The butanol extract of Asparagus cochinchinensis roots fermented with Weissella cibaria (BAW) effectively prevents inflammation and remodeling of airway in the ovalbumin (OVA)-induced asthma model. To characterize biomarkers that can predict the anti-asthmatic effects induced by BAW treatment, we measured the alteration of endogenous metabolites in the serum of OVA-induced asthma mice after administration of low concentration BAW (BAWLo, 250 mg/kg) and high concentration BAW (BAWHi, 500 mg/kg) using ¹H nuclear magnetic resonance (¹H-NMR) spectral data. The number of immune cells and serum concentration of IgE as well as thickness of the respiratory epithelium and infiltration of inflammatory cells in the airway significantly recovered in the OVA+BAW treated group as compared to the OVA+Vehicle treated group. In the metabolic profile analysis, the pattern recognition showed completely separate clustering of serum analysis parameters between the OVA+Vehicle and OVA+BAW treated groups. Of the total endogenous metabolites, 19 metabolites were upregulated or downregulated in the OVA+Vehicle treated group as compared to the Control treated group. However, only 4 amino acids (alanine, glycine, methionine and tryptophan) were significantly recovered after BAWLo and BAWHi treatment. This study provides the first results pertaining to metabolic changes in the asthma model mice treated with OVA+BAW. Additionally, these findings show that 4 metabolites can be used as one of biomarkers to predict the anti-asthmatic effects.
Amino Acids ; Animals ; Asthma ; Biomarkers ; Fermentation ; Glycine ; Immunoglobulin E ; Inflammation ; Magnetic Resonance Spectroscopy ; Metabolome ; Metabolomics ; Methionine ; Mice ; Ovalbumin ; Respiratory Mucosa ; Therapeutic Uses ; Weissella

The butanol extract of Asparagus cochinchinensis roots fermented with Weissella cibaria (BAfW) significantly suppressed the inflammatory response induced by lipopolysaccharide (LPS) treatment in RAW264.7 cells. To investigate the dose dependence and durability of BAfW on the anti-asthma effects, alterations in key parameters were measured in ovalbumin (OVA)-challenged Balb/c mice treated with the different doses of BAfW at three different time points. The number of immune cells, OVA-specific IgE level, thickness of respiratory epithelium and mucus score decreased significantly in a dose-dependent manner in response to treatment with 125 to 500 mg/kg BAfW (P < 0.05), although the highest level was detected in the 500 mg/kg treated group. Moreover, the decrease in these parameters was maintained from 24 to 48 h in the 500 mg/kg of BAfW treated group. At 72 h, the effects of BAfW on the number of immune cells, OVA-specific IgE level and thickness of respiratory epithelium partially disappeared. Overall, this study provides the first evidence that the anti-asthma effect of BAfW may reach the maximum level in OVA-challenged Balb/c mice treated with 500 mg/kg and that these effects can last for 48 h.
Animals ; Asthma* ; Fermentation ; Immunoglobulin E ; Mice ; Mucus ; Ovalbumin ; Respiratory Mucosa ; Therapeutic Uses* ; Weissella

OBJECTIVE: Newly identified human rhinovirus C (HRV-C) and human bocavirus (HBoV) cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and developing related vaccines are difficult. Therefore, it is necessary to develop a novel platform for the propagation of these types of viruses. METHODS: A platform for culturing human airway epithelia in a three-dimensional (3D) pattern using Matrigel as scaffold was developed. The features of 3D culture were identified by immunochemical staining and transmission electron microscopy. Nucleic acid levels of HRV-C and HBoV in 3D cells at designated time points were quantitated by real-time polymerase chain reaction (PCR). Levels of cytokines, whose secretion was induced by the viruses, were measured by ELISA. RESULTS: Properties of bronchial-like tissues, such as the expression of biomarkers CK5, ZO-1, and PCK, and the development of cilium-like protuberances indicative of the human respiration tract, were observed in 3D-cultured human airway epithelial (HAE) cultures, but not in monolayer-cultured cells. Nucleic acid levels of HRV-C and HBoV and levels of virus-induced cytokines were also measured using the 3D culture system. CONCLUSION Our data provide a preliminary indication that the 3D culture model of primary epithelia using a Matrigel scaffold in vitro can be used to propagate HRV-C and HBoV.
Collagen ; Drug Combinations ; Enterovirus ; growth & development ; isolation & purification ; Enterovirus Infections ; virology ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; virology ; Human bocavirus ; growth & development ; isolation & purification ; Humans ; Laminin ; Parvoviridae Infections ; virology ; Primary Cell Culture ; methods ; Proteoglycans ; Real-Time Polymerase Chain Reaction ; Respiratory Mucosa ; virology ; Virus Cultivation

An 8-year-old girl who had experienced intermittent cough and fever over a 3 year period, was admitted after experiencing a recurrence for one month. One year ago the patient experienced a recurrent oral mucosal ulcer. Physical examination showed vitiligo in the skin of the upper right back. Routine blood tests and immune function tests performed in other hospitals had shown normal results. Multiple lung CT scans showed pulmonary infection. The patient had recurrent fever and cough and persistent presence of some lesions after anti-infective therapy. The antitubercular therapy was ineffective. Routine blood tests after admission showed agranulocytosis. Gene detection was performed and she was diagnosed with dyskeratosis congenita caused by homozygous mutation in RTEL1. Patients with dyskeratosis congenita with RTEL1 gene mutation tend to develop pulmonary complications. Since RTEL1 gene sequence is highly variable with many mutation sites and patterns and can be inherited via autosomal dominant or recessive inheritance, this disease often has various clinical manifestations, which may lead to missed diagnosis or misdiagnosis. For children with unexplained recurrent pulmonary infection, examinations of the oral cavity, skin, and nails and toes should be taken and routine blood tests should be performed to exclude dyskeratosis congenita. There are no specific therapies for dyskeratosis congenita at present, and when bone marrow failure and pulmonary failure occur, hematopoietic stem cell transplantation and lung transplantation are the only therapies. Androgen and its derivatives are effective in some patients. Drugs targeting the telomere may be promising for patients with dyskeratosis congenita.
Child ; Dyskeratosis Congenita ; complications ; therapy ; Female ; Humans ; Mouth Diseases ; etiology ; Mouth Mucosa ; pathology ; Recurrence ; Respiratory Tract Infections ; etiology ; Telomere ; drug effects ; Ulcer ; etiology

PURPOSE: Dexmedetomidine, an α2-adrenergic agonist, provides sedative and analgesic effects without significant respiratory depression. Dexmedetomidine has been suggested to have an antiapoptotic effect in response to various brain insults. We developed an oral mucosa patch using dexmedetomidine for sedation. The effects of the dexmedetomidine oral mucosa patch on cell proliferation and apoptosis in the hippocampus were evaluated. METHODS: A hydrogel oral mucosa patch was adhered onto the oral cavity of physiologically normal rats, and was attached for 2 hours, 6 hours, 12 hours, or 24 hours. Plasma dexmedetomidine concentrations were determined by liquid chromatography– electrospray ionization–tandem mass spectrometry–multiple-ion reaction monitoring (LC-ESI-MS/MS-MRM). Cell proliferation in the hippocampus was detected by Ki-67 immunohistochemistry. Caspase-3 immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and Western blotting for Bax and Bcl-2 were performed to detect hippocampal apoptosis. The levels of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) in the hippocampus were also measured by Western blotting. RESULTS: Plasma dexmedetomidine concentration increased according to the attachment time of the dexmedetomidine oral mucosa patch. Hippocampal cell proliferation did not change due to the dexmedetomidine oral mucosa patch, and the dexmedetomidine oral mucosa patch exerted no significant effect on BDNF or TrkB expression. In contrast, the dexmedetomidine oral mucosa patch exerted an antiapoptotic effect depending on the attachment time of the dexmedetomidine oral mucosa patch. CONCLUSIONS: A dexmedetomidine oral mucosa patch can be used as a convenient tool for sedation, and is of therapeutic value due to its antiapoptotic effects under normal conditions.
Animals ; Apoptosis* ; Blotting, Western ; Brain ; Brain-Derived Neurotrophic Factor ; Caspase 3 ; Cell Proliferation ; Dexmedetomidine* ; Hippocampus* ; Hydrogel ; Immunohistochemistry ; Mouth ; Mouth Mucosa* ; Plasma ; Protein-Tyrosine Kinases ; Rats* ; Respiratory Insufficiency

A 63-year old Filipino female presented with epistaxis of undisclosed duration. Examination showed a vascular, pulsating, rubbery intranasal mass involving both nasal cavities. The clinical impression was that of a nasal hemangioma. She underwent excision of the tumor and the specimen was sent for histopathologic evaluation. The specimen consisted of several tan-brown irregular tissue fragments with an aggregate diameter of 2 cm. Microscopic examination showed a cellular spindle cell tumor underneath the respiratory mucosa. (Figure 1) The tumor cells formed a syncytial pattern arranged in whorls that were separated by thin fibrovascular bands. (Figure 2) The cells had round to oval nuclei with nuclear clearing and moderate amount of syncytial cytoplasm compatible with a meningothelial derivation. (Figure 3) There was absence of nuclear atypia, significant mitotic activity, and necrosis. Immunohistochemistry studies showed positivity for Epithelial Membrane Antigen (EMA) and Progesterone Receptors (PR), and absence of reaction for Smooth Muscle Actin (SMA) and CD34. (Figure 4) Our diagnosis was sinonasal tract meningioma. Primary extracranial meningioma of the sinonasal cavity is rare and thus secondary extension from a primary intracranial tumor should be ruled out. It involves a wide age range with no striking gender predilection.1,2 Most common symptoms include nasal obstruction, epistaxis, exophthalmos, and a mass. Etiogenesis is not completely established and is postulated to arise from meningocytes that are entrapped during closure of midline structures, very similar to the development of meningoceles.3 Histopathologic examination discloses a spindle cell tumor arranged predominantly in whorls composed of cells showing meningothelial differentiation. Most are histologically grade 1 tumors. Grade 2 and 3 sinonasal tract meningiomas are rare.4 Histologic differential diagnoses include a glomangiopericytoma, leiomyosarcoma, and a solitary fibrous tumor/hemangiopericytoma. Close histologic evaluation with appropriate immunohistochemistry studies point to the correct diagnosis. Meningioma shows strong diffuse positivity with EMA and PR, and is usually negative for other immunohistochemistry markers such as muscle actins (for glomangiopericytoma and leiomyosarcoma), and CD34 (for solitary fibrous tumor/hemangiopericytoma).1,3 A diagnosis of primary sinonasal meningioma should not be made if an intracranial mass is identified.4 Sinonasal meningiomas are benign tumors with no documented distant metastases.1,2 Although recurrences occur in about 30% (mostly due to incomplete excision), metastasis and malignant transformation has not been reported.
Human ; Female ; Middle Aged ; Meningioma ; Epistaxis ; Nasal Cavity ; Mucin-1 ; Immunohistochemistry ; Receptors, Progesterone ; Actins ; Meningeal Neoplasms ; Nose ; Hemangioma ; Respiratory Mucosa ; Muscle, Smooth

OBJECTIVETo investigate the effect of respiratory syncytial virus (RSV)-related pulmonary infection on endogenous metabolites in large intestinal mucosa in BALB/c mice using metabolomics technology based on gas chromatography-mass spectrometry (GC-MS).

METHODSMice were randomly divided into a control group and a RSV pneumonia model group (n=16 each). The mouse model of RSV pneumonia was established using intranasal RSV infection (100×TCID, 50 μL/mouse, once a day). After 7 days of intranasal RSV infection, the mice were sacrificed and GC-MS was used to identify endogenous metabolites and measure the changes in their relative content in colon tissue. SMCA-P12.0 software was used to perform principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) for endogenous metabolites in colon tissue. The differentially expressed metabolites in colon tissue were imported into the metabolic pathway platform Metaboanalyst to analyze related metabolic pathways.

RESULTSPCA and OPLS-DA showed significant differences between the control and RSV pneumonia model groups. A total of 32 metabolites were identified in the colon tissue of the mice with RSV pneumonia. The RSV pneumonia model group had significant increases in the content of leucine, isoleucine, glycine, alanine, arachidonic acid, and lactic acid, which were related to the valine, leucine, isoleucine, arachidonic acid, and pyruvic acid metabolic pathways.

CONCLUSIONSRSV pneumonia might cause metabolic disorders in the large intestinal tissue in mice.

Amino Acids, Branched-Chain ; metabolism ; Animals ; Female ; Gas Chromatography-Mass Spectrometry ; Intestinal Mucosa ; metabolism ; Intestine, Large ; metabolism ; pathology ; Lung ; pathology ; Mice ; Mice, Inbred BALB C ; Pneumonia, Viral ; metabolism ; Respiratory Syncytial Virus Infections ; metabolism

Herein, we report a rare case of concurrent gastric and pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas. A 65-year-old man who had been diagnosed with Helicobacter pylori-positive gastric MALT lymphoma received eradication therapy and achieved complete remission. During follow-up, he developed de novo pulmonary MALT lymphoma as a sequela of pulmonary tuberculosis, accompanied by recurrent gastric MALT lymphoma. Polymerase chain reaction (PCR) products of the CDR3 region of the immunoglobulin heavy chain gene showed an overall polyclonal pattern with bands at 400 base pairs (bp) and 200 bp predominant in the pulmonary tissue, as well as two distinctive bands in the gastric tissue at 400 bp and 200 bp. This case suggests that multiorgan lymphomas are more likely to be independent from each other when they are far apart, involve different organ systems, and have independent precipitating factors.
Aged ; Gastric Mucosa/pathology ; Humans ; Inflammation/pathology ; Lung Neoplasms/etiology/*pathology ; Lymphoma, B-Cell, Marginal Zone/etiology/*pathology ; Male ; Respiratory Mucosa/pathology ; Stomach Neoplasms/etiology/*pathology ; Tuberculosis, Pulmonary/complications

Herein, we report a rare case of concurrent gastric and pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas. A 65-year-old man who had been diagnosed with Helicobacter pylori-positive gastric MALT lymphoma received eradication therapy and achieved complete remission. During follow-up, he developed de novo pulmonary MALT lymphoma as a sequela of pulmonary tuberculosis, accompanied by recurrent gastric MALT lymphoma. Polymerase chain reaction (PCR) products of the CDR3 region of the immunoglobulin heavy chain gene showed an overall polyclonal pattern with bands at 400 base pairs (bp) and 200 bp predominant in the pulmonary tissue, as well as two distinctive bands in the gastric tissue at 400 bp and 200 bp. This case suggests that multiorgan lymphomas are more likely to be independent from each other when they are far apart, involve different organ systems, and have independent precipitating factors.
Aged ; Gastric Mucosa/pathology ; Humans ; Inflammation/pathology ; Lung Neoplasms/etiology/*pathology ; Lymphoma, B-Cell, Marginal Zone/etiology/*pathology ; Male ; Respiratory Mucosa/pathology ; Stomach Neoplasms/etiology/*pathology ; Tuberculosis, Pulmonary/complications

The regulated production of reactive oxygen species (ROS) has been considered a unique property of phagocytic cells which use this ROS system to induce innate defense system that enables it to successfully combat the pathogens. However, the mechanisms for how respiratory mucosa might produce ROS against respiratory viral infection still need to be completely defined. Respiratory mucosa and nasal epithelium has been known as the first defense site of human respiratory tract which is highly exposed and vulnerable to environmental pathogens, including air-bone microbes, viruses and allergens. We are especially interested in the innate immune response to respiratory virus infection in nasal epithelium and how this response might be influenced by ROS generation after viral infection. The interferon (IFN) signaling system is perhaps the most critical pathway for antiviral defense and protective actions of IFNs rely on signaling through IFN receptors, transcription factors and IFN-stimulated genes or antiviral cytokines requiring for virus degradation and suppression of viral transcription or translation. We verified that both type I and type III IFN genes expression and secreted proteins were more highly induced after influenza A virus infection in nasal epithelium. We also propose that type III IFNs are the primary IFNs to mediate an anti-viral defense in nasal epithelium and more sensitively reacted with ROS which were produced after respiratory virus infection. We estimate that ROS are necessary for the innate immune response and trigger the induction of IFN-related innate immune response to resist respiratory virus infection in human respiratory mucosa.
Allergens ; Critical Pathways ; Cytokines ; Humans ; Immunity, Innate* ; Influenza A virus ; Interferons* ; Nasal Mucosa* ; Phagocytes ; Reactive Oxygen Species* ; Respiratory Mucosa ; Respiratory System ; Transcription Factors