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*

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 ; 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

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 ; Calcium ; Echinococcosis/parasitology* ; Echinococcus/immunology* ; Echinococcus granulosus/immunology* ; Mucins

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 ; Male ; Animals ; 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 ; Mice, Inbred BALB C ; TRPV Cation Channels/metabolism* ; Drugs, Chinese Herbal

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 ; Helicobacter Infections/pathology* ; Helicobacter pylori/metabolism* ; Humans ; Mucins/metabolism* ; Stomach Neoplasms/pathology*

Adenocarcinoma ; Cervix Uteri ; Female ; Humans ; Mucins ; Uterine Cervical Neoplasms

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 ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Carcinoma/pathology* ; China ; Colorectal Neoplasms/genetics* ; Female ; Humans ; Male ; Middle Aged ; Mucins ; Prognosis

Adenocarcinoma, Follicular/surgery* ; Humans ; Mucins ; Thyroid Neoplasms/surgery*

BACKGROUND AND OBJECTIVES: Mucin is an important component of mucus that performs the first line of defense against inhaled pathogens and particles, lubrication of organs, and protection of airway. It is hyper-secreted in inflammatory airway diseases and is associated with morbidity and mortality of the affected patients. Resolvin, an autacoid of a specific lipid structure, exhibits anti-inflammatory property against inflammatory airway diseases although its effects on mucin secretion by human airway epithelial cells have not yet been demonstrated. In this regard, we investigated the effects of Resolvin on lipopolysaccharide (LPS)-induced mucin expression in human airway epithelial cells. MATERIALS AND METHOD: In mucin-producing human NCI-H292 epithelial cells, the effects and brief signaling pathways of Resolvin D1 (RvD1) and Resolvin E1 (RvE1) on the LPS-induced MUC4, MUC5AC, and MUC5B expression were investigated using reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot analysis. RESULTS: RvD1 attenuated LPS-induced MUC4, MUC5AC, and MUC5B mRNA expression and protein production in human NCI-H292 cells while RvE1 did not. RvD1 significantly blocked LPS-induced activated phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) and p38 MAPK and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) while RvE1 did not. CONCLUSION: These results suggest that RvD1 attenuates LPS-induced MUC4, MUC5AC, and MUC5B expressions via ERK1/2 MAPK, p38 MAPK, and NF-κB signaling pathways in airway epithelial cells. Therefore, RvD1 may modulate the control of mucus-hypersecretion in inflammatory airway diseases.
B-Lymphocytes ; Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells* ; Humans* ; Lubrication ; Methods ; Mortality ; Mucins* ; Mucus ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; RNA, Messenger

Spontaneous regression of tumors is an extremely rare event in hepatocellular carcinoma (HCC) with only a few reports available. With the accumulation of clinical information and tumor immunogenetics, several mechanisms for the cystic changes of HCC have been suggested, including arterial thrombosis, inflammation, and rapid tumor growth. This paper reports an uncommon case of the partial regression of HCC, which was initially misdiagnosed as a mucinous cystic neoplasm of the liver due to the unusual radiologic findings. A 78-year-old female with the hepatitis B virus and liver cirrhosis presented with an approximately 5 cm-sized cystic mass of the liver. From the radiologic evidence of a papillary-like projection from the cyst wall toward the inner side, the initial impression was a mucinous cystic neoplasm of the liver. The patient underwent a surgical resection and finally, cystic degeneration of HCC, in which approximately 80% necrosis was noted. This case suggests that if a cystic neoplasm of liver appears in a patient with a high risk of HCC on a hepatobiliary imaging study, it is prudent to consider the cystic degeneration of HCC in a differential diagnosis.
Aged ; Carcinoma, Hepatocellular ; Diagnosis, Differential ; Diagnostic Errors ; Female ; Hepatitis B virus ; Humans ; Immunogenetics ; Inflammation ; Liver ; Liver Cirrhosis ; Liver Neoplasms ; Magnetic Resonance Imaging ; Mucins ; Necrosis ; Thrombosis