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1.
ACS Appl Mater Interfaces ; 16(14): 17208-17218, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38530974

RESUMO

Bone defects are common with increasing high-energy fractures, tumor bone invasion, and implantation revision surgery. Bone is an electroactive tissue that has electromechanical interaction with collogen, osteoblasts, and osteoclasts. Hydrogel provides morphological plasticity and extracellular matrix (ECM) 3D structures for cell survival, and is widely used as a bone engineering material. However, the hydrogels have poor mechanical intensity and lack of cell adhesion, slow gelation time, and limited conductivity. MXenes are novel nanomaterials with hydrophilic groups that sense cell electrophysiology and improve hydrogel electric conductivity. Herein, gelatin had multiple active groups (NH2, OH, and COOH) and an accelerated gelation time. Acrylamide has Schiff base bonds to cross-link with gelatin and absorb metal ions. Deacetylated chitosan improved cell adhesion and active groups to connect MXene and acrylamide. We constructed Mo2Ti2C3 MXene hydrogel with improved elastic modulus and viscosity, chemical cross-linking structure, electric conductivity, and good compatibility. Mo2Ti2C3 MXene hydrogel exhibits outstanding osteogenesis in vitro. Mo2Ti2C3 MXene hydrogel promotes osteogenesis via alkaline phosphatase (ALP) and alizarin red S (ARS) staining, improving osteogenic marker genes and protein expressions in vitro. Mo2Ti2C3 MXene hydrogel aids new bone formation in the in vivo calvarial bone defect model via micro-CT and histology. Mo2Ti2C3 MXene hydrogel facilitates neurogenesis factors nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression, and aids newly born neuron marker Tuj-1 and sensory neuron marker serotonin (5-HT) and osteogenesis pathway proteins, runt-related transcription factor 2 (Runx2), osteocalcin (OCN), SMAD family member 4 (SMAD4), and bone morphogenetic protein-2 (BMP2) in the bone defect repair process. Mo2Ti2C3 MXene hydrogel promotes osteogenesis and neurogenesis, which extends its biomedical application in bone defect reconstruction.


Assuntos
Hidrogéis , Nitritos , Titânio , Elementos de Transição , Hidrogéis/farmacologia , Hidrogéis/química , Gelatina , Regeneração Óssea , Osteogênese , Neurogênese , Acrilamidas , Diferenciação Celular
2.
Joint Bone Spine ; 91(2): 105669, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38042362

RESUMO

OBJECTIVE: Disorders of bone homeostasis are the key factors leading to metabolic bone disease, such as senile osteoporosis, which is characterized by age-related bone loss. Bone marrow stromal cells (BMSCs) possess high osteogenic capacity which has been regarded as a practical approach to preventing bone loss. Previous studies have shown that the osteogenic differentiation ability of BMSCs is significantly decreased in senile osteoporosis. Recently, circular RNAs (circRNAs) have been regarded as critical regulators in controlling the osteogenic differentiation of BMSCs by sponging microRNAs (miRNAs). Our study aimed to discover new and critical osteogenesis-related circRNAs that can promote bone formation in senile osteoporosis. METHODS: We detected the dysregulated circRNAs of BMSCs upon osteogenic differentiation induction and identified the critical osteogenic circRNA (circ-3626). The relationship between circ-3626 and osteoporosis was further verified in clinical bone samples and aged mice by qPCR. Moreover, circ-3626 AAV was constructed to examine the osteogenic effect of circ-3626 on bone formation via using Micro-CT, double calcein labeling, and the three-point bending tests. Bioinformatics analysis, Luciferase report gene assays, FISH, RNA pull-down, qPCR, Western Blots, and alizarin red staining assay explore the effects and mechanisms of circ-3626 on osteogenic differentiation of BMSCs. RESULTS: Circ-3626 was identified as a pivotal osteogenesis-related circRNA via RNA sequencing. The results of alizarin red staining, Western blots, and qPCR assays suggest that overexpressing circ-3626 dramatically accelerates the osteogenic capability of BMSCs. Furthermore, the bone repair capability of aging mice could be significantly improved by circ-3626 AAV treatment. Micro RNA miR-338-3p was identified as the downstream target of circ-3626. Overexpression of circ-3626 increases the expression of Runx2 by sponging miR-338-3p, thereby promoting the osteogenic differentiation of BMSCs by upregulating the expression of osteogenic genes. In addition, Western blots, and qPCR assays suggest circ-3626 AAV treatment promote the expression of Runx2 and osteogenic marker genes. CONCLUSION: Thus, we demonstrate that circ-3626 plays a pivotal role in promoting bone formation through the miR-338-3p/Runx2 axis and may provide new strategies for preventing and treating the bone loss of senile osteoporosis.


Assuntos
Antraquinonas , MicroRNAs , Osteoporose , Humanos , Camundongos , Animais , Osteogênese/genética , RNA Circular/genética , RNA Circular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoporose/genética , Diferenciação Celular , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética
3.
Acta Pharm Sin B ; 13(11): 4535-4552, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37969743

RESUMO

Osteoporosis (OP) is a systemic skeletal disease that primarily affects the elderly population, which greatly increases the risk of fractures. Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass. Kindlin-2 specific deletion (K2KO) controlled by Adipoq-Cre mice or adipose tissue-targeting AAV (AAV-Rec2-CasRx-sgK2) significantly increases bone mass. Mechanistically, Kindlin-2 promotes peroxisome proliferator-activated receptor gamma (PPARγ) activation and downstream fatty acid binding protein 4 (FABP4) expression through stabilizing fatty acid synthase (FAS), and increased FABP4 inhibits insulin expression and decreases bone mass. Kindlin-2 inhibition results in accelerated FAS degradation, decreased PPARγ activation and FABP4 expression, and therefore increased insulin expression and bone mass. Interestingly, we find that FABP4 is increased while insulin is decreased in serum of OP patients. Increased FABP4 expression through PPARγ activation by rosiglitazone reverses the high bone mass phenotype of K2KO mice. Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice. Collectively, our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.

4.
J Orthop Surg Res ; 18(1): 770, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821993

RESUMO

OBJECTIVE: To construct a clinical prediction nomogram model using the 1-min IOF osteoporosis risk test as an evaluation tool for male osteoporosis. METHODS: The 1-min test results and the incidence of osteoporosis were collected from 354 patients in the osteoporotic clinic of our hospital. LASSO regression model and multi-factor logistic regression were used to analyze the risk factors of osteoporosis in patients, and the risk prediction model of osteoporosis was established. Verify with an additional 140 objects. RESULTS: We used logistic regression to construct a nomogram model. According to the model, the AUC value of the training set was 0.760 (0.704-0.817). The validation set has an AUC value of 0.806 (0.733-0.879). The test set AUC value is 0.714 (0.609-0.818). The calibration curve shows that its advantage is that the deviation correction curve of the nomogram model can maintain a good consistency with the ideal curve. In terms of clinical applicability, compared with the "total intervention" and "no intervention" schemes, the clinical net return rate of the nomogram model showed certain advantages. CONCLUSION: Using the 1-min osteoporosis risk test provided by IOF, we built a male osteoporosis risk prediction model with good prediction effect, which can provide greater reference and help for clinicians.


Assuntos
Instituições de Assistência Ambulatorial , Osteoporose , Humanos , Masculino , Calibragem , Hospitais , Nomogramas , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Estudos Retrospectivos
5.
Cell Death Dis ; 14(10): 709, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37903776

RESUMO

Insufficient pancreatic ß-cell mass and reduced insulin expression are key events in the pathogenesis of diabetes mellitus (DM). Here we demonstrate the high expression of Talin-1 in ß-cells and that deficiency of Talin-1 reduces ß-cell proliferation, which leads to reduced ß-cell mass and insulin expression, thus causing glucose intolerance without affecting peripheral insulin sensitivity in mice. High-fat diet fed exerbates these phenotypes. Mechanistically, Talin-1 interacts with the E3 ligase smad ubiquitination regulatory factor 1 (Smurf1), which prohibits ubiquitination of the signal transducer and activator of transcription 3 (Stat3) mediated by Smurf1, and ablation of Talin-1 enhances Smurf1-mediated ubiquitination of Stat3, leading to decreased ß-cell proliferation and mass. Furthermore, haploinsufficiency of Talin-1 and Stat3 genes, but not that of either gene, in ß-cell in mice significantly impairs glucose tolerance and insulin expression, indicating that both factors indeed function in the same genetic pathway. Finally, inducible deletion Talin-1 in ß-cell causes glucose intolerance in adult mice. Collectively, our findings reveal that Talin-1 functions as a crucial regulator of ß-cell mass, and highlight its potential as a therapeutic target for DM patients.


Assuntos
Intolerância à Glucose , Talina , Adulto , Animais , Humanos , Camundongos , Proliferação de Células , Insulina/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Talina/genética , Talina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
6.
Herit Sci ; 11(1): 223, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37869744

RESUMO

In recent years, the conservation and protection of ancient cultural heritage have received increasing attention, and non-destructive testing (NDT), which can minimize the damage done to the test subject, plays an integral role therein. For instance, NDT through active infrared thermal imaging can be applied to ancient polyptychs, which can realize accurate detection of damage and defects existing on the surface and interior of the polyptychs. In this study, infrared thermography is used for non-invasive investigation and evaluation of two polyptych samples with different pigments and artificial defects, but both reproduced based on a painting by Pietro Lorenzetti (1280/85-1348) using the typical tempera technique of the century. It is noted that, to avoid as far as possible secondary damages done to the ancient cultural heritages, repeated damage-detection experiments are rarely carried out on the test subjects. To that end, numerical simulation is used to reveal the heat transfer properties and temperature distributions, as to perform procedural verification and reduce the number of experiments that need to be conducted on actual samples. Technique-wise, to improve the observability of the experimental results, a total variation regularized low-rank tensor decomposition algorithm is implemented to reduce the background noise and improve the contrast of the images. Furthermore, the efficacy of image processing is quantified through the structural-similarity evaluation.

7.
ISA Trans ; 142: 420-426, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37544823

RESUMO

This note shows an elegant relationship between the quadratic optimal control and robust stabilization for linear time-invariant (LTI) systems, where the former control can robustly stabilize the latter system, provided that the matched uncertainty is bounded. Through reviewing the relevant literature, some common mistakes in regard to this relationship are found. The correct results are obtained and proved in both frequency and time domains. The results are applicable to both single- and multi-input cases. They are significant as the simple LQR design for the nominal system can be utilized to directly solve-with no further effort-the complex robust stabilization problem for a class of linear uncertain systems.

8.
J Orthop Translat ; 40: 58-71, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37457310

RESUMO

Background: Cell culture studies demonstrate the importance of ß3 integrin in osteocyte mechanotransduction. However, the in vivo roles of osteocyte ß3 integrin in the regulation of bone homeostasis and mechanotransduction are poorly defined. Materials and methods: To study the in vivo role of osteocyte ß3 integrin in bone, we utilized the 10-kb Dmp1 (dentin matrix acidic phosphoprotein 1)-Cre to delete ß3 integrin expression in osteocyte in mice. Micro-computerized tomography (µCT), bone histomorphometry and in vitro cell culture experiments were performed to determine the effects of osteocyte ß3 integrin loss on bone mass accrual and biomechanical properties. In addition, in vivo tibial loading model was applied to study the possible involvement of osteocyte ß3 integrin in the mediation of bone mechanotransduction. Results: Deletion of ß3 integrin in osteocytes resulted in a low bone mass and impaired biomechanical properties in load-bearing long bones in adult mice. The loss of ß3 integrin led to abnormal cell morphology with reduced number and length of dentritic processes in osteocytes. Furthermore, osteocyte ß3 integrin loss did not impact the osteoclast formation, but significantly reduced the osteoblast-mediated bone formation rate and reduced the osteogenic differentiation of the bone marrow stromal cells in the bone microenvironment. In addition, mechanical loading failed to accelerate the anabolic bone formation in mutant mice. Conclusions: Our studies demonstrate the essential roles of osteocyte ß3 integrin in regulating bone mass and mechanotransduction.

9.
Diagnostics (Basel) ; 13(11)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37296706

RESUMO

Studies have shown that the circulating tumor cell (CTC) is a necessary condition for the invasion and distant metastasis of renal cell carcimona (RCC). However, few CTCs-related gene mutations have been developed which could promote the metastasis and implantation of RCC. The objective of this study is to explore the potential driver gene mutations that promote RCC metastasis and implantation based on CTCs culture. Fifteen patients with primary mRCC and three healthy subjects were included, and peripheral blood was obtained. After the preparation of synthetic biological scaffolds, peripheral blood CTCs were cultured. Successful cultured CTCs were applied to construct CTCs-derived xenograft (CDX) models, followed by DNA extraction, whole exome sequencing (WES) and bioinformatics analysis. Synthetic biological scaffolds were constructed based on previously applied techniques, and peripheral blood CTCs culture was successfully performed. We then constructed CDX models and performed WES, and explored the potential driver gene mutations that may promote RCC metastasis and implantation. Bioinformatics analysis showed that KAZN and POU6F2 may be closely related to the prognosis of RCC. We successfully performed the culture of peripheral blood CTCs and, on this basis we initially explored the potential driver mutations for the metastasis and implantation of RCC.

10.
J Bone Miner Res ; 38(7): 1015-1031, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37129025

RESUMO

Dysregulation of bone homeostasis is closely related to the pathogenesis of osteoporosis. Suppressing bone resorption by osteoclasts to attenuate bone loss has been widely investigated, but far less effort has been poured toward promoting bone formation by osteoblasts. Here, we aimed to explore magnesium ascorbyl phosphate (MAP), a hydrophilic and stable ascorbic acid derivative, as a potential treatment option for bone loss disorder by boosting osteoblastogenesis and bone formation. We found that MAP could promote the proliferation and osteoblastic differentiation of human skeletal stem and progenitor cells (SSPCs) in vitro. Moreover, MAP supplementation by gavage could alleviate bone loss and accelerate bone defect healing through promoting bone formation. Mechanistically, we identified calcium/calmodulin-dependent serine/threonine kinase IIα (CaMKIIα) as the target of MAP, which was found to be directly bound and activated by MAP, then with a concomitant activation in the phosphorylation of ERK1/2 (extracellular regulated kinase 1/2) and CREB (cAMP-response element binding protein) as well as an elevation of C-FOS expression. Further, blocking CaMKII signaling notably abolished these effects of MAP on SSPCs and bone remodeling. Taken together, our data indicated that MAP played an important role in enhancing bone formation through the activation of CaMKII/ERK1/2/CREB/C-FOS signaling pathway and may be used as a novel therapeutic option for bone loss disorders such as osteoporosis. © 2023 American Society for Bone and Mineral Research (ASBMR).


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Osteoporose , Humanos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/uso terapêutico , Osteogênese , Transdução de Sinais , Diferenciação Celular , Sistema de Sinalização das MAP Quinases , Osteoblastos/metabolismo , Osteoporose/metabolismo
11.
Int J Pediatr Otorhinolaryngol ; 168: 111539, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37023557

RESUMO

OBJECTIVE: To characterize the risk factors for difficult removal of tracheobronchial foreign body (FB) by rigid bronchoscopy in children. METHODS: We retrospectively analyzed clinical data of 1026 pediatric patients (age: 0-18 years) diagnosed with tracheobronchial FB between September 2018 and August 2021. All patients underwent rigid bronchoscopy as the first intervention at our hospital. RESULTS: Children aged 1-3 years accounted for 83.7% cases in our cohort. The most common symptoms were cough and wheeze. FBs were more frequently found in the right bronchus, and trachea FBs accounted for only 8.19% cases. The success rate of rigid bronchoscopy in a single attempt was 97.27%. 12.18% of the cases were defined as difficult removal of FB. On univariate analysis, age, CT findings (pneumonia), type of FB, diameter of FB, FB location, granulation tissue formation, and the seniority of the surgeon were identified as risk factors for difficult removal of tracheobronchial FBs. On multivariate analysis, age ≥3 years, FB diameter ≥10 mm, FBs located in left bronchus, multiple FBs, granulation tissue, and the seniority of surgeon (<3 years, ≥5 years) were independent risk factors for difficult removal. CONCLUSIONS: Age, FB diameter, location of FB, granulation tissue formation, and the seniority of the surgeon were risk factors for difficult removal of FBs by rigid bronchoscopy.


Assuntos
Broncoscopia , Corpos Estranhos , Criança , Humanos , Lactente , Recém-Nascido , Pré-Escolar , Adolescente , Estudos Retrospectivos , Brônquios/diagnóstico por imagem , Brônquios/cirurgia , Fatores de Risco , Corpos Estranhos/cirurgia , Corpos Estranhos/diagnóstico , Traqueia/cirurgia
12.
Gene ; 865: 147327, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-36870428

RESUMO

In cell culture studies, immortalized primary cells have become a useful tool to investigate the molecular and cellular functions of different types of cells. Several immortalization agents, such as human telomerase reverse transcriptase (hTERT) and Simian Virus 40 (SV40) T antigens, are commonly used for primary cell immortalization. Astrocytes, as the most abundant glial cell type in the central nervous system, are promising therapeutical targets for many neuronal disorders, such as Alzheimer's disease and Parkinson's disease. Immortalized primary astrocytes can provide useful information for astrocytes biology, astrocytes-neuron interactions, glial interactions and astrocytes-associated neuronal diseases. In this study, we successfully purified primary astrocytes with immuno-panning method and examined the astrocyte functions after immortalization through both hTERT and SV40 Large-T antigens. As expected, both immortalized astrocytes presented unlimited lifespan and highly expressed multiple astrocyte-specific markers. However, SV40 Large-T antigen, but not hTERT, immortalized astrocytes displayed fast ATP-induced calcium wave in culture. Hence, SV40 Large-T antigen could be a better choice for primary astrocyte immortalization, which closely mimics the cell biology of primary astrocytes in culture. In summary, the purification and immortalization of primary astrocytes presented in this study can be used for studying astrocyte biology under physiological and pathological conditions.


Assuntos
Astrócitos , Telomerase , Camundongos , Animais , Humanos , Astrócitos/metabolismo , Linhagem Celular , Antígenos Virais de Tumores/metabolismo , Neuroglia/metabolismo , Telomerase/metabolismo
13.
Bioeng Transl Med ; 8(2): e10414, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36925715

RESUMO

Bone injury caused changes to surrounding tissues, leading to a large number of osteoclasts appeared to clear the damaged bone tissue before bone regeneration. However, overactive osteoclasts will inhibit bone formation. In this study, we prepared methacrylylated gelatin (GelMA)-based hydrogel to co-crosslink with OP3-4 peptide, a receptor activator of NF-κB ligand (RANKL) binding agent, to achieve the slow release of OP3-4 peptide to inhibit the activation of osteoclasts, thus preventing the long-term existence of osteoclasts from affecting bone regeneration, and promoting osteogenic differentiation. Moreover, CXCL9 secreted by osteoblasts will bind to endogenous VEGF and inhibit vascularization, finally hinder bone formation. Thus, anti-CXCL9 antibodies (A-CXCL9) were also loaded in the hydrogel to neutralize excess CXCL9. The hydrogel slow released of OP3-4 cyclic peptide and A-CXCL9 to simultaneously inhibiting osteoclast activation and promoting vascularization, thereby accelerating the healing of femur defect. Further analysis of osteogenic protein expression and signal pathways showed that the hydrogel may be through activating the AKT-RUNX2-ALP pathway and ultimately promote osteogenic differentiation. This dual-acting hydrogel can effectively prevent nonunion caused by low vascularization and provide long-term support for the treatment of bone injury.

14.
Aging Clin Exp Res ; 35(3): 531-539, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36708462

RESUMO

BACKGROUND: Percutaneous vertebroplasty was the most common strategy for osteoporotic vertebral compression fracture. However, refracture after vertebroplasty also occurred and bone mineral density (BMD) was one of the main factors associated with refracture after percutaneous vertebroplasty. AIMS: To investigate the efficacy of a short-sequential treatment of teriparatide followed by alendronate on prevention of refracture after percutaneous vertebroplasty in osteoporotic patients, and compare it with the therapy of alendronate alone. METHODS: From January 2018 to January 2020, we recruited 165 female osteoporosis patients after percutaneous vertebroplasty who were assigned into sequential treatment of teriparatide followed by alendronate group (TPTD + ALN group) and alendronate alone group (ALN group). The vertebral fracture occurred during this process was also recorded in both the groups. A total of 105 participants completed the 1-year follow-up. Furthermore, BMD and serum procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were compared between the two groups during 1-year follow-up. RESULTS: The 105 patients were finally included, with 59 in ALN group and 46 in TPTD + ALN group. During 1-year follow-up, the vertebral refracture rate in TPTD + ALN group was much lower than that in ALN group (2.2% vs. 13.6%, p < 0.05). At 12 months, the BMDs at lumbar in TPTD + ALN group were significantly elevated when compared to the ALN group (0.65 ± 0.10 vs. 0.57 ± 0.07, p < 0.001). DISCUSSION AND CONCLUSION: A short-sequential administration of teriparatide followed by alendronate was more effective in elevating the BMD and decreasing the refracture rate at 12-month follow-up, compared to the counterpart with alendronate alone.


Assuntos
Conservadores da Densidade Óssea , Fraturas por Compressão , Osteoporose Pós-Menopausa , Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Feminino , Teriparatida/uso terapêutico , Alendronato/uso terapêutico , Densidade Óssea , Estudos Prospectivos , Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/prevenção & controle , Fraturas por Compressão/cirurgia , Fraturas da Coluna Vertebral/prevenção & controle , Fraturas da Coluna Vertebral/cirurgia , Osteoporose/tratamento farmacológico
15.
Acta Pharmacol Sin ; 44(2): 268-287, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35896695

RESUMO

Fibrosis is caused by extensive deposition of extracellular matrix (ECM) components, which play a crucial role in injury repair. Fibrosis attributes to ~45% of all deaths worldwide. The molecular pathology of different fibrotic diseases varies, and a number of bioactive factors are involved in the pathogenic process. Mesenchymal stem cells (MSCs) are a type of multipotent stem cells that have promising therapeutic effects in the treatment of different diseases. Current updates of fibrotic pathogenesis reveal that residential MSCs may differentiate into myofibroblasts which lead to the fibrosis development. However, preclinical and clinical trials with autologous or allogeneic MSCs infusion demonstrate that MSCs can relieve the fibrotic diseases by modulating inflammation, regenerating damaged tissues, remodeling the ECMs, and modulating the death of stressed cells after implantation. A variety of animal models were developed to study the mechanisms behind different fibrotic tissues and test the preclinical efficacy of MSC therapy in these diseases. Furthermore, MSCs have been used for treating liver cirrhosis and pulmonary fibrosis patients in several clinical trials, leading to satisfactory clinical efficacy without severe adverse events. This review discusses the two opposite roles of residential MSCs and external MSCs in fibrotic diseases, and summarizes the current perspective of therapeutic mechanism of MSCs in fibrosis, through both laboratory study and clinical trials.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Fibrose Pulmonar , Animais , Fibrose , Cirrose Hepática/terapia , Cirrose Hepática/patologia , Fibrose Pulmonar/terapia , Fibrose Pulmonar/patologia , Inflamação/patologia
16.
Bioact Mater ; 20: 610-626, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35846848

RESUMO

A novel sprayable adhesive is established (ZnMet-PF127) by the combination of a thermosensitive hydrogel (Pluronic F127, PF127) and a coordination complex of zinc and metformin (ZnMet). Here we demonstrate that ZnMet-PF127 potently promotes the healing of traumatic skin defect and burn skin injury by promoting cell proliferation, angiogenesis, collagen formation. Furthermore, we find that ZnMet could inhibit reactive oxygen species (ROS) production through activation of autophagy, thereby protecting cell from oxidative stress induced damage and promoting healing of skin wound. ZnMet complex exerts better effects on promoting skin wound healing than ZnCl2 or metformin alone. ZnMet complex also displays excellent antibacterial activity against Staphylococcus aureus or Escherichia coli, which could reduce the incidence of skin wound infections. Collectively, we demonstrate that sprayable PF127 could be used as a new drug delivery system for treatment of skin injury. The advantages of this sprayable system are obvious: (1) It is convenient to use; (2) The hydrogel can cover irregular skin defect sites evenly in a liquid state. In combination with this system, we establish a novel sprayable adhesive (ZnMet-PF127) and demonstrate that it is a potential clinical treatment for traumatic skin defect and burn skin injury.

17.
Curr Stem Cell Res Ther ; 18(7): 917-925, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35980064

RESUMO

Bone and cartilage regeneration is a dynamic and complex process involving multiple cell types, such as osteoblasts, osteoclasts, endothelial cells, etc. Stem cells have been proved to have an efficient capability to promote bone and cartilage regeneration and repair, but the usage of cells harbors some important safety issues, such as immune rejection and carcinogenicity. Exosomes are non-cell structures secreted from various cells. The content of exosomes is enriched with proteins, such as cytoskeleton proteins, adhesion factors, transcription factors, etc., and a variety of nucleic acids, such as mRNA (Messenger RNA), long-chain non-coding RNA, microRNA (miRNA), etc. Exosomes can deliver a variety of contents from the parent cells to the recipient cells in different tissue backgrounds, influencing the phenotype and function of the recipient cells. Recent studies have demonstrated that miRNAs play significant roles in bone formation, suggesting that miRNAs may be novel therapeutic targets for bone and cartilage diseases. Exosomes have been shown with low/no immune rejection in vivo, no carcinogenic risk of infection, nor other side effects. In recent years, stem cell exosomes have been utilized to promote bone and cartilage regeneration processes during bone defect, bone fracture, cartilage repair, osteoporosis, and osteoarthritis. In this review, we discuss different exosomes derived from stem cells and their interactions with target cells, including osteoblasts, chondrocytes and osteoclasts. We also highlight the various signaling pathways involved in stem cell exosome-related bone and cartilage regeneration.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Exossomos/genética , Exossomos/metabolismo , Células Endoteliais/metabolismo , Cartilagem , Células-Tronco
18.
Artigo em Inglês | MEDLINE | ID: mdl-35955079

RESUMO

Although coal is difficult to replace in the short term, the large-scale production and consumption of coal have significant impacts on the ecological environment. The severe disturbances, such as land excavation and occupation, that accompany the mining of mineral resources have caused dramatic changes in land cover and a significant pressure on the sensitive and fragile ecological environment. To analyze the temporal and spatial evolution trends and the differences in land use in different typical mining areas in Inner Mongolia, as well as the evaluation system and driving mechanisms of land use evolution, this study takes the typical open-pit coal mines in Inner Mongolia as the research objects and, based on the Google Earth Engine (GEE) platform, analyzes the dynamic evolution characteristics and driving factors of land use in typical open-pit coal mines in Inner Mongolia from 2001 to 2020. The change trend of land use in typical open-pit mining areas in Inner Mongolia for the past 20 years is obvious, with the highest fluctuations for grassland, mining land, cropland, and residential/industrial land. Land use in the open-pit coal mining area is greatly affected by mining factors. From the perspective of spatial variation, the most important driving factor is the distance from national roads and railways, followed by the annual average temperature and annual average precipitation and topographical conditions, such as elevation. In terms of policy, land reclamation and ecological restoration in mining areas have a positive impact on land use change. Improving the mechanism for environmental compensation in mining areas can promote the efficient and rational use of mining areas and the protection of ecosystems.


Assuntos
Minas de Carvão , Ecossistema , China , Carvão Mineral , Planeta Terra , Monitoramento Ambiental
19.
Front Surg ; 9: 961616, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35983551

RESUMO

Background: The aim of the study was to compare the clinical characteristics of diabetic carpal tunnel syndrome between patients with neuropathic pain (NeuP) and non-NeuP. Methods: We enrolled 276 patients with diabetic carpal tunnel syndrome. Pain symptoms were evaluated using a visual analog scale. Douleur Neuropathique 4, the Neuropathic Pain Symptoms Inventory questionnaire, and the body map were used to assess neuropathic symptoms. Baseline information, clinical manifestations, electrophysiological test results, and psychological status were compared between the neuropathic pain (NeuP) and non-NeuP to identify the risk factor for NeuP occurrence. Results: Results showed that the degree of pain was more severe in NeuP patients than in nociceptive pain patients (p = 0.025). The frequencies of light touch and pinprick were more pronounced in the NeuP group than in the non-NeuP group (light touch: p = 0.001; pinprick: p = 0.004). There were 48 and 27 NeuP patients with extramedian and proximal spread, respectively, whereas in the non-NeuP group, there were 11 and 9 patients, respectively (p = 0.03). Electrophysiological results showed that patients in the NeuP group exhibited greater sensory nerve conduction velocity impairment compared with the non-NeuP group (p = 0.033). Pain Catastrophizing Scale total scores of the NeuP group were significantly higher than those of the non-NeuP group (p = 0.006). Conclusion: Of the 276 diabetic carpal tunnel syndrome patients studied, the majority had NeuP. Furthermore, light touch, electrophysiological test results, and psychological factors were found to be related to NeuP occurrence in patients with diabetic carpal tunnel syndrome.

20.
Front Surg ; 9: 849679, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711699

RESUMO

Objective: The efficacy of hybrid (Dynesys and fusion) surgery and the traditional transforaminal lumbar interbody fusion surgery was compared in patients with multi-segmental lumbar spinal stenosis. Methods: A total of 68 patients with multi-segmental lumbar spinal stenosis subjected to surgery were recruited between January 2013 and October 2020 in the First Affiliated Hospital of Southern University of Science and Technology. The patients were divided into a hybrid group (N = 33) and a TLIF group (N = 35) by surgery. After surgery, follow-up was conducted for 12 months. Between the two groups, the following parameters were compared: general conditions, clinical symptom scores, imaging parameters, and early complications. Results: A statistically significant difference in the duration of surgery was noted between the two groups. After 12 months of follow-up, the range of motion disappeared in the TLIF group, while 63.53% was preserved in the hybrid group with statistically significant differences. A statistically significant difference was identified in the Oswestry Disability Index one week after surgery. Nonetheless, no statistically significant differences were observed at the 12-month post-surgical follow-up. Pfirrmann grade showed a 3.03% upper adjacent segment degeneration rate in the hybrid group (1/33) at 12-month follow-up and 2.86% (1/35) in the TLIF group. Notably, no early complications (screw loosening and wound infection) were identified in the two groups. Conclusion: The Dynesys hybrid surgery combined the advantages of two systems of dynamic stabilization and rigid fusion. Besides, hybrid surgery is potentially a novel approach for the treatment of multi-segmental lumbar spinal stenosis.

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