Apoptotic Extracellular Vesicles Induced Endothelial Cell-Mediated Autologous Stem Cell Recruitment Dominates Allogeneic Stem Cell Therapeutic Mechanism for Bone Repair.

Although stem cell therapy is proved to be a promising strategy for bone repair and regeneration, transplanted allogeneic stem cells generally suffer from unfavorable apoptosis instead of differentiation into osteocytes. How the apoptotic stem cells promote bone regeneration still needs to be uncovered. In this work, we found that apoptotic extracellular vesicles released by allogeneic stem cells are critical mediators for promoting bone regeneration.

Engineered Extracellular Vesicles Driven by Erythrocytes Ameliorate Bacterial Sepsis by Iron Recycling, Toxin Clearing and Inflammation Regulation.

Sepsis poses a significant challenge in clinical management. Effective strategies targeting iron restriction, toxin neutralization, and inflammation regulation are crucial in combating sepsis. However, a comprehensive approach simultaneously targeting these multiple processes has not been established.

MSC-derived exosomes protect auditory hair cells from neomycin-induced damage via autophagy regulation.

Background: Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear.

Nanobody based immunoassay for alpha fetal protein detection using streptavidin-conjugated polymerized horseradish peroxidase for signal amplification.

The enzyme-linked immunosorbent assay (ELISA) offers several advantages, including simple operation, high throughput, and low cost, making it an ideal immunoassay method for efficient screening of disease-related biomarkers in clinical samples. However, the traditional colorimetric ELISA has relatively low sensitivity, which promotes the continuous emergence of various novel signal amplification technologies. In this work, we fused the AFP-specific nanobody (A1) with the streptavidin-binding peptide (SBP) to develop a fusion protein (A1-SBP) as biorecognition element in a colorimetric ELISA for detecting AFP.

Humoral regulation of iron metabolism by extracellular vesicles drives antibacterial response.

Immediate restriction of iron initiated by the host is a critical process to protect against bacterial infections and has been described in the liver and spleen, but it remains unclear whether this response also entails a humoral mechanism that would enable systemic sequestering of iron upon infection. Here we show that upon bacterial invasion, host macrophages immediately release extracellular vesicles (EVs) that capture circulating iron-containing proteins. Mechanistically, in a sepsis model in female mice, Salmonella enterica subsp.

MSCs-derived apoptotic extracellular vesicles promote muscle regeneration by inducing Pannexin 1 channel-dependent creatine release by myoblasts.

Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells.

Hybrid Biomaterial Initiates Refractory Wound Healing via Inducing Transiently Heightened Inflammatory Responses.

Inflammation plays a crucial role in triggering regeneration, while inadequate or chronic inflammation hinders the regenerative process, resulting in refractory wounds. Inspired by the ideal regeneration mode in lower vertebrates and the human oral mucosa, realigning dysregulated inflammation to a heightened and acute response provides a promising option for refractory wound therapy. Neutrophils play important roles in inflammation initiation and resolution.

Sympathetic Neurostress Drives Osteoblastic Exosomal MiR-21 Transfer to Disrupt Bone Homeostasis and Promote Osteopenia.

Innervation and extracellular vesicle secretion co-exist in the local tissue microenvironment for message transfer, but whether they are interconnected to regulate organ homeostasis remains unknown. Sympatho-adrenergic activation is implicated in stress-induced depression and leads to bone loss, but the mechanisms and therapeutics are incompletely elucidated. Here, it is revealed that sympathetic neurostress through the β -adrenergic receptor (β1/2-AR) signaling triggers the transcription response of a microRNA, miR-21, in osteoblasts, which is transferred to osteoclast progenitors via exosomes for dictating osteoclastogenesis.

Reproductive organ dysfunction and gene expression after orally administration of ZnO nanoparticles in murine.

ZnO nanoparticles (NPs) are among the most manufactured nanoparticles in the consumer products, industries, and researches. An increasing body of evidence indicated that ZnO NPs show toxicological effects in vivo. Sex differences in the toxicity of ZnO NPs are not clear, thus the aim of this study was to investigate the effects of ZnO NPs on the female and male reproductive organs (uterus, ovary and testes).

Circulating microRNAs in serum as novel biomarkers for osteoporosis: a case-control study.

Aims: Osteoporosis is underdiagnosed because of the lack of a convenient diagnostic method. Circulating microRNAs (miRNAs) emerge as novel biomarkers for disease diagnosis. Here, we conducted a case-control study that included a total of 448 serum samples collected from 182 healthy participants, 132 osteopenia participants, and 134 osteoporosis patients.

CdSe/ZnS Quantum Dots Impaired the First Two Generations of Placenta Growth in an Animal Model, Based on the Shh Signaling Pathway.

The toxicity, especially the transgenerational toxicity of quantum dots (QDs) in vivo, is still scarcely understood in spite of great promising applications of QDs in biomedicine. In this study, the maternal status, pregnancy outcome, and fetus development of parental generation (P0) to offspring in three generations (F3) were investigated after Kunming mice perinatal (GD 13-PND 5) exposure to Cd containing QDs (CdSe/ZnS QDs) and CdCl₂. The results show CdSe/ZnS QDs induced placenta injuries in P0 and diminished placenta diameters in F1 and F2.

Surface modification affect the biodistribution and toxicity characteristics of iron oxide magnetic nanoparticles in rats.

Various surface modifications of iron oxide magnetic nanoparticles (IOMNs) can improve their stability and long-term retention time , expanding applications of biomedical fields. However, whether the long-term retention of IOMNs coated with different surface modifications has toxic effects remains poorly understood. Here, the toxicity of IOMNs modified with polyethylene glycol (PEG), bovine serum albumin (BSA), and carboxyl group (COOH), forming PEG-IOMNs, BSA-IOMNs, and COOH-IOMNs, respectively, were evaluated in the rats.

Quantum dots cause acute systemic toxicity in lactating rats and growth restriction of offspring.

The in vivo toxicity of QDs in animals has been broadly studied; however, their reproductive toxicity towards lactating rodents is currently unknown. This study therefore aims to assess the potential toxicity against dams and offspring after postnatal QD exposure at two doses (5 and 1 nmol per rat) and unravel whether QDs can translocate to pups via breastfeeding. The dose-dependent systemic toxicity of QDs in dams was observed by examining the body weight, hematology, biochemistry, histopathological changes, and sex hormone levels.

Mesenchymal stem cells and extracellular matrix scaffold promote muscle regeneration by synergistically regulating macrophage polarization toward the M2 phenotype.

Background: Skeletal muscle plays an important role in the body's physiology but there are still no effective treatments for volumetric muscle loss (VML) resulting from severe traumatic injury or tumor excision. Recent studies show that a tissue engineering strategy using a compound containing mesenchymal stem cells (MSCs) and decellularized extracellular matrix (ECM) scaffold generates significant regenerative effects on VML injury, but the underlying mechanisms are not fully understood.

Methods: The characteristics of human umbilical cord MSCs, including multiplication capacity and multidifferentiation ability, were determined.

Redundant let-7a suppresses the immunomodulatory properties of BMSCs by inhibiting the Fas/FasL system in osteoporosis.

Bone marrow-derived mesenchymal stem cell (BMSC) cytotherapy has emerged as a promising treatment strategy for refractory immune diseases; however, the influence of the pathologic conditions of donors on the immunomodulatory properties of BMSCs is still poorly understand. Here, we found that BMSCs that were derived from donors with osteoporosis were ineffective as cytotherapy for patients with experimental colitis and graft- vs.-host disease (GVHD).

Comparisons of the biodistribution and toxicological examinations after repeated intravenous administration of silver and gold nanoparticles in mice.

Nanoparticles (NPs) size, surface functionalization, and concentration were claimed to contribute to distribution and toxicity outcomes of NPs in vivo. However, intrinsic chemical compositions of NPs caused inconsistent biodistribution and toxic profiles which attracted little attention. In this study, silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) were used to determine the biodistribution, toxickinetic, and genotoxicity variances in murine animals.

Mechanism of enhanced antibacterial activity of ultra-fine ZnO in phosphate buffer solution with various organic acids.

Ultra-fine-ZnO showed low toxicity in complex water matrix containing multiple components such as PBS buffer and the toxic mechanism of ultra-fine-ZnO has not been clearly elucidated. In present study, enhanced antibacterial activity of 200 nm diameter ultra-fine-ZnO in PBS buffer against Bacillus cereus and Escherichia coli were observed in the presence of several organic acids in comparison with ultra-fine-ZnO in PBS buffer alone. These findings indicated that the toxic effects of the ultra-fine-ZnO was dependent on the concentration of released Zn which was affected by organic acids.

Acute toxicity of quantum dots on late pregnancy mice: Effects of nanoscale size and surface coating.

In this study, the effects of cadmium containing QDs (such as CdSe/ZnS and CdSe QDs) and bulk CdCl2 in pregnant mice, their fetuses, and the pregnancy outcomes were investigated. It was shown that although the QDs and bulk CdCl2 were effectively blocked by the placental barrier, the damage on the placenta caused by CdSe QDs still led to fetus malformation, while the mice in CdSe/ZnS QDs treatment group exhibited slightly hampered growth but showed no significant abnormalities. Moreover, the Cd contents in the placenta and the uterus of CdSe QDs and CdSe/ZnS QDs treatment groups showed significantly higher than the CdCl2 treated group which indicated that the nanoscale size of the QDs allowed relative ease of entry into the gestation tissues.

Size dependent effect of ZnO nanoparticles on endoplasmic reticulum stress signaling pathway in murine liver.

ZnO nanoparticles (NPs) have been assessed to show adverse effects on the liver, but the molecular mechanisms and the role of nanoparticle properties in these adverse reactions have not been sufficiently studied. In this study, the toxicity of various sizes of ZnO particles (bulk, 90nm, and 30nm) that were ingested orally over a period of 3days were evaluated in mice. The blood biochemistry, hematological analyses, and histopathological evaluation showed that there was apparent toxicity caused by smaller ZnO NPs (30nm) in liver.

Synergistic in vitro and in vivo antimicrobial effect of a mixture of ZnO nanoparticles and Lactobacillus fermentation liquor.

In this study, we investigated the antibacterial activity of ZnO nanoparticles (NPs) and Lactobacillus-fermentation liquor (LFL) against two pathogenic bacteria in vitro and in vivo. Bactericidal tests were performed on solid agar plates and quantitative real-time PCR (qPCR), and denaturing gradient gel electrophoresis (DGGE) techniques were used to examine the antibacterial activity of the mixture of ZnO NPs and LFL in vivo. The results showed that the mixture exhibited higher antibacterial activity against Salmonella typhimurium in vitro in comparison with ZnO NPs alone.

Size dependent biodistribution and toxicokinetics of iron oxide magnetic nanoparticles in mice.

In spite of the immense benefits from iron oxide magnetic nanoparticles (IOMNs), there is scanty information regarding their metabolic activities and toxicity in vivo. In this study, we investigated the size dependent in vivo biodistribution, toxicokinetics, and toxicity and gene expression changes of various sizes of carboxyl coated IOMNs (diameters of 10, 20, 30, and 40 nm). Our findings demonstrated that the various sizes of IOMNs accumulated primarily in the liver and spleen on the first day post-injection.