Dynamics of ecosystems and anthropogenic drivers in the Yellow Sea Large Marine Ecosystem

In the developed world,governance of marine ecological environment is the important part of the national ecological and economic outcome.The Yellow Sea is one of large marine ecosystems in the seas of East Asia,which is an extension of one of the largest continental shelf areas,and forms a huge but shallow sediment body in its south area which is geographically unique in the world.As a region with the most fragile natural environment,unparalleled global ecological significance and the most urgent protection needs,the Yellow Sea ecological zone is becoming a common concern of countries around the Yellow Sea and beyond,such as tidal flats and the staging migratory birds(Murray et al.,2015).

Induction of deletion mutation on ompR gene of Salmonella enterica serovar Typhi isolates from asymptomatic typhoid carriers to evolve attenuated strains for vaccine development

Objective:To develop allenualed slrains of Salmonella enterica serorar Typhi(S.typhi) for the candidate vaccine by osmolar stress.Mothods:S.typhi SS3 and SS5 strains were isolated from asymptomatic typhoid carriers in Mamakkal,Tamil Nadu.India.Both strains were grown in LB(Luria Bertani) medium supplemented with various concentration of NaCl(0.1- 0.7M) respectively.The effecl of osmolar stress was determined at molecular level by PCR using MCR 06 and MCR07 primers corresponding to ompR with chromosomal DNA of S.typhi SS3 and SS5 strains.Attenuation by osmolar stress results in deletion mutation of the.S.typhi slrains was determined by agglutination assays,precipitation method.SDS PAGE analysis and by animal models.Results:The 799 bp amplified ompR gene product from wild type S.typhi SS3 and SS5 illustrate the presence of virulent gene.Interestingly,there was only a 282 bp amplified product from S.typhi SS3 and SS5 grown in the presence of 0.5.0.6 and 0.7 M NaCl.This illustrates the occurrence of deletion mutation in ompR gene al high concentration of NaCl.Furthermore,both the wildtype and mutant S.typhi outer membrane SDS-PAGF.profile reveals the differences in the expression of ompF.ompC and ompA proteins.In mice,wild type and mutant strains lethal dose(LD_(50)) were determined.The mice died within 72 h when both the wild type strains were injected intraperitoneally with 3 log CFU-mL^(-1).When the mice were injected with the mutants in same dosage,no clinical symptoms were observed;whereas the serum antibodv litre was elicited within two weeks indicated that the mutants have the ability to induce protective humoral immune response.These results suggest that S.typhi SS3 and SS5 may bo used as good candidate strains for the development of live attenuated vaccine against salmonellosis.Conclusions:This study demonstrates that the S.typhi strains were allenualed and could be good vaccine candidates in future.

Tidal water exchanges can shape the phytoplankton community structure and reduce the risk of harmful cyanobacterial blooms in a semi-closed lake

For estuaries,inland lakes play a vital role in the ecological balance under the impact of tide s.The effect of tides-induced water exchange on phytoplankton community in a semi-closed lake was studied and compared with that of an adjacent closed lake in the Oujiang River mouth in Zhejiang,East China Sea,from June 29,2020 to June 14,2021.Results show that the dominant species,abundance,dominance,and diversity of the phytoplankton species between the two lakes were significantly different.In the closed lake,cyanobacteria were the dominant species during the study period.However.in the semi-closed lake,the diversification of the dominant species was greater,and some species of diatoms and green algae became dominant.The average phytoplankton abundance in the closed lake was 6 times of that in the semi-closed lake.The average dominance of cyanobacteria in the closed lake was 0.96,and those in the semi-closed lake and the Oujiang River were 0.51 and 0.22,respectively.Cyanobacterial blooms occurred throughout the study time in the closed lake but not in the semi-closed one.Furthermore,the species diversity richness of the phytoplankton in the semi-closed lake was higher than that of the closed one,and the phytoplankton community between the closed lake and semi-closed lake could be divided into distinctly different groups based on non-metic multidimensional scaling analysis(NMDS)and analysis of similarities(ANOSIM)analysis.The salinity of the water was significantly greater and the transparency significantly smaller in the semi-closed lake than those in the closed lake.Therefore,water exchange driven by local tidal movement increased salinity and decreased transparency of water,which consequently shaped the community structures of different phytoplankton and reduced the risk of a cyanobacterial bloom outbreak in the semi-closed lake.

Novel perspectives for neurodegeneration prevention: effects of bioactive polyphenols

Neurodegenerative diseases are becoming a big challenge for modern society.Neurodegenerative disorders strongly impact on patient and their caregivers.Moreover, since the population is becoming older, these pathologies will deeply influence medical and socio-economic conditions in the next years.Therefore, efforts are needed to find new strategies devoted to define new protocols and identify novel substances able to prevent neurodegeneration or to improve the quality of life of people affected by neurodegenerative diseases(Alzheimer's Disease International, 2019).

The Application of Medicinal Plants in Traditional and Modern Medicine: A Review of <i>Thymus vulgaris</i>

Medicinal plants have played an essential role in the development of human culture. Medicinal plants are resources of traditional medicines and many of the modern medicines are produced indirectly from plants. This study illustrates the importance of traditional and modern medicines in the treatment and management of human diseases and ailments. It has been confirmed by WHO that herbal medicines serve the health needs of about 80 percent of the world’s population;especially for millions of people in the vast rural areas of developing countries. Meanwhile, consumers in developed countries are becoming disillusioned with modern health care and are seeking alternatives. Thymus vulgaris is a species of flowering plant in the mint family Lamiacea. Thymus is a widely used medicinal plant in food and pharmaceutical industries. Among different species of Thymus, Thymus vulgaris is used more than other species in therapeutic dosage forms. In Traditional medicine T. vulgaris is cultivated in many countries by most people especially in rural areas depending on herbal medicines to treat many diseases including inflammation-related ailments such as rheumatism, muscle swelling, insect bites, pains, etc. Also the modern medicine in essential oil of thyme has demonstrated that the compounds have shown anti-inflammatory, antioxidant, antibacterial and antifungal properties. In this review the objective is to consider the past and present value of medicinal plants such as Thymus vulgar is used in traditional and modern medical practices as bioactive natural compounds.

The protoplast two-way fusions and fusant characteristics of Antrodia cinnamomea and Cordyceps militaris

This study generated two fused protoplasts of Antrodia cinnamomea and Cordyceps militaris in two ways.The protoplasts of A.cinnamomea were inactivated by heat to inactivate biochemical processes and enzymatic activities in the cytoplasm,and the protoplasts of C.militaris were inactivated by UV radiation to invalidate their genome function,then they were fused under optimal conditions to get a fusion rate as(7.42±0.8)×10^(-6) fusants/mL;the new fusants were abbreviated as Ac-Cm.On the other hand,when A.cinnamomea and C.militaris were treated with heat and UV oppositely using similar experiments,the fusion rate was(9.70±0.68)×10^(-5) fusants/mL,and the new fusants were abbreviated as Cm-Ac.We selected each of two best-growing fused colonies Ac-Cm-1,Ac-Cm-2,Cm-Ac-1,and Cm-Ac-2,together with parental A.cinnamomea and C.militaris,and studied their morphology,growth antagonism tests,and genetic relationships by 18 S rRNA sequencing.In comparison with the initial cultures of 4 fusants,the yields of adenosine,biomass,cordycepic acid,cordycepin,total polysaccharide,and total triterpenoids were increased up 1.305-50.1563 times in the optimal medium conditions.For gene stability tests,those of the four fusants and their outputs were stabilized within 10 generations.

Research and development of Cordyceps in Taiwan

Cordyceps is treasured entomopathogenic fungi that have been used as antitumor,immunomodulating,antioxidant,and pro-sexual agent.Cordyceps,also called DongChongXiaCao in Chinese,Yartsa Gunbu(Tibetan),means winter worm-summer grass.Natural Cordyceps sinensis with parasitic hosts is difficult to be collected and the recent findings on its potential pharmacological functions,resulted in skyrocketing prices.Therefore,finding a mass-production method or an alternative for C.sinensis products is a top-priority task.In this review,we describe current status of Cordyceps research and its recent developments in Taiwan.The content and pharmacological activities of four major industrial species of Cordyceps(C.sinensis,Cordyceps militaris,Cordyceps cicadae and Cordyceps sobolifera)used in Taiwan,were reviewed.Moreover,we highlighted the effect of using different methods of fermentation and production on the morphology and chemical content of Cordyceps sp.Finally,we summarized the bottle-necks and challenges facing Cordyceps research as well as we proposed future road map for Cordyceps industry in Taiwan.

Protective Role of C-Phycocyanin Against Secondary Changes During Sodium Selenite Mediated Cataractogenesis

Age related cataract is the leading cause of blindness associated with accumulation of oxidative stress in the eye lens.The present investigation reveals the rational of the beneficial effects of the natural compound C-phycocyanin(CPC)is beneficial when administered to rat pups to protect against the secondary effects of sodium selenite induced cataractogenesis.A single subcutaneous dose of sodium selenite(19 lmol/kg body weight)on the 10th day of postpartum is adequate to induce cataract in rat pups.Serum biochemical parameters,such as the level of electrolytes,mean activities of anti-oxidant enzymes i.e.superoxide dismutase,catalase and reduced glutathione were observed to be significantly altered during selenite induced cataractogenic process.Histopathological examination revealed signs of degradation of normal cell architecture in the liver,kidney and eye lens.Interestingly,the deleterious effects of sodium selenite toxicity were restored with the simultaneous treatment with C-PC.The results suggest that an administration of 200 mg/kg body weight of C-PC has the ability to prevent/alter the secondary changes reflected in the serum biochemical and histological modifications in rats exposed to sodium selenite.These results complement the beneficial role of C-PC of cyanobacterial origin as a efficacious anti-cataractogenic agent against sodium selenite toxicity.

Chemical identification,antioxidant,cholinesterase inhibitory,and cytotoxic properties of fucoidan extracted from Persian Gulf Sargassumangustifolium

Marine macroalgal sulfated fucose-containing polysaccharides,like fucoidan,have drawn significant attention due to their biotechnological potentials,such as anti-cancer,antioxidant,and anti-cholinesterase activities.The fucoidan derived from brown macroalgae Sargassum angustifolium species(FSA)was investigated for its cytotoxic effects and alterations in cell proliferation,and cell cycle-related gene expression in the present study occurred on NB4 cell line.The results showed that FSA would induce p53,p21,pro-apoptotic genes and increase expression of the p15 gene as a cell arrest marker.Also,FSA inhibited the anti-apoptotic effect of the Bcl-2 gene and decreased dnmt-1 gene expression.FSA significantly exhibited potent 2,2-diphenyl-1-picrylhydrazyl(DPPH)radical scavenging activity(p<0.05)with an IC_(50) value of 0.157 mg/mL and showed moderate anti-acetylcholinesterase activity with an IC_(50) value of 1.20μg/mL.These results indicated the potential of FSA for the development of therapeutic or preventive agents of cancer and Alzheimer’s disease mainly through cytotoxic effect and AChE(acetylcholinesterase)inhibition as well as additional antioxidant capacities.

Evaluation of the Anti-Inflammatory Activities of 5,8,11-<i>cis</i>-Eicosatrienoic Acid

The main eicosanoids inflammatory mediators, prostaglandins and leukotrienes, are both generated from arachidonic acid (AA;20:4 n-6). AA is a member of polyunsaturated fatty acids (PUFAs). Numerous studies have demonstrated that various contents of PUFAs can modulate the inflammatory responses. However, fewer studies have examined n-9PUFAs and their effects on the inflammatory responses. In the present study, the role of 5,8,11-cis-eicosatrienoic acid (ETrA;20:3 n-9, also called Mead acid) in the inflammatory responses has been investigated. The anti-inflammatory activities of ETrA were examined using an in vitro macrophage system and the inhibitory effect was confirmed by western blot analysis for iNOS and COX-2 expressions. The interactions between ETrA and COX-2 protein were simulated to produce a computer modeling protein-ligand complexes and the results suggest a possible mechanism for the effects of ETrA. In this study, we described a significant inhibition of the inflammatory activities initiated by ETrA. Since ETrA is a substance presented in the tissues of young animals, we therefore anticipate that ETrA can be utilized as a natural therapeutic supplement to inhibit inflammatory activities.

Exploring the Environmental Physiology of the Indo-Pacific Reef Coral <em>Seriatopora hystrix</em>with Differential Proteomics

Although reef-building corals are threatened by a number of anthropogenic impacts, certain scleractinian-dinoflagellate (genus Symbiodinium) endosymbioses have proven markedly resilient to environmental change. For instance, corals from upwelling habitats of Southern Taiwan withstand both short- and long-term increases in temperature, potentially due to their routine exposure to highly variable temperature regimes in situ. To gain a greater understanding of the proteomic basis for such acclimatization to unstable environmental conditions, specimens of the Indo-Pacific reef-building coral Seriatopora hystrix Dana 1846 were sampled during a period of stable temperature conditions from 1) a site characterized by frequent upwelling events in Southern Taiwan and 2) a nearby, non-upwelling control site in the Taiwan Strait. Two-dimensional gel electrophoresis followed by sequencing of differentially concentrated proteins with mass spectrometry unveiled significantly more proteins involved in the cellular stress response in coral hosts of the upwelling site. Although such stress protein signatures could be indicative of sub-lethal levels of cellular stress, especially given the relatively higher sediment loads characteristic of the upwelling site, these proteins may, in contrast, have been constitutively maintained at high levels in preparation for large fluctuations in temperature and other abiotic parameters (e.g., nutrient levels) brought upon by upwelling events.

In silico assessment of human health risks caused by cyanotoxins from cyanobacteria

Harmful algal blooms(HABs)that are formed by cyanobacteria have become a serious issue worldwide in recent years.Cyanobacteria can release a type of secondary metabolites called cyanotoxins into aquatic systems which may indirectly or directly provide health risks to the environment and humans.Cyanotoxins provide some of the most powerful natural poisons including potent neurotoxins,hepatotoxins,cytotoxins,and endotoxins that may result in environmental health risks,and long-term morbidity and mortality to animals and humans.In this research,we used the chemcomputational tool Molinspiration for molecular property predictions,Pred-hERG 4.2 web software for cardiac toxicity prediction,and Pred-Skin 2.0 web software for predicting skin sensitization.We are predicting some toxicological aspects of cyanobacteria here using chemcomputational tools with the hypothesis that cyanotoxins are providing a risk to human health.We are using the tool Pred-hERG 4.2 to predict hERG channel blocking potential and the Pred-skin tool to predict skin sensitization due to cyanotoxins.The potential of anatoxin,ambigol,the microcystin group,and lyngbyatoxin A,lyngbyatoxin B,nodularin-R,and saxitoxin were predicted to cause skin sensitization in the final results(consensus model).Anatoxin-a and lyngbyatoxin were predicted to allow GI absorption and blood–brain barrier penetration.Among the 20 predicted cyanotoxins only aeruginosin 103-A,ambigol A,and ambigol were predicted by Pred-hERG 4.2 according to the applicability domain results as potential cardiotoxins with weak or moderate potency.Lyngbyatoxin shows activity through the GPCR ligand and protease,kinase,and enzyme inhibitor.

Gametogenic Cycle, the Spawning Season, First Sexual Maturity, and the Biological Minimum Size in Male Ruditapes philippinarum （Bivalvia： Veneridae） in Western Korea

The male gametogenic cycle, spawning season, first sexual maturity, and the biological minimum size in male Ruditapes philippinarum were investigated by qualitative and quantitative reproductive analyses. In the study of the male gametogenic cycle by qualitative histological analysis, the gametogenic cycle in male individuals can be classified into five successive stages： （1） early active stage, （2） late active stage, （3） ripe stage, （4） partially spawned stage, and （5） spent and inactive stage. Monthly changes in the gonad index in males measured by qualitative analysis showed a similar pattern to the male gametogenic cycle. In the study of the male gametogenic cycle by quantitative statistical analysis, monthly changes in the portions （%） of areas occupied by the testis areas to total tissue areas showed a rapid increase in March, and reached the maximum in May-June. And also monthly changes in the portions （%） of areas occupied by the spermatogenic stages to the testis area showed a maximum in May and gradually decreased from June to October. Therefore, this species showed a unimodal gametogenic cycle during the year, and the number of spawning seasons occurred once per year, from June to October, with a peak spawning between July and August. The percentage at the first sexual maturity of male clams ranging from 15.1-20.0 mm in shell length was 64.7%, and that of all individuals ranging from over 25.1 mm in shell length was 100%. The biological minimum size （shell lengths at 50% of sexual maturity （RMs0）） of male mature clams that was fitted to an exponential equation was 17.16 mm （considered to be 1 year old）. Because harvesting clams less than 17.16 mm in shell length could potentially cause a drastic reduction in recruitment, a measure indicating a prohibitory fishing size should be enacted for adequate fisheries management.

A synthetic biological secondary metabolite,Lycogen^TM,produced and extracted from Rhodobacter sphaeroides WL-APD911 in an optimizatioal scale-up strategy

The optimization of fermentation medium is important for synthetic biological secondary metabolite productions.The effect of rotation speed,inoculum amount,and medium supplements on the cell growth and Lycogen^TM secretion of photobacterium Rhodobacter sphaeroides WL-APD911 was evaluated.The results reveal that a higher rotational speed exhibit a higher cell density,and the increasing in the amount of inoculum amount show a slight augment on the growth of R.sphaeroides WL-APD911.In the case of nitrogen sources adding,Lycogen^TM production was achieved with a 0.5 mM l-lysine supplementation.Moreover,the attention of Tween 80 presented a tremendous increase in the secondary metabolite.Response surface methodology(RSM)exhibited the optimization of medium supplements for Lycogen^TM invention is accomplished at molasses concentration of 10 g/L,yeast extract concentration of 40 g/L,0.3%Tween 80 and NaCl concentration of 5 g/L,respectively.Further,the batch fermentation is carried out in both 5 L and 20 L fermentors to study the scale-up process factors to be adopted.At a 20 L fermentor,Lycogen^TM yields under the optimal culture condition are over 2 times than in the shake flask.The present results provide the Lycogen^TM optimal culture mediums,scale-up procedures and efficient extractions from R.sphaeroides WL-APD911.

Therapeutic effect of Guijiajiao (Colla Carapacis et Plastri) on bone regeneration in rats and zebrafish

OBJECTIVE:To investigate the effect of Guijiajiao(Colla Carapacis et Plastri, CCP), the glue of tortoise shell, on bone regeneration in zebrafish and male Wistar rats.METHODS: In this study, we applied in vitro and in vivo models, tissue section analysis, and quantitative polymerase chain reaction to assess the effects of CCP on bone repair. MG-63 cells were used in alkaline phosphatase(ALP) activity and mineralization assays. Zebrafish and male Wistar rats were used to evaluate the effects of CCP on bone repair in vivo.RESULTS: A simple preparation of CCP promoted osteogenesis in vivo and in vitro, and promoted MG-63 cell proliferation as well as ALP activity and mineralization. In addition, CCP activated Akt and extracellular signaling-regulated kinase pathways and significantly increased the expression of ossification-related genes and proteins such as runt-related transcription factor-2, osteocalcin, and osteopontin. The in vivo results revealed promotion of osteogenesis by immersing zebrafish in CCP for 72 h.An oral dose of 1.25 g/kg CCP significantly improved skull defects in rats, which was accompanied by an increase in serum ALP levels.CONCLUSION: One of the ingredients of Guilu Erxianjiao(tortoise shell and deer horn formula) pro-vides a practical alternative therapy for bone regeneration.

Increased susceptibility of algal symbionts to photo-inhibition resulting from the perturbation of coral gastrodermal membrane trafficking

The stability of cnidarian-dinoflagellate endosymbioses is dependent upon communication between the host gastrodermal cell and the symbionts housed within it. Although the molecular mechanisms remain to be elucidated, existing evidence suggests that the establishment of these endosymbioses may involve the sorting of membrane proteins. The present study examined the role of host gastrodermal membranes in regulating symbiont （genus Symbiodinium） photosynthesis in the stony coral Euphyllia glabrescens. In comparison with the photosynthetic behavior of Symbiodinium in culture, the Symbiodinium populations within isolated symbiotic gastrodermal cells （SGCs） exhibited a significant degree of photo-inhibition, as determined by a decrease in the photochemical efficiency of photosystem II （Fv/Fm）. This photo-inhibition coincided with increases in plasma membrane perturbation and oxidative activity in the SGCs. Membrane trafficking in SGCs was examined using the metabolism of a fluo- rescent lipid analog, N-[5-（5,7-dimethyl boron dipyrromethene difluoride）-l-pentanoyl]-D-erythro-Sphingosylpbosphoryl- choline （BODIPY-Sphingomyelin or BODIPY-SM）. Light irradiation altered both membrane distribution and trafficking of BODIPY-SM, resulting in metabolic changes. Cholesterol depletion of the SGC plasma membranes by methyl-13-cyclodextrin retarded BODIPY-SM degradation and further augmented Symbiodinium photo-inhibition. These results indicate that Symbio- dinium photo-inhibition may be related to perturbation of the host gastrodermal membrane, providing evidence for the pivotal role of host membrane trafficking in the regulation of this environmentally important coral-dinoflagellate endosymbiosis.

Pharmacological potentials of phenolic compounds from Prosopis spp.-a review

The shrub Prosopsis juliflora(Sw.)DC.revealed several medicinal properties due to its different chemical compounds such as alkaloids,flavonoids,terpenoids,saponins and phenolic compounds distributed in different parts of the plant body,such as woody parts(roots,stem,branches and bark)as well as leaves and pollen have been used for the extraction of medically active substances.Prosopsis juliflora containing a diverse group of secondary metabolites has unique and multifactorial medicinal properties.The utilization of this abundant resource provides a viable option for producing bioactive natural products that may serve as lead substances for the chemical and pharmaceutical industries.This review highlights accessible bioactive sources from this plant that are of potential interest for industrial applications.

Antioxidant and Cytotoxic Activities of A Novel Isomeric Molecule(PF5)Obtained from Methanolic Extract of Pleurotus Florida Mushroom

The Pleurotus florida is recognized as a medicinal and edible mushroom and the present study intends to reveal the active isomeric molecules from this mushroom.The P.florida was cultivated using different nutrient supplements:groundnut husk,maize powder,horse gram powder and coconut oil-cake powder.Horse gram supplement showed the higher mushroom yield and henceit was used for the cultivation of P.florida.Methanolic extract of P.florida was found to be efficient in antioxidant activity among ethanol,aqueous,ethyl acetate and hexane extracts.The bioactive fraction 3-methoxy-4-hydroxy cinnamic acid(PF5)was isolated and purified from the methanolic extract of P.florida by column chromatography,thin layer chromatography(TLC)and gas chromatography-mass spectrum(GC-MS)and further it was characterized by Nuclear magnetic resonance(NMR).The PF5 was tested for its DPPH and reducing power assays,and the IC_(50) values were found to be 21.7μg/mL and 105μg/mL,respectively.We found that the cytotoxic effect of 3-methoxy-4-hydroxy cinnamic acid was tested against the lung cancer cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT),sulphorodamine B(SRB)and trypan blue assays which exhibited a higher cytotoxic effect(CTC_(50),645μg/mL).These results suggested that 3-methoxy-4-hydroxy cinnamic acid from P.florida could be explored as a novel and potent natural antioxidant and cancer preventive agent,alternative to existing synthetic molecules.

In-vitro study:Immunomodulatory and cytotoxicity effects of ethanolic leave extracts of Aegle marmelos and Ficus benghalensis

Objective:To assess the immunomodulatory and antibacterial properties of the coastal trees Aegle marmelos(A.marmelos)and Ficus benghalensis(F.benghalensis)by in-vitro methods.Methods:A.marmelos and F.benghalensis leaves were extracted with the solvents di-ethyl ether,ethanol and methanol.The extracts were investigated for antibacterial activity against human pathogenic bacteria and immunomodulatory activity against human peripheral blood mononuclear cells(PBMC),respectively.Results:F.benghalensis ethanol cold extract gave maximum inhibition zones against Escherichia coli NCIM 2931(B2)at 18 mm and enhanced the growth of human PBMC.It was non-toxic to human PBMC shown by the Tryphan blue dye exclusion method,sulforhodamine B and MTT assays.IR phyto-chemical analysis demonstrated the presence of the functional groups:NH,CH_(2),CH_(3),CO,OH,-C-C=O,and C-S.We confirmed the presence of quantifiable amounts of tannins and alkaloids with traces of phenolic compounds by thin layer chromatography analysis.Conclusions:Leaves of A.marmelos and F.benghalensis provide both antibacterial and immunomodulatory properties.

Dust mite allergen-specific immunotherapy increases IL4 DNA methylation and induces Der p-specific T cell tolerance in children with allergic asthma

Allergen-specific immunotherapy(allergen-SIT)is a highly effective treatment for children with allergic asthma(AA),an immune-mediated chronic disease leading to bronchial muscle hypertrophy and airway obstruction in response to specific allergens.T helper cells and secreted cytokines play important roles in the pathogenesis of asthma,and epigenetic modulation controls genes important for T cell development and cytokine expression.This study evaluated T helper cell-secreted cytokines and DNA methylation patterns in children treated with Dermatophagoides pteronyssinus(Der p)allergen-SIT.Our results showed that after Der p challenge,peripheral blood mononuclear cells(PBMCs)from the SIT group,compared with the non-SIT AA group,produced lower levels of IL-4,IL-5 and IL-2.The SIT group,compared with the AA group,exhibited decreased sensitivity to the Der p allergen,concurrent with IL-4 down-modulation due to increased promoter DNA methylation,as estimated in PBMCs.Our results showed that SIT decreased IL-4 and IL-5,and inhibited T cell proliferation,by inhibiting IL-2 production after the specific allergen challenge.These results suggest that decreased IL-2 production and increased IL-4 cytokine promoter methylation is a potential mechanism of Der p-specific allergen desensitization immunotherapy.