RESUMO
BACKGROUND: Elevated soluble stimulating factor 2 (sST2) level is observed in cardiovascular diseases, such as heart failure and acute coronary syndrome, which reflects myocardial fibrosis and hypertrophy, indicating adverse clinical outcomes. However, the association between sST2 and hypertensive heart disease are less understood. This study aimed to determine the relationship of sST2 with left ventricular hypertrophy (LVH) and geometric remodeling in essential hypertension (EH). METHODS: We enrolled 483 patients (aged 18-80 years; 51.35% female). sST2 measurements and echocardiographic analyses were performed. RESULTS: Stepwise multiple linear regression analysis showed significant associations between sST2, left ventricular (LV) mass, and LV mass index. The prevalence of LVH and concentric hypertrophy (CH) increased with higher sST2 grade levels (p for trend<0.05). Logistic regression analysis suggested that the highest tertile of sST2 was significantly associated with increased LVH risk, compared with the lowest tertile (multivariate-adjusted odds ratio [OR] of highest group: 6.61; p<0.001). Similar results were observed in the left ventricular geometric remodeling; the highest tertile of sST2 was significantly associated with increased CH risk (multivariate-adjusted OR of highest group: 5.80; p<0.001). The receiver operating characteristic analysis results revealed that sST2 had potential predictive value for LVH (area under the curve [AUC]: 0.752, 95% confidence interval [CI]: 0.704-0.800) and CH (AUC: 0.750, 95% CI: 0.699-0.802) in patients with EH. CONCLUSIONS: High sST2 level is strongly related to LVH and CH in patients with EH and can be used as a biomarker for the diagnosis and risk assessment of hypertensive heart disease.
RESUMO
This research examines the unique Chinese approaches to implementing the Early Childhood Curriculum (ECC) in Shenzhen and Hong Kong, drawing on School-based Curriculum Development (SBCD) studies. A total of 200 administrators and teachers were interviewed in total, and transcripts from those interviews were examined, cross-checked, and assessed using document analysis and classroom observation. Through interviews that have been conducted by administrators and teachers analyzed by document analysis and classroom observation, the influence of Chinese culture on ECC implementation is explored using the Cultural-Historical Activity Theory (CHAT). An exploratory, inferential, and descriptive statistical approach evaluates the sociocultural mechanism of ECC in Chinese society. The proposed framework utilizes K-Nearest Neighbor (KNN) regression analysis to illustrate how social development leads to cultural fusion and conflicts. The overall sociocultural framework promotes cultural growth and inheritance in China's early childhood education settings.
RESUMO
BACKGROUND: A favorable regenerative microenvironment is essential for peripheral nerve regeneration. Neural tissue-specific extracellular matrix (ECM) is a natural material that helps direct cell behavior and promote axon regeneration. Both bone marrow-derived mesenchymal stem cells (BMSCs) and adipose-derived mesenchymal stem cells (ADSCs) transplantation are effective in repairing peripheral nerve injury (PNI). However, there is no study that characterizes the in vivo microenvironmental characteristics of these two MSCs for the early repair of PNI when combined with neural tissue-derived ECM materials, i.e., acellular nerve allograft (ANA). METHODS: In order to investigate biological characteristics, molecular mechanisms of early stage, and effectiveness of ADSCs- or BMSCs-injected into ANA for repairing PNI in vivo, a rat 10 mm long sciatic nerve defect model was used. We isolated primary BMSCs and ADSCs from bone marrow and adipose tissue, respectively. First, to investigate the in vivo response characteristics and underlying molecular mechanisms of ANA combined with BMSCs or ADSCs, eighty-four rats were randomly divided into three groups: ANA group, ANA+BMSC group, and ANA+ADSC group. We performed flow cytometry, RT-PCR, and immunofluorescence staining up to 4 weeks postoperatively. To further elucidate the underlying molecular mechanisms, changes in long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) were systematically investigated using whole transcriptome sequencing. We then constructed protein-protein interaction networks to find 10 top ranked hub genes among differentially expressed mRNAs. Second, in order to explore the effectiveness of BMSCs and ADSCs on neural tissue-derived ECM materials for repairing PNI, sixty-eight rats were randomized into four groups: ANA group, ANA+BMSC group, ANA+ADSC group, and AUTO group. In the ANA+BMSC and ANA+ADSC groups, ADSCs/BMSCs were equally injected along the long axis of the 10-mm ANA. Then, we performed histological and functional assessments up to 12 weeks postoperatively. RESULTS: The results of flow cytometry and RT-PCR showed that ANA combined with BMSCs exhibited more significant immunomodulatory effects, as evidenced by the up-regulation of interleukin (IL)-10, down-regulation of IL-1ß and tumor necrosis factor-alpha (TNF-α) expression, promotion of M1-type macrophage polarization to M2-type, and a significant increase in the number of regulatory T cells (Tregs). ANA combined with ADSCs exhibited more pronounced features of pro-myelination and angiogenesis, as evidenced by the up-regulation of myelin-associated protein gene (MBP and MPZ) and angiogenesis-related factors (TGF-ß, VEGF). Moreover, differentially expressed genes from whole transcriptome sequencing results further indicated that ANA loaded with BMSCs exhibited notable immunomodulatory effects and ANA loaded with ADSCs was more associated with angiogenesis, axonal growth, and myelin formation. Notably, ANA infused with BMSCs or ADSCs enhanced peripheral nerve regeneration and motor function recovery with no statistically significant differences. CONCLUSIONS: This study revealed that both ANA combined with BMSCs and ADSCs enhance peripheral nerve regeneration and motor function recovery, but their biological characteristics (mainly including immunomodulatory effects, pro-vascular regenerative effects, and pro-myelin regenerative effects) and underlying molecular mechanisms in the process of repairing PNI in vivo are different, providing new insights into MSC therapy for peripheral nerve injury and its clinical translation.
Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Regeneração Nervosa , Traumatismos dos Nervos Periféricos , Ratos Sprague-Dawley , Engenharia Tecidual , Animais , Ratos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Engenharia Tecidual/métodos , Traumatismos dos Nervos Periféricos/terapia , Traumatismos dos Nervos Periféricos/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Nervo Isquiático/lesões , Nervo Isquiático/metabolismo , Masculino , Tecido Adiposo/citologia , Tecido Adiposo/metabolismoRESUMO
Peripheral nerve injury (PNI) poses a significant public health issue, often leading to muscle atrophy and persistent neuropathic pain, which can drastically impact the quality of life for patients. Electrical stimulation represents an effective and non-pharmacological treatment to promote nerve regeneration. Yet, the postoperative application of electrical stimulation remains a challenge. Here, we propose a fully biodegradable, self-powered nerve guidance conduit (NGC) based on dissolvable zinc-molybdenum batteries. The conduit can offer topographic guidance for nerve regeneration and deliver sustained electrical cues between both ends of a transected nerve stump, extending beyond the surgical window. Schwann cell proliferation and adenosine triphosphate (ATP) production are enhanced by the introduction of the zinc-molybdenum batteries. In rodent models with 10-mm sciatic nerve damage, the device effectively enhances nerve regeneration and motor function recovery. This study offers innovative strategies for creating biodegradable and electroactive devices that hold important promise to optimize therapeutic outcomes for nerve regeneration.
Assuntos
Regeneração Nervosa , Traumatismos dos Nervos Periféricos , Nervo Isquiático , Zinco , Animais , Traumatismos dos Nervos Periféricos/terapia , Zinco/química , Nervo Isquiático/fisiologia , Nervo Isquiático/lesões , Ratos , Fontes de Energia Elétrica , Molibdênio/química , Células de Schwann , Ratos Sprague-Dawley , Humanos , Regeneração Tecidual Guiada/instrumentação , Regeneração Tecidual Guiada/métodos , Técnicas Biossensoriais , Implantes AbsorvíveisRESUMO
Here, a barbituric acid derivative containing pyrene rings (DPPT) was successfully synthesized, and two types of crystals were prepared by using crystal engineering methods. Orange sheet-like crystals (DPPT-O, observed in visible light), prepared in a DCM/CH3OH solution, exhibited brittleness and weak fluorescence emission, along with sunlight-induced bending and fracturing. Red needle-like crystals (DPPT-R, also observed in visible light), synthesized in a DCM/CH3CN solution, demonstrated elastic properties, strong fluorescence emission, and excellent optical waveguide performance (with an optical loss coefficient of 0.23-0.30 dB mm-1). Single-crystal data analysis revealed that the stacking arrangement of molecules critically influenced the elasticity of the crystals, while the reaction cavity size regulated the photomechanical properties of the crystals. This study achieved effective control over sunlight responsiveness and flexible optical waveguide transmission for the first time, providing innovative insights for the application of homogeneous organic polycrystalline molecular crystals in this field.
RESUMO
BACKGROUND Persistent truncus arteriosus is a rare congenital cyanotic heart defect characterized by a single ventricular outflow tract. Without surgical intervention, it has a poor prognosis in infancy. Here, we report an adult female patient with uncorrected truncus arteriosus type I, who presented with acute-onset abdominal pain due to torsion of a small bowel gastrointestinal stromal tumor (GIST). CASE REPORT A 41-year-old woman came to our Emergency Department with acute-onset lower abdominal pain for 2 days. Congenital heart disease, truncus arteriosus, had been diagnosed at birth, and there had been no surgical intervention. Abdominal computed tomography revealed a 10×9×12-cm mixed-density mass in the pelvic capacity. Transthoracic echocardiography revealed a 33-mm ventricular septal defect. The ascending aorta originated mainly from the right ventricle, and the pulmonary artery originated from the beginning of the aorta (type I truncus arteriosus, according to Collett and Edwards classification). After a quick and detailed preoperative workup, the patient underwent tumor resection by open surgery with general anesthesia. CONCLUSIONS This is the first case to report emergency surgery for a patient with uncorrected persistent truncus arteriosus due to torsion of a small bowel GIST. A multidisciplinary team with deep understanding of the disease entity was crucial. By considering the fixed hemodynamic and respiratory physiology, overtreatment and unrealistic goals were avoided. Eventually, the patient was discharged after being hospitalized for 2 weeks.
Assuntos
Tumores do Estroma Gastrointestinal , Humanos , Feminino , Adulto , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/cirurgia , Anormalidade Torcional/cirurgia , Anormalidade Torcional/diagnóstico , Persistência do Tronco Arterial/cirurgia , Persistência do Tronco Arterial/complicações , Intestino Delgado/anormalidadesRESUMO
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.
Assuntos
Tecido Adiposo , Quitosana , Células-Tronco Mesenquimais , Microesferas , Regeneração Nervosa , Ratos Sprague-Dawley , Quitosana/química , Regeneração Nervosa/fisiologia , Animais , Ratos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Tecido Adiposo/citologia , Nervo Isquiático/fisiologia , Porosidade , Alicerces Teciduais/química , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Proliferação de Células , Células CultivadasRESUMO
Optoelectronic neural interfaces can leverage the photovoltaic effect to convert light into electrical current, inducing charge redistribution and enabling nerve stimulation. This method offers a non-genetic and remote approach for neuromodulation. Developing biodegradable and efficient optoelectronic neural interfaces is important for achieving transdermal stimulation while minimizing infection risks associated with device retrieval, thereby maximizing therapeutic outcomes. We propose a biodegradable, flexible, and miniaturized silicon-based neural interface capable of transdermal optoelectronic stimulation for neural modulation and nerve regeneration. Enhancing the device interface with thin-film molybdenum significantly improves the efficacy of neural stimulation. Our study demonstrates successful activation of the sciatic nerve in rodents and the facial nerve in rabbits. Moreover, transdermal optoelectronic stimulation accelerates the functional recovery of injured facial nerves.
Assuntos
Regeneração Nervosa , Nervo Isquiático , Animais , Coelhos , Regeneração Nervosa/fisiologia , Regeneração Nervosa/efeitos dos fármacos , Nervo Isquiático/fisiologia , Nervo Facial/fisiologia , Nervos Periféricos/fisiologia , Masculino , Ratos , Silício/química , Ratos Sprague-Dawley , Estimulação ElétricaRESUMO
Irregular articular cartilage injury is a common type of joint trauma, often resulting from intense impacts and other factors that lead to irregularly shaped wounds, the limited regenerative capacity of cartilage and the mismatched shape of the scaffods have contributed to unsatisfactory therapeutic outcomes. While injectable materials are a traditional solution to adapt to irregular cartilage defects, they have limitations, and injectable materials often lack the porous microstructures favorable for the rapid proliferation of cartilage cells. In this study, an injectable porous polyurethane scaffold named PU-BDO-Gelatin-Foam (PUBGF) was prepared. After injection into cartilage defects, PUBGF forms in situ at the site of the defect and exhibits a dynamic microstructure during the initial two weeks. This dynamic microstructure endows the scaffold with the ability to retain substances within its interior, thereby enhancing its capacity to promote chondrogenesis. Furthermore, the chondral repair efficacy of PUBGF was validated by directly injecting it into rat articular cartilage injury sites. The injectable PUBGF scaffold demonstrates a superior potential for promoting the repair of cartilage defects when compared to traditional porous polyurethane scaffolds. The substance retention ability of this injectable porous scaffold makes it a promising option for clinical applications.
RESUMO
Background: Osteochondral regeneration has long been recognized as a complex and challenging project in the field of tissue engineering. In particular, reconstructing the osteochondral interface is crucial for determining the effectiveness of the repair. Although several artificial layered or gradient scaffolds have been developed recently to simulate the natural interface, the functions of this unique structure have still not been fully replicated. In this paper, we utilized laser micro-patterning technology (LMPT) to modify the natural osteochondral "plugs" for use as grafts and aimed to directly apply the functional interface unit to repair osteochondral defects in a goat model. Methods: For in vitro evaluations, the optimal combination of LMPT parameters was confirmed through mechanical testing, finite element analysis, and comparing decellularization efficiency. The structural and biological properties of the laser micro-patterned osteochondral implants (LMP-OI) were verified by measuring the permeability of the interface and assessing the recellularization processes. In the goat model for osteochondral regeneration, a conical frustum-shaped defect was specifically created in the weight-bearing area of femoral condyles using a customized trephine with a variable diameter. This unreported defect shape enabled the implant to properly self-fix as expected. Results: The micro-patterning with the suitable pore density and morphology increased the permeability of the LMP-OIs, accelerated decellularization, maintained mechanical stability, and provided two relative independent microenvironments for subsequent recellularization. The LMP-OIs with goat's autologous bone marrow stromal cells in the cartilage layer have securely integrated into the osteochondral defects. At 6 and 12 months after implantation, both imaging and histological assessments showed a significant improvement in the healing of the cartilage and subchondral bone. Conclusion: With the natural interface unit and zonal recellularization, the LMP-OI is an ideal scaffold to repair osteochondral defects especially in large animals. The translational potential of this article: These findings suggest that such a modified xenogeneic osteochondral implant could potentially be explored in clinical translation for treatment of osteochondral injuries. Furthermore, trimming a conical frustum shape to the defect region, especially for large-sized defects, may be an effective way to achieve self-fixing for the implant.
RESUMO
Numerous studies have clarified the impacts of magnesium (Mg) on leaf photosynthesis from the perspectives of protein synthesis, enzymes activation and carbohydrate partitioning. However, it still remains largely unknown how stomatal and mesophyll conductances (gs and gm, respectively) are regulated by Mg. In the present study, leaf gas exchanges, leaf hydraulic parameters, leaf structural traits and cell wall composition were examined in rice plants grown under high and low Mg treatments to elucidate the impacts of Mg on gs and gm. Our results showed that reduction of leaf photosynthesis under Mg deficiency was mainly caused by the decreased gm, followed by reduced leaf biochemical capacity and gs, and leaf outside-xylem hydraulic conductance (Kox) was the major factor restricting gs under Mg deficiency. Moreover, increased leaf hemicellulose, lignin and pectin contents and decreased cell wall effective porosity were observed in low Mg plants relative to high Mg plants. These results suggest that Kox and cell wall composition play important roles in regulating gs and gm, respectively, in rice plants under Mg shortages.
Assuntos
Deficiência de Magnésio , Oryza , Oryza/metabolismo , Estômatos de Plantas/fisiologia , Água/metabolismo , Folhas de Planta/metabolismo , Fotossíntese/fisiologia , Células do Mesofilo/metabolismo , Dióxido de Carbono/metabolismoRESUMO
Left ventricular hypertrophy (LVH) is a hypertensive heart disease that significantly escalates the risk of clinical cardiovascular events. Its etiology potentially incorporates various clinical attributes such as gender, age, and renal function. From mechanistic perspective, the remodeling process of LVH can trigger increment in certain biomarkers, notably sST2 and NT-proBNP. This multicenter, retrospective study aimed to construct an LVH risk assessment model and identify the risk factors. A total of 417 patients with essential hypertension (EH), including 214 males and 203 females aged 31-80 years, were enrolled in this study; of these, 161 (38.6%) were diagnosed with LVH. Based on variables demonstrating significant disparities between the LVH and Non-LVH groups, three multivariate stepwise logistic regression models were constructed for risk assessment: the "Clinical characteristics" model, the "Biomarkers" model (each based on their respective variables), and the "Clinical characteristics + Biomarkers" model, which amalgamated both sets of variables. The results revealed that the "Clinical characteristics + Biomarkers" model surpassed the baseline models in performance (AUC values of the "Clinical characteristics + Biomarkers" model, the "Biomarkers" model, and the "Clinical characteristics" model were .83, .75, and .74, respectively; P < .0001 for both comparisons). The optimized model suggested that being female (OR: 4.26, P <.001), being overweight (OR: 1.88, p = .02) or obese (OR: 2.36, p = .02), duration of hypertension (OR: 1.04, P = .04), grade III hypertension (OR: 2.12, P < .001), and sST2 (log-transformed, OR: 1.14, P < .001) were risk factors, while eGFR acted as a protective factor (OR: .98, P = .01). These findings suggest that the integration of clinical characteristics and biomarkers can enhance the performance of LVH risk assessment.
Assuntos
Hipertensão , Hipertrofia Ventricular Esquerda , Feminino , Humanos , Masculino , Biomarcadores , Hipertensão Essencial/complicações , Hipertensão Essencial/epidemiologia , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/etiologia , Nomogramas , Estudos Retrospectivos , Medição de Risco , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Xenograft kidney transplantation has been receiving increasing attention. The purpose of this study is to use bibliometric analysis to identify papers in this research field and explore their current status and development trends. METHODS: Using the data in the Web of Science core database from Clarivate Analytics as the object of study, we used 'TS = Kidney OR Renal AND xenotransplantation' as the search term to find all literature from 1980 to 2 November 2022. RESULTS: In total, 1005 articles were included. The United States has the highest number of publications and has made significant contributions in this field. Harvard University was at the forefront of this study. Professor Cooper has published 114 articles in this field. Xenotransplantation has the largest number of relevant articles. Transplantation was the most cited journal. High-frequency keywords illustrated the current state of development and future trends in xenotransplantation. The use of transgenic pigs and the development of coordinated co-stimulatory blockers have greatly facilitated progress in xenotransplantation research. We found that 'co-stimulation blockade', 'xenograft survival', 'pluripotent stem cell', 'translational research', and 'genetic engineering' were likely to be the focus of attention in the coming years. CONCLUSIONS: This study screened global publications related to xenogeneic kidney transplantation; analyzed their literature metrology characteristics; identified the most cited articles in the research field; understood the current situation, hot spots, and trends of global research; and provided future development directions for researchers and practitioners.
Assuntos
Transplante de Rim , Rim , Humanos , Animais , Suínos , Transplante Heterólogo , Rim/cirurgia , Bibliometria , Bases de Dados FactuaisRESUMO
PURPOSE: Ischemia and hypoxia are the main factors limiting limb replantation and transplantation. Static cold storage (SCS), a common preservation method for tissues and organs, can only prolong limb ischemia time to 4 - 6 h. The normothermic machine perfusion (NMP) is a promising method for the preservation of tissues and organs, which can extend the preservation time in vitro by providing continuous oxygen and nutrients. This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods. METHODS: The 6 forelimbs from beagle dogs were divided into 2 groups. In the SCS group (n = 3), the limbs were preserved in a sterile refrigerator at 4 °C for 24 h, and in the NMP group (n = 3), the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h, and the solution was changed every 6 h. The effects of limb storage were evaluated by weight gain, perfusate biochemical analysis, enzyme-linked immunosorbent assay, and histological analysis. All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance. The p value of less than 0.05 was considered to indicate statistical significance. RESULTS: In the NMP group, the weight gained percentage was 11.72% ± 4.06%; the hypoxia-inducible factor-1α contents showed no significant changes; the shape of muscle fibers was normal; the gap between muscle fibers slightly increased, showing the intercellular distance of (30.19 ± 2.83) µm; and the vascular α-smooth muscle actin (α-SMA) contents were lower than those in the normal blood vessels. The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion, decreased after each perfusate change, and remained stable at the end of perfusion showing a peak level of 4097.6 U/L. The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L. In the SCS group, the percentage of weight gain was 0.18% ± 0.10%, and the contents of hypoxia-inducible factor-1α increased gradually and reached the maximum level of (164.85 ± 20.75) pg/mL at the end of the experiment. The muscle fibers lost their normal shape and the gap between muscle fibers increased, showing an intercellular distance of (41.66 ± 5.38) µm. The contents of vascular α-SMA were much lower in the SCS group as compared to normal blood vessels. CONCLUSIONS: NMP caused lesser muscle damage and contained more vascular α-SMA as compared to SCS. This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.
Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Preservação de Órgãos , Animais , Cães , Temperatura , Preservação de Órgãos/métodos , Perfusão/métodos , Extremidade Superior , Membro Anterior , Aumento de Peso , FígadoRESUMO
Peripheral nerve injuries (PNI) can lead to mitochondrial dysfunction and energy depletion within the affected microenvironment. The objective is to investigate the potential of transplanting mitochondria to reshape the neural regeneration microenvironment. High-purity functional mitochondria with an intact structure are extracted from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) using the Dounce homogenization combined with ultracentrifugation. Results show that when hUCMSC-derived mitochondria (hUCMSC-Mitos) are cocultured with Schwann cells (SCs), they promote the proliferation, migration, and respiratory capacity of SCs. Acellular nerve allografts (ANAs) have shown promise in nerve regeneration, however, their therapeutic effect is not satisfactory enough. The incorporation of hUCMSC-Mitos within ANAs has the potential to remodel the regenerative microenvironment. This approach demonstrates satisfactory outcomes in terms of tissue regeneration and functional recovery. Particularly, the use of metabolomics and bioenergetic profiling is used for the first time to analyze the energy metabolism microenvironment after PNI. This remodeling occurs through the enhancement of the tricarboxylic acid cycle and the regulation of associated metabolites, resulting in increased energy synthesis. Overall, the hUCMSC-Mito-loaded ANAs exhibit high functionality to promote nerve regeneration, providing a novel regenerative strategy based on improving energy metabolism for neural repair.
Assuntos
Células-Tronco Mesenquimais , Tecido Nervoso , Traumatismos dos Nervos Periféricos , Humanos , Nervo Isquiático , Células de Schwann , Traumatismos dos Nervos Periféricos/terapia , Matriz Extracelular , Regeneração Nervosa/fisiologiaRESUMO
The pivotal role of lncRNAs in osteoporosis progression and development necessitates a comprehensive exploration of the functional and precise molecular mechanisms underlying lncRNA SNHG1's regulation of osteoblast differentiation and calcification. The study involved inducing BMSCs cells to differentiate into osteoblasts, followed by transfections of miR-497-5p inhibitors, pcDNA3.1-SNHG1, sh-HIF1AN, miR-497-5p mimics, and respective negative controls into BMSCs. Quantitative PCR (qPCR) was employed to assess the expression of SNHG1 and miR-497-5p. Western Blotting was conducted to measure the levels of short stature-related transcription factor 2 (RUNX2), osteopontin (OPN), osteocalcin (OCN), and HIF1AN. Alkaline phosphatase (ALP) activity was determined using appropriate assay kits. Calcium nodule staining was performed through Alizarin red staining. Dual luciferase reporter gene assays were executed to validate the interaction between SNHG1 and miR-497-5p, as well as HIF1AN. Throughout osteogenic differentiation, there was a down-regulation of SNHG1 and HIF1AN, in contrast to an elevation in miR-497-5p levels. Direct interactions between miR-497-5p and both SNHG1 and HIF1AN were observed. Notably, SNHG1 exhibited the ability to modulate HIF1AN by influencing miR-497-5p, thereby inhibiting osteogenic differentiation. Functioning as a competitive endogenous RNA, lncRNA SNHG1 exerts an inhibitory influence on osteogenic differentiation via the miR-497-5p/HIF1AN axis. This highlights the potential for lncRNA SNHG1 to emerge as a promising therapeutic target for osteoporosis. The study's findings pave the way for a novel target strategy in the future treatment of osteoporosis.
Assuntos
MicroRNAs , Osteoporose , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Osteogênese/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Diferenciação Celular/genética , Osteoporose/genética , Osteoporose/metabolismo , Células Cultivadas , Oxigenases de Função Mista , Proteínas RepressorasRESUMO
Osteoporosis (OP) has a significant detrimental impact on the health of the elder. Long-term clinical effectiveness of current drugs used for OP treatment is limited. Therefore, it is very important to explore novel treatment targets for OP. The expression of SNHG1, HMGB1, OCN and OPN in gene level was measured using RT-qPCR, and the protein expression was determined by Western blotting assay. The concentration of IL-1ß and IL-18 in supernatant of the bone marrow mesenchymal stem cells (BMSCs) was measured by ELISA. The interaction between SNHG1 and HMGB1 was confirmed by RNA pull down. Besides, alizarin red staining was performed to evaluate the differentiation of BMSCs into osteoblast. SNHG1 and HMGB1 were found to be upregulated in the serum of OP patients. During the osteogenic differentiation of BMSCs, the expression of osteoblastogenesis markers (OCN and OPN) and the activity of ALP were upregulated, while the expression levels of SNHG1 and HMGB1 were decreased in a time-dependent manner. In addition, the interaction between SNHG1 and HMGB1, expression of pyroptosis-associated factors (caspase-1 p20 and GSDMD-N), and secretion of IL-1ß and IL-18 were also decreased during osteogenic differentiation. Interestingly, increasing SNHG1 promoted HMGB1 expression, activated pyroptosis, but inhibited osteogenic differentiation. Silencing HMGB1 or inhibiting caspase-1 partially rescued the inhibitory effect of SNHG1 on osteogenic differentiation. Our findings indicate that SNHG1 suppresses the osteogenic differentiation of BMSCs by activating pyroptosis through interaction with HMGB1 and promotion of HMGB1 expression. Our work provides further evidence supporting SNHG1 acts as a potential target for OP treatment, and reveals for the first time that SNHG1 regulates osteogenic differentiation by affecting pyroptosis.
RESUMO
RATIONALE: Percutaneous transhepatic biliary drainage (PTBD) plays a significant role especially in the diagnosis and decompression of bile duct obstruction. However, it is associated with complications such as hemobilia, occlusion of drainage, bile leakage, and even bronchobiliary fistula (BBF). PATIENT CONCERNS AND DIAGNOSES: We herein describe a patient with a complication of BBF caused by long-term indwelling PTBD catheters. She underwent multiple operations including bilioenteric anastomosis, hepatic left lateral lobectomy, and long-term PTBD treatment. Her symptoms were mainly cough, fever, and yellow sputum and her diagnosis was confirmed by sputum culture (bilirubin detection was positive). INTERVENTIONS AND OUTCOMES: The patient recovered uneventfully by minimally invasive treatment, was discharged after 1 week of hospitalization, and the drainage tube was removed 2 weeks later. During 2 years of follow-up, no recurrence of BBF was observed. LESSONS: Patients with long-term indwelling PTBD catheters for biliary tract obstruction may lead to BBF. The treatment plan of BBF is tailored to the patient's individualized characteristics. And minimally invasive treatments might be an effective alternate way for the treatment of BBF. The accurate diagnosis, precision treatment, and multidisciplinary team play important roles in the treatment of BBF.