1.Common characteristics and regulatory mechanisms of airway mucus hypersecretion in lung disease.
Ze-Qiang LIN ; Shi-Man PANG ; Si-Yuan ZHU ; Li-Xia HE ; Wei-Guo KONG ; Wen-Ju LU ; Zi-Li ZHANG
Acta Physiologica Sinica 2025;77(5):989-1000
In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans
;
Mucus/metabolism*
;
Mucins/physiology*
;
Lung Diseases/metabolism*
;
Respiratory Mucosa/metabolism*
;
Pulmonary Disease, Chronic Obstructive/physiopathology*
;
Asthma/physiopathology*
;
Cystic Fibrosis/physiopathology*
;
Mucociliary Clearance/physiology*
2.Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production.
Ya-Jie CAI ; Jian-Hang LAN ; Shuo LI ; Yue-Ning FENG ; Fang-Hong LI ; Meng-Yu GUO ; Run-Ping LIU
Journal of Integrative Medicine 2025;23(4):429-444
OBJECTIVE:
Ulcerative colitis is closely associated with intestinal stem cell (ISC) loss and impaired intestinal mucus barrier. Sinisan (SNS), a compound Chinese herbal medicine, has a long history in the treatment of intestinal dysfunction, yet whether SNS can relieve acute experimental colitis by modulating ISC proliferation and secretory cell differentiation has not been studied. Our study tested the effect of SNS against acute colitis and focused on the mechanisms involving intestinal barrier recovery.
METHODS:
Network pharmacology analysis and blood entry component analysis of SNS were used to explore the underlying mechanism by which SNS affects the acute dextran sulfate sodium (DSS)-induced murine colitis model. RNA-sequencing was used to demonstrate the mechanism. Further, reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining, and alcian blue and periodic acid-Schiff staining were performed in vivo and in the colonic organoids to investigate the cell lineage differentiation-related mechanism of SNS. Furthermore, potential active ingredients from SNS were predicted by network pharmacology analysis.
RESULTS:
SNS dramatically suppressed DSS-induced acute colonic inflammation in mice. RNA-sequencing analysis revealed downregulation of inflammation and apoptosis-related genes, and upregulation of lipid metabolism and proliferation-related genes, such as Irf7, Pparα, Clspn and Hspa5. Additionally, ISC renewal and intestinal secretory cell lineage commitment were significantly promoted by SNS both in vivo and in vitro in colonic organoids, leading to enhanced mucin expression. Furthermore, potential active ingredients from SNS that mediated inflammation, lipid metabolism, proliferation, apoptosis, stem cells and secretory cells were predicted using a network pharmacology approach.
CONCLUSION
Our study shed light on the underlying mechanism of SNS in attenuating acute colitis from the perspective of ISC renewal and secretory lineage cell differentiation, suggesting a of novel therapeutic strategy against colitis. Please cite this article as: Cai YJ, Lan JH, Li S, Feng YN, Li FH, Guo MY, et al. Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production. J Integr Med. 2025; 23(4): 429-444.
Animals
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Drugs, Chinese Herbal/therapeutic use*
;
Mice
;
Colon/pathology*
;
Mucins/metabolism*
;
Mice, Inbred C57BL
;
Cell Differentiation/drug effects*
;
Male
;
Colitis/metabolism*
;
Cell Lineage/drug effects*
;
Dextran Sulfate
;
Stem Cells/drug effects*
;
Disease Models, Animal
3.Immunology of a unique biological structure: the Echinococcus laminated layer.
Álvaro DÍAZ ; Anabella A BARRIOS ; Leticia GREZZI ; Camila MOUHAPE ; Stephen J JENKINS ; Judith E ALLEN ; Cecilia CASARAVILLA
Protein & Cell 2023;14(2):87-104
The larval stages of the cestode parasites belonging to the genus Echinococcus grow within internal organs of humans and a range of animal species. The resulting diseases, collectively termed echinococcoses, include major neglected tropical diseases of humans and livestock. Echinococcus larvae are outwardly protected by the laminated layer (LL), an acellular structure that is unique to this genus. The LL is based on a fibrillar meshwork made up of mucins, which are decorated by galactose-rich O-glycans. In addition, in the species cluster termed E. granulosus sensu lato, the LL features nano-deposits of the calcium salt of myo-inositol hexakisphosphate (Insp6). The main purpose of our article is to update the immunobiology of the LL. Major recent advances in this area are (i) the demonstration of LL "debris" at the infection site and draining lymph nodes, (ii) the characterization of the decoy activity of calcium Insp6 with respect to complement, (iii) the evidence that the LL mucin carbohydrates interact specifically with a lectin receptor expressed in Kupffer cells (Clec4F), and (iv) the characterization of what appear to be receptor-independent effects of LL particles on dendritic cells and macrophages. Much information is missing on the immunology of this intriguing structure: we discuss gaps in knowledge and propose possible avenues for research.
Animals
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Calcium
;
Echinococcosis/parasitology*
;
Echinococcus/immunology*
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Echinococcus granulosus/immunology*
;
Mucins
4.Improvement effect of Shegan Mahuang Decoction on rats with cold-induced asthma based on TRPV1/NRF-1/mtTFA pathway.
Qiu-Hui LI ; Xiao-Xiao SHAN ; Xiao-Ying LIU ; Wei-Dong YE ; Ya-Mei YUAN ; Xun-Yan YIN ; Xiang-Ming FANG
China Journal of Chinese Materia Medica 2023;48(23):6414-6422
This study investigated the therapeutic effect of Shegan Mahuang Decoction(SGMHD) on cold-induced asthma in rats and explored its underlying mechanism. Seventy-two healthy male SD rats of specific pathogen free(SPF) grade were randomly divided into a blank group, a model group, a positive control group(dexamethasone, 0.4 mg·kg~(-1)), and low-, medium-, and high-dose SGMHD groups(3.2, 6.4, and 12.8 g·kg~(-1)). The blank group received saline, while the other groups were sensitized by intraperitoneal injection of ovalbumin(OVA) solution. Subsequently, the rats were placed in a cold chamber adjustable to 0-2 ℃, and OVA solution was ultrasonically nebulized to induce cold-induced asthma in rats. After three weeks of treatment, the general behaviors of rats were observed. Hematoxylin-eosin(HE) staining was used to evaluate pathological changes in lung tissues, periodic acid-Schiff(PAS) staining assessed mucin changes, and Masson staining was performed to examine collagen deposition. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of the inflammatory factors interleukin-4(IL-4) and vascular endothelial growth factor(VEGF) in serum and bronchoalveolar lavage fluid(BALF). Real-time quantitative polymerase chain reaction(RT-PCR) was employed to assess the mRNA expression levels of transient receptor potential vanilloid subfamily member 1(TRPV1), nuclear respiratory factor 1(NRF-1), and mitochondrial transcription factor A(mtTFA) in lung tissues. Western blot was used to measure the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues. Compared with the blank group, the model group exhibited signs of rapid respiration, increased frequency of defecation with looser stools, and disheveled and dull fur. Pathological results showed significant infiltration of inflammatory cells in lung tissues, narrowing of bronchial lumens, increased mucin secretion, and enhanced collagen deposition in the model group. Additionally, the levels of IL-4 and VEGF in serum and BALF were significantly elevated, and the mRNA and protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were significantly increased. Compared with the model group, SGMHD improved the behaviors of rats, alleviated pathological changes in lung tissues, mucin production, and collagen deposition, significantly decreased the levels of IL-4 and VEGF in serum and BALF, and reduced the mRNA expression levels of TRPV1, NRF-1, and mtTFA in lung tissues, with the medium-dose SGMHD group showing the most significant effect. Moreover, the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were also reduced, with the medium-dose SGMHD group exhibiting the most significant effect. In conclusion, this study demonstrates that SGMHD can alleviate airway inflammation and inhibit airway remodeling in cold-induced asthma rats. These effects may be associated with the modulation of the TRPV1/NRF-1/mtTFA signaling pathway.
Rats
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Male
;
Animals
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Mice
;
Interleukin-4/metabolism*
;
Vascular Endothelial Growth Factor A/metabolism*
;
Rats, Sprague-Dawley
;
Asthma/genetics*
;
Lung
;
Bronchoalveolar Lavage Fluid
;
RNA, Messenger/metabolism*
;
Collagen/metabolism*
;
Mucins/therapeutic use*
;
Ovalbumin
;
Disease Models, Animal
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Mice, Inbred BALB C
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TRPV Cation Channels/metabolism*
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Drugs, Chinese Herbal
5.Clinicopathological features of colorectal amphicrine carcinoma.
Zhi Wen LI ; Qi SUN ; Zhong ZHENG ; Lu Lu YANG ; Lu HE ; Dan Ni CHEN ; Biao ZHANG ; Hong Yan WU ; Wen Bin HUANG ; Xiang Shan FAN
Chinese Journal of Pathology 2022;51(8):708-712
Objective: To investigate the clinicopathological, immunophenotypic and molecular features of colorectal amphicrine carcinoma (AC). Methods: Eight cases of colorectal AC were collected at the Nanjing Drum Tower Hospital and Nanjing First Hospital, Nanjing, China from 2013 to 2020. The histopathological, immunohistochemical and molecular features were analyzed. The relevant literature was reviewed. Results: There were 6 males and 2 females, with an average age of 56 years (range 28-80 years). The tumor sites were as follows: 4 cases in sigmoid colon, 3 cases in rectum, and 1 case in transverse colon. Microscopically, there were three different patterns in the tumors, including nests with collagen hyperplasia, sheets of cells with scant stroma, and glandular or cribriform growth of goblet- or signet ring-like cells. The tumor cells generally had abundant cytoplasm with abundant mucin or eosinophilic granules. The nuclei were oval or irregular with fine chromatin and inconspicuous nucleoli. Mitotic figures were common. Neuroendocrine granules and mucin granules could be identified clearly under electron microscope. All cases showed frequent perineural and lymphovascular invasions, lymphatic metastasis, and advanced stage. Regarding immunohistochemical and specific stains, the tumor cells expressed more than two neuroendocrine markers, particularly CD56 and synaptophysin which were diffusely positive in 7 of the 8 cases. They also showed intracellular mucin in the amphicrine components which was positive for D-PAS. KRAS G12C or NRAS Q61 gene mutations were found in 2 patients. Among the six cases with complete follow-up, four of them died of the disease within three years of the diagnoses, while two were alive without known disease progression. Conclusions: Colorectal AC is a rare, distinct entity with both epithelial and neuroendocrine differentiation. It mainly occurs in the sigmoid colon and rectum. It typically has aggressive clinical courses, dismal prognosis and characteristic histological features and immunophenotype, which highlight the importance of recognizing this entity for clinicians and pathologists.
Adult
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Aged
;
Aged, 80 and over
;
Biomarkers, Tumor
;
Carcinoma/pathology*
;
China
;
Colorectal Neoplasms/genetics*
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Female
;
Humans
;
Male
;
Middle Aged
;
Mucins
;
Prognosis
8.Aberrant Expression and Glycosylation of Mucins in Gastric Mucosal Disease.
Acta Academiae Medicinae Sinicae 2022;44(2):294-298
Mucins,a family of heavily glycosylated proteins,present mainly in epithelial cells.They function as essential barriers for epithelium and play important roles in cellular physiological processes.Aberrant expression and glycosylation of mucins in gastric epithelium occur at pathological conditions,such as Helicobacter pylori infection,chronic atrophic gastritis,intestinal metastasis,dysplasia,and gastric cancer.This review addresses the major roles played by mucins and associated O-glycan structures in normal gastric epithelium.Further,we expound the alterations of expression patterns and glycan signatures of mucins at those pathological conditions.
Gastric Mucosa/pathology*
;
Glycosylation
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Helicobacter Infections/pathology*
;
Helicobacter pylori/metabolism*
;
Humans
;
Mucins/metabolism*
;
Stomach Neoplasms/pathology*
9.A Case of Mucinous Gland Adenomatoid Hamartoma Originated from Submental Space
Sang Wook KIM ; Sung Min LEE ; Kang Hyun LEE ; Ki Joon PARK ; Hae Sang PARK
Korean Journal of Head and Neck Oncology 2019;35(2):61-65
Hamartomas are non-neoplastic malformations or congenital errors of tissue development. Hamartoma is composed by an excessive growth of mature tissue present in wrong proportions and abnormal arrangements. The lesion usually presents as a submucosal mass with ill-defined margins. Hamartoma occurs in all areas of the body, especially in the liver, spleen, kidney and lung. However, hamartoma is very rare in the head and neck. Presenting symptoms of hamartoma are typically vague and nonspecific. Treatment of hamartomas consists of adequate surgical excision. We present a 59 year-old male patient who presented with submental swelling. Malignancy could not be ruled out with preoperative radiologic examination, so surgical excision was planned. The mass was excised with transcervical approach. Histopathologic examination has confirmed the mass as a mucinous gland adenomatoid hamartoma.
Hamartoma
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Head
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Humans
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Kidney
;
Liver
;
Lung
;
Male
;
Mucins
;
Neck
;
Spleen
10.Association between body composition measured by bioelectrical impedance analysis and platelet-to-lymphocyte ratio in colorectal cancer
Woo Jin SONG ; Kyeong Eui KIM ; Sung Uk BAE ; Woon Kyung JEONG ; Seong Kyu BAEK
Korean Journal of Clinical Oncology 2019;15(1):7-14
PURPOSE: This study investigated the relationship between body composition and platelet-to-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC).METHODS: This retrospective study included 110 patients who underwent anthropometric measurement by bioelectrical impedance analysis before surgical treatment for CRC between May 2015 and June 2018.RESULTS: According to PLR, 45 patients (40.9%) had low PLR (PLR<150), and 65 patients (59.1%) had high PLR (PLR≥150). Serum hemoglobin (P<0.001) and albumin levels (P=0.021) were significantly lower in high PLR group. Tumor mass diameter was significantly larger in high PLR group (P=0.048) and the proportion of poorly differentiated or mucinous tumors was significantly higher in high PLR group (P=0.037). All indices related to fat (body fat mass, percent body fat, body fat mass of trunk, visceral fat area, fat mass index, measured fat thickness of abdomen) and two indices related to muscle (arm muscle circumference, measured muscle circumference of abdomen) were significantly lower in high PLR group (P<0.05). According to subgroup analysis based on the sex, all indices significantly differed between PLR groups; however, in females no index was significantly different between PLR groups.CONCLUSION: Body composition indices including fat and muscle indices measured by InBody 770 were related to PLR in CRC, especially in male patients. These results suggest that low muscle and fat indices may be related to poor prognosis of CRC.
Adipose Tissue
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Body Composition
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Colorectal Neoplasms
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Electric Impedance
;
Female
;
Humans
;
Intra-Abdominal Fat
;
Male
;
Mucins
;
Nutrition Assessment
;
Prognosis
;
Retrospective Studies

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