The mucosal barrier remains a major barrier in the pulmonary drug delivery system,as mucociliary clearance in the airway accelerates the removal of inhaled nanoparticles(NPs).Herein,we designed and developed the inhal...The mucosal barrier remains a major barrier in the pulmonary drug delivery system,as mucociliary clearance in the airway accelerates the removal of inhaled nanoparticles(NPs).Herein,we designed and developed the inhalable Pluronic F127-modified silk fibroin NPs loading with quercetin(marked as QR-SF(PF127)NPs),aiming to solve the airway mucus barrier and improve the cancer therapeutic effect of QR.The PF127 coating on the SF NPs could attenuate the interaction between NPs and mucin proteins,thus facilitating the diffusion of SF(PF127)NPs in the mucus layer.The QR-SF(PF127)NPs had particle sizes of approximately 200 nm with negatively charged surfaces and showed constant drug release properties.Fluorescence recovery after photobleaching(FRAP)assay and transepithelial transport test showed that QR-SF(PF127)NPs exhibited superior mucus-penetrating ability in artificial mucus and monolayer Calu-3 cell model.Notably,a large amount of QR-SF(PF127)NPs distributed uniformly in the mice airway section,indicating the good retention of NPs in the respiratory tract.Themicemelanoma lungmetastasismodel was established,and the therapeutic effect of QR-SF(PF127)NPs was significantly improved in vivo.PF127-modified SF NPs may be a promising strategy to attenuate the interaction with mucin proteins and enhancemucus penetration efficiency in the pulmonary drug delivery system.展开更多
Mucus can effectively protect the exposed mucosal surfaces due to its adhesive and viscoelastic properties.Most foreign particulates are efficiently trapped in mucus layers via steric obstruction and adhesion.Trapped ...Mucus can effectively protect the exposed mucosal surfaces due to its adhesive and viscoelastic properties.Most foreign particulates are efficiently trapped in mucus layers via steric obstruction and adhesion.Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on their location sites.This article focuses on describing the tenacious mucus barrier properties,the strategies to investigate the interaction of nanoparticles with the mucus as well as the novel developments of mucus penetrating nanoparticles.展开更多
To reduce medication for patients with ulcerative colitis(UC),we need to establish the etiology of UC.The intestinal microbiota of patients with inflammatory bowel disease(IBD)has been shown to differ from that of hea...To reduce medication for patients with ulcerative colitis(UC),we need to establish the etiology of UC.The intestinal microbiota of patients with inflammatory bowel disease(IBD)has been shown to differ from that of healthy controls and abundant data indicate that it changes in both composition and localization.Small intestinal bacterial overgrowth is significantly higher in IBD patients compared with controls.Probiotics have been investigated for their capacity to reduce the severity of UC.The luminal surfaces of the gastrointestinal tract are covered by a mucus layer.This normally acts as a barrier that does not allow bacteria to reach the epithelial cells and thus limits the direct contact between the host and the bacteria.The mucus layer in the colon comprises an inner layer that is firmly adherent to the intestinal mucosa,and an outer layer that can be washed off with minimal rinsing.Some bacteria can dissolve the protective inner mucus layer.Defects in renewal and formation of the inner mucus layer allow bacteria to reach the epithelium and have implications for the causes of colitis.In this review,important elements of UC pathology are thought to be the intestinal bacteria,gut mucus,and the mucosa-associated immune system.展开更多
Objective:To study the antimicrobial,hemolytic activity and immunomodulatory activity of fish epidermal mucus and their chemical constituents from Cynoglossus arel(C.arel) and Alius caelatus(A.caelatus).Mucus plays an...Objective:To study the antimicrobial,hemolytic activity and immunomodulatory activity of fish epidermal mucus and their chemical constituents from Cynoglossus arel(C.arel) and Alius caelatus(A.caelatus).Mucus plays an important role in the prevention of colonization by parasites,bacteria and fungi.Methods:Epidermal mucus was obtained from two marine fishes,lyophilized and the chemical composition of epidermal mucus was analysed by FT-IR analysis.The in vitro antimicrobial activity against human pathogens(fungi,gram positive and gram-negative bacteria) and also the hemolytic activity and immunomodulatory activity were determined.Results:Totally ten human pathogens were tested against the fish mucus.Out of the ten pathogens,five pathogens have proved to be sensitive to the mucus.Maximum zone of inhibition was observed against Vibrio cholera(V.cholera)(9 mm and 2 mm in diameter),followed by Staphylococcus aureus(S.aureus) with a inhibition zone of(6 mm and 3 mm),Streptococcus areus(S.areus)(5 mm and 4 mm),Vibrio parahemolyticus(V.parahemolyticus)(4 mm and 5 mm) respectively.Conclusions:The present investigation has revealed that positive progresses in the fish mucus extracts against human pathogens and hemolytic activity.But further efforts are required for the purification and isolation of the active antimicrobial compounds in order to establish their possible applications.展开更多
Improving peroral delivery efficiency is always a persistent goal for both small-molecule and macromolecular drug development. However,intestinal mucus barrier which greatly impedes drug-loaded nanoparticles penetrati...Improving peroral delivery efficiency is always a persistent goal for both small-molecule and macromolecular drug development. However,intestinal mucus barrier which greatly impedes drug-loaded nanoparticles penetration is commonly overlooked. Therefore,in this study,taking fluorescent labeled PLGA(poly(lactic-co-glycolic acid)) nanoparticles as a tool,the influence of anionic and nonionic surfactants on mucus penetration ability of nanoparticles and their mucus barrier regulating ability were studied. The movement of PLGA nanoparticles in mucus was tracked by multiple particles tracking method(MPT).Alteration of mucus properties by addition of surfactants was evaluated by rheology and morphology study. Rat intestinal villus penetration study was used to further evaluate penetration enhancement of nanoparticles. The effective diffusivities of the nanoparticles in surfactants pretreated mucus were increased by 2–3 times and the mucus barrier regulating capacity was also surfactant type dependent. Sodium dodecyl sulfate(SDS) increased the complex viscosity and viscoelastic properties of mucus,but poloxamer presented a decreased trend. Tween 80 maintained the rheological property of the mucus. With the mucus barrier regulated by surfactants,the penetration of nanoparticles in intestinal villus was obviously increased. In summary,the mucus penetration ability of nanoparticles could be enhanced by altering mucus microenvironment with surfactants. Tween 80 which largely retains the original mucus rheology and morphology properties may be a promising candidate for facilitating nanoparticle penetration through the mucus barrier with good safety profile.展开更多
Self-nanoemulsifying systems(SNEs) have excellent ability to improve the solubility ofpoorly water-soluble drugs(PWSD). However, SNEs are likely to be degraded in gastroin-testinal(GIT) when their surface is recognize...Self-nanoemulsifying systems(SNEs) have excellent ability to improve the solubility ofpoorly water-soluble drugs(PWSD). However, SNEs are likely to be degraded in gastroin-testinal(GIT) when their surface is recognized by lipase/co-lipase enzyme complex, result-ing in rapid release and precipitation of encapsulated drugs. The precipitates are then cap-tured and removed by intestinal mucus, reducing the delivery efficacy of SNEs. Herein, theamphiphilic polymer Pluronic? F127 was incorporated into long and short-chain triglyc-erides(LCT, SCT) based SNEs to diminish the recognition and therefore minimized theirdegradation by enzymes and clearance by mucus. The SNEs were characterized in termsof particle size, zeta potential and stability. Ex vivo multiple particles tracking studies wereperformed by adding particle solution into fresh rat mucus. Cellular uptake of SNEs wereconducted by using E12 cells, the absorption and distribution in small intestine were alsostudied after oral administration in male Sprague-Dawley(SD) rats. The in vitro digestionrate of SNEs were found to be in following order SCT-SNE > SCT-F127-SNE > LCT-SNE > LCT-F127-SNE. Moreover, the LCT-F127-SNE was found to be most effective in enhancing cellularuptake, resulting in 3.5-fold, 2.1-fold and 1.7-fold higher than that of SCT-SNE, LCT-SNE andSCT-F127-SNE, respectively. After incubating the SNE with E12 cells, the LCT-F127-SNE ex-hibited the highest amount regarding both mucus penetration and cellular uptake, with anuptake amount number(via bicinchoninic acid(BCA) analysis) of 3.5-fold, 2.1-fold and 1.7-fold higher than that of SCT-SNE, LCT-SNE and SCT-F127-SNE, respectively. The in vivo results revealed that orally administered LCT-F127-SNE could significantly increase the bioavailability of Cyclosporine A(CsA), which was approximately 2.43-fold, 1.33-fold and 1.80-fold higher than that of SCT-SNE, SCT-F127-SNE and LCT-SNE, respectively. We address in this work that F127-modified SNEs have potentials to improve oral drug absorption by significantly reducing gastrointestinal enzymatic degradation and simultaneously enhancing mucus penetration.展开更多
Objective Mucus forms the physical barrier along the gastrointestinal(GI)tract.It plays an important role to prevent mucosal damage and inflammation.Our previous finding showed that antibacterial peptide 'cathelic...Objective Mucus forms the physical barrier along the gastrointestinal(GI)tract.It plays an important role to prevent mucosal damage and inflammation.Our previous finding showed that antibacterial peptide 'cathelicidin' increased mucus thickness and prevented inflammation in the colon.In the current study,we examined the protective mechanisms by which the peptide increased mucus synthesis in vitro.Methods Human colonic cell line(HT-29)was used to assess the stimulatory action of cathelicidin on mucus synthesis which was measured by the D-[6-3H] glucosamine incorporation assay.Results Human cathelicidin(LL-37)dose-dependently(10-40 μg·mL-1)and significantly stimulated mucus synthesis.Real-time PCR data showed that addition of LL-37 induced more than 50% increase in MUC1 and MUC2 mRNA levels.Treatment with MUC1 and MUC2 siRNAs normalized the stimulatory action of LL-37 on mucus synthesis.LL-37 also activated the phosphorylation of mitogen-activated protein(MAP)kinase in the cells.A specific inhibitor of the MAP kinase pathway,U0126,completely blocked the increase of MUC1 and MUC2 expression as well as mucus synthesis by LL-37.Conclusions Taken together LL-37 stimulates mucus synthesis through the activation of MUC1 and MUC2 expression and the MAP kinase pathway in human colonic cells.展开更多
Current methods for nasal spray formulations have been elementary evaluating the dripping characteristics of a formulation and have not assessed the behavior of the nasal formulation in the presence of varying types o...Current methods for nasal spray formulations have been elementary evaluating the dripping characteristics of a formulation and have not assessed the behavior of the nasal formulation in the presence of varying types of mucus depending on the indication or diseased state. This research investigated the effects of nasal mucus on the dripping behavior of nasal formulations and focused on developing an improved in vitro analytical test method that is more physiologically relevant in characterizing nasal formulation dripping behavior. Method development was performed using simulated nasal mucus preparations for both healthy and diseased states as coatings for the dripping experiment representing a wide range of viscosity. Factors evaluated during development of this in vitro test method included amount of mucus, application of mucus, drying times, and compatibility of the mucus on a C18 Thin Layer Chromatography(TLC) substrate. The dripping behavior of nasal formulations containing a range of 1%Avicel to 3.5% Avicel was assessed by actuating the nasal spray on a perpendicular TLC plate coated with either healthy or diseased simulated nasal mucus. After actuation of the nasal spray, the dripping of the formulation on the coated TLC plate was measured after the plate was repositioned vertically. The method that was developed generated reproducible results on the dripping behavior of nasal formulations and provided critical information about the compatibility of the formulation with the nasal mucus for different diseased states, aiding in nasal spray formulation development and physical characterization of the nasal spray.展开更多
AIM To determine the ability of intrapulmonary percussive ventilation(IPV) to promote airway clearance in spontaneously breathing patients and those on mechanical ventilation.METHODS An artificial lung was used to sim...AIM To determine the ability of intrapulmonary percussive ventilation(IPV) to promote airway clearance in spontaneously breathing patients and those on mechanical ventilation.METHODS An artificial lung was used to simulate a spontaneously breathing patient(Group 1), and was then connected to a mechanical ventilator to simulate a patient on mechanical ventilation(Group 2). An 8.5 mm endotracheal tube(ETT) connected to the test lung, simulated the patient airway. Artificial mucus was instilled into the mid-portion of the ETT. A filter was attached at both ends of the ETT to collect the mucus displaced proximally(mouth-piece filter) and distally(lung filter). The IPV machine was attached to the proximal end of the ETT and was applied for 10-min each to Group 1 and 2. After each experiment, the weight of the various circuit components were determined and compared to their dry weights to calculate the weight of the displaced mucus.RESULTS In Group 1(spontaneously breathing model), 26.8% ± 3.1% of the simulated mucus was displaced proximally, compared to 0% in Group 2(the mechanically ventilated model) with a P-value of < 0.01. In fact, 17% ± 1.5% of the mucus in Group 2 remained in the mid-portion of the ETT where it was initially instilled and 80% ± 4.2% was displaced distally back towards the lung(P < 0.01). There was an overall statistically significant amount of mucusmovement proximally towards the mouth-piece in the spontaneously breathing(SB) patient. There was also an overall statistically significant amount of mucus movement distally back towards the lung in the mechanically ventilated(MV) model. In the mechanically ventilated model, no mucus was observed to move towards the proximal/mouth piece section of the ETT. CONCLUSION This bench model suggests that IPV is associated with displacement of mucus towards the proximal mouthpiece in the SB patient, and distally in the MV model.展开更多
Objective:Xiaoqinglong decoction (XQL) has been used in traditional Chinese medicine as a prescription for asthma treatment.We explored the effects of XQL on mucus hypersecretion and ciliophagy in the airways of mice ...Objective:Xiaoqinglong decoction (XQL) has been used in traditional Chinese medicine as a prescription for asthma treatment.We explored the effects of XQL on mucus hypersecretion and ciliophagy in the airways of mice in which asthma had been induced by ovalbumin (OVA).Methods:Thirty-six mice were sensitized by OVA injection (i.p.) on day-0 and day-14 and challenged with 1% OVA on day 18-22.Then,they were divided into three groups:model,carbocysteine and XQL.From day-15 to day-22,the XQL group was administered XQL (10 g/kg,p.o.) 1 hour before each aerosol challenge with OVA.To evaluate the effect of XQL on mucus hypersecretion,AB-PAS staining,measurement of serum levels of interleukin (IL)-13,bronchoalveolar lavage fluid (BALF) analyses,ciliophagy analyses,as well as coexpression of Light Chain 3 (LC3) and acetylated α-tubulin by immunofluorescence staining were undertaken.Results:Treatment with XQL (10 g/kg) attenuated mucus secretion in the airways,and reduced the positive areas of AB-PAS staining in histopathologic lung tissues (P <.05).IL-13 expression in serum (P <.01),OVA-induced inflammatory changes,and the number of white blood cells (P <.01) in BALF samples were also reduced.However,the effect on mucus secretion was less apparent in the carbocysteine group compared with the XQL group.XQL treatment also improved the cilia length and elicited a substantial reduction in ciliophagy and LC3 expression in the tracheal epithelium.Conclusion:XQL can attenuate cilia shortening,aid the clearance function of ciliated epithelial cells,and reduce mucus production in an OVA-induced asthma model in mice.XQL can inhibit mucus hypersecretion and could be a new type of pharmacotherapy.展开更多
Little was known about mammalian colon mucus(CM)until the beginning of the 21^(st) century.Since that time considerable progress has been made in basic research addressing CM structure and functions.Human CM is formed...Little was known about mammalian colon mucus(CM)until the beginning of the 21^(st) century.Since that time considerable progress has been made in basic research addressing CM structure and functions.Human CM is formed by two distinct layers composed of gel-forming glycosylated mucins that are permanently secreted by goblet cells of the colonic epithelium.The inner layer is dense and impenetrable for bacteria,whereas the loose outer layer provides a habitat for abundant commensal microbiota.Mucus barrier integrity is essential for preventing bacterial contact with the mucosal epithelium and maintaining homeostasis in the gut,but it can be impaired by a variety of factors,including CM-damaging switch of commensal bacteria to mucin glycan consumption due to dietary fiber deficiency.It is proven that impairments in CM structure and function can lead to colonic barrier deterioration that opens direct bacterial access to the epithelium.Bacteria-induced damage dysregulates epithelial proliferation and causes mucosal inflammatory responses that may expand to the loosened CM and eventually result in severe disorders,including colitis and neoplastic growth.Recently described formation of bacterial biofilms within the inner CM layer was shown to be associated with both inflammation and cancer.Although obvious gaps in our knowledge of human CM remain,its importance for the pathogenesis of major colorectal diseases,comprising inflammatory bowel disease and colorectal cancer,is already recognized.Continuing progress in CM exploration is likely to result in the development of a range of new useful clinical applications addressing colorectal disease diagnosis,prevention and therapy.展开更多
Colonoscopy is currently the gold standard for diagnosis of inflammatory bowel disease(IBD)and colorectal cancer(CRC).This has the obvious drawback of being invasive as well as carrying a small risk.The most widely us...Colonoscopy is currently the gold standard for diagnosis of inflammatory bowel disease(IBD)and colorectal cancer(CRC).This has the obvious drawback of being invasive as well as carrying a small risk.The most widely used non-invasive approaches include the use of faecal calprotectin in the case of IBD and fecal immunochemical test in the case of CRC.However,the necessity of stool collection limits their acceptability for some patients.Over the recent years,there has been emerging data looking at the role of non-invasively obtained colorectal mucus as a screening and diagnostic tool in IBD and CRC.It has been shown that the mucus rich material obtained by self-sampling of anal surface following defecation,can be used to measure various biomarkers that can aid in diagnosis of these conditions.展开更多
Coronavirus disease 2019(COVID-19)caused by acute respiratory syndrome coronavirus 2(SARS-Cov-2)is still threatening the human life and society throughout the world.For those critically ill patients,mechanical ventila...Coronavirus disease 2019(COVID-19)caused by acute respiratory syndrome coronavirus 2(SARS-Cov-2)is still threatening the human life and society throughout the world.For those critically ill patients,mechanical ventilation(MV)is essential to provide life support during treatment.However,both the virus infection and MV disrupt the balance between secretion and elimination of airway mucus and lead to mucus accumulation in the lung.Postmortem examination verified that the lungs in patients died of COVID-19 are indeed filled with sticky mucus,suggesting a great need to improve airway mucus clearance in critically ill COVID-19 patients.Therefore,it may be helpful to comprehensively review the current understanding regarding the changes of biochemical and rheological features of airway mucus associated with the disease,as well as the physiological principles and algorithm to decide airway clearance techniques suitable for the critically ill COVID-19 patients.Based on these considerations,optimized strategies may be developed to eliminate the airway mucus accumulated in the airways of critically ill COVID-19 patients.展开更多
Objective:To detect effect of removing cervical mucus before performing intrauterine insemination(IUI)on pregnancy rate in patients with unexplained infertility.Methods:The randomized controlled trial was conducted in...Objective:To detect effect of removing cervical mucus before performing intrauterine insemination(IUI)on pregnancy rate in patients with unexplained infertility.Methods:The randomized controlled trial was conducted in Infertility Division of Department of Obstetrics and Gynaecology of a tertiary care hospital.Totally 80 patients of unexplained infertility were recruited.By computer generated block randomization in block size of 4 and 6,patients were randomly allocated at time of starting ovarian stimulation into the cervical mucus removal group or the non-removal of cervical mucus group before IUI,40 in each group.Ovarian stimulation with clomiphene 100 mg from day 2-6 of menstrual cycle along with human menopausal gonadotropin 150 IU was given alternate day starting from day 7.Follicular monitoring was done and further doses given as per response;trigger was planned when 1-3 follicle reach a diameter of>18 mm.IUI was planned after trigger.IUI was done as per the group allocated.Mucus cleaning was done in the cervical mucus removal group by aspirating mucus with IUI syringe and sterile cotton swab before IUI.The primary outcome was clinical pregnancy rate.Number of difficult IUIs and cycle cancellation due to ovarian hyperstimulation were also noted.Results:IUI was not done in 4 patients due to hyperstimulation.Pregnancies per IUI cycle occurred in 7.9%(3/38)in the cervical mucus removal group and 21.1%(8/38)in the non-removal of cervical mucus group.There was no statistically significant difference in clinical pregnancy rate between two groups(P=0.19).Conclusions:There is a trend towards a lower clinical pregnancy rate with removal of cervical mucus before IUI in women of unexplained infertility though the difference is not statistically significant.Further studies with large sample size need to be done on this intervention.展开更多
The deep-sea clam Calyptogena okutanii possesses a large gill containing vertically transmitted symbiotic sulfur-oxidizing bacteria. It produces large amounts of highly viscoelastic mucus from the gill, which is thoug...The deep-sea clam Calyptogena okutanii possesses a large gill containing vertically transmitted symbiotic sulfur-oxidizing bacteria. It produces large amounts of highly viscoelastic mucus from the gill, which is thought to be a physical and chemical barrier. The mucus collected from the gill was shown to be composed of glycoproteins having the following sugar composition: Man (17.4%), GlcNAc (16.6%), GalNAc (15%), Glc (1.1%), Gal (29.9%), Xyl (3.0%), Fuc (14.4%), and unknown (2.6%), indicating that it contained mucin-like glycoproteins. In a monoclonal antibody library against the gill tissue, we found a monoclonal antibody (mAb), CokG-B3C10, reacting to the mucus. Western blot analysis using the mAb showed that it reacted to several glycoproteins in the mucus from the gill tissue, but not with those of other tissues such as the mantle, foot, and ovary, where mucus production has been reported in bivalves. Further, immunohistochemical analysis showed the CokG-B3C10 mAb reacting to glycoproteins was detected in the inner area of the gill, which was occupied by many bacteriocytes in the row of gill filaments. Strong mAb signals were found on the outer surface of the bacteriocytes facing the interfilamental space, and in the interfilamental spaces between filaments. Weaker signals were also observed in the bacteriocyte cells. These results indicate that the CokG-B3C10 mAbbinding mucus glycoproteins were produced from cells including bacteriocytes and nonbacteriocyte cells in the inner area of the gill filaments.展开更多
Objective:To observe the effect of Elephantopus scaber Linn on chronic obstructive pulmonary disease(COPD),to investigate its effect on the MUC5AC hypersecretion of airway mucus mediated by neutrophil elastin in patie...Objective:To observe the effect of Elephantopus scaber Linn on chronic obstructive pulmonary disease(COPD),to investigate its effect on the MUC5AC hypersecretion of airway mucus mediated by neutrophil elastin in patients with acute exacerbation of COPD,and to observe its effect on lung function(FEV1,FEV1/FVC),so as to provide new ideas and theoretical basis for the prevention and treatment of COPD.Methods:160 patients with acute exacerbation of COPD were randomly divided into observation group and control group with 80 cases each according to the numerical table method.The observation group was treated with aerosol inhalation of Elephantopus scaber Linn on the basis of conventional treatment.Both groups were treated for 2 weeks.During the same period,80 healthy patients were selected as the healthy control group.The expression of NE and MUC5AC in serum of observation group,control group and healthy control group before and after treatment was detected by enzymelinked immunosorbent assay(ELISA).The changes of lung function(FEV1,FEV1/FVC)after treatment in the observation group and the control group were compared and analyzed,and the efficacy of Elephantopus scaber Linn in patients with acute exacerbation of copd was observed.Results:Compared with the control group,the total effective rate of the observation group was significantly better than that of the control group,with statistical significance(P<0.05).Compared with the healthy control group,there were significant differences in serum NE and MUC5AC between the observation group and the control group(P<0.05).Serum NE,MUC5AC,FEV1 and FEV1/FVC were significantly different in the observation group before and after treatment(P<0.05).Serum NE,MUC5AC,FEV1 and FEV1/FVC were significantly different in the observation group before and after treatment(P<0.05).Compared with the control group after treatment,there were significant differences in serum NE and MUC5AC in the observation group after treatment(P<0.05),and the increase of FEV1/FVC and FEV1 was significantly better than that of the control group after treatment(P<0.05).Conclusion:Elephantopus scaber Linn can significantly improve the clinical treatment effect of patients with acute exacerbation of COPD,improve lung function and airway mucus hypersecretion.It can effectively inhibit the expression of NE and MUC5AC in the blood.There were significant differences in serum NE and MUC5AC between the observation group and the control group after treatment(P<0.05),showing a positive correlation,suggesting that inhibition of MUC5AC secretion by Elephantopus scaber Linn in patients with COPD may be related to NE-mediated pathways.展开更多
The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells,as well as acts as the"mucus layer-soil"for intestinal flora adhesion and colonization.Its structural and funct...The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells,as well as acts as the"mucus layer-soil"for intestinal flora adhesion and colonization.Its structural and functional integrity is crucial to human health.Intestinal mucus is regulated by factors such as diet,living habits,hormones,neurotransmitters,cytokines,and intestinal flora.The mucus layer’s thickness,viscosity,porosity,growth rate,and glycosylation status affect the structure of the gut flora colonized on it.The interaction between"mucus layer-soil"and"gut bacteria-seed"is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease(NAFLD).Probiotics,prebiotics,fecal microbiota transplantation(FMT),and wash microbial transplantation are efficient methods for managing NAFLD,but their long-term efficacy is poor.FMT is focused on achieving the goal of treating diseases by enhancing the"gut bacteria-seed".However,a lack of effective repair and management of the"mucus layer-soil"may be a reason why"seeds"cannot be well colonized and grow in the host gut,as the thinning and destruction of the"mucus layer-soil"is an early symptom of NAFLD.This review summarizes the existing correlation between intestinal mucus and gut microbiota,as well as the pathogenesis of NAFLD,and proposes a new perspective that"mucus layer-soil"restoration combined with"gut bacteria-seed"FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.展开更多
Establishment of vaginal immune defenses at the mucosal interface layer through gene vaccines promise to prevent infectious diseases among females.Mucosal barriers composed of a flowing mucus hydrogel and tightly conj...Establishment of vaginal immune defenses at the mucosal interface layer through gene vaccines promise to prevent infectious diseases among females.Mucosal barriers composed of a flowing mucus hydrogel and tightly conjugated epithelial cells(ECs),which represent the main technical difficulties for vaccine development,reside in the harsh,acidic human vaginal environment.Different from frequently employed viral vectors,two types of nonviral nanocarriers were designed to concurrently overcome the barriers and induce immune responses.Differing design concepts include the charge-reversal property(DRLS)to mimic a virus that uses any cells as factories,as well as the addition of a hyaluronic acid coating(HA/RLS)to directly target dendritic cells(DCs).With a suitable size and electrostatic neutrality,these two nanoparticles penetrate a mucus hydrogel with similar diffusivity.The DRLS system expressed a higher level of the carried human papillomavirus type 16 L1 gene compared to HA/RLS in vivo.Therefore it induced more robust mucosal,cellular,and humoral immune responses.Moreover,the DLRS applied to intravaginal immunization induced high IgA levels compared with intramuscularly injected DNA(naked),indicating timely protection against pathogens at the mucus layer.These findings also offer important approaches for the design and fabrication of nonviral gene vaccines in other mucosal systems.展开更多
This research was directed to understand the bactericidal effect of epidermal mucus of two Asian cat fish species viz.Clarias batrachus and Heteropneustes fossilis.Epidermal mucus extracts(raw and diluted)of both cat ...This research was directed to understand the bactericidal effect of epidermal mucus of two Asian cat fish species viz.Clarias batrachus and Heteropneustes fossilis.Epidermal mucus extracts(raw and diluted)of both cat fish species were tested against several Gram negative(Pseudomonas aeruginosa,Escherichia coli,Klebsiella pneumonia,A.hydrophila)and Gram positive bacterial strains(Bacillius cereus,Staphylococcus aureus,S.epidermidis)and antibacterial results were also compared with two standard antibiotics viz.amikacin and chloramphenicol used as positive control.An A.hydrophila challenge experiment was also performed on all selected test fish species to examine the change in the amount of mucus production and its bactericidal impact..Both epidermal mucus extracts(raw and diluted)of all selected normal and bacterial challenged test objects showed potent bactericidal effect against all pathogenic bacterial strains taken under study.However,former was more effective than later.Also raw epidermal mucus extracts of both normal and bacterial challenged cat fish species exhibited significantly higher ZOI values against all selected microbial strains than diluted mucus extracts and antibiotic chloramphenicol.Hence,these outcomes have clearly revealed that this cost effective natural product acquired from fishes is the key component of their defensive system.Therefore,it could be utilized as a novel‘antimicrobial’in human as well as veterinary sector for combating against several bacterial diseases.展开更多
基金supported by the National Natural Science Foundation of China(No.52273123)the Graduate Scientific Research and Innovation Foundation of Chongqing,China(No.CYS21072)+1 种基金the Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0344,cstc2021jcyj-msxmX0342)the Open Research Project from State Key Laboratory of Silkworm GenomeBiology(No.SKLSGB-orp202010).
文摘The mucosal barrier remains a major barrier in the pulmonary drug delivery system,as mucociliary clearance in the airway accelerates the removal of inhaled nanoparticles(NPs).Herein,we designed and developed the inhalable Pluronic F127-modified silk fibroin NPs loading with quercetin(marked as QR-SF(PF127)NPs),aiming to solve the airway mucus barrier and improve the cancer therapeutic effect of QR.The PF127 coating on the SF NPs could attenuate the interaction between NPs and mucin proteins,thus facilitating the diffusion of SF(PF127)NPs in the mucus layer.The QR-SF(PF127)NPs had particle sizes of approximately 200 nm with negatively charged surfaces and showed constant drug release properties.Fluorescence recovery after photobleaching(FRAP)assay and transepithelial transport test showed that QR-SF(PF127)NPs exhibited superior mucus-penetrating ability in artificial mucus and monolayer Calu-3 cell model.Notably,a large amount of QR-SF(PF127)NPs distributed uniformly in the mice airway section,indicating the good retention of NPs in the respiratory tract.Themicemelanoma lungmetastasismodel was established,and the therapeutic effect of QR-SF(PF127)NPs was significantly improved in vivo.PF127-modified SF NPs may be a promising strategy to attenuate the interaction with mucin proteins and enhancemucus penetration efficiency in the pulmonary drug delivery system.
基金support from the National Natural Science Foundation of China(81173010).
文摘Mucus can effectively protect the exposed mucosal surfaces due to its adhesive and viscoelastic properties.Most foreign particulates are efficiently trapped in mucus layers via steric obstruction and adhesion.Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on their location sites.This article focuses on describing the tenacious mucus barrier properties,the strategies to investigate the interaction of nanoparticles with the mucus as well as the novel developments of mucus penetrating nanoparticles.
基金Supported by National Natural Science Foundation of China,No.81270471
文摘To reduce medication for patients with ulcerative colitis(UC),we need to establish the etiology of UC.The intestinal microbiota of patients with inflammatory bowel disease(IBD)has been shown to differ from that of healthy controls and abundant data indicate that it changes in both composition and localization.Small intestinal bacterial overgrowth is significantly higher in IBD patients compared with controls.Probiotics have been investigated for their capacity to reduce the severity of UC.The luminal surfaces of the gastrointestinal tract are covered by a mucus layer.This normally acts as a barrier that does not allow bacteria to reach the epithelial cells and thus limits the direct contact between the host and the bacteria.The mucus layer in the colon comprises an inner layer that is firmly adherent to the intestinal mucosa,and an outer layer that can be washed off with minimal rinsing.Some bacteria can dissolve the protective inner mucus layer.Defects in renewal and formation of the inner mucus layer allow bacteria to reach the epithelium and have implications for the causes of colitis.In this review,important elements of UC pathology are thought to be the intestinal bacteria,gut mucus,and the mucosa-associated immune system.
文摘Objective:To study the antimicrobial,hemolytic activity and immunomodulatory activity of fish epidermal mucus and their chemical constituents from Cynoglossus arel(C.arel) and Alius caelatus(A.caelatus).Mucus plays an important role in the prevention of colonization by parasites,bacteria and fungi.Methods:Epidermal mucus was obtained from two marine fishes,lyophilized and the chemical composition of epidermal mucus was analysed by FT-IR analysis.The in vitro antimicrobial activity against human pathogens(fungi,gram positive and gram-negative bacteria) and also the hemolytic activity and immunomodulatory activity were determined.Results:Totally ten human pathogens were tested against the fish mucus.Out of the ten pathogens,five pathogens have proved to be sensitive to the mucus.Maximum zone of inhibition was observed against Vibrio cholera(V.cholera)(9 mm and 2 mm in diameter),followed by Staphylococcus aureus(S.aureus) with a inhibition zone of(6 mm and 3 mm),Streptococcus areus(S.areus)(5 mm and 4 mm),Vibrio parahemolyticus(V.parahemolyticus)(4 mm and 5 mm) respectively.Conclusions:The present investigation has revealed that positive progresses in the fish mucus extracts against human pathogens and hemolytic activity.But further efforts are required for the purification and isolation of the active antimicrobial compounds in order to establish their possible applications.
基金financially supported by the National Natural Science Foundation of China (Grant No. 31870987)
文摘Improving peroral delivery efficiency is always a persistent goal for both small-molecule and macromolecular drug development. However,intestinal mucus barrier which greatly impedes drug-loaded nanoparticles penetration is commonly overlooked. Therefore,in this study,taking fluorescent labeled PLGA(poly(lactic-co-glycolic acid)) nanoparticles as a tool,the influence of anionic and nonionic surfactants on mucus penetration ability of nanoparticles and their mucus barrier regulating ability were studied. The movement of PLGA nanoparticles in mucus was tracked by multiple particles tracking method(MPT).Alteration of mucus properties by addition of surfactants was evaluated by rheology and morphology study. Rat intestinal villus penetration study was used to further evaluate penetration enhancement of nanoparticles. The effective diffusivities of the nanoparticles in surfactants pretreated mucus were increased by 2–3 times and the mucus barrier regulating capacity was also surfactant type dependent. Sodium dodecyl sulfate(SDS) increased the complex viscosity and viscoelastic properties of mucus,but poloxamer presented a decreased trend. Tween 80 maintained the rheological property of the mucus. With the mucus barrier regulated by surfactants,the penetration of nanoparticles in intestinal villus was obviously increased. In summary,the mucus penetration ability of nanoparticles could be enhanced by altering mucus microenvironment with surfactants. Tween 80 which largely retains the original mucus rheology and morphology properties may be a promising candidate for facilitating nanoparticle penetration through the mucus barrier with good safety profile.
基金financial support received from the National Natural Science Foundation of China(81373356,81573378 and 81703436)the Science and Technology Innovation Action Plan for Basic Research of Shanghai 2014 (14JC1493200)CASIMM0120153020,Shanghai Sailing Program 2017(17YF1423500)
文摘Self-nanoemulsifying systems(SNEs) have excellent ability to improve the solubility ofpoorly water-soluble drugs(PWSD). However, SNEs are likely to be degraded in gastroin-testinal(GIT) when their surface is recognized by lipase/co-lipase enzyme complex, result-ing in rapid release and precipitation of encapsulated drugs. The precipitates are then cap-tured and removed by intestinal mucus, reducing the delivery efficacy of SNEs. Herein, theamphiphilic polymer Pluronic? F127 was incorporated into long and short-chain triglyc-erides(LCT, SCT) based SNEs to diminish the recognition and therefore minimized theirdegradation by enzymes and clearance by mucus. The SNEs were characterized in termsof particle size, zeta potential and stability. Ex vivo multiple particles tracking studies wereperformed by adding particle solution into fresh rat mucus. Cellular uptake of SNEs wereconducted by using E12 cells, the absorption and distribution in small intestine were alsostudied after oral administration in male Sprague-Dawley(SD) rats. The in vitro digestionrate of SNEs were found to be in following order SCT-SNE > SCT-F127-SNE > LCT-SNE > LCT-F127-SNE. Moreover, the LCT-F127-SNE was found to be most effective in enhancing cellularuptake, resulting in 3.5-fold, 2.1-fold and 1.7-fold higher than that of SCT-SNE, LCT-SNE andSCT-F127-SNE, respectively. After incubating the SNE with E12 cells, the LCT-F127-SNE ex-hibited the highest amount regarding both mucus penetration and cellular uptake, with anuptake amount number(via bicinchoninic acid(BCA) analysis) of 3.5-fold, 2.1-fold and 1.7-fold higher than that of SCT-SNE, LCT-SNE and SCT-F127-SNE, respectively. The in vivo results revealed that orally administered LCT-F127-SNE could significantly increase the bioavailability of Cyclosporine A(CsA), which was approximately 2.43-fold, 1.33-fold and 1.80-fold higher than that of SCT-SNE, SCT-F127-SNE and LCT-SNE, respectively. We address in this work that F127-modified SNEs have potentials to improve oral drug absorption by significantly reducing gastrointestinal enzymatic degradation and simultaneously enhancing mucus penetration.
文摘Objective Mucus forms the physical barrier along the gastrointestinal(GI)tract.It plays an important role to prevent mucosal damage and inflammation.Our previous finding showed that antibacterial peptide 'cathelicidin' increased mucus thickness and prevented inflammation in the colon.In the current study,we examined the protective mechanisms by which the peptide increased mucus synthesis in vitro.Methods Human colonic cell line(HT-29)was used to assess the stimulatory action of cathelicidin on mucus synthesis which was measured by the D-[6-3H] glucosamine incorporation assay.Results Human cathelicidin(LL-37)dose-dependently(10-40 μg·mL-1)and significantly stimulated mucus synthesis.Real-time PCR data showed that addition of LL-37 induced more than 50% increase in MUC1 and MUC2 mRNA levels.Treatment with MUC1 and MUC2 siRNAs normalized the stimulatory action of LL-37 on mucus synthesis.LL-37 also activated the phosphorylation of mitogen-activated protein(MAP)kinase in the cells.A specific inhibitor of the MAP kinase pathway,U0126,completely blocked the increase of MUC1 and MUC2 expression as well as mucus synthesis by LL-37.Conclusions Taken together LL-37 stimulates mucus synthesis through the activation of MUC1 and MUC2 expression and the MAP kinase pathway in human colonic cells.
文摘Current methods for nasal spray formulations have been elementary evaluating the dripping characteristics of a formulation and have not assessed the behavior of the nasal formulation in the presence of varying types of mucus depending on the indication or diseased state. This research investigated the effects of nasal mucus on the dripping behavior of nasal formulations and focused on developing an improved in vitro analytical test method that is more physiologically relevant in characterizing nasal formulation dripping behavior. Method development was performed using simulated nasal mucus preparations for both healthy and diseased states as coatings for the dripping experiment representing a wide range of viscosity. Factors evaluated during development of this in vitro test method included amount of mucus, application of mucus, drying times, and compatibility of the mucus on a C18 Thin Layer Chromatography(TLC) substrate. The dripping behavior of nasal formulations containing a range of 1%Avicel to 3.5% Avicel was assessed by actuating the nasal spray on a perpendicular TLC plate coated with either healthy or diseased simulated nasal mucus. After actuation of the nasal spray, the dripping of the formulation on the coated TLC plate was measured after the plate was repositioned vertically. The method that was developed generated reproducible results on the dripping behavior of nasal formulations and provided critical information about the compatibility of the formulation with the nasal mucus for different diseased states, aiding in nasal spray formulation development and physical characterization of the nasal spray.
文摘AIM To determine the ability of intrapulmonary percussive ventilation(IPV) to promote airway clearance in spontaneously breathing patients and those on mechanical ventilation.METHODS An artificial lung was used to simulate a spontaneously breathing patient(Group 1), and was then connected to a mechanical ventilator to simulate a patient on mechanical ventilation(Group 2). An 8.5 mm endotracheal tube(ETT) connected to the test lung, simulated the patient airway. Artificial mucus was instilled into the mid-portion of the ETT. A filter was attached at both ends of the ETT to collect the mucus displaced proximally(mouth-piece filter) and distally(lung filter). The IPV machine was attached to the proximal end of the ETT and was applied for 10-min each to Group 1 and 2. After each experiment, the weight of the various circuit components were determined and compared to their dry weights to calculate the weight of the displaced mucus.RESULTS In Group 1(spontaneously breathing model), 26.8% ± 3.1% of the simulated mucus was displaced proximally, compared to 0% in Group 2(the mechanically ventilated model) with a P-value of < 0.01. In fact, 17% ± 1.5% of the mucus in Group 2 remained in the mid-portion of the ETT where it was initially instilled and 80% ± 4.2% was displaced distally back towards the lung(P < 0.01). There was an overall statistically significant amount of mucusmovement proximally towards the mouth-piece in the spontaneously breathing(SB) patient. There was also an overall statistically significant amount of mucus movement distally back towards the lung in the mechanically ventilated(MV) model. In the mechanically ventilated model, no mucus was observed to move towards the proximal/mouth piece section of the ETT. CONCLUSION This bench model suggests that IPV is associated with displacement of mucus towards the proximal mouthpiece in the SB patient, and distally in the MV model.
基金This study was supported by the National Natural Science Foundation of China(81403313).
文摘Objective:Xiaoqinglong decoction (XQL) has been used in traditional Chinese medicine as a prescription for asthma treatment.We explored the effects of XQL on mucus hypersecretion and ciliophagy in the airways of mice in which asthma had been induced by ovalbumin (OVA).Methods:Thirty-six mice were sensitized by OVA injection (i.p.) on day-0 and day-14 and challenged with 1% OVA on day 18-22.Then,they were divided into three groups:model,carbocysteine and XQL.From day-15 to day-22,the XQL group was administered XQL (10 g/kg,p.o.) 1 hour before each aerosol challenge with OVA.To evaluate the effect of XQL on mucus hypersecretion,AB-PAS staining,measurement of serum levels of interleukin (IL)-13,bronchoalveolar lavage fluid (BALF) analyses,ciliophagy analyses,as well as coexpression of Light Chain 3 (LC3) and acetylated α-tubulin by immunofluorescence staining were undertaken.Results:Treatment with XQL (10 g/kg) attenuated mucus secretion in the airways,and reduced the positive areas of AB-PAS staining in histopathologic lung tissues (P <.05).IL-13 expression in serum (P <.01),OVA-induced inflammatory changes,and the number of white blood cells (P <.01) in BALF samples were also reduced.However,the effect on mucus secretion was less apparent in the carbocysteine group compared with the XQL group.XQL treatment also improved the cilia length and elicited a substantial reduction in ciliophagy and LC3 expression in the tracheal epithelium.Conclusion:XQL can attenuate cilia shortening,aid the clearance function of ciliated epithelial cells,and reduce mucus production in an OVA-induced asthma model in mice.XQL can inhibit mucus hypersecretion and could be a new type of pharmacotherapy.
文摘Little was known about mammalian colon mucus(CM)until the beginning of the 21^(st) century.Since that time considerable progress has been made in basic research addressing CM structure and functions.Human CM is formed by two distinct layers composed of gel-forming glycosylated mucins that are permanently secreted by goblet cells of the colonic epithelium.The inner layer is dense and impenetrable for bacteria,whereas the loose outer layer provides a habitat for abundant commensal microbiota.Mucus barrier integrity is essential for preventing bacterial contact with the mucosal epithelium and maintaining homeostasis in the gut,but it can be impaired by a variety of factors,including CM-damaging switch of commensal bacteria to mucin glycan consumption due to dietary fiber deficiency.It is proven that impairments in CM structure and function can lead to colonic barrier deterioration that opens direct bacterial access to the epithelium.Bacteria-induced damage dysregulates epithelial proliferation and causes mucosal inflammatory responses that may expand to the loosened CM and eventually result in severe disorders,including colitis and neoplastic growth.Recently described formation of bacterial biofilms within the inner CM layer was shown to be associated with both inflammation and cancer.Although obvious gaps in our knowledge of human CM remain,its importance for the pathogenesis of major colorectal diseases,comprising inflammatory bowel disease and colorectal cancer,is already recognized.Continuing progress in CM exploration is likely to result in the development of a range of new useful clinical applications addressing colorectal disease diagnosis,prevention and therapy.
文摘Colonoscopy is currently the gold standard for diagnosis of inflammatory bowel disease(IBD)and colorectal cancer(CRC).This has the obvious drawback of being invasive as well as carrying a small risk.The most widely used non-invasive approaches include the use of faecal calprotectin in the case of IBD and fecal immunochemical test in the case of CRC.However,the necessity of stool collection limits their acceptability for some patients.Over the recent years,there has been emerging data looking at the role of non-invasively obtained colorectal mucus as a screening and diagnostic tool in IBD and CRC.It has been shown that the mucus rich material obtained by self-sampling of anal surface following defecation,can be used to measure various biomarkers that can aid in diagnosis of these conditions.
基金supported by the Key Program of the NSF of China[No.11532003]the NSF of China[Nos.12072048,31670950]+1 种基金the Science and Technology Innovation Leading Plan of High Tech Industry in Hunan Province[2020SK2018]the Applied Basic Research Project of Changzhou[No.CJ20179039].
文摘Coronavirus disease 2019(COVID-19)caused by acute respiratory syndrome coronavirus 2(SARS-Cov-2)is still threatening the human life and society throughout the world.For those critically ill patients,mechanical ventilation(MV)is essential to provide life support during treatment.However,both the virus infection and MV disrupt the balance between secretion and elimination of airway mucus and lead to mucus accumulation in the lung.Postmortem examination verified that the lungs in patients died of COVID-19 are indeed filled with sticky mucus,suggesting a great need to improve airway mucus clearance in critically ill COVID-19 patients.Therefore,it may be helpful to comprehensively review the current understanding regarding the changes of biochemical and rheological features of airway mucus associated with the disease,as well as the physiological principles and algorithm to decide airway clearance techniques suitable for the critically ill COVID-19 patients.Based on these considerations,optimized strategies may be developed to eliminate the airway mucus accumulated in the airways of critically ill COVID-19 patients.
文摘Objective:To detect effect of removing cervical mucus before performing intrauterine insemination(IUI)on pregnancy rate in patients with unexplained infertility.Methods:The randomized controlled trial was conducted in Infertility Division of Department of Obstetrics and Gynaecology of a tertiary care hospital.Totally 80 patients of unexplained infertility were recruited.By computer generated block randomization in block size of 4 and 6,patients were randomly allocated at time of starting ovarian stimulation into the cervical mucus removal group or the non-removal of cervical mucus group before IUI,40 in each group.Ovarian stimulation with clomiphene 100 mg from day 2-6 of menstrual cycle along with human menopausal gonadotropin 150 IU was given alternate day starting from day 7.Follicular monitoring was done and further doses given as per response;trigger was planned when 1-3 follicle reach a diameter of>18 mm.IUI was planned after trigger.IUI was done as per the group allocated.Mucus cleaning was done in the cervical mucus removal group by aspirating mucus with IUI syringe and sterile cotton swab before IUI.The primary outcome was clinical pregnancy rate.Number of difficult IUIs and cycle cancellation due to ovarian hyperstimulation were also noted.Results:IUI was not done in 4 patients due to hyperstimulation.Pregnancies per IUI cycle occurred in 7.9%(3/38)in the cervical mucus removal group and 21.1%(8/38)in the non-removal of cervical mucus group.There was no statistically significant difference in clinical pregnancy rate between two groups(P=0.19).Conclusions:There is a trend towards a lower clinical pregnancy rate with removal of cervical mucus before IUI in women of unexplained infertility though the difference is not statistically significant.Further studies with large sample size need to be done on this intervention.
文摘The deep-sea clam Calyptogena okutanii possesses a large gill containing vertically transmitted symbiotic sulfur-oxidizing bacteria. It produces large amounts of highly viscoelastic mucus from the gill, which is thought to be a physical and chemical barrier. The mucus collected from the gill was shown to be composed of glycoproteins having the following sugar composition: Man (17.4%), GlcNAc (16.6%), GalNAc (15%), Glc (1.1%), Gal (29.9%), Xyl (3.0%), Fuc (14.4%), and unknown (2.6%), indicating that it contained mucin-like glycoproteins. In a monoclonal antibody library against the gill tissue, we found a monoclonal antibody (mAb), CokG-B3C10, reacting to the mucus. Western blot analysis using the mAb showed that it reacted to several glycoproteins in the mucus from the gill tissue, but not with those of other tissues such as the mantle, foot, and ovary, where mucus production has been reported in bivalves. Further, immunohistochemical analysis showed the CokG-B3C10 mAb reacting to glycoproteins was detected in the inner area of the gill, which was occupied by many bacteriocytes in the row of gill filaments. Strong mAb signals were found on the outer surface of the bacteriocytes facing the interfilamental space, and in the interfilamental spaces between filaments. Weaker signals were also observed in the bacteriocyte cells. These results indicate that the CokG-B3C10 mAbbinding mucus glycoproteins were produced from cells including bacteriocytes and nonbacteriocyte cells in the inner area of the gill filaments.
基金National Natural Science Foundation of China(No.81660010,31660329,8191101552)。
文摘Objective:To observe the effect of Elephantopus scaber Linn on chronic obstructive pulmonary disease(COPD),to investigate its effect on the MUC5AC hypersecretion of airway mucus mediated by neutrophil elastin in patients with acute exacerbation of COPD,and to observe its effect on lung function(FEV1,FEV1/FVC),so as to provide new ideas and theoretical basis for the prevention and treatment of COPD.Methods:160 patients with acute exacerbation of COPD were randomly divided into observation group and control group with 80 cases each according to the numerical table method.The observation group was treated with aerosol inhalation of Elephantopus scaber Linn on the basis of conventional treatment.Both groups were treated for 2 weeks.During the same period,80 healthy patients were selected as the healthy control group.The expression of NE and MUC5AC in serum of observation group,control group and healthy control group before and after treatment was detected by enzymelinked immunosorbent assay(ELISA).The changes of lung function(FEV1,FEV1/FVC)after treatment in the observation group and the control group were compared and analyzed,and the efficacy of Elephantopus scaber Linn in patients with acute exacerbation of copd was observed.Results:Compared with the control group,the total effective rate of the observation group was significantly better than that of the control group,with statistical significance(P<0.05).Compared with the healthy control group,there were significant differences in serum NE and MUC5AC between the observation group and the control group(P<0.05).Serum NE,MUC5AC,FEV1 and FEV1/FVC were significantly different in the observation group before and after treatment(P<0.05).Serum NE,MUC5AC,FEV1 and FEV1/FVC were significantly different in the observation group before and after treatment(P<0.05).Compared with the control group after treatment,there were significant differences in serum NE and MUC5AC in the observation group after treatment(P<0.05),and the increase of FEV1/FVC and FEV1 was significantly better than that of the control group after treatment(P<0.05).Conclusion:Elephantopus scaber Linn can significantly improve the clinical treatment effect of patients with acute exacerbation of COPD,improve lung function and airway mucus hypersecretion.It can effectively inhibit the expression of NE and MUC5AC in the blood.There were significant differences in serum NE and MUC5AC between the observation group and the control group after treatment(P<0.05),showing a positive correlation,suggesting that inhibition of MUC5AC secretion by Elephantopus scaber Linn in patients with COPD may be related to NE-mediated pathways.
基金National Natural Science Funds of China(Nos.82204827,81970545,and 82170609)Zhejiang Provincial Basic Public Welfare Research Project(Nos.LQ23H270016 and LGF20H030010)+1 种基金Hangzhou Major Science and Technology Plan Project(No.20172016A02)Major Projects of Hangzhou Medical and Health Science and Technology Plan(No.0020191059)
文摘The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells,as well as acts as the"mucus layer-soil"for intestinal flora adhesion and colonization.Its structural and functional integrity is crucial to human health.Intestinal mucus is regulated by factors such as diet,living habits,hormones,neurotransmitters,cytokines,and intestinal flora.The mucus layer’s thickness,viscosity,porosity,growth rate,and glycosylation status affect the structure of the gut flora colonized on it.The interaction between"mucus layer-soil"and"gut bacteria-seed"is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease(NAFLD).Probiotics,prebiotics,fecal microbiota transplantation(FMT),and wash microbial transplantation are efficient methods for managing NAFLD,but their long-term efficacy is poor.FMT is focused on achieving the goal of treating diseases by enhancing the"gut bacteria-seed".However,a lack of effective repair and management of the"mucus layer-soil"may be a reason why"seeds"cannot be well colonized and grow in the host gut,as the thinning and destruction of the"mucus layer-soil"is an early symptom of NAFLD.This review summarizes the existing correlation between intestinal mucus and gut microbiota,as well as the pathogenesis of NAFLD,and proposes a new perspective that"mucus layer-soil"restoration combined with"gut bacteria-seed"FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.
基金financially supported by National Natural Science Foundation of China (NSFC,Nos.81873921 and 51903174)Sino-German Cooperation Group Project (GZ1512)+2 种基金Chengdu Science and Technology Program (2020-GH02-00007-HZ,China)Sichuan University Postdoctoral Interdisciplinary Innovation Startup Foundationthe Fundamental Research Funds for Central Universities (2021SCU12070,China)
文摘Establishment of vaginal immune defenses at the mucosal interface layer through gene vaccines promise to prevent infectious diseases among females.Mucosal barriers composed of a flowing mucus hydrogel and tightly conjugated epithelial cells(ECs),which represent the main technical difficulties for vaccine development,reside in the harsh,acidic human vaginal environment.Different from frequently employed viral vectors,two types of nonviral nanocarriers were designed to concurrently overcome the barriers and induce immune responses.Differing design concepts include the charge-reversal property(DRLS)to mimic a virus that uses any cells as factories,as well as the addition of a hyaluronic acid coating(HA/RLS)to directly target dendritic cells(DCs).With a suitable size and electrostatic neutrality,these two nanoparticles penetrate a mucus hydrogel with similar diffusivity.The DRLS system expressed a higher level of the carried human papillomavirus type 16 L1 gene compared to HA/RLS in vivo.Therefore it induced more robust mucosal,cellular,and humoral immune responses.Moreover,the DLRS applied to intravaginal immunization induced high IgA levels compared with intramuscularly injected DNA(naked),indicating timely protection against pathogens at the mucus layer.These findings also offer important approaches for the design and fabrication of nonviral gene vaccines in other mucosal systems.
文摘This research was directed to understand the bactericidal effect of epidermal mucus of two Asian cat fish species viz.Clarias batrachus and Heteropneustes fossilis.Epidermal mucus extracts(raw and diluted)of both cat fish species were tested against several Gram negative(Pseudomonas aeruginosa,Escherichia coli,Klebsiella pneumonia,A.hydrophila)and Gram positive bacterial strains(Bacillius cereus,Staphylococcus aureus,S.epidermidis)and antibacterial results were also compared with two standard antibiotics viz.amikacin and chloramphenicol used as positive control.An A.hydrophila challenge experiment was also performed on all selected test fish species to examine the change in the amount of mucus production and its bactericidal impact..Both epidermal mucus extracts(raw and diluted)of all selected normal and bacterial challenged test objects showed potent bactericidal effect against all pathogenic bacterial strains taken under study.However,former was more effective than later.Also raw epidermal mucus extracts of both normal and bacterial challenged cat fish species exhibited significantly higher ZOI values against all selected microbial strains than diluted mucus extracts and antibiotic chloramphenicol.Hence,these outcomes have clearly revealed that this cost effective natural product acquired from fishes is the key component of their defensive system.Therefore,it could be utilized as a novel‘antimicrobial’in human as well as veterinary sector for combating against several bacterial diseases.
