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Some organisms, such as the Mexican axolotl, have the capacity to regenerate complicated biological structures throughout their lives. Which molecular pathways are sufficient to induce a complete endogenous regenerative response in injured tissue is an important question that remains unanswered. Using a gain-of-function regeneration assay, known as the Accessory Limb Model (ALM), we and others have begun to identify the molecular underpinnings of the three essential requirements for limb regeneration; wounding, neurotrophic signaling, and the induction of pattern from cells that retain positional memory. We have previously shown that treatment of Mexican axolotls with exogenous retinoic acid (RA) is sufficient to induce the formation of complete limb structures from blastemas that were generated by deviating a nerve bundle into an anterior-located wound site on the limb. Here we show that these ectopic structures are capable of regenerating and inducing new pattern to form when grafted into new anterior-located wounds. We additionally found that the expression of Alx4 decreases, and Shh expression increases in these anterior located blastemas, but not in the mature anterior tissues, supporting the hypothesis that RA treatment posteriorizes blastema tissue. Based on these and previous observations, we used the ALM assay to test the hypothesis that a complete regenerative response can be generated by treating anterior-located superficial limb wounds with a specific combination of growth factors at defined developmental stages. Our data shows that limb wounds that are first treated with a combination of FGF-2, FGF-8, and BMP-2, followed by RA treatment of the resultant mid-bud stage blastema, will result in the generation of limbs with complete proximal/distal and anterior/posterior limb axes. Thus, the minimal signaling requirements from the nerve and a positional disparity are achieved with the application of this specific combination of signaling molecules.

The mechanisms that regulate the sizing of the regenerating limb in tetrapods such as the Mexican axolotl are unknown. Upon the completion of the developmental stages of regeneration, when the regenerative organ known as the blastema completes patterning and differentiation, the limb regenerate is proportionally small in size. It then undergoes a phase of regeneration that we have called the “tiny-limb” stage, that is defined by rapid growth until the regenerate reaches the proportionally appropriate size. In the current study we have characterized this growth and have found that signaling from the limb nerves is required for its maintenance. Using the regenerative assay known as the Accessory Limb Model, we have found that the size of the limb can be positively and negatively manipulated by nerve abundance. We have additionally developed a new regenerative assay called the Neural Modified-ALM (NM-ALM), which decouples the source of the nerve from the regenerating host environment. Using the NM-ALM we discovered that non-neural extrinsic factors from differently sized host animals do not play a prominent role in determining the size of the regenerating limb. We have also discovered that the regulation of limb size is not autonomously regulated by the limb nerves. Together, these observations show that the limb nerves provide essential and instructive cues to regulate the final size of the regenerating limb.

The mechanisms that regulate growth and size of the regenerating limb in tetrapods such as the Mexican axolotl are unknown. Upon the completion of the developmental stages of regeneration, when the regenerative organ known as the blastema completes patterning and differentiation, the limb regenerate is proportionally small in size. It then undergoes a phase of regeneration that we have called the ‘tiny-limb’ stage, which is defined by rapid growth until the regenerate reaches the proportionally appropriate size. In the current study we have characterized this growth and have found that signaling from the limb nerves is required for its maintenance. Using the regenerative assay known as the accessory limb model (ALM), we have found that growth and size of the limb positively correlates with nerve abundance. We have additionally developed a new regenerative assay called the neural modified-ALM (NM-ALM), which decouples the source of the nerves from the regenerating host environment. Using the NM-ALM we discovered that non-neural extrinsic factors from differently sized host animals do not play a prominent role in determining the size of the regenerating limb. We have also discovered that the regulation of limb size is not autonomously regulated by the limb nerves. Together, these observations show that the limb nerves provide essential cues to regulate ontogenetic allometric growth and the final size of the regenerating limb., eLife digest Humans’ ability to regrow lost or damaged body parts is relatively limited, but some animals, such as the axolotl (a Mexican salamander), can regenerate complex body parts, like legs, many times over their lives. Studying regeneration in these animals could help researchers enhance humans’ abilities to heal. One way to do this is using the Accessory Limb Model (ALM), where scientists wound an axolotl’s leg, and study the additional leg that grows from the wound. The first stage of limb regeneration creates a new leg that has the right structure and shape. The new leg is very small so the next phase involves growing the leg until its size matches the rest of the animal. This phase must be controlled so that the limb stops growing when it reaches the right size, but how this regulation works is unclear. Previous research suggests that the number of nerves in the new leg could be important. Wells et al. used a ALM to study how the size of regenerating limbs is controlled. They found that changing the number of nerves connected to the new leg altered its size, with more nerves leading to a larger leg. Next, Wells et al. created a system that used transplanted nerve bundles of different sizes to grow new legs in different sized axolotls. This showed that the size of the resulting leg is controlled by the number of nerves connecting it to the CNS. Wells et al. also showed that nerves can only control regeneration if they remain connected to the central nervous system. These results explain how size is controlled during limb regeneration in axolotls, highlighting the fact that regrowth is directly controlled by the number of nerves connected to a regenerating leg. Much more work is needed to reveal the details of this process and the signals nerves use to control growth. It will also be important to determine whether this control system is exclusive to axolotls, or whether other animals also use it.

Background Regeneration of complex patterned structures is well described amongst, although limited to a small sampling of, amphibians. This limitation impedes our understanding of the full range of regenerative competencies within this class of vertebrates, according to phylogeny, developmental life stage and age. To broaden the phylogenetic breath of this research, we characterized the regenerative capacity of the Texas blind salamander (Eurycea rathbuni), a protected salamander native to the Edwards Aquifer of San Marcos, Texas and colonized by the San Marcos Aquatic Resource Center. As field observations suggested regenerative abilities in this population, the forelimb stump of a live captured female was amputated in the hopes of restoring the structure, and thus locomotion in the animal. Tails were clipped from two males to additionally document tail regeneration. Results We show that the Texas blind salamander exhibits robust limb and tail regeneration, like all other studied Plethodontidae. Regeneration in this species is associated with wound epithelium formation, blastema formation and subsequent patterning and differentiation of the regenerate. Conclusions The study has shown that the Texas blind salamander is a valuable model to study regenerative processes, and that therapeutic surgeries offer a valuable means to help maintain and conserve this vulnerable species. This article is protected by copyright. All rights reserved.

Urodele amphibians such as the axolotl regenerate complete limbs as adults, and understanding how the "blueprint", or pattern, of the regenerate is established and manipulated are areas of intense interest. Nutrient signaling plays an important role in pattern formation during regeneration. Retinoic acid signaling is the most characterized pathway during this process. Exogenous retinoic acid (RA) reprograms the pattern information in regenerating cells to a more posterior, ventral, and proximal identity. Vitamin D signaling shares several molecular similarities with RA and has been shown to alter pattern formation during zebrafish pectoral fin regeneration. To determine if exogenous Vitamin D signaling is capable of reprograming pattern in the axolotl limb blastema, we treated regenerating limbs with a potent Vitamin D agonist. Under the studied conditions, exogenous Vitamin D did not act in a manner similar to RA and failed to proximalize the pattern of the resulting regenerates. The Vitamin D treatment did result in several skeletal defects during regeneration, including carpal fusions along the A/P axis; failure to integrate the newly regenerated tissue with the existing tissue, formation of ectopic nodules of cartilage at the site of amputation, and altered bone morphology in uninjured skeletal tissue.

Loss of regenerative capacity is a normal part of aging. However, some organisms, such as the Mexican axolotl, retain striking regenerative capacity throughout their lives. Moreover, the development of age-related diseases is rare in this organism. In this review, we will explore how axolotls are used as a model system to study regenerative processes, the exciting new technological advancements now available for this model, and how we can apply the lessons we learn from studying regeneration in the axolotl to understand, and potentially treat, age-related decline in humans.

Obesity is associated with the establishment and maintenance of a low grade, chronically inflamed state in the white adipose tissue (WAT) of the body. The WAT macrophage population is a major cellular participant in this inflammatory process that significantly contributes to the pathophysiology of the disease, with the adipose depots of obese individuals, relative to lean counterparts, having an elevated number of macrophages that are skewed towards a pro-inflammatory phenotype. Alterations in the WAT lipid micro-environment, and specifically the availability of free fatty acids, are believed to contribute towards the obesity-related quantitative and functional changes observed in these cells. This review specifically addresses the involvement of the five G-protein coupled free fatty acid receptors which bind exogenous FFAs and signal in macrophages. Particular focus is placed on the involvement of these receptors in macrophage migration and cytokine production, two important aspects that modulate inflammation.

Trimethylation of Histone 3 lysine 27 (H3K27me3) is a chromatin modification that is associated with transcriptional repression (Cao et al., 2002; Sarma et al., 2008; Pengelly et al., 2013) [1], [2], [3]. In this article we performed anti-H3K27me3 Chromosomal Immunoprecipitation (ChIP-PCR), to detect the abundance of H3K27me3 marks on Ef1-alpha, cyp26A, HoxC10, HoxD10 and HoxD11 in the Xenopus XTC cell line. We also performed RT-PCR for these genes to determine whether their expression is detectable in the XTC cell culture. The data we present here are the fold enrichment of Ef1-alpha, cyp26A, HoxC10, HoxD10 and HoxD11 on anti-H3K27me3 ChIP compared to no antibody controls. We also present RT-PCR data on the above listed genes.

The future vision of many cell-based regenerative therapies is to repair or replace damaged tissues by grafting in healthy cell populations. In some cases, this requires that the grafted population seamlessly integrate with the host tissues to generate a fully functional structure. Intriguingly, evidence from mammalian and amphibian model systems suggest that the ability of a graft to integrate into the host site is dependent on the positional information in both tissues, and that regeneration and integration do not appear to be necessarily coupled processes. In this chapter, we discuss the differences in the positional memory in the cell types that contribute to regenerating mammalian and amphibian organs, and how they impact the process of tissue integration. In addition, we dissect the potential causes of integration defects in cell-based regenerate therapies and present methods that could be utilized to overcome these challenges in specific tissue types.

Background & Aims Bacterial infections commonly occur in decompensated cirrhosis resulting from bacterial translocation from the intestine. We studied the role of intestinal macrophages and the epithelial barrier in cirrhosis. Methods Forty-four patients with NASH/ASH cirrhosis (decompensated n=29, compensated n=15) and nineteen controls undergoing endoscopy were recruited. Serum was obtained and LPS and LBP levels determined. Intestinal macrophages were characterized by flow cytometry, immunohistochemistry, and nitric oxide (NO) production measured in supernatant of cultured duodenal samples. Quantitative RT-PCR was performed on duodenal biopsies assessing 84 inflammatory genes. Protein levels of cytokines/chemokines were assessed in serum and supernatant. The duodenal wall was assessed by electron microscopy, tight junction protein expression determined by RT-PCR, immunohistochemistry, and Western blot and, functional analysis performed by transepithelial resistance measurement and permeability studies. Results Increased plasma LPS, LBP levels and higher numbers of duodenal CD33 + /CD14 + /Trem-1 + macrophages, synthesizing iNOS and secreting NO were present in decompensated cirrhosis. Upregulation of IL-8, CCL2, CCL13 at the transcriptional level, and increased IL-8, and IL-6 were detected in supernatant and serum in cirrhosis. IL-6 and IL-8 co-localised with iNOS + and CD68 + , but not with CD11c + cells. Electron microscopy demonstrated an intact epithelial barrier. Increased Claudin-2 was detected by Western blot and immunohistochemistry, while decreased transepithelial resistance and increased duodenal permeability were detected in decompensated cirrhosis. Conclusions Our study shows the presence of activated CD14 + Trem-1 + iNOS + intestinal macrophages, releasing IL-6, NO, and increased intestinal permeability in patients with cirrhosis, suggesting that these cells may produce factors capable of enhancing permeability to bacterial products.

Disease of, or trauma to, the human jaw account for thousands of reconstructive surgeries performed every year. One of the most popular and successful treatment options in this context involves the transplantation of bone tissue from a different anatomical region into the affected jaw. Although, this method has been largely successful, the integration of the new bone into the existing bone is often imperfect, and the integration of the host soft tissues with the transplanted bone can be inconsistent, resulting in impaired function. Unlike humans, several vertebrate species, including fish and amphibians, demonstrate remarkable regenerative capabilities in response to jaw injury. Therefore, with the objective of identifying biological targets to promote and engineer improved outcomes in the context of jaw reconstructive surgery, we explore, compare and contrast the natural mechanisms of endogenous jaw and limb repair and regeneration in regenerative model organisms. We focus on the role of different cell types as they contribute to the regenerating structure; how mature cells acquire plasticity in vivo; the role of positional information in pattern formation and tissue integration, and limitations to endogenous regenerative and repair mechanisms.

Platelets and fibrin play an important role in allergic processes, including allergic asthma. The asthmatic BALB/c mouse model was used to induce asthma, and asthmatic mice were treated with the anti-inflammatory plant Withania somnifera, separately and in combination with the antioxidant selenium. Selenium is an important supplement in asthma, because asthmatics may have a selenium deficiency. Hydrocortisone was used as positive control. Results indicate control mice possess major thick fibers, minor thin fibers, and tight round activated platelets with typical pseudopodia formation. Minor fibers of asthmatic mice have a netlike appearance covering the major fibers whereas the platelets form loosely connected, granular aggregates. Hydrocortisone made the fibrin more fragile and platelet morphology changes from a tight activated platelet to a more granular activated platelet, not closely fused to each other. The plant extracts, separately and in combination with selenium did not affect the fragility of the fibrin and reversed the formation of the dense minor netlike layer over the major fibers, and the platelets formed a dense aggregate. Asthmatic mice treated with selenium showed a dense minor fibrin layer; however, the platelets formed a dense aggregate. We conclude that the anti-inflammatory products affect the stability of fibrin networks but not platelet stability (seen with hydrocortisone). Selenium does not affect the stability of the fibrin networks, but affects platelet stability. These results suggests that asthmatic patients should indeed use an antioxidant supplement, e.g. selenium, because it stabilizes activated platelets, together with anti-inflammatory products.

Background Malaria remains a global health problem and the majority of deaths are caused by Plasmodium falciparum parasites. Due to the rapid emergence of drug-resistant strains, novel avenues of research on the biology of the parasite are needed. The massive proliferation of asexual, intra-erythrocytic parasites every 48 h could kill the human host prior to transmission of slow-developing gametocytes to the mosquito vector. A self-induced P. falciparum programmed cell death mechanism has been hypothesized to maintain this balance between the parasite and its two hosts, but molecular participants of the cell death pathway in P. falciparum have not been characterized. Proteins with SWIB/MDM2 domains play a key role in metazoan programmed cell death and this study provides the first evaluation of two parasite SWIB/MDM2 homologues, PF3D7_0518200 (PfMDM2) and PF3D7_0611400 (PfSWIB). Methods The function of these proteins was assessed by predicting their structural topology with the aid of bioinformatics and determining their location within live transgenic parasites, expressing green fluorescent protein-tagged PfMDM2 and PfSWIB under normal and elevated temperatures, which mimic fever and which are known to induce a programmed cell death response. Additionally, P. falciparum phage display library technology was used to identify binding partners for the two parasite SWIB/MDM2 domains. Results Structural features of the SWIB/MDM2 domains of PfMDM2 and PfSWIB, suggested that they are chromatin remodelling factors. The N-terminal signal sequence of PfMDM2 directed the protein to the mitochondrion under both normal and heat stress conditions. Plasmodium falciparum phage display library technology revealed that the C-terminal SWIB/MDM2 domain of PfMDM2 interacted with a conserved protein containing a LisH domain. PfSWIB localized to the cytoplasm under normal growth conditions, while approximately 10 % of the heat-stressed trophozoite-stage parasites presented a rapid but short-lived nuclear localization pattern. Two PfSWIB binding partners, a putative Aurora-related kinase and a member of the inner membrane complex, were identified. Conclusion These novel data provide insight into the function of two parasite SWIB/MDM2 homologues and suggest that PfMDM2 plays a role within the mitochondrion and that PfSWIB is involved in a stage-specific, heat-stress, response pathway. Electronic supplementary material The online version of this article (doi:10.1186/s12936-015-1065-9) contains supplementary material, which is available to authorized users.

The nuclear landscape plays an important role in the regulation of tissue and positional specific genes in embryonic and developing cells. Changes in this landscape can be dynamic, and are associated with the differentiation of cells during embryogenesis, and the de-differentiation of cells during induced pluripotent stem cell (iPSC) formation and in many cancers. However, tools to quantitatively characterize these changes are limited, especially in the in vivo context, where numerous tissue types are present and cells are arranged in multiple layers. Previous tools have been optimized for the monolayer nature of cultured cells. Therefore, we present a new algorithm to quantify the condensation of chromatin in two in vivo systems. We first developed this algorithm to quantify changes in chromatin compaction and validated it in differentiating spermatids in zebrafish testes. Our algorithm successfully detected the typical increase in chromatin compaction as these cells differentiate. We then employed the algorithm to quantify the changes that occur in amphibian limb cells as they participate in a regenerative response. We observed that the chromatin in the limb cells de-compacts as they contribute to the regenerating organ. We present this new tool as an open sourced software that can be readily accessed and optimized to quantify chromatin compaction in complex multi-layered samples.

2-Methoxyestradiol (2ME2) is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1–25 μM) was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 μM of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues.

La literatura cientifica, aunque limitada en esta area, apoya la hipotesis de que el asma, por medio del trafico selectivo de leucocitos entre los diferentes sitios y la mucosa glandular del cuerpo, puede tener los mismos efectos fisiopatologicos en el estomago y las vias respiratorias. Este estudio tuvo como objetivo determinar si el asma, en ausencia y presencia de diversos tratamientos para el asma (hidrocortisona y Modul8 TM), genero alguna alteracion morfologica en las celuals parietales y principales del estomago. El modelo murino BALB/c del raton asmatico fue el modelo de eleccion en este estudio. El protocolo de induccion de asma, asi como el tratamiento del asma demostro ser eficaz con la ayuda de lavado bronquial y cuantificacion leucocitaria del fluido. Biopsias de las regiones fundica y pilorica fueron extraidas y evaluadas por medio de microscopia electronica de transmision, de barrido y de luz. Las biopsias extraidas de la region fundica y pilorica revelaron que el asma solamente induce hipertrofia de las celulas parietales (aumento del tamano de las celulas parietales P

The muscular dystrophies (MDs) are genetic disorders of muscle degeneration due to mutations in genes that encode a wide variety of proteins. Dysferlinopathy are characterized by the absence of dysferlin in skeletal muscle and an autosomal recessive mode of inheritance. Both histological and ultrastructural pathology have been well established in dysferlinopathy patients and dysferlin-deficient animal models. To our knowledge the effect of antioxidant supplementation on this level has not been described previously. This article therefore focuses on the histopathology to reveal the effect of antioxidant supplementation. The study aimed to determine, at cellular level, the histopathological changes in the SJL/J mouse model following a 90 day trial with antioxidant supplementation. Markedly reduced inflammatory insult in the more affected quadriceps muscles of animals treated with high doses of CoQ10 and a combination of resveratrol/CoQ10 were observed. The outcome provides evidence that high doses of antioxidant supplementation resulted in decreased dystrophic markers and enhanced tissue integrity at cellular level.

Modul8® es una mezcla compuesta de productos naturales que es conocida por ser un inmunomodulador. En el presente estudio, el efecto de este inmunomodulador se prueba de forma experimental en el modelo de raton asmaticos BALB/c, para investigar sus propiedades sobre el conteo de globulos blancos en la sangre y lavado bronquial de los animales, ya que los globulos blancos desempenan un papel fundamental en el proceso de respuesta inflamatoria implicado en el asma. Como es sabido, tambien las plaquetas desempenan un papel importante en el sistema inmunologico, asi, la ultraestructura de las plaquetas y las redes de fibrina tambien fueron investigadas por microscopia electronica de barrido. Los animales fueron sensibilizados, nebulizados y tratados durante un periodo de 43 dias hasta el termino. Los resultados de los frotis de sangre, asi como los de lavado bronquial revelaron un numero significativamente mayor de eosinofilos en el grupo de asmaticos en comparacion con el control y grupos tratados. Cambios en la ultraestructura de las plaquetas y redes de fibrina tambien pueden ser observados, donde el grupo tratado con la Modul8® aparece similar a el grupo control, donde los fibras de mayor grosor y menor grosor pueden ser claramente distinguidas y ademas, puede ser observada una apretada masa de plaquetas aglutinadas. Considerando las redes de la fibrina en animales asmaticos parecen endebles con una apretada masa de fibras de menor grosor que cubren las fibras de mayor grosor. Los agregados de plaquetas en asmaticos aparecen granulares sin el aspecto apretado del agregado plaquetario que rodea al grupo control. Por tanto, se concluye que Modul8® positivamente influye en el conteo de globulos blancos mediante la alteracion del perfil de asmaticos a un aspecto similar al del control. Ademas, parece como si Modul8® tuviera un efecto estabilizador en las plaquetas y las redes de fibrina. De estos resultados se puede sugerir que Modul8® puede ser utilizado con exito en el tratamiento de procesos inflamatorios como el asma.

El proposito del presente estudio fue comparar la ultraestructura de plaquetas y las redes de fibrina de los seres humanos y de ocho diferentes especies de animales, con el fin de determinar las diferencias morfologicas de estas estructuras y si las diferencias pueden ser observadas por microscopia electronica de barrido. Las plaquetas y las redes de fibrina desempenan un papel importante tanto en el proceso de coagulacion como, fisiologicamente en procesos alergicos y mecanismos inmunologicos. Elgrosor de las redes de fibrina humana fue comparado con las del raton (Mus musculus), equino (Equus caballus), mono vervet (Chlorocebus aethiops, anteriormente Cercopithecus aethiops, antilope Africano (Oryx gazella), ovino (Ovis aries), pinguino (Spheniscus demersus), conejo (Oryctolagus cuniculus) y tortuga marina (Caretta caretta). Las fibras fueron medidas y agrupadas en fibras delgadas (menor), fibras intermedias y fibras gruesas (grandes). Los resultados obtenidos indicaron que para cada una de las tres clases de fibrina, los rangos de su tamano en el mono, antilope africano y en equino no fueron significativamente diferentes entre si, mientras que en humano, pinguino, antilope africano y ovino no fueron significativamente diferentes entre estos. De estos resultados se pudo concluir que mamiferos y aves poseen una distribucion tri-modal de fibras de fibrina, distinta a la de las especies de reptiles estudiadas, donde la tortuga de mar posee una distribucion bimodal de fibras de fibrina. Se puede sugerir que la utilizacion de los modelos mamiferos y aviar, en terminos de patrones de distribucion de fibras de fibrina, pueden ser una alternativa adecuada para los estudios ultraestructurales.

Warren Antonio Vieira, Etheresia PretoriusDepartment of Anatomy, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South AfricaAbstract: The gastrointestinal tract (GIT) of vertebrates is composed of several distinct ­compartments and glands as well as an extensive mucosal surface. Its primary function is that of chemical and physical digestion of food and the absorption of nutrients; however, due to its continual antigen exposure, the GIT also has an important defensive immunological function. The GIT’s immunological participation is facilitated by the mucosa-associated lymphoid tissues, thought to share the mucosal immunological system with the respiratory mucosa-associated lymphoid tissues. As a result of this shared mucosal immunity, it has been hypothesized that bronchial asthma may be able to affect the body’s GIT in the same pathophysiological manner as the airways and lungs. Here we discuss the link between bronchial asthma and ­pathophysiological features in the GIT – including leukocyte influx, goblet cell alterations, fibrosis, and epithelial and villous atrophy.Keywords: fundus, pylorus, common mucosal system, asthma, gastrointestinal tract