Human gingival mesenchymal stem cells improve movement disorders and tyrosine hydroxylase neuronal damage in Parkinson disease rats.

BACKGROUND AIMS: Gingival mesenchymal stem cells (GMSCs) demonstrate high proliferation, trilineage differentiation and immunomodulatory properties. Parkinson disease (PD) is the second most common type of neurodegenerative disease. This study aimed to explore the effect and mechanism of GMSC-based therapy in 6-hydroxydopamine-induced PD rats. METHODS: RNA sequencing and quantitative proteomics technology was used to validate the neuroprotective role of GMSCs therapeutic in 6-Hydroxydopamine -induced PD model in vitro and in vivo. Western blotting, immunofluorescence and real-time quantitative PCR verified the molecular mechanism of GMSCs treatment. RESULTS: Intravenous injection of GMSCs improved rotation and forelimb misalignment behavior, enhanced the anti-apoptotic B-cell lymphoma 2/B-cell lymphoma 2-associated X axis, protected tyrosine hydroxylase neurons, decreased the activation of astrocytes and reduced the astrocyte marker glial fibrillary acidic protein and microglia marker ionized calcium-binding adaptor molecule 1 in the substantia nigra and striatum of PD rats. The authors found that GMSCs upregulated nerve regeneration-related molecules and inhibited metabolic disorders and the activation of signal transducer and activator of transcription 3. GMSCs showed a strong ability to protect neurons and reduce mitochondrial membrane potential damage and reactive oxygen species accumulation. The safety of GMSC transplantation was confirmed by the lack of tumor formation following subcutaneous transplantation into nude mice for up to 8 weeks. CONCLUSIONS: The authors' research helps to explain the mechanism of GMSC-based therapeutic strategies and promote potential clinical application in Parkinson disease.

Metformin pre-treatment of stem cells from human exfoliated deciduous teeth promotes migration and angiogenesis of human umbilical vein endothelial cells for tissue engineering.

BACKGROUND AIMS: Stem cells from human exfoliated deciduous teeth (SHED) play a significant role in tissue engineering and regenerative medicine. Angiogenesis is crucial in tissue regeneration and a primary target of regenerative medicine. As a first-line anti-diabetic drug, metformin demonstrates numerous valuable impacts on stem cells. This study aimed to explore metformin's impact and mechanism of action on SHED-mediated angiogenesis. METHODS: First, cell proliferation; flow cytometry; osteogenic, adipogenic and chondrogenic induction; and proteomics analyses were conducted to explore the role of metformin in SHED. Subsequently, migration and tube formation assays were used to evaluate chemotaxis and angiogenesis enhancement by SHED pre-treated with metformin under co-culture conditions in vitro, and relative messenger RNA expression levels were determined by quantitative reverse transcription polymerase chain reaction. Finally, nude mice were used for in vivo tube formation assay, and sections were analyzed through immunohistochemistry staining with anti-human CD31 antibody. RESULTS: Metformin significantly promoted SHED proliferation as well as osteogenic, adipogenic and chondrogenic differentiation. Proteomics showed that metformin significantly upregulated 124 differentially abundant proteins involved in intracellular processes, including various proteins involved in cell migration and angiogenesis, such as MAPK1. The co-culture system demonstrated that SHED pre-treated with metformin significantly improved the migration and angiogenesis of human umbilical vein endothelial cells. In addition, SHED pre-treated with metformin possessed greater ability to promote angiogenesis in vivo. CONCLUSIONS: In summary, the authors' findings illustrate metformin's mechanism of action on SHED and confirm that SHED pre-treated with metformin exhibits a strong capacity for promoting angiogenesis. This helps in promoting the application of dental pulp-derived stem cells pre-treated with metformin in regeneration engineering.

Hydrogel supplemented with human platelet lysate enhances multi-lineage differentiation of mesenchymal stem cells.

Stem cells from human exfoliated deciduous teeth (SHED) can be used as a potential clinical material. But the use of xenogeneic ingredients will increase the risk of zoonotic disease transmission. Human platelet lysate (HPL) is a potential surrogate and used in human cell expansion with reliability in clinical applications. In this study, we synthesized chitosan/gelatin/gellan gum hydrogel supplemented with HPL and investigated the effect of 3D culture for SHED. TMT-tagged proteomics was used to decipher the secretome protein profiles of SHEDs and a total of 3209 proteins were identified, of which 23 were up-regulated and 192 were down-regulated. The results showed that hydrogel supplemented with HPL promoted SHED proliferation. After induction, the hydrogel coating contributed to osteogenic differentiation, adipogenic differentiation and differentiation into neural-like cells of SHED. SHED encapsulated in a hydrogel promotes migration and angiogenesis of HUVEC. In conclusion, our research found that hydrogel supplemented with HPL can be used as a method for SHED in standardized production and can contribute to the clinical application of SHED in cell therapy.

Chitosan Hydrogel Supplemented with Metformin Promotes Neuron-like Cell Differentiation of Gingival Mesenchymal Stem Cells.

Human gingival mesenchymal stem cells (GMSCs) are derived from migratory neural crest stem cells and have the potential to differentiate into neurons. Metformin can inhibit stem-cell aging and promotes the regeneration and development of neurons. In this study, we investigated the potential of metformin as an enhancer on neuronal differentiation of GMSCs in the growth environment of chitosan hydrogel. The crosslinked chitosan/ß-glycerophosphate hydrogel can form a perforated microporous structure that is suitable for cell growth and channels to transport water and macromolecules. GMSCs have powerful osteogenic, adipogenic and chondrogenic abilities in the induction medium supplemented with metformin. After induction in an induction medium supplemented with metformin, Western blot and immunofluorescence results showed that GMSCs differentiated into neuron-like cells with a significantly enhanced expression of neuro-related markers, including Nestin (NES) and ß-Tubulin (TUJ1). Proteomics was used to construct protein profiles in neural differentiation, and the results showed that chitosan hydrogels containing metformin promoted the upregulation of neural regeneration-related proteins, including ATP5F1, ATP5J, NADH dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3), and Glutamate Dehydrogenase 1 (GLUD1). Our results help to promote the clinical application of stem-cell neural regeneration.

Effects of exogenous sulfur on maize (Zea mays L.) growth and Cd accumulation in Cd-contaminated plastic shed soil.

Cadmium (Cd) pollution in plastic shed soils has become increasingly severe, posing a great threat to human health and social stability. Phytoremediation of cadmium pollution is an environmentally friendly and inexpensive remediation method. In this study, maize (Zea mays L.) was selected as the phytoremediation crop by a potted method, and the bioavailability of cadmium was investigated by adding exogenous elemental sulfur. The relationships among the sulfur content, maize growth, cadmium accumulation, and soil parameters were systematically studied. The results showed that, with the supplement of sulfur, the soil pH and activities of soil enzymes (urease, catalase, and sucrase) decreased gradually, and the available heavy metals (Cd, Cr, Zn, and Cu) in soil showed an upward trend. The optimal cadmium enrichment was achieved under T2 by increasing both the biomass of the maize plant and the cadmium concentration in roots and stems. However, T3 and T4 significantly inhibited the growth of maize roots and shoots, leading to a much lower plant biomass compared with that of CK (sulfur-free treatment) and T2. In addition, the cumulative cadmium was not increased because of the low accumulation of cadmium in some parts of the plant. Correlation analyses showed that the sulfur content was negatively correlated with soil pH and maize biomass (P < 0.01), and the cadmium content of whole maize was positively correlated with the dry weight of maize (P < 0.05) and the cadmium content in roots and stems (P < 0.01). In summary, to optimize cadmium phytoremediation of the plastic shed soil, an appropriate concentration of sulfur should be selected in practical applications to ensure that the biomass of the maize is maximized, and the cadmium concentration in different parts of the maize is increased or stabilized.

cRGD-functionalized polymeric magnetic nanoparticles as a dual-drug delivery system for safe targeted cancer therapy.

In this paper we give a method of integrated treatment for cancer and drug-induced complications in the process of cancer therapy through dual-drug delivery system (DDDS). Two hydrophilic drugs, doxorubicin (an antitumor drug) and verapamil (an antiangiocardiopathy drug) combined preliminarily with chitosan shell coated on magnetic nanoparticles (MNPs), followed by entrapping into the PLGA nanoparticles. Further modification was conducted by conjugating tumor-targeting ligand, cyclo(Arg-Gly-Asp-D-Phe-Lys) (c(RGDfK)) peptide, onto the end carboxyl groups on the PLGA-NPs. The size of the resulting cRGD-DOX/VER-MNP-PLGA NPs was approximately 144nm under simulate physiological environment. Under present experiment condition, the entrapment efficiencies of DOX and VER were approximately 74.8 and 53.2wt% for cRGD-DOX/VER-MNP-PLGA NPs. This paper contains interesting pilot data such as NIR-triggered drug release, in vivo drug distribution studies and whole-mouse optical imaging. Histopathological examinations and electrocardiogram comparison demonstrated that the intelligent DDDS could markedly inhibit the growth of tumor and potentially offer an approach for safe cancer therapy.

Stem cells from human exfoliated deciduous teeth relieves Alzheimer's disease symptoms in SAMP8 mice by up-regulating the PPARγ pathway.

The pathology of Alzheimer's disease (AD) is complex and heterogeneous, and there are currently no drugs that can stop its progression. The failure of traditional chemical small-molecule drug development showed the weakness of single target and made researchers look to cell therapy with multiple regulatory effects. Stem cells from human exfoliated deciduous teeth (SHED) are a kind of neural crest-derived mesenchymal stem cells which have broad prospects in the treatment of neurodegenerative diseases. In this study, we demonstrated the therapeutic effects of SHED in AD mice, including behavioral improvement, neuronal protection, and alleviation of neuroinflammation. Tracking experiments on SHED showed that some of the transplanted cells could enter the brain. To elucidate the role played by the majority of cells transplanted into veins, blood proteomic assays were performed. Data are available via ProteomeXchange with identifier PXD030313. Among the altered proteins, the PPAR pathway related to energy metabolism was considered to be an important signaling pathway involved in regulation through gene ontology analysis and pathway analysis. Western blot showed that the transplantation of SHED improved the glucose metabolism in AD mice by increasing the PPARγ signaling pathway. These results suggested that SHED have a potential in relieving AD pathological symptoms and improving behavioral cognition. The therapeutic mechanism of SHED is related to up-regulating PPARγ signaling pathway and reducing neuronal damage.

The potential therapy with dental tissue-derived mesenchymal stem cells in Parkinson's disease.

Parkinson's disease (PD), the second most common neurodegenerative disease worldwide, is caused by the loss of dopaminergic (DAergic) neurons in the substantia nigra resulting in a series of motor or non-motor disorders. Current treatment methods are unable to stop the progression of PD and may bring certain side effects. Cell replacement therapy has brought new hope for the treatment of PD. Recently, human dental tissue-derived mesenchymal stem cells have received extensive attention. Currently, dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED) are considered to have strong potential for the treatment of these neurodegenerative diseases. These cells are considered to be ideal cell sources for the treatment of PD on account of their unique characteristics, such as neural crest origin, immune rejection, and lack of ethical issues. In this review, we briefly describe the research investigating cell therapy for PD and discuss the application and progress of DPSCs and SHED in the treatment of PD. This review offers significant and comprehensive guidance for further clinical research on PD.

Factors that affect the quality of life of patients with oral cancer who have had their defects reconstructed immediately after excision of the tumour.

Physical, social, and psychological factors profoundly affect the quality of life (QoL) of patients with oral cancer. Here we have investigated these factors in patients who have had resection and reconstruction of their oral cancer. We have assessed patients who had reconstructions with a pectoralis major myocutaneous (PMM) flap or a free anterolateral thigh (ALT) perforator flap using the University of Washington Quality of Life version 4 questionnaires (Chinese version). Data were analysed to investigate how age, sex, type of neck dissection, size of resection, dental condition, use of radiotherapy and need for mandibulotomy affected their QoL. Of the 72 patients who were sent a questionnaire, 61 (85%) returned them completed. Twenty-eight patients(46%) had had ALT perforator flaps and 33 patients (54%) PMM flaps. In the group who had ALT perforator flaps, age, sex, type of neck dissection, mandibulotomy, and the use of radiotherapy affected QoL. Among those who the PMM flaps, age, neck dissection, mandibulotomy, and use of radiotherapy affected QoL. The only factors that the two flaps had in common were age, neck dissection, use of radiotherapy, and mandibulotomy.

Hepatotoxicity assessment of Mn-doped ZnS quantum dots after repeated administration in mice.

Doped ZnS quantum dots (QDs) have a longer dopant emission lifetime and potentially lower cytotoxicity compared to other doped QDs. The liver is the key organ for clearance and detoxification of xenobiotics by phagocytosis and metabolism. The present study was designed to synthesize and evaluate the hepatotoxicity of Mn-doped ZnS QDs and their polyethylene glycol-coated counterparts (1 mg/kg and 5 mg/kg) in mice. The results demonstrated that daily injection of Mn-doped ZnS QDs and polyethylene glycol-coated QDs via tail vein for 7 days did not influence body weight, relative liver weight, serum aminotransferases (alanine aminotransferase and aspartate aminotransferase), the levels of antioxidant enzymes (catalase, glutathione peroxidase, and superoxide dismutase), or malondialdehyde in the liver. Analysis of hepatocyte ultrastructure showed that Mn-doped ZnS QDs and polyethylene glycol-coated QDs mainly accumulated in mitochondria at 24 hours after repeated intravenous injection. No damage to cell nuclei or mitochondria was observed with either of the QDs. Our results indicate that Mn-doped ZnS QDs did not cause obvious damage to the liver. This study will assist in the development of Mn-doped ZnS QDs-based bioimaging and biomedical applications in the future.

Assessment of quality of life and sociocultural aspects in patients with ameloblastoma after immediate mandibular reconstruction with a fibular free flap.

Our aim was to evaluate the quality of life (QoL) in patients with ameloblastoma who had been treated by immediate mandibular reconstruction with a fibular free flap, and to analyse the association between QoL and their sociocultural and medical characteristics. We assessed the QoL outcomes of 33/45 patients using the University of Washington quality of life (UW-QoL) questionnaire and the 14-item Oral Health Impact Profile (OHIP-14). Thirty-three of the 45 questionnaires were returned (73%). In the UW-QoL the best-scoring domain was "shoulder", whereas the lowest scores were for "chewing" and "activity". In the OHIP-14 the lowest-scoring domain was "handicap", followed by "social disability" and "psychological discomfort". Mandibular reconstruction with a fibular free flap significantly influenced the patients' QoL and oral function. Their sociocultural data showed that most patients had a fairly low level of education.

Toxicity and biodistribution of aqueous synthesized ZnS and ZnO quantum dots in mice.

In the present study, ZnS and ZnO quantum dots (QDs) were synthesized via an all-aqueous process with polyethylene glycol (PEG) chains on their surface, and their toxicity as well as biodistribution were evaluated. No haemolysis occurred at a high concentration of 1600 µg/mL in vitro haemolytic assay, which demonstrated that the QDs-PEG displayed good blood compatibility. Following intravenous administration at 2, 6, and 20 mg/kg of the QDs-PEG in mice, the biodistribution, excretion and biocompatibility were characterized at 1 h, 24 h and 7 days, respectively. Quantitative analysis results indicated that the biodistribution trend of ZnS QDs-PEG was similar to that of ZnO QDs-PEG. The QDs-PEG were mainly trapped in the lung and liver, and almost removed from blood within 1 h. QDs-PEG were primarily excreted in faeces at the 2 and 6 mg/kg doses. Coefficients, haematology, blood biochemistry and histopathology results indicated that the QDs-PEG were safe and biocompatible.

Assessment of quality of life of patients with oral cavity cancer who have had defects reconstructed with free anterolateral thigh perforator flaps.

The aim of this study was to evaluate quality of life (QoL) in patients who have had resections of oral cancer and reconstruction by free anterolateral thigh perforator flaps. QoL was assessed by the 14-item Oral Health Impact Profile (OHIP-14) and the University of Washington Quality of Life (UW-QoL) questionnaires 12 months postoperatively. Fifty-one of the 69 questionnaires were returned (74%). In the UW-QoL the best-scoring domain was pain, whereas the lowest scores were for chewing, saliva, and taste. In the OHIP-14 the lowest-scoring domain was handicap, followed by psychological disability, and social disability. Free anterolateral thigh perforator flaps for reconstruction of defects of the head and neck after resection for cancer significantly influenced the patients' quality of life.

Photoluminescent silicon nanocrystal-based multifunctional carrier for pH-regulated drug delivery.

A core-shell structured multifunctional carrier with nanocrystalline silicon (ncSi) as the core and a water-soluble block copolymer as the shell based on a poly(methacrylic acid) (PMAA) inner shell and polyethylene glycol (MPEG) outer shell (ncSi-MPM) was synthesized for drug delivery. The morphology, composition, and properties of the resulting ncSi-MPM were determined by comprehensive multianalytical characterization, including (1)H NMR spectroscopy, FTIR spectroscopy, XPS spectroscopy, TEM, DLS, and fluorescence spectroscopy analyses. The size of the resulting ncSi-MPM nanocarriers ranged from 40 to 110 nm under a simulated physiological environment. The loading efficiency of model drug doxorubicin (DOX) was approximately 6.1-7.4 wt % for ncSi-MPM and the drug release was pH controlled. Cytotoxicity studies demonstrated that DOX-loaded ncSi-MPM showed high anticancer activity against Hela cells. Hemolysis percentages (<2%) of ncSi-MPM were within the scope of safe values. Fluorescent imaging studies showed that the nanocarriers could be used as a tracker at the cellular level. Integration of the above functional components may result in ncSi-MPM becoming a promising multifunctional carrier for drug delivery and biomedical applications.