Autoantigen Exposure in Murine Fetuses Elicited Nonpathogenic Autoimmunity.

Background And Aim: Autoimmunity refers to the presence of autoantibodies and autoreactive lymphocytes against the structural molecules of an individual's cells or tissues, known as self-antigens or autoantigens. It might exist in the absence of autoimmune disease. However, how autoimmunity develops remains a mystery, despite the discovery of autoantibodies in human cord blood.

Twenty years' experience of midgut malrotation and volvulus in a tertiary center in northern Taiwan: A retrospective study.

Background: Early diagnosis and surgical intervention for midgut malrotation with bowel obstruction are crucial. We aimed to identify risk factors for adverse outcomes in infants with midgut malrotation and to develop a prediction model.

Methods: We reviewed the operation records of infants surgically diagnosed with midgut malrotation at Chang Gung Children's Medical Center between January 2000 and December 2020.

Enteric neurospheres retain the capacity to assemble neural networks with motile and metamorphic gliocytes and ganglia.

Background: Neurosphere medium (NSM) and self-renewal medium (SRM) were widely used to isolate enteric neural stem cells (ENSCs) in the form of neurospheres. ENSCs or their neurosphere forms were neurogenic and gliogenic, but the compelling evidence for their capacity of assembling enteric neural networks remained lacking, raising the question of their aptitude for rebuilding the enteric nervous system (ENS) in ENSC therapeutics. It prompted us to explore an effective culture protocol or strategy for assembling ENS networks, which might also be employed as an in vitro model to simplify the biological complexity of ENS embedded in gut walls.

Adeno-Associated Viral Vector-Delivered Pannexin-1 Mimetic Peptide Alleviates Airway Inflammation in an Allergen-Sensitized Mouse Model.

Asthma is a chronic inflammatory disease around the world. Extracellular adenosine triphosphate works as a dangerous signal in responding to cellular stress, irritation, or inflammation. It has also been reported its association with the pathogenicity in asthma, with increased level in lungs of asthmatics.

L1cam alternative shorter transcripts encoding the extracellular domains were overexpressed in the intestine of L1cam knockdown mice.

Hirschsprung disease (HSCR) is a congenital disorder of functional bowel obstruction due to the absence of enteric ganglia in distal bowel. Different L1cam variants were reportedly associated with L1cam syndrome and HSCR, whose phenotypes lacked predictable relevance to their genotypes. Using next-generation sequencing (NGS), we found an L1CAM de novo frameshift mutation in a female with mild hydrocephalus and skip-type HSCR.

Enteric neurosphere cells injected into rectal submucosa might migrate caudorostrally to reconstitute enteric ganglia along the entire length of postnatal colon.

Background: In enteric neural stem cell (ENSC) therapy for enteric neuropathy, the gut is ostensibly accessible via laparotomy, laparoscopy or endoscopy, whereas its elongated configuration and multilayered structures substantially complicate the targeting of ENSC delivery. This study aimed to evaluate the feasibility of ENSC delivery via trans-anal rectal submucosal injection.

Methods: ENSC transplantation was conducted in an immunologically compatible model of FVB/NCrl-Tg(Pgk1-EGFP)01Narl into FVB/N murine strain combination.

Enteric Neural Network Assembly Was Promoted by Basic Fibroblast Growth Factor and Vitamin A but Inhibited by Epidermal Growth Factor.

Extending well beyond the original use of propagating neural precursors from the central nervous system and dorsal root ganglia, neurosphere medium (NSM) and self-renewal medium (SRM) are two distinct formulas with widespread popularity in enteric neural stem cell (ENSC) applications. However, it remains unknown what growth factors or nutrients are crucial to ENSC development, let alone whether the discrepancy in their components may affect the outcomes of ENSC culture. Dispersed enterocytes from murine fetal gut were nurtured in NSM, SRM or their modifications by selective component elimination or addition to assess their effects on ENSC development.

Perilla Fruit Water Extract Attenuates Inflammatory Responses and Alleviates Neutrophil Recruitment via MAPK/JNK-AP-1/c-Fos Signaling Pathway in ARDS Animal Model.

Airway respiratory distress syndrome (ARDS) is usually caused by a severe pulmonary infection. However, there is currently no effective treatment for ARDS. Traditional Chinese medicine (TCM) has been shown to effectively treat inflammatory lung diseases, but a clear mechanism of action of TCM is not available.

Adeno-Associated Virus-Mediated Interleukin-12 Gene Expression Alleviates Lung Inflammation and Type 2 T-Helper-Responses in Ovalbumin-Sensitized Asthmatic Mice.

High levels of allergen exposure increase the prevalence of asthma in developed countries. The asthmatic type 2 T-helper (Th2) response is characterized with high eosinophil infiltration, elevated Th2 cytokines, and immunoglobulin (Ig) E secretion resulting in local or systemic inflammation. However, the treatment with palliative Th2 inhibitor drugs cannot completely control asthma and that is why the development of novel approaches is still important.

Allergen Exposure in Murine Neonates Promoted the Development of Asthmatic Lungs.

We previously demonstrated that fetal allergen exposure caused T-helper 2 (Th2) cell sensitization. Although neonates are immunologically more mature than fetuses, asthmatic lungs were reportedly mitigated by neonatal allergen administration, mechanically referring to regulatory T-cells and TGF- signaling but lacking the immunological profiles after neonatal exposure. To reappraise the immunological outcome of neonatal allergen exposure, we injected adjuvant-free ovalbumin intraperitoneally into 2-day-old BALB/c neonates, followed by aerosolized ovalbumin inhalation in adulthood.

Reducing Lung ATP Levels and Alleviating Asthmatic Airway Inflammation through Adeno-Associated Viral Vector-Mediated CD39 Expression.

Asthma is a chronic respiratory inflammatory disease. Patients usually suffer long-term symptoms and high medical expenses. Extracellular ATP (eATP) has been identified as a danger signal in innate immunity and serves as a potent inflammatory mediator for asthma.

Immunological Consequences of Exposure to Foreign Antigens.

Immunologic tolerance refers to a state of immune nonreactivity specific to particular antigens as an important issue in the field of transplantation and the management of autoimmune diseases. Tolerance conceptually originated from Owen's observation of blood cell sharing in twin calves. Owen's conceptual framework subsequently constituted the backbone of Medawar's "actively acquired tolerance" as the major tenet of modern immunology.

Fetal Macrophages Exposed to Antigens Elicit Protective Immunity Against Overwhelming Challenge in A Murine Model.

Despite the evidence for fetal immunization following maternal infection, it remained a mystery how the fetal immune system was primed by vertically-transmitted pathogens or microbial antigens, especially before its full maturation. We previously demonstrated the capacity of fetal macrophages for endocytosing oncoprotein and allergens to bridge towards adaptive immunity in postnatal life. To investigate the immunological consequences of fetal contact with microbial antigens and the role of fetal macrophages in the defense against infection before T-cell development, we exposed gestational day 14 murine fetuses and their macrophages to flagellin and heat-killed Typhimurium.

Fetal exposure to oncoantigen elicited antigen-specific adaptive immunity against tumorigenesis.

Background: Envisioned as a similar process to tumorigenesis in terms of biological behaviors and molecular basis, embryogenesis necessitates an immune surveillance system to eliminate erratically transformed cells. Our previous study demonstrated that fetal macrophage-like phagocytes triggered Th2-skewed immunity following endocytosing prenatally administered ovalbumin to facilitate postnatal allergic airway responses, highlighting the critical role fetal phagocytes played in dealing with antigens present in developing fetuses and shaping subsequent immune responses. It prompted us to examine whether fetuses could mount Th1 tumoricidal immunity against tumorigenesis following in utero exposure to tumor antigens.

Distinctive genetic variation of long-segment Hirschsprung's disease in Taiwan.

Background: Hirschsprung's disease (HSCR) is a congenital disorder with the absence of myenteric and submucosal ganglion cells within distal gut. Due to multigenic inheritance and interactions, we employed next-generation sequencing (NGS) to investigate genetic backgrounds of long-segment HSCR (L-HSCR) in Taiwan.

Methods: Genomic DNA extracted from peripheral blood of L-HSCR patients was subjected to capture-based NGS, based on a 31-gene panel.

Exposure to Exosomal and B-Cell Alloantigens Lessens Alloreactivity of Recipients' Lymphocytes Rather than Confers Allograft Tolerance.

According to actively acquired tolerance, antigen exposure before full immune development in fetal or early neonatal life will cause tolerance to this specific antigen. In this study, we aimed to examine whether allogeneic tolerance could be elicited by exposure to surface MHC antigens of allogenic cells or soluble form of MHC exosomes. Gestational day 14 FVB/N fetuses were subjected to intraperitoneal injection of allogeneic major histocompatibility complex (MHC) exosomes or highly enriched B-cells.

An Age-Stratified Longitudinal Study of Primary Spontaneous Pneumothorax.

Purpose: The objective of this study was to determine the age-stratified incidence, frequency, and duration of recurrence of primary spontaneous pneumothorax (PSP).

Methods: This study analyzed the epidemiology of PSP among hospitalized patients using the National Health Research Institutes of Taiwan database. The incidence of PSP was determined from a cohort of 19,562 deidentified individuals with PSP between 2001 and 2013.

Experience of single-incision laparoscopy in children.

Context: Laparoscopic surgery is commonly used for the treatment of many pediatric surgical diseases at our department. Single-incision laparoscopic surgery (SILS) is well-known for its cosmetic benefit. We, hereby, present our experience of SILS and evaluate its efficacy.