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Stem Cell Research & Therapy Jun 2024Nerve guide conduits are a promising strategy for reconstructing peripheral nerve defects. Improving the survival rate of seed cells in nerve conduits is still a...
BACKGROUND
Nerve guide conduits are a promising strategy for reconstructing peripheral nerve defects. Improving the survival rate of seed cells in nerve conduits is still a challenge and microcarriers are an excellent three-dimensional (3D) culture scaffold. Here, we investigate the effect of the 3D culture of microcarriers on the biological characteristics of adipose mesenchymal stem cells (ADSCs) and to evaluate the efficacy of chitosan nerve conduits filled with microcarriers loaded with ADSCs in repairing nerve defects.
METHODS
In vitro, we prepared porous chitosan microspheres by a modified emulsion cross-linking method for loading ADSCs and evaluated the growth status and function of ADSCs. In vivo, ADSCs-loaded microcarriers were injected into chitosan nerve conduits to repair a 12 mm sciatic nerve defect in rats.
RESULTS
Compared to the conventional two-dimensional (2D) culture, the prepared microcarriers were more conducive to the proliferation, migration, and secretion of trophic factors of ADSCs. In addition, gait analysis, neuro-electrophysiology, and histological evaluation of nerves and muscles showed that the ADSC microcarrier-loaded nerve conduits were more effective in improving nerve regeneration.
CONCLUSIONS
The ADSCs-loaded chitosan porous microcarrier prepared in this study has a high cell engraftment rate and good potential for peripheral nerve repair.
Topics: Chitosan; Nerve Regeneration; Animals; Microspheres; Rats; Mesenchymal Stem Cells; Adipose Tissue; Rats, Sprague-Dawley; Sciatic Nerve; Porosity; Tissue Scaffolds; Male; Mesenchymal Stem Cell Transplantation; Cell Proliferation; Cells, Cultured
PubMed: 38824568
DOI: 10.1186/s13287-024-03753-w -
Carbohydrate Polymers Sep 2024This paper reports on biofunctionalisation of a poly(lactic acid) (PLA) film by surface activation through cold plasma treatment followed by coating with a...
This paper reports on biofunctionalisation of a poly(lactic acid) (PLA) film by surface activation through cold plasma treatment followed by coating with a chitosan-gelatin xerogel. The UV cross-linking of the xerogel precursor was simultaneously performed with the fixation onto the PLA support. This has a strong effect on surface properties, in terms of wettability, surface free energy, morphology and micromechanical features. The hydrophilic - hydrophobic character of the surface, determined by contact angle measurements, was tuned along the process, passing from moderate hydrophobic PLA to enhanced hydrophilic plasma activated surface, which favors coating adhesion, then to moderate hydrophobic chitosan-gelatin coating. The coating has a Lewis amphoteric surface, with a porous xerogel-like morphology, as revealed by scanning electron microscopy images. By riboflavin mediated UV cross-linking the chitosan-gelatin coating becomes high adhesive and with a more pronounced plasticity, as shown by AFM force-distance spectroscopy. Thus prepared surface-coated PLA supports were successfully tested for growth of dermal fibroblasts, which are known for their induction potential of chondrogenic cells, which is very important in cartilage tissue engineering.
Topics: Chitosan; Gelatin; Polyesters; Fibroblasts; Humans; Surface Properties; Gels; Ultraviolet Rays; Plasma Gases; Hydrophobic and Hydrophilic Interactions; Coated Materials, Biocompatible; Cross-Linking Reagents; Wettability
PubMed: 38823936
DOI: 10.1016/j.carbpol.2024.122288 -
Journal of Nanobiotechnology Jun 2024Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional...
BACKGROUND
Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies.
RESULTS
In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-β/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats.
CONCLUSION
In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation.
Topics: Animals; Gastrointestinal Microbiome; Rats; Fibrosis; Administration, Oral; Male; Kidney; Rats, Sprague-Dawley; Nanoparticles; Microgels; Lacticaseibacillus casei; Probiotics; Renal Insufficiency, Chronic; Chitosan; Alginates; Pentacyclic Triterpenes; Drug Delivery Systems; Tissue Distribution; Cell Wall
PubMed: 38822364
DOI: 10.1186/s12951-024-02586-2 -
BMC Cancer May 2024The causal impact of lipid-lowering drugs on ovarian cancer (OC) and cervical cancer (CC) has received considerable attention, but its causal relationship is still a...
BACKGROUND
The causal impact of lipid-lowering drugs on ovarian cancer (OC) and cervical cancer (CC) has received considerable attention, but its causal relationship is still a subject of debate. Hence, the objective of this study is to evaluate the impact of lipid-lowering medications on the occurrence risk of OC and CC through Mendelian randomization (MR) analysis of drug targets.
METHODS
This investigation concentrated on the primary targets of lipid-lowering medications, specifically, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and proprotein convertase kexin 9 (PCSK9). Genetic variations associated with HMGCR and PCSK9 were derived from published genome-wide association study (GWAS) findings to serve as substitutes for HMGCR and PCSK9 inhibitors. Employing a MR approach, an analysis was conducted to scrutinize the impact of inhibitors targeting HMGCR and PCSK9 on the occurrence of OC and CC. Coronary heart disease (CHD) risk was utilized as a positive control, and the primary outcomes encompassed OC and CC.
RESULTS
The findings of the study suggest a notable elevation in the risk of OC among patients treated with HMGCR inhibitors (OR [95%CI] = 1.815 [1.316, 2.315], p = 0.019). In contrast, no significant correlation was observed between PCSK9 inhibitors and the occurrence of OC. Additionally, the analysis did not reveal any noteworthy connection between HMGCR inhibitors, PCSK9 inhibitors, and CC.
CONCLUSION
HMGCR inhibitors significantly elevate the risk of OC in patients, but their mechanism needs further investigation, and no influence of PCSK9 inhibitors on OC has been observed. There is no significant relationship between HMGCR inhibitors, PCSK9 inhibitors, and CC.
Topics: Humans; Female; Uterine Cervical Neoplasms; Mendelian Randomization Analysis; Hydroxymethylglutaryl CoA Reductases; Ovarian Neoplasms; Genome-Wide Association Study; Proprotein Convertase 9; Hypolipidemic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Polymorphism, Single Nucleotide
PubMed: 38822303
DOI: 10.1186/s12885-024-12434-z -
Scientific Reports May 2024Designing materials capable of disinfecting water without releasing harmful by-products is an ongoing challenge. Here, we report a novel polycationic sponge material...
Designing materials capable of disinfecting water without releasing harmful by-products is an ongoing challenge. Here, we report a novel polycationic sponge material synthesized from chitosan derivatives and cellulose fibers, exhibiting antibacterial properties. The design of such material is based on three key principles. First, the formation of a highly porous structure through cryogelation for an extensive surface area. Second, the incorporation of cationic quaternary ammonium moieties onto chitosan to enhance bacterial adsorption and antibacterial activity. Lastly, the reinforcement of mechanical properties through integration of cellulose fibers. The presented sponge materials exhibit up to a 4-log (99.99%) reduction within 6 h against both gram-positive B. subtilis and gram-negative E. coli. Notably, QCHI90/Cell, with the highest surface charge, exhibits a 2-4.5 log reduction within 1 h of incubation time. The eco-friendly synthesis from water and readily available biomaterials, along with cost-effectiveness and simplicity, underscores its versatility and feasibility of upscaling. Together with its outstanding antibacterial activity, this macroporous biomaterial emerges as a promising candidate for water disinfection applications.
Topics: Escherichia coli; Biocompatible Materials; Cellulose; Anti-Bacterial Agents; Water Purification; Chitosan; Water Microbiology; Bacillus subtilis; Porosity; Quaternary Ammonium Compounds; Adsorption
PubMed: 38821995
DOI: 10.1038/s41598-024-61483-8 -
International Journal of Biological... Jun 2024Peripheral nerve injury often leads to symptoms of motor and sensory impairment, and slow recovery of nerves after injury and limited treatment methods will aggravate...
Peripheral nerve injury often leads to symptoms of motor and sensory impairment, and slow recovery of nerves after injury and limited treatment methods will aggravate symptoms or even lead to lifelong disability. Curcumin can promote peripheral nerve regeneration, but how to accurately deliver the appropriate concentration of curcumin in the local peripheral nerve remains to be solved. In this study, we designed a human hair keratin/chitosan (C/K) hydrogel with sodium tripolyphosphate ions crosslinked to deliver curcumin topically. Chitosan improves the mechanical properties of hydrogels and keratin improves the biocompatibility of hydrogels. C/K hydrogel showed good cytocompatibility, histocompatibility and degradability. In vitro experiments showed that hydrogels can continuously release curcumin for up to 10 days. In addition, a comprehensive analysis of behavioral, electrophysiological, histology, and target organ recovery results in animal experiments showed that locally delivered curcumin can enhance nerve regeneration in addition to hydrogels. In short, we provide a new method that combines the advantages of human hair keratin, chitosan, and curcumin for nerve damage repair.
Topics: Curcumin; Chitosan; Hydrogels; Nerve Regeneration; Animals; Humans; Keratins; Rats; Peripheral Nerve Injuries; Mice
PubMed: 38821302
DOI: 10.1016/j.ijbiomac.2024.132448 -
Journal of the American Heart... Jun 2024A phase 3 trial was conducted to evaluate the efficacy and safety of ongericimab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, as... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
A phase 3 trial was conducted to evaluate the efficacy and safety of ongericimab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, as an add-on treatment to optimized lipid-lowering therapy in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia.
METHODS AND RESULTS
A total of 806 patients who were receiving stable and optimized lipid-lowering therapy but did not achieve their low-density lipoprotein cholesterol (LDL-C) targets were enrolled and randomly assigned in a 2:1:2:1 ratio to receive either ongericimab 150 mg or matching placebo every 2 weeks, or ongericimab 300 mg or matching placebo every 4 weeks for 52 weeks. Efficacy and safety were evaluated in 802 patients who received at least 1 dose of ongericimab or placebo. The primary end point was the percentage change in LDL-C from baseline to week 24. Our findings demonstrated that the least-squares mean difference of percentage change in LDL-C from baseline to week 24 was -67.7% (95% CI, -72.5% to -63.0%; <0.0001) in the ongericimab 150 mg every 2 weeks group compared with the placebo every 2 weeks group, and -61.2% (95% CI, -67.1% to -55.2%; <0.0001) in the ongericimab 300 mg every 4 weeks group compared with the placebo every 4 weeks group. These reductions were sustained up to week 52. Furthermore, treatment with ongericimab favorably altered other lipid parameters. A similar incidence of adverse events was observed in the ongericimab and placebo groups.
CONCLUSIONS
Ongericimab, as an add-on treatment to optimized lipid-lowering therapy, significantly reduced LDL-C and was well-tolerated in Chinese patients with primary hyperlipidemia and mixed dyslipidemia who did not achieve their LDL-C targets.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04781114.
Topics: Humans; Male; Female; Middle Aged; Hypercholesterolemia; Cholesterol, LDL; China; Dyslipidemias; Treatment Outcome; Antibodies, Monoclonal, Humanized; Aged; Double-Blind Method; PCSK9 Inhibitors; Adult; Asian People; Proprotein Convertase 9; Biomarkers; Time Factors; Drug Therapy, Combination; Anticholesteremic Agents; Antibodies, Monoclonal; East Asian People
PubMed: 38818934
DOI: 10.1161/JAHA.123.033669 -
Nature Communications May 2024Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction...
Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction mechanism by environmental causes of chronic inflammation is unknown. Herein, we demonstrate that Toll-like receptor (TLR)3/4-TBK1-IRF3 pathway activation links environmental insults to IL-33 induction in the skin and pancreas inflammation. An FDA-approved drug library screen identifies pitavastatin to effectively suppress IL-33 expression by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevents chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. The IRF3-IL-33 axis is highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlates with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3-IL-33 signaling axis suppresses cancer-prone chronic inflammation. Statins present a safe and effective prophylactic strategy to prevent chronic inflammation and its cancer sequela.
Topics: Interleukin-33; Animals; Interferon Regulatory Factor-3; Humans; Pancreatic Neoplasms; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mice; Protein Serine-Threonine Kinases; Signal Transduction; Quinolines; Inflammation; Pancreatitis, Chronic; Toll-Like Receptor 3; Mice, Inbred C57BL; Toll-Like Receptor 4; Mevalonic Acid; Male; Female; Mice, Knockout
PubMed: 38816352
DOI: 10.1038/s41467-024-48441-8 -
Ecotoxicology and Environmental Safety Jul 2024Microbially induced carbonate precipitation (MICP), as an eco-friendly and promising technology that can transform free metal ions into stable precipitation, has been...
Microbially induced carbonate precipitation (MICP), as an eco-friendly and promising technology that can transform free metal ions into stable precipitation, has been extensively used in remediation of heavy metal contamination. However, its depressed efficiency of heavy metal elimination remains in question due to the inhibition effect of heavy metal toxicity on bacterial activity. In this work, an efficient, low-cost manganese (Mn) elimination strategy by coupling MICP with chitosan biopolymer as an additive with reduced treatment time was suggested, optimized, and implemented. The influences of chitosan at different concentrations (0.01, 0.05, 0.10, 0.15 and 0.30 %, w/v) on bacterial growth, enzyme activity, Mn removal efficiency and microstructure properties of the resulting precipitation were investigated. Results showed that Mn content was reduced by 94.5 % within 12 h with 0.15 % chitosan addition through adsorption and biomineralization as MnCO (at an initial Mn concentration of 3 mM), demonstrating a two-thirds decrease in remediation time compared to the chitosan-absent system, whereas maximum urease activity increased by ∼50 %. Microstructure analyses indicated that the mineralized precipitates were spherical-shaped MnCO, and a smaller size and more uniform distribution of MnCO is obtained by the regulation of abundant amino and hydroxyl groups in chitosan. These results demonstrate that chitosan accelerates nucleation and tunes the growth of MnCO by providing nucleation sites for mineral formation and alleviating the toxicity of metal ions, which has the potential to upgrade MICP process in a sustainable and effective manner. This work provides a reference for further understanding of the biomineralization regulation mechanism, and gives a new perspective into the application of biopolymer-intensified strategies of MICP technology in heavy metal contamination.
Topics: Chitosan; Manganese; Carbonates; Adsorption; Biopolymers; Chemical Precipitation; Water Pollutants, Chemical; Urease; Environmental Restoration and Remediation; Biomineralization; Biodegradation, Environmental
PubMed: 38816322
DOI: 10.1016/j.ecoenv.2024.116496 -
Journal of Medicine and Life Feb 2024Insulin is the cornerstone of treatment in type 1 diabetes mellitus. However, because of its protein structure, insulin has to be administered via injection, and many...
Insulin is the cornerstone of treatment in type 1 diabetes mellitus. However, because of its protein structure, insulin has to be administered via injection, and many attempts have been made to create oral formulations, especially using nanoparticles (NPs). The aim of this study was to compare the hypoglycemic effect of insulin-loaded NPs to that of subcutaneous insulin in an in vivo rat model of diabetes. We used biodegradable D-α-tocopherol polyethylene glycol succinate-emulsified, chitosan-capped poly(lactic-co-glycolic acid) NPs loaded with soluble human insulin in a dose of 20 IU/kg body weight, and examined the physical characteristics of NPs in vivo and in vitro. Serum glucose levels were reduced after 6 h, but the difference was not significant compared to subcutaneous insulin; at 12 h and 24 h, insulin levels were significantly higher in rats treated with NPs than in rats treated with subcutaneous insulin. There was no significant difference in serum insulin levels at 12 h and 24 h compared to non-diabetic rats. Our findings suggest that chitosan-based NPs are able to maintain good glycemic control for up to 24 h and can be considered a potential carrier for oral insulin delivery.
Topics: Animals; Nanoparticles; Diabetes Mellitus, Experimental; Insulin; Rats; Administration, Oral; Male; Streptozocin; Hyperglycemia; Chitosan; Blood Glucose; Hypoglycemic Agents; Disease Models, Animal; Rats, Sprague-Dawley
PubMed: 38813352
DOI: 10.25122/jml-2023-0355