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Numerous studies have aimed to develop novel advanced vaccines, in part because traditional vaccines have been unsuccessful in preventing rapidly emerging and reemerging viral and bacterial infections. There is a need for an advanced vaccine delivery system to ensure the successful induction of humoral and cellular immune responses. In particular, the ability of nanovaccines to modulate intracellular antigen delivery by inducing exogenous antigens (loaded onto major histocompatibility complex class 1 molecules) in CD8+ T cells, the so-called cross-presentation pathway, has attracted a great deal of attention. Protection against viral and intracellular bacterial infections relies on cross-presentation.This review discusses the advantages, requirements, and preparation of nanovaccines, the cross-presentation mechanism, the several parameters affecting cross-presentation by nanovaccines, and future perspectives.
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Bone morphogenic protein-2 (BMP-2)-conjugated three-dimensional (3-D)-printed poly (L-lactic acid)(PLLA) scaffold is likely promising as an effective bone substitute for enhancing bone regeneration of massive bone defects caused by tumor resection, traumatic injury, or congenital diseases. The authors developed a new bone substitute using a novel strategy composed of 3-D-printed PLLA scaffolds through a sequential coating of catechol-conjugated alginate (C-AL), BMP-2, and collagen (CO). The 3-D-printed PLLA scaffold was successfully obtained with 5 mm of diameter, 1 mm of thickness, 400 lm of pore size, 187–230 lm of grid thickness, and 82% of porosity. Alkaline phosphatase (ALP) activity of the BMP-2-immobilized PLLA scaffold in MC3T3-E1 and W-20-17 cells was more increased than BMP-2 itself due to the controlled release of BMP-2 from the scaffold. Tenfold new bone formation for the BMP-2-immobilized PLLA scaffold was obtained by micro-CT analysis than PLLA scaffold without BMP-2 weeks after 4 weeks of transplantation model mouse. Further another big animal model study should be performed before clinical trials.
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BACKGROUND/OBJECTIVES@#Probiotics have been suggested as potent modulators of agerelated disorders in immunological functions, yet little is known about sex-dependent effects of probiotic supplements. Therefore, we aimed to investigate sex-dependent effects of probiotics on profiles of the gut microbiota and peripheral immune cells in healthy older adults. @*SUBJECTS/METHODS@#In a randomized, double-blind, placebo-controlled, multicenter trial, healthy elderly individuals ≥ 65 yrs old were administered probiotic capsules (or placebo) for 12 wk. Gut microbiota was analyzed using 16S rRNA gene sequencing and bioinformatic analyses. Peripheral immune cells were profiled using flow cytometry for lymphocytes (natural killer, B, CD4 + T, and CD8 + T cells), dendritic cells, monocytes, and their subpopulations. @*RESULTS@#Compared with placebo, phylum Firmicutes was significantly reduced in the probiotic group in women, but not in men. At the genus level, sex-specific responses included reductions in the relative abundances of pro-inflammatory gut microbes, including Catabacter and unclassified_Coriobacteriales, and Burkholderia and unclassified Enterobacteriaceae, in men and women, respectively. Peripheral immune cell profiling analysis revealed that in men, probiotics significantly reduced the proportions of dendritic cells and CD14 + CD16 - monocytes; however, these effects were not observed in women. In contrast, the proportion of total CD4 + T cells was significantly reduced in women in the probiotic group. Additionally, serum lipopolysaccharide-binding protein levels showed a decreasing tendency that were positively associated with changes in gut bacteria, including Catabacter (ρ = 0.678, P < 0.05) and Burkholderia (ρ = 0.673, P < 0.05) in men and women, respectively. @*CONCLUSIONS@#These results suggest that probiotic supplementation may reduce the incidence of inflammation-related diseases by regulating the profiles of the gut microbiota and peripheral immune cells in healthy elders in a sex-specific manner.
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Vaccination has been recently attracted as one of the most successful medical treatments of the prevalence of many infectious diseases. Mucosal vaccination has been interested in many researchers because mucosal immune responses play part in the first line of defense against pathogens. However, mucosal vaccination should find out an efficient antigen delivery system because the antigen should be protected from degradation and clearance, it should be targeted to mucosal sites, and it should stimulate mucosal and systemic immunity. Accordingly, mucoadhesive polymeric particles among the polymeric particles have gained much attention because they can protect the antigen from degradation, prolong the residence time of the antigen at the target site, and control the release of the loaded vaccine, and results in induction of mucosal and systemic immune responses. In this review, we discuss advances in the development of several kinds of mucoadhesive polymeric particles for mucosal vaccine delivery.
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Vaccination has been recently attracted as one of the most successful medical treatments of the prevalence of many infectious diseases. Mucosal vaccination has been interested in many researchers because mucosal immune responses play part in the first line of defense against pathogens. However, mucosal vaccination should find out an efficient antigen delivery system because the antigen should be protected from degradation and clearance, it should be targeted to mucosal sites, and it should stimulate mucosal and systemic immunity. Accordingly, mucoadhesive polymeric particles among the polymeric particles have gained much attention because they can protect the antigen from degradation, prolong the residence time of the antigen at the target site, and control the release of the loaded vaccine, and results in induction of mucosal and systemic immune responses. In this review, we discuss advances in the development of several kinds of mucoadhesive polymeric particles for mucosal vaccine delivery.
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BACKGROUND@#Despite the many advantages of recombinant subunit vaccines, they have critical weaknesses that include a low efficacy for promoting cellular and humoral immune responses against antigens because of their poor immunogenicity, and a rapidly cleared properties as a result of proteolytic enzymes in the body. To circumvent these problems, we developed mannan-decorated inulin acetate microparticles (M-IA MPs) that functioned as carriers and adjuvants for immunization with the recombinant foot-and-mouth disease multi-epitope subunit vaccine (M5BT). @*METHODS@#The M5BT-loaded M-IA MPs were obtained by a double-emulsion solvent-evaporation method. Their properties including morphology, size and release ability were determined by field emission scanning electron microscope, dynamic light-scattering spectrophotometer and spectrophotometer. To assess the immunization efficacy of the MPs, mice were immunized with MPs and their sera were analyzed by ELISA. @*RESULTS@#The M-IA MPs obtained by a double-emulsion solvent-evaporation method were spherical and approximately 2–3 µm, and M5BT was encapsulated in the M-IA MPs. The M5BT-loaded M-IA MPs showed higher antigen-specific IgG, IgG1, IgG2a and anti-FMDV antibodies than the M5BT-loaded IA MPs and the Freund’s adjuvant as a control. @*CONCLUSION@#The M-IA MPs showed a powerful and multifunctional polymeric system that combined two toll-like receptor agonists compared to the conventional adjuvant.
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BACKGROUND@#Despite the many advantages of recombinant subunit vaccines, they have critical weaknesses that include a low efficacy for promoting cellular and humoral immune responses against antigens because of their poor immunogenicity, and a rapidly cleared properties as a result of proteolytic enzymes in the body. To circumvent these problems, we developed mannan-decorated inulin acetate microparticles (M-IA MPs) that functioned as carriers and adjuvants for immunization with the recombinant foot-and-mouth disease multi-epitope subunit vaccine (M5BT). @*METHODS@#The M5BT-loaded M-IA MPs were obtained by a double-emulsion solvent-evaporation method. Their properties including morphology, size and release ability were determined by field emission scanning electron microscope, dynamic light-scattering spectrophotometer and spectrophotometer. To assess the immunization efficacy of the MPs, mice were immunized with MPs and their sera were analyzed by ELISA. @*RESULTS@#The M-IA MPs obtained by a double-emulsion solvent-evaporation method were spherical and approximately 2–3 µm, and M5BT was encapsulated in the M-IA MPs. The M5BT-loaded M-IA MPs showed higher antigen-specific IgG, IgG1, IgG2a and anti-FMDV antibodies than the M5BT-loaded IA MPs and the Freund’s adjuvant as a control. @*CONCLUSION@#The M-IA MPs showed a powerful and multifunctional polymeric system that combined two toll-like receptor agonists compared to the conventional adjuvant.
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Porcine epidemic diarrhea (PED) is a highly contagious enteric swine disease. The large economic impact of PED on the swine industry worldwide has made the development of an effective PED vaccine a necessity. S0, a truncated region of the porcine epidemic diarrhea virus (PEDV) spike protein, has been suggested as a candidate antigen for PED subunit vaccines; however, poor solubility problems when the protein is expressed in Escherichia coli, and the inherent problems of subunit vaccines, such as low immunogenicity, remain. Flagellin has been widely used as a fusion partner to enhance the immunogenicity and solubility of many difficult-to-express proteins; however, the conjugation effect of flagellin varies depending on the target antigen or the position of the fusion placement. Here, we conjugated flagellin, Vibrio vulnificus FlaB, to the N- and C-termini of S0 and evaluated the ability of the fusion to enhance the solubility and immunogenicity of S0. Flagellin conjugation in the presence of the trigger factor chaperone tig greatly improved the solubility of the fusion protein (up to 99%) regardless of its conjugation position. Of importance, flagellin conjugated to the N-terminus of S0 significantly enhanced S0-specific humoral immune responses compared to other recombinant antigens in Balb/c mice. The mechanism of this phenomenon was investigated through in vitro and in vivo studies. These findings provide important information for the development of a novel PED vaccine and flagellin-based immunotherapeutics.
Subject(s)
Animals , Mice , Diarrhea , Escherichia coli , Flagellin , Immunity, Humoral , In Vitro Techniques , Porcine epidemic diarrhea virus , Solubility , Swine , Swine Diseases , Vaccines, Subunit , Vibrio vulnificus , VibrioABSTRACT
BACKGROUND/OBJECTIVES: This cross-sectional study assessed household food security status and determined its association with diet quality and weight status among indigenous women from the Mah Meri tribe in Peninsular Malaysia. SUBJECTS/METHODS: The Radimer/Cornell Hunger and Food Insecurity Instrument and the Malaysian Healthy Eating Index (HEI) were used to assess household food security status and diet quality, respectively. Information on socio-demographic characteristics and 24-hour dietary recall data were collected through face-to-face interview, and anthropometric measurements including weight, height, and body mass index (BMI) were obtained from 222 women. RESULTS: Majority of households (82.9%) experienced different levels of food insecurity: 29.3% household food insecurity, 23.4% individual food insecurity, and 30.2% fell into the child hunger group. The food-secure group had significantly fewer children and smaller household sizes than the food-insecure groups (P < 0.05). The mean household income, income per capita, and food expenditure significantly decreased as food insecurity worsened (P < 0.001). The food-secure group had significantly higher Malaysian HEI scores for grains and cereals (P < 0.01), as well as for meat, poultry, and eggs (P < 0.001), than the food-insecure groups. The child-hunger group had significantly higher fat (P < 0.05) and sodium (P < 0.001) scores than the food-secure and household food-insecure groups. Compared to the individual food-insecure and child-hunger groups, multivariate analysis of covariance showed that the food-secure group was significantly associated with a higher Malaysian HEI score while the household food-insecure group was significantly associated with a higher BMI after controlling for age (P < 0.025). CONCLUSIONS: The majority of indigenous households faced food insecurity. Food insecurity at the individual and child levels was associated with lower quality of diet, while food insecurity at the household level was associated with higher body weight. Therefore, a substantial effort by all stakeholders is warranted to improve food insecurity among poorer households. The results suggest a pressing need for nutritional interventions to improve dietary intake among low income households.
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Child , Female , Humans , Body Mass Index , Body Weight , Cross-Sectional Studies , Diet , Eating , Edible Grain , Eggs , Family Characteristics , Food Supply , Health Expenditures , Hunger , Malaysia , Meat , Multivariate Analysis , Ovum , Poultry , SodiumABSTRACT
BACKGROUND: Injectable biomaterials have attracted increasing attention for volume restoration and tissue regeneration. The main aim of this review is to discuss the current status of the injectable biomaterials for correction of tissue defects in plastic and reconstructive surgery. METHODS: Requirements of injectable biomaterials, mechanism of in situ gelation, characteristics, and the combinational usage of adipose-derived stem cells (ADSCs) and growth factors were reviewed. RESULTS: The ideal injectable biomaterials should be biocompatible, non-toxic, easy to use, and cost-effective. Additionally, it should possess adequate mechanical properties and stability. In situ gelation method includes physical, chemical, enzymatic and photo-initiated methods. Natural and synthetic biomaterials carry their pros and cons due to their inherent properties. The combined use of ADSCs and growth factors provides enhanced potential for adipose tissue regeneration. CONCLUSION: The usage of injectable biomaterials has been increasing for the tissue restoration and regeneration. The future of incorporating ADSCs and growth factors into the injectable biomaterials is promising.
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Adipose Tissue , Biocompatible Materials , Intercellular Signaling Peptides and Proteins , Methods , Plastics , Regeneration , Stem CellsABSTRACT
Objective:To investigate the effects of Hydroxychloroquine on cell apoptosis in peripheral blood mononuclear cells of systemic lupus erythematosus and its mechanisms.Methods:The peripheral blood mononuclear cells of 30 active SLE patients and 15 healthy persons were separated for cell culture.There were four groups:control group,SLE group and HCQ 5 mg/L and HCQ 25 mg/L group.MTT was used to measure the inhibitory effect.Annexin V/PI flow cytometry was performed to analyze cell apoptosis.Western blot was used to evaluate the expressions of PI3 K,pAKt,mTOR,BCL-2,BAX and caspase-3.Besides,the PBMCs of SLE patients were treated with HCQ 25 mg/L and the PI3K/Akt pathway inhibitor LY294002 20 μmol/L and its cell growth inhibition and apoptosis were observed.Results:Compared with the control group,the cell growth inhibition and apoptosis rate of SLE patients group were significantly increased(P＜0.05);while the cell growth inhibition and apoptosis rate of HCQ 5 mg/L and 25 mg/L were increased significantly than the SLE patients group(P＜0.05).Compared with SLE patients group,the expression levels of PI3K,pAKt,mTOR and BCL-2 of HCQ group were significantly increased while the expression of BAX and caspase-3 decreased significantly (P＜ 0.05).The PI3K/Akt pathway inhibitor LY294002 could block the PBMCs apoptosis of SLE patients.Conclusion:Hydroxychloroquine can promote the PBMCs apoptosis of SLE patients by PI3K/Akt signaling pathways.
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Nanoliposomes are considered to be the most successful nanoparticle drug delivery system, but their fate in vivo has not been fully understood due to lack of reliable bioanalytical methods, which seriously limits the development of liposomal drugs. Hence, an overview of currently used bioanalytical methods is imperative to lay the groundwork for the need of developing a bioanalytical method for liposome measurements in vivo. Currently, major analytical methods for nanoliposomes measurement in vivo include fluorescence labeling, radiolabeling, magnetic resonance imaging (MRI), mass spectrometry and computed tomography.In this review, these bioanalytical methods are summarized, and the advantages and disadvantages of each are discussed. We provide insights into the applicability and limitations of these analytical methods in the application of nanoliposomes measurement in vivo, and highlight the recent development of instrumental analysis techniques. The review is devoted to providing a comprehensive overview of the investigation of nanoliposomes design and associated fate in vivo, promoting the development of bioanalytical techniques for nanoliposomes measurement, and understanding the pharmacokinetic behavior, effectiveness and potential toxicity of nanoliposomes in vivo.
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Several barriers such as gastric pH, enzymatic degradation and rapid transit should be overcome to orally deliver antigens for taking up by epithelial microfold cells in Peyer's patches of small intestine. To solve the above mentioned problems, we designed pH-sensitive and mucoadhesive polymeric microparticles (MPs) prepared by double emulsion technique using cellulose acetate phthalate (CAP) to enhance immune response of foot-and-mouth disease (FMD) virus (FMDV) subunit vaccine. Thiolation of CAP improved mucoadhesive property of CAP to prolong the MPs transit time through the gastrointestinal tract. Thiolated CAP (T-CAP) also slowed down antigen release in acidic pH of stomach but released more antigens in neutral pH of small intestine due to the pH-sensitivity of the T-CAP. Oral immunization of a chimerical multi-epitope recombinant protein as the FMD subunit vaccine via T-CAP MPs effectively delivered the vaccine to Peyer's patches eliciting mucosal IgA response. It will make a step forward into a promising oral subunit vaccine development in livestock industry.
Subject(s)
Animals , Cellulose , Foot-and-Mouth Disease , Gastrointestinal Tract , Hydrogen-Ion Concentration , Immunization , Immunoglobulin A , Intestine, Small , Livestock , Peyer's Patches , Polymers , Staphylococcal Protein A , StomachABSTRACT
Coronary artery disease (CAD) has been reported to be a major cause of death worldwide. Current treatment methods include atherectomy, coronary angioplasty (as a percutaneous coronary intervention), and coronary artery bypass. Among them, the insertion of stents into the coronary artery is one of the commonly used methods for CAD, although the formation of in-stent restenosis (ISR) is a major drawback, demanding improvement in stent technology. Stents can be improved using the delivery of DNA, siRNA, and miRNA rather than anti-inflammatory/anti-thrombotic drugs. In particular, genes that could interfere with the development of plaque around infected regions are conjugated on the stent surface to inhibit neointimal formation. Despite their potential benefits, it is necessary to explore the various properties of gene-eluting stents. Furthermore, multifunctional electronic stents that can be used as a biosensor and deliver drug- or gene-based on physiological condition will be a very promising way to the successful treatment of ISR. In this review, we have discussed the molecular mechanism of restenosis, the use of drug- and gene-eluting stents, and the possible roles that these stents have in the prevention and treatment of coronary restenosis. Further, we have explained how multifunctional electronic stents could be used as a biosensor and deliver drugs based on physiological conditions.
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Angioplasty , Atherectomy, Coronary , Biosensing Techniques , Cause of Death , Coronary Artery Bypass , Coronary Artery Disease , Coronary Restenosis , Coronary Vessels , DNA , Drug-Eluting Stents , MicroRNAs , RNA, Small Interfering , StentsABSTRACT
Coronary artery disease (CAD) has been reported to be a major cause of death worldwide. Current treatment methods include atherectomy, coronary angioplasty (as a percutaneous coronary intervention), and coronary artery bypass. Among them, the insertion of stents into the coronary artery is one of the commonly used methods for CAD, although the formation of in-stent restenosis (ISR) is a major drawback, demanding improvement in stent technology. Stents can be improved using the delivery of DNA, siRNA, and miRNA rather than anti-inflammatory/anti-thrombotic drugs. In particular, genes that could interfere with the development of plaque around infected regions are conjugated on the stent surface to inhibit neointimal formation. Despite their potential benefits, it is necessary to explore the various properties of gene-eluting stents. Furthermore, multifunctional electronic stents that can be used as a biosensor and deliver drug- or gene-based on physiological condition will be a very promising way to the successful treatment of ISR. In this review, we have discussed the molecular mechanism of restenosis, the use of drug- and gene-eluting stents, and the possible roles that these stents have in the prevention and treatment of coronary restenosis. Further, we have explained how multifunctional electronic stents could be used as a biosensor and deliver drugs based on physiological conditions.
Subject(s)
Angioplasty , Atherectomy, Coronary , Biosensing Techniques , Cause of Death , Coronary Artery Bypass , Coronary Artery Disease , Coronary Restenosis , Coronary Vessels , DNA , Drug-Eluting Stents , MicroRNAs , RNA, Small Interfering , StentsABSTRACT
Objective To study the effectiveness of electroacupuncture plus bloodletting in treating deglutition disorder after cerebral stroke.Method Eighty-four patients were randomized into a treatment group and a control group, 42 cases in each group. The treatment group was intervened by electroacupuncture plus bloodletting and rehabilitation training, while the control group was intervened by rehabilitation training. After 2 treatment courses and 6 months after the treatment, Kubota's water drinking test and clinical bedside assessment were evaluated to measure the short-term and long-term therapeutic efficacies. By observing the change of clinical bedside assessment score, the effect of electroacupuncture plus bloodletting on certain symptoms of deglutition disorder was analyzed.Result The total effective rate was 90.5% in the treatment group versus54.8% in the control group, and the between-group difference was statistically significant (P<0.01).Respectively after 2 treatment courses and 6 months after the intervention, the drinking water test scores in the treatment group were superior to those in the control group (P<0.05). The bedside assessment scores in the treatment group were better than those in the control group respectively after 2 treatment courses and 6 months after the intervention (P<0.05). Post-treatment water drinking and bedside assessment scores were significantly better than pre-treatment scores in both groups (P<0.05). According to the observation of short-term and long-term change of bedside assessment, electroacupuncture plus bloodletting significantly improved both short-term and long-term scores of throat function, pharynx reflex, involuntary cough, throat movement, and swallowing cough (P<0.05).Conclusion Clinical observation showed that electroacupuncture plus bloodletting can produce significant short-term and long-term therapeutic efficacies in treating deglutition disorder after cerebral stroke. Electroacupuncture plus bloodletting can produce satisfactory effects in improving mouth-phase and pharynx-phase symptoms and signs in treating deglutition disorder after cerebral stroke.
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Objective:To explore a scheduling method of rehabilitation medical resource for smart traditional Chinese medicine(TCM) for dysphagia because of cerebral apoplexy in order to save diagnosis time for patient and reasonably arrange treatment process for medical personnel.Methods: We designed the framework of smart TCM rehabilitation system, and proposed the medical resource scheduling model including acupuncture, massage and rehabilitation training. In addition, the genetic algorithm was employed to establish the scheduling method under the optimal objective towards the scheduling time.Results: (1) The treatment time of five dysphagia patients by using rehabilitation resource scheduling in Beijing Zhongguancun Hospital were saved 42.5% from the total treatment time compared to without scheduling; (2)The rehabilitation process of twenty virtual dysphagia patients were treated by the simulation scheduling, and 71% of total treatment time was saved. The efficiency of diagnosis and treatment was improved obviously .Conclusion: Smart TCM rehabilitation resource scheduling method can be used in an assisted rehabilitation therapy for dysphagia because of cerebral apoplexy, and it can improve the efficiency of diagnosis and treatment for patient and save a lot of medical resources.