[Research progress on pollen food allergy syndrome].

Pollen food allergy syndrome (PFAS) is an IgE-mediated allergic reaction that occurs when some pollinosis patients ingest certain plant-derived food that contains cross-reactive allergenic components. PFAS is prevalent in both children and adult pollinosis patients. In most cases, PFAS symptoms are confined to the oropharynx and occur within several minutes after oral contact with food. Therefore, PFAS has been also referred as oral allergy syndrome (OAS). A small proportion of PFAS patients would experience systemic symptoms or anaphylaxis. Currently, the diagnosis of PFAS is mainly based on clinical history and allergic tests [skin prick tests and(or) serum specific IgE tests]. Oral provocation tests are used to verify atypical patients. Component-resolved diagnosis is essential for further precise diagnosis and treatment. Management options for PFAS include lifestyle adjustment, symptomatic medication, and immunotherapy. The efficacy and appropriate population for immunotherapy need further investigation. This article aims to update the knowledge on epidemiology, pathogenesis and clinical management of PFAS, thereby enhancing clinicians' understanding as well as treatment progress of this disease entity.

[Appropriate protocol of treatment modulation for seasonal allergic rhinitis caused by cypress pollens].

Objective: To investigate appropriate protocol of treatment modulation for seasonal allergic rhinitis (AR) patients, in order to promote the implementation of personalized medicine. Methods: Total of 124 AR patients allergic to cypress pollens were recruited from January to February 2020 in Department of Allergy in Peking Union Medical College Hospital, 43 males and 81 females with an average age of (41±9) years. The patients were divided into two groups with block randomization method. In the first group, treatment was modulated every two days according to the average daily rhinoconjunctivitis symptom score of the last two days (short-term symptom-score group); while in the second group, therapy regimen was adjusted every week based on the Allergic Rhinitis Control Test (ARCT) score of the last week (long-term ARCT group). The treatment level was up-regulated when the cypress pollen count increased and stayed at a high level (step-up pharmacotherapy stage); and treatment was down-regulated while the pollen count decreased (step-down pharmacotherapy stage). Daily symptom scores, medicine scores, and ARCT scores of the two groups were recorded and compared. Results: During the whole cypress pollen season, the daily rhinoconjunctivitis symptom score of short-term symptom-score group was significantly lower than that in long-term ARCT group(2.4±1.0 vs 2.7±1.0, P<0.01), and the difference between the two groups was more pronounced in the step-up pharmacotherapy stage than that in the step-down pharmacotherapy stage, while there was no statistical difference between the daily medicine scores of the two groups (P>0.05). During the pollen rising period, the ARCT score of short-term symptom-score group was significantly better than that of long-term ARCT group (21(19, 22) vs 20 (17, 21), P=0.049); while in the pollen peak period and decreasing period, the ARCT scores of the two groups showed no statistical difference (P>0.05). The proportion of incompliance with doctor's advice was higher in long-term ARCT group compared to that in short-term symptom-score group (30.1% vs 6.7%, P<0.001). Conclusion: The protocol of treatment modulation for seasonal AR patients allergic to pollens should be developed flexibly according to the variation trend of pollen allergen exposure, so as to implement the idea of personalized medicine.

[The effect on patient life quality of prophylactic treatment to seasonal allergic rhinitis and related transcriptomics research].

Objective: The preseason prophylactic treatment of seasonal allergic rhinitis (AR) caused by pollens could alleviate AR symptoms during the pollen season. This study aimed to evaluate the effect of prophylaxis usage of suplatast tosilate on the life quality of AR patients in the pollen season, and investigate the potential mechanism of action through transcriptomic analysis. Methods: This is a randomized controlled study. AR patients allergic to weed pollens were recruited from Allergy Clinic of Peking Union Medical College Hospital from January 2020 to June 2020, and divided into prophylactic group who started to take suplatast tosilate as prophylaxis 2 weeks before the spread of weed pollens[n=10, 4 men and 6 women with age range of (34±6) years old] and control group who did not use any prophylactic treatment[n=24, 12 men and 12 women with age range of (33±9) years old]. The differences of age (t=0.381, P=0.706) and gender (χ²=0.595, P=0.715) distribution between the patients of two groups were not statistically significant. All the subjects filled in the rhinoconjunctivitis quality of life questionnaire (RQLQ) while onset of AR symptoms, and peripheral blood was drawn for transcriptomic analysis 1 month before and during the pollen season. Differences between groups were statistically analyzed through chi-square test and t test. Results: There was no significant difference in visual analogue scale of rhinitis symptom in the last pollen season between prophylactic group and control group[ 8.0 (6.4, 9.3) vs 7.3 (6.1, 8.0), Z=1.180, P=0.254]. The RQLQ score of prophylactic group was superior to that of control group in the weed pollen season (2.9±0.9 vs 3.7±0.9, t=-2.438, P=0.026). 210 differentially expressed genes of fold change ≥2 were identified, with 147 genes upregulated and 63 genes downregulated in the prophylactic group compared to the control group. Gene Ontology annotation showed that IL-12 and IL-23 related pathways were downregulated in prophylactic group (P=0.006 48). Polymerase Chain Reaction (PCR) verification of differentially expressed genes indicated that the relative expression level of HLA-G in prophylactic group was significantly lower than that in control group (0.23±0.19 vs 1.00±0.49,t=4.016, P=0.006). Conclusion: The prophylactic treatment of suplatast tosilate showed some benefit to the life quality of seasonal AR patients during the pollen season, and the potential mechanism might be related with the downregulation of IL-12 and IL-23 pathways and decreased expression of HLA-G.

[The comparison of step-down pharmacotherapy and maintaining dose therapy for seasonal allergic rhinitis].

Objective:There is no standard algorithm for the modulation of pharmacologic treatment of allergic rhinitis. This study aimed to recruited allergic rhinitis patients caused by cypress pollens, and compare the step-down pharmacotherapy guided by pollen count and the maintaining therapy which keeps the previous medicine dose when the pollen count decreased. Method:This was a randomized, open-labelled, parallel control study. During the period after the pollen peak when the cypress pollen count decreased and stayed at a low level, allergic rhinitis patients were randomly divided into two groups. In the step-down group（n=67） medicine dose was reduced, while the maintaining group（n=68） kept taking the same dose as in the peak season. The rhinitis symptom score and medicine score of these two groups were recorded and compared. Result:The daily rhinitis symptom score of the step-down group showed no significant difference with the symptom score of the maintaining group, 2.45±0.32 vs 2.43±0.41, P=0.788. But the medicine score of step-down group（3.67±0.98） was significantly lower than that of maintaining group（4.78±0.70）, P<0.001. The compliance of step-down group（80.6%） was also better than maintaining group（60.3%）, P=0.014. However, in the subgroup of patients with severe rhinitis symptoms, the symptoms of patients taking step-down therapy tended to be more severe than those maintaining the same dose. Conclusion:During the later period of the pollen season when the pollen count was relatively low, the step-down pharmacotherapy guided by pollen count could reduce the medication use, increase the compliance of patients while controlling their rhinitis symptoms effectively. But this strategy might be more suitable for patients with milder symptoms, the severe rhinitis sufferers should be cautious before reducing their medicine dose.

[Treatment effect of sodium pyruvate nasal spray on allergic rhinitis].

Objective:Pyruvate is a key intermediate in several metabolic pathways of human body Sodium pyruvate possesses anti-oxidation and anti-inflammatory effects, which make it a possible novel therapy for allergic rhinitis. However, the relevant clinical research is rare. The aim of the present study is to evaluate the treatment effect of sodium pyruvate nasal spray on allergic rhinitis.Method:This was a randomized, parallel-group, single-center study, and 53 adult patients with seasonal allergic rhinitis caused by Artemisia pollen were recruited. In the pollen season, all the participants were given corticosteroid nasal spray of standard dose for two weeks, and during the next two weeks they were randomized to treatment group (n = 23) taking nasal sodium pyruvate, and control group (n = 30) without sodium pyruvate. Daily rhinoconjunctivitis symptom score and daily rescue medication score were analyzed. Also the fraction of exhaled nitric oxide of the upper airway was measured before and after the treatment of sodium pyruvate. Result:The demographic characteristics and baseline disease severity were not significantly different between the treatment group and control group. Both the daily symptom score (1.4±0.6 vs 1.7±0.4, P= 0.006) and rescue medication score (4.8±1.2 vs 5.8±1.2, P= 0.000) of the treatment group was significantly lower than the scores of control group. In addition, nasal fraction of exhaled nitric oxide of the treatment group (596.3±134.6)ppb tended to be lower than control group (709.6±311.3)ppb, although the difference was not significant, P= 0.408. Conclusion:Sodium pyruvate nasal spray was effective in attenuating the rhinoconjunctivitis symptoms and reducing the rescue medication use of allergic rhinitis patients. The application value and mechanism of action of sodium pyruvate are worth further studying.

Modulation of sarcomere organization during embryonic stem cell-derived cardiomyocyte differentiation.

Myofibrillogenesis - sarcomeres - mouse embryonic stem cells - cardiomyocytes - beta1 integrin Mouse embryonic stem (ES) cells, when cultivated as embryoid bodies, differentiate in vitro into cardiomyocytes of ventricle-, atrium- and pacemaker-like cell types characterized by developmentally controlled expression of cardiac-specific genes, structural proteins and ion channels. Using this model system, we show here, (I) that during cardiac myofibrillogenesis sarcomeric proteins are organized in a developmentally regulated manner following the order: titin (Z-disk), alpha-actinin, myomesin, titin (M-band), myosin heavy chain, alpha-actin, cardiac troponin T and M-protein, recapitulating the sarcomeric organization in the chicken embryonal heart in vivo. Our data support the view that the formation of I-Z-I complexes is developmentally delayed with respect to A-band assembly. We show (2) that the process of cardiogenic differentiation in vitro is influenced by medium components: Using a culture medium supplemented with glucose, amino acids, vitamins and selenium ions, we were able to increase the efficiency of cardiac differentiation of wild-type, as well as of beta1 integrin-deficient (beta1-/-) ES cells, and to improve the degree of organization of sarcomeric structures in wild-type and in beta1-/- cardiac cells. The data demonstrate the plasticity of cardiogenesis during the differentiation of wild-type and of genetically modified ES cells.

Elevated levels of ERK2 in human breast carcinoma MCF-7 cells transfected with protein kinase C alpha.

We investigated the effect of elevated levels of protein kinase C alpha (PKC alpha) on cell proliferation in human breast carcinoma cells (MCF-7). MCF-7 cells transfected with either the pSV2M(2)6 vector without the insert (MCF-7/Vector) or containing a full length cDNA encoding PKC alpha (MCF-7/PKC alpha) were compared. MCF-7/PKC alpha cells were found to have an increased proliferative rate with a doubling time of 15 h as compared to 42 h for MCF-7/Vector cells. Flow cytometry illustrated a greater percentage of MCF-7/PKC alpha cells in the S phase of the cell cycle. Western and Northern blot analyses demonstrated an increase in extracellular regulated protein kinase 2 (ERK2) gene expression in MCF-7/PKC alpha cells but no alteration of this gene expression in MCF-7/Vector cells. These results suggested that the elevated level of ERK2 which is also known as mitogen activated protein kinase is probably involved in the increase in MCF-7/PKC alpha cell proliferation.

MEK-2, a Caenorhabditis elegans MAP kinase kinase, functions in Ras-mediated vulval induction and other developmental events.

Activated Ras initiates a cascade of sequential phosphorylation events, including the protein kinases Raf, MEK, and MAP kinase. The Let-60 Ras-mediated signal transduction pathway controls vulval induction in Caenorhabditis elegans. Both Lin-45 Raf and Sur-1 MAP kinase have been determined to be essential factors during vulval induction; however, the C. elegans mek gene has not been identified. In this paper, we have cloned a C. elegans mek gene, mek-2, and demonstrated that the MEK-2 protein possesses the biochemical properties of MAP kinase kinases: The C. elegans MEK-2 protein can phosphorylate and activate a human MAP kinase (ERK1), and MEK-2 itself can be phosphorylated and activated by immunoprecipitated mammalian Raf. The mek-2 gene plays a key role in the let-60 ras-mediated vulval induction pathway, as loss-of-function mutations in the gene (ku114 and h294) significantly reduce the signal transmitted through Ras. mek-2(ku114) completely suppressed the Multivulva (Muv) phenotype of a hyperactive let-60 ras mutation, and animals homozygous for mek-2(ku114) also displayed a partial larval lethal phenotype. Animals homozygous for mek-2(h294) exhibited a highly penetrant sterile and Vulvaless phenotype. Microinjection of a gain-of-function mek-2 mutation resulted in Muv and other mutant phenotypes, whereas microinjection of a dominant-negative mutation not only suppressed the Muv phenotype of an activated let-60 ras mutation but also caused an egg-laying defective phenotype in otherwise wild type animals. Our results demonstrate that mek-2 acts between lin-45 raf and sur-1/mpk-1 in a signal transduction pathway used in the control of vulval differentiation and other developmental events.

Cloning and expression of a protein-tyrosine-phosphatase.

A rat brain cDNA library was screened by using a mixture of oligonucleotides whose sequences were deduced from the amino acid sequence of a human placental protein-tyrosine-phosphatase (PTPase; EC 3.1.3.48) reported by Charbonneau et al. [Charbonneau, H., Tonks, N. K., Walsh, K. A. & Fischer, E. H. (1988) Proc. Natl. Acad. Sci. USA 85, 7182-7186]. The isolated clones encode a PTPase of 432 amino acids having a mass of 49,679 daltons and showing 97% sequence identity to the corresponding 321 residues of the placental enzyme. The coding sequence of the PTPase was placed behind a bacteriophage T7 promoter and the protein was expressed in Escherichia coli. The recombinant protein had a molecular weight of 50,000 by SDS/PAGE analysis and showed an absolute specificity for phosphotyrosine-containing substrates. Northern analysis documented that there were two sizes of RNA, 4.3 and 2.0 kilobases, which encode the PTPase. Both transcripts were present in a number of tissues, and the smaller RNA appears to arise by the use of an alternative polyadenylylation signal. The PTPase was also localized by in situ hybridization in the rat central nervous system. A diffuse pattern of hybridization signal is seen in a number of brain areas, with the hippocampus showing the highest levels of mRNA. Sequences located at the C terminus of the rat brain PTPase contain possible sites for phosphorylation as well as signals which could serve for membrane attachment.