Objective:To investigate the anti-inflammatory,antioxidant,and goblet cell-stimulating effects of a suspension of Ophiopogon japonicus(L.f.)Ker Gawl.(O.japonicus,Mai Dong)extract combined with hyaluronic acid(HA)in th...Objective:To investigate the anti-inflammatory,antioxidant,and goblet cell-stimulating effects of a suspension of Ophiopogon japonicus(L.f.)Ker Gawl.(O.japonicus,Mai Dong)extract combined with hyaluronic acid(HA)in the mouse model with dry eye disease(DED).Methods:A DED mouse model was induced using benzalkonium chloride(BAK),followed by treatment with O.japonicus extract-containing eye drops at varying concentrations.Experimental groups included a normal control,a DED model control,a positive control,and an O.japonicus extract-treated group.Corneal fluorescein staining and tear break-up time(TBUT)were used to assess tear film stability and ocular surface integrity.Enzyme-linked immunosorbent assay(ELISA)measured inflammatory factor levels in corneal and conjunctival tissues,whereas Western blot(WB)analyzed key antioxidant and inflammatory markers,including nuclear factor erythroid 2-related factor(2Nrf2)and heme oxygenase 1(HO-1).Periodic acid-schiff(PAS)staining and immunofluorescence were used to evaluate goblet cell density and mucin secretion.Results:O.japonicus extract significantly improved corneal damage,reduced fluorescein staining scores,prolonged TBUT,and increased tear secretion.It downregulated inflammatory markers,including interleukin-8(IL-8),interleukin-1β(IL-1β),and interferon-g(IFN-γ)while upregulating Nrf2,HO-1,and the interleukin-13(IL-13)/IFN-γ ratio,alleviating oxidative stress and inflammation.PAS staining showed increased conjunctival goblet cell density and restored mucin secretion,enhancing tear film stability.Conclusion:O.japonicus extract demonstrated significant anti-inflammatory,antioxidant,and goblet cell-stimulating effects in a DED model,with good biocompatibility and promising therapeutic potential.Future research should optimize extraction processes and validate their efficacy and safety in clinical settings.展开更多
Conjunctival goblet cells are of great significance to the ocular surface.By secreting mucins-particularly MUC5AC-they play a pivotal role in stabilizing the tear film,safeguarding the cornea from environmental insult...Conjunctival goblet cells are of great significance to the ocular surface.By secreting mucins-particularly MUC5AC-they play a pivotal role in stabilizing the tear film,safeguarding the cornea from environmental insults,and preserving overall ocular homeostasis.Over the past decade,remarkable progress has been made in understanding the distinctive biological characteristics and regenerative potential of these specialized cells,opening novel avenues for treating various ocular surface disorders,ranging from dry eye syndrome and allergic conjunctivitis to more severe conditions such as Stevens-Johnson syndrome.This review comprehensively examines the morphology,function,and regulation of conjunctival goblet cells.Advanced imaging modalities,such as transmission electron microscopy,have provided in-depth insights into their ultrastructure.Densely packed mucin granules and a specialized secretory apparatus have been uncovered,highlighting the cells’proficiency in producing and releasing MUC5AC.These structural characterizations have significantly enhanced our understanding of how goblet cells contribute to maintaining a stable and protective mucosal barrier,which is crucial for ocular surface integrity.The review further delves into the intricate signaling networks governing the differentiation and regeneration of these cells.Key pathways,including Notch,Wnt/β-catenin,and TGF-β,have emerged as essential regulators of cell fate decisions,ensuring that goblet cells maintain their specialized functions.Critical transcription factors,such as Klf4,Klf5,and SPDEF,have been identified as indispensable for driving the differentiation process and sustaining the mature phenotype of goblet cells.Additionally,the modulatory effects of inflammatory mediators-such as IL-6,IL-13,and TNF-α-and growth factors,such as EGF and FGF,are explored.These molecular insights offer a robust framework for understanding the pathophysiological mechanisms underlying ocular surface diseases,wherein the dysregulation of these processes often results in diminished goblet cell numbers and impaired tear film stability.Innovative methodological approaches have provided a strong impetus to this field.The development of three-dimensional(3D)in vitro culture systems that replicate the native conjunctival microenvironment has enabled more physiologically relevant investigations of goblet cell biology.Moreover,the integration of stem cell technologies-including the use of induced pluripotent stem cells(iPSCs)and bone marrow-derived mesenchymal stem cells(BM-MSCs)-has made it possible to generate goblet cell-like epithelia,thereby presenting promising strategies for tissue engineering and regenerative therapies.The application of artificial intelligence in optimizing drug screening and biomaterial scaffold design represents an exciting frontier that may accelerate the translation of these findings into effective clinical interventions.In conclusion,this review underscores the central role of conjunctival goblet cells in preserving ocular surface health and illuminates the transformative potential of emerging regenerative approaches.Continued research focused on deciphering the intricate molecular mechanisms governing goblet cell function and regeneration is essential for developing innovative,targeted therapies that can significantly improve the management of ocular surface diseases and enhance patient quality of life.展开更多
BACKGROUND Goblet cell carcinoid(GCC)of the appendix is a rare tumor characterized by neuroendocrine and adenocarcinoma features.Accurate preoperative diagnosis is very difficult,with most patients complaining mainly ...BACKGROUND Goblet cell carcinoid(GCC)of the appendix is a rare tumor characterized by neuroendocrine and adenocarcinoma features.Accurate preoperative diagnosis is very difficult,with most patients complaining mainly of abdominal pain.Computed tomography shows swelling of the appendix,so diagnosis is usually made incidentally after appendectomy based on a preoperative diagnosis of appendicitis.Even if a patient undergoes preoperative colonoscopy,accurate endoscopic diagnosis is very difficult because GCC shows a submucosal growth pattern with invasion of the appendiceal wall.CASE SUMMARY Between 2017 and 2022,6 patients with GCC were treated in our hospital.The presenting complaint for 5 of these 6 patients was abdominal pain.All 5 patients underwent appendectomy,including 4 for a preoperative diagnosis of appendicitis and the other for diagnosis and treatment of an appendiceal tumor.The sixth patient presented with vomiting and underwent ileocecal resection for GCC diagnosed from preoperative biopsy.Although 2 patients with GCC underwent colonoscopy,no neoplastic changes were identified.Two of the six patients showed lymph node metastasis on pathological examination.As of the last followup(median:15 mo),all cases remained alive without recurrence.CONCLUSION As preoperative diagnosis of GCC is difficult,this possibility must be considered during surgical treatments for presumptive appendicitis.展开更多
[Objective] This study aimed to investigate the distribution law of different goblet cells in the intestinal tracts of African ostrich chicks. [Method] Alcian blue/pe- riodic acid-schiff reaction （AB/PAS） was adopte...[Objective] This study aimed to investigate the distribution law of different goblet cells in the intestinal tracts of African ostrich chicks. [Method] Alcian blue/pe- riodic acid-schiff reaction （AB/PAS） was adopted to observe and analyze the types and distribution of goblet cells in the intestinal tracts of ostrich chicks. Acid mu- copolysaccharide could be stained blue with alcian blue （AB）, and neutral mu- copolysaccharide could be stained red with periodic acid-schiff reagent （PAS）. [Result] According to AB/PAS results, goblet cells in the intestinal tracts were divided in- to four types： TypeⅠ was pure red, with AB negative result and PAS positive result containing neutral mucoitin; type Ⅱ was pure blue, with AB positive result and PAS negative result containing acidic mucoitin; type Ⅲ was purple reddish, with PAS posi- tive result greater than AB; typeⅣ was purple blue, with AB positive result greater than PAS. Large quantities of goblet cells were found in the intestinal tracts of os- trich chicks, mostly type III and IV.The quantities of goblet cells were decreased gradually in the duodenum, jejunum and ileum, while the quantities were increased in the cecum, colon and rectum. The goblet cells in the large intestine are more than that in the small intestine. The most quantities of goblet cells were contained in rectum. [Conclusion] These results indicate that the distribution of goblet cells is closely related with the structure and function of intestinal tracts. The mucus secret- ed by the goblet Cells plays a series of important roles in the digestion and mucosal immunization.展开更多
[Objective] This study aimed to investigate the effects of traditional Chinese medicine additives on numbers of lymphocytes and goblet cells in villus epithelia of layers under heat stress.[Method] A total of 180 88-d...[Objective] This study aimed to investigate the effects of traditional Chinese medicine additives on numbers of lymphocytes and goblet cells in villus epithelia of layers under heat stress.[Method] A total of 180 88-d-old healthy Esa Brown cocks were selected.They were randomly divided into 9 experimental groups：Room temperature control,High temperature control,VC addition group,High formula I,Moderate formula I,Low formula I,High formula II,Moderate formula II and Low formula II.The formula I and formula II were to add different herbal extracts to the diet of cocks with different doses.The cocks in the VC addition group were administered orally with same-concentration VC solution.After certain time,the cocks were slaughtered.Then the numbers of epithelial lymphocytes and goblet cells in various segments of small intestine were counted by using conventional histological section and HE staining.[Result] The numbers of lymphocytes and goblet cells in villus epithelia of layers under heat stress were decreased gradually with the proceeding of experiment.The herbal extracts of formula I and formula II all could promote the generation of lymphocytes and goblet cells.But the promoting effect of formula II was best.[Conclusion] The Chinese herbal medicine additives have a good relieving effect on heat stress in layers.展开更多
Goblet cell carcinoid is an enigmatic and rare tumor involving the appendix almost exclusively. Since its identification in 1969, understanding of this disease has evolved greatly, but issues regarding its histogenesi...Goblet cell carcinoid is an enigmatic and rare tumor involving the appendix almost exclusively. Since its identification in 1969, understanding of this disease has evolved greatly, but issues regarding its histogenesis, nomenclature and management are still conjectural. The published English language literature from 1966 to 2009 was retrieved via PubMed and reviewed. Various other names have been used for this entity such as adenocarcinoid, mucinous carcinoid, crypt cell carcinoma, and mucin-producing neuroendocrine tumor, although none have been found to be completely satisfactory or universally accepted. The tumor is thought to arise from pluripotent intestinal epithelial crypt-base stem cells by dual neuroendocrine and mucinous differentiation. GCCs present in the fifth to sixth decade and show no definite sex predominance. The most common clinical presentation is acute appendicitis, followed by abdominal pain and a mass. Fifty percent of the female patients present with ovarian metastases. The histologic hallmark of this entity is the presence of clusters of goblet cells in the lamina propria or submucosa stain for various neuroendocrine markers, though the intensity is often patchy. Atypia is usually minimal, but carcinomatous growth patterns may be seen. These may be of signet ring cell type or poorly differentiated adenocarcinoma. Recently molecular studies have shown these tumors to lack the signatures of adenocarcinoma but they have some changes similar to that of ileal carcinoids (allelic loss of chromosome 11q, 16q and 18q). The natural history of GCC is intermediate between carcinoids and adenocarcinomas of the appendix. The 5-year overall survival is 76%. The most important prognostic factor is the stage of disease. Appendectomy and right hemicolectomy are the main modalities of treatment, followed by adjuvant chemotherapy in select cases. There is some debate about the surgical approach for these tumors, and a summary of published series and recommendations are provided.展开更多
Malignant neoplasms of the appendix are rare and represent less than 1% of gastrointestinal cancers.Goblet cell carcinoids(GCC) tumors are a distinctive group of heterogeneous appendiceal neoplasm that exhibit unique ...Malignant neoplasms of the appendix are rare and represent less than 1% of gastrointestinal cancers.Goblet cell carcinoids(GCC) tumors are a distinctive group of heterogeneous appendiceal neoplasm that exhibit unique clinical and pathologic features.This review focuses on the current diagnostic procedures,pathogenesis,possible signaling mechanisms and treatment options for GCC.Perspectives for future research are discussed.The tumor likely arises from pluripotent intestinal epithelial crypt base stem cells.Previous findings of Notch signaling as a tumor suppressor in Neuroendocrine tumors may have a similar role in this tumor too.Loss of Notch signaling may be the driver mutation with other successive downstream mutations likely favors them into progressing and behavior similar to poorly differentiated adenocarcinoma with minimal neuroendocrine differentiation.A multidisciplinary approach is suggested for optimal outcomes.Surgery remains the main treatment modality.Simple appendectomy may be sufficient in early stages while right hemicolectomy is recommended for advanced tumors.Cytoreductive surgery with heated intraperitoneal chemotherapy may improve survival in a select few with metastatic peritoneal disease.These tumors have an unpredictable behavior even in early stages and local recurrence and delayed metastases may be seen.Lifelong surveillance is warranted.展开更多
Goblet cell carcinoid is an uncommon primary tumor of the vermiform appendix, characterized by dual endocrine and glandular differentiation. Whether goblet cell carcinoid represents a morphological variant of appendic...Goblet cell carcinoid is an uncommon primary tumor of the vermiform appendix, characterized by dual endocrine and glandular differentiation. Whether goblet cell carcinoid represents a morphological variant of appendiceal classical carcinoid or a mucin-producing adenocarcinoma is a matter of conjecture. Rare cases of goblet cell carcinoid with other concomitant appendiceal epithelial neoplasms have been documented. In this report, we describe a rare case of combined appendiceal goblet cell carcinoid and mucinous cystadenoma, and discuss the possible histopathogenesis of this combination.展开更多
Objective To determine the number of goblet cells, the change of MUC5AC expression in chronic obstructive pul- monary disease (COPD) patients and the relationship of smoking with goblet cell, MUC5AC, and lung function...Objective To determine the number of goblet cells, the change of MUC5AC expression in chronic obstructive pul- monary disease (COPD) patients and the relationship of smoking with goblet cell, MUC5AC, and lung function. Methods Eighteen patients undergoing lung resections for a solitary peripheral carcinoma were classified by lung function as having COPD. Twenty patients with normal lung function served as the control group. Normal lobe bronchioles far away from the lesion site were taken for paraffin section. Goblet cells were identified by AB/PAS staining and the ex- pression of MUC5AC in the paraffin’s section was tested by immunohistochemistry. Results Goblet cell hyperplasia was observed in the COPD group. The positive rate of goblet cell in COPD group (0.20% ± 0.10%) was significantly higher than that in the normal lung function group (0.13% ± 0.06%, P < 0.05). The posi- tive rate of MUC5AC expression in the COPD group (0.27% ± 0.09%) was higher than that in the normal lung function group (0.20% ± 0.10%, P < 0.05). The positive rate of goblet cell in smokers (27.93% ± 9.00%) of the COPD group and normal lung function group was higher than that in non-smokers (17.70% ± 9.37%, P < 0.05), while MUC5AC expression had no significant difference between smokers and non-smokers (17.88% ± 6.44% and 10.88% ± 7.10%, respectively). Conclusion For COPD patients with declined lung function, there were goblet cell hyperplasia and increased expres- sion of MUC5AC. MUC5AC expression up-regulation may due to goblet cell hyperplasia. Smoking may be an important factor for goblet cell hyperplasia.展开更多
Neuroendocrine neoplasms are the most common epithelial tumors among appendix tumors. Appendix tumors that are completely or partially composed of neuroendocrine cells are divided into two categories: Classic carcinoi...Neuroendocrine neoplasms are the most common epithelial tumors among appendix tumors. Appendix tumors that are completely or partially composed of neuroendocrine cells are divided into two categories: Classic carcinoid tumors and goblet cell carcinoid tumors(GCCT). They are known to progress more aggressively than classic(neuro) endocrine tumors. In this study, three cases with acute appendicitis symptoms are presented, including their clinical and histopathological findings. Microscopic examination detected GCCT in two cases and mixed adenoneuroendocrine carcinoma in one case, in addition to acute appendicitis.展开更多
To study the effects of estrogen on the structure of the intestinal mucosal barrier, 18 healthy female Wistar Rats underwent estrus synchronization. In diestrus, they were divided into three groups： one sham operated...To study the effects of estrogen on the structure of the intestinal mucosal barrier, 18 healthy female Wistar Rats underwent estrus synchronization. In diestrus, they were divided into three groups： one sham operated control group （SHAM） ; one ovariec- tomized group （OVX） ; and one ovariectomized plus estradiol benzoate group （ OVX ＋ E2 ）. Intestinal mu- cosal epithelial cells, intraepithelial lymphocytes （[EL）, and goblet cells （GCs） were observed by light microscope. The results showed that in the OVX group, the intestinal mucosa damaged obviously, the villus atrophied, the ratio of villus height to crypt depth reduced, and the number of IELs and GCs re- duced. The indicators of OVX ＋ Ez group were signif- icantly higher than OVX group, but some indicators were lower than SHAM. These indicated that the function of intestinal mucosal barrier was greatly dam- aged in ovariectomied rat, and proper dosage of estra- diol benzoate Would improve the function of small in- testinal mucosal barrier in ovariectomied rat to some degree.展开更多
[ Objective] To study the effects of Chinese herbal additives on the number of intraepithelial lymphocyte and goblet cells of intestinal villus of heat stress layers. [Method] 180 healthy 88-day-old ISA brown egg roos...[ Objective] To study the effects of Chinese herbal additives on the number of intraepithelial lymphocyte and goblet cells of intestinal villus of heat stress layers. [Method] 180 healthy 88-day-old ISA brown egg roosters were selected and randomly divided into nine treatment groups, nor- mal temperature control group, high temperature control group, VC group, prescription one high-dose group, prescription one middle-dose group, prescription one low-dose group, prescription two high-dose group, prescription two middle-dose group, prescription two low-dose group, respec- tively. Prescription one and two groups were respectively fed with low, medium and high concentrations of the three doses of Chinese herbal ex- tracts, and VC group was fed with the VC in aqueous solution. Histological sections conventional technology and HE staining method were used to observe the number of intraepithelial lymphocytes and goblet cells in each sections of small intestine of chicken. [ Result] The number of chicken in- testinal epithelial lymphocytes and goblet cells showed a gradually decreasing trend in a high-temperature state. [ Conclusion] Prescription one and two groups could promote the cytopoiesis of goblet cells and lymphocytes, and the effect of prescription two was the best. Moreover, Adding the Chinese herbs had good effects on relieving the heat stress of layers.展开更多
Goblet cells(GCs)are specialised guardians lining the intestine.They play a critical role in gut defence and immune regulation.GCs continuously secrete mucus creating a physical barrier to protect from pathogens while...Goblet cells(GCs)are specialised guardians lining the intestine.They play a critical role in gut defence and immune regulation.GCs continuously secrete mucus creating a physical barrier to protect from pathogens while harbouring symbiotic gut bacteria adapted to live within the mucus.GCs also form specialised GC-associated passages in a dynamic and regulated manner to deliver luminal antigens to immune cells,promoting gut tolerance and preventing inflammation.The composition of gut bacteria directly influences GC function,highlighting the intricate interplay between these components of a healthy gut.Indeed,imbalances in the gut microbiome can disrupt GC function,contributing to various gastrointestinal diseases like colorectal cancer,inflammatory bowel disease,cystic fibrosis,pathogen infections and liver diseases.This review explores the interplay between GCs and the immune system.We delve into the underlying mechanisms by which GC dysfunction contributes to the development and progression of gastrointestinal diseases.Finally,we examine current and potential treatments that target GCs and represent promising avenues for further investigation.展开更多
BACKGROUND Runchangningshen paste(RCNSP)is a paste made of four medicinal and edible homologous Chinese medicine mixed with honey.It is known for its ability to nourish yin and blood as well as to loosen the bowel to ...BACKGROUND Runchangningshen paste(RCNSP)is a paste made of four medicinal and edible homologous Chinese medicine mixed with honey.It is known for its ability to nourish yin and blood as well as to loosen the bowel to relieve constipation.The pathophysiology of functional constipation(FC)is associated with a reduction in mucin-2(MUC2)secretion and microbial dysbiosis.AIM To investigate the underlying mechanism of RCNSP against FC through MUC2 and the gut mucosal microbiota.METHODS Ultra-performance liquid chromatography tandem mass spectrometry characterized RCNSP composition to elucidate the material basis of action.FC model was induced via loperamide gavage(16 mg/kg)twice daily for 7 days.Applying defecation function and gastrointestinal motility to assess constipation severity.Hematoxylin and eosin and Alcian blue-periodic acid-schiff staining analyzed colonic mucosal morphology.Transmission electron microscope was used to observe the ultrastructure of goblet cells(GCs).Immunofluorescence colocalization,quantitative PCR,and western blot assessed the impact of RCNSP on gene and protein expression within the NLRP6/autophagy pathway.16S rDNA was employed to sequence the gut mucosal microbiota.RESULTS RCNSP contained 12 components with potential laxative effects.It enhanced defecation function,accelerated gastrointestinal motility,and maintained colonic mucosal integrity.RCNSP treatment significantly increased GC abundance and MUC2 production while preserving GC ultrastructure.At the molecular level,RCNSP enhanced the colocalized expression of key regulatory proteins and modulated mRNA and protein expressions in the NLRP6/autophagy pathway.Through 16S rDNA sequencing analysis,RCNSP significantly altered the mucosal microbiota composition.Specifically,it increased beneficial bacterial strains while reducing harmful ones.Simultaneously,RCNSP reduced butyrate-producing bacteria like Proteobacteria,Enterobacteriaceae,Blautia,and Eubacterium and decreased hydrogen sulfide-producing species,such as Prevotellaceae.It also reduced bile acidinhibiting species,such as g_Eubacter_coprostanoligenes_group and Erysipelotrichaceae while increasing bile acidproducing species,such as Colidextribacter.CONCLUSION Our findings suggested that RCNSP ameliorated constipation through a dual mechanism:It stimulated colonic MUC2 secretion by activating NLRP6 inflammasome-mediated autophagy and modulated the composition of the mucosal microbiota.展开更多
Iron is an important micronutrient that plays a vital role in host defenses and bacterial pathogenicity. As iron treatments increase the risk of infection by stimulating the growth and virulence of bacterial pathogens...Iron is an important micronutrient that plays a vital role in host defenses and bacterial pathogenicity. As iron treatments increase the risk of infection by stimulating the growth and virulence of bacterial pathogens, their roles in anti-infection immunity have frequently been underestimated. To estimate whether adequate dietary iron intake would help defend against pathogenic bacterial infection, mice were fed iron-deficient(2 mg kg-1feed), iron-sufficient(35 mg kg-1feed), or iron-enriched diet(350 mg kg-1feed) for 12 weeks, followed by oral infection with Salmonella typhimurium. Our results revealed that dietary iron intake improved mucus layer function and decelerated the invasion of the pathogenic bacteria, Salmonella typhimurium. Positive correlations between serum iron and the number of goblet cells and mucin2 were found in response to total iron intake in mice.Unabsorbed iron in the intestinal tract affected the gut microbiota composition, and the abundance of Bacteroidales, family Muribaculaceae, was positively correlated with their mucin2 expression. However, the results from antibiotic-treated mice showed that the dietary iron-regulated mucin layer function was not microbial-dependent. Furthermore, in vitro studies revealed that ferric citrate directly induced mucin2 expression and promoted the proliferation of goblet cells in both ileal and colonic organoids. Thus, dietary iron intake improves serum iron levels, regulates goblet cell regeneration and mucin layer function, and plays a positive role in the prevention of pathogenic bacteria.展开更多
基金the National Natural Science Foundation of China(82070928 and 82171026).
文摘Objective:To investigate the anti-inflammatory,antioxidant,and goblet cell-stimulating effects of a suspension of Ophiopogon japonicus(L.f.)Ker Gawl.(O.japonicus,Mai Dong)extract combined with hyaluronic acid(HA)in the mouse model with dry eye disease(DED).Methods:A DED mouse model was induced using benzalkonium chloride(BAK),followed by treatment with O.japonicus extract-containing eye drops at varying concentrations.Experimental groups included a normal control,a DED model control,a positive control,and an O.japonicus extract-treated group.Corneal fluorescein staining and tear break-up time(TBUT)were used to assess tear film stability and ocular surface integrity.Enzyme-linked immunosorbent assay(ELISA)measured inflammatory factor levels in corneal and conjunctival tissues,whereas Western blot(WB)analyzed key antioxidant and inflammatory markers,including nuclear factor erythroid 2-related factor(2Nrf2)and heme oxygenase 1(HO-1).Periodic acid-schiff(PAS)staining and immunofluorescence were used to evaluate goblet cell density and mucin secretion.Results:O.japonicus extract significantly improved corneal damage,reduced fluorescein staining scores,prolonged TBUT,and increased tear secretion.It downregulated inflammatory markers,including interleukin-8(IL-8),interleukin-1β(IL-1β),and interferon-g(IFN-γ)while upregulating Nrf2,HO-1,and the interleukin-13(IL-13)/IFN-γ ratio,alleviating oxidative stress and inflammation.PAS staining showed increased conjunctival goblet cell density and restored mucin secretion,enhancing tear film stability.Conclusion:O.japonicus extract demonstrated significant anti-inflammatory,antioxidant,and goblet cell-stimulating effects in a DED model,with good biocompatibility and promising therapeutic potential.Future research should optimize extraction processes and validate their efficacy and safety in clinical settings.
基金supported by grants from the National Natural Science Foundation of China(81970771)Project supported by the Natural Science Foundation of Fujian Province,China(2020D027).
文摘Conjunctival goblet cells are of great significance to the ocular surface.By secreting mucins-particularly MUC5AC-they play a pivotal role in stabilizing the tear film,safeguarding the cornea from environmental insults,and preserving overall ocular homeostasis.Over the past decade,remarkable progress has been made in understanding the distinctive biological characteristics and regenerative potential of these specialized cells,opening novel avenues for treating various ocular surface disorders,ranging from dry eye syndrome and allergic conjunctivitis to more severe conditions such as Stevens-Johnson syndrome.This review comprehensively examines the morphology,function,and regulation of conjunctival goblet cells.Advanced imaging modalities,such as transmission electron microscopy,have provided in-depth insights into their ultrastructure.Densely packed mucin granules and a specialized secretory apparatus have been uncovered,highlighting the cells’proficiency in producing and releasing MUC5AC.These structural characterizations have significantly enhanced our understanding of how goblet cells contribute to maintaining a stable and protective mucosal barrier,which is crucial for ocular surface integrity.The review further delves into the intricate signaling networks governing the differentiation and regeneration of these cells.Key pathways,including Notch,Wnt/β-catenin,and TGF-β,have emerged as essential regulators of cell fate decisions,ensuring that goblet cells maintain their specialized functions.Critical transcription factors,such as Klf4,Klf5,and SPDEF,have been identified as indispensable for driving the differentiation process and sustaining the mature phenotype of goblet cells.Additionally,the modulatory effects of inflammatory mediators-such as IL-6,IL-13,and TNF-α-and growth factors,such as EGF and FGF,are explored.These molecular insights offer a robust framework for understanding the pathophysiological mechanisms underlying ocular surface diseases,wherein the dysregulation of these processes often results in diminished goblet cell numbers and impaired tear film stability.Innovative methodological approaches have provided a strong impetus to this field.The development of three-dimensional(3D)in vitro culture systems that replicate the native conjunctival microenvironment has enabled more physiologically relevant investigations of goblet cell biology.Moreover,the integration of stem cell technologies-including the use of induced pluripotent stem cells(iPSCs)and bone marrow-derived mesenchymal stem cells(BM-MSCs)-has made it possible to generate goblet cell-like epithelia,thereby presenting promising strategies for tissue engineering and regenerative therapies.The application of artificial intelligence in optimizing drug screening and biomaterial scaffold design represents an exciting frontier that may accelerate the translation of these findings into effective clinical interventions.In conclusion,this review underscores the central role of conjunctival goblet cells in preserving ocular surface health and illuminates the transformative potential of emerging regenerative approaches.Continued research focused on deciphering the intricate molecular mechanisms governing goblet cell function and regeneration is essential for developing innovative,targeted therapies that can significantly improve the management of ocular surface diseases and enhance patient quality of life.
文摘BACKGROUND Goblet cell carcinoid(GCC)of the appendix is a rare tumor characterized by neuroendocrine and adenocarcinoma features.Accurate preoperative diagnosis is very difficult,with most patients complaining mainly of abdominal pain.Computed tomography shows swelling of the appendix,so diagnosis is usually made incidentally after appendectomy based on a preoperative diagnosis of appendicitis.Even if a patient undergoes preoperative colonoscopy,accurate endoscopic diagnosis is very difficult because GCC shows a submucosal growth pattern with invasion of the appendiceal wall.CASE SUMMARY Between 2017 and 2022,6 patients with GCC were treated in our hospital.The presenting complaint for 5 of these 6 patients was abdominal pain.All 5 patients underwent appendectomy,including 4 for a preoperative diagnosis of appendicitis and the other for diagnosis and treatment of an appendiceal tumor.The sixth patient presented with vomiting and underwent ileocecal resection for GCC diagnosed from preoperative biopsy.Although 2 patients with GCC underwent colonoscopy,no neoplastic changes were identified.Two of the six patients showed lymph node metastasis on pathological examination.As of the last followup(median:15 mo),all cases remained alive without recurrence.CONCLUSION As preoperative diagnosis of GCC is difficult,this possibility must be considered during surgical treatments for presumptive appendicitis.
基金Supported by National Natural Science Foundation of China (30972152)Specialized Research Fund for the Doctoral Program of Higher Education of China (200805040023)~~
文摘[Objective] This study aimed to investigate the distribution law of different goblet cells in the intestinal tracts of African ostrich chicks. [Method] Alcian blue/pe- riodic acid-schiff reaction （AB/PAS） was adopted to observe and analyze the types and distribution of goblet cells in the intestinal tracts of ostrich chicks. Acid mu- copolysaccharide could be stained blue with alcian blue （AB）, and neutral mu- copolysaccharide could be stained red with periodic acid-schiff reagent （PAS）. [Result] According to AB/PAS results, goblet cells in the intestinal tracts were divided in- to four types： TypeⅠ was pure red, with AB negative result and PAS positive result containing neutral mucoitin; type Ⅱ was pure blue, with AB positive result and PAS negative result containing acidic mucoitin; type Ⅲ was purple reddish, with PAS posi- tive result greater than AB; typeⅣ was purple blue, with AB positive result greater than PAS. Large quantities of goblet cells were found in the intestinal tracts of os- trich chicks, mostly type III and IV.The quantities of goblet cells were decreased gradually in the duodenum, jejunum and ileum, while the quantities were increased in the cecum, colon and rectum. The goblet cells in the large intestine are more than that in the small intestine. The most quantities of goblet cells were contained in rectum. [Conclusion] These results indicate that the distribution of goblet cells is closely related with the structure and function of intestinal tracts. The mucus secret- ed by the goblet Cells plays a series of important roles in the digestion and mucosal immunization.
基金Supported by National Natural Science Foundation of China(31472230)Hebei Provinceial Natrual Science Foundation of China(2014407068)Project of HebeiScience and Technology Department(14966610D,13826615D,12220408D)~~
文摘[Objective] This study aimed to investigate the effects of traditional Chinese medicine additives on numbers of lymphocytes and goblet cells in villus epithelia of layers under heat stress.[Method] A total of 180 88-d-old healthy Esa Brown cocks were selected.They were randomly divided into 9 experimental groups：Room temperature control,High temperature control,VC addition group,High formula I,Moderate formula I,Low formula I,High formula II,Moderate formula II and Low formula II.The formula I and formula II were to add different herbal extracts to the diet of cocks with different doses.The cocks in the VC addition group were administered orally with same-concentration VC solution.After certain time,the cocks were slaughtered.Then the numbers of epithelial lymphocytes and goblet cells in various segments of small intestine were counted by using conventional histological section and HE staining.[Result] The numbers of lymphocytes and goblet cells in villus epithelia of layers under heat stress were decreased gradually with the proceeding of experiment.The herbal extracts of formula I and formula II all could promote the generation of lymphocytes and goblet cells.But the promoting effect of formula II was best.[Conclusion] The Chinese herbal medicine additives have a good relieving effect on heat stress in layers.
文摘Goblet cell carcinoid is an enigmatic and rare tumor involving the appendix almost exclusively. Since its identification in 1969, understanding of this disease has evolved greatly, but issues regarding its histogenesis, nomenclature and management are still conjectural. The published English language literature from 1966 to 2009 was retrieved via PubMed and reviewed. Various other names have been used for this entity such as adenocarcinoid, mucinous carcinoid, crypt cell carcinoma, and mucin-producing neuroendocrine tumor, although none have been found to be completely satisfactory or universally accepted. The tumor is thought to arise from pluripotent intestinal epithelial crypt-base stem cells by dual neuroendocrine and mucinous differentiation. GCCs present in the fifth to sixth decade and show no definite sex predominance. The most common clinical presentation is acute appendicitis, followed by abdominal pain and a mass. Fifty percent of the female patients present with ovarian metastases. The histologic hallmark of this entity is the presence of clusters of goblet cells in the lamina propria or submucosa stain for various neuroendocrine markers, though the intensity is often patchy. Atypia is usually minimal, but carcinomatous growth patterns may be seen. These may be of signet ring cell type or poorly differentiated adenocarcinoma. Recently molecular studies have shown these tumors to lack the signatures of adenocarcinoma but they have some changes similar to that of ileal carcinoids (allelic loss of chromosome 11q, 16q and 18q). The natural history of GCC is intermediate between carcinoids and adenocarcinomas of the appendix. The 5-year overall survival is 76%. The most important prognostic factor is the stage of disease. Appendectomy and right hemicolectomy are the main modalities of treatment, followed by adjuvant chemotherapy in select cases. There is some debate about the surgical approach for these tumors, and a summary of published series and recommendations are provided.
文摘Malignant neoplasms of the appendix are rare and represent less than 1% of gastrointestinal cancers.Goblet cell carcinoids(GCC) tumors are a distinctive group of heterogeneous appendiceal neoplasm that exhibit unique clinical and pathologic features.This review focuses on the current diagnostic procedures,pathogenesis,possible signaling mechanisms and treatment options for GCC.Perspectives for future research are discussed.The tumor likely arises from pluripotent intestinal epithelial crypt base stem cells.Previous findings of Notch signaling as a tumor suppressor in Neuroendocrine tumors may have a similar role in this tumor too.Loss of Notch signaling may be the driver mutation with other successive downstream mutations likely favors them into progressing and behavior similar to poorly differentiated adenocarcinoma with minimal neuroendocrine differentiation.A multidisciplinary approach is suggested for optimal outcomes.Surgery remains the main treatment modality.Simple appendectomy may be sufficient in early stages while right hemicolectomy is recommended for advanced tumors.Cytoreductive surgery with heated intraperitoneal chemotherapy may improve survival in a select few with metastatic peritoneal disease.These tumors have an unpredictable behavior even in early stages and local recurrence and delayed metastases may be seen.Lifelong surveillance is warranted.
文摘Goblet cell carcinoid is an uncommon primary tumor of the vermiform appendix, characterized by dual endocrine and glandular differentiation. Whether goblet cell carcinoid represents a morphological variant of appendiceal classical carcinoid or a mucin-producing adenocarcinoma is a matter of conjecture. Rare cases of goblet cell carcinoid with other concomitant appendiceal epithelial neoplasms have been documented. In this report, we describe a rare case of combined appendiceal goblet cell carcinoid and mucinous cystadenoma, and discuss the possible histopathogenesis of this combination.
文摘Objective To determine the number of goblet cells, the change of MUC5AC expression in chronic obstructive pul- monary disease (COPD) patients and the relationship of smoking with goblet cell, MUC5AC, and lung function. Methods Eighteen patients undergoing lung resections for a solitary peripheral carcinoma were classified by lung function as having COPD. Twenty patients with normal lung function served as the control group. Normal lobe bronchioles far away from the lesion site were taken for paraffin section. Goblet cells were identified by AB/PAS staining and the ex- pression of MUC5AC in the paraffin’s section was tested by immunohistochemistry. Results Goblet cell hyperplasia was observed in the COPD group. The positive rate of goblet cell in COPD group (0.20% ± 0.10%) was significantly higher than that in the normal lung function group (0.13% ± 0.06%, P < 0.05). The posi- tive rate of MUC5AC expression in the COPD group (0.27% ± 0.09%) was higher than that in the normal lung function group (0.20% ± 0.10%, P < 0.05). The positive rate of goblet cell in smokers (27.93% ± 9.00%) of the COPD group and normal lung function group was higher than that in non-smokers (17.70% ± 9.37%, P < 0.05), while MUC5AC expression had no significant difference between smokers and non-smokers (17.88% ± 6.44% and 10.88% ± 7.10%, respectively). Conclusion For COPD patients with declined lung function, there were goblet cell hyperplasia and increased expres- sion of MUC5AC. MUC5AC expression up-regulation may due to goblet cell hyperplasia. Smoking may be an important factor for goblet cell hyperplasia.
文摘Neuroendocrine neoplasms are the most common epithelial tumors among appendix tumors. Appendix tumors that are completely or partially composed of neuroendocrine cells are divided into two categories: Classic carcinoid tumors and goblet cell carcinoid tumors(GCCT). They are known to progress more aggressively than classic(neuro) endocrine tumors. In this study, three cases with acute appendicitis symptoms are presented, including their clinical and histopathological findings. Microscopic examination detected GCCT in two cases and mixed adenoneuroendocrine carcinoma in one case, in addition to acute appendicitis.
文摘To study the effects of estrogen on the structure of the intestinal mucosal barrier, 18 healthy female Wistar Rats underwent estrus synchronization. In diestrus, they were divided into three groups： one sham operated control group （SHAM） ; one ovariec- tomized group （OVX） ; and one ovariectomized plus estradiol benzoate group （ OVX ＋ E2 ）. Intestinal mu- cosal epithelial cells, intraepithelial lymphocytes （[EL）, and goblet cells （GCs） were observed by light microscope. The results showed that in the OVX group, the intestinal mucosa damaged obviously, the villus atrophied, the ratio of villus height to crypt depth reduced, and the number of IELs and GCs re- duced. The indicators of OVX ＋ Ez group were signif- icantly higher than OVX group, but some indicators were lower than SHAM. These indicated that the function of intestinal mucosal barrier was greatly dam- aged in ovariectomied rat, and proper dosage of estra- diol benzoate Would improve the function of small in- testinal mucosal barrier in ovariectomied rat to some degree.
基金Supported by Hebei Science and Technology Department Item(08150132A,12220408D)Hebei Education Department Item(ZH2011244 )+1 种基金Shijiazhuang Science and Technology Bureau Item(1150093A )Hebei Science and Technology Normal University Doctor Fund Item(2007YB002)
文摘[ Objective] To study the effects of Chinese herbal additives on the number of intraepithelial lymphocyte and goblet cells of intestinal villus of heat stress layers. [Method] 180 healthy 88-day-old ISA brown egg roosters were selected and randomly divided into nine treatment groups, nor- mal temperature control group, high temperature control group, VC group, prescription one high-dose group, prescription one middle-dose group, prescription one low-dose group, prescription two high-dose group, prescription two middle-dose group, prescription two low-dose group, respec- tively. Prescription one and two groups were respectively fed with low, medium and high concentrations of the three doses of Chinese herbal ex- tracts, and VC group was fed with the VC in aqueous solution. Histological sections conventional technology and HE staining method were used to observe the number of intraepithelial lymphocytes and goblet cells in each sections of small intestine of chicken. [ Result] The number of chicken in- testinal epithelial lymphocytes and goblet cells showed a gradually decreasing trend in a high-temperature state. [ Conclusion] Prescription one and two groups could promote the cytopoiesis of goblet cells and lymphocytes, and the effect of prescription two was the best. Moreover, Adding the Chinese herbs had good effects on relieving the heat stress of layers.
基金supported in part by NIH grants R01 AA029106-01A1,1R21 AA030654-01A1,P30 AR073761the D34 HP31027 UC San Diego's Hispanic Center of Excellence,by the Southern California Research Center for Alcoholic Liver and Pancreatic Diseases(ALPD)and Cirrhosis(P50 AA011999)funded by the National Institute on Alcohol Abuse and Alcoholism(NIAAA)and its Animal Core facilities,by the American Association for the Study of Liver Diseases(AASLD)Pinnacle Research Award in Liver Disease(8998GA)+1 种基金by the Isenberg Endowed Fellowship jointly awarded by the Pilot/Feasibility Program of the San Diego Digestive Diseases Research Center(SDDRC),the Hellman Family Foundation(P30 DK120515)(to CL)the postdoctoral program(POS_2023_2_0015),Basque Government(to AE).
文摘Goblet cells(GCs)are specialised guardians lining the intestine.They play a critical role in gut defence and immune regulation.GCs continuously secrete mucus creating a physical barrier to protect from pathogens while harbouring symbiotic gut bacteria adapted to live within the mucus.GCs also form specialised GC-associated passages in a dynamic and regulated manner to deliver luminal antigens to immune cells,promoting gut tolerance and preventing inflammation.The composition of gut bacteria directly influences GC function,highlighting the intricate interplay between these components of a healthy gut.Indeed,imbalances in the gut microbiome can disrupt GC function,contributing to various gastrointestinal diseases like colorectal cancer,inflammatory bowel disease,cystic fibrosis,pathogen infections and liver diseases.This review explores the interplay between GCs and the immune system.We delve into the underlying mechanisms by which GC dysfunction contributes to the development and progression of gastrointestinal diseases.Finally,we examine current and potential treatments that target GCs and represent promising avenues for further investigation.
基金Supported by National Natural Science Foundation of China,No.82174309and Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Siming Fund Special Project for Scientific Research,No.SGKJ-202304.
文摘BACKGROUND Runchangningshen paste(RCNSP)is a paste made of four medicinal and edible homologous Chinese medicine mixed with honey.It is known for its ability to nourish yin and blood as well as to loosen the bowel to relieve constipation.The pathophysiology of functional constipation(FC)is associated with a reduction in mucin-2(MUC2)secretion and microbial dysbiosis.AIM To investigate the underlying mechanism of RCNSP against FC through MUC2 and the gut mucosal microbiota.METHODS Ultra-performance liquid chromatography tandem mass spectrometry characterized RCNSP composition to elucidate the material basis of action.FC model was induced via loperamide gavage(16 mg/kg)twice daily for 7 days.Applying defecation function and gastrointestinal motility to assess constipation severity.Hematoxylin and eosin and Alcian blue-periodic acid-schiff staining analyzed colonic mucosal morphology.Transmission electron microscope was used to observe the ultrastructure of goblet cells(GCs).Immunofluorescence colocalization,quantitative PCR,and western blot assessed the impact of RCNSP on gene and protein expression within the NLRP6/autophagy pathway.16S rDNA was employed to sequence the gut mucosal microbiota.RESULTS RCNSP contained 12 components with potential laxative effects.It enhanced defecation function,accelerated gastrointestinal motility,and maintained colonic mucosal integrity.RCNSP treatment significantly increased GC abundance and MUC2 production while preserving GC ultrastructure.At the molecular level,RCNSP enhanced the colocalized expression of key regulatory proteins and modulated mRNA and protein expressions in the NLRP6/autophagy pathway.Through 16S rDNA sequencing analysis,RCNSP significantly altered the mucosal microbiota composition.Specifically,it increased beneficial bacterial strains while reducing harmful ones.Simultaneously,RCNSP reduced butyrate-producing bacteria like Proteobacteria,Enterobacteriaceae,Blautia,and Eubacterium and decreased hydrogen sulfide-producing species,such as Prevotellaceae.It also reduced bile acidinhibiting species,such as g_Eubacter_coprostanoligenes_group and Erysipelotrichaceae while increasing bile acidproducing species,such as Colidextribacter.CONCLUSION Our findings suggested that RCNSP ameliorated constipation through a dual mechanism:It stimulated colonic MUC2 secretion by activating NLRP6 inflammasome-mediated autophagy and modulated the composition of the mucosal microbiota.
基金supported by Outstanding Youth Fund of Hunan Natural Science Foundation (2021JJ20045)the National Natural Science Foundation of China (32130099)+4 种基金the Science and Technology Program of Hunan Province (2020NK2013, 2020GK4095)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2022370)the key R&D Program of Guangxi Province (2021AB20063)the China Agriculture Research System of MOF and MARAthe National Center of Technology Innovation for Pigs。
文摘Iron is an important micronutrient that plays a vital role in host defenses and bacterial pathogenicity. As iron treatments increase the risk of infection by stimulating the growth and virulence of bacterial pathogens, their roles in anti-infection immunity have frequently been underestimated. To estimate whether adequate dietary iron intake would help defend against pathogenic bacterial infection, mice were fed iron-deficient(2 mg kg-1feed), iron-sufficient(35 mg kg-1feed), or iron-enriched diet(350 mg kg-1feed) for 12 weeks, followed by oral infection with Salmonella typhimurium. Our results revealed that dietary iron intake improved mucus layer function and decelerated the invasion of the pathogenic bacteria, Salmonella typhimurium. Positive correlations between serum iron and the number of goblet cells and mucin2 were found in response to total iron intake in mice.Unabsorbed iron in the intestinal tract affected the gut microbiota composition, and the abundance of Bacteroidales, family Muribaculaceae, was positively correlated with their mucin2 expression. However, the results from antibiotic-treated mice showed that the dietary iron-regulated mucin layer function was not microbial-dependent. Furthermore, in vitro studies revealed that ferric citrate directly induced mucin2 expression and promoted the proliferation of goblet cells in both ileal and colonic organoids. Thus, dietary iron intake improves serum iron levels, regulates goblet cell regeneration and mucin layer function, and plays a positive role in the prevention of pathogenic bacteria.
