ABSTRACT
BACKGROUND: Stem cell-laden hydrogel microcapsules construction is important for a wide application in tissue engineering and cell-based medicine, such as building an ideal immune barrier. Challenges are emerging for effectively storing such microcapsules by cryopreservation, and a large proportion of research has been on the cryopreservation of single cells encapsulated into microcapsules without a core-shell structure. OBJECTIVE: To achieve the effective cryopreservation of stem cell-laden hydrogel microcapsules with a core-shell structure. MATERIALS AND METHODS: A novel core-shell alginate hydrogel encapsulation method was used to produce mesenchymal stem cell-laden microcapsules by microfluidic technique. RESULTS: This microcapsule could inhibit ice formation to achieve vitreous cryopreservation with a low concentration (2 M) of penetrating cryoprotectants. CONCLUSION: Cell laden hydrogel microcapsules may have the potential to be the basis of a new strategy of cell cryopreservation and applications. https://doi.org/10.54680/fr24210110212.
Subject(s)
Hydrogels , Mesenchymal Stem Cells , Hydrogels/pharmacology , Capsules/pharmacology , Cryopreservation/methods , Cryoprotective Agents/pharmacology , Alginates/pharmacologyABSTRACT
Although mitochondria are crucial for recovery after spinal cord injury (SCI), therapeutic strategies to modulate mitochondrial metabolic energy to coordinate the immune response and nerve regeneration are lacking. Here, a ligand-screened cerium-based metal-organic framework (MOF) with better ROS scavenging and drug-loading abilities is encapsulated with polydopamine after loading creatine to obtain microcapsules (Cr/Ce@PDA nanoparticles), which reverse the energy deficits in both macrophages and neuronal cells by combining ROS scavenging and energy supplementation. It reprogrames inflammatory macrophages to the proregenerative phenotype via the succinate/HIF-1α/IL-1ß signaling axis. It also promotes the regeneration and differentiation of neural cells by activating the mTOR pathway and paracrine function of macrophages. In vivo experiments further confirm the effect of the microcapsules in regulating early ROS-inflammation positive-feedback chain reactions and continuously promoting nerve regeneration. This study provides a new strategy for correcting mitochondrial energy deficiency in the immune response and nerve regeneration following SCI.
Subject(s)
Metal-Organic Frameworks , Spinal Cord Injuries , Humans , Metal-Organic Frameworks/metabolism , Ligands , Capsules/metabolism , Capsules/pharmacology , Capsules/therapeutic use , Reactive Oxygen Species/metabolism , Nerve Regeneration/physiology , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/metabolism , Mitochondria/metabolismABSTRACT
Dyslipidemia is an imbalance of various lipids, and propolis, as a natural resinous viscos mixture made by Apis mellifera L. could improve in this condition. In this single-blind, randomized trial, 60 women with type 2 diabetes and dyslipidemia were divided into four groups: (1) the patients who did not apply the combined training and 500 mg propolis capsules supplement (Control group); (2) subjects performed combined training, including aerobic and resistance training (EXR); (3) subjects received the 500 mg propolis supplement capsules (SUPP); (4) Subjects performed combined training along with receiving the 500 mg propolis supplement capsules (EXR + SUPP). We evaluated the concentration of CTRP12, SFRP5, interleukin-6 (IL6), superoxide dismutase (SOD), malondialdehyde (MDA), adiponectin, and total antioxidant capacity (TAC) before and after the intervention. MDA, TAC, IL6, CTRP12, SFRP5 IL6, adiponectin, and lipid profile levels ameliorated in the EXR + SUPP group. We found that 8 weeks of treatment by combined exercise training and propolis supplement decreased inflammation activity and increased antioxidant defense in women with diabetic dyslipidemia.Trial registration This study was registered in the Iranian Registry of Clinical Trials; IRCT code: IRCT20211229053561N1.
Subject(s)
Diabetes Mellitus, Type 2 , Propolis , Humans , Adult , Female , Animals , Propolis/therapeutic use , Propolis/pharmacology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Antioxidants/pharmacology , Iran , Adiponectin/pharmacology , Adiponectin/therapeutic use , Capsules/pharmacology , Capsules/therapeutic use , Interleukin-6 , Single-Blind Method , Oxidative StressABSTRACT
Improved therapies for inflammatory bowel diseases are sorely needed. Novel therapeutic agents and the development of controlled release systems for targeted tissue delivery are interesting approaches to overcome these barriers. We investigated the activity of trans-chalcone (T) in acetic acid-induced colitis in mice and developed, characterized, and determined the therapeutic effect of pectin/casein polymer microcapsules containing T (MT) in a colitis mouse model. In vitro, compound release was achieved in simulated intestinal fluid but not in the simulated gastric fluid. In vivo, since T at the dose of 3 mg/kg but not 0.3 mg/kg ameliorated colitis, we next tested the effects of MT at 0.3 mg/kg (non-effective dose). MT, but not free T at 0.3 mg/kg, significantly improved colitis outcomes such as neutrophil recruitment, antioxidant capacity, cytokine production, and NF-kB activation. This translated into reduced macro and microscopic damage in the colon. T release from the microcapsules is mediated by a pH-dependent and pectinase-regulated mechanism that provide controlled and prolonged release of T. Moreover, MT lowered the required dose for T therapeutic effect, indicating that could be a suitable pharmaceutical approach to colitis treatment. This is the first demonstration that T or MT is effective at reducing the signs of colitis.
Subject(s)
Chalcone , Chalcones , Colitis , Mice , Animals , Caseins , Chalcone/pharmacology , Capsules/pharmacology , Pectins , Colitis/chemically induced , Colitis/drug therapy , Colon , NF-kappa B , Disease Models, AnimalABSTRACT
OBJECTIVE: In this study, it was aimed to provide a therapeutic approach for T1DM by encapsulating the pancreatic islets with mesenchymal stem cells and decellularized pancreatic extracellular matrix to support the survival of islets while maintaining their cellular activity. METHOD: Pancreatic extracellular matrix was decellularized using different concentrations of detergent series. After the preparation of the protein-based tissue extracellular matrix was shown to be free of cells or any genetic material by molecular, immunofluorescence and histochemical techniques. Following the homogenization of the decellularized pancreatic extracellular matrix and the analysis of its protein composition by LC-MS, the matrix proteins were incorporated with pancreatic islets and rat adipose tissue-derived MSCs (rAT-MSCs) in alginate microcapsules. Glucose-stimulated insulin secretion property of the islet cells in the microbeads was evaluated by insulin ELISA. The gene expression profile of the encapsulated cells was analyzed by Real-Time PCR. RESULTS: Unlike the protein composition of whole pancreatic tissue, the decellularized pancreas matrix was free of histone proteins or proteins originated from mitochondria. The protein matrix derived from pancreatic tissue was shown to support the growth and maintenance of the islet cells. When compared to the non-encapsulated pancreatic islet, the encapsulated cells demonstrate to be more efficient in terms of insulin expression. CONCLUSION: The extracellular pancreatic matrix obtained in this study was directly used as supplementary in the alginate-based microcapsule enhancing the cell survival. The tissue matrix protein and alginate had a synergistic effect on total insulin secretion, which might have the potential to overcome the insulin deficiency. Despite the improvement in the cell viability and the number, the efficiency of the insulin secretion in response to glucose stimulation from the alginate microcapsules did not meet the expectation when compared with the non-encapsulated pancreatic islets.
Subject(s)
Islets of Langerhans Transplantation , Islets of Langerhans , Mesenchymal Stem Cells , Rats , Animals , Capsules/metabolism , Capsules/pharmacology , Insulin/metabolism , Glucose/pharmacology , Glucose/metabolism , Mesenchymal Stem Cells/metabolism , Alginates/chemistryABSTRACT
Blocking of nutrient uptake and amino acid biosynthesis are considered potential targets for next-generation antifungal drugs against pathogenic fungi, including Cryptococcus neoformans. In this regard, the sulfate assimilation pathway is particularly attractive, as it is only present in eukaryotes such as plants and fungi, yet not in mammals. Here, we demonstrated that the adenylyl sulfate kinase (Met14) in the sulfate assimilation pathway is not essential yet is required for the viability of C. neoformans due to its involvement in biosynthesis of two sulfur-containing amino acids, cysteine and methionine. Met14-dependent cysteine and methionine biosynthesis was found to significantly contribute to a diverse range of pathobiological processes in C. neoformans. Met14-dependent cysteine rather than methionine biosynthesis was also found to play pivotal roles in cell growth and tolerance to environmental stresses and antifungal drugs. In contrast, the Met14-dependent methionine biosynthesis was found to be more important than cysteine biosynthesis for the production of major cryptococcal virulence factors of melanin pigments and polysaccharide capsules. Finally, we also found that despite its attenuated virulence in an insect model, Galleria mellonella, the met14Δ mutant yielded no difference in virulence in a murine model of systemic cryptococcosis. Hence, clinical inhibition of Met14-dependent amino acid biosynthetic pathways may not be advantageous for the treatment of systemic cryptococcosis. IMPORTANCE Current antifungal drugs have several limitations, such as drug resistance, severe side effects, and a narrow spectrum. Therefore, novel antifungal targets are urgently needed. To this end, fungal sulfur amino acid biosynthetic pathways are considered potential targets for development of new antifungal agents. Here, we demonstrated that Met14 in the sulfate assimilation pathway promotes growth, stress response, and virulence factor production in C. neoformans via synthesis of sulfur-containing amino acids methionine and cysteine. Met14-dependent cysteine rather than methionine synthesis was found to be critical for growth and stress responses, whereas Met14-dependent methionine synthesis was more important for the production of antiphagocytic capsules and antioxidant melanin in C. neoformans. Surprisingly, deletion of the MET14 gene was found to attenuate cryptococcal virulence in an insect model, yet not in a murine model. Collectively, our results showed that Met14-dependent cysteine and methionine biosynthesis play roles that are distinct from each other in C. neoformans. Moreover, Met14 is unlikely to be a suitable anticryptococcal drug target.
Subject(s)
Cryptococcosis , Cryptococcus neoformans , Animals , Mice , Cryptococcus neoformans/genetics , Cysteine/metabolism , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Disease Models, Animal , Melanins/metabolism , Melanins/pharmacology , Capsules/metabolism , Capsules/pharmacology , Cryptococcosis/microbiology , Virulence Factors/metabolism , Methionine/metabolism , Methionine/pharmacology , Sulfur/metabolism , Sulfates/metabolism , Sulfates/pharmacology , MammalsABSTRACT
INTRODUCTION: Little is known about the protective effects of butylphthalide on cerebral ischemia-reperfusion injury. This study aims to investigate the impact on the second mitochondrial-derived activator of Caspases (Smac) and X-linked inhibitor of apoptosis protein (XIAP) expression in the ischemic semidark area using a rat model of carotid artery stenosis. METHODS: Thirty Sprague-Dawley rats were randomly divided into the sham-operated group, carotid stenosis model controls, low-dose (20 mg/kg), medium-dose (40 mg/kg), and high-dose (80 mg/kg) butylphthalide groups. The neurological function was scored by the balance beam test (BBT). The morphological changes of brain tissue were detected by Hematoxylin-eosin (HE) staining, with apoptosis detected by Terminal Deoxynucleotidyl Transferase mediated dUTP Nick-End Labeling (TUNEL) staining. Smac and XIAP protein expression were detected by immunohistochemistry (IHC). The expressions of Smac and XIAP mRNA were detected by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: HE showed that neuronal loss, nuclear consolidation, and vacuolar degeneration were significantly reduced in the medium and high-dose butylphthalide groups compared with the model controls. The BBT scores and apoptotic index were significantly lower in the medium and high doses of butylphthalide compared with the model controls. RT-qPCR and IHC showed that Smac, XIAP mRNA and protein expressions in the ischemic hemispheric region were significantly reduced in low, medium, and high doses of butylphthalide compared with the model controls (P < 0.05), showing some concentration effect. CONCLUSIONS: Butylphthalide can significantly reduce Smac and XIAP mRNA and protein expression, inhibit neuronal apoptosis induced by ischemia-reperfusion injury in rats with carotid stenosis, and exert neuroprotective effects.
Subject(s)
Brain Ischemia , Carotid Stenosis , Reperfusion Injury , Rats , Animals , Caspases/metabolism , Caspases/pharmacology , X-Linked Inhibitor of Apoptosis Protein/metabolism , X-Linked Inhibitor of Apoptosis Protein/pharmacology , Rats, Sprague-Dawley , Capsules/pharmacology , Apoptosis , Ischemia , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Reperfusion , RNA, Messenger , Brain Ischemia/drug therapyABSTRACT
In response to current trends in the modification of guided bone regeneration (GBR) materials, we aimed to build upon our previous studies on epigallocatechin-3-gallate (EGCG) by immersing a commonly used bone graft primarily composed of hydroxyapatite (HA) in EGCG solution, expecting to obtain superior bone material integration after implantation. Bone grafts are commonly used for bone repair, in which the bone extracellular matrix is stimulated to promote osteogenesis. However, due to its profibrosis effect, this osteoconductive material commonly exhibits implant failure. In addition to providing a basic release profile of EGCG-modified bone graft (E-HA) to clarify the relationship between this material and the environment, we have examined the integration effect via subcutaneous implantation experiments. In this manner, we have assessed the aggregation of proinflammatory macrophages, the formation of fibrous capsules, and an enhanced cell viability observed in cultured RAW 264.7 cells. Among these results, we focus on proinflammatory macrophages due to their close relationship with fibrosis, which is the most important process in the immune response. Immunofluorescent staining results showed that E-HA substantially compromised the formation of fibrous capsules in hematoxylin-eosin-stained sections, which exhibited less proinflammatory macrophage recruitment; meanwhile, the cell viability was improved. This work lays the foundation for future studies on GBR.
Subject(s)
Catechin , Osteogenesis , Mice , Animals , Disease Models, Animal , Capsules/pharmacology , Bone Regeneration/physiology , Macrophages , Catechin/pharmacology , Durapatite/pharmacologyABSTRACT
One of the complications of menopause is sleep disorders, which affect women's health. Ocimum basilicum contains compounds that may affect sleep. The aim of this study was to determine the effect of an oral capsule of O. basilicum leaf extract on sleep quality and the severity of insomnia in menopausal women. This triple-blind, randomized clinical trial study was performed on 60 Iranian menopausal women aged 40 to 65 years. Subjects were randomly assigned into two groups of intervention (each capsule containing 250 mg of O. basilicum extract and 250 mg Avicel) per day for 1 month and placebo. The Pittsburgh Sleep Quality and Insomnia Intensity Index were used to assess sleep quality and severity of insomnia before, 2 weeks after and 1 month after the intervention. There was no statistically significant difference in the baseline variables between the intervention and placebo groups (p > .05). The total sleep quality scores in the two groups of intervention and placebo were 6.2 ± 0.3 versus 9.3 ± 0.3 (p < .001) and 3.7 ± 0.3 versus 9.1 ± 0.3 (p = .015) 2 weeks and 1 month after the intervention, respectively. The total insomnia severity scores in the two groups of intervention and placebo were 9.0 ± 0.3 versus 12.1 ± 0.3 (p < .001) and 5.6 ± 0.5 versus 11.0 ± 0.5 (p < .001) 2 weeks and 1 month after the intervention, respectively. Consumption of O. basilicum capsules improved sleep quality and insomnia in menopausal women. This study was approved (code IR.MUMS.NURSE.REC.1398.070) by the Ethic committee of Mashhad University of Medical Sciences and registered at the Iranian Registry of Clinical Trials, with the No. IRCT20200104046001N1 in January 2020.
Subject(s)
Lamiaceae , Ocimum basilicum , Sleep Initiation and Maintenance Disorders , Humans , Female , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Quality , Capsules/pharmacology , Iran , Menopause , Sleep , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Treatment OutcomeABSTRACT
Alginate-based microcapsule has becoming a promising carrier for probiotic encapsulation due to the improved stress resistant ability. Besides the physical protection of microcapsules, bacterial quorum sensing (QS) is another prominent factor affecting microbial stress resistance in microcapsules. In the present study, Vibrio harveyi cells were entrapped and proliferated into cell aggregates in alginate-based microcapsules. The microenvironment composed of cells and biomacromolecules was regulated by the diameter, alginate concentration and core state of microcapsule. Then the effect of microenvironment on bacterial QS capacity was investigated, including bioluminescence, autoinducers (AIs) production and QS related genes expression. The highest diameter of 1200 µm and highest alginate concentration of 2.0 % w/v under the investigation range presented strongest QS capacity, and the maintenance of hydrogel core could enhance bacterial QS. Moreover, the mechanism analysis revealed that the formed biofilm on the surface of cell aggregates hampered the outward transfer of AIs, and the local AIs inside the cell aggregates induced stronger bacteria QS by close-range interaction. As a whole, these findings are helpful to guide the technological development and optimization of microencapsulated probiotics with stronger stress resistance, and the potential application in food, dairy, wastewater treatment and biosensor.
Subject(s)
Alginates , Quorum Sensing , Capsules/pharmacology , Alginates/pharmacology , BiofilmsABSTRACT
BACKGROUND: Glyphosate-based herbicides have been one of the most intensively used pollutants worldwide and food products containing glyphosate are an essential component of human and animal diet. The aim of present study was to determine the effect of glyphosate intoxication on the neurochemical properties of the enteric nervous system (ENS) neurons located in the wall of the porcine duodenum. METHODS: Fifteen sexually immature gilts divided into 3 groups were used: control-animals receiving empty gelatin capsules; G1-animals receiving a low dose of glyphosate-corresponding to the theoretical maximum daily intake (TMDI) - 0.05 mg/kg bw/day; G2-animals receiving a higher dose of glyphosate-corresponding to the acceptable daily intake (ADI)-0.5 mg/kg/day in gelatin capsules orally for 28 days. After this time, the animals were euthanized and small intestine samples were collected. Frozen sections were then subjected to the procedure of double immunofluorescent staining. KEY RESULTS: Glyphosate supplementation led to alterations in the neurochemical code of the ENS neurons in the porcine duodenum. Generally, increased population of neurons immunoreactive to PACAP, CGRP, CART, nNOS, and a decreased number of VAChT-like immunoreactive neurons were noted. CONCLUSIONS AND INFERENCES: It may be a first preclinical symptom of digestive tract dysfunction in the course of glyphosate intoxication and further studies are needed to assess the toxicity and risks of glyphosate to humans.
Subject(s)
Duodenum , Gelatin , Humans , Swine , Animals , Female , Capsules/pharmacology , Gelatin/pharmacology , Sus scrofa , Neurons , Phenotype , GlyphosateABSTRACT
Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct delivery of stem cells to repair periodontal defects may yield suboptimal effects due to the complexity of the periodontal inflammatory environment. Herein, stem cell spheroid is encapsulated by interfacial assembly of metal-phenolic network (MPN) nanofilm to form a stem cell microsphere capsule. Specifically, periodontal ligament stem cells (PDLSCs) spheroid was coated with FeIII/tannic acid coordination network to obtain spheroid@[FeIII-TA] microcapsules. The formed biodegradable MPN biointerface acted as a cytoprotective barrier and exhibited antioxidative, antibacterial and anti-inflammatory activities, effectively remodeling the inflammatory microenvironment and maintaining the stemness of PDLSCs. The stem cell microencapsulation proposed in this study can be applied to multiple stem cells with various functional metal ion/polyphenol coordination, providing a simple yet efficient delivery strategy for stem cell stemness maintenance in an inflammatory environment toward a better therapeutic outcome.
Subject(s)
Cell Encapsulation , Polyphenols , Anti-Bacterial Agents/pharmacology , Capsules/pharmacology , Cell Differentiation , Cells, Cultured , Ferric Compounds/pharmacology , Osteogenesis/physiology , Periodontal Ligament , Polyphenols/pharmacology , Stem Cells , Tannins/pharmacologyABSTRACT
A retrospective cohort study to explore the clinical efficacy and safety evaluation of calcitriol combined with bisphosphonates in the therapy of postmenopausal osteoporosis is conducted. The postmenopausal osteoporosis sufferers admitted to our hospital from January 2020 to June 2021 are retrospectively collected and divided into a contrast set and a study set, with 60 cases in each set. For the contrast set, all sufferers are treated with bisphosphonates. For the study set, on the basis of the therapy drugs in the contrast set, they are treated with calcitriol capsules. Firstly, the curative effects, bone mineral density standards, and bone metabolism standards of the two sets are contrasted; then, the lumbar spine bone mineral density, VAS score, and quality of life between the two sets of sufferers before therapy and 1 year after therapy are contrasted, and the correlation between bone mineral density and VAS and quality of life of the sufferers is analyzed. Lastly, the readmission situation between the two sets at one year is contrasted. The experimental results show that for postmenopausal women with osteoporosis, calcitriol combined with bisphosphonate therapy can notoriously enhance the clinical therapy effect of sufferers, with low adverse reactions, and can effectively enhance the bone mineral density and bone density of sufferers.
Subject(s)
Bone Density Conservation Agents , Osteoporosis, Postmenopausal , Bone Density , Bone Density Conservation Agents/adverse effects , Calcitriol/pharmacology , Calcitriol/therapeutic use , Capsules/pharmacology , Diphosphonates/adverse effects , Female , Humans , Osteoporosis, Postmenopausal/drug therapy , Quality of Life , Retrospective Studies , Treatment OutcomeABSTRACT
Microcapsules serve as a feasible formulation to load phenolic substances such as salicylic acid, a natural and safe antimicrobial agent. However, the antibacterial efficacy of salicylic acid microcapsules (SAMs) remains to be elucidated. Here, salicylic acid/ß-cyclodextrin inclusion microcapsules were subjected to systematic antibacterial assays and preliminary antibacterial mechanism tests using Escherichia coli and Staphylococcus aureus as target organisms. It was found that the core-shell rhomboid-shaped SAMs had a smooth surface. SAMs exhibited a minimum inhibitory concentration (MIC) and a minimum bactericidal concentration (MBC) of 4 mg/mL against both bacteria. In the growth inhibition assay, 1/4 × MIC, 1/2 × MIC, and 1 × MIC of SAMs effectively retarded bacterial growth, and this effect was more prominent with the rise in the level of SAMs. Practically, SAMs possessed a rapid bactericidal effect at the 1 × MIC level with a reduction of more than 99.9% bacterial population within 10 min. A pronounced sterilization activity against E. coli and S. aureus was also observed when SAMs were embedded into hand sanitizers as antimicrobial agents. Moreover, exposure of both bacteria to SAMs resulted in the leakage of intracellular alkaline phosphatases and macromolecular substances (nucleic acids and proteins), which indicated the disruption of bacterial cell walls and cell membranes. In conclusion, SAMs were able to inactivate E. coli and S. aureus both in vitro and in situ, highlighting the promising utilization of this formulation for antimicrobial purposes in the area of food safety and public health.
Subject(s)
Hand Sanitizers , Nucleic Acids , beta-Cyclodextrins , Anti-Bacterial Agents/pharmacology , Bacteria , Capsules/pharmacology , Escherichia coli , Hand Sanitizers/pharmacology , Microbial Sensitivity Tests , Phosphoric Monoester Hydrolases/pharmacology , Salicylic Acid/pharmacology , Staphylococcus aureusABSTRACT
Intracerebral transplantation of neural stem cells (NSCs) for ischemic stroke treatment has been demonstrated to be inefficient, with only <5% of delivered cells being retained. Microcapsules may be a good carrier for NSC delivery; however, the current microcapsules do not fully meet the demands for cell survival after transplantation. In the present study, we designed a strategy for the encapsulation of NSCs in a novel lipid-alginate (L-A) microcapsule based on a two-step method. The protective effect of a L-A microcapsule on oxygen-glucose deprivation (OGD) was investigated by using the CCK8 test, the LDH release test, and flow cytometry. Mechanisms underlying the prosurvival effect were investigated by detecting autophagy markers like P62, LC3-I, and LC3-II, and autophagy flux analysis was also performed. Lastly, the ability of the L-A microcapsule to support NSCs delivery for ischemic stroke was investigated in the middle cerebral artery occlusion (MCAO) model. We found that L-A microcapsules exerted a good protective effect against OGD compared with control and alginate microcapsules. The L-A microcapsules were found to promote cell survival by not only providing a "physical" barrier but also altering autophagy markers like P62 and LC3-II, which enhanced autophagy flux. This novel microcapsule was confirmed to be suitable for NSC delivery in vivo, which alleviated transplanted NSC apoptosis, reduced the infarct volume, decreased brain edema, improved neurological deficit scores, and lastly, improved survival rate. The findings of this study may provide a new method for stem cell delivery, raising the prospect that intracerebral cell transplantation may be used to treat, for instance, ischemic stroke, traumatic brain injury, and so on.
Subject(s)
Brain Ischemia , Ischemic Stroke , Neural Stem Cells , Alginates/pharmacology , Animals , Autophagy , Brain Ischemia/therapy , Capsules/pharmacology , Glucose/pharmacology , Infarction , Lipids/pharmacology , Mice , Oxygen/pharmacologyABSTRACT
Antithrombotic therapy is confronted with short half-lives of thrombolytic agents and high bleeding risks. Challenges remain in the development of drug delivery systems for thorough destruction of thrombi and timely restoration of blood flow while minimizing side effects. Herein, polydopamine capsule-like micromotors with urokinase (uPA) loadings and Arg-Gly-Asp (RGD) grafts (r-u@PCM) were constructed using rod-shaped bacteria as the template, and one single opening was created on each capsule through bacterial ghost (BG) formation. Glucose oxidase and catalase were encapsulated in the large cavity of microcapsules, and their successive oxidation of glucose produced O2 bubbles, which ejected out through the single opening to propel the motion of r-u@PCM. In vitro targeting testing of r-u@PCM shows significant higher accumulations on the activated platelets than those without RGD grafts (u@PCM, 7 folds) or without enzyme loadings (r-u@PC, 11 folds). Compared with the major distribution of r-u@PC on the clot surface, r-u@PCM efficiently penetrates into clots with dense fibrin networks, and near-infrared (NIR) irradiation (r-u@PCM/NIR) promotes thrombus infiltration through increasing uPA release and thermolysis of the networks. Pharmacokinetic study shows that the loading of uPA in r-u@PCM extends the terminal half-life from 24 min to 5.5 h and the bioavailability increased 13 times. In a hindlimb venous thrombosis model, r-u@PCM/NIR treatment promotes uPA accumulations in thrombi and disrupts all the thrombi after 8 h with a full recovery of blood flows. Effective thrombolysis is also achieved even after reducing the uPA dose 5 times. Thus, this is the first attempt to fabricate rod-shaped microcapsule motors through a biologically derived method, including bacterial templating and BG formation-induced opening generation. r-u@PCM/NIR treatment promotes thrombolysis through the photothermal effect, self-propelled infiltration into thrombi, and accelerated local release of uPA, providing a prerequisite for reducing uPA dose and bleeding side effects.
Subject(s)
Fibrinolytic Agents , Thrombosis , Animals , Bacteria , Capsules/pharmacology , Fibrinolysis , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/therapeutic use , Thrombosis/drug therapy , Urokinase-Type Plasminogen ActivatorABSTRACT
Potato tubers tend to sprout during long-term storage, resulting in quality deterioration and shortened shelf life. Restrictions on the use of chlorpropham, the major potato sprout suppressant, have led to a need to seek alternative methods. In this study, the effects of methyl jasmonate (MeJA) solutions and MeJA microcapsules on sprouting and other key quality attributes of the potato tuber were investigated. The results showed that the MeJA solution was most effective at 300 µmol L-1 according to TOPSIS analysis. To prepare MeJA microcapsules, the optimal formulation is with 0.04% emulsifier, 2.5% sodium alginate, 0.5% chitosan and 3% CaCl2. Compared to 300 µmol L-1 MeJA solution, MeJA microcapsules consumed a lower dose of MeJA but demonstrated a better retaining effect on the overall quality attributes of potato tubers. MeJA microcapsules are promising agents for the preservation of postharvest potato tubers.
Subject(s)
Solanum tuberosum , Acetates , Capsules/pharmacology , Cyclopentanes/pharmacology , Oxylipins/pharmacologyABSTRACT
Objectives: The study is aimed at exploring the effect of the controlled release of the glial-derived neurotrophic factor (GDNF) on nerve regeneration. Methods: The PLGA/chitosan composite nerve conduit was used to bridge the dissected trunk of the rat facial nerve. GDNF microcapsules were loaded into the nerve conduit. Nine weeks after surgery, the facial nerve zygomatic and buccal branches were labeled with fluorescent indicators. The incorrectly grown facial neurons were reversed and counted. The facial nerve functional recovery was assessed by measuring the maximum evoked potential. Results: The nerve conduit was filled with different regenerating factors, such as the GDNF, GDNF microcapsules, or saline (control). The number of incorrectly regenerated neurons was lower with the nerve conduits filled with GDNF microcapsules than with those supplied with just the GDNF. However, neither the GDNF nor GDNF microcapsules affected the number of regenerated neurons. The functional recovery of the facial nerve was the best, with the nerve conduit filled with GDNF microcapsules closest to the healthy uncut facial nerve. Conclusion: The stable slow-release GNDF microcapsule inside the biodegradable nerve conduit can reduce the extent of incorrect growth of the facial nerve neuron when bridging the dissected rat facial nerve trunk. The technique has a good effect on functional nerve recovery.
Subject(s)
Facial Nerve , Glial Cell Line-Derived Neurotrophic Factor , Animals , Capsules/pharmacology , Delayed-Action Preparations/pharmacology , Facial Nerve/surgery , Glial Cell Line-Derived Neurotrophic Factor/pharmacology , Nerve Regeneration , RatsABSTRACT
The common and frequent disease, ulcerative colitis (UC), causes serious physical and mental distress to patients. M2 macrophages have proven to play a role in anti-inflammation, which is a new potential target for UC therapy. In this study, we designed a safe and macrophages-targeting oral drug delivery system. Natural products, berberine (BBR), and Epigallocatechin Gallate (EGCG) with anti-inflammatory activity were assembled and encapsulated into yeast microcapsule (YM), generating therapeutic system BBR/MPN@YM. BBR and EGCG exhibited synergistic effects against UC through the effect of antioxidation. Through the interaction between ß-1,3-d-glucan on the surface of YM and dectin-1 receptors on macrophages, BBR/MPN@YM could be effectively transported to inflammation parts and internalized into macrophages, avoiding gastric degradation. In the in vivo UC mouse model, BBR/MPN@YM could transform M1 macrophages into anti-inflammatory M2 macrophages, thus exerting specific anti-inflammatory effects. Therefore, this BBR/MPN@YM targeted oral drug delivery system provided a new macrophages-targeting strategy for the clinical treatment of UC.
Subject(s)
Biological Products , Colitis, Ulcerative , Animals , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Biological Products/pharmacology , Capsules/pharmacology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Macrophages/metabolism , Mice , Saccharomyces cerevisiaeABSTRACT
Posterior capsular opacification (PCO) can cause postoperative visual loss after cataract surgery. Residual human lens epithelial cell (HLEC) proliferation, migration, epithelial-mesenchymal transition (EMT) and synthesis of extracellular matrix (ECM) are the entitative reasons for PCO. Low expression of Ral-binding protein 1-associated Eps domain-containing 2 (REPS2) and high levels of basic fibroblast growth factor (b-FGF) were observed in the lens and postoperative aqueous humor of cataract patients. REPS2 was identified as a negative regulator in growth factor signaling; however, its function in HLECs is unknown. This was first investigated in the present study by evaluating REPS2 expression in anterior lens capsules from cataract patients, a mouse cataract model, and HLE-b3 cells. The biological function of REPS2 in HLE-B3 cells was assessed by REPS2 silencing and Cell Counting Kit 8, wound healing, Transwell migration, F-actin staining, G-protein pulldown and western blot assays. In the present study, REPS2 was significantly downregulated in human and mouse cataract capsules and H2O2-treated HLE-B3 cells. REPS2 knockdown increased fibronectin, type I collagen, and α-smooth muscle actin expression levels and stimulated HLECs proliferation and migration; these effects were enhanced by FGF treatment and accompanied with focal adhesion kinase (FAK) phosphorylation, cell division cycle 42 (Cdc42) activation, focal adhesion protein upregulation, and F-actin cytoskeleton reorganization. However, treatment with the FAK inhibitor PF573228 abolished these effects. Thus, REPS2 downregulation in cataract HLECs induces their proliferation and facilitates FGF-induced ECM synthesis, EMT, cell adhesion and migration by activating FAK/Cdc42 signaling, which may underlie PCO pathogenesis.