HLA-DP5-binding allergen peptides. A competitive binding assay showed that the double mutation of Ser(-2) and Lys(-3) to Glu [S(P-2)E/K(P-3)E] in a 13-residue Cry j 1 peptide (NF-pCj1) decreased its affinity for HLA-DP5 by about 2-fold. Similarly, this double mutation reduced, by about 2-fold, the amount of NF-pCj1 presented on the surface of mouse antigen-presenting dendritic cell line 1 (mDC1) cells stably expressing HLA-DP5. We established NF-pCj1-specific and HLA-DP5-restricted CD4+ T-cell clones from HLA-DP5 positive cedar pollinosis (CP) patients, and analyzed their IL-2 production due to the activation of mouse TG40 cells expressing the cloned T-cell receptor by the NF-pCj1-presenting mDC1 cells. The T-cell activation was actually decreased by the S(P-2)E/K(P-3)E mutation, corresponding to the reduction in the peptide presentation by this mutation. In contrast, the affinity of NF-pCj1·HLA-DP5 for the T-cell receptor was not affected by the S(P-2)E/K(P-3)E mutation, as analyzed by surface plasmon resonance. Considering the positional and side-chain differences of these NF residues from previously reported T-cell activating sequences, the mechanisms of enhanced T-cell activation by Ser(-2) and Lys(-3) of NF-pCj1 may be novel.

Effectiveness of sublingual immunotherapy in pediatric cedar pollinosis: A real-world database study.

BACKGROUND: Pediatric allergic rhinitis (AR), including cedar pollinosis (CP), is increasing in Japan. We investigated the effects of sublingual immunotherapy (SLIT), which has limited studies of its effectiveness in real-world settings, on children with CP. METHODS: This retrospective cohort study used a claim database in 2018-2021. Children aged ≤15 years with CP records in 2019 were eligible and were followed up through 2021. We included 2962 CP children undergoing SLIT and 547 who were not. The medication score was used to evaluate SLIT effectiveness in the cedar pollen dispersal season each year. Adverse events and the occurrence of allergic diseases were also evaluated. RESULTS: Medication score was higher in the SLIT group during the index period but lower in 2021 compared to the non-SLIT group (mean ± standard deviation: 5.17 ± 2.39 and 4.74 ± 2.38 in 2019, 3.13 ± 2.30 and 3.55 ± 2.48 in 2021, respectively). The adjusted mean difference between groups from 2019 to 2021 was -0.62 (95% confidence interval: -0.86 to -0.39, p < .0001), and the medication score was reduced in the SLIT group (risk ratio: 1.2: 1.1 to 1.3). The occurrence of adverse events involving abdominal disorders (adjusted odds ratio [aOR]: 0.64: 0.51 to 0.81), asthma exacerbation (aOR: 0.37: 0.24 to 0.57), and allergic diseases involving hay fever unrelated to CP (aOR: 0.60: 0.45 to 0.80) or asthma (aOR: 0.71: 0.58 to 0.86) was lower in the SLIT group. CONCLUSION: In children with CP, SLIT is effective, well tolerated, and could decrease the occurrence of other allergic diseases.

Potential of Thuja occidentalis L. Essential Oil and Water Extracts against Field Crop Pests.

Thuja occidentalis L. essential oil (EOTO) and its compounds, such as terpinyl acetate, bornyl acetate, and ß-thujone, are claimed to be highly effective against some storage pests, sanitary insects, or pests of fruit trees, while data about its use in protecting field crops are very scarce. There is also a lack of information in the literature about the insecticidal value of water extracts from T. occidentalis (WETOs). Both essential oils (EOs) and water extracts (WEs) from various plants have advantages and disadvantages in terms of their use as insecticides. EOs are generally more effective, but their preparation is more complicated and quite expensive. In turn, WEs are simple to prepare and cheap, but they often have limited effectiveness. Moreover, significant differences in responses exist depending on the species of the donor plant, the method of preparing the extract, its concentration, the species of the pest being controlled, the developmental stage, and even the gender of the pest. The goals of the research were to assess the effect of EOTO and WETOs prepared from dry and fresh matter on the mortality, feeding, and body mass changes of important crop pests, i.e., the black bean aphid, pea leaf weevil, and Colorado potato beetle (CPB), respectively, as well as on the mortality and voracity of non-target organism Asian lady beetle young larvae. EOTO showed significant aphicidal activity with LC50 = 0.8267% and 0.2453% after 42 h of the experiment for nymphs and wingless females of black bean aphid, respectively. Adults of CPB were more resistant to EOTO than aphids, with LC50 values for females equal to 1.5327% and 1.3113% after 48 h and after 72 h of the experiment. There was no significant effect of EOTO on CPB foraging. Calculated LC50 values for pea leaf weevil adults were lower than those for CPB (0.9638% and 0.8573% for males after 12 h and 24 h, respectively). In the case of this pest, a clear reduction in foraging was obtained, with higher concentrations of EOTO resulting in more pronounced reductions in foraging behavior. Concentrations of EOTO above 0.5%, which showed efficacy against the aphid, were lethal to 3-day-old larvae of the Asian lady beetle. WETOs, in turn, showed significant potential in inhibiting adult pea leaf weevil feeding, with very low or no effectiveness in reducing A. fabae and CPB, respectively.

Study of the Effect of Cedar Sawdust Content on Physical and Mechanical Properties of Cement Boards.

The growing demand for sustainable building materials, amid escalating costs, has spurred interest in alternative solutions such as wood cement composites. This study explores the feasibility of producing wood cement boards (WCBs) using locally sourced cedar sawdust as a reinforcing agent. Boards with a thickness of 10 mm and a target density of 1200 kg/m3 were manufactured under pressures ranging from 2 to 6 MPa for 24 h. Cedar sawdust, used as raw and untreated material, was incorporated into the mixture as a partial substitute for cement in varying proportions, ranging from 10% to 25% (by weight). The WCBs were cured for 28 days under ambient conditions. Physical properties including density, water absorption (WA), and thickness swelling (TS) were assessed, along with mechanical properties through flexural tests. The results showed that increasing cedar sawdust content decreased both density and mechanical performance while increasing WA and TS. Microstructural analysis (SEM and EDS) revealed significant porosity at higher sawdust contents, while lower contents had better matrix-reinforcement cohesion. Additionally, substantial levels of calcium and silicon were detected on the sawdust surface, indicating stabilized cement hydration products. These findings, supported by thermal (TGA and DSC) and FTIR analyses, clearly demonstrate that cement boards with 10% cedar sawdust exhibit favorable properties for non-structural applications, such as wall and partition cladding.

[TWO CASES OF ALLERGIC VULVOVAGINITIS DIAGNOSED BY DIRECT MICROSCOPIC URINE SEDIMENT EXAMINATION].

Cedar pollen is known as a typical allergen that causes various allergic symptoms in the nasal mucosa, conjunctiva, and skin. However, inflammation of the vulvar mucosa due to sensitization to cedar pollen is not well-known. We experienced two cases in which the detection of cedar pollen during microscopic urine sediment examination led to the diagnosis of allergic vulvovaginitis caused by cedar pollen. The cases involved a 4-year-old girl and a 10-year-old girl. In both cases, the patients presented with chief complaints of pruritis in the vulva and insomnia due to frequent urination during the season of cedar pollen dissemination. Both patients were afebrile. No inflammatory skin changes such as erythema, swelling, or non-purulent discharge from mucous membranes of the vulva were observed. Microscopic urine sediment examination revealed large amounts of shed cedar pollen. The patients' conditions improved after treatment with oral antihistamines and instruction to dry their underwear indoors. Follow-up blood tests revealed high levels of specific anti-IgE antibodies to cedar pollen, thus confirming a diagnosis of allergic vulvovaginitis due to cedar pollen. Cedar pollen can cause allergic vulvovaginitis. Microscopic urine sediment examination is useful, and when combined with specific IgE antibody testing, leads to an appropriate diagnosis. This disease should also be considered in patients with complaints of vulvar discomfort during the season of cedar pollen dissemination.

Plant chemical traits define functional and phylogenetic axes of plant biodiversity.

To determine which types of plant traits might better explain ecosystem functioning and plant evolutionary histories, we compiled 42 traits for each of 15 perennial species in a biodiversity experiment. We used every possible combination of three traits to cluster species. Across these 11,480 combinations, clusters generated using tissue %Ca, %N and %K best mapped onto phylogeny. Moreover, for the 15 best combinations of three traits, 82% of traits were chemical, 16% morphological and 2% metabolic. The diversity-dependence of ecosystem productivity was better explained by the %Ca, %N and %K clusters: compared to adding a new species at random, adding a species from an absent cluster/clade better-explained gains in productivity. Species number impacted productivity only when all clusters were present. Our results suggest that tissue elemental chemistry might be more phylogenetically conserved and more strongly related to ecosystem functioning than commonly measured morphological and physiological traits, a possibility that merits exploration.

The soothing effect of phlorotannins on cedar pollinosis in Cry j 1-stimulated mice.

The antiallergic properties of phlorotannins, algal polyphenols, have been widely reported. This study examined the soothing effect of phlorotannin concentrate (PTC) from Eisenia nipponica on cedar pollinosis in Cry j 1-stimulated mice. PTC reduced the mice's sneezing and nasal rubbing, which was attributed to decreased levels of immunoglobulin E and Th2-type cytokines [interleukin (IL)-4, IL-5, and IL-13].

Single-cell immunoprofiling after immunotherapy for allergic rhinitis reveals functional suppression of pathogenic TH2 cells and clonal conversion.

BACKGROUND: Allergic rhinitis is a growing problem worldwide. Currently the only treatment that can modify the disease is antigen-specific immunotherapy, but its mechanism of action is not fully understood. OBJECTIVE: We comprehensively investigated the role and changes of antigen-specific T cells before and after sublingual immunotherapy (SLIT) for Japanese cedar pollinosis. METHODS: We cultured peripheral blood mononuclear cells obtained both before and 1 year after initiating SLIT and used a combination of single-cell RNA sequencing and repertoire sequencing. To investigate biomarkers, we used cells from patients participating a phase 2/3 trial of SLIT tablets for Japanese cedar pollinosis and cells from outpatients with good and poor response. RESULTS: Antigen-stimulated culturing after SLIT led to clonal expansion of TH2 and regulatory T cells, and most of these CD4+ T cells retained their CDR3 regions before and after treatment, indicating antigen-specific clonal responses and differentiation resulting from SLIT. However, SLIT reduced the number of clonal functional TH2 cells but increased the trans-type TH2 cell population that expresses musculin (MSC), TGF-ß, and IL-2. Trajectory analysis suggested that SLIT induced clonal differentiation of the trans-type TH2 cells differentiated into regulatory T cells. Using real-time PCR, we found that the MSC levels increased in the active SLIT group and those with good response after 1 year of treatment. CONCLUSION: The combination of single-cell RNA sequencing and repertoire analysis helped reveal part of the underlying mechanism: SLIT promotes the expression of MSC on pathogenic TH2 cells and suppresses their function. MSC may be a potential biomarker of SLIT for allergic rhinitis.

Statistical Design and Optimization of Cr (VI) Adsorption onto Native and HNO3/NaOH Activated Cedar Sawdust Using AAS and a Response Surface Methodology (RSM).

The removal of heavy metals from wastewater has become the subject of considerable interest at present. Thus, the use of novel adsorbents that are highly efficient is of critical importance for the removal of Cr (VI) ions from aqueous media. The adsorption of Cr (VI) ions from aqueous solutions by a new adsorbent, cedar wood sawdust, and the optimization of its adsorption parameters, were investigated in this study. Cedar wood sawdust was used in its native and HNO3/NaOH chemically modified forms as new low-cost sorbents to remove Cr (VI) ions from aqueous solutions in a batch system. The adsorption conditions were analyzed via response surface methodology. The RSM results showed that the optimal adsorption conditions yielding the best response were an adsorbent mass of 2 g for native Cedar and 1.125 g for its activated form, a metal concentration of 150 mg/L for native Cedar and 250 mg/L for activated, a temperature of 50 °C, a pH of 1, and a contact time of 67.5 min. At optimum adsorption conditions, the maximum adsorption capacities and the adsorption yields were 23.64 mg/g and 84% for native Cedar and 48.31 mg/g and 99% for activated Cedar, respectively.

Gymnosperms of Idaho: Chemical Compositions and Enantiomeric Distributions of Essential Oils of Abies lasiocarpa, Picea engelmannii, Pinus contorta, Pseudotsuga menziesii, and Thuja plicata.

Conifers are of great economic value in terms of lumber production, important for construction and other uses such as pulp and paper. They are also important sources of essential oils. Conifer species have been vital to the ethnobotany and traditional herbal medicine of many different Native American groups. The objective of this work was to obtain and analyze the essential oils of several conifer species (Abies lasiocarpa, Picea engelmannii, Pinus contorta, Pseudotsuga menziesii, and Thuja plicata) growing in Idaho. The foliar essential oils were obtained by hydrodistillation and then analyzed by gas chromatographic methods, including GC-MS, GC-FID, and chiral GC-MS. The essential oils were obtained in varying yields from 0.66% up to 4.70%. The essential oil compositions were largely dominated by monoterpene hydrocarbons and oxygenated monoterpenoids. The chiral monoterpenoids were generally rich in the (-)-enantiomers for members of the Pinaceae, but the (+)-enantiomers predominated in the Cupressaceae. The essential oil compositions obtained in this work are qualitatively similar, but quantitatively different, to previously reported compositions and confirm and complement the previous reports. However, this is the first comprehensive analysis of the chiral terpenoid components in these conifer species. Additional research on essential oils of the Pinaceae and Cupressaceae is needed to describe the chemical profiles, chemical compositions, and enantiomeric distributions more reliably in the various species and infraspecific taxa of these two families.

Effect of birth season on allergic rhinitis and cedar pollinosis considering allergen and vitamin D exposure: The Japan Environment and Children's study (JECS).

BACKGROUND: The relationship between the season of birth, allergen sensitization, and allergic rhinitis have been inconsistent, and there are no studies that simultaneously consider vitamin D and allergen exposure. This study aimed to determine the associations between the season of birth, house dust mite (HDM) and Japanese cedar pollen (JCP) sensitization, and allergic rhinitis and pollinosis, while taking vitamin D levels and allergen exposure into account. METHODS: This study included 4323 participants in the Sub-Cohort Study of the Japan Environment and Children's Study. A logistic regression model was used to analyze the association between the season of birth and sensitization to JCP or HDM (judged by specific immunoglobulin E) at age 2 and allergic rhinitis or pollinosis at age 3, adjusted for HDM or JCP exposure and vitamin D levels with potential confounders. RESULTS: Participants born in spring or summer were more likely to have pollinosis than were those born in winter (adjusted odds ratio [aOR]: 2.08, 95% confidence interval [CI]: 1.13-3.82 for spring; aOR: 1.89, 95% CI: 1.03-3.47 for summer). Participants born in summer were more likely to have HDM sensitization than were those born in winter (Der p 1, aOR: 1.53, 95% CI: 1.10-2.15; Der f 1, aOR: 1.44, 95% CI: 1.03-2.01). Exposure to JCP and HDM were associated with pollinosis and HDM sensitization, respectively. CONCLUSIONS: Spring and summer births were associated with the development of pollinosis, and summer birth was associated with HDM sensitization, even when vitamin D and allergen exposure were considered. Further studies on mechanisms other than vitamin D and allergen exposure are required.

[A MULTICENTER CLINICAL SURVEY ABOUT THE PREVALENCE OF JAPANESE CYPRESS POLLINOSIS AND THE EFFICACY OF SUBLINGUAL IMMUNOTHERAPY WITH JAPANESE CEDAR POLLEN EXTRACT DURING JAPANESE CYPRESS POLLEN DISPERSAL PERIOD].

BACKGROUND: Little is known whether sublingual immunotherapy using Japanese cedar pollen extract (cedar SLIT) is effective for not only Japanese cedar pollinosis but also Japanese cypress pollinosis. We investigated the prevalence rate of Japanese cypress pollinosis, efficacy of cedar SLIT on cypress pollinosis and patients' wish to receive cypress SLIT. METHODS: We investigated a multi-center (31 institutions), cross-sectional survey using a self-administrated questionnaire with four questions for patients received cedar SLIT aged from 5 to 69 years old. RESULTS: 2523 subjects were enrolled for analysis. 83.4% of them had pollinosis symptoms during cypress season before cedar SLIT. In such patients, 37.4% experienced lessened efficacy of cedar SLIT during cypress season. Both the prevalence of cypress pollinosis and the lessened efficacy of cedar SLIT on cypress pollinosis were significantly seen in western Japan as compared to eastern Japan. 76.1% of the subject having cypress pollinosis before SLIT wished to receive cypress SLIT if it is available. CONCLUSION: A lessened efficacy of cedar SLIT during cypress season was broadly seen in Japan, and further showed a regional difference. Together with the finding of high wish by patients, these results suggest a development of cypress SLIT is desirable.

[CLINICAL EFFICACY OF SUBLINGUAL IMMUNOTHERAPY WITH CEDAR POLLEN IN A YEAR OF MASSIVE CEDAR POLLEN DISPERSAL AND ITS EFFECT ON JAPANESE CYPRESS POLLINOSIS].

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 (p＜0.01), rhinorrhea, itchy eyes and total symptoms (p＜0.05) 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.

Headless Henipaviral Receptor Binding Glycoproteins Reveal Fusion Modulation by the Head/Stalk Interface and Post-receptor Binding Contributions of the Head Domain.

Cedar virus (CedV) is a nonpathogenic member of the Henipavirus (HNV) genus of emerging viruses, which includes the deadly Nipah (NiV) and Hendra (HeV) viruses. CedV forms syncytia, a hallmark of henipaviral and paramyxoviral infections and pathogenicity. However, the intrinsic fusogenic capacity of CedV relative to NiV or HeV remains unquantified. HNV entry is mediated by concerted interactions between the attachment (G) and fusion (F) glycoproteins. Upon receptor binding by the HNV G head domain, a fusion-activating G stalk region is exposed and triggers F to undergo a conformational cascade that leads to viral entry or cell-cell fusion. Here, we demonstrate quantitatively that CedV is inherently significantly less fusogenic than NiV at equivalent G and F cell surface expression levels. We then generated and tested six headless CedV G mutants of distinct C-terminal stalk lengths, surprisingly revealing highly hyperfusogenic cell-cell fusion phenotypes 3- to 4-fold greater than wild-type CedV levels. Additionally, similarly to NiV, a headless HeV G mutant yielded a less pronounced hyperfusogenic phenotype compared to wild-type HeV. Further, coimmunoprecipitation and cell-cell fusion assays revealed heterotypic NiV/CedV functional G/F bidentate interactions, as well as evidence of HNV G head domain involvement beyond receptor binding or G stalk exposure. All evidence points to the G head/stalk junction being key to modulating HNV fusogenicity, supporting the notion that head domains play several distinct and central roles in modulating stalk domain fusion promotion. Further, this study exemplifies how CedV may help elucidate important mechanistic underpinnings of HNV entry and pathogenicity. IMPORTANCE The Henipavirus genus in the Paramyxoviridae family includes the zoonotic Nipah (NiV) and Hendra (HeV) viruses. NiV and HeV infections often cause fatal encephalitis and pneumonia, but no vaccines or therapeutics are currently approved for human use. Upon viral entry, Henipavirus infections yield the formation of multinucleated cells (syncytia). Viral entry and cell-cell fusion are mediated by the attachment (G) and fusion (F) glycoproteins. Cedar virus (CedV), a nonpathogenic henipavirus, may be a useful tool to gain knowledge on henipaviral pathogenicity. Here, using homotypic and heterotypic full-length and headless CedV, NiV, and HeV G/F combinations, we discovered that CedV G/F are significantly less fusogenic than NiV or HeV G/F, and that the G head/stalk junction is key to modulating cell-cell fusion, refining the mechanism of henipaviral membrane fusion events. Our study exemplifies how CedV may be a useful tool to elucidate broader mechanistic understanding for the important henipaviruses.

The role of N-linked glycosylation in proteolytic processing and cell surface transport of the Cedar virus fusion protein.

BACKGROUND: N-linked glycans on viral glycoproteins have been shown to be important for protein expression, processing and intracellular transport. The fusion glycoprotein F of Cedar virus (CedV) contains six potential N-glycosylation sites. FINDINGS: To investigate their impact on cell surface transport, proteolytic cleavage and biological activity, we disrupted the consensus sequences by conservative mutations (Asn to Gln) and found that five of the six potential N-glycosylation sites are actually utilized. The individual removal of N-glycan g1 (N66), g2 (N79) and g3 (N98) in the CedV F2 subunit had no or only little effect on cell surface transport, proteolytic cleavage and fusion activity of CedV F. Interestingly, removal of N-linked glycan g6 (N463) in the F1 subunit resulted in reduced cell surface expression but slightly increased fusogenicity upon co-expression with the CedV receptor-binding protein G. Most prominent effects however were observed for the disruption of N-glycosylation motif g4 (N413), which significantly impaired the transport of CedV F to the cell surface, thereby also affecting proteolytic cleavage and fusion activity. CONCLUSIONS: Our findings indicate that the individual N-linked modifications, with the exception of glycan g4, are dispensable for processing of CedV F protein in transfection experiments. However, removal of g4 led to a phenotype that was strongly impaired concerning cell surface expression and proteolytic activation.

Cloudwater Deposition Process of Radionuclides Based on Water Droplets Retrieved from Pollen Sensor Data.

Radionuclides released during the Fukushima Daiichi nuclear accident caused altitude-dependent surface contamination in the mountainous areas of Japan. To explore the possible cloudwater deposition that formed a distinctive contamination profile, data from pollen sensors deployed nationwide were analyzed. Utilizing the polarization of scattered light, Cedar pollen and water droplets were distinguished. On March 15, when surface contamination was simulated in previous studies, dense clouds with high droplet number concentrations were observed outside the 137Cs surface deposition areas, indicating that the sensor sites were immersed amid cloud layers. In contrast, cloud droplets with moderate number concentrations were measured at altitudes of approximately 570-840 m, which overlapped with the surface contamination areas. Considering the existing knowledge on vertical gradients of cloudwater composition, these suggest that contaminated cloud droplets were localized near the cloud base where a moderate number concentration of cloud droplets was measured. A formation process was proposed for the observed vertical distribution, that is, surface contamination occurred intensively at the contact line between the cloud base and mountain slopes via cloudwater deposition, and the descending cloud base formed the contamination zone. This study sheds light on the deposition processes of radionuclides, which have not previously been clarified.

Cedrus libani tar prompts reactive oxygen species toxicity and DNA damage in colon cancer cells.

BACKGROUND: Many chemotherapeutic drugs used in cancer treatment have anticancer properties by inducing reactive oxygen species (ROS). However, the same effect occurs in normal cells, limiting the availability of these drugs. Therefore, studies on the detection of new herbal anticancer agents that have selective effects on cancer cells are of great importance. The aim of this study is to investigate the metabolite profile of Cedrus libani tar and its mechanism of anticancer effect on colon cancer cells. METHODS AND RESULTS: Effect of cedar tar on cells (12 cancers and 5 normal cell lines) viability was determined by MTT, apoptosis induction was determined by Annexin-V, ROS and MMP determined by flow cytometry assay. Cleaved caspase-8, 9 and Ɣ-H2AX expression determined by western blot. Apoptotic and antioxidant genes expression level determined by qPCR. Metabolite profiling was performed with LC-MS/MS and GC-MS. Cedar tar showed the highest cytotoxic effect among cancer cells in colon cancer (HCT-116, IC50: 30.4 µg/mL) and its toxic effect on normal cells (HUVEC, IC50: 74.07 µg/mL) was less than cancer cell. Cedar tar increases ROS production in colon cancer cells. The metabolite profile of the cedar tar contains high amounts of metabolites such as fatty acids mainly (Duprezianene, Himachalene and Chamigrene), phenolic compounds (mostly Coumarin, p-coumaric acid, Vanillic acid and tr-Ferulic acid etc.) and organic acids (mainly 3-oh propanoic acid, 2-oh butyric acid and 3-oh isovaleric acid etc.). CONCLUSION: As a result, it has been found that cedar tar has the potential to be used in the treatment of colon cancer.

Structural and functional analyses reveal promiscuous and species specific use of ephrin receptors by Cedar virus.

Cedar virus (CedV) is a bat-borne henipavirus related to Nipah virus (NiV) and Hendra virus (HeV), zoonotic agents of fatal human disease. CedV receptor-binding protein (G) shares only ∼30% sequence identity with those of NiV and HeV, although they can all use ephrin-B2 as an entry receptor. We demonstrate that CedV also enters cells through additional B- and A-class ephrins (ephrin-B1, ephrin-A2, and ephrin-A5) and report the crystal structure of the CedV G ectodomain alone and in complex with ephrin-B1 or ephrin-B2. The CedV G receptor-binding site is structurally distinct from other henipaviruses, underlying its capability to accommodate additional ephrin receptors. We also show that CedV can enter cells through mouse ephrin-A1 but not human ephrin-A1, which differ by 1 residue in the key contact region. This is evidence of species specific ephrin receptor usage by a henipavirus, and implicates additional ephrin receptors in potential zoonotic transmission.

Investigation of the sensitization rate for gibberellin-regulated protein in patients with Japanese cedar pollinosis.

BACKGROUND: Pollen-food allergy syndrome (PFAS) usually manifests as an itching sensation in the mouth and throat immediately after eating fresh fruits and vegetables. However, some patients with PFAS experience systemic symptoms including anaphylaxis. In Europe, cypress gibberellin-regulated protein (GRP) has been noted to cause allergenicity and exhibit cross-reactivity with peach GRP. Japanese cedar (Cryptomeria japonica), classified in the cypress family, is the primary causative substance among all environmental allergens in Japan. However, studies on the prevalence of GRP sensitization in patients with cedar pollinosis are lacking. OBJECTIVE: This study examined the prevalence of GRP sensitization in patients with Japanese cedar pollinosis. METHODS: We enrolled 52 patients who had requested sublingual immunotherapy treatment with mild-to-severe rhinitis during spring, and had a JCP-specific immunoglobulin E (IgE) levels of >0.7 UA/mL. Peach GRP was purified using affinity chromatography with a monoclonal antibody column. Specific IgE levels to peach GRP were measured using an enzyme-linked immunosorbent assay. Samples exhibiting absorbance at 450 nm of over mean plus three standard deviations of the negative control value were defined as positive. Sera from three patients with severe peach allergy were used as positive controls. RESULTS: Eleven sera from 52 patients with JCP-induced allergic rhinitis were positive for peach GRP. CONCLUSION: Twenty percent of patients with cedar pollinosis were sensitized to peach GRP. Well-powered studies are needed to clarify whether these patients are at an increased risk for systemic symptoms or whether they primarily demonstrate only localized symptoms.

Studies on safety and efficacy of particles containing a mixture of hydroxyapatite-argentum-titanium oxide (HAT) and sheets coated with HAT particles to be used in masks to improve nasal allergy: II. Cellular, in vivo, and clinical studies.

PURPOSE: We report the manufacture of particles containing a mixture of hydroxyapatite-argentum-titanium oxide (HAT), followed by attachment to nonwoven polyester fabrics to produce HAT-coated sheets (HATS) for use in masks. The purpose of the present study was to perform cellular, in vivo, and clinical studies to further examine the safety of HATS for use in masks to improve nasal allergy. METHODS: Reverse mutation tests for HAT were performed using five bacterial strains. A cellular toxicity test was performed using a Chinese hamster cell line incubated with the HATS extracts. Skin reactions after intradermal administration were examined in rabbits. Skin sensitization tests in guinea pigs were performed using the HATS extracts. HAT was administered to the nasal cavity and conjunctival sac of the rabbits. An oral administration study was performed in rats. Finally, a human skin patch test was performed using the HATS. RESULTS: Reverse mutation tests showed negative results. The cellular toxicity test showed that the HATS extract had moderate cytotoxicity. The intradermal skin reaction and skin sensitization tests were all negative. The administration of HAT to the nasal cavity and intraocular administration showed negative results. No toxicity was observed after oral administration of HAT powder up to a dose of 2000 mg/kg. Finally, the skin patch test result was negative. CONCLUSION: Although HAT showed moderate cytotoxicity, in vivo results indicated that HAT is safe because it does not come in direct contact with cells in normal usage, and HATS is safe when used in masks.