Wood mouse(Apodemus sylvaticus)populations are expected to show a peak in autumn in the year after a mast year of sessile oak(Quercus petraea),because stored acorns increase winter survival.In Aust-Agder,South Norway,...Wood mouse(Apodemus sylvaticus)populations are expected to show a peak in autumn in the year after a mast year of sessile oak(Quercus petraea),because stored acorns increase winter survival.In Aust-Agder,South Norway,only 16 of 34 mast years from 1939-2014 were followed by a year with a peak in the wood mouse population.For many of the remaining instances,there rather was a minor peak 2 or 3 years after the mast.In multiple logistic regression models,the probability of a wood mouse population peak after a mast year of sessile oak was positively related to a snow-corrected temperature index of the previous winter and negatively to a small rodent population index of the previous autumn.The present study thus supports the hypothesis that longer periods with snow-free ground and subzero temperatures negatively affect wood mouse winter survival.Because it may be difficult for wood mice to survive on a diet consisting of acorns alone,the negative relationship with the rodent population index of the previous year is most likely caused by an over-exploitation of necessary alternative food resources,such as other plant seeds and arthropods.Stored acorns not utilized during one winter are assumed to benefit wood mice in a succeeding winter,giving a delayed population peak relative to the mast year.展开更多
Aims Understanding fluctuations in plant reproductive investment can constitute a key challenge in ecology,conservation and manage-ment.Masting events of trees(i.e.the intermittent and synchronous production of abunda...Aims Understanding fluctuations in plant reproductive investment can constitute a key challenge in ecology,conservation and manage-ment.Masting events of trees(i.e.the intermittent and synchronous production of abundant seeding material)is an extreme example of such fluctuations.Our objective was to establish the degree of spa-tial and temporal synchrony in common four masting tree species in boreal Finland and account for potential causal drivers of these patterns.Methods We investigated the spatial intraspecific and temporal interspe-cific fluctuations in annual seed production of four tree species in Finland,silver birch Betula pendula Roth,downy birch Betula pubescens Ehrh.,Norway spruce Picea abies(L.)H.Karst.and row-anberry Sorbus aucuparia L.We also tested to see whether varia-tions in seed production were linked to annual weather conditions.Seeding abundance data were derived from tens of stands per spe-cies across large spatial scales within Finland during 1979 to 2014(for rowanberries only 1986 to 2014).Important Findings All species showed spatial synchrony in seed production at scales up to 1000 km.Annual estimates of seed production were strongly correlated between species.Spring and summer temperatures explained most variation in crop sizes of tree species with 0-to 2-year time lags,whereas rainfall had relatively little influence.Warm weather during flowering(May temperature)in the flower-ing year(Year t)and 2 years before(t−2)were correlated with seed production.However,high May temperatures during the previous year(t−1)adversely affected seed production.Summer tempera-tures in Year t−1 was positively correlated with seed production,likely because this parameter enhances the development of flower primordials,but the effect was negative with a time lag of 2 years.The negative feedback in temperature coefficients is also likely due to patterns of resource allocation,as abundant flowering and seed production in these species is thought to reduce the sub-sequent initiation of potential new flower buds.Since the most important weather variables also showed spatial correlation up to 1000 km,weather parameters likely explain much of the spatial and temporal synchrony in seed production of these four studied tree species.展开更多
Acorn production in oaks(Quercus spp.)shows considerable inter-annual variation,known as masting.The effects of pollen sourced from trees within or outside the stand on acorn production were investigated in pedunculat...Acorn production in oaks(Quercus spp.)shows considerable inter-annual variation,known as masting.The effects of pollen sourced from trees within or outside the stand on acorn production were investigated in pedunculate oak(Quercus robur L.)in an ancient mixed woodland during two moderate masting years.Comparisons were made between natural pollination,hand pollinations with out-of-stand pollen,in-stand pollen or a 1:1 combination of the two pollen sources,and for bagged flowers left unpollinated.After all treatments,>85%of the flowers or developing acorns were aborted between May and August of both years.When flowers were protected with pollen bags and no pollen added,no acorns were produced.In contrast,hand pollination with out-of-stand pollen produced the most acorns both years and significantly more than within-stand pollen or natural pollination in 2022.Hand pollination with out-of-stand or within-stand pollen provided significantly more acorns than natural pollination in 2023.In 2022,hand pollination with a 1:1 mixture of out-of-stand and within-stand pollen yielded an intermediate number of mature acorns between those for the out-of-stand and within-stand pollination treatments.The study provides clear evidence of maternal choice during acorn development in pedunculate oak and of the benefits of pollen supplementation.It also confirms that pedunculate oak is a fruit-maturation masting species;abortion of pollinated flowers and immature acorns determines a mast year(rather than the number of flowers produced)at this site.展开更多
Droughts impact forests by influencing various processes such as canopy greenness,tree growth,and reproduction,but most studies have only examined a few of these processes.More comprehensive assessments of forest resp...Droughts impact forests by influencing various processes such as canopy greenness,tree growth,and reproduction,but most studies have only examined a few of these processes.More comprehensive assessments of forest responses to climate variability and water shortages are needed to improve forecasts of post-drought dynamics.Iberian forests are well-suited for evaluating these effects because they experience diverse climatic conditions and are dominated by various conifer and broadleaf species,many of which exhibit masting.We assessed how greenness,evaluated using the normalized difference vegetation index(NDVI),tree radial growth,and seed or cone production responded to drought in five tree species(three conifers:silver fir(Abies alba),Scots pine(Pinus sylvestris),and stone pine(Pinus pinea);two broadleaves:European beech(Fagus sylvatica)and holm oak(Quercus ilex)inhabiting sites with different aridity.We correlated these data with the standardized precipitation evapotranspiration index(SPEI)using the climate window analysis(climwin)package,which identifies the most relevant climate window.Drought constrained growth more than greenness and seed or cone production.Dry conditions led to high seed or cone production in species found in cool,moist sites(silver fir,beech,and Scots pine).We also found negative associations of cone production with summer SPEI in the drought-tolerant stone pine,which showed lagged growth-cone negative correlations.However,in the seasonally dry holm oak forests,severe droughts constrained both growth and acorn production,leading to a positive correlation between these variables.Drought impacts on greenness,growth,seed,and cone production depended on species phenology and site aridity.A negative correlation between growth and reproduction does not necessarily indicate trade-offs,as both may be influenced by similar climatic factors.展开更多
To investigate the mechanisms of apigenin(API)and proanthocyanidins(PC)in soothing sensitive skin(SS),a mast cell degranulation model was established by stimulating RBL-2H3 cells with the calcium ionophore A23187.Base...To investigate the mechanisms of apigenin(API)and proanthocyanidins(PC)in soothing sensitive skin(SS),a mast cell degranulation model was established by stimulating RBL-2H3 cells with the calcium ionophore A23187.Based on the combinatorial experiments,it was found that when API and PC were combined at the molar ratios of 4∶1 and 2∶1,they exhibited the antagonistic effects on histamine release(combination index CI>1);when they are combined at the molar ratios of 1∶1,1∶2 or 1∶4,they showed the synergistic effects on histamine release(CI<1).Among them,the combination of API and PC at a molar ratio of 1∶1 showed the better potent synergistic antihistamine release effect(CI=0.70).Histamine is a hallmark of the mast cell degranulation,consequently,the combination of API and PC at a molar ratio of 1∶1 yields the better efficiency in inhibiting the mast cell degranulation with the lowest IC_(50)value.Compared to the utilization of API or PC alone,the IC_(50)value was reduced by 11.150 and 6.503μmol/L,respectively.Compared to the positive control paeonol(PA),the treatment with the combination significantly reduced theβ-hex secretion,decreased the F-actin cytoskeleton rearrangement,and markedly suppressed the release of TNF-α,IL-4,and MCP-1.Further studies on the signaling pathways related to the mast cell degranulation indicated that the combination effectively inhibited the intracellular Ca^(2+)influx and significantly suppressed the phosphorylation of calmodulin-dependent protein kinase(CaMK)and phospholipase C/protein kinase C(PLC/PKC).In summary,the combination of API and PC at a molar ratio of 1∶1 exhibited the better synergistic antagonistic effect on the histamine release,inhibited the mast cell degranulation model activation by reducing Ca^(2+)influx and inhibiting the activation of Ca^(2+)/CaMK and PLC/PKC pathways,stabilized the cell membranes,regulated the inflammatory factor secretion,and exerted an effect in alleviating sensitive skin.展开更多
Objective The present study evaluated the effects of deep acupuncture at Weizhong acupoint(BL40)on bladder function and brain activity in a rat model of overactive bladder(OAB),and investigated the possible mechanisms...Objective The present study evaluated the effects of deep acupuncture at Weizhong acupoint(BL40)on bladder function and brain activity in a rat model of overactive bladder(OAB),and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture.Methods Adult female Sprague-Dawley rats were randomly divided into six groups,comprising a control group,model group,group treated with deep acupuncture at BL40,group treated with shallow acupuncture at BL40,group treated with acupuncture at non-acupoint next to BL40,and group treated with acupuncture at Xuanzhong(GB39).Urodynamic evaluation was used to observe the urination,and functional magnetic resonance imaging was used to observe the brain activation.The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay,and the mechanism was verified by stabilizing mast cells(MCs)or blocking tibial nerve.Results Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex(M1),periaquaductal gray matter(PAG),and pontine micturition center(PMC).It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC.Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes.Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine,substance P,and histamine in the tissues around BL40.Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats.Conclusion Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve,thereby regulating the activation of the brain area that controls the lower urinary tract.展开更多
Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesi...Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture.This paper investigated the role of acupuncture needle surface textures on acupuncture’s analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation.Methods Four types of acupuncture needles with different surface textures(the lined needle,circle needle,sandpaper needle,and threaded needle)were designed.Additionally,the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation.To perform acupuncture analgesia experiments,four experimental acupuncture needles and a normal needle were inserted into the Zusanli(ST36)acupoint of rats with inflammatory pain.By comparing the force and torque and the analgesic efficacy of the different acupuncture needles,these experiments tested the role of acupuncture needle body texture on acupuncture analgesia.Results The analgesic effects of different acupuncture needle body textures varied.Specifically,the force required to penetrate the skin with the lined needle was not greater than that for the normal needle;however,the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion.Additionally,the torque of the lined needle reached 2×10^(-4)N·m under twisting manipulation,which was four times greater the torque of a normal needle(5×10^(-5)N·m).Furthermore,the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle.Conclusion Optimizing the texture of acupuncture needles can enhance acupuncture analgesia.The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle;it was also linked to variable analgesic effects.This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy.展开更多
Polyphenol is a kind of natural active substance with immunoregulatory activity.In this study,the immunoregulatory activities of Sargassum carpophyllum polyphenol(SCP)on the allergic reactions induced by shrimp tropom...Polyphenol is a kind of natural active substance with immunoregulatory activity.In this study,the immunoregulatory activities of Sargassum carpophyllum polyphenol(SCP)on the allergic reactions induced by shrimp tropomyosin were investigated.As the results,the SCP performed high hyaluronidase inhibition ability,which even greater than sodium chromoglycate(an anti-allergic medicine).SCP was able to affect the allergic reactions of RAW 264.7 macrophage cells via regulating the nuclear factor kappa-B(NF-κB),c-Jun N-terminal kinase 1/2(JNK1/2),extracellular regulated protein kinase 1/2(Erk1/2)and p38 mitogen-activated protein kinase(MAPK)cellular signaling pathways,weakened the degranulation degree and secretion of interleukin-4(IL-4),tumor necrosis factor-α(TNF-α)and histamine,and promoted the secretion of interleukin-10(IL-10)from RBL-2H3 mast cells.In BALB/c mouse model assay,after gavage of SCP,the mouse allergic symptoms got significantly alleviated,the cytokine(IL-4,IL-10 and interferon-γ(IFN-γ))secretion of mouse spleen lymphocytes were significantly declined and the allergic lung damage was relieved,which indicated SCP performed strong both in vitro and in vivo anti-allergic functions.Therefore,SCP could serve as candidate anti-allergic bioactive substances for shrimp induced allergy via immunoregulation.展开更多
Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion a...Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion after epicutaneous sensitization can trigger severe allergic responses.Therefore,this study focused on the initial stages of allergic symptoms before they become severe and investigated the mechanisms underlying food ingestion-induced mild itching following epicutaneous sensitization.Methods:Female mice were epicutaneously sensitized with ovalbumin(OVA).Scratching behavior was recorded,and serum and tissue samples were collected.Levels of OVA-specific immunoglobulin(Ig)E/IgG1,histamine,and mast cell protease-1(MCPT-1)were measured by ELISA.Histological analysis of skin tissues and immune cell infiltration was performed via staining.Results:OVA challenge following epicutaneous sensitization induced mild itching in the OVA group.Scratching behavior peaked between 1 and 2 h and persisted for 8 h before returning to baseline.This itching was accompanied by dynamic fluctuations in OVA-specific IgE and IgG1,histamine,and MCPT-1 levels.Histological analysis revealed increased epidermal thickness and granulocytic infiltration,particularly of mast cells and eosinophils,within 2 h of OVA challenge.Mast cell and eosinophil migration into the skin tissues was significant,with eosinophil migration into the dermis persisted despite normalization of histamine levels and mast cell degranulation.These results suggest that mast cells and eosinophils play significant roles even in mild itching.Conclusion:This study provides insights into the early immune responses involved in food allergies,contributing to a better understanding of how mild symptoms can progress to more severe reactions.展开更多
Hereditary alpha tryptasemia was first described in 2016 and is the most common(up to 72%)cause of elevated serum basal tryptase(TPS).The clinical presentation of this condition,which is caused by copy number gains in...Hereditary alpha tryptasemia was first described in 2016 and is the most common(up to 72%)cause of elevated serum basal tryptase(TPS).The clinical presentation of this condition,which is caused by copy number gains in the TPSAB1 gene encoding serumαTPS,is variable for each patient.Some patients are asymptomatic,whereas in others,especially those with increased mast cell activation,it has been associated with a higher risk of anaphylaxis.Better characterization of this entity is important to identify atrisk patients and to develop new treatment strategies.This review provided an overview of hereditary alpha tryptasemia and increased awareness of this condition by discussing the current information in the literature.展开更多
Wei et al reported a comprehensive single-cell transcriptomic analysis of the small intestine during early acute pancreatitis(AP)and identified activated mast cells and their secretion of CCL5 as pivotal factors drivi...Wei et al reported a comprehensive single-cell transcriptomic analysis of the small intestine during early acute pancreatitis(AP)and identified activated mast cells and their secretion of CCL5 as pivotal factors driving gut barrier dysfunction.By integrating scRNA-seq with in vitro and in vivo functional assays,this study advances our understanding of the cellular and molecular events underlying AP-associated intestinal injury.In this commentary,I highlight the methodological innovations employed in the study,contextualize its findings in the literature,and propose directions for future research.As an avid researcher in single-cell sequen-cing,I approached this letter with a spirit of academic inquiry and welcome any further discussion or corrections that may enhance my understanding.展开更多
BACKGROUND Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis(AP).Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood.AIM To explore th...BACKGROUND Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis(AP).Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood.AIM To explore the biological processes and mechanisms of intestinal injury associated with AP,and to find potential targets for early prevention or treatment of intestinal barrier injury.METHODS This study utilized single-cell RNA sequencing of the small intestine,alongside in vitro and in vivo experiments,to examine intestinal barrier function homeostasis during the early stages of AP and explore involved biological processes and potential mechanisms.RESULTS Seventeen major cell types and 33232 cells were identified across all samples,including normal,AP1(4x caerulein injections,animals sacrificed 2 h after the last injection),and AP2(8x caerulein injections,animals sacrificed 4 h after the last injection).An average of 980 genes per cell was found in the normal intestine,compared to 927 in the AP1 intestine and 1382 in the AP2 intestine.B cells,dendritic cells,mast cells(MCs),and monocytes in AP1 and AP2 showed reduced numbers compared to the normal intestine.Enterocytes,brush cells,enteroendocrine cells,and goblet cells maintained numbers similar to the normal intestine,while cytotoxic T cells and natural killer(NK)cells increased.Enterocytes in early AP exhibited elevated programmed cell death and intestinal barrier dysfunction but retained absorption capabilities.Cytotoxic T cells and NK cells showed enhanced pathogen-fighting abilities.Activated MCs,secreted chemokine(C-C motif)ligand 5(CCL5),promoted neutrophil and macrophage infiltration and contributed to barrier dysfunction.CONCLUSION These findings enrich our understanding of biological processes and mechanisms in AP-associated intestinal injury,suggesting that CCL5 from MCs is a potential target for addressing dysfunction.展开更多
[Objectives]To observe the effects of chloramphenicol prednisone liniment on anti-inflammatory and anti-pruritic responses and skin barrier function in an acute eczema mouse model and explore its potential underlying ...[Objectives]To observe the effects of chloramphenicol prednisone liniment on anti-inflammatory and anti-pruritic responses and skin barrier function in an acute eczema mouse model and explore its potential underlying mechanism.[Methods]Twenty-four female SPF-grade ICR mice were randomly and equally assigned to three groups:the blank control group,the acute eczema group,and the chloramphenicol prednisone liniment group according to the random number table method,with 8 mice per group.Except for the blank control group,the acute eczema model was established by applying 2,4-dinitrochlorobenzene(DNCB)to the right dorsal area.On day 10(d10),0.1 mL of normal saline was administered to the modeling site in both the blank control group and the acute eczema group,whereas chloramphenicol prednisone liniment was applied to the positive drug group.Medication was applied twice daily in all three groups for a total duration of 14 d.Sixty minutes following the final administration of the drug,the development of eczema in mice was visually assessed,and the severity of skin lesions was scored.Trans-epidermal water loss(TEWL)was measured using a multifunctional skin tester.Experiments inducing and alleviating pruritus were performed to compare the frequency of mice licking their bodies,the latency period before pruritus onset,and the duration of pruritus episodes.Levels of histamine and substance P(SP)in the lesion tissues were quantified using enzyme-linked immunosorbent assay(ELISA).[Results]Compared to the acute eczema group,the chloramphenicol prednisone liniment group exhibited a prolonged latency period of pruritus,an increased inhibition rate,and a shortened duration of pruritus.Additionally,there was a significant reduction in the frequency of mice licking their bodies,as well as in six eczema severity indicators:redness and swelling,scratch marks,papules,blisters,exudation or erosion at the lesion site,and the degree of skin swelling.Furthermore,levels of TEWL,histamine,and SP were also significantly decreased(P<0.05).[Conclusions]Chloramphenicol prednisone liniment exhibits anti-inflammatory and anti-pruritic properties.Its mechanism of action may involve the inhibition of mast cell activation within the lesion tissues of eczema model mice,thereby reducing the release of histamine and other active substances.This process alleviates inflammatory damage associated with eczema and contributes to the restoration of skin barrier function.展开更多
BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)cortic...BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.展开更多
Mast cells(MCs)under stress conditions contribute to the development of irritable bowel syndrome(IBS),yet their precise mechanisms in IBS remain unclear.AIM To investigate the role of MC-derived thymosinβ4(Tβ4)in st...Mast cells(MCs)under stress conditions contribute to the development of irritable bowel syndrome(IBS),yet their precise mechanisms in IBS remain unclear.AIM To investigate the role of MC-derived thymosinβ4(Tβ4)in stress-induced intestinal barrier dysfunction.METHODS The colonic mucus Tβ4 levels in IBS patients were determined and their effects on the epithelial barrier were assessed in vitro and in vivo.Specifically,rats genetically deficient in Tβ4(Tβ4^(-/-))or mice deficient in MCs(Kit^(w-sh/w-sh))were used to observe the effects of reintroducing Tβ4 or wild-type peritoneal MCs(wt-PMCs)into these animals.Additionally,the regulatory mechanism underlying Tβ4 secretion in MCs was investigated.RESULTS We demonstrated that high levels of Tβ4 in IBS mucus and intestinal MCs mediate stress-associated disruptive changes to the epithelial barrier.Moreover,Tβ4 treatment of wild-type or MC-deficient Kit^(w-sh/w-sh)mice caused a reduction in tight junction proteins and the interleukin 22 receptor A1(IL22RA1)/Reg3γcascade,but an increase in myosin light chain kinase.Furthermore,Tβ4^(-/-)rats were resistant to stress,though reintroduction of Tβ4 or wt-PMCs restored stress or corticotropin-releasing hormone(CRH)-induced barrier disturbance.Consistently,Tβ4 release from MCs was dependent on the CRH receptor 1,but not degranulation.The effect of Tβ4 was accompanied by IL22RA1/Janus kinase 1(JAK1)/signal transducer and activation of transcription 3(STAT3)pathway inhibition,suggesting a mechanism for physical and immune barrier suppression.CONCLUSION Collectively,these results suggest that Tβ4,which is abundant in IBS mucus and the secretome of MCs,plays a crucial role in the pathogenesis of IBS via IL22RA1/JAK1/STAT3 signaling,with potential implications for diagnostic and therapeutic targeting.展开更多
文摘Wood mouse(Apodemus sylvaticus)populations are expected to show a peak in autumn in the year after a mast year of sessile oak(Quercus petraea),because stored acorns increase winter survival.In Aust-Agder,South Norway,only 16 of 34 mast years from 1939-2014 were followed by a year with a peak in the wood mouse population.For many of the remaining instances,there rather was a minor peak 2 or 3 years after the mast.In multiple logistic regression models,the probability of a wood mouse population peak after a mast year of sessile oak was positively related to a snow-corrected temperature index of the previous winter and negatively to a small rodent population index of the previous autumn.The present study thus supports the hypothesis that longer periods with snow-free ground and subzero temperatures negatively affect wood mouse winter survival.Because it may be difficult for wood mice to survive on a diet consisting of acorns alone,the negative relationship with the rodent population index of the previous year is most likely caused by an over-exploitation of necessary alternative food resources,such as other plant seeds and arthropods.Stored acorns not utilized during one winter are assumed to benefit wood mice in a succeeding winter,giving a delayed population peak relative to the mast year.
基金A.L.received financial support from the Academy of Finland(grant no.275606).
文摘Aims Understanding fluctuations in plant reproductive investment can constitute a key challenge in ecology,conservation and manage-ment.Masting events of trees(i.e.the intermittent and synchronous production of abundant seeding material)is an extreme example of such fluctuations.Our objective was to establish the degree of spa-tial and temporal synchrony in common four masting tree species in boreal Finland and account for potential causal drivers of these patterns.Methods We investigated the spatial intraspecific and temporal interspe-cific fluctuations in annual seed production of four tree species in Finland,silver birch Betula pendula Roth,downy birch Betula pubescens Ehrh.,Norway spruce Picea abies(L.)H.Karst.and row-anberry Sorbus aucuparia L.We also tested to see whether varia-tions in seed production were linked to annual weather conditions.Seeding abundance data were derived from tens of stands per spe-cies across large spatial scales within Finland during 1979 to 2014(for rowanberries only 1986 to 2014).Important Findings All species showed spatial synchrony in seed production at scales up to 1000 km.Annual estimates of seed production were strongly correlated between species.Spring and summer temperatures explained most variation in crop sizes of tree species with 0-to 2-year time lags,whereas rainfall had relatively little influence.Warm weather during flowering(May temperature)in the flower-ing year(Year t)and 2 years before(t−2)were correlated with seed production.However,high May temperatures during the previous year(t−1)adversely affected seed production.Summer tempera-tures in Year t−1 was positively correlated with seed production,likely because this parameter enhances the development of flower primordials,but the effect was negative with a time lag of 2 years.The negative feedback in temperature coefficients is also likely due to patterns of resource allocation,as abundant flowering and seed production in these species is thought to reduce the sub-sequent initiation of potential new flower buds.Since the most important weather variables also showed spatial correlation up to 1000 km,weather parameters likely explain much of the spatial and temporal synchrony in seed production of these four studied tree species.
基金supported by Future Trees TrustThe Patsy Wood Trust+2 种基金Scottish Forestry TrustAitchinson Tait TrustAction Oak
文摘Acorn production in oaks(Quercus spp.)shows considerable inter-annual variation,known as masting.The effects of pollen sourced from trees within or outside the stand on acorn production were investigated in pedunculate oak(Quercus robur L.)in an ancient mixed woodland during two moderate masting years.Comparisons were made between natural pollination,hand pollinations with out-of-stand pollen,in-stand pollen or a 1:1 combination of the two pollen sources,and for bagged flowers left unpollinated.After all treatments,>85%of the flowers or developing acorns were aborted between May and August of both years.When flowers were protected with pollen bags and no pollen added,no acorns were produced.In contrast,hand pollination with out-of-stand pollen produced the most acorns both years and significantly more than within-stand pollen or natural pollination in 2022.Hand pollination with out-of-stand or within-stand pollen provided significantly more acorns than natural pollination in 2023.In 2022,hand pollination with a 1:1 mixture of out-of-stand and within-stand pollen yielded an intermediate number of mature acorns between those for the out-of-stand and within-stand pollination treatments.The study provides clear evidence of maternal choice during acorn development in pedunculate oak and of the benefits of pollen supplementation.It also confirms that pedunculate oak is a fruit-maturation masting species;abortion of pollinated flowers and immature acorns determines a mast year(rather than the number of flowers produced)at this site.
基金funded by the Science and Innovation Ministry of Spain(projects AGL 2012-33465,AGL 2016-76463-P,PID 2021-123675OB-C43,and TED 2021-129770B-C21)support by Margarita Salas postdoctoral fellowship(reference RCMS-22-G1T6IW-17-NLHJ80)of the Universidad Politécnica de Madrid
文摘Droughts impact forests by influencing various processes such as canopy greenness,tree growth,and reproduction,but most studies have only examined a few of these processes.More comprehensive assessments of forest responses to climate variability and water shortages are needed to improve forecasts of post-drought dynamics.Iberian forests are well-suited for evaluating these effects because they experience diverse climatic conditions and are dominated by various conifer and broadleaf species,many of which exhibit masting.We assessed how greenness,evaluated using the normalized difference vegetation index(NDVI),tree radial growth,and seed or cone production responded to drought in five tree species(three conifers:silver fir(Abies alba),Scots pine(Pinus sylvestris),and stone pine(Pinus pinea);two broadleaves:European beech(Fagus sylvatica)and holm oak(Quercus ilex)inhabiting sites with different aridity.We correlated these data with the standardized precipitation evapotranspiration index(SPEI)using the climate window analysis(climwin)package,which identifies the most relevant climate window.Drought constrained growth more than greenness and seed or cone production.Dry conditions led to high seed or cone production in species found in cool,moist sites(silver fir,beech,and Scots pine).We also found negative associations of cone production with summer SPEI in the drought-tolerant stone pine,which showed lagged growth-cone negative correlations.However,in the seasonally dry holm oak forests,severe droughts constrained both growth and acorn production,leading to a positive correlation between these variables.Drought impacts on greenness,growth,seed,and cone production depended on species phenology and site aridity.A negative correlation between growth and reproduction does not necessarily indicate trade-offs,as both may be influenced by similar climatic factors.
文摘To investigate the mechanisms of apigenin(API)and proanthocyanidins(PC)in soothing sensitive skin(SS),a mast cell degranulation model was established by stimulating RBL-2H3 cells with the calcium ionophore A23187.Based on the combinatorial experiments,it was found that when API and PC were combined at the molar ratios of 4∶1 and 2∶1,they exhibited the antagonistic effects on histamine release(combination index CI>1);when they are combined at the molar ratios of 1∶1,1∶2 or 1∶4,they showed the synergistic effects on histamine release(CI<1).Among them,the combination of API and PC at a molar ratio of 1∶1 showed the better potent synergistic antihistamine release effect(CI=0.70).Histamine is a hallmark of the mast cell degranulation,consequently,the combination of API and PC at a molar ratio of 1∶1 yields the better efficiency in inhibiting the mast cell degranulation with the lowest IC_(50)value.Compared to the utilization of API or PC alone,the IC_(50)value was reduced by 11.150 and 6.503μmol/L,respectively.Compared to the positive control paeonol(PA),the treatment with the combination significantly reduced theβ-hex secretion,decreased the F-actin cytoskeleton rearrangement,and markedly suppressed the release of TNF-α,IL-4,and MCP-1.Further studies on the signaling pathways related to the mast cell degranulation indicated that the combination effectively inhibited the intracellular Ca^(2+)influx and significantly suppressed the phosphorylation of calmodulin-dependent protein kinase(CaMK)and phospholipase C/protein kinase C(PLC/PKC).In summary,the combination of API and PC at a molar ratio of 1∶1 exhibited the better synergistic antagonistic effect on the histamine release,inhibited the mast cell degranulation model activation by reducing Ca^(2+)influx and inhibiting the activation of Ca^(2+)/CaMK and PLC/PKC pathways,stabilized the cell membranes,regulated the inflammatory factor secretion,and exerted an effect in alleviating sensitive skin.
基金supported by grants from the Shanghai Science and Technology Commission(No.21ZR1461000)Shanghai Municipal Health Commission(No.ZY[2021–2023]−0204).
文摘Objective The present study evaluated the effects of deep acupuncture at Weizhong acupoint(BL40)on bladder function and brain activity in a rat model of overactive bladder(OAB),and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture.Methods Adult female Sprague-Dawley rats were randomly divided into six groups,comprising a control group,model group,group treated with deep acupuncture at BL40,group treated with shallow acupuncture at BL40,group treated with acupuncture at non-acupoint next to BL40,and group treated with acupuncture at Xuanzhong(GB39).Urodynamic evaluation was used to observe the urination,and functional magnetic resonance imaging was used to observe the brain activation.The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay,and the mechanism was verified by stabilizing mast cells(MCs)or blocking tibial nerve.Results Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex(M1),periaquaductal gray matter(PAG),and pontine micturition center(PMC).It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC.Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes.Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine,substance P,and histamine in the tissues around BL40.Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats.Conclusion Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve,thereby regulating the activation of the brain area that controls the lower urinary tract.
基金funded by National Natural Science Foundation of China(No.12172092,82174488,and 82305416)Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function(No.21DZ2271800)+1 种基金Shanghai Municipal Science and Technology Commission(No.23YF1418300)Scientific Research Project on Traditional Chinese Medicine of Shanghai Municipal Health Commission—Youth Guidance Category(No.2022QN018).
文摘Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture.This paper investigated the role of acupuncture needle surface textures on acupuncture’s analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation.Methods Four types of acupuncture needles with different surface textures(the lined needle,circle needle,sandpaper needle,and threaded needle)were designed.Additionally,the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation.To perform acupuncture analgesia experiments,four experimental acupuncture needles and a normal needle were inserted into the Zusanli(ST36)acupoint of rats with inflammatory pain.By comparing the force and torque and the analgesic efficacy of the different acupuncture needles,these experiments tested the role of acupuncture needle body texture on acupuncture analgesia.Results The analgesic effects of different acupuncture needle body textures varied.Specifically,the force required to penetrate the skin with the lined needle was not greater than that for the normal needle;however,the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion.Additionally,the torque of the lined needle reached 2×10^(-4)N·m under twisting manipulation,which was four times greater the torque of a normal needle(5×10^(-5)N·m).Furthermore,the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle.Conclusion Optimizing the texture of acupuncture needles can enhance acupuncture analgesia.The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle;it was also linked to variable analgesic effects.This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy.
基金financial support from National Natural Science Foundation of China(32102091)Fujian Province Specialized Project of Promoting High-Quality Development of Marine and Fishery Industry(FJHYF-L-2023-26)+4 种基金Shandong Provincial Natural Science Foundation(ZR2021QC086)China Postdoctoral Science Foundation(2021M693026)Postdoctoral Innovation Project of Shandong Province(862105033022)Qingdao Postdoctoral Applied Research Project(862105040045)Research Funding of Ocean University of China(862001013187).
文摘Polyphenol is a kind of natural active substance with immunoregulatory activity.In this study,the immunoregulatory activities of Sargassum carpophyllum polyphenol(SCP)on the allergic reactions induced by shrimp tropomyosin were investigated.As the results,the SCP performed high hyaluronidase inhibition ability,which even greater than sodium chromoglycate(an anti-allergic medicine).SCP was able to affect the allergic reactions of RAW 264.7 macrophage cells via regulating the nuclear factor kappa-B(NF-κB),c-Jun N-terminal kinase 1/2(JNK1/2),extracellular regulated protein kinase 1/2(Erk1/2)and p38 mitogen-activated protein kinase(MAPK)cellular signaling pathways,weakened the degranulation degree and secretion of interleukin-4(IL-4),tumor necrosis factor-α(TNF-α)and histamine,and promoted the secretion of interleukin-10(IL-10)from RBL-2H3 mast cells.In BALB/c mouse model assay,after gavage of SCP,the mouse allergic symptoms got significantly alleviated,the cytokine(IL-4,IL-10 and interferon-γ(IFN-γ))secretion of mouse spleen lymphocytes were significantly declined and the allergic lung damage was relieved,which indicated SCP performed strong both in vitro and in vivo anti-allergic functions.Therefore,SCP could serve as candidate anti-allergic bioactive substances for shrimp induced allergy via immunoregulation.
基金supported by JSPS KAKENHI Grant Number(22K11779).
文摘Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion after epicutaneous sensitization can trigger severe allergic responses.Therefore,this study focused on the initial stages of allergic symptoms before they become severe and investigated the mechanisms underlying food ingestion-induced mild itching following epicutaneous sensitization.Methods:Female mice were epicutaneously sensitized with ovalbumin(OVA).Scratching behavior was recorded,and serum and tissue samples were collected.Levels of OVA-specific immunoglobulin(Ig)E/IgG1,histamine,and mast cell protease-1(MCPT-1)were measured by ELISA.Histological analysis of skin tissues and immune cell infiltration was performed via staining.Results:OVA challenge following epicutaneous sensitization induced mild itching in the OVA group.Scratching behavior peaked between 1 and 2 h and persisted for 8 h before returning to baseline.This itching was accompanied by dynamic fluctuations in OVA-specific IgE and IgG1,histamine,and MCPT-1 levels.Histological analysis revealed increased epidermal thickness and granulocytic infiltration,particularly of mast cells and eosinophils,within 2 h of OVA challenge.Mast cell and eosinophil migration into the skin tissues was significant,with eosinophil migration into the dermis persisted despite normalization of histamine levels and mast cell degranulation.These results suggest that mast cells and eosinophils play significant roles even in mild itching.Conclusion:This study provides insights into the early immune responses involved in food allergies,contributing to a better understanding of how mild symptoms can progress to more severe reactions.
文摘Hereditary alpha tryptasemia was first described in 2016 and is the most common(up to 72%)cause of elevated serum basal tryptase(TPS).The clinical presentation of this condition,which is caused by copy number gains in the TPSAB1 gene encoding serumαTPS,is variable for each patient.Some patients are asymptomatic,whereas in others,especially those with increased mast cell activation,it has been associated with a higher risk of anaphylaxis.Better characterization of this entity is important to identify atrisk patients and to develop new treatment strategies.This review provided an overview of hereditary alpha tryptasemia and increased awareness of this condition by discussing the current information in the literature.
基金Supported by the Top-level Talents Support Program of Yangzhou University“Lv Yang Jin Feng”Outstanding Doctor of YangzhouNatural Science Foundation of Jiangsu Province,No.BK20240907。
文摘Wei et al reported a comprehensive single-cell transcriptomic analysis of the small intestine during early acute pancreatitis(AP)and identified activated mast cells and their secretion of CCL5 as pivotal factors driving gut barrier dysfunction.By integrating scRNA-seq with in vitro and in vivo functional assays,this study advances our understanding of the cellular and molecular events underlying AP-associated intestinal injury.In this commentary,I highlight the methodological innovations employed in the study,contextualize its findings in the literature,and propose directions for future research.As an avid researcher in single-cell sequen-cing,I approached this letter with a spirit of academic inquiry and welcome any further discussion or corrections that may enhance my understanding.
基金Supported by National Natural Science Foundation of China,No.82300739Hunan Provincial Natural Science Foundation,No.2023JJ40821Changsha Natural Science Foundation,No.kq2208308.
文摘BACKGROUND Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis(AP).Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood.AIM To explore the biological processes and mechanisms of intestinal injury associated with AP,and to find potential targets for early prevention or treatment of intestinal barrier injury.METHODS This study utilized single-cell RNA sequencing of the small intestine,alongside in vitro and in vivo experiments,to examine intestinal barrier function homeostasis during the early stages of AP and explore involved biological processes and potential mechanisms.RESULTS Seventeen major cell types and 33232 cells were identified across all samples,including normal,AP1(4x caerulein injections,animals sacrificed 2 h after the last injection),and AP2(8x caerulein injections,animals sacrificed 4 h after the last injection).An average of 980 genes per cell was found in the normal intestine,compared to 927 in the AP1 intestine and 1382 in the AP2 intestine.B cells,dendritic cells,mast cells(MCs),and monocytes in AP1 and AP2 showed reduced numbers compared to the normal intestine.Enterocytes,brush cells,enteroendocrine cells,and goblet cells maintained numbers similar to the normal intestine,while cytotoxic T cells and natural killer(NK)cells increased.Enterocytes in early AP exhibited elevated programmed cell death and intestinal barrier dysfunction but retained absorption capabilities.Cytotoxic T cells and NK cells showed enhanced pathogen-fighting abilities.Activated MCs,secreted chemokine(C-C motif)ligand 5(CCL5),promoted neutrophil and macrophage infiltration and contributed to barrier dysfunction.CONCLUSION These findings enrich our understanding of biological processes and mechanisms in AP-associated intestinal injury,suggesting that CCL5 from MCs is a potential target for addressing dysfunction.
文摘[Objectives]To observe the effects of chloramphenicol prednisone liniment on anti-inflammatory and anti-pruritic responses and skin barrier function in an acute eczema mouse model and explore its potential underlying mechanism.[Methods]Twenty-four female SPF-grade ICR mice were randomly and equally assigned to three groups:the blank control group,the acute eczema group,and the chloramphenicol prednisone liniment group according to the random number table method,with 8 mice per group.Except for the blank control group,the acute eczema model was established by applying 2,4-dinitrochlorobenzene(DNCB)to the right dorsal area.On day 10(d10),0.1 mL of normal saline was administered to the modeling site in both the blank control group and the acute eczema group,whereas chloramphenicol prednisone liniment was applied to the positive drug group.Medication was applied twice daily in all three groups for a total duration of 14 d.Sixty minutes following the final administration of the drug,the development of eczema in mice was visually assessed,and the severity of skin lesions was scored.Trans-epidermal water loss(TEWL)was measured using a multifunctional skin tester.Experiments inducing and alleviating pruritus were performed to compare the frequency of mice licking their bodies,the latency period before pruritus onset,and the duration of pruritus episodes.Levels of histamine and substance P(SP)in the lesion tissues were quantified using enzyme-linked immunosorbent assay(ELISA).[Results]Compared to the acute eczema group,the chloramphenicol prednisone liniment group exhibited a prolonged latency period of pruritus,an increased inhibition rate,and a shortened duration of pruritus.Additionally,there was a significant reduction in the frequency of mice licking their bodies,as well as in six eczema severity indicators:redness and swelling,scratch marks,papules,blisters,exudation or erosion at the lesion site,and the degree of skin swelling.Furthermore,levels of TEWL,histamine,and SP were also significantly decreased(P<0.05).[Conclusions]Chloramphenicol prednisone liniment exhibits anti-inflammatory and anti-pruritic properties.Its mechanism of action may involve the inhibition of mast cell activation within the lesion tissues of eczema model mice,thereby reducing the release of histamine and other active substances.This process alleviates inflammatory damage associated with eczema and contributes to the restoration of skin barrier function.
基金Supported by the Excellent Youth Project of Anhui Universities,No.2022AH030065National Natural Science Foundation of China,No.82474224 and No.82405244+3 种基金Anhui Provincial Natural Science Foundation,No.2408085MH223Open Projects of Anhui Province Key Laboratory of Meridian Viscera Correlationship,No.2024AHMVC04Research Project of Xin’an Medical and Chinese Medicine Modernization Research Institute,No.2023CXMMTCM016the Anhui Province Scientific Research Planning Project,No.2022AH050438.
文摘BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.
基金Supported by the National Natural Science Foundation of China,No.81270465the Sichuan Science and Technology Program,No.2024NSFSC0631,No.2023JDRC0088,and No.MZGC20240097+4 种基金the Basic Research Cultivation Support Program of Fundamental Research Funds for the Central Universities,No.2682023ZTPY071the Baiqiuen Public Welfare Foundation Program,No.BCF-LX-XH-20221014-12the Third People’s Hospital of Chengdu Clinical Research Program,No.CSY-YN-01-2023-012the Yibin Science and Technology Program,No.2021ZYY009the Chengdu Medical Research Project Foundation,No.2022284.
文摘Mast cells(MCs)under stress conditions contribute to the development of irritable bowel syndrome(IBS),yet their precise mechanisms in IBS remain unclear.AIM To investigate the role of MC-derived thymosinβ4(Tβ4)in stress-induced intestinal barrier dysfunction.METHODS The colonic mucus Tβ4 levels in IBS patients were determined and their effects on the epithelial barrier were assessed in vitro and in vivo.Specifically,rats genetically deficient in Tβ4(Tβ4^(-/-))or mice deficient in MCs(Kit^(w-sh/w-sh))were used to observe the effects of reintroducing Tβ4 or wild-type peritoneal MCs(wt-PMCs)into these animals.Additionally,the regulatory mechanism underlying Tβ4 secretion in MCs was investigated.RESULTS We demonstrated that high levels of Tβ4 in IBS mucus and intestinal MCs mediate stress-associated disruptive changes to the epithelial barrier.Moreover,Tβ4 treatment of wild-type or MC-deficient Kit^(w-sh/w-sh)mice caused a reduction in tight junction proteins and the interleukin 22 receptor A1(IL22RA1)/Reg3γcascade,but an increase in myosin light chain kinase.Furthermore,Tβ4^(-/-)rats were resistant to stress,though reintroduction of Tβ4 or wt-PMCs restored stress or corticotropin-releasing hormone(CRH)-induced barrier disturbance.Consistently,Tβ4 release from MCs was dependent on the CRH receptor 1,but not degranulation.The effect of Tβ4 was accompanied by IL22RA1/Janus kinase 1(JAK1)/signal transducer and activation of transcription 3(STAT3)pathway inhibition,suggesting a mechanism for physical and immune barrier suppression.CONCLUSION Collectively,these results suggest that Tβ4,which is abundant in IBS mucus and the secretome of MCs,plays a crucial role in the pathogenesis of IBS via IL22RA1/JAK1/STAT3 signaling,with potential implications for diagnostic and therapeutic targeting.
